title
stringlengths 2
239
| text
stringlengths 100
21.8M
|
|---|---|
Congenital_malformations_of_heart | Congenital heart disease (CHD) is the most common type of birth defect, accounting for about 1% of all cases [4]. Although mild cases of CHD are not detected until after discharge, most of the critical CHD cases are identified soon after birth requiring surgery or catheter-based intervention in the first year of life. CHD is broadly classified into three major groups, namely, cyanotic CHD, ductal-dependent CHD and critical CHD. Cyanotic CHD involves defects that lead to mixing of deoxygenated blood into the systemic circulation. Ductal-dependent CHD relies on the patency of the ductus arteriosus for supply of blood to the pulmonary or systemic outflow which allows adequate mixing between the parallel circulations. Lesions requiring surgery or catheter-based intervention in the first year of life are referred to as critical CHD which includes ductal-dependent and cyanotic lesions, as well as forms of CHD that, although not requiring surgery in the neonatal period, do necessitate intervention in the first year of life, such as a big ventricular septal defect or an atrioventricular canal defect (or atrioventricular septal defect).
Aortic stenosis | Atrial septal defect (ASD) | Atrial septal defect sinus venosus | Atrioventricular canal | Atrioventricular septal defect (AVSD) | Bicuspid aortic valve | Brugada syndrome | Cardiomyopathy | Coarctation of the aorta (CoA) | dextro-Transposition of the great arteries (d-TGA) | Dextrocardia | Ebstein's anomaly | Hypoplastic left heart syndrome (HLHS) | Hypoplastic right heart syndrome | Interrupted aortic arch (IAA) | levo-Transposition of the great arteries (l-TGA) | Lutembacher's syndrome | Mitral stenosis | Ostium primum | Ostium secundum | Partial anomalous pulmonary venous connection (PAPVC) | Patent ductus arteriosus (PDA) | Pulmonary atresia | Pulmonary stenosis | Septum primum | Subaortic stenosis | Tetralogy of Fallot (ToF) | Total anomalous pulmonary venous connection (TAPVC) | Tricuspid atresia | Truncus arteriosus | Ventricular septal defect (VSD)
Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | MRI | CT | Echocardiography | Prenatal Ultrasound | Other Imaging Findings
Medical Therapy | Surgery | Prevention | Outcomes | Reproduction
Case #1
Template:WikiDoc Sources
|
Camillo_Golgi | Camillo Golgi (July 7, 1843 – January 21, 1926) was an Italian physician and scientist.
Camillo Golgi was born in Corteno (Brescia). His father was a physician and district medical officer. Golgi studied at University of Pavia, where he worked in the experimental pathology laboratory under Giulio Bizzozero, who elucidated the properties of bone marrow. He graduated in 1865. He spent much of his career studying the central nervous system. Tissue staining techniques in the latter half of the 19th century were inadequate for studying nervous tissue. While working as chief medical officer in a psychiatric hospital, he experimented with metal impregnation of nervous tissue, using mainly silver (silver staining). He discovered a method of staining nervous tissue which would stain a limited number of cells at random, in their entirety. This enabled him to view the paths of nerve cells in the brain for the first time. He called his discovery the "black reaction" (in Italian, reazione nera), which later received his name (Golgi's method) or Golgi stain. The reason for the random staining is still not understood.
The black reaction consisted in fixing silver chromate particles to the neurilemma (the neuron membrane) by reacting silver nitrate with potassium dichromate. This resulted in a stark black deposit on the soma as well as on the axon and all dendrites, providing an exceedingly clear and well contrasted picture of neuron against a yellow background. The ability to visualize separate neurons led to the eventual acceptance of the neuron doctrine.
In addition to this discovery, Golgi discovered a tendon sensory organ that bears his name (Golgi receptor). He studied the life cycle of Plasmodium falciparum and related the timing of fevers seen in malaria with the life cycle of this organism. Using his staining technique, Golgi identified the intracellular reticular apparatus in 1898 which bears his name, the Golgi apparatus.
In renal physiology Golgi is renown for being the first to show that the distal tubulus of the nephron returns to its originating glomerulus (nerve ending of the Bombula) a finding that he published in 1889 ("Annotazioni intorno all'Istologia dei reni dell'uomo e di altri mammifieri e sull'istogenesi dei canalicoli oriniferi". Rendiconti R. Acad. Lincei 5: 545-557, 1889.).
Golgi, together with Santiago Ramón y Cajal, received the Nobel Prize in Physiology or Medicine in 1906 for his studies of the structure of the nervous system.
Golgi died in Pavia, Italy, in January 1926.
In Pavia several landmarks stand as Golgi’s memory.
A marble statue, in a yard of the old buildings of the University of Pavia, at N.65 of the central “Strada Nuova”. On the basament, there is the following inscription in Italian language: "Camillo Golgi / patologo sommo / della scienza istologica / antesignano e maestro / la segreta struttura / del tessuto nervoso / con intenta vigilia / sorprese e descrisse / qui operò / qui vive / guida e luce ai venturi / MDCCCXLIII - MCMXXVI" (Camillo Golgi / outstanding pathologist / of histological science / precursor and master / the secret structure / of the nervous tissue / with strenuous effort / discovered and described / here he worked / here he lives / here he guides and enlightens future scholars / 1843 - 1926).
"Golgi’s home", also in Strada Nuova, at N.77, a few hundreds meters away from the University, just in front to the historical “Teatro Fraschini”. It is the home in which Golgi spent the most of his family life, with his wife Lina.
Golgi’ tomb is in the Monumental Cemetery of Pavia (viale San Giovannino), along the central lane, just before the big monument to the falls of the First World War. It is a very simple granite grave, with a bronze medallion representing the scientist’s profile. Near Golgi’s tomb, apart his wife, other two important italian medical scientists are buried: Bartolomeo Panizza and Adelchi Negri. |
Children%27s_Claritin | Loratadine is an antihistamine that is FDA approved for the treatment of runny nose, sneezing, itchy, watery eyes, itching of the nose or throat. Common adverse reactions include xerostomia, headache, somnolence and fatigue.
Dose: 10 mg PO daily
Dose: 10 mg PO daily
There is limited information regarding Off-Label Guideline-Supported Use of Loratadine in adult patients.
10-20 mg PO daily up to 8 weeks
Dose (2-5 years): 5 mg PO daily
Dose (>6 years): 10 mg PO daily
Dose 2-5 years: 5 mg PO daily
Dose >6 years: 10 mg PO daily
There is limited information regarding Off-Label Guideline-Supported Use of Loratadine in pediatric patients.
<30 kg: 10 mg PO daily
>30 kg: 20 mg PO daily
Hypersensitivity to loratadine
Do not use if you have ever had an allergic reaction to this product or any of its ingredients
Ask a doctor before use if you have liver or kidney disease. Your doctor should determine if you need a different dose.
When using this product do not take more than directed. Taking more than directed may cause drowsiness.
Stop use and ask a doctor is an allergic reaction to this product occurs. Seek medical help right away.
If pregnant or breast-feeding, ask a health professional before use.
Keep out of reach of children.
In case of overdose, get medical help or contact a Poison Control Center right away.
Rash
Abdominal pain
Diarrhea
Stomatitis
Xerostomia
Hepatic necrosis
Hepatitis
Jaundice
Anxiety
Headache
Hyperactivity
Somnolence
Epistaxis
Pharyngitis
Upper respiratory infections
Viral disease
Wheezing
Dysphonia
Fatigue
Influenza-like symptoms
Malaise
Somnolence
Tooth disorder
There is limited information regarding Loratadine Postmarketing Experience in the drug label.
Amiodarone: QT interval prolongation and Torsade de Pointes have been reported with the co-administration of loratadine and amiodarone.
Carbamazepine: Loratadine increase plasma concentration of carbamazepine.
Cimetidine: increases plasma concentrations of loratadine
Ketoconazole: increases plasma concentrations of loratadine
Mepenzolate
Morphine: increases risk of paralytic ileus
Morphine sulfate liposome: increases risk of paralytic ileus
Oximorphone
Umeclidinium
Pregnancy Category (FDA): B
Ask a health professional before use.
Pregnancy Category (AUS): B1
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Loratadine in women who are pregnant.
There is no FDA guidance on use of Loratadine during labor and delivery.
Ask a health professional before use.
In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222)
There is no FDA guidance on the use of Loratadine in geriatric settings.
There is no FDA guidance on the use of Loratadine with respect to specific gender populations.
There is no FDA guidance on the use of Loratadine with respect to specific racial populations.
There is no FDA guidance on the use of Loratadine in patients with renal impairment.
There is no FDA guidance on the use of Loratadine in patients with hepatic impairment.
There is no FDA guidance on the use of Loratadine in women of reproductive potentials and males.
There is no FDA guidance one the use of Loratadine in patients who are immunocompromised.
Oral
There is limited information regarding Loratadine Monitoring in the drug label.
There is limited information regarding the compatibility of Loratadine and IV administrations.
There is limited information regarding Loratadine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H1-receptors.
There is limited information regarding Loratadine Structure in the drug label.
There is limited information regarding Loratadine Pharmacodynamics in the drug label.
Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism; it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others. Loratadine is almost totally (97–99%) bound to plasma proteins. Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.
There is limited information regarding Loratadine Nonclinical Toxicology in the drug label.
There is limited information regarding Loratadine Clinical Studies in the drug label.
Supplied as tablets of 10 mg in 30 tablet carton and 40 tablet bottle carton.
Store at 20°-25°C (68°-77°F)
{{#ask: Page Name::Loratadine
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Loratadine
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
There is limited information regarding Loratadine Patient Counseling Information in the drug label.
Alcohol-Loratadine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Alavert
Claritin
Claritin Reditabs
Clearatadine
Triaminic Allerchews
Children's Clear-Atadine
Children's Dimetapp ND Allergy
Children's Claritin
There is limited information regarding Loratadine Look-Alike Drug Names in the drug label.
|
Mesothelioma_historical_perspective | The association between mesothelioma and asbestos exposure was first described by Dr. Wagner in his seminal study of South African miners. It was discovered later that people who live near to factors and mines developed mesothelioma despite not working in the mines.
The association between mesothelioma and exposure to asbestos fibers was elucidated by Dr. Wagner in his seminal study of South African miners.
In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds.
In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighborhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.
Despite proof that the dust associated with asbestos mining and milling causes asbestos related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.
By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.
In the landmark study by Vogelzang et al., cisplatin and pemetrexed led to an objective response rate of 41% and median survival of 12.1 months, compared to 17% and 9.3 months in patients treated with cisplatin alone.
The first lawsuits against asbestos manufacturers were in 1929.
s between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898).
The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.
The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.
Main article: asbestos and the law |
Coronary_heart_disease_secondary_prevention_target_population | Patients who should be treated with secondary prevention are those with established atherosclerosis including peripheral artery
disease; carotid artery disease; atherosclerotic aortic disease; diabetes and those with a Framingham Risk Score of > 20%.
|
Caplans_syndrome_medical_therapy |
Pharmacologic medical therapies for Caplan Syndrome include steroid therapy, Disease modifying antirheumatic drugs(DMARDS) for Rheumatoid arthritis. Irreversible lung fibrosis requires lung transplantation. |
Continuous_murmur | A continuous murmur begins in systole and continues into diastole. They are caused by blood flow from high pressure chambers into low pressure chambers. The most common causes of continuous murmurs are patent ductus arteriosus, arteriovenous fistula and arterial stenosiPulmonary embolism
Anemia
Aortic coarctation
Arteriovenous fistula
Cervical venous hum
Patent ductus arteriosus
Pericardial friction rub
Pregnancy
Pulmonary arteriovenous fistula
Renal artery stenosis
Valvular heart disease
Abdominal aortic aneurysm
Anemia
Aortic coarctation
Aortic-atrial fistulas
Arteriovenous fistula
Arteriovenous malformation
Atrial septal defect with mitral stenosis
Carotid artery stenosis
Celiac artery stenosis
Cervical venous hum
Cholangiocarcinoma
Cimino fistula
Cirrhosis
Coronary artery fistula
Fistula between an internal mammary graft and the pulmonary vasculature
Hepatic hemangioma
Hepatic hum
Hepatoma
Hyperthyroidism
Liver metastasis
Lutembacher's syndrome
Mammary souffle
Mitral stenosis with a persistent left superior vena cava
Paget's disease
Pulmonary embolism
Patent ductus arteriosus
Pericardial friction rub
Pregnancy
Pulmonary arteriovenous fistula
Pulmonary artery stenosis
Pulmonary atresia with ventricular septal defect
Renal artery stenosis
Renal cell carcinoma
Ruptured aneurysm of sinus of valsalva
Takayasu arteritis
Total anomalous pulmonary venous drainage
Tricuspid atresia
Tricuspid regurgitation
Truncus arteriosus
Valvular heart disease
|
Graves%27_disease_echocardiography_or_ultrasound | Goiter, which is caused by an enlarged thyroid gland, can be present with other forms of hyperthyroidism, although Graves' disease is the most common cause. A large goiter is visible to the naked eye, but a smaller goiter may not be clinically detectable, though ultrasound can assist in detecting it.
On US it appears as :
Diffusely enlarged hyper-vascular thyroid gland a patterns on echo called "thyroid inferno"
Hyper-echoic and enlarged
Nodularity is present only in case of complicated cases as co-existing viral infection or autoimmune thyroid disease.
Echo-texture is heterogeneous
USG with contrast showing thyroid mass.(Source: Case courtesy of Dr Erik Ranschaert, <a867">rID: 10867</a> ) |
Fever_of_unknown_origin_resident_survival_guide | Management of fever of unknown origin should generally be withheld until the etiology is ascertained so that treatment can be targeted toward a specific pathology.
Fever of unknown origin (FUO) may be considered providing all the following criteria are fulfilled:
Fever higher than 38.3°C (100.9°F) on several occasions
Persisting without diagnosis for at least 3 weeks
At least 1 week's investigation in hospital
Minimum diagnostic evaluation to qualify as FUO includes:
Comprehensive history
Repeated physical examination
Complete blood count, including differential and platelet count
Routine blood chemistry, including lactate dehydrogenase, bilirubin, and liver enzymes
Urinalysis, including microscopic exmination
Chest radiograph
Erythrocyte sedimentation rate
Antinuclear antibodies
Rheumatoid factor
Three or more sets of blood cultures while not receiving antibiotics
Cytomegalovirus IgM antibodies or virus detection in blood
Heterophile antibody test in children and young adults
Tuberculin skin test
CT of abdomen or radionuclide scan
HIV antibodies or virus detection assay
Further evaluation of any abnormalities detected by above tests
Common causes of fever of unknown origin are as follows:
Infections
Localized
– Endocarditis
– Intra-abdominal infections
– Urinary tract infections
– Osteomyelitis
– Upper respiratory tract infections
– Infected peripheral vessels
Generalized
– Bacterial
– Mycobacterial
– Fungal
– Viral
– Parasitic
Neoplasia
– Lymphoproliferative disorders
– Leukemia
– Myelodysplastic syndrome
– Solid tumors
Rheumatic disorders
– Adult onset Still's disease
– Giant cell arteritis
– Polymyalgia rheumatica
– Other forms of vasculitis (e.g., polyarteritis nodosa, Wegener's granulomatosis, Takayasu's arteritis)
– Other rheumatologic disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome)
Endocrine disorders
– Hyperthyroidism
– Thyroiditis
– Adrenocortical insufficiency
Hereditary disorders (e.g., familial Mediterranean fever)
Factitious fever
Miscellaneous
– Granulomatous disorders
– Hepatitis
– Vascular disorders (e.g., pulmonary embolism, hematoma)
– Drug fever
Respiratory tract infections cause FUO in infants more often than in children older than 12 months, whereas connective tissue diseases predominate as the cause of FUO in children and adults. For patients older than 65 years, non-infectious inflammatory disorders including polymyalgia rheumatica and temporal arteritis are identified as the major causes of FUO in developed countries. Intra-abdominal abscesses, complicated urinary tract infections, tuberculosis, and endocarditis are the most common infectious causes of FUO in the elderly.
Abbreviations:
ALP, alkaline phosphatase;
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
CBC, complete blood count;
CMV, cytomegalovirus;
DC, differential count;
HIV, human immunodeficiency virus;
PET, positron emission tomography;
s/o, suggestive of;
SMA-7, sequential multiple analysis-7.
Suspected Fever of Unknown Origin
Focused History
Verify the presence of fever and its pattern
Sustained fever (s/o brucellosis, drug fever, Gram-negative pneumonia, tularemia, typhoid, typhus)
Remittent fever (s/o tuberculosis, mycoplasma pneumonia, malaria, legionellosis)
Intermittent fever (s/o malaria, kala-azar, pyaemia)
Double quotidian fever (s/o Still's disease, legionellosis, miliary tuberculosis, kala-azar)
Quotidian fever (s/o Plasmodium falciparum or Plasmodium knowlesi malaria)
Tertian fever (s/o Plasmodium vivax or Plasmodium ovale malaria)
Quartan fever (s/o Plasmodium malariae malaria)
Alternate-day fever (s/o response to antipyretic dosage schedule)
Hyperpyrexia (s/o intracranial hemorrhage, septicemia, Kawasaki disease, thyroid storm, drug fever)
Hectic or spiking pattern (s/o biliary or urinary tract infection, endocarditis)
Morning temperature spikes (s/o typhoid fever, tuberculosis, polyarteritis nodosa)
Relapsing pattern (s/o Borrelia recurrentis, typhoid fever, malaria, brucellosis, rat-bite fever)
Irregular pattern (s/o factitious fever)
Pel-Ebstein pattern (s/o Hodgkin's lymphoma)
Picket fence pattern (s/o acute mastoiditis complicated by transverse sinus thrombosis)
Saddleback (dromedary) pattern (s/o dengue fever, leptospirosis, poliomyelitis, ehrlichiosis)
Wunderlich curve pattern (s/o typhoid fever)
History of previous surgeries or procedures
History of malignancy and related therapy
History of previously treated infections
History of sick or animal contacts
History of psychiatric illness
History of recent traveling
History of comorbidities
History of medications
History of transfusions
Social and family history
Physical Examination
VitalsSkin–.
Erythematous papules, pustules, subcutaneous nodules, or cellulitis may be present in cryptococcosis.
Sister Mary Joseph nodule (palpable nodule bulging into the umbilicus) may be present in metastasis of a malignant tumor in the pelvis or abdomen.
Multiple purplish papules, nodules, and plaques may be present on the scalp, face, and neck in lymphoma.
Multiple erythematous, painful plaques with small bumps, pustules, and vesicles may be present in Sweet's syndrome.
Palpable purpura may be present on the lower extremities and other areas of dependency in cutaneous vasculitis.
Head
Temporal artery tenderness with weak pulse may be present in temporal arteritis.
Sinus tenderness may be present in sinusitis.
Eyes
Roth's spots or conjunctival hemorrhage may be present in infective endocarditis.
Photophobia or ocular pain on palpation suggestive of uveitis may be present in Wegener's granulomatosis, Behcet syndrome, Vogt-Koyanagi-Harada syndrome, or infections.
MouthNeck
Cervical lymph nodes may be present in inflammation, infection, lymphoma, or Kikuchi disease.
Enlargement of the thyroid gland may be present in thyroiditis.
Lungs
Rales or rhonchi may be present in pneumonia.
Fremitus with diminished breath sounds may be present in pneumonia.
Heart
Heart murmurs may be present in endocarditis secondary to infections (infective endocarditis), systemic lupus erythematosus (Libman-Sacks endocarditis), or chronic diseases (marantic endocarditis).
Abdomen
Abdominal tenderness may be present in intra-abdominal infections.
Rebound tenderness may be present in intra-abdominal infections.
An acute abdomen may be present in intra-abdominal infections.
Guarding may be present in intra-abdominal infections.
Flank pain may be present in psoas muscle abscess, perinephric abscess, or pyelonephritis.
An inguinal mass may be present in psoas muscle abscess.
Splenomegaly may be present in infectious mononucleosis, splenic abscess, or hepatitis.
Genitourinary
Prostatic enlargement may be present in prostatic abscess.
Epididymal nodule may be present in epididymitis.
Testicular nodule may be present in polyarteritis nodosa.
ExtremitiesNeurologic
Altered mental status may be present.
Cranial nerve deficits may be present in cerebral vasculitis associated with systemic lupus erythematosus.
Laboratory Workup
CBC with DC
SMA-7
AST, ALT, LDH, bilirubin, and ALP
Creatine kinase
Blood cultures, at least 2 sets
Urinalysis with microscopic examination
Urine cultures
Erythrocyte sedimentation rate
C-reactive protein
Gamma-glutamyl transferase
Coombs test
Cold agglutinins
Ferritin
Angiotensin-converting enzyme
Thyroid peroxidase and anti-thyroglobulin antibodies
Antinuclear antibodies
Rheumatoid factor
Cryoglobulins
CMV serology and heterophile antibody test if ⊕ atypical lymphocytes
Q fever serology if ⊕ exposure to livestocks
HIV serology
Serum protein electrophoresis
Tuberculin skin test
Fecal occult blood test
Imaging Study
Chest Radiograph
Chest radiograph should be considered as a part of the initial diagnostic workup.
Echocardiography
Echocardiography should be considered when suspecting endocarditis.
Abdominal Ultrasonography
Abdominal ultrasonography should be considered when suspecting hepatobiliary pathology.
Chest CT Scan
Chest CT scan may detect nodular lesions (s/o malignancy or fungal/mycobacterial/nocardial infection) or mediastinal adenopathy (s/o lymphoma, histoplasmosis, or sarcoidosis).
Abdominal CT Scan
Abdominal CT scan should be considered when suspecting intra-abdominal abscess or malignancy.
Positron Emission Tomography
PET may be useful in localizing the nidus of fever of unknown origin.
Other Investigation
Lymph Node Biopsy
Lymph node biopsy may be useful when suspecting lymphoma, lymphogranuloma venereum, toxoplasmosis, and Kikuchi disease.
Granuloma may indicate disorders associated with granulomatous inflammation (eg, tuberculosis, sarcoidosis) or lymphoma.
Bone Marrow Biopsy
Bone marrow biopsy may be considered when suspecting intracellular infectious pathogens or hematologic malignancies.
Discontinuation of Nonessential Medications
Nonessential medications should be discontinued.
Defervescence in less than 72 hours after discontinuing the culprit medication suggests drug fever.
Rechallenge with the offending agent usually results in recurrence of drug fever.
Trial of Empiric Antibiotics
Therapeutic trials of antimicrobial agents may be considered if other techniques fail to disclose the etiology.
An infectious etiology is likely if abatement of fever occurs after the administration of empiric antibiotics.
Naproxen Test
Naproxen test (375 mg twice daily) can be used to distinguish neoplastic fever from other etiologies.
Naproxen test is considered positive when there is a rapid or sustained abatement of fever during the 3 days of the trial period.
Defervescence within 12 hours occurs in almost all patients with neoplastic fever.
Fever recurs after discontinuation of naproxen in patients with neoplasms.
Naproxen demonstrated no antipyretic activity against fever in patients with occult infection.
Management should be withheld until the etiology is ascertained so that treatment can be directed toward a specific pathology.
Empiric corticosteroids may be appropriate in patients with suspected temporal arteritis to prevent vascular complications.
Patients with febrile neutropenia should receive broad-spectrum antipseudomonal antibiotics immediately after specimens for cultures have been obtained.
FUOD/C nonessential Rx
Defervescence in 72h Fever persists
Drug fever CT or nuclear scanFocus identified Focus undetermined
Verify with tissue biopsy IE suspected? Duke criteria fulfilled IE unlikely
Treat as IE GCA suspected? GCA likely GCA unlikely
Treat as GCA ANC < 500? Febrile neutropenia Normal ANC
Antipseudomonal abx Follow up
|
R-ICE_regimen | ICE-R regimen refers to a chemoimmunotherapy regimen consisting of rituximab, ifosfamide, carboplatin and etoposide used to treat indolent and aggressive forms of non-Hodgkin's lymphoma; also used to treat relapsed and refractory non-Hodgkin's lymphoma.
RRituximab
IIfosfamide
CCarboplatin
EEtoposide
Relapsed and refractory non-Hodgkin's lymphoma. |
Tricuspid_stenosis_surgery | Surgical tricuspid valve replacement in tricuspid stenosis (TS) is recommended amongtricuspid stenosis (TS).
Surgery is the mainstay of treatment for tricuspid stenosis (TS), which includes the following:
Valvotomy
Valvotomy in tricuspid stenosis (TS) patients is done by using 1, 2, or 3 balloons.
By undergoing balloon valvotomy the tricuspid valve area increase from less than 1 to almost 2 cm2.
In cases of severe rheumatic tricuspid stenosis using a inoue balloon is much more useful and a simplified approach.
With valvotomy there is significant change in transvalvular pressure gradient across tricuspid valve and there is a decrease in right atrial pressure.
Balloon Valvuloplasty for Bioprosthetic Tricuspid Valve Stenosis. Case courtesy by Emmanouil Petrou, MD et al
Valve surgery
In tricuspid stenosis (TS) patients valve surgery include either valve repair or valve replacement.
Consider repair of the tricuspid valve if its feasible.
If tricuspid valve repair not an option consider valve replacement.
Patients who are undergoing tricuspid valve replacement the mortality rate is little higher when compared to patients who are undergoing tricuspid valve repair.
While considering tricuspid valve replacement it can be done in 2 ways: Open tricuspid valve replacement, Transcatheter replacement
Surgeon can choose either a bioprosthetic valve or an mechanical valve, the outcome is same using either of the valves with some conditions as an exception.
Survival in patients with bioprosthetic valve or an mechanical valve is almost the same.
In patients with carcinoid syndrome, using a mechanical valve over a bioprosthetic valve is better choice to avoid the degeneration on the valve.
|
Moxatag | Amoxicillin is an antibiotic that is FDA approved for the treatment of infections of the ear, nose, throat, genitourinary tract and lower respiratory tract. Also for Gonorrhea and Helicobacter infections. Common adverse reactions include rash, diarrhea, nausea, headache and vulvovaginitis.
‡ Dosing for infections caused by less susceptible organisms should follow the recommendations for severe infections. § The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. π Each strength of the suspension of amoxicillin is available as a chewable tablet for use by older children.
Triple Therapy: Amoxicillin, Clarithromycin, Lansoprazole
The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (q12h) for 14 days.
In patients wit comorbidities or use of antimicrobials within the previous 3 month, Dosage: 875mg PO q12h OR 500mg q8h
Mild/Moderate: 500mg q12h or 250mg q8h
Severe: 875mg q12h or 500mg q8h
Dosage: 3g as single oral dose
Triple Therapy for 14 days, Amoxicillin: 1g q12h PO, Clarithromycin: 500mg q12h, Lansoprazole: 30mg q12h
Dual Therapy, Amoxicillin: 1g q8h, Lansoprazole: 30mg q8h
Mild/moderate: 500mg q12h or 250mg q8h
Severe: 875mg q12h or 500mg q8h
Mild/Moderate: 500 mg q12h or 250mg q8h
Severe: 875mg q8h or 500mg q8h
Dosage: 875 mg q12h or 500 mg q8h
Dosage: 775mg once daily taken within 1 hour of finishing a meal, for 10 days.
Dosage: 2g PO q24h
Pregnant women: 500mg q8h PO for 7 days.
Eritema migrans dosage: 500mg PO TID for 14-21 days
Seventh-cranial nerve palsy: 500mg PO TID for 14-21 days
Lyme's arthritis: 500mg PO TID for 14-21 days
Dosage: 500mg q8h PO (in combination with cotrimoxazole (80mg/400mg) 2 tablets q12h for 2-5 months for home regimen)
Dosage: 1g q12h PO.
When first-line drugs are contraindicated in the patient, Dosage: 1g q8h PO
Dosage: 500mg Amoxicillin q8h in combination with metronidazole 250-400mgMild/Moderate: 25 mg/kg/day in divided doses q12h or 20 mg/kg/day in divided doses q8h
Severe: 45 mg/kg/day in divided doses q12h or 40 mg/kg/day in divided doses q8h
Dosage: 50 mg/kg Amoxicillin combined with 25 mg/kg Probenecid (Only in pediatric population >2 years old).mg/kg/day in divided doses q8h
Mild/Moderate: 25mg/kg/day in divided doses q12h or 20mg/kg/day in divided doses q8h
Severe: 45mg/kg/day in divided doses q12h or 40 mg/kg/day in divided doses q8h
Dosage: 45mg/kg/day in divided doses q12h or 40mg/kg/day in divided doses q8h
Dosage: (>12 year old) 775mg once daily taken within 1 hour of finishing a meal, for 10 days.
Eritema migrans dosage: 50mg/kg/day PO in 3 divided doses (Max: 1500mg)
Lyme's arthritis: 50 mg/kg/day PO in 3 divided doses (Max: 1500mg)
Seventh-cranial nerve palsy: 50 mg/kg/day PO in 3 divided doses (Max: 1500mg)
Dosage: 50 mg/kg once daily (Max: 1 g/day)
Dosage: 500mg Amoxicillin q8h in combination with metronidazole 250-400mg q8h
Dosage: 40mg/kg/day (Max: 2g/day) for 10-14 days in combination with an antirheumathic drug.
Dosage: Ampicillin 2 g IV every 6 hours with erythromycin 250 mg every 6 hours, for 48 hours followed by amoxicillin 250 mg orally every 8 hours and erythromycin base 333 mg every 8 hours for 5 days.
A history of allergic reaction to any of the penicillins is a contraindication.
amoxamoxioxMucocutaneous candidiasis.
Nausea
Vomiting
Diarrhea
Black hairy tongue
Hemorrhagic/pseudomembranous colitis
Anaphylaxis
Serum sickness-like reactions
Erythematous maculopapular rashes
Erythema multiforme
Stevens-Johnson syndrome
Exfoliative dermatitis
Toxic epidermal necrolysis
Acute generalized exanthematous pustulosis
Hypersensitivity vasculitis
Urticaria
NOTE: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxicillin therapy.
Rise in AST (SGOT) and/or ALT (SGPT)
Cholestatic jaundice
Hepatic cholestasis
Acute cytolytic hepatitis
Crystalluria
Anemia, including hemolytic anemia
Thrombocytopenia
Thrombocytopenic purpura
Eosinophilia
Leukopenia
Agranulocytosis
NOTE: These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.
Hyperactivity
Agitation
Anxiety
Insomnia
Confusion
Convulsions
Behavioral changes
Dizziness
Tooth discoloration: brown, yellow, or gray staining.
In clinical trials using combination therapy with amoxicillin plus clarithromycin and lansoprazole, and amoxicillin plus lansoprazole, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxicillin, clarithromycin, or lansoprazole.
Amoxicillin/Clarithromycin/Lansoprazole:The most frequently reported adverse events for patients who received triple therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen.
The most frequently reported adverse events for patients who received amoxicillin three times daily plus lansoprazole three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with amoxicillin three times daily plus lansoprazole three times daily dual therapy than with lansoprazole alone.
There is limited information regarding Amoxicillin Postmarketing Experience in the drug label.
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.
Pregnancy Category (FDA): B
Reproduction studies have been performed in mice and rats at doses up to 10amoxThere is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amoxicillin in women who are pregnant.
Oral ampicillin-class antibiotics are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of ampicillin slightly decreased the uterine tone and frequency of contractions but moderately increased the height and duration of contractions. However, it is not known whether use of amoxiPenicillins have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.
Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of amoxicillin should be modified in pediatric patients 12 weeks or younger (≤ 3 months)
An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of the 1,811 subjects treated with capsules of amoxicillin, 85% were < 60 years old, 15% were ≥ 61 years old and 7% were ≥ 71 years old. This analysisoxicillin with respect to specific gender populations.
There is no FDA guidance on the use of Amoxicillin with respect to specific racial populations.
There is no FDA guidance on the use of Amoxicillin in patients with renal impairment.
There is no FDA guidance on the use of Amoxicillin in patients with hepatic impairment.
Amoxicillin and potassium clavulanate was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test, and was negative in each of these assays. In a multi-generation reproduction study in rats, no impairment of fertility or other adverse reproductive effects were seen at doses up to 500 mg/kg (approximately 3 times the human dose in mg/m2).
There is no FDA guidance one the use of Amoxicillin in patients who are immunocompromised.
oral
As with any potent drug, periodic assessment of renal, hepatic, and hematopoietic function should be made during prolonged therapy. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with amoxicillin should have a follow-up serologic test for syphilis after 3 months.
There is limited information regarding the compatibility of Amoxicillin and IV administrations.
In case of overdosage, discontinue medication,-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.
Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin may be removed from circulation by hemodialysis.
Amoxicillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide.
Chemically it is (2S,5R,6R)-6-[(R)-(-)-2- amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid trihydrate. The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45.
There is limited information regarding Amoxicillin Pharmacodynamics in the drug label.
Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxicillin from amoxicillin tablets and amoxicillin suspension has been partially investigated. The 400 mg and 875 mg formulations have been studied only when administered at the start of a light meal. However, food effect studies have not been performed with the 200 mg and 500 mg formulations. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxicillin is approximately 20% protein-bound.
Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 3.5 mcg/mL to 5 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.
Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of amoxicillin with 875 mg of amoxicillin/ clavulanate potassium showed that the 875 g tablet of amoxicillin produces an AUC0-∞ of 35.4 ±8.1 mcg•hr/mL and a Cmax of 13.8 ±4.1 mcg/mL. Dosing was at the start of a light meal following an overnight fast.
Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.
There is limited information regarding Amoxicillin Nonclinical Toxicology in the drug label.
Randomized, double-blind clinical studies performed in the United States in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within 1 year) evaluated the efficacy of lansoprazole in combination with amoxicillin capsules and clarithromycin tablets as triple 14 day therapy, or in combination with amoxicillin capsules as dual 14 day therapy, for the eradication of H. pylori. Based on the results of these studies, the safety and efficacy of 2 different eradication regimens were established:
Triple Therapy: Amoxicillin 1 gram twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice daily.
Dual Therapy: Amoxicillin 1 gram three times daily/ lansoprazole 30 mg three times daily.
All treatments were for 14 days. H. pylori eradication was defined as 2 negative tests (culture and histology) at 4 to 6 weeks following the end of treatment.
Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.
H. pylori Eradication Rates – Triple Therapy (amoxicillin/clarithromycin/lansoprazole) Percent of Patients Cured [95% Confidence Interval] (Number of Patients)
H. pylori Eradication Rates – Dual Therapy (amoxicillin/lansoprazole) Percent of Patients Cured [95% Confidence Interval] (Number of Patients)
Each capsule contains 250 mg or 500 mg amoxicillin as the trihydrate.
250 mg yellow opaque cap and yellow opaque body, size 2, printed “RX654” on both cap and body. NDC 63304-654-20 bottles of 20, NDC 63304-654-30 bottles of 30, NDC 63304-654-01 bottles of 100, NDC 63304-654-05 bottles of 500, NDC 63304-654-77 Unit-dose 100s
500 mg maroon opaque cap and yellow opaque body, size 0-el, printed “RX655” on both cap and bodyEach tablet contains 500 mg or 875 mg amoxicillin as the trihydrate.
500 mg pink colored, film coated, capsule shaped tablets; debossed with “RX762” on one side and plain on the other side. NDC 63304-762-82 bottles of 12, NDC 63304-762-20 bottles of 20, NDC 63304-762-01 bottles of 100, NDC 63304-762-13 bottles of 120, NDC 63304-762-05 bottles of 500
875 mg pink colored, film coated, capsule shaped tablets; debossed with “RX763” on one side and scored on reverse side. NDC 63304-763-82 bottles of 12, NDC 63304-763-20 bottles of 20, NDC 63304-763-01 bottles of 100, NDC 63304-763-13 bottles of 120, NDC 63304-763-05 bottles of 500
Each chewable tablet contains 125 mg, 200 mg, 250 mg or 400 mg amoxicillin as the trihydrate.
125 mg pink colored, strawberry flavored, oval biconvex tablets, with mottled appearance; debossed with “RX514” on one side. NDC 63304-514-01 bottles of 100, NDC 63304-514-05 bottles of 500
260” on one side. NDC 63304-760-20 bottles of 20, NDC 63304-760-01 bottles of 100, NDC 63304-760-05 bottles of 500
250 mg pink colored, strawberry flavored, circular, flat faced, beveled edge tablets, with mottled appearance; debossed with “RX515” on one side. NDC 63304-515-30 bottles of 30, NDC 63304-515-01 bottles of 100, NDC 63304-515-04 bottles of 250
400 mg light716” on one side. NDC 63304-761-20 bottles of 20, NDC 63304-761-01 bottles of 100, NDC 63304-761-05 bottles of 500
The 200 mg per 5 mL oral suspension is off white to light orange granular powder forming a light orange to orange suspension NDC 63304-969-03 50 mL bottles, NDC 63304-969-01 75 mL bottles, NDC 63304-969-04 100 mL bottles
The 4* on constitution with water. The resulting suspension has a characteristic fruity flavor and is available as follows:
NDC 63304-970-03 50 mL bottle, NDC 63304-970-01 75 mL bottle, NDC 63304-970-04 100 mL bottle
SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration preferable, but not required.
Store amoxicillin capsules 250 mg and 500 mg, amoxicillin tablets 500 mg and 875 mg, amoxicillin chewable tablets 125 mg, 200 mg, 250 mg and 400 mg and amoxicillin unreconstituted powder 200 mg/5 mL and 400 mg/5 mL at controlled room temperature 15° – 30° C (59° – 86° F) (see USP).
{{#ask: Page Name::Amoxicillicillin Patient Counseling Information in the drug label.
Alcohol-Amoxicillioxil
Trimox
Wymox
Moxatag
There is limited information regarding Amoxicillin Look-Alike Drug Names in the drug label.
|
Osteoarthritis_screening | Routine screening for osteoarthritis is not indicated unless the patient is symptomatic.
Accurate data about the prevalence of OA can be useful for the health care system to have appropriate plans for management of OA patients. Nowadays, the OA screening in general population depends on the self-reported symptoms recorded during the clinical evaluation. An approved screening algorithm OA with sufficient sensitivities and specificities is necessary for OA management. Due to the lack of a reliable screening test for OA, the assessments of the prevalence of OA in a general population is difficult. Meanwhile, some scientist have worked on the screening questionnaires for identifying the knee or hip OA. Using only a questionnaire to identify OA cases without the physical examinations and radiographs would be non-verifiable.
|
Hypercoagulable_state | History and Symptoms | Physical Examination | Laboratory Findings | X Ray | CT | MRI | Ultrasound | Other Imaging Studies | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Future or Investigational Therapies | Cost Effectiveness of Therapy
Case #1
Template:WH
Template:WS
|
Hypolipoproteinemia_pathophysiology#Primary_Lipoprotein_Disorders | Multiple mechanisms have been described in different diseases and clinical conditions that are found to be associated with hypolipidemia. Secondary causes are far more common than primary causes and include anemia, hyperthyroidism, critical illness, malignancy, malabsorption, infection, Chronic liver disease, and Chronic inflammation.
.
Hypolipedemia has been found in association with different clinical conditions.
Anemia: Hypolipedemia has been identified in association with different types of anemia e.g.congenital dyserythropoietic anemia, congenital spherocytosis, sickle cell anemia, beta-thalassemia, aplastic anemia, and sideroblastic anemia. The exact etiology of hypolipidemia in anemic patients is not known, some studies outlined different mechanisms, another study suggest that hypolipidemia might be the cause rather than the consequence of anemia, which is explained by that cholesterol deficiency leads to rigidity of the erythrocytes, making them more prone to destruction.
Hyperthyroidism: Thyroid hormone influence lipid metabolism and are common in dyslipidemic patients, and its dysfunction affect composition and transport of lipoproteins, hence the importance of Biochemical screening for thyroid dysfunction in all dyslipidemic patients.
Critical illness: Cholesterol levels drop at the onset of acute illness, and normalize after recovery. This may predispose the critically ill patient to sepsis and adrenal failure, .
Malignancy: .
Malabsorption: Fat malabsorption can lead to hypolipidemia, as the dietary fats constitute the exogenous source of body lipids. .
Infection: The chronic effect of proinflammatory cytokines on lipoprotein metabolism seen in acute and chronic, bacterial, viral, and parasitic infections all might induce hypocholesterolemia.
Chronic liver disease: Hypolipidemia is frequently observed in severe chronic hepatic insufficiency, as the hepatocytes is the main site for lipid metabolism.
Chronic inflammation: In the acute phase response to inflammation, reduction in plasma lipid levels is a well known phenomenon, it is explained by the chronic effect of proinflammatory cytokines on lipoprotein metabolism. |
Neosar | Cyclophosphamide is a antineoplastic, immunosuppressive agent that is FDA approved for the treatment of malignant diseases, minimal change nephrotic syndrome in pediatric patients. Common adverse reactions include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.
Dosing Information
Single agent: 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Single agent: oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Single agent: 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Single agent: 1 to 5 mg/kg/day ORALLY, for both initial and maintenance dosing.
Dosing Information
Single agent: 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Single agent: oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic lymphoid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic lymphoid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic myeloid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic myeloid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant histiocytosis (clinical): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant histiocytosis (clinical): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - mixed small and large cell: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - mixed small and large cell: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Multiple myeloma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Multiple myeloma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mycosis fungoides, Advanced: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mycosis fungoides, Advanced: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Neuroblastoma, Disseminated disease: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Neuroblastoma, Disseminated disease: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Non-Hodgkin's lymphoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Non-Hodgkin's lymphoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Ovarian carcinoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Ovarian carcinoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Retinoblastoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Retinoblastoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
There is limited information regarding Off-Label Guideline-Supported Use of Cyclophosphamide in adult patients.
Bone marrow transplant
Pheochromocytoma, Malignant
Wegener's granulomatosis
Dosing Information
Acute lymphoid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Acute lymphoid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Acute myeloid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Acute myeloid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Burkitt's lymphoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Burkitt's lymphoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic lymphoid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic lymphoid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic myeloid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic myeloid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant histiocytosis (clinical): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant histiocytosis (clinical): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - mixed small and large cell: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - mixed small and large cell: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatrics patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy.
Dosing Information
Minimal change disease, In patients who fail to respond to or are unable to tolerate adrenocorticosteroid therapy: 2 mg/kg ORALLY every day for 8 to 12 weeks; MAX cumulative dose 168 mg/kg; treatment beyond 90 days in males increases probability of sterility.
Limitations of Use:
The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established.
Dosing Information
Multiple myeloma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Multiple myeloma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mycosis fungoides, Advanced: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mycosis fungoides, Advanced: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Neuroblastoma, Disseminated disease: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Neuroblastoma, Disseminated disease: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Non-Hodgkin's lymphoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Non-Hodgkin's lymphoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Ovarian carcinoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Ovarian carcinoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Retinoblastoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Retinoblastoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
There is limited information regarding Off-Label Guideline-Supported Use of Cyclophosphamide in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cyclophosphamide in pediatric patients.
Hypersensitivity
Cyclophosphamide is contraindicated in patients who have a history of severe hypersensitivity reactions to it, any of its metabolites, or to other components of the product. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur.
Urinary Outflow Obstruction
Cyclophosphamide is contraindicated in patients with urinary outflow obstruction.
Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections
Cyclophosphamide can cause myelosuppression (leukopenia, neutropenia, thrombocytopenia and anemia), bone marrow failure, and severe immunosuppression which may lead to serious and sometimes fatal infections, including sepsis and septic shock. Latent infections can be reactivated.
Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. In case of neutropenic fever, antibiotic therapy is indicated. Antimycotics and/or antivirals may also be indicated.
Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed. Cyclophosphamide should not be administered to patients with neutrophils ≤1,500/mm3 and platelets <50,000/mm3. Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. G-CSF may be administered to reduce the risks of neutropenia complications associated with cyclophosphamide use. Primary and secondary prophylaxis with G-CSF should be considered in all patients considered to be at increased risk for neutropenia complications. The nadirs of the reduction in leukocyte count and thrombocyte count are usually reached in weeks 1 and 2 of treatment. Peripheral blood cell counts are expected to normalize after approximately 20 days. Bone marrow failure has been reported. Severe myelosuppression may be expected particularly in patients pretreated with and/or receiving concomitant chemotherapy and/or radiation therapy.
Urinary Tract and Renal Toxicity
Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Medical and/ or surgical supportive treatment may be required to treat protracted cases of severe hemorrhagic cystitis. Discontinue cyclophosphamide therapy in case of severe hemorrhagic cystitis. Urotoxicity (bladder ulceration, necrosis, fibrosis, contracture and secondary cancer) may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Urotoxicity can occur with short-term or long-term use of cyclophosphamide.
Before starting treatment, exclude or correct any urinary tract obstructions. Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of urotoxicity and/or nephrotoxicity. Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections. Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity. Mesna has been used to prevent severe bladder toxicity.
Cardiotoxicity
Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy.
Supraventricular arrhythmias (including atrial fibrillation and flutter) and ventricular arrhythmias (including severe QT prolongation associated with ventricular tachyarrhythmia) have been reported after treatment with regimens that included cyclophosphamide.
The risk of cardiotoxicity may be increased with high doses of cyclophosphamide, in patients with advanced age, and in patients with previous radiation treatment to the cardiac region and/or previous or concomitant treatment with other cardiotoxic agents.
Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with pre-existing cardiac disease.
Monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease.
Pulmonary Toxicity
Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with increased mortality. Pneumonitis may develop years after treatment with cyclophosphamide.
Monitor patients for signs and symptoms of pulmonary toxicity.
Secondary Malignancies
Cyclophosphamide is genotoxic. Secondary malignancies (urinary tract cancer, myelodysplasia, acute leukemias, lymphomas, thyroid cancer, and sarcomas) have been reported in patients treated with cyclophosphamide-containing regimens. The risk of bladder cancer may be reduced by prevention of hemorrhagic cystitis.
Veno-occlusive Liver Disease
Veno-occlusive liver disease (VOD) including fatal outcome has been reported in patients receiving cyclophosphamide- containing regimens. A cytoreductive regimen in preparation for bone marrow transplantation that consists of cyclophosphamide in combination with whole-body irradiation, busulfan, or other agents has been identified as a major risk factor. VOD has also been reported to develop gradually in patients receiving long-term low-dose immunosuppressive doses of cyclophosphamide. Other risk factors predisposing to the development of VOD include preexisting disturbances of hepatic function, previous radiation therapy of the abdomen, and a low performance status.
Embryo-Fetal Toxicity
Cyclophosphamide can cause fetal harm when administered to a pregnant woman. Exposure to cyclophosphamide during pregnancy may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn. Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys.
Advise female patients of reproductive potential to avoid becoming pregnant and to use highly effective contraception during treatment and for up to 1 year after completion of therapy.
Infertility
Male and female reproductive function and fertility may be impaired in patients being treated with cyclophosphamide. Cyclophosphamide interferes with oogenesis and spermatogenesis. It may cause sterility in both sexes. Development of sterility appears to depend on the dose of cyclophosphamide, duration of therapy, and the state of gonadal function at the time of treatment. Cyclophosphamide-induced sterility may be irreversible in some patients. Advise patients on the potential risks for infertility [see Use in Specific Populations (8.4 and 8.6)].
Impairment of Wound Healing
Cyclophosphamide may interfere with normal wound healing.
Hyponatremia
Hyponatremia associated with increased total body water, acute water intoxication, and a syndrome resembling SIADH (syndrome of inappropriate secretion of antidiuretic hormone), which may be fatal, has been reported.
The following adverse reactions are discussed in more detail in other sections of the labeling.
Hypersensitivity.
Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections
Urinary Tract and Renal Toxicity
Cardiotoxicity
Pulmonary Toxicity
Secondary Malignancies
Veno-occlusive Liver Disease
Embryo-Fetal Toxicity
Reproductive System Toxicity
Impaired Wound Healing
Hyponatremia
Common Adverse Reactions
Hematopoietic system:
Neutropenia occurs in patients treated with cyclophosphamide. The degree of neutropenia is particularly important because it correlates with a reduction in resistance to infections. Fever without documented infection has been reported in neutropenic patients.
Gastrointestinal system:
Nausea and vomiting occur with cyclophosphamide therapy. Anorexia and, less frequently, abdominal discomfort or pain and diarrhea may occur. There are isolated reports of hemorrhagic colitis, oral mucosal ulceration and jaundice occurring during therapy.
Skin and its structures:
Alopecia occurs in patients treated with cyclophosphamide. Skin rash occurs occasionally in patients receiving the drug. Pigmentation of the skin and changes in nails can occur.
The following adverse reactions have been identified from clinical trials or post-marketing surveillance. Because they are reported from a population from unknown size, precise estimates of frequency cannot be made.
Cardiac: cardiac arrest, ventricular fibrillation, ventricular tachycardia, cardiogenic shock, pericardial effusion (progressing to cardiac tamponade), myocardial hemorrhage, myocardial infarction, cardiac failure (including fatal outcomes), cardiomyopathy, myocarditis, pericarditis, carditis, atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, bradycardia, tachycardia, palpitations, QT prolongation.
Congenital, Familial and Genetic: intrauterine death, fetal malformation, fetal growth retardation, fetal toxicity (including myelosuppression, gastroenteritis).
Ear and Labyrinth: deafness, hearing impaired, tinnitus.
Endocrine: water intoxication.
Eye: visual impairment, conjunctivitis, lacrimation.
Gastrointestinal: gastrointestinal hemorrhage, acute pancreatitis, colitis, enteritis, cecitis, stomatitis, constipation, parotid gland inflammation.
General Disorders and Administrative Site Conditions: multiorgan failure, general physical deterioration, influenza-like illness, injection/infusion site reactions (thrombosis, necrosis, phlebitis, inflammation, pain, swelling, erythema), pyrexia, edema, chest pain, mucosal inflammation, asthenia, pain, chills, fatigue, malaise, headache.
Hematologic: myelosuppression, bone marrow failure, disseminated intravascular coagulation and hemolytic uremic syndrome (with thrombotic microangiopathy).
Hepatic: veno-occlusive liver disease, cholestatic hepatitis, cytolytic hepatitis, hepatitis, cholestasis; hepatotoxicity with hepatic failure, hepatic encephalopathy, ascites, hepatomegaly, blood bilirubin increased, hepatic function abnormal, hepatic enzymes increased.
Immune: immunosuppression, anaphylactic shock and hypersensitivity reaction.
Infections: The following manifestations have been associated with myelosuppression and immunosuppression caused by cyclophosphamide: increased risk for and severity of pneumonias (including fatal outcomes), other bacterial, fungal, viral, protozoal and, parasitic infections; reactivation of latent infections, (including viral hepatitis, tuberculosis), Pneumocystis jiroveci, herpes zoster, Strongyloides, sepsis and septic shock.
Investigations: blood lactate dehydrogenase increased, C-reactive protein increased.
Metabolism and Nutrition: hyponatremia, fluid retention, blood glucose increased, blood glucose decreased.
Musculoskeletal and Connective Tissue: rhabdomyolysis, scleroderma, muscle spasms, myalgia, arthralgia.
Neoplasms: acute leukemia, myelodysplastic syndrome, lymphoma, sarcomas, renal cell carcinoma, renal pelvis cancer, bladder cancer, ureteric cancer, thyroid cancer.
Nervous System: encephalopathy, convulsion, dizziness, neurotoxicity has been reported and manifested as reversible posterior leukoencephalopathy syndrome, myelopathy, peripheral neuropathy, polyneuropathy, neuralgia, dysesthesia, hypoesthesia, paresthesia, tremor, dysgeusia, hypogeusia, parosmia.
Pregnancy: premature labor.
Psychiatric: confusional state.
Renal and Urinary: renal failure, renal tubular disorder, renal impairment, nephropathy toxic, hemorrhagic cystitis, bladder necrosis, ulcerative cystitis, bladder contracture, hematuria, nephrogenic diabetes insipidus, atypical urinary bladder epithelial cells.
Reproductive System: infertility, ovarian failure, ovarian disorder, amenorrhea, oligomenorrhea, testicular atrophy, azoospermia, oligospermia.
Respiratory: pulmonary veno-occlusive disease, acute respiratory distress syndrome, interstitial lung disease as manifested by respiratory failure (including fatal outcomes), obliterative bronchiolitis, organizing pneumonia, alveolitis allergic, pneumonitis, pulmonary hemorrhage; respiratory distress, pulmonary hypertension, pulmonary edema, pleural effusion, bronchospasm, dyspnea, hypoxia, cough, nasal congestion, nasal discomfort, oropharyngeal pain, rhinorrhea.
Skin and Subcutaneous Tissue: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, palmar-plantar erythrodysesthesia syndrome, radiation recall dermatitis, toxic skin eruption, urticaria, dermatitis, blister, pruritus, erythema, nail disorder, facial swelling, hyperhidrosis.
Tumor lysis syndrome: like other cytotoxic drugs, cyclophosphamide may induce tumor-lysis syndrome and hyperuricemia in patients with rapidly growing tumors.
Vascular: pulmonary embolism, venous thrombosis, vasculitis, peripheral ischemia, hypertension, hypotension, flushing, hot flush.
Cyclophosphamide is a pro-drug that is activated by cytochrome P450s.
An increase of the concentration of cytotoxic metabolites may occur with:
Protease inhibitors: Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. Use of protease inhibitor-based regimens was found to be associated with a higher incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regimen.
Combined or sequential use of cyclophosphamide and other agents with similar toxicities can potentiate toxicities.
Increased hematotoxicity and/or immunosuppression may result from a combined effect of cyclophosphamide and, for example:
ACE inhibitors: ACE inhibitors can cause leukopenia.
Natalizumab
Paclitaxel: Increased hematotoxicity has been reported when cyclophosphamide was administered after paclitaxel infusion.
Thiazide diuretics
Zidovudine
Increased cardiotoxicity may result from a combined effect of cyclophosphamide and, for example:
Anthracyclines
Cytarabine
Pentostatin
Radiation therapy of the cardiac region
Trastuzumab
Increased pulmonary toxicity may result from a combined effect of cyclophosphamide and, for example:
Amiodarone
G-CSF, GM-CSF (granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor): Reports suggest an increased risk of :*pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF or GMCSF.
Increased nephrotoxicity may result from a combined effect of cyclophosphamide and, for example:
Amphotericin B
Indomethacin: Acute water intoxication has been reported with concomitant use of indomethacin
Increase in other toxicities:
Azathioprine: Increased risk of hepatotoxicity (liver necrosis)
Busulfan: Increased incidence of hepatic veno-occlusive disease and mucositis has been reported.
Protease inhibitors: Increased incidence of mucositis
Increased risk of hemorrhagic cystitis may result from a combined effect of cyclophosphamide and past or concomitant radiation treatment.
Etanercept: In patients with Wegener's granulomatosis, the addition of etanercept to standard treatment, including cyclophosphamide, was associated with a higher incidence of non-cutaneous malignant solid tumors.
Metronidazole: Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Causal association is unclear. In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity.
Tamoxifen: Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications.
Coumarins: Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide.
Cyclosporine: Lower serum concentrations of cyclosporine have been observed in patients receiving a combination of cyclophosphamide and cyclosporine than in patients receiving only cyclosporine. This interaction may result in an increased incidence of graft-versus-host disease.
Depolarizing muscle relaxants: Cyclophosphamide treatment causes a marked and persistent inhibition of cholinesterase activity. Prolonged apnea may occur with concurrent depolarizing muscle relaxants (e.g., succinylcholine). If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, alert the anesthesiologist.
Pregnancy Category (FDA): D
Pregnancy Category D
Risk Summary
Cyclophosphamide can cause fetal harm when administered to a pregnant woman based on its mechanism of action and published reports of effects in pregnant patients or animals. Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn. Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus.
Human Data
Malformations of the skeleton, palate, limbs and eyes as well as miscarriage have been reported after exposure to cyclophosphamide in the first trimester. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide.
Animal Data
Administration of cyclophosphamide to pregnant mice, rats, rabbits and monkeys during the period of organogenesis at doses at or below the dose in patients based on body surface area resulted in various malformations, which included neural tube defects, limb and digit defects and other skeletal anomalies, cleft lip and palate, and reduced skeletal ossification.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cyclophosphamide in women who are pregnant.
There is no FDA guidance on use of Cyclophosphamide during labor and delivery.
Cyclophosphamide is present in breast milk. Neutropenia, thrombocytopenia, low hemoglobin, and diarrhea have been reported in infants breast fed by women treated with cyclophosphamide. Because of the potential for serious adverse reactions in nursing infants from cyclophosphamide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pre-pubescent girls treated with cyclophosphamide generally develop secondary sexual characteristics normally and have regular menses. Ovarian fibrosis with apparently complete loss of germ cells after prolonged cyclophosphamide treatment in late pre-pubescence has been reported. Girls treated with cyclophosphamide who have retained ovarian function after completing treatment are at increased risk of developing premature menopause.
Pre-pubescent boys treated with cyclophosphamide develop secondary sexual characteristics normally, but may have oligospermia or azoospermia and increased gonadotropin secretion. Some degree of testicular atrophy may occur.
Cyclophosphamide-induced azoospermia is reversible in some patients, though the reversibility may not occur for several years after cessation of therapy.
There is insufficient data from clinical studies of cyclophosphamide available for patients 65 years of age and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac functioning, and of concomitant disease or other drug therapy.
There is no FDA guidance on the use of Cyclophosphamide with respect to specific gender populations.
There is no FDA guidance on the use of Cyclophosphamide with respect to specific racial populations.
In patients with severe renal impairment, decreased renal excretion may result in increased plasma levels of cyclophosphamide and its metabolites. This may result in increased toxicity. Monitor patients with severe renal impairment (CrCl =10 mL/min to 24 mL/min) for signs and symptoms of toxicity.
Cyclophosphamide and its metabolites are dialyzable although there are probably quantitative differences depending upon the dialysis system being used. In patients requiring dialysis, use of a consistent interval between cyclophosphamide administration and dialysis should be considered.
Patients with severe hepatic impairment have reduced conversion of cyclophosphamide to the active 4-hydroxyl metabolite, potentially reducing efficacy.
Contraception
Pregnancy should be avoided during treatment with cyclophosphamide because of the risk of fetal harm.
Female patients of reproductive potential should use highly effective contraception during and for up to 1 year after completion of treatment.
Male patients who are sexually active with female partners who are or may become pregnant should use a condom during and for at least 4 months after treatment.
Infertility
Females
Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide. Affected patients generally resume regular menses within a few months after cessation of therapy. The risk of premature menopause with cyclophosphamide increases with age. Oligomenorrhea has also been reported in association with cyclophosphamide treatment.
Animal data suggest an increased risk of failed pregnancy and malformations may persist after discontinuation of cyclophosphamide as long as oocytes/follicles exist that were exposed to cyclophosphamide during any of their maturation phases. The exact duration of follicular development in humans is not known, but may be longer than 12 months.
Males
Men treated with cyclophosphamide may develop oligospermia or azoospermia which are normally associated with increased gonadotropin but normal testosterone secretion.
There is no FDA guidance one the use of Cyclophosphamide in patients who are immunocompromised.
During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide should be administered in the morning.
Dosing for Malignant Diseases
Adults and Pediatric Patients
Intravenous
When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.
Oral
Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.
Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/ or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.
When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide as well as that of the other drugs.
Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients
An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males.
Preparation, Handling and Administration
Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing Cyclophosphamide for Injection, USP. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide for Injection, USP.
Cyclophosphamide for Injection, USP
Intravenous Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide vials if there are signs of melting. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.
Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.
For Direct Intravenous Injection
Reconstitute Cyclophosphamide with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.
For Intravenous Infusion
Reconstitution of Cyclophosphamide:
Reconstitute Cyclophosphamide using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.
Dilution of Reconstituted Cyclophosphamide:
Further dilute the reconstituted Cyclophosphamide solution to a minimum concentration of 2 mg per mL with any of the following diluents:
5% Dextrose Injection, USP
5% Dextrose and 0.9% Sodium Chloride Injection, USP
0.45% Sodium Chloride Injection, USP
To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.
Storage of Reconstituted and Diluted Cyclophosphamide Solution:
If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 3.
Use of Reconstituted Solution for Oral Administration
Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.
Cyclophosphamide for Injection, USP is a sterile white powder available in
500 mg
1 g
2 g
There is limited information regarding Monitoring of Cyclophosphamide in the drug label.
Description
There is limited information regarding IV Compatibility of Cyclophosphamide in the drug label.
No specific antidote for cyclophosphamide is known.
Overdosage should be managed with supportive measures, including appropriate treatment for any concurrent infection, myelosuppression, or cardiac toxicity should it occur.
Serious consequences of overdosage include manifestations of dose dependent toxicities such as myelosuppression, urotoxicity, cardiotoxicity (including cardiac failure), veno-occlusive hepatic disease, and stomatitis.
Patients who received an overdose should be closely monitored for the development of toxicities, and hematologic toxicity in particular.
Cyclophosphamide and its metabolites are dialyzable. Therefore, rapid hemodialysis is indicated when treating any suicidal or accidental overdose or intoxication.
Cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects with cyclophosphamide overdose.
The mechanism of action is thought to involve cross-linking of tumor cell DNA.
Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. The chemical name for cyclophosphamide is 2-[bis(2-chloroethyl)amino] tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, and has the following structural formula:
Cyclophosphamide is a white crystalline powder with the molecular formula C7H15Cl2N2O2P•H2O and a molecular weight of 279.1. Cyclophosphamide is soluble in water, saline, or ethanol.
Cyclophosphamide for Injection, USP is for intravenous or oral use, it has no inactive ingredients. When reconstituted in water Cyclophosphamide for Injection, USP has a pH range of 3.0 to 9.0.
Cyclophosphamide for Injection, USP is a sterile white powder available as 500 mg, 1 g, and 2 g strength vials.
500 mg vial contains 534.5 mg cyclophosphamide monohydrate equivalent to 500 mg cyclophosphamide
1 g vial contains 1069.0 mg cyclophosphamide monohydrate equivalent to 1 g cyclophosphamide
2 g vial contains 2138.0 mg cyclophosphamide monohydrate equivalent to 2 g cyclophosphamide
Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells.
Following IV administration, elimination half-life (t1/2) ranges from 3 to 12 hours with total body clearance (CL) values of 4 to 5.6 L/h. Pharmacokinetics are linear over the dose range used clinically. When cyclophosphamide was administered at 4.0 g/m2 over a 90 minutes infusion, saturable elimination in parallel with first-order renal elimination describe the kinetics of the drug.
Absorption
After oral administration, peak concentrations of cyclophosphamide occurred at one hour. Area under the curve ratio for the drug after oral and IV administration (AUCpo : AUCiv) ranged from 0.87 to 0.96.
Distribution
Approximately 20% of cyclophosphamide is protein bound, with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%. Volume of distribution approximates total body water (30 to 50 L).
Metabolism
The liver is the major site of cyclophosphamide activation. Approximately 75% of the administered dose of cyclophosphamide is activated by hepatic microsomal cytochrome P450s including CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18 and 2C19, with 2B6 displaying the highest 4-hydroxylase activity. Cyclophosphamide is activated to form 4-hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. 4-hydroxycyclophosphamide and aldophosphamide can undergo oxidation by aldehyde dehydrogenases to form the inactive metabolites 4-ketocyclophosphamide and carboxyphosphamide, respectively. Aldophosphamide can undergo B-elimination to form active metabolites phosphoramide mustard and acrolein. This spontaneous conversion can be catalyzed by albumin and other proteins.
Less than 5% of cyclophosphamide may be directly detoxified by side chain oxidation, leading to the formation of inactive metabolites 2-dechloroethylcyclophosphamide. At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced resulting in non-linear elimination of cyclophosphamide in patients. Cyclophosphamide appears to induce its own metabolism. Auto-induction results in an increase in the total clearance, increased formation of 4-hydroxyl metabolites and shortened t1/2 values following repeated administration at 12- to 24-hour interval.
Elimination
Cyclophosphamide is primarily excreted as metabolites. 10 to 20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration.
Special Populations
Renal Impairment
The pharmacokinetics of cyclophosphamide were determined following one-hour intravenous infusion to renally impaired patients. The results demonstrated that the systemic exposure to cyclophosphamide increased as the renal function decreased. Mean dose-corrected AUC increased by 38% in the moderate renal group,(Creatinine clearance (CrCl of 25 to 50 mL/min), by 64% in the severe renal group (CrCl of 10 to 24 mL/min) and by 23% in the hemodialysis group (CrCl of <10 mL/min) compared to the control group. The increase in exposure was significant in the severe group (p>0.05); thus, patients with severe renal impairment should be closely monitored for toxicity [see Use in Specific Populations (8.7)].
The dialyzability of cyclophosphamide was investigated in four patients on long-term hemodialysis. Dialysis clearance calculated by arterial-venous difference and actual drug recovery in dialysate averaged 104 mL/min, which is in the range of the metabolic clearance of 95 mL/min for the drug. A mean of 37% of the administered dose of cyclophosphamide was removed during hemodialysis. The elimination half-life (t1/2) was 3.3 hours in patients during hemodialysis, a 49% reduction of the 6.5 hours to t1/2 reported in uremic patients. Reduction in t1/2, larger dialysis clearance than metabolic clearance, high extraction efficiency, and significant drug removal during dialysis, suggest that cyclophosphamide is dialyzable.
Hepatic Impairment
Total body clearance (CL) of cyclophosphamide is decreased by 40% in patients with severe hepatic impairment and elimination half-life (t1/2) is prolonged by 64%. Mean CL and t1/2 were 45 ± 8.6 L/kg and 12.5 ± 1.0 hours respectively, in patients with severe hepatic impairment and 63 ± 7.6 L/kg and 7.6 ± 1.4 hours respectively in the control group.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Cyclophosphamide administered by different routes, including intravenous, subcutaneous or intraperitoneal injection, or in drinking water, caused tumors in both mice and rats. In addition to leukemia and lymphoma, benign and malignant tumors were found at various tissue sites, including urinary bladder, mammary gland, lung, liver, and injection site.
Cyclophosphamide was mutagenic and clastogenic in multiple in vitro and in vivo genetic toxicology studies.
Cyclophosphamide is genotoxic in male and female germ cells. Animal data indicate that exposure of oocytes to cyclophosphamide during follicular development may result in a decreased rate of implantations and viable pregnancies, and in an increased risk of malformations. Male mice and rats treated with cyclophosphamide show alterations in male reproductive organs (e.g., decreased weights, atrophy, changes in spermatogenesis), and decreases in reproductive potential (e.g., decreased implantations and increased post-implantation loss) and increases in fetal malformations when mated with untreated females.
There is limited information regarding Clinical Studies of Cyclophosphamide in the drug label.
Cyclophosphamide for Injection, USP is a sterile white powder containing cyclophosphamide and is supplied in vials for single dose use.
Cyclophosphamide for Injection, USP
NDC 0781-3233-94- 500 mg vial, carton of 1
NDC 0781-3244-94- 1 g vial, carton of 1
NDC 0781-3255-94- 2 g vial, carton of 1
Store vials at or below 25°C (77°F). During transport or storage of cyclophosphamide vials, temperature influences can lead to melting of the active ingredient, cyclophosphamide.
Cyclophosphamide is an antineoplastic product. Follow special handling and disposal procedures.
{{#ask: Page Name::Cyclophosphamide
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Cyclophosphamide
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
Advise the patient of the following:
Inform patients of the possibility of myelosuppression, immunosuppression, and infections. Explain the need for routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever.
Advise the patient to report urinary symptoms (patients should report if their urine has turned a pink or red color) and the need for increasing fluid intake and frequent voiding.
Advise patients to contact a healthcare professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness.
Warn patients of the possibility of developing non-infectious pneumonitis. Advise patients to report promptly any new or worsening respiratory symptoms.
Advise female patients of reproductive potential to use highly effective contraception during treatment and for up to 1year after completion of therapy. There is a potential for harm to a fetus if a patient becomes pregnant during this period. Patients should immediately contact their healthcare provider if they become pregnant or if pregnancy is suspected during this period.
Advise male patients who are sexually active with a female partner who is or may become pregnant to use condoms during treatment and for up to 4 months after completion of therapy. There is a potential for harm to a fetus if a patient fathers a child during this period. Patients should immediately contact their healthcare provider if their female partner becomes pregnant or if pregnancy is suspected during this period.
Advise nursing mothers treated with cyclophosphamide to discontinue nursing or discontinue cyclophosphamide, taking into account the importance of the drug to the mother.
Explain to patients that side effects such as nausea, vomiting, stomatitis, impaired wound healing, amenorrhea, premature menopause, sterility and hair loss may be associated with cyclophosphamide administration. Other undesirable effects (including, e.g., dizziness, blurred vision, visual impairment) could affect the ability to drive or use machines.
Alcohol-Cyclophosphamide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Cytoxan
Cytoxan Lyophilized
There is limited information regarding Cyclophosphamide Look-Alike Drug Names in the drug label.
|
AST | Aspartate transaminase (AST) also called serum glutamic oxaloacetic transaminase (SGOT) or aspartate aminotransferase (ASAT/AAT) (EC 2.6.1.1) is similar to alanine transaminase (ALT) in that it is another enzyme associated with liver parenchymal cells.
It facilitates the conversion of aspartate and alpha-ketoglutarate to oxaloacetate and glutamate.
Two isoenzymes are present in humans. They have high similarity.
GOT1, the cytosolic isoenzyme derives mainly from red blood cells and heart.
GOT2, the mitochondrial isoenzyme is predominantly present in liver.
It is raised in acute liver damage. It is also present in red blood cells and cardiac muscle.
AST was defined as a biochemical marker for the diagnosis of acute myocardial infarction in 1954. However the use of AST for such a diagnosis is now redundant and has been superseded by the cardiac troponins.
AST / ALT is commonly measured clinically as a part of a diagnostic liver function test, to determine liver health. This is because of hepatic deficiency of pyrodoxal-6-phosphate in alcoholics, which is a cofactor for the enzymatic activity of ALT., Amoxicillin, Anidulafungin, Artemether and lumefantrin, Asparaginase Erwinia Chrysanthemi, Asenapine maleate, Axitinib, Aztreonam, Bicalutamide, Cefadroxil, Cefepime, Cefotaxime sodium, Cefprozil, Ceftazidime, Cladribine, Crizotinib, Desmopressin, Doxorubicin Hydrochloride, Idelalisib, Indinavir, Interferon gamma, Ivacaftor, Lamivudine, Lincomycin Hydrochloride, Meropenem, Niacin, Pralidoxime, Ritonavir, Ruxolitinib, Streptozocin, Vedolizumab
Epstein-Barr Virus
Fatty liver
Hepatic tumor
Hypothyroid myopathy
Infliximab |
Hyperfocus | Hyperfocus is an intense form of mental concentration or visualization that focuses consciousness on a narrow subject, or beyond objective reality and onto subjective mental planes, daydreams, concepts, fiction, the imagination, and other objects of the mind.
From a neurodiversity perspective, hyperfocus is a mental ability that is a natural expression of personality. However, hyperfocus can also be regarded as a psychiatric diagnosis, as a distraction from reality and a symptom of attention deficit hyperactivity disorder (ADHD), adult attention-deficit disorder (AADD), or autistic spectrum disorders.
Some people say that hyperfocus is an important element of meditation. In common parlance, hyperfocus is sometimes referred to as "zoning out." In sports, it is sometimes referred to as "being in the zone".
The term hyperfocus is not in common use among academics, and seldom appears in peer-reviewed articles. However, related terms such as concentration, absorption and 'focused attention' are widely used.
A positive aspect of hyperfocus might be the ability to use detachment from ordinary mentality to create new approaches to familiar situations. It may also improve learning speed and comprehension.
On the other hand, it sometimes presents a challenge to common teaching and parenting techniques. Schools and parents generally expect obedience from children and reward them for it, but hyperfocused children do not always cooperate under these circumstances. This can be overcome with investments of time and effort by the teacher or parent, but it is not always possible to spend a lot of time focusing on one child in a typical classroom situation.
Psychiatry describes only the distraction aspect of hyperfocus, referring to ADHD as 'inattentiveness and impulsiveness'. Hyperfocus is not recognised by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), and no article using the term appears in PubMed.
Besides hyperfocus, various special abilities have been suggested to occur in ADHD, including vigilance, response-readiness, enthusiasm, and flexibility. But current ADHD research does not recognize these characteristics. Greater creativity has also been suggested, but formal measures of this are no higher in children with ADHD than in control groups.
Nevertheless, psychiatric research suggests that there are several reasons for the persistence of the notion that people with ADHD have the ability to hyperfocus, such as the well-recognised comorbidity of ADHD with autistic spectrum disorders, of which excessive focus is a part. Special abilities do occur in some ADHD people, so it is easy to generalize from this minority to the whole ADHD group. ADHD is sometimes regarded as a disorder that is remarkably common (affecting 4-8% of school age children), but primarily genetically determined.
Professional psychiatry does not completely discount the existence of hyperfocus, as many adults with ADHD attribute accomplishments in their lives to this mental ability. As ADHD in adults is a relatively new area of learning in comparison with the condition in children, many clinicians feel that hyperfocus is an aspect of adult ADHD which is not well understood and merits more thorough research.
hunter vs. farmer theory
Flow (psychology)
A Deepness in the Sky (a science fiction novel) explores a society in which artificially-hyperfocused individuals are used as biological appliances |
Altitude_sickness_physical_examination | Patients with altitude sickness usually appear cyanotic.
Hypothermia may be present
Tachycardia
Tachypnea
High/low blood pressure with normal pulse pressure / wide pulse pressure / narrow pulse pressure
Pale or bluish appearance
Visual impairment
Neck examination of patients with altitude sickness is usually normal.
Crackles or wheezing may be present
Cardiovascular examination of patients with altitude sickness is usually normal.
Abdominal examination of patients with altitude sickness is usually normal.
Back examination of patients with altitude sickness is usually normal.
Genitourinary examination of patients with altitude sickness is usually normal.
Altered mental status may be present
Loss of coordination
Cyanosis may be present |
Kawasaki_disease_natural_history,_complications_and_prognosis | Common complications of Kawasaki disease include vasculitis and coronary artery aneurysms. Prognosis is generally excellent and the mortality rate of patients with Kawasaki disease is approximately 2%.
If left untreated, the symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction.
If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short.
Patients with Kawasaki disease may progress to develop long term cardiovascular illness such as coronary artery disease, and pre-mature atherosclerosis.
The cardiac complications are, by far, the most important aspect of Kawasaki disease: Vasculitic changes in the coronary arteries, Coronary artery aneurysms, These aneurysms can lead to myocardial infarction even in young children. Other complications associated with Kawasaki disease are:
With early treatment, rapid recovery from the acute symptoms can be expected and the risk of coronary artery aneurysms greatly reduced.
Untreated, the acute symptoms of Kawasaki disease are self-limited, but the risk of coronary artery involvement is much greater.
Patients who have had Kawasaki disease should have an echocardiogram initially every few weeks, and then every 1 - 2 years to screen for the progression of cardiac involvement.
Overall, about 2% of the patients die from complications of coronary vasculitis.
It is also not uncommon that a relapse of symptoms may occur soon after initial treatment with IVIG. This usually requires re-hospitalization and retreatment. Treatment with IVIG can cause allergic and non-allergic acute reactions, aseptic meningitis, fluid overload and rarely other serious reactions. Aspirin may increase the risk of bleeding from other causes and may be associated with Reye's syndrome. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of non-treatment. |
Chordae_tendineae_rupture | History and Symptoms | Physical Examination | Chest X Ray | Echocardiography
Medical Therapy | Surgery
vteCardiovascular disease (heart)IschaemicCoronary disease
Coronary artery disease (CAD)
Coronary artery aneurysm
Spontaneous coronary artery dissection (SCAD)
Coronary thrombosis
Coronary vasospasm
Myocardial bridge
Active ischemia
Angina pectoris
Prinzmetal's angina
Stable angina
Acute coronary syndrome
Myocardial infarction
Unstable angina
Sequelae
hours
Hibernating myocardium
Myocardial stunning
days
Myocardial rupture
weeks
Aneurysm of heart / Ventricular aneurysm
Dressler syndrome
LayersPericardium
Pericarditis
Acute
Chronic / Constrictive
Pericardial effusion
Cardiac tamponade
Hemopericardium
Myocardium
Myocarditis
Chagas disease
Cardiomyopathy
Dilated
Alcoholic
Hypertrophic
Tachycardia-induced
Restrictive
Loeffler endocarditis
Cardiac amyloidosis
Endocardial fibroelastosis
Arrhythmogenic right ventricular dysplasia
Endocardium / valvesEndocarditis
infective endocarditis
Subacute bacterial endocarditis
non-infective endocarditis
Libman–Sacks endocarditis
Nonbacterial thrombotic endocarditis
Valves
mitral
regurgitation
prolapse
stenosis
aortic
stenosis
insufficiency
tricuspid
stenosis
insufficiency
pulmonary
stenosis
insufficiency
Conduction / arrhythmiaBradycardia
Sinus bradycardia
Sick sinus syndrome
Heart block: Sinoatrial
AV
1°
2°
3°
Intraventricular
Bundle branch block
Right
Left
Left anterior fascicle
Left posterior fascicle
Bifascicular
Trifascicular
Adams–Stokes syndrome
Tachycardia (paroxysmal and sinus)Supraventricular
Atrial
Multifocal
Junctional
AV nodal reentrant
Junctional ectopic
Ventricular
Accelerated idioventricular rhythm
Catecholaminergic polymorphic
Torsades de pointes
Premature contraction
Atrial
Junctional
Ventricular
Pre-excitation syndrome
Lown–Ganong–Levine
Wolff–Parkinson–White
Flutter / fibrillation
Atrial flutter
Ventricular flutter
Atrial fibrillation
Familial
Ventricular fibrillation
Pacemaker
Ectopic pacemaker / Ectopic beat
Multifocal atrial tachycardia
Pacemaker syndrome
Parasystole
Wandering atrial pacemaker
Long QT syndrome
Andersen–Tawil
Jervell and Lange-Nielsen
Romano–Ward
Cardiac arrest
Sudden cardiac death
Asystole
Pulseless electrical activity
Sinoatrial arrest
Other / ungrouped
hexaxial reference system
Right axis deviation
Left axis deviation
QT
Short QT syndrome
T
T wave alternans
ST
Osborn wave
ST elevation
ST depression
Strain pattern
Cardiomegaly
Ventricular hypertrophy
Left
Right / Cor pulmonale
Atrial enlargement
Left
Right
Athletic heart syndrome
Other
Cardiac fibrosis
Heart failure
Diastolic heart failure
Cardiac asthma
Rheumatic fever
Template:WikiDoc Sources
|
Ebstein%27s_anomaly_of_the_tricuspid_valve_differential_diagnosis | Disorders that Ebstein's anomaly must be distinguished from include:
Accessory pathway-mediated WPW syndrome and SVT
Atrial septal defect (ASD)
Cyanotic congenital heart diseases
Isolated, severe tricuspid regurgitation
L-transposition of the great vessels
Severe right heart failure with dilation of the anulus
Ebstein's anomaly should be differentiated from other cynotic diseases and others
|
Gastrointestinal_perforation_screening | There is insufficient evidence to recommend routine screening for gastrointestinal perforation
There is insufficient evidence to recommend routine screening for gastrointestinal perforation |
Congenital_chloride_diarrhea | Congenital chloride diarrhea (CCD, also congenital chloridorrhea) is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins. More than 20 mutations in the gene are known to date. A rare disease, CCD occurs in all parts of the world but is more common in some populations with genetic founder effects, most notably in Finland.
CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.
CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.
An important feature in this diarrhea that helps in the diagnosis, is that its the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.
Available treatments address the symptoms of CCD, not the underlying defect. Early diagnosis and aggressive salt replacement therapy result in normal growth and development, and generally good outcomes. Replacement of NaCl and KCl has been shown to be effective in children.
A potential treatment is butyrate.
Observations leading to the characterization of the SLC26 family were based on research on rare human diseases. Three rare recessive diseases in humans have been shown to be caused by genes of this family. Diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome are caused by the highly related genes SLC26A2 (first called DTDST), SLC26A3 (first called CLD or DRA), and SLC26A4 (first called PDS), respectively. Two of these diseases, diastrophic dysplasia and congenital chloride diarrhea, are Finnish heritage diseases.
|
Verapamil_hydrochloride_tablet_nonclinical_toxicology | Verapamil is a calcium channel blocker that is FDA approved for the treatment of essential hypertension (tablet and capsule)
rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias
and temporary control of rapid ventricular rate in atrial flutter or atrial fibrillation (injection)
Common adverse reactions include edema
The dose of verapamil HCl extended-release should be individualized by titration and the drug should be administered with food
180 mg in the morning
120 mg PO qd may be warranted in patients who may have an increased response to verapamil (e
the elderly or small people etc
Upward titration should be based on therapeutic efficacy and safety evaluated weekly and approximately 24 hours after the previous dose
The antihypertensive effects of verapamil HCl extended-release are evident within the first week of therapy
If adequate response is not obtained with 180 mg of verapamil HCl extended-release
the dose may be titrated upward in the following manner
180 mg each morning plus 180 mg each evening
or 240 mg each morning plus 120 mg each evening
240 mg every twelve hours
When switching from immediate release verapamil to extended-release verapamil
the total daily dose in milligrams may remain the same
Administer Verapamil Hydrochloride Extended-release Capsules (PM) once daily at bedtime
200 mg PO qd at bedtime
In rare instances
initial doses of 100 mg PO qd may be warranted in patients who have an increased response to verapamil [e
patients with impaired renal function
Base upward titration on therapeutic efficacy and safety evaluated approximately 24 hours after dosing
The antihypertensive effects of Verapamil Hydrochloride Extended-release Capsules (PM) are evident within the first week of therapy
If an adequate response is not obtained with 200 mg of Verapamil Hydrochloride Extended-release Capsules (PM)
the dose may be titrated upward in the following manner
a) 300 mg each evening
b) 400 mg each evening (2 × 200 mg)
When Verapamil Hydrochloride Extended-release Capsules (PM) is administered at bedtime
office evaluation of blood pressure during morning and early afternoon hours is essentially a measure of peak effect
The usual evaluation of trough effect
which sometimes might be needed to evaluate the appropriateness of any given dose of Verapamil Hydrochloride Extended-release Capsules (PM)
would be just prior to bedtime
THE CONTENTS OF THE Verapamil Hydrochloride Extended-release Capsules (PM) CAPSULE SHOULD NOT BE CRUSHED OR CHEWED
Verapamil Hydrochloride Extended-release Capsules (PM) ARE TO BE SWALLOWED WHOLE OR THE ENTIRE CONTENTS OF THE CAPSULE SPRINKLED ONTO APPLESAUCE
Sprinkling the Capsule Contents on Food
Verapamil Hydrochloride Extended-release Capsules (PM) capsules may also be administered by carefully opening the capsule and sprinkling the pellets onto one tablespoonful of applesauce
Swallow the applesauce immediately without chewing and follow with a glass of cool water to ensure complete swallowing of the pellets
The applesauce used should not be hot and it should be soft enough to be swallowed without chewing
Use any pellet/applesauce mixture immediately and do not store for future use
Absorption of the pellets sprinkled onto other foods has not been tested
This method of administration may be beneficial for patients who have difficulty swallowing whole capsules
Subdividing the contents of a Verapamil Hydrochloride Extended-release Capsules (PM) capsule is not recommended
Rapid conversion to sinus rhythm of Paroxysmal supraventricular tachycardia
including those associated with accessory bypass tracts (Wolff-Parkinson-White [W-P-W] and Lown-Ganong- Levine [L-G-L] syndromes)
Valsalva maneuver) should be attempted prior to verapamil hydrochloride administration
Temporary control of rapid ventricular rate in atrial flutter or atrial fibrillation except when the atrial flutter and/or atrial fibrillation are associated with accessory bypass tracts (Wolff-Parkinson-White (W-P-W) and Lown-Ganong-Levine (L-G-L) syndromes)
In controlled studies in the United States
about 60% of patients with supraventricular tachycardia converted to normal sinus rhythm within 10 minutes after intravenous verapamil hydrochloride
Uncontrolled studies reported in the world literature describe a conversion rate of about 80%
About 70% of patients with atrial flutter and/or fibrillation with a faster ventricular rate respond with a decrease in ventricular rate of at least 20%
Conversion of atrial flutter or fibrillation to sinus rhythm is uncommon (about 10%) after verapamil hydrochloride and may reflect the spontaneous conversion rate
since the conversion rate after placebo was similar
Slowing of the ventricular rate in patients with atrial fibrillation/flutter lasts 30 to 60 minutes after a single injection
Because a small fraction (<1%) of patients treated with verapamil hydrochloride respond with life-threatening adverse responses (rapid ventricular rate in atrial flutter/fibrillation
and an accessory bypass tract
the initial use of verapamil hydrochloride injection should
be in a treatment setting with monitoring and resuscitation facilities
As familiarity with the patient’s response is gained
use in an office setting may be acceptable
Cardioversion has been used safely and effectively after verapamil hydrochloride injection
5 to 10 mg (0
15 mg/kg body weight) given as an intravenous bolus over at least 2 minutes
15 mg/kg body weight) 30 minutes after the first dose if the initial response is not adequate
An optimal interval for subsequent I
doses has not been determined
and should be individualized for each patient
Older patients − The dose should be administered over at least 3 minutes to minimize the risk of untoward drug effects
American College of Cardiology Foundation (ACCF) and American Heart Association (AHA)
120 mg PO tid
240 mg PO bid
120 to 1200 mg/day
120 mg bid
120 mg/day
120 mg tid
120 mg PO at bedtime
60 mg tid
80 mg tid
240 mg/day
5 mg over 25 minutes
5 mg IV
2 mg/kg body weight (usual single dose range
75 to 2 mg) should be administered as an intravenous bolus over at least 2 minutes under continuous ECG monitoring
3 mg/kg body weight (usual single dose range
2 to 5 mg) should be administered as an intravenous bolus over at least 2 minutes
Do not exceed 5 mg
2 mg/kg body weight (usual single dose range
75 to 2 mg) 30 minutes after the first dose if the initial response is not adequate (under continuous ECG monitoring)
An optimal interval for subsequent I
doses has not been determined
and should be individualized for each patient
3 mg/kg body weight (usual single dose range
2 to 5 mg) 30 minutes after the first dose if the initial response is not adequate
Do not exceed 10 mg as a single dose
An optimal interval for subsequent I
doses has not been determined
and should be individualized for each patient
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration
whenever solution and container permit
Use only if solution is clear and vial seal is intact
Unused amount of solution should be discarded immediately following withdrawal of any portion of contents
For stability reasons this product is not recommended for dilution with Sodium Lactate Injection
USP in polyvinyl chloride bags
Verapamil is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions
Admixing verapamil hydrochloride injection with albumin
hydralazine hydrochloride and trimethoprim with sulfamethoxazole should be avoided
Verapamil hydrochloride injection will precipitate in any solution with a pH above 6
There is limited information regarding Off-Label Guideline-Supported Use of Verapamil in pediatric patients
1-Severe left ventricular dysfunction (see WARNINGS)
2-Hypotension (systolic pressure less than 90 mm Hg) or cardiogenic shock
3-Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker)
4-degree AV block or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker)
5-Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (eg
Lown-Ganong-Levine syndrome)
6-Patients with known hypersensitivity to verapamil hydrochloride
Severe congestive heart failure (unless secondary to a supraventricular tachycardia amenable to verapamil therapy)
Administration of intravenous verapamil to patients with wide-complex ventricular tachycardia (QRS ≥ 0
12 sec) can result in marked hemodynamic deterioration and ventricular fibrillation
Proper pretherapy diagnosis and differentiation from wide-complex supraventricular tachycardia is imperative in the emergency room setting
Verapamil has a negative inotropic effect
which in most patients is compensated by its afterloadreduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance
In clinical experience with 4
8%) developed congestive heart failure orpulmonary edema
Verapamil should be avoided in patients with severe left ventricular dysfunction (eg
ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker
Patients with milder ventricular dysfunction should
be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment
the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels
which may result in dizziness or symptomatic hypotension
The incidence of hypotension observed in 4
954 patients enrolled in clinical trials was 2
decreases in blood pressure below normal are unusual
Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported
Such elevations have sometimes been transient and may disappear even with continued verapamil treatment
Several cases of hepatocellular injury related to verapamil have been proven by rechallenge
half of these had clinical symptoms (malaise
and/or right upper quadrant pain)
in addition to elevation of SGOT
Periodic monitoring of liver function in patients receiving verapamil is therefore prudent
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node
producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis)
Although a risk of this occurring with oral verapamil has not been established
such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated
Cardioversion has been used safely and effectively after oral Verapamil
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia
sometimes accompanied by nodal escape rhythms
PR-interval prolongation is correlated with verapamil plasma concentrations especially during the early titration phase of therapy
Higher degrees of AV block
Marked first-degree block or progressive development to second-degree AV blockor third-degree AV block requires a reduction in dosage or
discontinuation of verapamil HCl and institution of appropriate therapy
depending on the clinical situation
In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day
a variety of serious adverse effects were seen
Three patients died in pulmonary edema
all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction
Eight other patients had pulmonary edema and/or severe hypotension
abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients
Concomitant administration of quinidine preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema)
Sinus bradycardia occurred in 11% of the patients
second-degree AV block in 4%
and sinus arrest in 2%
It must be appreciated that this group of patients had a serious disease with a high mortality rate
Most adverse effects responded well to dose reduction
and only rarely did verapamil use have to be discontinued
There is limited information regarding Verapamil Clinical Trials Experience in the drug label
There is limited information regarding Verapamil Postmarketing Experience in the drug label
In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4
Clinically significant interactions have been reported with inhibitors of CYP3A4 (e
ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e
rifampin) have caused a lowering of plasma levels of verapamil
The use of statins that are CYP3A4substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis
Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2
5-fold that following simvastatin alone
Limit the dose of simvastatin in patients on verapamil to 10 mg daily
Limit the daily dose of lovastatin to 40 mg
Lower starting and maintenance doses of other CYP3A4 substrates (e
atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs
In a few reported cases
co-administration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone
Grapefruit juice may increase plasma levels of verapamil
Verapamil may increase blood alcohol concentrations and prolong its effects
Controlled studies in small numbers of patients suggest that the concomitant use of Verapamil and oral beta-adrenergic blocking agents may be beneficial in certain patients with chronic stable angina or hypertension
but available information is not sufficient to predict with confidence the effects of concurrent treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities
Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart rate
atrioventricular conduction and/or cardiac contractility
In one study involving 15 patients treated with high doses of propranolol (median dose
280 mg/day) for severe angina
with preserved left ventricular function (ejection fraction greater than 35%)
the hemodynamic effects of additional therapy with verapamil HCl were assessed using invasive methods
The addition of verapamil to high-dose beta-blockers induced modest negative inotropic and chronotropic effects that were not severe enough to limit short-term (48 hours) combination therapy in this study
These modest cardiodepressant effects persisted for greater than 6 but less than 30 hours after abrupt withdrawal of beta-blockers and were closely related to plasma levels of propranolol
The primary verapamil/beta-blocker interaction in this study appeared to be hemodynamic rather than electrophysiologic
verapamil did not generally induce significant negative inotropic
or dromotropic effects in patients with preserved left ventricular function receiving low or moderate doses of propranolol (less than or equal to 320 mg/day)
combined therapy did produce such effects
if combined therapy is used
close surveillance of clinical status should be carried out
Combined therapy should usually be avoided in patients with atrioventricular conduction abnormalities and those with depressed left ventricular function
Asymptomatic bradycardia (36 beats/min) with a wandering atrial pacemaker has been observed in a patient receiving concomitant timolol (a beta-adrenergic blocker) eyedrops and oral verapamil
A decrease in metoprolol and propranolol clearance has been observed when either drug is administered concomitantly with verapamil
A variable effect has been seen when verapamil and atenolol were given together
Clinical use of verapamil in digitalized patients has shown the combination to be well tolerated if digoxin doses are properly adjusted
chronic verapamil treatment can increase serum digoxin levels by 50% to 75% during the first week of therapy
and this can result in digitalis toxicity
In patients with hepatic cirrhosis
the influence of verapamil on digoxin kinetics is magnified
Verapamil may reduce total body clearance and extrarenal clearance of digitoxin by 27% and 29%
Maintenance and digitalization doses should be reduced when verapamil is administered
and the patient should be reassessed to avoid over- or under-digitalization
the daily dose of digitalis should be reduced or temporarily discontinued
On discontinuation of Verapamil use
the patient should be reassessed to avoid under-digitalization
Verapamil administered concomitantly with oral antihypertensive agents (e
beta-blockers) will usually have an additive effect on lowering blood pressure
Patients receiving these combinations should be appropriately monitored
Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in a reduction in blood pressure that is excessive in some patients
Such an effect was observed in one study following the concomitant administration of verapamil and prazosin
Until data on possible interactions between verapamil and disopyramide are obtained
disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration
A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility
Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction
In a small number of patients with hypertrophic cardiomyopathy (IHSS)
concomitant use of verapamil and quinidine resulted in significant hypotension
Until further data are obtained
combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided
The electrophysiologic effects of quinidine and verapamil on AV conduction were studied in 8 patients
Verapamil significantly counteracted the effects of quinidine on AV conduction
There has been a report of increased quinidine levels during verapamil therapy
Verapamil has been given concomitantly with short- and long-acting nitrates without any undesirable drug interactions
The pharmacologic profile of both drugs and the clinical experience suggest beneficial interactions
The interaction between cimetidine and chronically administered verapamil has not been studied
Variable results on clearance have been obtained in acute studies of healthy volunteers
clearance of verapamil was either reduced or unchanged
Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil-lithium therapy
lithium levels have been observed sometimes to increase
and sometimes to be unchanged
Patients receiving both drugs must be monitored carefully
Verapamil therapy may increase carbamazepine concentrations during combined therapy
This may produce carbamazepine side effects such as diplopia
Therapy with rifampin may markedly reduce oral verapamil bioavailability
Phenobarbital therapy may increase verapamil clearance
Verapamil therapy may increase serum levels of cyclosporine
Verapamil may inhibit the clearance and increase the plasma levels of theophylline
Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward movement of calcium ions
inhalation anesthetics and calcium antagonists
should each be titrated carefully to avoid excessive cardiovascular depression
Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing)
It may be necessary to decrease the dose of verapamil and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly
Hypotension and bradyarrhythmias have been observed in patients receiving concurrent telithromycin
an antibiotic in the ketolide class
Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil
Monitor heart rate in patients receiving concomitant verapamil and clonidine
Reproduction studies have been performed in rabbits and rats at oral doses up to 1
5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose
and have revealed no evidence of teratogenicity
this multiple of the human dose was embryocidal and retarded fetal growth and development
probably because of adverse maternal effects reflected in reduced weight gains of the dams
This oral dose has also been shown to cause hypotension in rats
There are no adequate and well-controlled studies in pregnant women
Because animal reproduction studies are not always predictive of human response
this drug should be used during pregnancy only if clearly needed
Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Verapamil in women who are pregnant
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus
or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention
Such adverse experiences have not been reported in the literature
despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor
Verapamil is excreted in human milk
Because of the potential for adverse reactions in nursing infants from verapamil
nursing should be discontinued while verapamil is administered
Safety and effectiveness in pediatric patients have not been established
There is no FDA guidance on the use of Verapamil in geriatric settings
There is no FDA guidance on the use of Verapamil with respect to specific gender populations
There is no FDA guidance on the use of Verapamil with respect to specific racial populations
About 70% of an administered dose of verapamil is excreted as metabolites in the urine
Verapamil is not removed by hemodialysis
Until further data are available
verapamil should be administered cautiously to patients with impaired renal function
These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage
Since verapamil is highly metabolized by the liver
it should be administered cautiously to patients with impaired hepatic function
Severe liver dysfunction prolongs the elimination half-life of verapamil to about 14 to 16 hours
approximately 30% of the dose given to patients with normal liver function should be administered to these patients
Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects should be carried out
There is no FDA guidance on the use of Verapamil in women of reproductive potentials and males
There is no FDA guidance one the use of Verapamil in patients who are immunocompromised
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy
prolongs recovery from the neuromuscular blocking agent vecuronium
and causes a worsening of myasthenia gravis
It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission
FDA Package Insert for Verapamil contains no information regarding drug monitoring
FDA Package Insert for Verapamil contains no information regarding IV compatibility
Treat all verapamil overdoses as serious and maintain observation for at least 48 hours (especially Verapamil SR)
preferably under continuous hospital care
Delayed pharmacodynamic consequences may occur with the sustained-release formulation
Verapamil is known to decrease gastrointestinal transit time
Treatment of overdosage should be supportive
Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil
In a few reported cases
overdose with calcium channel blockers has been associated with hypotension and bradycardia
initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride
Verapamil cannot be removed by hemodialysis
Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing
Asystole should be handled by the usual measures including cardiopulmonary resuscitation
The precise mechanism of action of Verapamil as an antianginal agent remains to be fully determined
but includes the following two mechanisms
Relaxation and prevention of coronary artery spasm
Verapamil dilates the main coronary arteries and coronary arterioles
both in normal and ischemic regions
and is a potent inhibitor of coronary artery spasm
This property increases myocardial oxygen delivery in patients with coronary artery spasm and is responsible for the effectiveness of Verapamil in vasospastic (Prinzmetal's or variant) as well as unstable angina at rest
Whether this effect plays any role in classical effort angina is not clear
but studies of exercise tolerance have not shown an increase in the maximum exercise rate–pressure product
a widely accepted measure of oxygen utilization
relief of spasm or dilation of coronary arteries is not an important factor in classical angina
Verapamil regularly reduces the total peripheral resistance (afterload) against which the heart works both at rest and at a given level of exercise by dilating peripheral arterioles
This unloading of the heart reduces myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of Verapamil in chronic stable effort angina
Electrical activity through the AV node depends
upon calcium influx through the slow channel
By decreasing the influx of calcium
Verapamil prolongs the effective refractory period within the AV node and slows AV conduction in a rate-related manner
This property accounts for the ability of Verapamil to slow the ventricular rate in patients with chronic atrial flutter or atrial fibrillation
Normal sinus rhythm is usually not affected
but in patients with sick sinus syndrome
Verapamil may interfere with sinus-node impulse generation and may induce sinus arrest or sinoatrial block
Atrioventricular block can occur in patients without preexisting conduction defects
Verapamil decreases the frequency of episodes of paroxysmal supraventricular tachycardia
Verapamil does not alter the normal atrial action potential or intraventricular conduction time
but in depressed atrial fibers it decreases amplitude
Verapamil may shorten the antegrade effective refractory period of the accessory bypass tract
Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway following administration of verapamil
Verapamil has a local anesthetic action that is 1
6 times that of procaine on an equimolar basis
It is not known whether this action is important at the doses used in man
Verapamil exerts antihypertensive effects by decreasing systemic vascular resistance
usually without orthostatic decreases in blood pressure or reflex tachycardia
bradycardia (rate less than 50 beats/min) is uncommon (1
During isometric or dynamic exercise
Verapamil does not alter systolic cardiac function in patients with normal ventricular function
Verapamil does not alter total serum calcium levels
one report suggested that calcium levels above the normal range may alter the therapeutic effect of Verapamil
Verapamil hydrochloride is a calcium antagonist or slow-channel inhibitor
nonpyrogenic solution containing verapamil hydrochloride 2
5 mg/mL and sodium chloride 8
5 mg/mL in water for injection
The solution contains no bacteriostat or antimicrobial agent and is intended for single-dose intravenous administration
May contain hydrochloric acid for pH adjustment
The chemical name of Verapamil Hydrochloride
Verapamil hydrochloride is a white or practically white crystalline powder
It is practically odorless and has a bitter taste
It is soluble in water
It has the following structural formula
This image is provided by the National Library of Medicine
Verapamil hydrochloride is not chemically related to other antiarrhythmic drugs
Verapamil reduces afterload and myocardial contractility
Improved left ventricular diastolic function in patients with Idiopathic Hypertrophic Subaortic Stenosis (IHSS) and those with coronary heart disease has also been observed with Verapamil therapy
including those with organic cardiac disease
the negative inotropic action of Verapamil is countered by reduction of afterload
and cardiac index is usually not reduced
in patients with severe left ventricular dysfunction (eg
pulmonary wedge pressure above 20 mm Hg or ejection fraction less than 30%)
or in patients taking beta-adrenergic blocking agents or other cardiodepressant drugs
deterioration of ventricular function may occur
More than 90% of the orally administered dose of Verapamil is absorbed
Because of rapid biotransformation of verapamil during its first pass through the portal circulation
bioavailability ranges from 20% to 35%
Peak plasma concentrations are reached between 1 and 2 hours after oral administration
Chronic oral administration of 120 mg of verapamil HCl every 6 hours resulted in plasma levels of verapamil ranging from 125 to 400 ng/ml
with higher values reported occasionally
A nonlinear correlation between the verapamil dose administered and verapamil plasma levels does exist
No relationship has been established between the plasma concentration of verapamil and a reduction in blood pressure
In early dose titration with verapamil
a relationship exists between verapamil plasma concentration and prolongation of the PR interval
during chronic administration this relationship may disappear
The mean elimination half-life in single-dose studies ranged from 2
the half-life increased to a range from 4
0 hours (after less than 10 consecutive doses given 6 hours apart)
Half-life of verapamil may increase during titration
Aging may affect the pharmacokinetics of verapamil
Elimination half-life may be prolonged in the elderly
orally administered Verapamil undergoes extensive metabolism in the liver
Twelve metabolites have been identified in plasma
all except norverapamil are present in trace amounts only
Norverapamil can reach steady-state plasma concentrations approximately equal to those of verapamil itself
The cardiovascular activity of norverapamil appears to be approximately 20% that of verapamil
Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days
About 3% to 4% is excreted in the urine as unchanged drug
Approximately 90% is bound to plasma proteins
In patients with hepatic insufficiency
metabolism is delayed and elimination half-life prolonged up to 14 to 16 hours
the volume of distribution is increased and plasma clearance reduced to about 30% of normal
Verapamil clearance values suggest that patients with liver dysfunction may attain therapeutic verapamil plasma concentrations with one third of the oral daily dose required for patients with normal liver function
After four weeks of oral dosing (120 mg q
verapamil and norverapamil levels were noted in the cerebrospinal fluid with estimated partition coefficient of 0
06 for verapamil and 0
An 18-month toxicity study in rats
at a low multiple (6-fold) of the maximum recommended human dose
and not the maximum tolerated dose
did not suggest a tumorigenic potential
There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10
and 120 mg/kg/day or approximately 1
the maximum recommended human daily dose (480 mg/day or 9
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation
Studies in female rats at daily dietary doses up to 5
5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility
Effects on male fertility have not been determined
In chronic animal toxicology studies
verapamil caused lenticular and/or suture line changes at 30 mg/kg/day or greater
and frank cataracts at 62
5 mg/kg/day or greater in the beagle dog but not in the rat
Development of cataracts due to verapamil has not been reported in man
FDA Package Insert for Verapamil contains no information regarding clinical studies
USP 120 mg are supplied as ivory
film-coated tablets debossed with “120” on one side
packaged in bottles of 100 tablets and unit-dose boxes of 100 tablets
Verapamil Hydrochloride Extended-Release Tablets USP
180 mg are supplied as light orange
film-coated tablets debossed with “7301” on one side
packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets
Verapamil Hydrochloride Extended-Release Tablets USP
240 mg are supplied as ivory
film-coated tablets debossed with “7300” on one side
packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets
Verapamil Hydrochloride Extended-release Capsules (PM)
pellet filled capsules are supplied in three dosage strengths
This image is provided by the National Library of Medicine
5 mg/mL is supplied in single-dose containers as follows
This image is provided by the National Library of Medicine
Store between 20˚ to 25˚ C (68˚ to 77˚ F) [See USP Controlled Room Temperature
excursions permitted to 15-30°C (59-86°F)
light-resistant container as defined in USP
Store at 20 to 25°C (68 to 77°F)
Protect from light by retaining in package until ready to use
There is limited information regarding Verapamil Patient Counseling Information in the drug label
Alcohol-Verapamil interaction has not been established
Talk to your doctor about the effects of taking alcohol with this medication
FDA Package Insert for Verapamil contains no information regarding look-alike names |
African_trypanosomiasis_physical_examination | Physical examination findings of African trypanosomiasis depend on the stage of the disease. Skin lesions are more prominent in stage 1 and neurological findings such as altered level of consciousness and hemiparesis predominate in stage 2.
|
Xanthogranulomatous_cholecystitis | Xanthogranulomatous cholecystitis (XGC) It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and colleagues.
|
Malignant_fibrous_histiocytoma | Fibrosarcoma (fibroblastic sarcoma) is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. Fibrosarcoma is classified into 3 grades: low grade (differentiated), intermediate, and high grade (anaplastic). There are 3 stages of fibrosarcoma based on the grade and extent of the lesion. The tumor may be localized at the end of the long bones. Most often it affects the upper end of tibia or lower end of femur. Fibrosarcoma is a rare disease that affects approximately one in two million people annually. Patients of all age groups may develop fibrosarcoma, but are most common between the third and sixth decades of life. Fibrosarcoma is associated with a 5-year survival rate of 30% among patients with high grade medullary lesions and 50-80% among patients with surface fibrosarcomas and low grade fibrosarcomas. Common risk factors for the development of fibrosarcoma are preexisting benign lesions, radiation therapy, surgically treated fractures, and infarction of bone. The most common symptoms of fibrosarcoma include pain, swelling, loss of range of motion. Fibrosarcoma must be differentiated from other conditions that cause pain, swelling, and lesions that may appear similar to fibrosarcoma on radiological imaging.
Fibrosarcoma may be classified according to degrees of differentiation into three subtypes
Low grade malignancy (differentiated)
Intermediate malignancy
High grade malignancy (anaplastic)
Fibrosarcoma may be classified into 3 stages based on grade and extent of lesion.
Stage I
Stage IA: Low grade lesion that is confined to its anatomic compartment
Stage IB: Low grade lesion that have extended outside of its compartment
Stage II
Stage IIA: High grade lesion that is confined to its anatomic compartment
Stage IIB: High grade lesion that have extended outside of its compartment
Stage III
lesions are any grade or anatomic site that have metastasized
The tumor may be localized at the end of the long bones. Most often it affects the upper end of tibia or lower end of femur. The tumor is typically well demarcated but not encapsulated.
Tumor cells may resemble mature fibroblasts (spindle-shaped), secreting collagen, with rare mitoses. These cells are arranged in short fascicles which split and merge, giving the appearance of "fish bone". Poorly differentiated tumors consist in more atypical cells, pleomorphic, giant cells, multinucleated, numerous atypical mitoses and reduced collagen production. Presence of immature blood vessels (sarcomatous vessels lacking endothelial cells) favors the bloodstream metastasizing. The malignant cells are characteristically arranged in a "herringbone" pattern.
Fibrosarcoma accounts for about 5% of all primary bone sarcomas.
Fibrosarcoma is a rare disease. Worldwide, the incidence of fibrosarcoma is 0.05 per 100,000 persons.
Patients of all age groups may develop fibrosarcoma, but are most common between the third and sixth decades of life. In infants, fibrosarcoma is usually congenital. Children presenting with fibrosarcoma usually do so in the first two years of their life.
It affects men and women equally.
Prognosis of fibrosarcoma depends on the tumor grade. It is associated with a 5-year survival rate of 30% among patients with high grade medullary lesions and 50-80% among patients with surface fibrosarcomas and low grade fibrosarcomas.
Secondary sarcoma, presence of eccentric permeative lesions, primary tumor in the axial skeleton are associated with a particularly poor prognosis among patients with fibrosarcoma.
Common risk factors for the development of fibrosarcoma are preexisting benign lesions such as:
Giant cell tumor
Enchondroma
Fibrous dysplasia
Bizarre parosteal osteochondromatous proliferation
Chronic osteomyelitis
Other risk factors include Paget's disease, radiation therapy, surgically treated fracture and infarction of bone.
Screening for fibrosarcoma is not recommended.
The most common symptoms of fibrosarcoma include:
Localized Pain
Swelling
Loss of range of motion
Pain with weight-bearing that is relieved by rest and night pain may be observed. Many patients with fibrosarcoma neither feel sick nor experience classic symptoms of cancer such as weight loss and fatigue. Sometimes, patients with fibrosarcoma may present with pathological fracture of the affected bone.
Fibrosarcoma must be differentiated from other conditions that cause pain, swelling, and lesions that may appear similar to fibrosarcoma on radiological imaging such as
Osteosarcoma
Chondrosarcoma
Leiomyosarcoma
Malignant fibrous histiocytoma
Myofibromatosis
Desmoplastic fibroma
Intra-osseous fibrosarcoma that affects the jaw must be differentiated from odontogenic sarcomas such as
Ameloblastic fibrodentinosarcoma
Ameloblastic fibrosarcoma
Odontogenic carcinosarcoma
The radiological picture of fibrosarcoma typically shows the osteolytic lesion with a permeative or moth-eaten appearance. Margins of lesion can range from well-demarcated to ragged appearance.
CT scan is performed at initial diagnosis of fibrosarcoma to determine the metastasis of the tumor to the lungs. The lungs are most common site of fibrosarcoma metastasis.
MRI of the entire bone is necessary among patients with fibrosarcoma. The benefits include:
Determination of the extent of bone marrow and soft tissue involvement
Identification of non-contiguous skip lesions that can arise within the same bone
Surgery is the mainstay of treatment for fibrosarcoma.
Chemotherapy and radiation therapy have not proven to be effective.
Radiation therapy may be administered as palliative therapy.
Fibrous connective tissue
Fibroma
Neurofibrosarcoma |
Trifluperidol | Trifluperidol is a typical antipsychotic of the butyrophenone chemical class. It has general properties similar to those of haloperidol, but is considerably more potent by weight, and causes relatively more severe side effects, especially tardive dyskinesia and other extrapyramidal effects. It is used in the treatment of psychoses including mania and schizophrenia. It was discovered at Janssen Pharmaceutica in 1959.
Trifluperidol Synthesis: P. Janssen, J. Adriaan, GB 895309 (1962), Template:US Patent (1969). |
Phenovarm | It is commonly used as an intermediate chemical in the manufacture of various antipsychotic neuroleptic psychotropic drugs. It originally was developed as a synthetic dye in 1883, and it was introduced by DuPont as an insecticide in 1935.
It is sometimes used as an antihelminthic in livestock. It is used as an industrial chemical in the manufacture of rubber additives.
Phenothiazine pesticides work by affecting the nervous system of insects, inhibiting the breakdown of acetylcholine by disabling the enzyme acetylcholinesterase. Many of the side effects of phenothiazine neuroleptic antipsychotics are due to their anticholinergic blocking effects.
Phenothiazine is also a potent alpha-adrenergic blocking agent.
The term "phenothiazines" is used to describe the largest of the five main classes of neuroleptic antipsychotic drugs. These drugs have antipsychotic and, often, antiemetic properties, although they may also cause severe side effects such as akathisia, tardive dyskinesia, extrapyramidal symptoms, and the rare but potentially fatal neuroleptic malignant syndrome as well as substantial weight gain.
The phenothiazine class of neuroleptic antipsychotic psychotropics are closely related to the thioxanthenes which are very similar pharmacologically.
There are three groups of phenothiazine antipsychotics, differing by their chemical structure and their pharmacological effects. They are the aliphatic compounds, the piperidines and piperazines. An aliphatic compound, piperidine or piperazine functional group is added to the phenothiazine molecule for the purpose of enhancing absorption and bioavailability of the phenothiazine chemical.
|
Primary_sclerosing_cholangitis_risk_factors | The most important risk factors associated with primary sclerosing cholangitis include family history and personal history of IBD.
The most common risk factors associated with the development of primary sclerosing cholangitis are:
IBD: Primary sclerosing cholangitis is more associated with ulcerative colitis than Crohn's disease.
Family history: Those with siblings with primary sclerosing cholangitis are 9-39 times more likely to develop the disease than the general population. |
Adventitia_externa | The tunica externa, also known as the tunica adventitia, is the outermost layer of a blood vessel, surrounding the tunica media. It is mainly composed of collagen. The collagen serves to anchor the blood vessel to nearby organs, giving it stability.
A common pathological disorder concerning the tunica externa is scurvy, also known as vitamin C deficiency. Scurvy occurs because vitamin C is essential for the synthesis of collagen, and without it, the faulty collagen cannot maintain the vein walls, and they rupture, leading to a wide multitude of problems.
, , Schematic view of an artery,
, , Anatomy of the arterial wall,
Adventitia
Tunica media
Tunica intima
Template:UCDavisOrganology - "Bird, vessels (LM, High)"
Template:EMedicineDictionary
Image at About.com
Template:Gray's
Template:WikiDoc Sources
|
Gastrointestinal_tract#Submucosa | Template:Digestive system diagram
The digestive tract is the system of organs within multicellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The major functions of the GI tract are ingestion, digestion, absorption, and defecation.
The GI tract differs substantially from animal to animal. Some animals have multi-chambered stomachs, while some animals' stomachs contain a single chamber. In a normal human adult male, the GI tract is approximately 6.5 meters (20 feet) long and consists of the upper and lower GI tracts. The tract may also be divided into foregut, midgut, and hindgut, reflecting the embryological origin of each segment of the tract.
The upper GI tract consists of the mouth, pharynx, esophagus, and stomach.
The mouth contains the buccal mucosa, which contains the openings of the salivary glands; the tongue; and the teeth.
Behind the mouth lies the pharynx, which leads to a hollow muscular tube, the esophagus.
Peristalsis takes place, which is the contraction of muscles to propel the food down the esophagus which extends through the chest and pierces the diaphragm to reach the stomach.
The lower GI tract comprises the intestines and anus.
Bowel or intestine, Small intestine, which has three parts: Duodenum, Jejunum, Ileum, Large intestine, which has three parts: Cecum (the vermiform appendix is attached to the cecum). Colon (ascending colon, transverse colon, descending colon and sigmoid flexure), Rectum
Anus
Accessory organs to the alimentary canal include the liver, gallbladder, and pancreas. The liver secretes bile into the small intestine via the biliary system, employing the gallbladder as a reservoir. Apart from storing and concentrating bile, the gallbladder has no other specific function. The pancreas secretes an isosmotic fluid containing bicarbonate and several enzymes, including trypsin, chymotrypsin, lipase, and pancreatic amylase, as well as nucleolytic enzymes (deoxyribonuclease and ribonuclease), into the small intestine. Both of these secretory organs aid in digestion.
The gut is an endoderm-derived structure. At approximately the 16th day of human development, the embryo begins to fold ventrally (with the embryo's ventral surface becoming concave) in two directions: the sides of the embryo fold in on each other and the head and tail fold towards one another. The result is that a piece of the yolk sac, an endoderm-lined structure in contact with the ventral aspect of the embryo, begins to be pinched off to become the primitive gut. The yolk sac remains connected to the gut tube via the vitelline duct. Usually this structure regresses during development; in cases where it does not, it is known as Meckel's diverticulum.
During fetal life, the primitive gut can be divided into three segments: foregut, midgut, and hindgut. Although these terms are often used in reference to segments of the primitive gut, they are nevertheless used regularly to describe components of the definitive gut as well.
Each segment of the primitive gut gives rise to specific gut and gut-related structures in the adult. Components derived from the gut proper, including the stomach and colon, develop as swellings or dilatations of the primitive gut. In contrast, gut-related derivatives—that is, those structures that derive from the primitive gut but are not part of the gut proper—in general develop as outpouchings of the primitive gut. The blood vessels supplying these structures remain constant throughout development.
Four organs are subject to specialization in the kingdom Animalia.
The first organ is the tongue which is only present in the phylum Chordata.
The second organ is the esophagus. The crop is an enlargement of the esophagus in birds, insects and other invertebrates that is used to store food temporarily.
The third organ is the stomach. In addition to a glandular stomach (proventriculus), birds have a muscular "stomach" called the ventriculus or "gizzard." The gizzard is used to mechanically grind up food.
The fourth organ is the large intestine. An outpouching of the large intestine called the cecum is present in non-ruminant herbivores such as rabbits. It aids in digestion of plant material such as cellulose
Several studies have linked the human brain and the gastrointestinal system. Emotional state is strongly linked to gastrointestinal symptoms; many people experience altered bowel habits as a result of stress, anxiety, and depression. Many researchers consider the gastrointestinal system to be a "second brain".
For example, Irritable Bowel Syndrome is strongly linked to emotional state, and the symptoms of a number of gastrointestinal disorders, including IBS and inflammatory bowel disease, are exacerbated, but not caused by, stress and axiety.
There are a number of diseases and conditions affecting the gastrointestinal system, including:
Irritable Bowel Syndrome
Inflammatory Bowel Disease (Crohn's Diseae and ulcerative colitis)
Giardiasis
Colorectal cancer
Gastroenteritis, also known as "stomach flu";an inflammation of the stomach and intestines
Diverticulitis
Pancreatitis
The gastrointestinal tract is also a prominent part of the immune system. The low pH (ranging from 1 to 4) of the stomach is fatal for many microorganisms that enter it. Similarly, mucus (containing IgA antibodies) neutralizes many of these microorganisms. Other factors in the GI tract help with immune function as well, including enzymes in the saliva and bile. Enzymes such as Cyp3A4, along with the antiporter activities, are also instrumental in the intestine's role of detoxification of antigens and xenobiotics, such as drugs, involved in first pass metabolism. Health-enhancing intestinal bacteria serve to prevent the overgrowth of potentially harmful bacteria in the gut. Microorganisms are also kept at bay by an extensive immune system comprising the gut-associated lymphoid tissue (GALT).
The gastrointestinal tract has a uniform general histology with some differences which reflect the specialization in functional anatomy. The GI tract can be divided into 4 concentric layers:
Mucosa
Submucosa
Muscularis externa (the external muscle layer)
Adventitia or serosa
General structure of the gut wall.
The mucosa is the innermost layer of the gastrointestinal tract, surrounding the lumen, or space within the tube. This layer comes in direct contact with the food (or bolus), and is responsible for absorption and secretion, important processes in digestion.
The mucosa can be divided into:
Epithelium
Lamina propria
Muscularis mucosae
The mucosae are highly specialized in each organ of the gastrointestinal tract, facing a low pH in the stomach, absorbing a multitude of different substances in the small intestine, and also absorbing specific quantities of water in the large intestine. Reflecting the varying needs of these organs, the structure of the mucosa can consist of invaginations of secretory glands (e.g., gastric pits), or it can be folded in order to increase surface area (examples include villi and plicae circulares).
The submucosa consists of a dense irregular layer of connective tissue with large blood vessels, lymphatics and nerves branching into the mucosa and muscularis. It contains Meissner's plexus, an enteric nervous plexus, situated on the inner surface of the muscularis externa.
The muscularis externa consists of an inner circular layer and a longitudinal outer muscular layer. The circular muscle layer prevents the food from going backwards and the longitudinal layer shortens the tract. The coordinated contractions of these layers is called peristalsis and propels the bolus, or balled-up food, through the GI tract.
Between the two muscle layers are the myenteric or Auerbach's plexus.
The adventitia consists of several layers of epithelia.
When the adventitia is facing the mesentery or peritoneal fold, the adventitia is covered by a mesothelium supported by a thin connective tissue layer, together forming a serosa, or serous membrane.
The stomachs of calves have commonly been used as a source of rennet for making cheese.
The use of animal gut strings by musicians can be traced back to the third dynasty of Egypt. In the recent past, strings were made out of lamb gut. With the advent of the modern era, musicians have tended to use strings made of silk, or synthetic materials such as nylon or steel. Some instrumentalists, however, still use gut strings in order to evoke the older tone quality. Although such strings were commonly referred to as "catgut" strings, cats were never used as a source for gut strings.
Sheep gut was the original source for natural gut string used in racquets, such as for tennis. Today, synthetic strings are much more common, but the best strings are now made out of cow gut.
Gut cord has also been used to produce strings for the snares which provide the snare drum's characteristic buzzing timbre. While the snare drum currently almost always uses metal wire rather than gut cord, the North African bendir frame drum still uses gut for this purpose.
"Natural" sausage hulls (or casings) are made of animal gut, especially hog, beef, and lamb.
Animal gut was used to make the cord lines in longcase clocks and for fusee movements in bracket clocks, but may be replaced by metal wire.
The oldest known condoms, from 1640, were made from animal intestine.
Dysbiosis
Gastrointestinal hormone
Dorland's Illustrated Medical Dictionary
Major systems of the human body
↑ Maton, Anthea (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. Unknown parameter |coauthors= ignored (help)
↑ Bruce M. Carlson (2004). Human Embryology and Developmental Biology (3rd edition ed.). Saint Louis: Mosby. ISBN 0-323-03649-X.CS1 maint: Extra text (link)
↑ Richard Coico, Geoffrey Sunshine, Eli Benjamini (2003). Immunology: a short course. New York: Wiley-Liss. ISBN 0-471-22689-0.CS1 maint: Multiple names: authors list (link)
↑ Abraham L. Kierszenbaum (2002). Histology and cell biology: an introduction to pathology. St. Louis: Mosby. ISBN 0-323-01639-1.
|
Choledocholithiasis_(patient_information) | Choledocholithiasis is the presence of a gallstone in the common bile duct. The stone may consist of bile pigments or calcium and cholesterol salt:
Abdominal pain in the right upper or middle upper abdomen that may: Come and go, Be sharp, cramping, or dull, Spread to the back or below the right shoulder blade, Get worse after eating fatty or greasy foods, Occurs within minutes of a meal
Fever
Loss of appetite
Jaundice (yellowing of skin and whites of eyes)
Nausea
Vomiting
While stones can frequently pass through the common bile duct into the duodenum, some stones may be too large to pass through the CBD and will cause an obstruction.
Risk Factors include:
A previous medical history of gallstones
Choledocholithiasis can occur in people who have had their gallbladder removed
Tests that show the location of stones in the bile duct include the following:
Abdominal CT scan
Abdominal ultrasound
Endoscope retrograde cholangiography (ERCP)
Endoscopic ultrasound
Magnetic resonance cholangiopancreatography (MRCP)
Percutaneous transhepatic cholangiogram (PTCA)
Your doctor may order the following blood tests:
Bilirubin
Liver function tests
Pancreatic enzymesCall for an appointment with your health care provider if abdominal pain with or without fever develops that is not attributable to other causes, if jaundice develops, or if other symptoms suggestive of choledocholithiasis occur.
The goal of treatment is to relieve the blockage.
Treatment may involve:
Surgery to remove the gallbladder and stones
ERCP and a procedure called a sphincterotomy, which makes a surgical cut into the muscle in the common bile duct.
Directions to Hospitals Treating Choledocholithiasis
Blockage and infection caused by stones in the biliary tract can be life threatening. However, with prompt diagnosis and treatment, the outcome is usually very good.
Biliary cirrhosis
Cholangitis
Pancreatitis
http://www.nlm.nih.gov/medlineplus/ency/article/000274.htm
Template:WH
Template:WS
|
Nefazodone | Nefazodone is a 5-HT2 Antagonists that is FDA approved for the {{{indicationType}}} of major depressiveorthostatic hypotension (2.8% to 4), gastrointestinal: constipation (10% to 17% ), nausea (14% to 23% ), xerostomia (25% ), neurologic: asthenia (7% to 13% ), confusion (7% ), dizziness (11% to 22% ), headache (26% to 52% ), lightheadedness (10% ), somnolence (16% to 32% ),ophthalmic: blurred vision (3% to 9% ).
Major depressive disorder
There is limited information about Off-Label Guideline-Supported Use of Nefazodoefazodone in adult patients.
There is limited information about FDA-labeled indications and dosage information of Nefazodone in pediatric patients.
There is limited information about Off-Label Guideline-Supported Use of Nefazodopediatric patients.
Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see Warnings and Precautions).
Nefazodone hydrochloride tablets are contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury (see Boxed Warning). Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.
The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see Warnings and Precautions), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and nefazodone should be avoided for most patients, including the elderlynefazodone hydrochloridnefazodone hydrochloride tablets is not approved for use in treating bipolar depression.
(See Boxed Warning.)
Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone.
The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,000 patient-years of nefazodone treatment. This represents a rate of about 3 to 4 times the estimated background rate of liver failure. This rate is an underestimate because of under reporting, and the true risk could be considerably greater than this. A large cohort study of antidepressant users found no cases of liver failure leading to death or transplant among nefazodone users in about 30,000 patient-years of exposure. The spontaneous report data and the cohort study results provide estimates of the upper and lower limits of the risk of liver failure in nefazodone-treated patients, but are not capable of providing a precise risk estimate.
The time to liver injury for the reported liver failure cases resulting in death or transplant generally ranged from 2 weeks to 6 months on nefazodone therapy. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symptoms), other reports did not describe the onset of clear prodromal symptoms prior to the onset of jaundice.
The physician may consider the value of liver function testing. Periodic serum transaminase testing has not beenjaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctorNefazodone should be discontinued if clinical signs or symptoms suggest liver failure (see Precautions: Information for Patients). Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels ≥ 3 times the upper limit of Normal, while on nefazodone should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if nefazodone is reintroduced. Accordingly, such patients should not be considered for re-treatment.
Associated With Discontinuation of Treatment
Approximately 16% of the 3496 patients who received nefazodone in worldwide premarketing clinical trials discontinued treatment due to an adverse experience. The more common (≥ 1%) events in clinical trials associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for nefazodone compared to placebo) included: nausea (3.5%), dizziness (1.9%), insomnia (1.5%), asthenia (1.3%), and agitation (1.2%).
Commonly Observed Adverse Events in Controlled Clinical Trials
The most commonly observed adverse events associated with the use of nefazodone (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., significantly higher incidence for nefazodone compared to placebo, p ≤ 0.05), derived from the table below, were: somnolence, dry mouth, nausea, dizziness, constipation, asthenia, lightheadedness, blurred vision, confusion, and abnormal vision.
Adverse Events Occurring at an Incidence of 1% or More Among Nefazodone-Treated Patients
The table that followsnefazodone-treated patients who participated in short-term (6 to 8 week) placebo-controlled trials in which patients were dosed with nefazodone to ranges of 300 to 600 mg/day. Thisstandard Costartvents reported by at least 1% of patients treated with nefazodone and more frequent than the placebo group are included; incidence is rounded to the nearest 1% (< 1% indicates an incidence less than 0.5%). Events for which the nefazodone incidence was equal to or less than placebo are not listed in the table, but included the following: abdominal pain, pain, back pain, accidental injury, chest pain, neck pain, palpitation, migraine, sweating, flatulence, vomiting, anorexia, tooth disorder, weight gain, edema, myalgia, cramp, agitation, anxiety, depression, hypesthesia, CNS stimulation, dysphoria, emotional lability, sinusitis, rhinitis, dysmenorrhea, dysuria.
Vasodilatation – flushing, feeling warm.
Abnormal vision – scotoma, visual trails.# Incidence adjusted for gender.
Dose Dependency of Adverse Events
The table that follows enumerates adverse events that were more frequent in the nefazodone dose range of 300 to 600 mg/day than in the nefazodone dose range of up to 300 mg/day. This table shows only those adverse events for which there was a statistically significant difference (p ≤ 0.05) in incidence between the nefazodone dose ranges as well as a difference between the high dose range and placebo.
This image is provided by the National Library of Medicine.
Visual Disturbances
In controlled clinical trials, blurred vision occurred in 9% of nefazodone-treated patients compared to 3% of placebo-treated patients. In these same trials abnormal vision, including scotomata and visual trails, occurred in 7% of nefazodone-treated patients compared to 1% of placebo-treated (see Treatment-Emergent Adverse Experience table, above). Dose-dependency was observed for these events in these trials, with none of the scotomata and visual trails at doses below 300 mg/day. However, scotomata and visual trails observed at doses below 300 mg/day have been reported in postmarketing experience with nefazodone (see Precautions, Information for Patients).
Vital Sign Changes
(See Precautions, Postural Hypotension.)
Weight Changes
In a pooled analysis of placebo-controlled premarketing studies, there were no differences between nefazodone and placebo groups in the proportions of patients meeting criteria for potentially important increases or decreases in body weight (a change of ≥ 7%).
Laboratory Changes
Of the serum chemistry, serum hematology, and urinalysis parameters monitored during placebo-controlled premarketing studies with nefazodone, a pooled analysis revealed a statistical trend between nefazodone and placebo for hematocrit, i.e., 2.8% of nefazodone patients met criteria for a potentially important decrease in hematocrit (≤ 37% male or ≤ 32% female) compared to 1.5% of placebo patients (0.05 < p ≤ 0.10). Decreases in hematocrit, presumably dilutional, have been reported with many other drugs that block alpha1-adrenergic receptors. There was no apparent clinical significance of the observed changes in the few patients meeting these criteria.
ECG Changes
Of the ECGly significant difference between nefazodone and placebo for sinus bradycardia, i.e., 1.5% of nefazodone patients met criteria for a potentially important decrease in heart rate (≤ 50 bpm and a decrease of ≥ 15 bpm) compared to 0.4% of placebo patients (p < 0.05). There was no obvious clinical significance of the observed changes in the few patients meeting these criteria.
Other Events Observed During the Premarketing Evaluation of Nefazodone
During its premarketing assessment, multiple doses of nefazodone were administered to 3496 patients in clinical studies, including more than 250 patients treated for at least one year. The conditions and duration of exposure to nefazodostandard Costart-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 3496 patients exposed to multiple doses of nefazodone who experienced an event of the type cited on at least one occasion while receiving nefazodone. All reported events are included except those already listed in the Treatment-Emergent Adverse Experience Incidence table, those events listed in other safety-related sections of this insert, those adverse experiences subsumed under Costart terms that are either overly general or excessively specific so as to be uninformative, those events for which a drug cause was very remote, and those events which were not serious and occurred in fewer than two patients.
It is important to emphasize that, although the events reported occurred during treatment with nefazodo– Infrequent: allergic reaction, malaise, photosensitivity reaction, face edema, hangover effect, abdomen enlarged, hernia, pelvic pain, and halitosis. Rare: cellulitis.
Cardiovascular system – Infrequent: tachycardia, hypertension, syncope, ventricular extrasystoles, and angina pectoris. Rare: AV block, congestive heart failure, hemorrhage, pallor, and varicose vein.
Dermatological system – Infrequent: dry skin, acne, alopecia, urticaria, maculopapular rash,vesiculobullous rash, and eczema.
Gastrointestinal system – Frequent: gastroenteritis. Infrequent: eructation, periodontal abscess, abnormal liver function tests, gingivitis, colitis, gastritis, mouth ulceration, stomatitis, esophagitis, peptic ulcer, and rectal hemorrhage. Rare: glossitis, hepatitis, dysphagia, gastrointestinal hemorrhage, oral moniliasis, and ulcerative colitis.
Hemic and lymphatic system – Infrequent: ecchymosis, anemia, leukopenia, and lymphadenopathy .
Metabolic and nutritional system – Infrequent: weight loss, gout, dehydration, lactic dehydrogenase increased, SGOT increased, and SGPT increased. Rare: hypercholesteremia and hypoglycemia.
Musculoskeletal system – Infrequent: arthritis, tenosynovitis, muscle stiffness, and bursitis. Rare: tendinous contracture.
Nervous system – Infrequent: vertigo, twitching, depersonalization, hallucinations, suicide attempt, apathy, euphoria, hostility, suicidal thoughts, abnormal gait, thinking abnormal, attention decreased, derealization, neuralgia, paranoid reaction, dysarthria, increased libido, suicide, and myoclonus. Rare: hyperkinesia, increased salivation, cerebrovascular accident, hyperesthesia, hypotonia, ptosis, and neuroleptic malignant syndrome.
Respiratory system – Frequent: dyspnea and bronchitis. Infrequent:asthma, pneumonia, laryngitis, voice alteration, epistaxis, hiccup. Rare: hyperventilation and yawn.
Special senses – Frequent: eye pain. Infrequent: dry eye, ear pain, abnormality of accommodation, diplopia, conjunctivitis, mydriasis, keratoconjunctivitis, hyperacusis, and photophobia. Rare: deafness, glaucoma, night blindness, and taste loss.
Urogenital system – Frequent: impotence. Infrequent: cystitis, urinary urgency, metrorrhagiaa, amenorrheaa, polyuria, vaginal hemorrhagea, breast enlargementa, menorrhagiaa, urinary incontinence, abnormal ejaculationa, hematuria, nocturia, and kidney calculus. Rare: uterine fibroids enlarged, uterine hemorrhagea, anorgasmia, and oliguria.
Adjusted for gender.
Postmarketing experience with nefazodone has shown an adverse experience profile similar to that seen during the premarketing evaluation of nefazodone. Voluntary reports of adverse events temporally associated with nefazodone have been received since market introduction that are not listed above and for which a causal relationship has not been established. These include:
Anaphylactic reactions; angioedema; convulsions (including grand mal seizures); galactorrhea; gynecomastia (male); hyponatremia; liver necrosis and liver failure, in some cases leading to liver transplantation and/or death (see Warnings); priapism (see Precautions); prolactin increased; rhabdomyolysis involving patients receiving the combination of nefazodone and lovastatin or simvastatin (see Precautions); serotonin syndrome; and Stevens-Johnson syndrome; and thrombocytopenia.
Drugs Highly Bound to Plasma Protein
Because nefazodone is highly bound to plasma protein (see Clinical Pharmacology, Pharmacokinetics), administration of nefazodon, potentially resulting in adverse events. Conversely, adverse effects could result from displacement of nefazodone by other highly bound drugs.
Warfarin – There were no effects on the prothrombin or bleeding times or upon the pharmacokinetics of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had been pretreated for 2 weeks with warfarin. Although the coadministration of nefazodone did decrease the subjects’ exposure to S-warfarin by 12%, the lack of effects on the prothrombin and bleeding times indicates this modest change is not clinically significant. Although these results suggest no adjustments in warfarin dosage are required when nefazodone is administered to patients stabilized on warfarin, such patients should be monitored as required by standard medical practices.
CNS-Active Drugs
Monoamine Oxidase Inhibitors – See Warnings
Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak. This change is of unknown clinical significance. Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes in the pharmacokinetic parameters for nefazodone. Dosage adjustment of haloperidol may be necessary when coadministered with nefazodone.
Lorazepam – When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state, there was no change in any pharmacokinetic parameter for either drug compared to each drug administered alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.
Triazolam/Alprazolam – See Contrandications and Warnings.
Alcohol – Although nefazodon, the concomitant use of nefazodone and alcohol in depressed patients is not advised.
Buspirone – In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BIDpyrimidinylpiperazine. With 5 mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (17%) and mCPP (9%). Subjects receiving nefazodone 250 mg BID and buspirone 5 mg BID experienced lightheadedness, asthenia, dizziness, and somnolence, adverse events also observed with either drug alone. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg QDPimozide – See Contraindications, Warnings, and Precautions, .
Fluoxetine – When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively. When a 200 mg dose of nefazodone was administered to subjects who had been receiving fluoxetine for 1 week, there was an increased incidence of transient adverse events such as headache, lightheadedness, nausea, or paresthesia, possibly due to the elevated mCPP levels. Patients who are switched from fluoxetine to nefazodone without an adequate washout period may experience similar transient adverse events. The possibility of this happening can be minimized by allowing a washout period before initiating nefazodone therapy and by reducing the initial dose of nefazodone. Because of the long half-life of fluoxetine and its metabolites, this washout period may range from one to several weeks depending on the dose of fluoxetine and other individual patient variables.
Phenytoin – Pretreatment for 7 days with 200 mg BID of nefazodone had no effect on the pharmacokinetics of a single 300 mg oral dose of phenytoin. However, due to the nonlinear pharmacokinetics ofphenytoin, the failure to observe a significant effect on the single-dose pharmacokinetics of phenytoin does not preclude the possibility of a clinically significant interaction with nefazodone when phenytoin is dosed chronically. However, no change in the initial dosage of phenytoin is considered necessary and any subsequent adjustment of phenytoin dosage should be guided by usual clinical practices.
Desipramine – When nefazodone (150 mg BID) and desipramine (75 mg QD) were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite, 2-hydroxy desipramine. There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.
Lithium – In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5 days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.
Carbamazepine – The coadministration of nefazodone (200 mg BID) for 5 days to 12 healthy subjects on carbamazepine who had achieved steady state (200 mg BID) was found to be well tolerated. Steady-state conditions for carbamazepine, nefazodone, and several of their metabolites were achieved by day 5 of coadministration. With coadministration of the two drugs there were significant increases in the steady-state Cmax and AUC of carbamazepine (23% and 23%, respectively), while the steady-state Cmax and the AUC of the carbamazepine metabolite, 10,11 epoxycarbamazepine, decreased by 21% and 20%, respectively. The coadministration of the two drugs significantly reduced the steady-state Cmax and AUC of nefazodone by 86% and 93%, respectively. Similar reductions in the Cmax and AUC of HO-NEF were also observed (85% and 94%), while the reductions in Cmax and AUC of mCPP and triazole-dione were more modest (13% and 44% for the former and 28% and 57% for the latter). Due to the potential for coadministration of carbamazepine to result in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for nefazodone, it is recommended that nefazodone not be used in combination with carbamazepine (see Contraindications And Warnings).
General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible.
Other CNS-Active Drugs – The use of nefazodone in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised if concomitant administration of nefazodone and such drugs is required.
Cimetidine
When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.
Theophylline
When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadministered.
Cardiovascular-Active Drugs
Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%, and 15%, respectively. Digoxin had no effects on the pharmacokinetics of nefazodone and its active metabolites. Because of the narrow therapeutic index of digoxin, caution should be exercised when nefazodone and digoxin are coadministered; plasma level monitoring for digoxin is recommended.
Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics of nefazodone, hydroxynefazodone, and triazole-dione were not affected by coadministration of propranolol. However, Cmax, Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.
HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by nefazodone because, in the same study, nefazodone had no significant effect on the plasma concentrations of pravastatin, which is not metabolized by CYP3A4 to a clinically significant extent.
There have been rare reports of rhabdomyolysis involving patients receiving the combination of nefazodone and either simvastatin or lovastatin, also a substrate of CYP3A4 (see Adverse Reactions, Postintroduction Clinical Experience). Rhabdomyolysis has been observed in patients receiving HMG-CoA reductase inhibitors administered alone (at recommended dosages) and in particular, for certain drugs in this class, when given in combination with inhibitors of the CYP3A4 isozyme.
Caution should be used if nefazodone is administered in combination with HMG-CoA reductase inhibitors that are metabolized by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, and dosage adjustments of these HMG-CoA reductase inhibitors are recommended. Since metabolic interactions are unlikely between nefazodone and HMG-CoA reductase inhibitors that undergo little or no metabolism by the CYP3A4 isozyme, such as pravastatin or fluvastatin, dosage adjustments should not be necessary.
There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, blood concentrations of the immunosuppressive agent should be monitored and dosage adjusted accordingly.
Pharmacokinetics of Nefazodone in ‘Poor Metabolizers’ and Potential Interaction With Drugs That Inhibit and/or Are Metabolized by Cytochrome P450 Isozymes
CYP3A4 Isozyme – Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. This is consistent with the interactions observed between nefazodone and triazolam, alprazolam, buspirone, atorvastatin, and simvastatin, drugs metabolized by this isozyme. Consequently, caution is indicated in the combined use of nefazodone with any drugs known to be metabolized by CYP3A4. In particular, the combined use of nefazodone with triazolam should be avoided for most patients, including the elderly. The combined use of nefazodone with terfenadine, astemizole, cisapride, or pimozide is contraindicated (see Contraindications and Warnings).
CYP2D6 Isozyme – A subset (3% to 10%) of the population has reduced activity of the drug-metabolizing enzyme CYP2D6. Such individuals are referred to commonly as “poor metabolizers” of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. The pharmacokinetics of nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. Thus, it is not likely that nefazodone will decrease the metabolic clearance of drugs metabolized by this isozyme.
CYP1A2 Isozyme – Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. Thus, metabolic interactions between nefazodone and drugs metabolized by this isozyme are unlikely.
[Electroconvulsive therapy
Pregnancy Category (FDA): C
Reproduction studies have been performed in pregnant rabbits and rats at daily doses up to 200 and 300 mg/kg, respectively (approximately 6 and 5 times, respectively, the maximum human daily dose on a mg/m2 basis). No malformations were observed in the offspring as a result of nefazodone treatment. However, increased early pup mortality was seen in rats at a dose approximately five times the maximum human dose, and decreased pup weights were seen at this and lower doses, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. The no-effect dose for rat pup mortality was 1.3Nefazodfazodone in women who are pregnant.
The effect of nefazodone on labor and delivery in humans is unknown.
It is not known whether nefazodoefazodone is administered to a nursing woman.
Safety and effectiveness in the pediatric population have not been established (see BOXED WARNING and WARNINGS, Clinical Worsening and Suicide Risk). Two placebo-controlled trials in 286 pediatric patients with MDD have been conducted with nefazodonenefazodone hydrochloride tablets in a child or adolescent must balance the potential risks with the clinical need.
Of the approximately 7000 patients in clinical studies who received nefazodone for the treatment of depression, 18% were 65 years and older, while 5% were 75 years and older. Based on monitoring of adverse events, vital signs, electrocardiograms, and results of laboratory tests, no overall differences in safety between elderly and younger patients were observed in clinical studies. Efficacy in the elderly has not been demonstrated in placebo-controlled trials. ue to the increased systemic exposure to nefazodone seen in single-dose studies in elderly patients (see Clinical Pharmacology, Pharmacokinetics), treatment should be initiated at half the usual dose, but titration upward should take place over the same range as in younger patients (see Dosage and Administration). The usual precautions should be observed in elderly patients who have concomitant medical illnesses or who are receiving concomitant drugs.
There is no FDA guidance on the use of Nefazodone with respect to specific gender populations.
There is no FDA guidance on the use of Nefazodone with respect to specific racial populations.
There is no FDA guidance on the use of Nefazodone in patients with renal impairment.
There is no FDA guidance on the use of Nefazodone in patients with hepatic impairment.
There is no FDA guidance on the use of Nefazodone in women of reproductive potentials and males.
There is no FDA guidance one the use of Nefazodone in patients who are immunocompromised.
There is limited information regarding Nefazodone Administration in the drug label.
There is limited information regarding Nefazodone Monitoring in the drug label.
There is limited information regarding the compatibility of Nefazodone and IV administrations.
Human Experience<\b>
In premarketing clinical studies, there were seven reports of nefazodone overdose alone or in combination with other pharmacological agents. The amount of nefazodone ingested ranged from 1000 mg to 11,200 mg. Commonly reported symptoms from overdose of nefazodone included nausea, vomiting, and somnolence. One nonstudy participant took 2000 to 3000 mg of nefazodone with methocarbamol and alcohol; this person reportedly experienced a convulsion (type not documented). None of these patients died.
In postmarketing experience, overdose with nefazodone alone and in combination with alcohol and/or other substances has been reported. Commonly reported symptoms were similar to those reported from overdose in premarketing experience. While there have been rare reports of fatalities in patients taking overdoses of nefazodone, predominantly in combination with alcohol and/or other substances, no causal relationship to nefazodone has been established.
Overdosage Management=the wide distribution of nefazodone in body tissuesnefazodo.
Pharmacology
Nefazodone
Systematic (IUPAC) name
1-(3-[4-(3-chlorophenyl)piperazin-1-yl]propyl)-3-ethyl-4-(2-phenoxyethyl)-1H-1,2,4-triazol-5(4H)-one
Identifiers
CAS number
83366-66-9
ATC code
N06AX06
PubChem
4449
DrugBank
DB01149
Chemical data
Formula
Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBox atom
Mol. mass
470.01 g/mol
SMILES
eMolecules & PubChem
Pharmacokinetic data
Bioavailability
20% (variable)
Protein binding
>99%
Metabolism
Hepatic (active metabolites, including mCPP)
Half life
2–4 hours
Excretion
Urine (55%), Feces (20–30%)
Therapeutic considerations
Pregnancy cat.
C
Legal status
Prescription Only (S4)(AU) Template:Unicode Prescription only
Routes
Oral
Mechanism of Action
The mechanism of action of nefazodone, as with other antidepressants, is unknown.
Structure
Nefazodone hydrochloride tablets USP are an antidepressant for oral administration with a chemical structure unrelated to selective serotonin reuptake inhibitors, tricyclics, tetracyclics, or monoamine oxidase inhibitors (MAOI).
Nefazodone hydrochloride is a synthetically derived phenylpiperazine antidepressant. The chemical name for nefazodone hydrochloride is 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one monohydrochloride. The structural formula is:
This image is provided by the National Library of Medicine.
C25H32CIN5O2•HCl M.W. 506.5
Nefazodone hydrochloride is a nonhygroscopic, white crystalline solid. It is freely soluble in chloroform, soluble in propylene glycol, and slightly soluble in polyethylene glycol and water.
Nefazodone hydrochloride tablets USP are supplied as capsule-shaped tablets containing 50 mg, 100 mg, 150 mg, 200 mg, or 250 mg of nefazodone hydrochlorstarch glycolate and povidone. Additionally, the 50 mg tablets include ferric oxide red as a colorant, the 150 mg tablets include ferric oxide red and yellow as colorants, and the 200 mg tablets include ferric oxide yellow as a colorant.
Pharmacodynamics
Preclinical studies have shown that nefazodone inhibits neuronal uptake of serotonin and norepinephrine.
Nefazodone occupies central 5-HT2 receptors at nanomolar concentrations, and acts as an antagonist at this receptor. Nefazodone was shown to antagonize alpha1-adrenergic receptors, a property which may be associated with postural hypotension. In vitro binding studies showed that nefazodone had no significant affinity for the following receptors: alpha2 and beta adrenergic, 5-HT1A, cholinergic, dopaminergic, or benzodiazepine.
Pharmacokinetics
Nefazodone is rapidly and completely absorbed but is subject to extensive metabolism, so that its absolute bioavailability is low, about 20%, and variable. Peak plasma concentrations occur at about one hour and the half-life of nefazodone is 2 to 4 hours.
Both nefazodone and its pharmacologically similar metabolite, hydroxynefazodone, exhibit nonlinear kinetics for both dose and time, with AUC and Cmax increasing more than proportionally with dose increases and more than expected upon multiple dosing over time, compared to single dosing. For example, in a multiple-dose study involving BID dosing with 50, 100, and 200 mg, the AUC for nefazodone and hydroxynefazodone increased by about 4 fold with an increase in dose from 200 to 400 mg per day; Cmax increased by about 3 fold with the same dose increase. In a multiple-dose study involving BID dosing with 25, 50, 100, and 150 mg, the accumulation ratios for nefazodone and hydroxynefazodone AUC, after 5 days of BID dosing relative to the first dose, ranged from approximately 3 to 4 at the lower doses (50 to 100 mg/day) and from 5 to 7 at the higher doses (200 to 300 mg/day); there were also approximately 2 to 4 fold increases in Cmax after 5 days of BID dosing relative to the first dose, suggesting extensive and greater than predicted accumulation of nefazodone and its hydroxy metabolite with multiple dosing. Steady-state plasma nefazodone and metabolite concentrations are attained within 4 to 5 days of initiation of BID dosing or upon dose increase or decrease.
Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine. Attempts to characterize three metabolites identified in plasma, hydroxynefazodone (HO-NEF), meta-chlorophenylpiperazine (mCPP), and a triazole-dione metabolite, have been carried out. The AUC (expressed as a multiple of the AUC for nefazodone dosed at 100 mg BID) and elimination half-lives for these three metabolites were as follows:
This image is provided by the National Library of Medicine.
HO-NEF possesses a pharmacological profile qualitatively and quantitatively similar to that of nefazodone. mCPP has some similarities to nefazodone, but also has agonist activity at some serotonergic receptor subtypes. The pharmacological profile of the triazole-dione metabolite has not yet been well characterized. In addition to the above compounds, several other metabolites were present in plasma but have not been tested for pharmacological activity.
After oral administration of radiolabeled nefazodone, the mean half-life of total label ranged between 11 and 24 hours. Approximately 55% of the administered radioactivity was detected in urine and about 20 to 30% in feces.
Distribution
Nefazodone is widely distributed in body tissues, including the central nervous system (CNS). In humans the volume of distribution of nefazodone ranges from 0.22 to 0.87 L/kg.
Protein Binding
At concentrations of 25 to 2500 ng/mL nefazodone is extensively (> 99%) bound to human plasma proteins in vitro. The administration of 200 mg BID of nefazodone for 1 week did not increase the fraction of unbound warfarin in subjects whose prothrombin times had been prolonged by warfarin therapy to 120 to 150% of the laboratory control (see Precautions, Drug Interactions). While nefazodone did not alter the in vitro protein binding of chlorpromazine, desipramine, diazepam, diphenylhydantoin, lidocaine, prazosin, propranolol, or verapamil, it is unknown whether displacement of either nefazodone or these drugs occurs in vivo. There was a 5% decrease in the protein binding of haloperidol; this is probably of no clinical significance.
Effect of Food
Food delays the absorption of nefazodone and decreases the bioavailability of nefazodone by approximately 20%.
Renal Disease
In studies involving 29 renally impaired patients, renal impairment (creatinine clearances ranging from 7 to 60 mL/min/1.73 m2) had no effect on steady-state nefazodone plasma concentrations.
Liver Disease
In a multiple-dose study of patients with liver cirrhosis, the AUC values for nefazodone and HO-NEF at steady state were approximately 25% greater than those observed in normal volunteers.
Age/Gender Effects
After single doses of 300 mg to younger (18 to 45 years) and older patients (> 65 years), Cmax and AUC for nefazodone and hydroxynefazodone were up to twice as high in the older patients. With multiple doses, however, differences were much smaller, 10 to 20%. A similar result was seen for gender, with a higher Cmax and AUC in women after single doses but no difference after multiple doses.
Treatment with nefazodone should be initiated at half the usual dose in elderly patients, especially women (see DOSAGE AND ADMINISTRATION), but the therapeutic dose range is similar in younger and older patients.
Clinical Efficacy Trial Results
Studies in Outpatients With Depression
During its premarketing development, the efficacy of nefazodone was evaluated at doses within the therapeutic range in five well-controlled, short-term (6 to 8 weeks) clinical investigations. These trials enrolled outpatients meeting DSM-III or DSM-IIIR criteria for major depression. Among these trials, two demonstrated the effectiveness of nefazodone, and two provided additional support for that conclusion.
One trial was a 6 week dose-titration study comparing nefazodone in two dose ranges (up to 300 mg/day and up to 600 mg/day [mean modal dose for this group was about 400 mg/day], on a BID schedule) and placebo. The second trial was an 8 week dose-titration study comparing nefazodone (up to 600 mg/day; mean modal dose was 375 mg/day), imipramine (up to 300 mg/day), and placebo, all on a BID schedule. Both studies demonstrated nefazodone, at doses titrated between 300 mg to 600 mg/day (therapeutic dose range), to be superior to placebo on at least three of the following four measures: 17 Item Hamilton Depression Rating Scale or HDRS (total score), Hamilton Depressed Mood item, Clinical Global Impressions (CGI) Severity score, and CGI Improvement score. Significant differences were also found for certain factors of the HDRS (e.g., anxiety factor, sleep disturbance factor, and retardation factor). In the two supportive studies, nefazodone was titrated up to 500 or 600 mg/day (mean modal doses of 462 mg/day and 363 mg/day). In the fifthree additional trials were conducted using subtherapeutic doses of nefazodone.
Overall, approximately two thirds of patients in these trials were women, and an analysis of the effects of gender on outcome did not suggest any differential responsiveness on the basis of sex. There were too few elderly patients in these trials to reveal possible age-related differences in response.
Since its initial marketing as an antidepressant drug product, additional clinical investigations of nefazodone have been conducted. These studies explored nefazodone’s use under conditions not evaluated fully at the time initial marketing approval was granted.
Studies in “Inpatients”
Two studies were conducted to evaluate nefazodone’s effectiveness in hospitalized depressed patients. These were 6 week, dose-titration trials comparing nefazodone (up to 600 mg/day) and placebo, on a BID schedule. In one study, nefazodone was superior to placebo. In this study, the mean modal dose of nefazodone was 503 mg/day, and 85% of these inpatients were melancholic; at baseline, patients were distributed at the higher end of the 7 point CGI Severity scale, as follows: 4 = moderately ill (17%); 5 = markedly ill (48%); 6 = severely ill (32%). In the other study, the differentiation in response rates between nefazodone and placebo was not statistically significant. This result may be explained by the “high” rate of spontaneous improvement among the patients randomized to placebo.
Studies of “Relapse Prevention in Patients Recently Recovered (Clinically) From Depression”
Two studies were conducted to assess nefazodone’s capacity to maintain a clinical remission in acutely depressed patients who were judged to have responded adequately (HDRS total score ≤ 10) after a 16 week period of open treatment with nefazodone (titration up to 600 mg/day). In one study, nefazodone was superior to placebo. In this study, patients (n = 131) were randomized to continuation on nefazodone or placebo for an additional 36 weeks (1 year total). This study demonstrated a significantly lower relapse rate (HDRS total score ≥ 18) for patients taking nefazodone compared to those on placebo. The second study was of appropriate design and power, but the sample of patients admitted for evaluation did not suffer relapses at a high enough incidence to provide a meaningful test of nefazodone’s efficacy for this use.
Comparisons of Clinical Trial Results
Highly variable results have been seen in the clinical development of all antidepressant drugs. Furthermore, in those circumstances when the drugs have not been studied in the same controlled clinical trial(s), comparisons among the findingr more of the confounding factors just enumerated.
Nonclinical Toxicology
There is limited information regarding Nefazodone Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Nefazodone Clinical Studies in the drug label.
How Supplied
Nefazodone hydrochloride tablets USP, 50 mg, are light-pink to pink (mottled), capsule-shaped, beveled-edged tablets, debossed “7178” on one side and debossed “93” on the other side. They are available in bottles of 100.
Nefazodone hydrochloride tablets USP, 100 mg, are white to off-white, capsule-shaped tablets, debossed “1024” on one side and scored on the other side with a debossed “93” on one side of the score. They are available in bottles of 60.
Nefazodone hydrochloride tablets USP, 150 mg, are peach (mottled), capsule-shaped tablets, debossed “7113200 mg, are light-yellow to yellow (mottled), capsule-shaped tablets, debossed “1025” on one side and debossed “93” on the other side. They are available in bottles of 60.
Nefazodone hydrochloride tablets USP, 250 mg, are white to off-white, capsule-shaped tablets, debossed “1026” on one side and debossed “93” on the other side. They are available in bottles of 60.
Storage.
Images
Drug Images
{{#ask: Page Name::Nefazod{{#ask: Label Page::NefazodonRead this information completely before using nefazodone.
Read the information each time you get more medicine. There may be new information. This leaflet provides a summary about nefazodone and does not include everything there is to know about your medicine. This information is not meant to take the place of talking with your doctor.
What is the most important information that I should know about nefazodone?
Rarely, people who take nefazodone can develop serious liver problems. If you get any of the following symptoms while taking nefazodone, call your doctor right away because you may be developing a liver problem:
Yellowing of the skin or whites of eyes (jaundice)
Unusually dark urine
Loss of appetite that lasts several days or longer
Nausea
Abdominal (lower stomach) pain
People who currently have liver problems should not take nefazodone.
What is nefazodone?
Nefazodone is a medicine used to treat depression. Nefazodone is thought to treat depression by correcting an imbalance in the amounts of certain natural chemicals, such as serotonin and norepinephrine, which are in your brain.
Who should not take nefazodone?
Do not take nefazodone if you
Are allergic to nefazodone or the related medicine Desyrel® (trazodone).
Are taking Seldane® (terfenadine), an antihistamine; Hismanal® (astemizole), an antihistamine; Propulsid® (cisapride), used for heartburn; Halcion® (triazolam), used for insomnia; Orap® (pimozide), used to treat Tourette’s syndrome; or Tegretol® (carbamazepine), used to control seizures.
Currently have liver problems.
Are taking or have taken within the last 14 days one of the medicines for depression known as monoamine oxidase inhibitors (MAOIs), such as Nardil® or Parnate®.
Be sure to tell your doctor if you
Have ever had liver problems;
Are taking any other medicine, vitamin supplement, or herbal remedy, including those sold without a prescription (over-the-counter);
Have heart problems or have had a heart attack or stroke;
Have had manic episodes (extreme agitation or excitability);
Have ever attempted suicide;
Have had convulsions (seizures);
Are pregnant or breast-feeding.
How should I take nefazodone?
Take nefazodone at the same time every day exactly as prescribed by your doctor. You may take nefazodone with or without food.
It may take a while for you to feel that nefazodone is working. You may not feel the full effect for several weeks. Once you feel better, it is important to keep taking nefazodone as directed by your doctor.
If you miss a dose of nefazodone, skip that dose and continue with your regular schedule. Never take 2 doses at the same time.
If you think that you have taken more nefazodone than prescribed, contact your doctor, local poison control center, or emergency room right away.
What should I avoid while taking nefazodone?
Do not drive or operate possibly dangerous machinery (such as an automobile, power mower, or power tool) or participate in any hazardous activity that requires full mental alertness until you know how nefazodone affects you.
Before taking nefazodone, tell your doctor about any medicines you are taking, including vitamin supplements, herbal remedies, and any non-prescription (over-the-counter) medicines. Some of these medicines may affect how nefazodone works and should not be used in combination without talking to your doctor.
Do not drink alcoholic beverages while taking nefazodone.
Tell your doctor if you are pregnant, planning to become pregnant, or become pregnant while taking nefazodone. It is not known whether nefazodone can harm your unborn baby.
Talk with your doctor before taking nefazodone if you are breast-feeding. It is not known whether nefazodone can pass through your breast milk to the baby.
What are the possible side effects of nefazodone?
The most common side effects of nefazodone are sleepiness, dry mouth, nausea, dizziness, constipation, weakness, lightheadedness, problems with vision, and confusion.
Call your doctor right away if you have any of the following side effectsSevere nausea
Abdominal (lower stomach) pain
Rash or hives
Seizure (convulsion)
Fainting
Erection that lasts too long
Tell your doctor right away about any side effects that you have or discomfort that you experience. Do not change your dose or stop taking nefazodone without talking with your doctor firstYour doctor has prescribed nefazodone for you and you alone. Do not give nefazodone to other people even if they have the same condition. It may harm them.
This leaflet provides a summary of the most important information about nefazodone. If you would like more information, talk with your doctor or pharmacist. You can ask for information about nefazodone that is written for healthcare professionals.
Seldane® is a registered trademark of Hoechst Marion Roussel Inc. (now Aventis Pharmaceuticals).
Hismanal® and Propulsid® are registered trademarks of Janssen Pharmaceutica Products, L.P.
Nardil® is a registered trademark of Parke-Davis.
Parnate® is a registered trademark of SmithKline Beecham Pharmaceuticals.
Halcion® is a registered trademark of Pharmacia & Upjohn.
Orap® is a registered trademark of Gate Pharmaceuticals, a division of TEVA Pharmaceuticals USA.
Tegretol® is a registered trademark of Novartis Pharmaceuticals Corporation.
Manufactured In Israel By:
TEVA PHARMACEUTICAL IND. LTD.
Jerusalem, 91010, Israel
Manufactured For:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. A 8/2008
This Patient Information Leaflet has been approved by the U.S. Food and Drug Administration.x only
Read the Medication Guide that comes with your’s, healthcare provider about:
all risks and benefits of treatment with antidepressant medicines
all treatment choices for depression or other serious mental illness
1. ithin the first few months of treatment.
2. .
3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
started or when the dose is changed.
Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
thoughts about suicide or dying
attempts to commit suicide
new or worse depression
new or worse anxiety
feeling very agitated or restless
panic attacks
trouble sleeping (insomnia)
new or worse irritability
acting aggressive, being angry, or violent
acting on dangerous impulses
an extreme increase in activity and talking (mania)
other unusual changes in behavior or mood
What else do I need to know about antidepressant medicines?
Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
Antidepressants are medicines used to treat depression and other illnesses. . , not just the use of antidepressants.
Antidepressant medicines have other side effects. .
s. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
’s healthcare provider for more informatioE 5/2008
Precautions with Alcohol
Alcohol-NefazodThere is limited information regarding Nefazodone Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Nefazodone Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
↑ Invalid <ref> tag; no text was provided for refs named Lexi-Comp
|
Lactose_intolerance_historical_perspective | Lactose intolerance was first discovered by Hippocrate, the ancient Greek physician 2500 years ago. In 1906, Pimmer discovered lactase enzyme in the intestine of infant dogs, pigs, and rats. . In 1978, breath hydrogen test was used by Levitt to diagnose lactose intolerance.
Lactose intolerance was first discovered by Hippocrate, the ancient Greek physician 2500 years ago.
In 1906, Pimmer was the first scientist to discover lactase enzyme in the intestine of infant dogs, pigs, and rats. He also found that this enzyme decreased in the adult intestine of these animals.
In 1959, Durand and Holzei et al decribed congenital lactase deficiency
The association between the ethnicity and lactose intolerance was discovered in 1966 by Bayless and Rosensweig and in 1968 by Neale.
In the early 1970s, lactase-phlorizin hydrolase (LPH) gene mutations were first implicated in the pathogenesis of lactose intolerance.
In 1978, breath hydrogen test was used by Levitt to diagnose lactose intolerance
|
Infantile_hemangioendothelioma | Infantile hemangioendothelioma is a rare benign vascular tumour arising from mesenchymal tissue and is usually located in the liver. It often presents in infancy with cardiac failure because of extensive arteriovenous shunting within the lesion. It is the third most common liver tumor in children, the most common benign vascular tumor of the liver in infancy, and the most common symptomatic liver tumor during the first 6 months of life.
Infantile hemangioendotheliomas have a variable sonographic appearance and may be either hypoechoic or hyperechoic or may have mixed echogenicity.
Color Doppler US evaluation will show increased flow.
, , ,
, , ,
, , ,
|
Melanoma_electrocardiogram | There are no ECG findings associated with melanoma.
There are no ECG findings associated with melanoma.
|
Strongyloidiasis_laboratory_findings | The diagnosis of strongyloidiasis is made by presence of clinical signs and symptoms, eosinophilia, and positive serological findings. Definitive diagnosis of strongyloidiasis is generally made by the detection of larvae in the stool. Sputum examination may rarely be used to identify organisms in cases of hyperinfection. Agar tracking (detection of larval tracks on agar culture plates) has been shown to be more sensitive than the conventional stool examination. However, agar tracking is usually unavailable on a routine basis in clinical microbiology laboratories. repeated examinations of stool. Enzyme immunoassay (EIA) is currently recommended because of its greater sensitivity (90%). Antibody test results cannot be used to differentiate between the past and current infection. In disseminated cases of strongyloidiasis, larvae can be detected in sputum by simple wet-mount in fluid from a bronchoalveolar lavage (BAL).
Eosinophilia is generally present during the acute and chronic stages but may be absent with dissemination.
The gold standard for the diagnosis of strongyloidiasis is serial stool examination.
The diagnosis rests on the microscopic identification of larvae (rhabditiform and occasionally filariform) in the stool.
Single ova and parasite examination can have negative results in up to 70% of cases.
Repeated examinations of stool specimens increase the chances of detecting larvae.
The diagnostic sensitivity increases to 50% with three stool examinations and can approach 100% if seven serial stool samples are examined
Specialized stool examinations techniques include Baermann concentration, Horadi-Mori filter paper culture, quantitative acetate concentration technique, and nutrient agar plate cultures.
Diagnostic characteristics: length 200 to 250 µm (up to 380 µm), Short buccal cavity, Prominent genital primordium.
Strongyloides stercoralis:The prominent genital primordium in the mid-section of the larva (black arrow) is readily evident. Note also the Entamoeba coli cyst (white arrow) near the posterior end of the larva. Source:https://commons.wikimedia.org/w/index.php?curid=219824
Immunodiagnostic tests for strongyloidiasis are indicated when the infection is suspected and the organism cannot be demonstrated by duodenal aspiration, string tests, or by repeated examinations of stool.
Antibody detection tests should use antigens derived from Strongyloides stercoralis filariform larvae for the highest sensitivity and specificity.
Although indirect fluorescent antibody (IFA) and indirect hemagglutination (IHA) tests have been used,
Immunocompromised persons with disseminated strongyloidiasis usually have detectable IgG antibodies despite their immunosuppression.
Cross-reactions in patients with filariasis and other nematode infections can occur.
Antibody test results cannot be used to differentiate between the past and current infection.
A positive test warrants continuing efforts to establish a parasitological diagnosis followed by antihelminthic treatment.
Serologic monitoring may be useful in the follow-up of immunocompetent treated patients: antibody levels decrease markedly within 6 months after successful chemotherapy.
More sensitive and specific serologic tests using recombinant antigens have been and are being developed, and are available at specific laboratories.
An additional advantage of these serologic tests is that there is typically a significant drop in titer by 6 months after parasite eradication, which may make it possible to use these tests as a check the response to medical therapy.
{{#ev:youtube|TSwN602mcn4}}
Serology can be useful but is not commonly available and can give false-negative results.
Results for ELISA should be used in conjunction with clinical history and geographical data |
Simvastatin_use_in_specific_populations | Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the {{{indicationType}}} of reductions in risk of CHD mortality and cardiovascular events, hyperlipidemia, adolescent patients with heterozygous familial hypercholesterolemia (HeFH). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection.
The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
Patients taking Verapamil, Diltiazem, or Dronedarone
The dose of simvastatin should not exceed 10 mg/day.
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin should not exceed 20 mg/day.
The recommended dosage is 40 mg/day in the evening. simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin should be reduced by 50% if initiating lomitapide. simvastatin dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.
Because simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin is administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored.
Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in adult patients.
Dosing Information
40 mg/day for 1 month followed by 80 mg/day thereafter
Dosing Information
40 mg
Dosing Information
10 to 20 mg/day
Dosing Information
5 mg
Dosing information
80 mg/day
Dosing information
20 mg twice daily
Dosing information
80 mg/day
Dosing information
80 mg/day
Dosing information
20 mg daily
Dosing Information
The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products).
Concomitant administration of gemfibrozil, cyclosporine, or danazol.
Hypersensitivity to any component of this medication.
Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
Women who are pregnant or may become pregnant
Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.
Nursing mothers
It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin should not breastfeed their infants.
Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.
The risk of myopathy, including rhabdomyolysis, is dose related. In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively. The incidence of myopathy with 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin. Therefore, the 80-mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. If, however, a patient who is currently tolerating the 80-mg dose of simvastatin needs to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction. Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing simvastatin. simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with simvastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.
Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. simvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. simvastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Drug Interactions
The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or grapefruit juice. Combination of these drugs with simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
The combined use of simvastatin with gemfibrozil, cyclosporine, or danazol is contraindicated.
Caution should be used when prescribing other fibrates with simvastatin, as these agents can cause myopathy when given alone and the risk is increased when they are co-administered.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
The benefits of the combined use of simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine.
Cases of myopathy, including rhabdomyolysis, have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. In an ongoing, double-blind, randomized cardiovascular outcomes trial, an independent safety monitoring committee identified that the incidence of myopathy is higher in Chinese compared with non-Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses of a niacin-containing product. Caution should be used when treating Chinese patients with simvastatin in doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. It is unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
Prescribing recommendations for interacting agents are summarized in the table below.
This image is provided by the National Library of Medicine.
Persistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity.
In the Scandinavian Simvastatin Survival Study (4S), the number of patients with more than one transaminase elevation to >3X ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 [0.7%] vs. 12 [0.6%]). Elevated transaminases resulted in the discontinuation of 8 patients from therapy in the simvastatin group (n=2,221) and 5 in the placebo group (n=2,223). Of the 1,986 simvastatin treated patients in 4S with normal liver function tests (LFTs) at baseline, 8 (0.4%) developed consecutive LFT elevations to >3X ULN and/or were discontinued due to transaminase elevations during the 5.4 years (median follow-up) of the study. Among these 8 patients, 5 initially developed these abnormalities within the first year. All of the patients in this study received a starting dose of 20 mg of simvastatin; 37% were titrated to 40 mg.
In 2 controlled clinical studies in 1,105 patients, the 12-month incidence of persistent hepatic transaminase elevation without regard to drug relationship was 0.9% and 2.1% at the 40- and 80-mg dose, respectively. No patients developed persistent liver function abnormalities following the initial 6 months of treatment at a given dose.
It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with simvastatin, promptly interrupt therapy. If an alternate etiology is not found do not restart simvastatin. Note that ALT may emanate from muscle, therefore ALT rising with CK may indicate myopathy.
The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin.
As with other lipid-lowering agents, moderate (less than 3X ULN) elevations of serum transaminases have been reported following therapy with simvastatin. These changes appeared soon after initiation of therapy with simvastatin, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.
Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia(0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).
Scandinavian Simvastatin Survival Study
In 4S involving 4,444 (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of simvastatin (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.
This image is provided by the National Library of Medicine.
Heart Protection Study
In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simvastatin compared with 5.1% in patients treated with placebo. The incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.
Other Clinical Studies
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.
Laboratory Tests
Marked persistent increases of hepatic transaminases have been noted. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK.
Adolescent Patients (ages 10-17 years)
In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or simvastatin(10-40 mg daily), the most common adverse reactions observed in both groups were upper respiratory infection, headache, abdominal pain, and nausea.
Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during postapproval use of simvastatin: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting, anemia, erectile dysfunction, interstitial lung disease, rhabdomyolysis, hepatitis/jaundice, fatal and non-fatal hepatic failure, and depression.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1)].
An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4.
Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [SeeWarnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated.
Gemfibrozil: Contraindicated with simvastatin.
Other fibrates: Caution should be used when prescribing with simvastatin.
The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day Niacin) of Niacin-containing products. In particular, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of Niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of Niacin-containing products.
In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in digoxin concentrations in plasma. Patients taking digoxin should be monitored appropriately when simvastatin is initiated.
In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
Pregnancy Category (FDA): X
simvastatin is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to statins in utero. Animal reproduction studies of simvastatin in rats and rabbits showed no evidence of teratogenicity. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. If simvastatin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
There are rare reports of congenital anomalies following intrauterine exposure to statins. In a review3 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related statin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the general population. However, the study was only able to exclude a 3- to 4-fold increased risk of congenital anomalies over the background rate. In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified.
Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed in rats and mice.
Women of childbearing potential, who require treatment with simvastatin for a lipid disorder, should be advised to use effective contraception. For women trying to conceive, discontinuation of simvastatin should be considered. If pregnancy occurs, simvastatin should be immediately discontinued.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Simvastatin in women who are pregnant.
There is no FDA guidance on use of Simvastatin during labor and delivery.
It is not known whether simvastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother
Safety and effectiveness of simvastatin in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with simvastatin had an adverse reaction profile similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on menstrual cycle length in girls. Adolescent females should be counseled on appropriate contraceptive methods while on simvastatin therapy. Simvastatin has not been studied in patients younger than 10 years of age, nor in pre-menarchal girls.
Of the 2,423 patients who received simvastatin in Phase III clinical studies and the 10,269 patients in the Heart Protection Study who received simvastatin, 363 (15%) and 5,366 (52%), respectively were ≥65 years old. In HPS, 615 (6%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, simvastatin should be prescribed with caution in the elderly.
A pharmacokinetic study with simvastatin showed the mean plasma level of statin activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age. In 4S, 1,021 (23%) of 4,444 patients were 65 or older. Lipid-lowering efficacy was at least as great in elderly patients compared with younger patients, and simvastatin significantly reduced total mortality and CHD mortality in elderly patients with a history of CHD. In HPS, 52% of patients were elderly (4,891 patients 65-69 years and 5,806 patients 70 years or older). he relative risk reductions of CHD death, non-fatal MI, coronary and non-coronary revascularization procedures, and stroke were similar in older and younger patients. In HPS, among 32,145 patients entering the active run-in period, there were 2 cases of myopathy/rhabdomyolysis; these patients were aged 67 and 73. Of the 7 cases of myopathy/rhabdomyolysis among 10,269 patients allocated to simvastatin, 4 were aged 65 or more (at baseline), of whom one was over 75. There were no overall differences in safety between older and younger patients in either 4S or HPS.
Because advanced age (≥65 years) is a predisposing factor for myopathy, including rhabdomyolysis, simvastatin should be prescribed with caution in the elderly. In a clinical trial of patients treated with simvastatin 80 mg/day, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.
There is no FDA guidance on the use of Simvastatin with respect to specific gender populations.
There is no FDA guidance on the use of Simvastatin with respect to specific racial populations.
Caution should be exercised when simvastatin is administered to patients with severe renal impairment
Simvastatin is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels
There is no FDA guidance on the use of Simvastatin in women of reproductive potentials and males.
There is no FDA guidance one the use of Simvastatin in patients who are immunocompromised.
Oral
There is limited information regarding motoring of Simvastatin in the drug label.
There is limited information regarding the compatibility of Simvastatin and IV administrations.
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.
A few cases of overdosage with simvastatinhave been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae. Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C25H38O5 and its molecular weight is 418.57. Its structural formula is:
This image is provided by the National Library of Medicine.
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Simvastatin talets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, citric acid, hydroxypropyl cellulose, hypromellose, iron oxides, lactose, magnesium stearate, microcrystalline cellulose, starch, talc, and titanium dioxide. Butylated hydroxyanisole is added as a preservative.
Epidemiological studies have demonstrated that elevated levels of total-C, LDL-C, as well as decreased levels of HDL-C are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus 14C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (<5%).
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.
The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. While the recommended therapeutic dose range is 5 to 40 mg/day, there was no substantial deviation from linearity of AUC of inhibitors in the general circulation with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal.
In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age. Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and younger patients [see Use in Specific Populations (8.5)].
Kinetic studies with another statin, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency (as measured by creatinine clearance).
Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of statins. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4.
The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy.
This image is provided by the National Library of Medicine.
In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a single 0.4 mg dose on day 10) by approximately 0.3 ng/mL.
In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day.
In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).
In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC).
A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose.
No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
There was decreased fertility in male rats treated with simvastatin for 34 weeks at 25 mg/kg body weight (4 times the maximum human exposure level, based on AUC, in patients receiving 80 mg/day); however, this effect was not observed during a subsequent fertility study in which simvastatin was administered at this same dose level to male rats for 11 weeks (the entire cycle of spermatogenesis including epididymal maturation). No microscopic changes were observed in the testes of rats from either study. At 180 mg/kg/day, (which produces exposure levels 22 times higher than those in humans taking 80 mg/day based on surface area, mg/m2), seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. In dogs, there was drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation at 10 mg/kg/day, (approximately 2 times the human exposure, based on AUC, at 80 mg/day). The clinical significance of these findings is unclear.
CNS Toxicity
Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.
A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.
CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.
There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).
Reductions in Risk of CHD Mortality and Cardiovascular Events
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol 212-309 mg/dL (5.5-8.0 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20-40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Over the course of the study, treatment with simvastatin led to mean reductions in total-C, LDL-C and TG of 25%, 35%, and 10%, respectively, and a mean increase in HDL-C of 8%. simvastatin significantly reduced the risk of mortality by 30% (p=0.0003, 182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p=0.00001, 111 vs 189 deaths). There was no statistically significant difference between groups in non-cardiovascular mortality. simvastatin significantly decreased the risk of having major coronary events (CHD mortality plus hospital-verified and silent non-fatal myocardial infarction MI) by 34% (p<0.00001, 431 vs 622 patients with one or more events). The risk of having a hospital-verified non-fatal MI was reduced by 37%. simvastatin significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (p<0.00001, 252 vs 383 patients). simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p=0.033, 75 vs 102 patients). simvastatin reduced the risk of major coronary events to a similar extent across the range of baseline total and LDL cholesterol levels. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be adequately assessed. However, simvastatin significantly lessened the risk of having major coronary events by 34% (60 vs 91 women with one or more event). The randomization was stratified by angina alone (21% of each treatment group) or a previous MI. Because there were only 57 deaths among the patients with angina alone at baseline, the effect of simvastatin on mortality in this subgroup could not be adequately assessed. However, trends in reduced coronary mortality, major coronary events and revascularization procedures were consistent between this group and the total study cohort. Additionally, simvastatin resulted in similar decreases in relative risk for total mortality, CHD mortality, and major coronary events in elderly patients (≥65 years), compared with younger patients.
The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on simvastatin 40 mg and 10,267 on placebo). Patients were allocated to treatment using a covariate adaptive method which took into account the distribution of 10 important baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients had a mean age of 64 years (range 40-80 years), were 97% caucasian and were at high risk of developing a major coronary event because of existing CHD (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males ≥65 years (6%). At baseline, 3,421 patients (17%) had LDL-C levels below 100 mg/dL, of whom 953 (5%) had LDL-C levels below 80 mg/dL; 7,068 patients (34%) had levels between 100 and 130 mg/dL; and 10,047 patients (49%) had levels greater than 130 mg/dL.
The HPS results showed that simvastatin 40 mg/day significantly reduced: total and CHD mortality; non-fatal MI, stroke, and revascularization procedures (coronary and non-coronary), see table below.
This image is provided by the National Library of Medicine.
Two composite endpoints were defined in order to have sufficient events to assess relative risk reductions across a range of baseline characteristics, see Figure 1. A composite of major coronary events (MCE) was comprised of CHD mortality and non-fatal MI (analyzed by time-to-first event; 898 patients treated with simvastatin had events and 1,212 patients on placebo had events). A composite of major vascular events (MVE) was comprised of MCE, stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures (analyzed by time-to-first event; 2,033 patients treated with simvastatin had events and 2,585 patients on placebo had events). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p<0.0001). Treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetics showed risk reductions for MCE and MVE due to simvastatin treatment regardless of baseline HbA1c levels or obesity with the greatest effects seen for diabetics without CHD.
This image is provided by the National Library of Medicine.
Angiographic Studies
In the Multicenter Anti-Atheroma Study, the effect of simvastatin on atherosclerosis was assessed by quantitative coronary angiography in hypercholesterolemic patients with CHD. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were evaluated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. Simvastatin significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.
Modifications of Lipid Profiles
Primary Hyperlipidemia (Fredrickson type lla and llb)
Simvastatin has been shown to be effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hyperlipidemia and in mixed hyperlipidemia. Maximal to near maximal response is generally achieved within 4-6 weeks and maintained during chronic therapy. Simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C, see table below.
This image is provided by the National Library of Medicine.
Hypertriglyceridemia (Fredrickson type IV)
The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in the table below.
This image is provided by the National Library of Medicine.
Dysbetalipoproteinemia (Fredrickson type lll)
The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented the table below.
This image is provided by the National Library of Medicine.
Homozygous Familial Hypercholesterolemia
In a controlled clinical study, 12 patients 15-39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. In 11 patients with reductions in LDL-C, the mean LDL-C changes for the 40- and 80-mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80-mg dose.
Endocrine Function
In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4,444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadalaxis in pre-menopausal women are unknown.
In a double-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10-17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH) were randomized to simvastatin (n=106) or placebo (n=67) for 24 weeks (base study). Inclusion in the study required a baseline LDL-C level between 160 and 400 mg/dL and at least one parent with an LDL-C level >189 mg/dL. The dosage of simvastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter. In a 24-week extension, 144 patients elected to continue therapy with simvastatin 40 mg or placebo.
Simvastatin significantly decreased plasma levels of total-C, LDL-C, and Apo B see table below. Results from the extension at 48 weeks were comparable to those observed in the base study.
This image is provided by the National Library of Medicine.
After 24 weeks of treatment, the mean achieved LDL-C value was 124.9 mg/dL (range: 64.0-289.0 mg/dL) in the simvastatin 40 mg group compared to 207.8 mg/dL (range: 128.0-334.0 mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children with HeFH. The long-term efficacy of simvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
No. 8360 — Tablets ZOCOR 5 mg are buff, oval, film-coated tablets, coded MSD 726 on one side and ZOCOR 5 on the other. They are supplied as follows:
NDC 0006-0726-31 unit of use bottles of 30.
No. 8146 — Tablets ZOCOR 10 mg are peach, oval, film-coated tablets, coded MSD 735 on one side and plain on the other. They are supplied as follows:
NDC 0006-0735-31 unit of use bottles of 30
NDC 0006-0735-54 unit of use bottles of 90.
No. 8147 — Tablets ZOCOR 20 mg are tan, oval, film-coated tablets, coded MSD 740 on one side and plain on the other. They are supplied as follows:
NDC 0006-0740-31 unit of use bottles of 30
NDC 0006-0740-54 unit of use bottles of 90.
No. 8148 — Tablets ZOCOR 40 mg are brick red, oval, film-coated tablets, coded MSD 749 on one side and plain on the other. They are supplied as follows:
NDC 0006-0749-31 unit of use bottles of 30
NDC 0006-0749-54 unit of use bottles of 90.
No. 6577 — Tablets ZOCOR 80 mg are brick red, capsule-shaped, film-coated tablets, coded 543 on one side and 80 on the other. They are supplied as follows:
NDC 0006-0543-31 unit of use bottles of 30
NDC 0006-0543-54 unit of use bottles of 90.
Store between 5-30°C (41-86°F).
{{#ask: Page Name::Simvastatin
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Simvastatin
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.
Patients should be advised about substances they should not take concomitantly with simvastatin. Patients should also be advised to inform other healthcare professionals prescribing a new medication or increasing the dose of an existing medication that they are taking simvastatin.
All patients starting therapy with simvastatin should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing simvastatin. Patients using the 80-mg dose should be informed that the risk of myopathy, including rhabdomyolysis, is increased with use of the 80-mg dose. The risk of myopathy, including rhabdomyolysis, occurring with use of simvastatin is increased when taking certain types of medication or consuming grapefruit juice. Patients should discuss all medication, both prescription and over the counter, with their healthcare professional.
It is recommended that liver function tests be performed before the initiation of simvastatin, and thereafter when clinically indicated. All patients treated with simvastatin should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using simvastatin. Discuss future pregnancy plans with your patients, and discuss when to stop taking simvastatin if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking simvastatin and call their healthcare professional.
Women who are breastfeeding should not use simvastatin. Patients who have a lipid disorder and are breastfeeding should be advised to discuss the options with their healthcare professional.
Alcohol-Simvastatin detailed information interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Zocor
Zocor - Cozaar
Zocor - ZyrTEC
Drug Shortage
|
Urinary_frequency | Polyuria is the passage of a large volume of urine in a given period (>= 2.5L/24 hours in adult humans). It often appears with increased thirst (polydipsia). Various causes of polyuria include
Central diabetes inispidus (CDI), Idiopathic CDI: the most common cause of CDI, Familial CDI, Wolfram syndrome ( DIDOMAD syndrome), Congenital hypopituitarism, Septo-optic dysplasia, Surgery/trauma, Cancer (lung cancer, leukemia, lymphoma), Hypoxic encephalopathy, Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis), Post-supraventricular tachycardia, Anorexia nervosa
Nephrogenic diabetes inspidous (NDI), Hereditary NDI, Lithium, Hypercalcemia, Hypokalemia, Renal disease: Bilateral urinary tract obstruction, Medullary cystic kidney disease, Amyloidosis, Sjogren's syndrome, Autosomal dominant polycystic kidney disease, Sickle cell disease, Medications: Cidofovir, Foscarnet, Amphotericin B, Demeclocycline, Ifosfamide, Ofloxacin, Orlistat, Didanosine, V2 receptor antagonists, Gestational diabetes insipidus, Craniopharyngioma surgery, Bardet-biedl syndrome, Bartter syndrome, Cystinosis
Primary Polydipsia
Osmotic diuresis: Diabetes mellitus
3,3-dichlorobenzidine
Aceruloplasminemia
Acid-base imbalance
Acute tubular necrosis
Adrenal adenoma
Adrenal cancer
Adrenal cortex neoplasms
Adrenal gland hyperfunction
Adrenal incidentaloma
Adrenocortical carcinoma
Aldosteronism
Alsing syndrome
Altitude diuresis
Amelogenesis imperfeca
Amitraz
Anorexia nervosa
Apparent mineralocorticoid excess
Back tumor
Bartter syndrome
BCG vaccine
Bendrofluazide
Benign prostatic hyperplasia
Bladder cancer
Bladder compression
Bladder diverticulum
Boichis syndrome
Bumetanide
Caffeine poisoning
Canagliflozin
Cardiorespiratory disease
Cerebral salt-wasting syndrome
Chemotherapy-induced cystitis
Chronic glomerulonephritis
Chronic interstitial nephritis
Chronic kidney disease
Chronic renal failure
Chronic wasting disease
Combat stress reaction
Congestive heart failure
Conivaptan
Conn-louis carcinoma
Conn's adenoma
Conn's syndrome
Cushing syndrome
Cushing's syndrome
Cystinosis
Cystitis
Danubian endemic familial nephropathy
Dapagliflozin
Dend syndrome
Diabetes insipidus
Diabetes mellitus
Diabetic nephropathy
Diencephalic syndrome
Diuretic therapY
DKA
Early chronic pyelonephritis
East syndrome
Ectopic ACTH syndrome
Electrolyte abnormality
Empagliflozin
Eosinophilic cystitis
Erdheim-chester syndrome
Excessive riboflavin
Excessive vitamin d
Familial hypopituitarism
Fanconi syndrome
Foscarnet sodium
Froelich's syndrome
Frusemide
Generalized anxiety disorder
Gestational diabetes
Gitelman syndrome
Glomerulonephritis
Gonococcal urethritis
Goserelin
Hair-an syndrome
Heerfordt syndrome
Hemochromatosis
Hereditary primary fanconi disease
Hhns
Hip cancer
Hormonal
Hydrochlorothiazide
Hyperadrenalism
Hypercalcemia
Hypercalcuria
Hyperglycemia
Hyperosmolar hyperglycemic nonketotic syndrome
Hyperosmolarity
Hyperparathyroidism
Hyperthyroidism
Hypervitaminosis a
Hypervitaminosis d
Hypokalemia
Hypokalemic periodic paralysis
Hypopituitarism
Hypothalamic dysfunction
Intermediate cystinosis
Interstitial cystitis
Isosorbide
Juniper tar poisoning
Juvenile nephronophthisis
Langerhans cell histiocytosis
Leukemia
Lithium
Machado-joseph disease
Mannitol
Medullary cystic kidney disease
Megalocytic interstitial nephritis
Membranoproliferative glomerulonephritis
Migraine
Multiple endocrine neoplasia
Nabilone
Nephrocalcinosis
Nephrogenic diabetes insipidus
Nephrolithiasis
Nephronophthisis
Nephronophthisis type 1
Nephropathic cystinosis
Neurologic damage
Neurosarcoidosis
Noctural polyuria syndrome
Oak poisoning
Oligomeganephronic renal hypoplasia
Olivopontocerebellar atrophy type 3
Osmotic diuresis
Ovarian cysts
Overactive bladder
Panhypopituitarism
Parathyroid cancer
Paroxysmal tachycardia
Pathological water intake
Pelvic lipomatosis
Phendimetrazine
Pheochromocytoma
Pituitary tumors
Polycystic kidney disease
Polydipsia
Postobstructive uropathy
Postural orthostatic tachycardia syndrome
Premenstrual syndrome
Primary hyperaldosteronism
Primary tubular proximal acidosis
Probenecid
Prostate cancer
Proximal renal tubular acidosis
Proximal tubulopathy
Psychogenic polydipsia
Pyelonephritis
Radiation cystitis
Radiographic contrast media
Reflux nephropathy
Reiter’s syndrome
Renal cell cancer
Renal failure
Renal tubular acidosis
Renal tubular transport disorders
Resolving hematoma
Rib tumor
Sassoon hospital syndrome
Secondary bone cancer
Seizures
Senior-loken syndrome
Serratia urinary tract infection
Sicca syndrome
Sickle-cell anemia
Silicon dioxide
Sodium ferrocyanide
Sorbitol
Streptococcal group b invasive disease
Syndrome of inappropriate antidiuretic hormone
Tiagabine
Tolvaptan
Toni-fanconi syndrome type 1
Urethral cancer
Urethritis
Urinary outflow obstruction
Urinary stones
Urinary tract infection
Uterine fibroids
Uterine leiomyoma
Vagina cancer
Wandering spleen
Wolfram's disease
Results from a deficiency in production, and release of functional AVP, hence respond to administration of exogenous AVP.
CDI can be acquired or hereditary. ADH-producing cells' injury in hypothalamus/pituitary can be idiopathic, or due to trauma or infection.
Hereditary forms of familial CDI can occur secondary to 66 different mutations of the genes encoding AVP-neurophysin II precursor.
It results from an inappropriate renal response to AVP and usually reflects a functional defect in V2R or AQP2 protein.
Administration of AVP, therefore is not sufficient to rectify the concentration defect. It is more commonly an acquired disease.
Over 225 different mutations in AVPR2 represent almost 90% of hereditary NDI cases.
Glucose-induced osmotic diuresis is the major etiology of polyuria in patients with hyperglycemia.
It is presumed that a central defect in thirst regulation has an important role in pathophysiology of polydipsia.
In some polydipsia patients for example, the osmotic threshold for thirst is reduced below the threshold for release of AVP.
AVP is suppressed by fall in plasma osmolality(because of excessive water intake), and causes rapid excretion of the excess water and continued stimulation of thirst.
Polyuria can result in dehydration, hypernatremia and electrolyte abnormalities if the etiology is solute diuresis. |
Phosphates | A phosphate, in inorganic chemistry, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Phosphates are important in biochemistry and biogeochemistry or ecology.
The general chemical structure of a phosphate
This is the structural formula of the phosphoric acid functional group as found in a weakly acidic aqueous solution. In more basic aqueous solutions, the group will donate the two hydrogen atoms and ionize as a phosphate group with a negative charge of 2.
The phosphate ion is a polyatomic ion with the empirical formula PO43− and a molar mass of 94.97 g/mol; it consists of one central phosphorus atom surrounded by four identical oxygen atoms in a tetrahedral arrangement. The phosphate ion carries a negative three formal charge and is the conjugate base of the hydrogenphosphate ion, HPO42−, which is the conjugate base of H2PO4−, the dihydrogen phosphate ion, which in turn is the conjugate base of H3PO4, phosphoric acid. It is a hypervalent molecule (the phosphorus atom has 10 electrons in its valence shell). Phosphate is also an organophosphorus compound with the formula OP(OR)3.
A phosphate salt forms when a positively charged ion attaches to the negatively charged oxygen atoms of the ion, forming an ionic compound. Many phosphates are insoluble in water at standard temperature and pressure, except for the alkali metal salts.
In dilute aqueous solution, phosphate exists in four forms. In strongly basic conditions, the phosphate ion (PO43−) predominates, while in weakly basic conditions, the hydrogen phosphate ion (HPO42−) is prevalent. In weakly acid conditions, the dihydrogen phosphate ion (H2PO4−) is most common. In strongly acid conditions, aqueous phosphoric acid (H3PO4) is the main form.
, , H3PO4,
, , H2PO4−,
, , HPO42−,
, , PO43−,
More precisely, considering the following three equilibrium reactions:
H3PO4 ⇌ H+ + H2PO4−
H2PO4− ⇌ H+ + HPO42−
HPO42− ⇌ H+ + PO43−
the corresponding constants at 25°C (in mol/L) are (see phosphoric acid):
<math> K_{a1}=\frac{[\mbox{H}^+][\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^{-3}</math>
<math>K_{a2}=\frac{[\mbox{H}^+][\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^{-8}</math>
<math> K_{a3}=\frac{[\mbox{H}^+][\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-13}</math>
For a strongly basic pH (pH=13), we find
<math>\frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^{10} \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^5 \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14</math>
showing that only PO43− and HPO42− are in significant amounts.
For a neutral pH (for example the cytosol pH=7.0), we find
<math> \frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^4 \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 0.62 \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-6}</math>
so that only H2PO4− and HPO42− ions are in significant amounts (62% H2PO4−, 38% HPO42−). Note that in the extracellular fluid (pH=7.4), this proportion is inverted (61% HPO42−, 39% H2PO4−).
For a strongly acid pH (pH=1), we find
<math>\frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 0.075 \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^{-7} \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-12}</math>
showing that H3PO4 is dominant with respect to H2PO4−. HPO42− and PO43− are practically absent.
Phosphate can form many polymeric ions, diphosphate (also pyrophosphate), P2O74−, triphosphate, P3O105−, et cetera. The various metaphosphate ions have an empirical formula of PO3− and are found in many compounds.
Phosphate deposits can contain significant amounts of naturally occurring uranium. Subsequent uptake of such soil amendments can lead to crops containing uranium concentrations.
Elemental phosphorus and phosphides are not found (rare phosphide minerals may be found in meteorites).
Phosphates are the naturally occurring form of the element phosphorus, found in many phosphate minerals. In mineralogy and geology, phosphate refers to a rock or ore containing phosphate ions.
The largest rock phosphate deposits in North America lie in the Bone Valley region of central Florida, United States, the Soda Springs region of Idaho, and the coast of North Carolina. Smaller deposits are located in Montana, Tennessee, Georgia and South Carolina near Charleston along Ashley Phosphate road. The small island nation of Nauru and its neighbor Banaba Island, which used to have massive phosphate deposits of the best quality, have been mined excessively. Rock phosphate can also be found on Egypt, Israel, Morocco, Navassa Island, Tunisia, Togo and Jordan have large phosphate mining industries as well.
In biological systems, phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate, to distinguish it from phosphates bound in various phosphate esters. Inorganic phosphate is generally denoted Pi and can be created by the hydrolysis of pyrophosphate, which is denoted PPi:
P2O74− + H2O → 2HPO42−
However, phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. Similar reactions exist for the other nucleoside diphosphates and triphosphates. Phosphoanhydride bonds in ADP and ATP, or other nucleoside diphosphates and triphosphates, contain high amounts of energy which give them their vital role in all living organisms. They are generally referred to as high energy phosphate, as are the phosphagens in muscle tissue. Compounds such as substituted phosphines, have uses in organic chemistry but do not seem to have any natural counterparts.
In ecological terms, because of its important role in biological systems, phosphate is a highly sought after resource. Consequently, it is often a limiting reagent in environments, and its availability may govern the rate of growth of organisms. Addition of high levels of phosphate to environments and to micro-environments in which it is typically rare can have significant ecological consequences. For example, booms in the populations of some organisms at the expense of others, and the collapse of populations deprived of resources such as oxygen (see eutrophication). In the context of pollution, phosphates are a principal component of total dissolved solids, a major indicator of water quality.
Calcium hydroxyapatite and calcite precipitates can be found around bacteria in alluvial topsoil. As clay minerals promote biomineralization, the presence of bacteria and clay minerals resulted in calcium hydroxyapatite and calcite precipitates.
Phosphate deposits can contain significant amounts of naturally occurring heavy metals such as uranium. Mining operations processing phosphate rock can leave tailings piles containing elevated levels of cadmium, lead, nickel, copper, chromium, and uranium. Unless carefully managed, these waste products can leach heavy metals into groundwater or nearby estuaries. Uptake of these substances by plants and marine life can lead to concentration of toxic heavy metals in food products.
Phosphates were once commonly used in laundry detergent in the form trisodium phosphate (TSP), but because of algae boom-bust cycles tied to emission of phosphates into watersheds, phosphate detergent sale or usage is restricted in some areas.
In agriculture phosphate is one of the three primary plant nutrients, and it is a component of fertilizers. Rock phosphate is quarried from phosphate beds in sedimentary rocks. In former times it was simply crushed and used as is, but the crude form is now used only in organic farming. Normally it is chemically treated to make superphosphate, triple superphosphate, or ammonium phosphates, which have higher concentration of phosphate and are also more soluble, therefore more quickly usable by plants.
Fertilizer grades normally have three numbers; the first is the available nitrogen, the second is the available phosphate (expressed on a P2O5 basis), and the third is the available potash (expressed on a K2O basis). Thus a 10-10-10 fertilizer would contain ten percent of each, with the remainder being filler.
Surface runoff of phosphates from excessively fertilized farmland can be a cause of phosphate pollution leading to eutrophication (nutrient enrichment), algal bloom and consequent oxygen deficit. This can lead to anoxia for fish and other aquatic organisms in the same manner as phosphate-based detergents.
Phosphate compounds are occasionally added to the public drinking water supply to counter plumbosolvency.
The food industry uses phosphates to perform several different functions. For example, in meat products, it solubilizes the protein. This improves its water-holding ability and increases its moistness and succulence. In baked products, such as cookies and crackers, phosphate compounds can act as part of the leavening system when it reacts with an alkalai, usually sodium bicarbonate (baking soda).
organophosphorus compounds
Phosphine - PR3
Phosphine oxide - OPR3
Phosphinite - P(OR)R2
Phosphonite - P(OR)2R
Phosphite - P(OR)3
Phosphinate - OP(OR)R2
Phosphonate - OP(OR)2R
Phosphate - OP(OR)3, such as triphenyl phosphate
Phosphorus oxoacids |
Esters | A carboxylic acid ester. R and R' denote any alkyl or aryl group
A phosphoric acid ester
Esters are a class of chemical compounds and functional groups. Esters consist of an inorganic or organic acid in which at least one -OH (hydroxy) group is replaced by an -O-alkyl (alkoxy) group. The most common type of esters are carboxylic acid esters (R1-C(=O)-O-R2), other esters include phosphoric acid, sulfuric acid, nitric acid, and boric acid esters. Volatile esters often have a smell and are found in perfumes, essential oils, and pheromones and give many fruits their scent. Ethyl acetate and methyl acetate are important solvents, fatty acid esters form fat and lipids, and polyesters are important plastics. Cyclic esters are called lactones. The name "ester" is derived from the German Essig-Äther (literally:vinegar ether), an old name for ethyl acetate. Esters can be synthesized in a condensation reaction between an acid and an alcohol in a reaction known as esterification.
An ester is an often fragrant organic or partially organic compound formed by the reaction between an acid (including amino acids) and an alcohol (alkyl, R) or aromatic alcohol (aryl, R') (including a more basic amino acid) with the elimination of water. For examples,
acetic acid + an alcohol <=> acetic ester + water,
CH3COOH + ROH <=> CH3COOR + H2O,
or
CH3COO- + H+ + R+ + OH- <=> CH3COOR + H2O;
with one amino acid acting as a base:
formic acid + L-methionine <=> N-formyl-L-methionine (an amino acid) + H2O,
or
two amino acids:
Cys + Gly <=> Cys-Gly + H2O,
forming a dipeptide. A reaction between an inorganic hydroxide (e.g. sodium hydroxide) and an organic acid (e.g. acetic acid) produces a salt of acetic acid (sodium acetate). A compound is an ester when the hydroxide donor is organic and a salt when the hydroxide donor is inorganic. Hence, a carbonate can be thought of as a salt or an ester of carbonic acid.
An ester is named according to the two parts that make it up: the part from the alcohol and the part from the acid (in that order), for example ethyl sulfuric acid ester.
Since most esters are derived from carboxylic acids, a specific nomenclature is used for them. For esters derived from the simplest carboxylic acids, the traditional name for the acid constituent is generally retained, e.g. formate, acetate, propionate, butyrate. For esters from more complex carboxylic acids, the systematic name for the acid is used, followed by the suffix -oate. For example, methyl formate is the ester of methanol and methanoic acid (formic acid): the simplest ester. It could also be called methyl methanoate.
Esters of aromatic acids are also encountered, including benzoates such as methyl benzoate, and phthalates, with substitution allowed in the name.
The chemical formulas of esters are typically in the format of R-COO-R', in which the alkyl group (R') is mentioned first, and the carboxylate group (R) is mentioned last. For example the ester: butyl ethanoate - derived from butanol (C4H9OH) and ethanoic acid (CH3COOH) would have the formula: CH3COOC4H9. Sometimes the formula may be 'broken up' to show the structure, in this case: CH3COO[CH2]3CH3.
The acetic ester, N-formyl-L-methionine, and the dipeptide examples above are each monoesters.
The term oligoester refers to any ester polymer containing a small number of component esters. As an example, chemically, fats are generally diesters of glycerol and fatty acids. Most of the mass of a fat/triester is in the 3 fatty acids.
Tetraesters can be found as part of membrane-spanning lipids in bacteria from the order Thermotogales.
Pentaesters have been used as indicators or in isotopic labelling compounds.
Hexaesters such as calix[6]arene have been used in optodes as sensing devices for optical determination of potassium ion concentration in pH-buffer solutions.
Heptaesters have been found in Euphorbia species.
Octaesters can be inclusions of ester moieties within cavitand cavities.
The number of esters can be up to ten as in oligo-(R)-3-hydroxybutyrate.
Esters participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding makes them more water-soluble than their parent hydrocarbons. However, the limitations on their hydrogen bonding also make them more hydrophobic than either their parent alcohols or parent acids. Their lack of hydrogen-bond-donating ability means that ester molecules cannot hydrogen-bond to each other, which makes esters generally more volatile than a carboxylic acid of similar molecular weight. This property makes them very useful in organic analytical chemistry: unknown organic acids with low volatility can often be esterified into a volatile ester, which can then be analyzed using gas chromatography, gas liquid chromatography, or mass spectrometry.
Many esters have distinctive odors, which has led to their use as artificial flavorings and fragrances. For example:
"Esterification" (condensation of an alcohol and an acid) is not the only way to synthesize an ester. Esters can be prepared in the laboratory in a number of other ways:
by transesterifications between other esters
by Dieckmann condensation or Claisen condensation of esters carrying acidic α-protons
by Favorskii rearrangement of α-haloketones in presence of base
by nucleophilic displacement of alkyl halides with carboxylic acid salts
by Baeyer-Villiger oxidation of ketones with peroxides
by Pinner reaction of nitriles with an alcohol
Ester saponification (basic hydrolysis)
Esters react in a number of ways:
Esters may undergo hydrolysis - the breakdown of an ester by water. This process can be catalyzed both by acids and bases. The base-catalyzed process is called saponification. The hydrolysis yields an alcohol and a carboxylic acid or its carboxylate salt.
Esters also react if heated with primary or secondary amines, producing amides.
Phenyl esters react to hydroxyarylketones in the Fries rearrangement.
Di-esters such as diethyl malonate react as nucleophile with alkyl halides in the malonic ester synthesis after deprotonation.
Specific esters are functionalized with an α-hydroxyl group in the Chan rearrangement
Esters are converted to isocyanates through intermediate hydroxamic acids in the Lossen rearrangement.
Esters with β-hydrogen atoms can be converted to alkenes in ester pyrolysis
An introduction to esters
Molecule of the month: Ethyl acetate and other esters
Making an Ester A simple guide to naming and making esters, as well as the chemistry behind it. |
Ellis_Tonic_Sherry | A multivitamin is a preparation intended to supplement a human diet with vitamins
dietary minerals and other nutritional elements
Such preparations are available in the form of tablets
which are only available and administered under medical supervision
multivitamins are recognized by the Codex Alimentarius Commission (the United Nations' highest authority on food standards) as a category of food
Many multivitamins are formulated and/or labelled to differentiate consumer sectors e
Consumer multivitamin formulas are available as tablets
Once and twice per day multivitamin formulas dominate common usage
although some formulas are designed for consumption 3 - 7 times per day or even allow hourly use
Compositional variation amongst brands and lines allows substantial consumer choices
Modern multivitamin products roughly classify into RDA centric multivitamins with or without iron
RDA centric multivitamin/multimineral formulas with or without iron
higher potency formulas with mostly above RDA components with or without iron
and more specialized formulas by condition
such as for diabetics or by less common components
herbal extracts or premium vitamin and mineral forms
the US FDA allows a multivitamin to be called "high potency" if at least two-thirds of its nutrients have at least 100 percent of the DV
"high potency" usually means substantially increased vitamin C and Bs with some other enhanced vitamin and mineral levels
but some minerals may still be much less than DV
Some components are typically much lower than RDA amounts
usually the most expensive vitamin component
at over $4000 per active pound
is typically added in at only 5%-30% of RDA in many one per day formulations
Sometimes low content composition is for population subgroups
where the RDA would be inappropriate
such often occurs with iron
where the original population intake calculation was ca 12-13 mg iron per day by including menstruating females but some percentage of HFE gene bearing males
may only need as little as ~1 mg iron per day including the normal dietary contribution
Basic commercial multivitamin supplement products often contain the following ingredients
Other formulas may include additional ingredients such as other carotenes (e
higher than RDA amounts of B
C or E vitamins including gamma-tocopherol
citrus bioflavinoids or nutrient forms variously described as more easily absorbable
By supplementing the diet with additional vitamins and minerals
multivitamins can be a valuable tool for those with dietary imbalances or different nutritional needs
People with dietary imbalances may include those on restrictive diets and those who can't or won't eat a nutritious diet
Pregnant women and elderly adults have different nutritional needs than other adults
and a multivitamin may be indicated by their physicians
RDA centric multivitamins are not to be confused with the basic orthomolecular medicine daily recommendations
The proponents of that also generally recommend individually optimized
They also recommend more absorbable forms of vitamins and minerals
in inexpensive but higher potency formulas
While multivitamins can be a valuable tool to correct dietary imbalances
it is worth exercising basic caution before taking them
especially if any medical conditions exist
pregnant women should generally consult their doctors before taking any multivitamins
Because high doses of vitamin A are believed to cause birth defects
special multivitamin formulations exist for pregnant women that do not contain this nutrient
Severe vitamin and mineral deficiencies require medical treatment and can be very difficult to treat with common over-the-counter multivitamins
special vitamin or mineral forms with much higher potencies are available
either as individual components or as specialized formulations
Multivitamins in bottle related quantites may risk acute overdosage if taken in large amounts
due to the slight toxicity of certain components
other components at extraordinary levels in high potency forms include (but are not limited to) vitamin A
Total iron content of the whole bottle is the primary concern for child safety
There also are strict limits on the retinol content for vitamin A during pregnancies that are specifically addressed by prenatal formulas
various medical conditions and medications may adversely interact with multivitamins
For normal adults taking a multivitamin for general health purposes
conventional medicine and government authorities recommend that a multivitamin should contain 100% DRI/RDA or less for each ingredient
many common brand supplements in the United States contain above-DRI amounts for some vitamins or minerals
Many brands offer low iron or iron-free versions of their multivitamin supplements
Some analyses have suggested that high potency synthetic beta-carotene
without adequate other redox antioxidants such as vitamin C
may shorten life rather than extend it in cases of oxidative stress (e
liver disease and liver stressing chemicals (e
suggest that there appears to be little risk to supplement users of experiencing adverse side effects due to excessive intakes of micronutrients
the Journal of the American Medical Association stated that "it appears prudent for all adults to take vitamin supplements
which examined the clinical applications of vitamins for the prevention of chronic diseases in adults
Fairfield from the Harvard School of Medicine
examined English-language articles about vitamins in relation to chronic diseases published between 1966 and 2002
and concluded that inadequate intake of several vitamins has been linked to the development of diseases including coronary heart disease
1998 issue of the New England Journal of Medicine featured an editorial entitled "Eat Right and Take a Multivitamin" that was based on studies that showed health benefits resulting from the consumption of nutritional supplements
professor of Biochemistry and Molecular Biology at the University of California
and a senior scientist at Children's Hospital Oakland Research Institute (CHORI)
suggests that "to maximize human health and lifespan
scientists must abandon outdated models of micronutrients" and that "a metabolic tune-up through an improved supply of micronutrients is likely to have great health benefits
In 2006 the National Institutes of Health convened an expert panel to examine the available evidence on nutrient supplements
This review concluded that "Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly
or in combinations of three or more
" They noted that multivitamins could provide health benefits to some groups of people
but that there was "disturbing evidence of risk" in other groups
The panel's report concluded that the "present evidence is insufficient to recommend either for or against the use of Multivitamin/Mineral Supplements by the American public to prevent chronic disease
a 2006 report for the United States Department of Health and Human Services concluded that "regular supplementation with a single nutrient or a mixture of nutrients for years has no significant benefits in the primary prevention of cancer
age-related macular degeneration or cognitive decline
the report noted that multivitamins have beneficial effects in people with poor nutritional status
vitamin D and calcium can help prevent fractures in older people
and that zinc and antioxidants can help prevent age-related macular degeneration in people at a high risk of developing this disease
In 2007 the United Kingdom Food Standards Agency published an updated set of recommendations for eating a healthy diet
The recommendations stated that pregnant women should take extra folic acid and iron and that older people might need extra vitamin D and iron
the report advised that "Vitamin and mineral supplements are not a replacement for good eating habits" and stated that supplements are unnecessary for healthy adults who eat a balanced diet
Because of their categorization as a dietary supplement by the Food and Drug Administration (FDA)
most multivitamins sold in the U
are not required to undergo the rigorous testing procedures typical of pharmaceutical drugs
some multivitamins contain very high doses of one or several vitamins or minerals
or are specifically intended to treat
and therefore require a prescription or medicinal license in the U
Since such drugs contain no new substances
they do not require the same testing as would be required by a New Drug Application
but were allowed on the market as drugs due to Drug Efficacy Study Implementation program |
Allergic_conjunctivitis_future_or_investigational_therapies | Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.
They are capable of inducing local immunosuppression by blocking Th2 lymphocyte proliferation and IL-2 production and reducing eosinophils via inhibition of IL-5.
Topical and systemic cyclosporine a (CsA) have been suggested in the treatment of severe atopic keratoconjunctivitis.
Use of CsA appears to be safe and can eliminate the need/dependence of steroids.
Others calcineurin inhibitors that appears to be well tolerated by patients with severe atopic blepharoconjunctivitis and severe atopic keratoconjunctivitis are tacrolimus and pimecrolimus.
Mapracorat is a novel selective agonist of the glucocorticoid receptor, resulting in a lower potential for side effect.
In vitro, it inhibited migration and IL-8 release from eosinophils and the secretion of IL-6, IL-8, CCL5/RANTES, and TNF-α from a human mast cell line with equal potency as dexamethasone, but it was less potent in inducing annexin I and CXCR4 expression on the human eosinophils.
Animal model of allergic conjunctivitis demonstrated mapracorat was similar to dexamethasone eye drops in analogous reduction of clinical symptoms and conjunctival eosinophil. Hence,studies suggest this compound as a candidate for clinical trials of ocular allergy.
It is a biological engineered molecule, targeting the Cε3 domain of the IgE molecule. It binds with free IgE and prevents its attachment to high-affinity receptor (FcεRI) on mast cells, basophils and dendritic cells. An IgE-anti-IgE complex is formed, lowering free IgE.
Omalizumab has been established for use in asthma ,urticaria and and rhinitis.
Clinical trials are needed to asses its real impact in ocular allergies.
A novel target spleen tyrosine kinase (Syk) regulates the phosphorylation of phospholipase-C, phosphatidylinositol-3 kinase and protein kinase which mediate histamine release. Hence, studies will focus Syk inhibitors.
Janus protein kinase-3 is involved in the activation and proliferation of T-cells. Thus, novel inhibitors of JAK-3 may be an effective therapy. |
Volvulus_pathophysiology | Regardless of cause, volvulus causes symptoms by two mechanisms: One is bowel obstruction, manifested as abdominal distension and vomiting. The other is ischemia (loss of blood flow) to the affected portion of intestine. This causes severe pain and progressive injury to the intestinal wall, with accumulation of gas and fluid in the portion of the bowel obstructed. Ultimately, this can result in necrosis of the affected intestinal wall, acidosis, and death. Acute volvulus therefore requires immediate surgical intervention to untwist the affected segment of bowel and possibly resect any unsalvageable portion.
In western society, chronic constipation can lead to an overloaded sigmoid colon.
In developing nations, a high fiber diet leads to sigmoidal overload.
When the bowel loop is overloaded with material, it becomes susceptible to torsion along the axis of an elongated mesentery.
A large pelvic mass or a large gravid uterus can alter the position of the intra-abdominal organs, predisposing to the formation of volvulus.
With recurrent attacks of torsion, the base of the mesentery can become chronically inflammed and eventually shortens.
This leads to recurrent volvulus.
The twisting of a mobile loop of bowel can happen spontaneously and may be congenital or acquired.
Acquired causes of volvulus include: Adhesions, Iatrogenic e.g. lower GI endoscopy, Bowel atony, Hirschsprung's disease, Pregnancy
Congenital causes are discussed below.
Malrotation occurs when there is arrest of the normal rotation of the embryonic gut.
During weeks 4-8 of development, the embryonic coelom, or cavity, normally cannot accommodate the rapidly expanding gastrointestinal (GI) tract.
Consequently, the primary intestinal loop pushes back into the yolk stalk, and will become the future umbilicus.
The direction in which the loop grows takes the axis of the future superior mesenteric artery.
As the primary intestinal loop grows out of the abdomen, it begins to rotate by twisting 90 degrees counterclockwise.
There are two factors that force this rotation: The proximal bowel (gastroduodenal) grows faster than the distal bowel (cecocolic). The liver has rapidly develops.
During weeks 8 - 10, the primary intestinal loop continues to grow and returns back into the abdomen cavity and a further 180 degree counterclockwise rotation occurs.
Overall, the primary loop twists a total of 270 degrees in a counterclockwise direction.
Once the primary loop is in its final position, fixation to the posterior abdominal wall begins.
The proximal bowel portion including the stomach and duodenum are fixated early in gestation through the ligament of Treitz.
The colon takes a longer time to become fixated and usually, fixation is completed near term.
Normal gut development means that: A wide-based mesentery will extend from the ligament of Treitz in the left upper quadrant to the ileocecal valve in the right lower quadrant. The primary loop will continue its rotation upon return to the abdominal cavity. Both proximal (duodenojejunal) and distal (cecocolic) limbs rotate at the same rate and to the same degree.
Congenital volvulus happens when the following anomalies have occurred: Narrow mesenteric base: The midgut becomes suspended by a narrow pedicle. Non-rotation:: In malrotation, the proximal (duodenojejunal) limb remains in a position of non-rotation, and the distal (cecocolic) limb partially rotates (usually only 90 degrees instead of 180 degrees). Consequently,the cecum is relocated to the mid-upper abdomen, instead of the right lower quadrant. The abnormally-positioned cecum is attached by bands of peritoneum (Ladd bands) to the right lateral abdominal wall. Ladd bands can cause compression and obstruction of the duodenum extrinsically.
Other anomalies of rotation can rarely occur, these include: Rotation of the proximal (duodenojejunal) limb is reversed resulting in a duodenum that is located anterior to the superior mesenteric artery. Rotation of the distal (cecocolic) limb is reversed resulting in a transverse colon that is located posterior to the superior mesenteric artery. Finally, a combination of reversed rotation of the proximal (duodenojejunal) limb with normal rotation of the distal (cecocolic) limb can lead to a paraduodenal hernia. In this anomaly, anterior to the superior mesenteric artery lies the duodenum. Anterior to the duodenum, the distal (cecocolic) limb rotates normally. The mesentery of the right colon creates a pouch, the small bowel then herniates into it.
The mesentery anchors the ileum and sigmoid colon to the posterior abdominal wall.
An air filled loop of the sigmoid colon or the terminal ileum, sometimes, twists itself about the axis of the mesentery.
The incidence of volvulus occurring increases with a redundant or longer than normal mesentery.
If the degree of twisting is beyond 180 - 360 degress, then the bowel loop will become obstructed and ischemia will develop.
Ileosigmoid knotting is a variant of sigmoid volvulus where the ileum wraps around the sigmoid in a clockwise direction.
Normally, there are ligaments such as the gastrocolic, gastrohepatic, gastrosplenic and gastrophrenic ligaments that keeps the stomach in place by attaching it to other abdominal organs and the diaphragm.
However, the stomach can twist around its horizontal or vertical axis.
Gastric outlet obstruction may occur as a result of abnormal rotation more than 180 degrees.
Chronic rotation can cause bleeding by decreasing venous return and increasing capillary pressure.
The cecum is especially liable to being mobile congenitally. The cecum becomes mobile when failure of the ascending colon mesentery to fuse with the posterior parietal peritoneum occurs. Autopsy studies have shown that about 10-25% of the population have a mobile cecum and ascending colon sufficient to develop a volvulus. A congenital mobile cecum can also cause mobile cecum syndrome.
There are three types of cecal volvulus, type I and II are the most common, type III accounts for the remaining 20% of cases: Type I - organoaxial: The cecum twists in a clockwise manner along its axis. The cecum fills with air and remains in right lower quadrant. Type II - organoaxial: The cecum and a proximal part of the ileum twist in a counterclockwise direction. The cecum becomes inverted and is relocated to the left lower quadrant. Type III - mesentericoaxial: The cecum folds upwards and back on itself rather than rotating along its axis.
Several genetic and chromosomal mutations have been implicated in causing intestinal malrotation and other gastrointestinal abnormalities that may later be complicated by volvulus.
The forkhead box transcription factor Foxf1 plays a role in normal division and attachments of organs in the gastrointestinal tract. Then Foxf1 is knocked out in mice, it was found that somatic and splanchnic layers remain fused or incompletely separated. Ultimately, this leads to an inability of the dorsal mesentery to tilt to the left.
Pitx2 and Isl1 mutations lead to asymmetry of the gastrointestinal organs, attachments and rotations.
Mutations in beta2 and beta4 subunits of the neuronal nicotinic acetylcholine receptor have been associated with a MMIH syndrome (megacystis, microcolon and intestinal hypoperistalsis)
Deletions at chromosome 16q24.1 are associated with a number of GI tract abnormalities including malrotation and other abnormalities that result in: Reduced life expectancy, Restricted growth, Dysmorphic facial features, Learning disability, if the child survives.
Deletions of the long arm of chromosome 13 are associated with Hirschsprung disease and other GI tract malformations: malrotation, jejunal and ileal atresia, agenesis of mesentery and hypoplastic gallbladder.
Heterozygous mutations in EDNRB (endothelin receptor type B) gene, which is found within the deleted interval, results in Hirschsprung disease, but other GI tract malformations have not been reported in conjunction with EDNRB mutations.
On gross pathology, a distended, air-filled bowel twisted around its mesentery with or without ischemia, necrosis and/or gangrene are characteristic findings of volvulus.
Red arrow indicates a distended and air-filled segment of bowel. By آرمین - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=30092149
On microscopic histopathological analysis, thrombi, inflammatory cells, and necrotic changes are characteristic findings of volvulus.
|
Breast_cancer_screening_resident_survival_guide | Breast cancer screening is an attempt to find unsuspected cancers. The most common screening methods include self and clinical breast exams, x-ray mammography, breast magnetic resonance imaging (MRI), ultrasound, and genetic testing.
Algorithm based on the 2013 US Preventive Services Task Force recommendation statement.
|
Anagen | A hair follicle is part of the skin that grows hair by packing old cells together. Attached to the follicle is a sebaceous gland, a tiny sebum-producing gland found everywhere except on the palms, lips and soles of the feet. The thicker density of hair, the more sebaceous glands are found.
Also attached to the follicle is a tiny bundle of muscle fiber called the arrector pili that is responsible for causing the follicle and hair to become more perpendicular to the surface of the skin, and causing the follicle to protrude slightly above the surrounding skin. This process results in goose bumps (or goose flesh). Stem cells are located at the junction of the arrector and the follicle, and are principally responsible for the ongoing hair production during a process known as the Anagen stage.
The average growth rate of hair follicles on the scalp is .04 cm per day.
Certain species of Demodex mites live in the hair follicles of mammals (including those of humans) where they feed on sebum.
At the base of the follicle is a large structure that is called the papilla. The papilla is made up mainly of connective tissue and a capillary loop. Cell division in the papilla is either rare or non-existent.
Around the papilla is the hair matrix, a collection of epithelial cells often interspersed with the pigment producing cells, melanocytes. Cell division in the hair matrix is responsible for the cells that will form the major structures of the hair fiber and the inner root sheath. The hair matrix epithelium is one of the fastest growing cell populations in the human body, which is why some forms of chemotherapy that kill dividing cells or radiotherapy may lead to temporary hair loss, by their action on this rapidly dividing cell population. The papilla is usually ovoid or pear shaped with the matrix wrapped completely around it except for a short stalk-like connection to the surrounding connective tissue that provides access for the capillary.
The root sheath is composed of an external root sheath (Henle's layer), a middle layer (Huxley's layer), and an internal cuticle that is continuous with the outermost layer of the hair fiber.
The hair fiber is composed of a cuticle that is continuous with the root sheath, an intermediate cortex, and an inner medulla.
Other structures associated with the hair follicle include arrector pili muscles, sebaceous glands and apocrine sweat glands.
Hair grows in cycles of various phases: anagen is the growth phase; catagen is the involuting or regressing phase; and telogen, the resting or quiescent phase. Each phase has several morphologically and histologically distinguishable sub-phases. Prior to the start of cycling is a phase of follicular morphogenesis (formation of the follicle). There is also a shedding phase, or exogen, that is independent of anagen and telogen in which one of several hairs that might arise from a single follicle exits. Normally up to 90% of the hair follicles are in anagen phase while, 10–14% are in telogen and 1–2% in catagen. The cycle's length varies on different parts of the body. For eyebrows, the cycle is completed in around 4 months, while it takes the scalp 3–4 years to finish; this is the reason eyebrow hairs have a fixed length, while hairs on the head seem to have no length limit. Growth cycles are controlled by a chemical signal like epidermal growth factor.
Scalp: The time these phases last varies from person to person. Different hair colour and follicle shape affects the timings of these phases. anagen phase, 2–3 years (occasionally much longer), catagen phase, 2–3 weeks, telogen phase, around 3 months
Eyebrows etc: anagen phase, 4–7 months, catagen phase, 3–4 weeks, telogen phase, about 9 months
Hair follicles are extracted from a donor patch of a patient’s head during a hair restoration procedure.
, , Cross-section of all skin layers. |
Herxheimer_reaction | The Herxheimer reaction (also known as Jarisch-Herxheimer or herx) occurs when large quantities of toxins are released into the body as bacteria (typically Spirochetal bacteria) die, due to antibiotic treatment.
Typically the death of these bacteria and the associated release of endotoxins occurs faster than the body can remove the toxins via the natural detoxification process performed by the kidneys and liver.
It is manifested by fever, chills, headache, myalgias, and exacerbation of cutaneous lesions. Duration in syphilis is normally only a few hours but can be much longer in other diseases. The intensity of the reaction reflects the intensity of inflammation present.
The Herxheimer Reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, Interleukin-6 and Interleukin-8.
Both Adolf Jarisch, an Austrian dermatologist, and Karl Herxheimer, a German dermatologist, are credited with the discovery of the Herxheimer reaction.
Both Jarish and Herxheimer observed reactions in patients with syphilis treated with mercury. The reaction was first seen following treatment in early and later stages of syphilis treated with Salvarsan, mercury, or antibiotics. It is seen in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis.
The reaction is also seen in other diseases, such as borreliosis (Lyme disease and tick-borne relapsing fever), brucellosis, typhoid fever, and trichinellosis and Q fever.
Drug Side Effect
Metronidazole
Syphilis |
Pediatric_inflammation_of_heart_muscle | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Endomyocardial Biopsy | Chest X Ray | MRI | Echocardiography | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Template:WikiDoc Sources
Template:WH
Template:WS
|
Criteria_for_Renal_Stenosis | Diagnostic Criteria | History and Symptoms | Physical Examination | X Ray | CT | MRI | Echocardiography or Ultrasound
Medical Therapy | Angioplasty and Stenting | Surgery
Case #1
|
Malarial_parasite | A plasmodium is also the macroscopic form of the protist known as a slime mould.
Plasmodium is a genus of parasitic protozoa. Infection with this genus is known as malaria. The parasite always has two hosts in its life cycle: a mosquito vector and a vertebrate host. At least ten species infect humans. Other species infect other animals, including birds, reptiles and rodents.
The genus Plasmodium was created in 1885 by Marchiafava and Celli and there are over 175 species currently recognized. New species continue to be described.
The genus is currently (2006) in need of reorganization as it has been shown that parasites belonging to the genera Haemocystis and Hepatocystis appear to be closely related to Plasmodium. It is likely that other species such as Haemoproteus meleagridis will be included in this genus once it is revised.
Host range among the mammalian orders is non uniform. At least 29 species infect non human primates; rodents outside the tropical parts of Africa are rarely affected; a few species are known to infect bats, porcupines and squirrels; carnivores, insectivores and marsupials are not known to act as hosts.
In 1898 Ronald Ross demonstrated the existence of Plasmodium in the wall of the midgut and salivary glands of a Culex mosquito. For this discovery he won the Nobel Prize in 1902. However credit must also be given to the Italian professor Giovanni Battista Grassi, who showed that human malaria could only be transmitted by Anopheles mosquitoes. It is worth noting, however, that for some species the vector may not be a mosquito.
Mosquitoes of the genera Culex, Anopheles, Culiceta, Mansonia and Aedes may act as vectors. The currently known vectors for human malaria (> 100 species) all belong to the genus Anopheles. Bird malaria is commonly carried by species belonging to the genus Culex. Only female mosquitoes bite. Aside from blood both sexes live on nectar, but one or more blood meals are needed by the female for egg laying as the protein content of nectar is very low. The life cycle of Plasmodium was discovered by Ross who worked with species from the genus Culex.
The life cycle of Plasmodium is very complex. Sporozoites from the saliva of a biting female mosquito are transmitted to either the blood or the lymphatic system of the recipient. The sporozoites then migrate to the liver and invade hepatocytes. This latent or dormant stage of the Plasmodium sporozoite in the liver is called the hypnozoite.
The development from the hepatic stages to the erythrocytic stages has until very recently been obscure. In 2006 it was shown that the parasite buds off the hepatocytes in merosomes containing hundreds or thousands of merozoites. These merosomes have been subsequently shown to lodge in the pulmonary capilaries and to slowly disintergrate there over 48-72 hours releasing merozoites. Erythrocyte invasion is enhanced when blood flow is slow and the cells are tightly packed: both of these conditions are found in the alveolar capilaries.
Within the erythrocytes the merozoite grow first to a ring-shaped form and then to a larger trophozoite form. In the schizont stage, the parasite divides several times to produce new merozoites, which leave the red blood cells and travel within the bloodstream to invade new red blood cells. Most merozoites continue this replicative cycle, but some merozoites differentiate into male or female sexual forms (gametocytes) (also in the blood), which are taken up by the female mosquito.
In the mosquito's midgut, the gametocytes develop into gametes and fertilize each other, forming motile zygotes called ookinetes. The ookinetes penetrate and escape the midgut, then embed themselves onto the exterior of the gut membrane. Here they divide many times to produce large numbers of tiny elongated sporozoites. These sporozoites migrate to the salivary glands of the mosquito where they are injected into the blood of the next host the mosquito bites. The sporozoites move to the liver where they repeat the cycle.
Reactivation of the hypnozoites has been reported for up to 30 years after the initial infection in humans. The factors precipating this reactivation are not known. In the species Plasmodium malariae, Plasmodium ovale and Plasmodium vivax hypnozoites have been shown to occur. Reactivation does not occur in infections with Plasmodium falciparum. It is not known if hypnozoite reactivaction may occur with any of the remaining species that infect humans but this is presumed to be the case.
This life cycle is best understood in terms of its evolution.
The Apicomplexia - the phylum to which Plasmodium belongs - are thought to have originated within the Dinoflagellates - a large group of photosynthetic protozoa. It is currently thought that the ancestors of the Apicomplexia were originally prey organisms that evolved the ability to invade the intestinal cells and subsequently lost their photosynthetic ability. Some extant dinoflagelates, however, can invade the bodies of jellyfish and continue to photosynthesize, which is possible because jellyfish bodies are almost transparent. In other organisms with opaque bodies this ability would most likely rapidly be lost.
It is thought that Plasmodium evolved from a parasite spread by the orofaecal route which infected the intestinal wall. At some point this parasite evolved the ability to infect the liver. This pattern is seen in the genus Cryptosporidium to which Plasmodium is distantly related. At some later point this ancestor developed the ability to infect blood cells and to survive and infect mosquitoes. Once mosquito transmission was firmly established the previous orofecal route of transmission was lost.
Current (2007) theory suggests that the genera Plasmodium, Hepatocystis and Haemoproteus evolved from Leukocytozoon species. Parasites of the genus Leukocytozoan infect white blood cells (leukocytes), liver and spleen cells and are transmitted by 'black flies' (Simulium species) - a large genus of flies related to the mosquitoes.
Leukocytes, hepatocytes and most spleen cells actively phagocytose particulate matter making entry into the cell easier for the parasite. The mechanism of entry of Plasmodium species into erythrocytes is still very unclear taking as it does less than 30 seconds. It is not yet known if this mechanism evolved before mosquitoes became the main vectors for transmission of Plasmodium.
Plasmodium evolved about 130 million years ago. This period is coincidental with the rapid spread of the angiosperms (flowering plants). This expansion in the angiosperms is thought to be due to at least one genomic duplication event. It seems probable that the increase in the number of flowers led to an increase in the number of mosquitoes and their contact with vertebrates.
Mosquitoes evolved in what is now South America about 230 million years ago. There are over 3500 species recognised but to date their evolution has not been well worked out so a number of gaps in our knowledge of the evolution of Plasmodium remain.
Presently it seems probable that birds were the first group infected by Plasmodium followed by the reptiles - probably the lizards. At some point primates and rodents became infected. The remaining species infected outside these groups seem likely to be due to relatively recent events.
At the present time (2007) DNA sequences are available from fewer than sixty species and most of these are from species infecting either rodent or primate hosts. The evolution proposed here should be regarded as speculative and subject to revision as data becomes available.
The pattern of alternation of sexual and asexual reproduction which may seem confusing at first is a very common pattern in parasitic species. The evolutionary advantages of this type of life cycle were recognised by Mendel.
Under favourable conditions asexual reproduction is superior to sexual as the parent is well adapted to its environment and its descendents share these genes. Transferring to a new host or in times of stress, sexual reproduction is generally superior as this produces a shuffling of genes which on average at a population level will produce individuals better adapted to the new environment.
All the species examined to date have 14 chromosomes, one mitochondrion and one plastid. The chromosomes vary from 500 kilobases to 3.5 megabases in length. It is presumed that this is the pattern throughout the genus.
The plastid unlike those found in algae is not photosynthetic. Its function is not known but there is some suggestive evidence that it may be involved in reproduction.
On a molecular level, the parasite damages red blood cells using plasmepsin enzymes - aspartic acid proteases which degrade hemoglobin.
Forms gamonts in erythrocytes
Merogony occurs in erythrocytes and in other tissues
Hemozoin is present
Vectors are either mosquitos or sandflies
Vertebrate hosts include mammals, birds and reptiles
Plasmodium belongs to the family Plasmodiidae (Levine, 1988), order Haemosporidia and phylum Apicomplexia. There are currently 450 recognised species in this order. Many species of this order are undergoing reexamination of their taxonomy with DNA analysis. It seems likely that many of these species will be re assigned after these studies have been completed. For this reason the entire order is outlined here.
Notes:
The genera Plasmodium, Fallisia and Saurocytozoon all cause malaria in lizards. All are carried by Dipteria (roughly speaking the flies). Pigment is absent in the Garnia. Non pigmented gametocytes are typically the only forms found in Saurocytozoon: pigmented forms may be found in the leukocytes occasionally. Fallisia produce non pigmented asexual and gametocyte forms in leukocytes and thrombocytes.
The full taxonomic name of a species includes the subgenus but this is often omitted. The full name indicates some features of the morphology and type of host species.
The only two species in the sub genus Laverania are P. falciparum and P. reichenowi.
Species infecting monkeys and apes (the higher primates) with the exceptions of P. falciparum and P. reichenowi are classified in the subgenus Plasmodium.
Parasites infecting other mammals including lower primates (lemurs and others) are classified in the subgenus Vinckeia.
The distinction between P. falciparum and P. reichenowi and the other species infecting higher primates was based on the morphological findings but have since been confirmed by DNA analysis. Vinckeia while previously considered to be something of a taxonomic 'rag bag' has been recently shown - perhaps rather surprisingly - to form a coherent grouping.
The remaining groupings here are based on the morphology of the parasites. Revisions to this system are likely to occur in the future as more species are subject to analysis of their DNA.
The four subgenera Giovannolaia, Haemamoeba, Huffia and Novyella were created by Corradetti et al for the known avian malarial species. A fifth - Bennettinia - was created in 1997 by Valkiunas. The relationships between the subgenera are the matter of current investigation. Martinsen et al 's recent (2006) paper outlines what is currently (2007) known.
P. juxtanucleare is currently (2007) the only known member of the subgenus Bennettinia.
Unlike the mammalian and bird malarias those affecting reptiles have been more difficult to classify. In 1966 Garnham classified those with large schizonts as Sauramoeba, those with small schizonts as Carinamoeba and the single then known species infecting snakes (Plasmodium wenyoni) as Ophidiella. He was aware of the arbitrariness of this system and that it might not prove to be biologically valid. Telford in 1988 used this scheme as the basis for the currently accepted (2007) system.
Classification criteria
Species in the subgenus Bennettinia have the following characteristics:
Schizonts contain scant cytoplasm, are often round, do not exceed the size of the host nucleus and stick to it.
Gametocytes while varying in shape tend to be round or oval, do not exceed the size of the nucleus and stick to it.
Species in the subgenus Giovanolaia have the following characteristics:
Schizonts contain plentiful cytoplasm, are larger than the host cell nucleus and frequently displace it. They are found only in mature erythrocytes.
Gametocytes are elongated.
Exoerythrocytic schizogony occurs in the mononuclear phagocyte system.
Species in the subgenus Haemamoeba have the following characteristics:
Mature schizonts are larger than the host cell nucleus and commonly displace it.
Gametocytes are large, round, oval or irregular in shape and are substantially larger than the host nucleus.
Species in the subgenus Huffia have the following characteristics:
Mature schizonts, while varying in shape and size, contain plentiful cytoplasm and are commonly found in immature erthryocytes.
Gametocytes are elongated.
Species in the subgenus Novyella have the following characteristics:
Mature schisonts are either smaller than or only slightly larger than the host nucleus. They contain scanty cytoplasm.
Gametocytes are elongated. Sexual stages in this subgenus resemble those of Haemoproteus.
Exoerythrocytic schizogony occurs in the mononuclear phagocyte system
Species in the subgenus Carinamoeba have the following characteristics:
Infect lizards
Schizonts normally give rise to less than 8 merozoites
Species in the subgenus Sauramoeba have the following characteristics:
Infect lizards
Schizonts normally give rise to more than 8 merozoites
Notes
The erythrocytes of both reptiles and birds retain their nucleus, unlike those of mammals. The reason for the loss of the nucleus in mammalian erythocytes remains unknown.
The presence of elongated gametocytes in several of the avian subgenera and in Laverania in addition to a number of clinical features suggested that these might be closely related. This is is no longer thought to be the case.
Plasmodium falciparum (the cause of malignant tertian malaria)
Plasmodium vivax (the most frequent cause of benign tertian malaria)
Plasmodium ovale (the other, less frequent, cause of benign tertian malaria)
Plasmodium malariae (the cause of benign quartan malaria)
Plasmodium knowlesi
Plasmodium brasilianum
Plasmodium cynomolgi
Plasmodium cynomolgi bastianellii
Plasmodium inui
Plasmodium rhodiani
Plasmodium schweitzi
Plasmodium semiovale
Plasmodium simium
The first four listed here are the most common species that infect humans. With the use of the polymerase chain reaction additional species have been and are still being identified that infect humans.
One possible experimental infection has been reported with Plasmodium eylesi. Fever and low grade parasitemia were apparent at 15 days. The volunteer (Dr Bennett) had previously been infected by Plasmodium cynomolgi and the infection was not transferable to a gibbon (P. eylesi 's natural host) so this cannot be regarded as definitive evidence of its ability to infect humans. A second case has been reported that may have been a case of P. eylesi but the author was not certain of the infecting species.
A possible infection with Plasmodium tenue has been reported. This report described a case of malaria in a three year old black girl from Georgia, USA who had never been outside the US. She suffered from both P. falciparum and P. vivax malaria and while forms similar to those described for P. tenue were found in her blood even the author was skeptical about the validity of the diagnosis.
Confusingly Plasmodium tenue was proposed in the same year (1914) for a species found in birds. The human species is now considered to be likely to have been a misdiagnosis and the bird species is described on the Plasmodium tenue page.
Notes:
The only known host of P. falciparum are humans; neither is any other host currently known for P. malariae.
P. vivax will infect chimpanzees. Infection tends to be low grade but may be persistent and remain as source of parasites for humans for some time.
P. vivax is also known to infect orangutans.
Like P. vivax, P. ovale has been shown to be transmittable to chimpanzees. P. ovale has a unusual distribution pattern being found in Africa, the Philippines and New Guinea. In spite of its admittedly poor transmission to chimpanzees given its discontigous spread, it is suspected that P. ovale may in fact be a zooenosis with an as yet unidentified host. If this is actually the case, the host seems likely to be a primate.
The remaining species capable of infecting humans all have other primate hosts.
Plasmodium shortii and Plasmodium osmaniae are now considered to be junior synonyms of Plasmodium inui
Species no longer recognised as valid
Taxonomy in parasitology until the advent of DNA based methods has always been a problem and revisions in this area are continuing. A number of synonoms have been given for the species infecting humans that are no longer recognised as valid. Since perusal of the older literature may be confusing some of these are listed here...
The species that infect primates other than humans include: P. bouillize, P. brasilianum, P. bucki, P. cercopitheci,P. coatneyi, P. coulangesi, P. cynomolgi, P. eylesi, P. fieldi, P. foleyi, P. fragile, P. girardi, P. georgesi, P. gonderi, P. hylobati, P. inui, P. jefferyi, P. joyeuxi,P. knowlesi, P. lemuris, P. percygarnhami, P. petersi, P. reichenowi, P. rodhaini, P. sandoshami, P. semnopitheci, P. silvaticum, P. simiovale, P. simium, P. uilenbergi, P. vivax and P. youngei.
Host records - Most if not all Plasmodium species infect more than one host: the host records shown here should be regarded as being incomplete.
|
Hypocalcemia_surgery | Surgical intervention is not recommended for the management of hypocalcemia.
Surgical intervention is not recommended for the management of hypocalcemia.
|
Dermatitis_herpetiformis_history_and_symptoms | Dermatitis Herpetiformis (also called Duhring's disease), is a chronic itchy rash which is frequently associated with Celiac Disease. The rash is made of papules and vesicles which are present on different parts of the body mostly commonly on neck, trunk, buttocks and knees. It is an autoimmune mediated skin condition, which is IgA mediated reaction and is associated with gluten sensitivity of small bowel. There is presence of antibodies which leads to positive serology test results.
Dermatitis herpetiformis is associated with high prevalence of other autoimmune diseases.
The patients with dermatitis herpetiformis will have a history of:
Papulovesicular skin rash.
gluten insensitivity.
Family history of Celiac disease.
Autoimmune Thyroid disease and other autoimmune disease.
Rash on the extensor surfaces of skin
Diarrhea due to inflammation of the small intestine. |
Premenstrual | Premenstrual syndrome (PMS) (also called PMT or Premenstrual Tension) is a collection of physical, psychological, and emotional symptoms related to a woman's menstrual cycle. While most women (about 80 to 95 percent) of child-bearing age have some premenstrual symptoms, women with PMS have symptoms of "sufficient severity to interfere with some aspects of life". Further, such symptoms are predictable and occur regularly during the two weeks prior to menses. The symptoms may vanish after the bleeding starts, but may continue even after bleeding has begun. Also, many females get easily irritated during PMS. About 14 percent of women between the ages of 20 to 35 become so affected that they must stay home from school or work.
For some women with PMS, the symptoms are so severe that they are considered disabling. This form of PMS has its own psychiatric designation: premenstrual dysphoric disorder (PMDD).
Culturally, the abbreviation PMS is widely understood in the United States to refer to difficulties associated with menses, and the abbreviation is used frequently even in casual and colloquial settings, without regard to medical rigor. In these contexts, the syndrome is rarely referred to without abbreviation, and the connotations of the reference are frequently more broad than the clinical definition.
The exact causes of PMS are not fully understood. While PMS is linked to the luteal phase, measurements of sex hormone levels are within normal levels. PMS tends to be more common among twins suggesting the possibility of some genetic component. Current thinking suspects that central-nervous-system neurotransmitter interactions with sex hormones are affected. It is thought to be linked to activity of serotonin (a neurotransmitter) in the brain.
. Ethynodiol diacetate and ethinyl estradiol can cause premenstrual syndrome.
There is no laboratory test or unique physical findings to verify the diagnosis of PMS. To establish a pattern, a woman's physician may ask her to keep a prospective record of her symptoms on a calendar for at least two menstrual cycles.
This will help to establish the symptoms are, indeed, premenstrual and predictably recurring. In addition, other conditions that may explain symptoms better may have to be excluded.
A number of standardized instruments have been developed to describe PMS, including the Calendar of Premenstrual syndrome Experiences (COPE), the Prespective Record of the Impact and Severity of Menstruation (PRISM), and the Visual Anague Scales (VAS).
A number of medical conditions are subject to exacerbation at menstruation, a process called menstrual magnification. These conditions may lead the patient to believe that she may have PMS, when the underlying disorder may be some other problem. A key feature is that these conditions may also be present outside of the luteal phase. Conditions that can be magnified perimenstrually include depression, migraine, seizure disorders, chronic fatigue syndrome, irritable bowel syndrome, asthma, and allergies. PMS is more common in women with stress.
PMS is a collection of symptoms. 150 separate symptoms have been identified.
The exact symptoms and how severe they are vary from person to person and from month to month. Most women with premenstrual syndrome experience only a few of the problems. The most common symptoms are:
Abdominal bloating
Breast tenderness
Stress or anxiety
Depression
Crying spells
Mood swings, irritability or anger
Appetite changes and food cravings
Trouble falling asleep (insomnia)
Joint or muscle pain
Headache
Fatigue (medical)
Acne
Swelling of Breasts
Trouble concentrating
Social withdrawal
Body temperature increase
Worsening of existing skin disorders, and respiratory (e.g. allergies, infection) or eye (e.g. visual disturbances, conjunctivitis) problems
Many treatments have been suggested for PMS, including diet or lifestyle changes, and other supportive means. Medical interventions are primarily concerned with hormonal intervention and use of selective serotonin reuptake inhibitors (SSRIs).
Supportive therapy includes evaluation, reassurance, and informational counseling, and is an important part of therapy in an attempt to help the patient regain control over her life. In addition, aerobic exercise has been found in some studies to be helpful. Some PMS symptoms may be relieved by leading a healthy lifestyle: Reduction of caffeine, sugar, and sodium intake and increase of fiber, and adequate rest and sleep.
Dietary intervention studies indicate that calcium supplementation (1200 mg/d) may be useful. Also vitamin E (400 IU/d) has shown some effectiveness. A number of other treatments have been suggested, even though there is not convincing research evidence that these treatments work: Vitamin B6, magnesium, manganese and tryptophan.
SSRIs have become the "initial drug of choice for severe PMS" The drug most widely studied is fluoxetine at doses of 20-60 mg/d. Other drugs include sertraline, paroxetine, clomipramine, fluvoxamine, and nefadozone. These drugs can also be given intermittently, that is when symptoms reappear.
Hormonal intervention may take many forms: Hormonal contraception is commonly used; common forms include the combined oral contraceptive pill and the contraceptive patch. Progesterone support has been used for many years but evidence of its efficacy is inadequate. Gonadotropin-releasing hormone agonists can be useful in severe forms of PMS but have their own set of significant potential side effects.
Diuretics have been used to handle water retention. Spironolactone has been shown in some studies to be useful.
Non-steroidal anti-inflammatory drugs (NSAIDs; eg ibuprofen) have been used.
Evening Primrose Oil, which contains gamma-Linolenic acid (GLA), has been advocated but lacks scientific support.
Some medical professionals suggest that PMS might be a socially constructed disorder.
Supporters of PMS's medical validity claim support from the non-disputed status of a more serious but similar problem, Premenstrual dysphoric disorder ("PMDD"). In women with PMDD, studies have shown a correlation between self-reported emotional distress and levels of a serotonin precursor as measured by Positron emission tomography (PET). PMDD also has a consistent treatment record with SSRIs, when compared with placebos.
However, most supporters of PMS as a social construct do not dispute PMDD's medical status. Rather, they believe PMS and PMDD to be unrelated issues, one a product of brain chemistry, the other a product of a hypochondriatic culture. There has not been enough debate between the two views to come to any sound conclusion.
Part of the reason the validity of the emotional aspects of PMS is being doubted is the lack of scientifically-sound studies on the matter. Many Western studies on PMS (PMS is primarily seen in Western Europe and North America) rely solely on self-reporting, and since Western women are socially conditioned to expect PMS or to at least know of its purported existence, they report their symptoms accordingly.
Another view holds that PMS is too frequently or wrongly diagnosed in many cases. A variety of problems, such as chronic depression, infections, and outbursts of frustration can be mis-diagnosed as PMS if they happen to coincide with the premenstrual period. Often, says this theory, PMS is used as an explanation for outbursts of rage or sadness, even when it is not the primary cause.
|
Complex_regional_pain_syndrome_epidemiology_and_demographics | Complex regional pain syndrome is more common between the ages of 40 and 60, and it affects women more frequently.
CRPS can strike at any age, but is more common between the ages of 40 and 60.The number of reported CRPS cases among adolescents and young adults is increasing.
It affects both men and women, but is more frequently seen in women.
|
Cavernous_sinus_thrombosis_classification | middle lesions and posterior lesions. Although more number of patients could be classified in Ishikawa classification, there is no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of cavernous sinus lesions.
The Jefferson classification and Ishikawa classification has been used to localize cavernous sinus lesions.
According to the the location of the intracranial orifice of the optic canal and the entry of the maxillary nerve into the cavernous sinus, lesions may be classified in Ishikawa and Jefferson classification into three groups: Anterior lesions, Middle lesions, Posterior lesions
|
Pulmonary_embolism_support_group | to pulmonary embolism patients. The help may take the form of, and establishing social networks. A support group may also provide ancillary support, such as serving as a voice for the public or engaging in advocacy.
PE, due to its sudden appearance in an otherwise healthy person, comes as a surprise and disbelief for most of the patients. The support group helps patients deal with that feeling of anxiety and shock. Various non-profit organizations have been developed, and they are helping patients cope with the emotional trauma. One such non-profit organizations is North American Thrombosis Forum.
|
Left_main_artery | The origin of the left main coronary artery (LMCA) is from the left sinus valsalva (LSV). Prior to entry into the coronary sulcus, it travels between the left auricle and the main pulmonary artery (PA). The left circumflex (LCX) and left anterior descending (LAD) arteries arise from the bifurcation of the LMCA, which does not have any significant branches. It is 1 to 25 mm long, and is normally 3 to 5 mm wide. Severe narrowing of the left main coronary artery can result in death due to coronary ischemia, and is an indication for coronary artery bypass grafting or coronary stenting.
Left main artery bifurcates into the left anterior descending artery and the left circumflex artery.
Shown below is an image depicting the left main artery.
<figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline>
Anomalous origin of LCA from PA (ALCAPA) is also known as Bland-White-Garland syndrome was described in 1956.
ALCAPA is a very rare and a serious congenital coronary artery anomaly (0.008%).
In this anomaly RCA is often dilated and provides an extensive collateral circulation to the LMCA territory.
The specific findings are dilated collateral arteries and coronary veins in imaging.
Additional components have been demonstrated in this syndrome as aortic coarctation and patent ductus arteriosus.
The suggested method of the treatment is reimplantation surgery of LMCA onto the aorta.
This anomaly is characterized by the absence of LMCA. In this case, the LCX and LAD are normal in their distribution pattern but arise from adjacent, separate ostia in the LSV.
Absent LMCA is a common benign anomaly, occurring in 0.41%-0.67% of cases.
Cases of left system dominance and aortic valve disease have been found to have increased incidence.
This condition is associated with no hemodynamic impairment. However, lack of identification of this anomaly may lead to clinical consequences during coronary catheterization or surgery.
There are often prominent right-to-left collateral vessels between the coronary arteries, although these vessels are usually inadequate to meet the oxygen requirements of left ventricle.
A large conus collateral branch supplying the LAD may mimic a pre-pulmonic vessel.
Atresia of the LMCA is associated with formation of a fibrous connection between the left sinus valsalva and the LCX-LAD arterial junction.
It usually affects patients in first year of life, but has also been described in elderly patients.
The lumen may not be identifiable or may be abnormal and nearly obliterated. Right-to-left collateral circulation may exist between coronary arteries to compensate for oxygen requirements, but may still be inadequate to meet the oxygen demand. A large conus collateral branch supplying the LAD may resemble a pre pulmonic vessel.
Shown below are an animated and a static angiography images depicting the left main artery in the RAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO cranial view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the RAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO cranial view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
In carefully selected patients, percutaneous left main intervention can safely and effectively treat patients in whom coronary artery bypass graft surgery is a suboptimal option. Data from the SYNTAX trial supports such an approach.
Careful selection of patients for PCI is critical.
Fractional Flow Reserve (FFR) may be helpful in determining if a lesion is critical.
Mortality and procedural results vary depending upon whether the lesion is ostial and/or in the shaft versus distal and involves the bifurcation.
Thus, careful and meticulous angiography in multiple views is critical to fully assess the left main at it's ostium and bifurcation. Optimal views include but are not limited to the AP caudal and the LAO Caudal.
Coronary Artery Bypass Grafting (CABG) is currently the standard of care for patients with left main disease. However, this recommendation may be modified as data emerge regarding:
Very low in-hospital mortality among patients treated with left main stenting
Comparable or better MACE-free survival rates vs CABG in some registries
Low restenosis rate with drug eluting stent use
Nonoperative candidates
Low-risk patients who decline CABG
A patient who is both able and willing to take life long aspirin and clopidogrel (dual antiplatelet therapy)
High-risk features in patients undergoing left main disease PCI include:
Absence of saphenous vein or internal mammary artery grafts distally
Concomitant RCA disease
Lack of collaterals from RCA
Distal bifurcation involvement
LV dysfunction
Presence of clot
Extensive calcification
The anatomy should be well characterized before the PCI.
Evaluation of the potential to occlude or 'snowplow' a ramus is critical.
Hemodynamic support with intra aortic balloon pump (IABP) placement is not mandatory, but should be considered for high-risk patients.
If an Intra aortic balloon pump is not placed, consideration should be given to placement of a 4 or 5 French sheath in the contralateral groin in case one needs to be placed urgently.
Percutaneous cardiopulmonary support (CPS) is an option for very-high-risk patient.
Pulmonary artery line monitoring may be helpful.
Characterizes extent of plaque
Characterizes extent of calcification
Can be used to calculate the MLD/MLA (minimal lumen diameter/area) accurately and ascertain the significance of stenosis
QCA alone may not be adequate to determine the physiologic significance of an often eccentric LM stenosis
IVUS may assist in sizing the stent appropriately to avoid stent malaposition and consequent higher risk of stent thrombosis and restenosis
In the presence of bifurcation disease you can use IVUS to determine the degree of plaque extent in the circumflex and use Murray's Law to calculate the stent size (diameter of the proximal main branch (diameter of distal main branch + diameter of distal side branch) X 0.67
Use of larger guiding catheters (i.e.: 7 or 8 French) in case distal bifurcation intervention is necessary.
Select a guide that provides good support, but which can be backed out of the ostium if you are dealing with an ostial stenosis.
Do not occlude ostium with the guide.
Make side holes with an 18 gauge needle if necessary.
Short occlusion/inflation times are critical to reduce ischemic time.
Consideration should be given to a perfusion balloon in a very high risk patient and the distal tip should be placed in the LAD.
Select equipment in advance.
Use a rapid exchange system.
Dilute contrast in the indeflator to allow faster deflation.
Adequate stent sizing and post-dilation cannot be understated.
Stent selection: Consider using a drug eluting stent especially if the vessel is less than 4.5 mm, Good radial strength (larger Taxus stents tend to recoil), High visibility for ostial or bifurcation placement, Assure that aorto-ostial region covered by stent if there is ostial lesion (stent positioning in two orthogonal views is particularly important)
Calcified lesions: Rotational atherectomy, Stenting
Bulky plaque: Directional atherectomy + stenting, Stenting alone
Distal bifurcation involvement: Similar to other bifurcation therapies but higher risk, DCA alone, DCA + stenting of principal vessel, Stenting of principal vessel (usually LAD) & rescuing circumflex, Bifurcation stenting (V stenting with kissing balloons, crush or reverse crush, T stenting, or Y, Culotte; in double barrel V or crush stenting LCX limb is often the site of restenosis and re-crossing into the barrel is often challenging )
Antiplatelet regimen:
ASA 325 mg PO prior to the procedure, use non-enteric coated to assure rapid absorption
Clopidogrel at a loading dose of 600 mg at least 2 hours prior to the intervention
Glycoprotein IIb/IIIa inhibitor administration is typical for this high risk lesion morphology
If unfractionated heparin (UFH) is used as an antithrombin, then UFH should be dosed to achieve an activated clotting time (ACT) of 250 seconds in the presence of a Glycoprotein IIb/IIIa inhibitor or 300 seconds in the absence of a Glycoprotein IIb/IIIa inhibitor
A bad vagal reaction in a freshly implanted stent or in a patient awaiting PCI who has a significant LM lesion can be very hazardous (risk of thrombosis, or a downward spiral of poor perfusion leading to subendocardial ischemia leading to poorer LV function, leading to poorer forward output).
Some operators will preemptively administer an ampule of atropine prior to the sheath pull or will have a low threshold to administer a full ampule of atropine.
In patients with LMCA disease, CABG is known to have high efficacy and safety.
In patients who were not candidates for CABG, performing PCI with stenting to the left main coronary artery was adopted.
Evidence from literature has shown that these two techniques of revascularization have equivalent outcomes in patients with LMCA disease.
The complexity of coronary artery disease can be evaluated by using the SYNTAX score or by determining the number of vessels requiring revascularization.
With increasing complexity of coronary artery disease (CAD), CABG is preferred over PCI with stenting.
CABG has been found to have a higher incidence of adverse in-hospital outcomes, including stroke, MI and death.
PCI with stenting has a higher incidence of repeat (usually target vessel) revascularization at long-term follow up. (OR 1.85, 95% CI 1.53-2.23). There is no significant difference in the long term rates of stroke, MI and death.
Outcomes may be better in CABG depending on CAD severity and follow-up duration.
A retrospective multicenter registry study has demonstrated favorable long-term outcomes after the implantation of drug eluting stents (DES) in non-bifurcation lesions involving unprotected left main coronary arteries.
The study, which was published in the online edition of Circulation, examined registry data among 147 patients who were electively treated with percutaneous coronary intervention (PCI) with DES in unprotected left main coronary artery lesions.
At a median follow-up of 886 days, the major adverse cardiac event rate was 7.4% with a cumulative cardiac mortality of 2.7%. Only seven patients required target vessel revascularization.
The restenosis rate at six-month angiographic follow-up was 0.9% with a late loss of -0.01 mm.
Additionally, there were no angiographically proven cases of stent thrombosis, although stent thrombosis could not be excluded in the four patients who died of unknown causes.
While the results of the study suggest that the use of drug eluting stents in nonbifurcation unprotected left main coronary artery stenosis is both safe and effective, Dr. Alaide Chieffo and colleagues note that the results are from a retrospective registry with a relatively small number of patients due to the low occurrence of this anatomical subset.
Currently there is no randomized data comparing PCI with DES implantation versus coronary artery bypass graft surgery. The ongoing SYNTAX trial will evaluate 710 patients with left main disease who have been randomized to either a DES or CABG.
Unprotected left main stem PCI with drug eluting stents is associated with favorable long-term outcomes.
Among patients with significant left main stem stenosis, coronary artery bypass surgery is still the favored method of revascularization.
However, previous observational studies suggest favorable outcomes with percutaneous intervention using drug eluting stents (DES). But the use of DES however is associated with an increase in late stent thrombosis.
Meliga and colleagues determine the long term (3 years) clinical outcomes with left main PCI using DES. Their study is an international, multicenter, retrospective registry design consisting of real world population recruited between April 2002 and April 2004 from Europe and United States. 358 patients underwent PCI with sirolimus eluting and paclitaxel eluting stents for de novo lesions located in the ostium, shaft and distal segments of the unprotected left main stem. Patients with EuroSCORE >6 were considered high risk and >9 were considered very high risk. The mean age of study patients was 66.1±11.2 and 30.2% of patients had diabetes mellitus (IDDM 16.2%, NIDDM 14%), 18.9% had prior coronary artery bypass surgery, the mean left ventricular ejection fraction was 48.6±12.8% and the mean EuroSCORE was 6.4±4.1. The most common admission diagnosis was stable angina (44.1%), unstable angina (41.9%), acute myocardial infarction (8.4%), cardiogenic shock (2.8%) and silent ischemia (2.8%). 19.6% of cases underwent emergent PCI. The lesion was located in the ostium/shaft in 26.3% of cases and the remaining lesions were located in the distal segment of the left main stem. Multiple stents were used in 43.3% of cases. Cypher and Taxus stents were used in almost equal proportions (54.5% and 45.5%). Provisional stenting was adopted in majority of the cases (56.7%) and crush stenting was used in 26.5% of cases. Intra-aortic balloon pump was used in 13.9% of cases. Technical procedural success was achieved in all patients (100%). The overall in-hospital major adverse cardiac event (MACE-cardiac death, nonfatal myocardial infarction, or target vessel revascularization) rate was 11.1%, which occurred more frequently following emergency PCI than elective PCI (22.8% vs. 8.3%, p<0.001). Likewise the in-hospital cardiac death was more frequent in the emergency cases (12.8% vs. 0.7%, p<0.001). At one year, the overall MACE rate was 24.3% (elective: 22.2% vs. emergency: 32.9%, p=0.046). The difference in MACE at one year between elective and emergent cases was attributed to an increase in cardiac death in the emergency group (18.6% vs. 3.8%, p<0.001). At 3 years, the overall MACE rate was 32.1%, with no difference in MACE between elective and emergency cases (p=0.126). However, at 3 years, the elective group underwent more target vessel revascularization compared with the emergency group (16% vs. 7.1%, p=0.037). Beyond 3 years, the overall incidence of cardiac death was 10.6% (elective: 6.9% vs. emergency 25.7%, p<0.001) and the overall MACE rate was 34.9% (elective: 31.6% vs. emergency: 48.5%, p=0.006). In total, stent thrombosis according to the ARC definition occurred in 6.1% of cases (acute 0.6%, subacute 0.6%, late 2.2% and very late stent thrombosis in 10 cases). In a multivariate analysis, age [HR 1.06 (95% CI 1.01 to 1.11, p=0.010)], shock [HR 11.0 (1.88 to 63.9), p=0.008], and EuroSCORE [HR 1.15 (1.01 to 1.31), p=0.046] were identified as independent predictors of cardiac death. The IDDM [HR 2.85 (1.29 to 6.17), p=0.009] and EuroSCORE [HR 1.10 (1.02 to 1.19), p=0.014] were predictors of MACE whereas, impaired ejection fraction [HR 1.03 (1.01 to 1.05), p=0.050], IDDM [HR 2.92 (1.60 to 5.30), p<0.001] and multiple stenting [HR 4.51 (1.07 to 19.0), p=0.040] were independent predictors of the need for target vessel revascularization. The investigators concluded that PCI to unprotected left main stem using DES is associated with “a satisfactory rate in both single and composite outcomes”. Beneficial effects were more frequently observed in elective population compared with the emergency cases over a 3 year period with lower rates of stent thrombosis.
Left main restenosis may present as sudden death rather than recurrent angina.
Screen aggressively for restenosis (with either angiography or Multi Detector CT for ostial disease).
Some operators perform platelet inhibition testing to confirm that the patient is not a clopidogrel non-responder.
Some operators dose the patient with 150 mg of clopidogrel per day in case the patient is a clopidogrel non-responder.
Relook angiography recommended even in absence of sx at 2-3 months post-procedure to catch early restenosis and some operators recommend additional angiography at 6 months to identify late restenosis
Angioscopy may aid in determining if clot is present at the end of the procedure, and if clot is present on repeat evaluation. |
Blue_rubber_bleb_nevus_syndrome_other_diagnostic_studies | Technetium Tc-99m may be helpful in the diagnosis of blue rubber bleb nevus syndrome. Findings suggestive of blue rubber bleb nevus syndrome include it gives extent of bleeding in GI tract
Technetium Tc-99m :
It gives extent of bleeding in GI tract
Abdomen RBC scan shows abnormal pooling attributable to venous malformations |
Superior_mediastinal_syndrome | History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Radiation Therapy | Primary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Pemberton's sign
Cough causes
Oncologic emergencies
Mediastinal tumor
vteCardiovascular disease (heart)IschaemicCoronary disease
Coronary artery disease (CAD)
Coronary artery aneurysm
Spontaneous coronary artery dissection (SCAD)
Coronary thrombosis
Coronary vasospasm
Myocardial bridge
Active ischemia
Angina pectoris
Prinzmetal's angina
Stable angina
Acute coronary syndrome
Myocardial infarction
Unstable angina
Sequelae
hours
Hibernating myocardium
Myocardial stunning
days
Myocardial rupture
weeks
Aneurysm of heart / Ventricular aneurysm
Dressler syndrome
LayersPericardium
Pericarditis
Acute
Chronic / Constrictive
Pericardial effusion
Cardiac tamponade
Hemopericardium
Myocardium
Myocarditis
Chagas disease
Cardiomyopathy
Dilated
Alcoholic
Hypertrophic
Tachycardia-induced
Restrictive
Loeffler endocarditis
Cardiac amyloidosis
Endocardial fibroelastosis
Arrhythmogenic right ventricular dysplasia
Endocardium / valvesEndocarditis
infective endocarditis
Subacute bacterial endocarditis
non-infective endocarditis
Libman–Sacks endocarditis
Nonbacterial thrombotic endocarditis
Valves
mitral
regurgitation
prolapse
stenosis
aortic
stenosis
insufficiency
tricuspid
stenosis
insufficiency
pulmonary
stenosis
insufficiency
Conduction / arrhythmiaBradycardia
Sinus bradycardia
Sick sinus syndrome
Heart block: Sinoatrial
AV
1°
2°
3°
Intraventricular
Bundle branch block
Right
Left
Left anterior fascicle
Left posterior fascicle
Bifascicular
Trifascicular
Adams–Stokes syndrome
Tachycardia (paroxysmal and sinus)Supraventricular
Atrial
Multifocal
Junctional
AV nodal reentrant
Junctional ectopic
Ventricular
Accelerated idioventricular rhythm
Catecholaminergic polymorphic
Torsades de pointes
Premature contraction
Atrial
Junctional
Ventricular
Pre-excitation syndrome
Lown–Ganong–Levine
Wolff–Parkinson–White
Flutter / fibrillation
Atrial flutter
Ventricular flutter
Atrial fibrillation
Familial
Ventricular fibrillation
Pacemaker
Ectopic pacemaker / Ectopic beat
Multifocal atrial tachycardia
Pacemaker syndrome
Parasystole
Wandering atrial pacemaker
Long QT syndrome
Andersen–Tawil
Jervell and Lange-Nielsen
Romano–Ward
Cardiac arrest
Sudden cardiac death
Asystole
Pulseless electrical activity
Sinoatrial arrest
Other / ungrouped
hexaxial reference system
Right axis deviation
Left axis deviation
QT
Short QT syndrome
T
T wave alternans
ST
Osborn wave
ST elevation
ST depression
Strain pattern
Cardiomegaly
Ventricular hypertrophy
Left
Right / Cor pulmonale
Atrial enlargement
Left
Right
Athletic heart syndrome
Other
Cardiac fibrosis
Heart failure
Diastolic heart failure
Cardiac asthma
Rheumatic fever
Template:WH
Template:WS
|
Asphyxiant | Asphyxia (from Greek a-, "without" and σφυγμός (sphygmos), "pulse, heartbeat") is a condition of severely deficient supply of oxygen to the body that arises from being unable to breathe normally. Asphyxia causes generalized hypoxia, which primarily affects the tissues and organs most sensitive to hypoxia first, such as the brain, hence resulting in cerebral hypoxia. Asphyxia is usually characterized by air hunger but this is not always the case; the urge to breathe is triggered by rising carbon dioxide levels in the blood rather than diminishing oxygen levels. Sometimes there is not enough carbon dioxide to cause air hunger, and victims become hypoxic without knowing it. In any case, the absence of effective remedial action will very rapidly lead to unconsciousness, brain damage and death. The time to death is dependent on the particular mechanism of asphyxia.
Smothering refers to the mechanical obstruction of the flow of air from the environment into the mouth and/or nostrils, for instance by covering the mouth and nose with a hand, pillow, or a plastic bag. Smothering can be either partial or complete, where partial indicates that the person being smothered is able to inhale some air, although less than required. Normally, smothering requires at least partial obstruction of both the nasal cavities and the mouth to lead to asphyxia. Smothering with the hands or chest is used in some combat sports to distract the opponent, and create openings for transitions, as the opponent is forced to react to the smothering. It is also used in BDSM as a type of facesitting.
In some cases, smothering is combined with simultaneous compressive asphyxia. One example is overlay, in which an adult accidentally rolls over an infant during co-sleeping; an accident that often goes unnoticed and is mistakenly thought to be sudden infant death syndrome. Other accidents involving a similar mechanism are cave-ins or when an individual is buried in sand or grain. In homicidal cases, the term burking is often ascribed to a killing method that involves simultaneous smothering and compression of the torso.
The knee-on-belly position compresses the chest, making it difficult for the person on the bottom to breathe.
Compressive asphyxia (also called chest compression) refers to the mechanical limitation of the expansion of the lungs by compressing the torso, hence interfering with breathing. Compressive asphyxia occurs when the chest or abdomen is compressed posteriorly.
In accidents, the term traumatic asphyxia or crush asphyxia is usually used to describe compressive asphyxia resulting from being crushed or pinned under a large weight or force. An example of traumatic asphyxia include cases where an individual has been using a car-jack to repair a car from below only to be crushed under the weight of the vehicle when the car-jack slips.
In fatal crowd disasters, contrary to popular belief, it is not the blunt trauma from trampling that causes the large part of the deaths, but rather the compressive asphyxia from being crushed against the crowd. In confined spaces, people push and lean against each other; evidence from bent steel railings in several fatal crowd accidents have shown horizontal forces over 4500 N (comparative weight approximately 460kg). In cases where people have stacked up on each other forming a human pile, estimations have been made of around 380kg of compressive weight in the lowest layer.
Chest compression is also featured in various grappling combat sports, where it is sometimes called wringing. Such techniques are either used to tire the opponent, or as complementary or distractive moves in combination with pinning holds, or sometimes even as submission holds.
Examples of chest compression include the knee-on-stomach position, or techniques such as leg scissors (also referred to as body scissors and in budo referred to as do-jime, 胴絞, "trunk strangle") where you wrap the legs around the opponent's midsection and squeeze them together.
Pressing is a form of torture or execution which works through asphyxia.
Asphyxia is used to maim or kill in capital punishment, suicide, torture, and warfare. It is also used non-fatally in martial arts, combat sports, BDSM and during sex as erotic asphyxia. Because the need to breathe is triggered by the level of carbon dioxide in the blood, some victims may not experience an urgent need to breathe and may remain unaware of the onset of hypoxia.
Various chemical and physiological situations can interfere with the body's ability to absorb and use oxygen or regulate blood oxygen levels:
Carbon monoxide inhalation, such as from a car exhaust, carbon monoxide has a higher affinity than oxygen to the hemoglobin in the blood's red blood corpuscles bonding with it tenaciously, displacing oxygen and preventing the blood from transporting it around the body.
Contact with certain chemicals, including pulmonary agents (such as phosgene) and blood agents (such as hydrogen cyanide).
Self-induced hypocapnia by hyperventilation, as in shallow water or deep water blackout and the choking game.
A seizure which stops breathing activity.
Sleep apnea.
Drug overdose.
Ondine's curse, central alveolar hypoventilation syndrome, or primary alveolar hypoventilation, a disorder of the autonomic nervous system in which a patient must consciously breathe. Although it is often said that persons with this disease will die if they fall asleep, this is not usuall the case.
Acute respiratory distress syndrome |
Levo-transposition_of_the_great_arteries_natural_history,_Complications_%26_Prognosis | The prognosis on simple levll-TGA
The prognosis on simple ll-TGA, if the foramen ovale and ductus arteriosus are allowed to close naturally, the newborn will likely not survive long enough to receive corrective surgery.Complex
lev |
Inferior_peduncle | The upper part of the posterior district of the medulla oblongata is occupied by the inferior peduncle, a thick rope-like strand situated between the lower part of the fourth ventricle and the roots of the glossopharyngeal and vagus nerves.
The inferior peduncles connect the medulla spinalis and medulla oblongata with the cerebellum, and are sometimes named the restiform bodies.
The inferior cerebellar peduncle carries many types of input and output fibers that are mainly concerned with integrating proprioceptive sensory input with motor vestibular functions such as balance and posture maintenance.
Proprioceptive information from the body is carried to the cerebellum via the posterior spinocerebellar tract.
This tract passes through the inferior cerebellar peduncle and synapses within the paleocerebellum.
Vestibular information projects onto the archicerebellum.
This peduncle also carries information directly from the Purkinje cells to the vestibular nuclei in the dorsal brainstem located at the junction between the pons and medulla.
Superior cerebellar peduncles
Middle cerebellar peduncles
Cerebral peduncle
, , Upper part of medulla spinalis and hind- and mid-brains; posterior aspect, exposed in situ.
, , Superficial dissection of brain-stem. Lateral view.
, , Dissection of brain-stem. Lateral view.
, , Deep dissection of brain-stem. Lateral view.
, , Dissection of brain-stem. Dorsal view. ,
, , Diagram showing the course of the arcuate fibers.
, , Dissection showing the course of the cerebrospinal fibers.
Template:UMichAtlas
Template:NeuroanatomyWisc
Template:Gray's
Cerebellum
Template:Rhombencephalon
Template:WikiDoc Sources
|
Hirsutism_case_studies | A 19-year-old woman complains of slowly progressive hair growth. Since high school, she has shaved her upper lip weekly and waxed her abdomen and thighs monthly. Her menstrual periods are regular. Physical examination is unremarkable except for a body-mass index of 31 and trace hair over the abdomen and thighs, with a moderate amount over her back. There are no signs of virilization.
|
Hybrid_coronary_revascularization | It is not to be confused with a MIDCAB procedure, which uses the smaller thoracotomy incision but does not involve coronary stenting. Hybrid bypass offers all the benefits of a MIDCAB:
Less pain for the patient and quicker recovery time.
Less risk of complications, infections etc and also decreases the necessity for two separate cardiac procedures (bypass and stenting).
Not all hospitals and/or surgeons offer this procedure and it requires a specially equipped OR. As such, it is worth inquiring to determine which hospitals do and whether or not a patient can benefit from this procedure.
Coronary artery bypass surgery
Percutaneous coronary intervention |
Esophageal_web | Esophageal webs are mucosal folds that partially obstructs the esophageal lumen. The exact pathogenesis of esophageal webs is not known but it is thought to be due to either esophageal inflammation, congenital anomaly, or iron deficiency. They can be classified into type A, B, and C according to their site and extent; type B being the most common. The most common causes are Plummer-Vinson syndrome, celiac sprue and Zenker’s diverticulum. Esophageal webs most commonly present with dysphagia that has a slow onset and is rarely complicated with weight loss. Esophageal webs must be differentiated from other causes of dysphagia such esophageal strictures and achalasia. In barium esophagogram, esophageal webs appear as a uniform narrowing of the esophagus and on endoscopy, esophageal webs appear as a smooth narrowing of the esophagus that is not present in the whole circumference of the lumen. Esophageal dilation is the cornerstone of treatment and it is effective in relieving the symptoms but with high recurrence rate.
In 1944, esophageal webs were first described by Templeton and it was thought to be a congenital disease because most of the patients were children.
In 1953, a series of case reports of patients having dysphagia and radiological signs denoting esophageal narrowing made the diagnosis of esophageal rings not confined to the pediatric population.
In 1968, histological examination of specimens from the esophageal rings proved that none of them had muscle involvement.
Esophageal webs can be classified according to their site and extent in three categories
Type A esophageal rings describe webs that involve the muscle layer of the esophageal wall and lies in close proximity to the squamo-columnar junction.
It is less common than type B esophageal webs.
Type B esophageal rings describe the webs that involve only the mucosa and submucosa of the esophagus.
It is often named “Schatzki ring”.
It is located exactly at the squamo-columnar junction.
Type C esophageal rings refer to wall invaginations due to pressure from the diaphragm.
It is rare with no clinical significance.
There are multiple theories explaining the origin of esophageal webs.
Esophageal webs are thought to be due to the chronic damage to the esophageal mucosa.
This is supported by the presence of inflammatory cells in the wall of the web.
In eosinophilic esophagitis, eosinophils were found while in cases of chronic inflammation as GERD, lymphocytes prevailed.
Esophageal webs are thought to be due to failure of the esophagus to recanalize.
Specimens showed that the esophageal webs contained respiratory epithelium supporting this theory.
The webs mostly remain asymptomatic for long times and that is why it is not correlated with being congenital.
The esophageal webs of Plummer-Vinson syndrome have been associated with iron deficiency anemia in many studies.
The exact mechanism by which iron deficiency causes esophageal webs is not known, but it was hypothesized that iron deficiency starts a sequence of events in the esophageal epithelium that ends in its damage and formation of a web.
Moreover, treatment of iron deficiency in Plummer-Vinson syndrome patients leads to resolution of dysphagia even before the laboratory results become normal.
Esophageal webs appear as an eccentric narrowing of the esophageal lumen (while rings cause circumferential narrowing).
Esophageal webs are covered normally by mucosa and submucosa.
It is characterized by the presence of basal cell hyperplasia.
The tissue is often heavily infiltrated with chronic inflammatory cells.
Eosinophilic esophagitis is characterized by the presence of eosinophil infiltration.
Iron deficiency anemia
Plummer-Vinson syndrome
Celiac sprue
Zenker’s diverticulum
Epidermolysis bullosa
Bullous pemphigoid
Graft versus host disease
Pemphigus Vulgaris
Esophageal webs must be differentiated from other causes of dysphagia such as achalasia and esophageal carcinoma.
Webs are diagnosed in 5-15% of patients doing barium esophagogram for diagnosing the cause of dysphagia.
Congenital esophageal webs are estimated to be 1 in 25,000 to 1 in 50,000 live births.
Esophageal webs affects the whites more than other population.
Esophageal webs tend to be more common in females.
This may be due to the increased prevalence of iron deficiency anemia.
Esophageal has no predilection for an age group, however, it is usually not symptomatic until after the age of 40.
According to USPSTF, there are no screening measures recommended for esophageal webs.
The disease can start at any age but symptoms usually start in the fifth decade of life.
The dysphagia is usually to solids at the beginning then it progresses to both solids and liquids.
If left untreated, the webs may progress causing esophageal strictures and esophageal carcinoma.
Progression to esophageal carcinoma.
Choking spells.
Esophagitis from chronic injury of the mucosa.
Progression to esophageal stricture.
The prognosis of esophageal webs is generally good especially with treatment of the underlying cause.
One of out of ten patients with Plummer-Vinson syndrome will develop esophageal carcinoma.
Patients are usually older than 40 years because it can be asymptomatic for a long time.
The patient may give a history of the cause such as iron deficiency anemia, GERD, or autoimmune disease.
There may be a history of excessive food chewing to facilitate swallowing.
Most of the esophageal webs are asymptomatic.
The major symptom of esophageal webs is dysphagia.
Dysphagia is usually more for solid food.
Esophageal webs do not usually result in malnutrition nor to weight loss.
Esophageal webs do not have significant physical exam findings, however, it might show the signs of the cause such as:
Koilonychia and glossitis in the cases of Plummer-Vinson syndrome.
It might also show the findings in in the cases of skin disorders such as epidermolysis bullosa, bullous pemphigoid, and pemphigus vulgaris.
A Laboratory workup is not necessary for the diagnosis of esophageal webs because the diagnosis is dependent on the symptoms and radiological tests.
CBC might show microcytic hypochromic anemia in cases of Plummer-Vinson syndrome as it is the primary cause of the esophageal web.
Antibody panel might be done to screen for the primary cause.
Barium esophagogram is more sensitive in detecting esophageal webs than endoscopy.
Webs appear as a uniform narrowing of the esophageal lumen.
Endoscopy is less sensitive in detecting webs than barium esophagram.
Esophageal webs appear as a smooth membrane that is not encircling the whole lumen.
It allows obtaining a biopsy from the lesion in addition to excluding other causes of dysphagia.
Esophageal webs can go unnoticed during the esophagram as it is only a mucous membrane fold with no muscle support.
Patients should be educated to change their diet and food habits, especially in the cases when esophageal webs are secondary to GERD.
H2 blockers or proton pump inhibitors can be used for managing the symptoms of GERD and the prevention of progression to webs.
Proper management of acid reflux after esophageal dilation is associated with decreased recurrence of symptoms.
Esophageal dilation is the cornerstone of treating esophageal webs especially in cases refractory to medical treatment.
In cases of eosinophilic esophagitis, dilation should be gradual as sudden forced dilation is associated with muscle tears.
In cases of non-eosinophilic esophagitis, dilation using a single dilator is more effective than graded dilation.
Esophageal dilation is associated with improved dysphagia.
Esophageal dilation is associated with symptom recurrence in about 89% at five years and often requires redoing of the procedure. |
Phenylalanine#D-,_L-_and_DL-phenylalanine | Phenylalanine (abbreviated as Phe or F) is an α-amino acid with the formula HO2CCH(NH2)CH2C6H5. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for L-phenylalanine are UUU and UUC. It is a white, powdery solid. L-Phenylalanine (LPA) is an electrically-neutral amino acid, one of the twenty common amino acids used to biochemically form proteins, coded for by DNA.
Phenylalanine cannot be made by animals, which have to obtain it from their diet. It is produced by plants and most microorganisms from prephenate, an intermediate on the shikimate pathway.
Prephenate is decarboxylated with loss of the hydroxyl group to give phenylpyruvate. This species is transaminated using glutamate as the nitrogen source to give phenylalanine and α-ketoglutarate.
L-phenylalanine can also be converted into L-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into L-DOPA, which is further converted into dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) (the latter three are known as the catecholamines).
Phenylalanine uses the same active transport channel as tryptophan to cross the blood-brain barrier, and, in large quantities, interferes with the production of serotonin.
Lignin is derived from phenylalanine and from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia lyase.
Main article: Phenylketonuria
The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. Individuals with this disorder are known as "phenylketonurics" and must abstain from consumption of phenylalanine. This dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) because they do not properly metabolize the amino acid phenylalanine. Persons suffering from PKU must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.
A related issue is the compound present in many sugarless gums and mints, snack foods, sugarless soft drinks (such as diet sodas including CocaCola Zero, Pepsi Max, some forms of Lipton Tea, diet Nestea, Clear Splash flavored water), and a number of other low calorie food products. The artificial sweetener aspartame, sold under the names "Equal" and "NutraSweet", is an ester that is hydrolyzed in the body to give phenylalanine, aspartic acid, and methanol (wood alcohol). The breakdown problems phenylketonurics have with protein and the attendant build up of phenylalanine in the body also occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in the U.S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredients panels that refer to the presence of 'aspartame or E951', [2]and they must be labeled with a warning "Contains a source of phenylalanine". These warnings are specifically placed to aid individuals who suffer from PKU so that they can avoid such foods.
Interestingly, the macaque genome was recently sequenced and it was found that macaques naturally have a mutation that is found in humans who have PKU.[3]
D-phenylalanine (DPA) either as a single enantiomer or as a component of the racemic mixture is available through conventional organic synthesis. It does not participate in protein biosynthesis although it is found in proteins, in small amounts, particularly aged proteins and food proteins that have been processed. The biological functions of D-amino acids remain unclear. Some D-amino acids, such as D-phenylalanine, may have pharmacological activity.
DL-Phenylalanine is marketed as a nutritional supplement for its putative analgesic and antidepressant activities. The putative analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. The mechanism of DL-phenylalanine's putative antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
D-phenylalanine is absorbed from the small intestine, following ingestion, and transported to the liver via the portal circulation. A fraction of D-phenylalanine appears to be converted to L-phenylalanine. D-phenylalanine is distributed to the various tissues of the body via the systemic circulation. D-phenylalanine appears to cross the blood-brain barrier with less efficiency than L-phenylalanine. A fraction of an ingested dose of D-phenylalanine is excreted in the urine.
The genetic codon for phenylalanine was the first to be discovered. Marshall W. Nirenberg discovered that insertion of m-RNA made up of multiple uracil repeats into E. coli, the bacterium produced a new protein, made up solely of repeated phenylalanine amino acids.
|
Chronic_pancreatitis_(patient_information) | Chronic pancreatitis is swelling (inflammation) of the pancreas that leads to scarring and loss of function. The pancreas is an organ located behind the stomach that produces chemicals needed to digest food. It also produces the hormones insulin and glucagon.
Symptoms of Chronic pancreatitis include
Abdominal pain, Greatest in the upper abdomen, May last from hours to days, Eventually may be continuous, May be worsened by eating or drinking, May be worsened by drinking alcohol, May spread (radiate) to the back
Digestive problems
Fatty stools
Nausea and vomiting
Pale or clay-colored stools
Unintentional weight loss
The symptoms may become more frequent as the condition gets worse. The symptoms may mimic pancreatic cancer. Sitting up and leaning forward may sometimes relieve the abdominal pain of pancreatitis.
Chronic pancreatitis causes inflammation and scarring of tissue in the pancreas. This makes the pancreas unable to produce the right amount of chemicals (enzymes) needed to digest fat. It also interferes with insulin production, which may lead to diabetes.
The condition is most often caused by alcoholism and alcohol abuse. Sometimes the cause cannot be determined, however. Genetic causes have become more common. Other conditions have also been linked to chronic pancreatitis, such as:
Chronic blockage of the pancreatic duct
Injury
Hyperlipidemia
Hyperparathyroidism
Chronic pancreatitis occurs more frequently in men than in women. This may be because alcohol-use disorders are more common in men.
Chronic pancreatitis is often confused with acute pancreatitis because the symptoms are similar. As with acute pancreatitis, the doctor will conduct a thorough medical history and physical examination. Blood tests may help the doctor know if the pancreas is still making enough digestive enzymes, but sometimes these enzymes appear normal even though the person has chronic pancreatitis.
In more advanced stages of pancreatitis, when malabsorption and diabetes can occur, the doctor may order blood, urine, and stool tests to help diagnose chronic pancreatitis and monitor its progression.
After ordering x rays of the abdomen, the doctor will conduct one or more of the tests used to diagnose acute pancreatitis—abdominal ultrasound, CT scan, EUS, and MRCP.
Call for an appointment with your health care provider if:
You develop symptoms of pancreatitis
You have pancreatitis and your symptoms worsen or do not improve with treatment
Treatment for chronic pancreatitis may require hospitalization for pain management, IV hydration, and nutritional support. Nasogastric feedings may be necessary for several weeks if the person continues to lose weight.
When a normal diet is resumed, the doctor may prescribe synthetic pancreatic enzymes if the pancreas does not secrete enough of its own. The enzymes should be taken with every meal to help the person digest food and regain some weight. The next step is to plan a nutritious diet that is low in fat and includes small, frequent meals. A dietitian can assist in developing a meal plan. Drinking plenty of fluids and limiting caffeinated beverages is also important.
People with chronic pancreatitis are strongly advised not to smoke or consume alcoholic beverages, even if the pancreatitis is mild or in the early stages
Acute pancreatitis
Cholelithiasis
Diabetes mellitus
Pancreatic cancer
Irritable bowel syndrome
Directions to Hospitals Treating Chronic pancreatitis
Determining the cause of acute pancreatitis and treating it promptly may help to prevent chronic pancreatitis. Avoiding heavy consumption of alcohol dramatically reduces the risk of developing this condition.
This is a serious disease that may lead to disability and death. You can reduce the risk by avoiding alcohol.
Ascites
Blockage (obstruction) of the small intestine or bile ducts
Blood clot in the vein of the spleen
Fluid collections in the pancreas (pancreatic pseudocysts) that may become infected
Poor function of the pancreas, Diabetes, Fat malabsorption
http://www.nlm.nih.gov/medlineplus/ency/article/000221.htm
http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis/#chronic
Template:WikiDoc Sources
|
Staphylococcal | Staphylococcus (from the Template:Lang-el, staphylē, "grape" and κόκκος, kókkos, "granule") is a genus of Gram-positive bacteria. Under the microscope, they appear round (cocci), and form in grape-like clusters.
The Staphylococcus genus includes at least 40 species. Of these, nine have two subspecies and one has three subspecies. Most are harmless and reside normally on the skin and mucous membranes of humans and other organisms. Found worldwide, they are a small component of soil microbial flora.
The taxonomy is based on 16s rRNA sequences, and most of the staphylococcal species fall into 11 clusters:
S. aureus group – S. aureus, S. simiae
S. auricularis group – S. auricularis
S. carnosus group – S. carnosus, S. condimenti, S. massiliensis, S. piscifermentans, S. simulans
S. epidermidis group – S. capitis, S. caprae, S. epidermidis, S. saccharolyticus
S. haemolyticus group – S. devriesei, S. haemolyticus, S. hominis
S. hyicus-intermedius group – S. chromogenes, S. felis, S. delphini, S. hyicus, S. intermedius, S. lutrae, S. microti, S. muscae, S. pseudintermedius, S. rostri, S. schleiferi
S. lugdunensis group – S. lugdunensis
S. saprophyticus group – S. arlettae, S. cohnii, S. equorum, S. gallinarum, S. kloosii, S. leei, S. nepalensis, S. saprophyticus, S. succinus, S. xylosus
S. sciuri group – S. fleurettii, S. lentus, S. sciuri, S. stepanovicii, S. vitulinus
S. simulans group – S. simulans
S. warneri group – S. pasteuri, S. warneri
A twelfth group – that of S. caseolyticus – has now been moved to a new genus Macrococcus, the species of which are currently the closest known relatives of the Staphylococci.
S. aureus subsp. aureus
S. aureus subsp. anaerobius
S. capitis subsp. capitis
S. capitis subsp. urealyticus
S. carnosus subsp. carnosus
S. carnosus subsp. utilis
S. cohnii subsp. cohnii
S. cohnii subsp. urealyticus
S. equorum subsp. equorum
S. equorum subsp. linens
S. hominis subsp. hominis
S. hominis subsp. novobiosepticus
S. saprophyticus subsp. bovis
S. saprophyticus subsp. saprophyticus
S. schleiferi subsp. coagulans
S. schleiferi subsp. schleiferi
S. sciuri subsp. carnaticus
S. sciuri subsp. rodentium
S. sciuri subsp. sciuri
S. succinus subsp. casei
S. succinus subsp. succinus
As with all generic names in binomial nomenclature, Staphylococcus is capitalized when used alone or with a specific species. Also, the abbreviations Staph and S. when used with a species (S. aureus) are correctly italicized and capitalized (though often errors in this are seen in popular literature). However, Staphylococcus is not capitalized or italicized when used in adjectival forms, as in a staphylococcal infection, or as the plural (staphylococci).
The S. saprophyticus and S. sciuri groups are generally novobiocin-resistant, as is S. hominis subsp. novobiosepticus.
Members of the S. sciuri group are oxidase-positive due to their possession of the enzyme cytochrome c oxidase. This group is the only clade within the Staphylococci to possess this gene.
The S. sciuri group appears to be the closest relations to the genus Macrococcus.
Staphylococcus pulvereri has been shown to be a junior synonym of Staphylococcus vitulinus.
Within these clades, the S. haemolyticus and S. simulans groups appear to be related, as do the S. aureus and S. epidermidis groups.
S. lugdunensis appears to be related to the S. haemolyticus group.
S. croceolyticus may be related to S. haemolyticus, but this needs to be confirmed.
The taxonomic position of S. croceolyticus, S. leei, S. lyticans and S. pseudolugdunensis has yet to be clarified. The published descriptions of these species do not appear to have been validly published to date (2010).
Assignment of a strain to the genus Staphylococcus requires it to be a Gram-positive coccus that forms clusters, produces catalase, has an appropriate cell wall structure (including peptidoglycan type and teichoic acid presence) and G + C content of DNA in a range of 30–40 mol%.
Staphylococcus species can be differentiated from other aerobic and facultative anaerobic, Gram-positive cocci by several simple tests. Staphylococcus spp. are facultative anaerobes (capable of growth both aerobically and anaerobically). All species grow in the presence of bile salts.
It was believed that all species were coagulase-positive however it is now known that not all Staphylococcus are coagulase positive.
Growth can also occur in a 6.5% NaCl solution. On Baird Parker medium, Staphylococcus spp. grow fermentatively, except for S. saprophyticus, which grows oxidatively. Staphylococcus spp. are resistant to bacitracin (0.04 U disc: resistance = < 10 mm zone of inhibition) and susceptible to furazolidone (100 μg disc: resistance = < 15 mm zone of inhibition). Further biochemical testing is needed to identify to the species level.
When the bacterium divides it divides along two axes, so forming clumps of bacteria. This is as opposed to streptococci which divide along one axis and so form chains (strep. meaning twisted or pliant).
One of the most important phenotypical features used in the classification of staphylococci is their ability to produce coagulase, an enzyme that causes blood clot formation.
Six species are currently recognised as being coagulase-positive: S. aureus, S. delphini, S. hyicus, S. intermedius, S. lutrae,S. pseudintermedius and S. schleiferi subsp. coagulans. These species belong to two separate groups – the S. aureus (S. aureus alone) group and the S. hyicus-intermedius group (the remaining five). S. aureus can also be found as being coagulase-negative.
A seventh species has also been described – Staphylococcus leei – from patients with gastritis.
S. aureus is coagulase-positive, meaning it produces coagulase. However, while the majority of S. aureus strains are coagulase-positive, some may be atypical in that they do not produce coagulase. S. aureus is catalase-positive (meaning that it can produce the enzyme catalase) and able to convert hydrogen peroxide (H2O2) to water and oxygen, which makes the catalase test useful to distinguish staphylococci from enterococci and streptococci.
S. pseudintermedius inhabits and sometimes infects the skin of domestic dogs and cats. This organism, too, can carry the genetic material that imparts multiple bacterial resistance. It is rarely implicated in infections in humans, as a zoonosis.
S. epidermidis, a coagulase-negative species, is a commensal of the skin, but can cause severe infections in immune-suppressed patients and those with central venous catheters.
S. saprophyticus, another coagulase-negative species that is part of the normal vaginal flora, is predominantly implicated in genitourinary tract infections in sexually active young women.
In recent years, several other Staphylococcus species have been implicated in human infections, notably S. lugdunensis, S. schleiferi, and S. caprae.
Staphylococcus epidermidis
Staphylococcus haemolyticus
Staphylococcus lugdunensis
Staphylococcus saprophyticus
Staphylococcus auricularis
Staphylococcus capitis
Staphylococcus caprae
Staphylococcus carnosus
Staphylococcus cohnii
Staphylococcus hominis
Staphylococcus pasteuri
Staphylococcus pettenkoferi
Staphylococcus pulvereri
Staphylococcus saccharolyticus
Staphylococcus simulans
Staphylococcus schleiferi
Staphylococcus warneri
Staphylococcus xylosus
The first S. aureus genomes to be sequenced were those of N315 and Mu50 in 2001. Many more complete S. aureus genomes have been submitted to the public databases, making it one of the most extensively sequenced bacteria. The use of genomic data is now widespread and provides a valuable resource for researchers working with S. aureus. Whole genome technologies, such as sequencing projects and microarrays, have shown an enormous variety of S. aureus strains. Each contains different combinations of surface proteins and different toxins. Relating this information to pathogenic behaviour is one of the major areas of staphylococcal research. The development of molecular typing methods has enabled the tracking of different strains of S. aureus. This may lead to better control of outbreak strains. A greater understanding of how the staphylococci evolve, especially due to the acquisition of mobile genetic elements encoding resistance and virulence genes is helping to identify new outbreak strains and may even prevent their emergence.
The widespread incidence of antibiotic resistance across various strains of S. aureus, or across different species of Staphylococcus has been attributed to horizontal gene transfer of genes encoding antibiotic/metal resistance and virulence. A recent study demonstrated the extent of horizontal gene transfer among Staphylococcus to be much greater than previously expected, and encompasses genes with functions beyond antibiotic resistance and virulence, and beyond genes residing within the mobile genetic elements.
Various strains of Staphylococcus are available from biological research centres, such as the National Collection of Type Cultures (NCTC).
File:20101017 231210 Staphylococcus.jpgUnknown variety of Staphylococcus, Gram-stained - numbered ticks on the scale are 11 µm apart.
Members of the genus Staphylococcus frequently colonize the skin and upper respiratory tracts of mammals and birds. Some species specificity has been observed in host range, such that the Staphylococcus species observed on some animals appear more rarely on more distantly related host species.
Some of the observed host specificity includes:
S. arlattae – chickens, goats
S. auricularis – deer, dogs, humans
S. capitis – humans
S. caprae – goats, humans
S. cohnii – chickens, humans
S. delphini – dolphins
S. devriesei – cattle
S. epidermiditis – humans
S. equorum – horses
S. felis – cats
S. fleurettii – goats
S. gallinarum – chickens, goats, pheasants
S. haemolyticus – humans, Cercocebus, Erythrocebus, Lemur, Macca, Microcebus, Pan
S. hyicus – pigs
S. leei – humans
S. lentus – goats, rabbits, sheep
S. lugdunensis – humans, goats
S. lutrae – otters
S. microti – voles (Microtus arvalis)
S. nepalensis – goats
S. pasteuri – humans, goats
S. pettenkoferi – humans
S. pseudintermedius – dogs
S. rostri – pigs
S. schleiferi – humans
S. sciuri – humans, dogs, goats
S. simiae – South American squirrel monkeys (Saimiri sciureus)
S. simulans – humans
S. warneri – humans, Cercopithecoidea, Pongidae
S. xylosus – humans
Main article: Staphylococcal infection
Staphylococcus can cause a wide variety of diseases in humans and animals through either toxin production or penetration. Staphylococcal toxins are a common cause of food poisoning, as they can be produced by bacteria growing in improperly stored food items.
The most common sialadenitis is caused by staphylococci, as bacterial infections.
MRSA
Staphylococcal enteritis
Staphylococcus aureus
Vancomycin-resistant S. aureus |
Holography | File:Hologrammit.jpgHologram Artwork in MIT Museum
Holography was invented in 1947 by Hungarian physicist Dennis Gabor (Hungarian name: Gábor Dénes) (1900–1979), work for which he received the Nobel Prize in physics in 1971. It was made possible by pioneering work in the field of physics by other scientists like Mieczysław Wolfke who resolved technical issues that previously made advancements impossible. The discovery was an unexpected result of research into improving electron microscopes at the British Thomson-Houston Company in Rugby, England. The British Thomson-Houston company filed a patent in December 1947(patent GB685286), but the field did not really advance until the development of the laser in 1960.
The first holograms that recorded 3D objects were made in 1962 by Yuri Denisyuk in the Soviet Union; and by Emmett Leith and Juris Upatnieks in University of Michigan, USA. Advances in photochemical processing techniques, to produce high-quality display holograms were achieved by Nicholas J. Phillips.
Several types of holograms can be made. Transmission holograms, such as those produced by Leith and Upatnieks, are viewed by shining laser light through them and looking at the reconstructed image from the side of the hologram opposite the source. A later refinement, the "rainbow transmission" hologram allows more convenient illumination by white light rather than by lasers or other monochromatic sources. Rainbow holograms are commonly seen today on credit cards as a security feature and on product packaging. These versions of the rainbow transmission hologram are commonly formed as surface relief patterns in a plastic film, and they incorporate a reflective aluminium coating which provides the light from "behind" to reconstruct their imagery.
Another kind of common hologram, the reflection or Denisyuk hologram, is capable of multicolour image reproduction using a white light illumination source on the same side of the hologram as the viewer.
One of the most promising recent advances in the short history of holography has been the mass production of low-cost solid-state lasers—typically used by the millions in DVD recorders and other applications, but which are sometimes also useful for holography. These cheap, compact, solid-state lasers can under some circumstances compete well with the large, expensive gas lasers previously required to make holograms, and are already helping to make holography much more accessible to low-budget researchers, artists, and dedicated hobbyists.
Though holography is often referred to as 3D photography, this is a misconception. A better analogy is sound recording where the sound field is encoded in such a way that it can later be reproduced. In holography, some of the light scattered from an object or a set of objects falls on the recording medium. A second light beam, known as the reference beam, also illuminates the recording medium, so that interference occurs between the two beams. The resulting light field is an apparently random pattern of varying intensity which is the hologram. It can be shown that if the hologram is illuminated by the original reference beam, a light field is diffracted by the reference beam which is identical to the light field which was scattered by the object or objects. Thus, someone looking into the hologram 'sees' the objects even though they may no longer be present. There are a variety of recording materials which can be used, including photographic film.
Interference occurs when one or more wavefronts are superimposed. Diffraction occurs whenever a wavefront encounters an object. The process of producing a holographic reconstruction is explained below purely in terms of interference and diffraction. It is somewhat simplistic, but is accurate enough to provide an understanding of how the holographic process works.
A diffraction grating is a structure with a repeating pattern. A simple example is a metal plate with slits cut at regular intervals. Light rays travelling through it are bent at an angle determined by λ, the wavelength of the light and d, the distance between the slits and is given by sinθ = λ/d.
A very simple hologram can be made by superimposing two plane waves from the same light source. One(the reference beam)hits the photographic plate normally and the other one (the object beam) hits the plate at an angle θ. The relative phase between the two beams varies across the photographic plate as 2π y sinθ/λ where y is the distance along the photographic plate. The two beams interfere with one another to form an interference pattern. The relative phase changes by 2π at intervals of d = λ/sinθ so the spacing of the interference fringes is given by d. Thus, the relative phase of object and reference beam is encoded as the maxima and minima of the fringe pattern.
When the photographic plate is developed, the fringe pattern acts as a diffraction grating and when the reference beam is incident upon the photographic plate, it is partly diffracted into the same angle θ at which the original object beam was incident. Thus, the object beam has been re-constructed. The diffraction grating created by the two waves interfering has reconstructed the "object beam" and it is therefore a hologram as defined above.
A slightly more complicated hologram can be made using a point source of light as object beam and a plane wave as reference beam to illuminate the photographic plate. An interference pattern is formed which in this case is in the form of curves of decreasing separation with increasing distance from the centre.
The photographic plate is developed giving a complicated pattern which can be considered to be made up of a diffraction pattern of varying spacing. When the plate is illuminated by the reference beam alone, it is diffracted by the grating into different angles which depend on the local spacing of the pattern on the plate. It can be shown that the net effect of this it to re-construct the object beam, so that it appears that light is coming from a point source behind the plate, even when the source has been removed. The light emerging from the photographic plate is identical to the light emerging when the point source which used to be there. An observer looking into the plate from the other side will 'see' a point source of light whether the original source of light is there or not.
This sort of hologram is effectively a concave lens, since it 'converts' a plane wavefront into a divergent wavefront. It will also increase the divergence of any wave which is incident on it in exactly the same way as a normal lens does. Its focal length is the distance between the point source and the plate.
File:Holograph-record.svgHolographic recording process
The diagram on the right shows the optical arrangement for making a hologram of a complex object. The laser beam is split in two by the beam splitter. One beam illuminates the object which then scatters light onto the recording medium. The second (reference) beam illuminates the recording medium directly.
According to diffraction theory, each point in the object acts as a point source of light. Each of these point sources interferes with the reference beam, giving rise to an interference pattern. The resulting pattern is the sum of a large number (strictly speaking, an infinite number) of point source + reference beam interference patterns.
File:Holography-reconstruct.svgHolographic reconstruction process
The diagram on the left shows the optical arrangement for re-constructing the object beam. The object is no longer present, and the hologram is illuminated by the reference beam. Each point source diffraction grating will diffract part of the reference beam to re-construct the wavefront from its point source. These individual wavefronts add together to recontstruct the whole of the object beam.
The viewer perceives a wavefront which is identical to the wavefront scattered by the object, so that it appears to him/her that the object is still in place. This image is known as a 'virtual' image as it is generated even though the object is no longer there.
This explains, albeit in somewhat simplistic terms, how transmission holograms work. Other holograms, such as rainbow and Denisyuk holgrams are somewhat more complex but the principles are the same
A light wave can be modelled by a complex number U which represents the electric or magnetic field of the light wave. The amplitude and phase of the light are represented by the absolute value and angle of the complex number. The object and reference waves at any point in the holographic system are given by UO and UR. The combined beam is given be UO + UR. The energy of the combined beams is proportional to the square of magnitude of the electric wave:
<math>|U_O + U_R|^2=U_O U_R^*+|U_R|^2+|U_O|^2+ U_O^*U_R</math>
If a photographic plate is exposed to the two beams, and then developed, its transmittance, T, is proportional to the light energy which was incident on the plate, and is given by
<math>T=k[U_O U_R^*+|U_R|^2+|U_O|^2+ U_O^*U_R]</math>
where k is a constant. When the developed plate is illuminated by the reference beam, the light transmitted through the plate, UH is
<math>U_H=TU_R=k[U_O U_R^*+|U_R|^2+|U_O|^2+ U_O^*U_R]U_R=k[U_O+|U_R|^2U_R+|U_O|^2U_R+ U_O^*U_R^2]</math>
It can be seen that UH has four terms. The first of these is kUO, since URUR* is equal to one, and this is the re-constructed object beam. The second term represents the reference beam whose amplitude has been modifed by UR2. The third also represent the reference beam which has had its amplitude modifed by UO2; this modification will cause the reference beam to be diffracted around its central direction. The fourth term is know as the 'conjugate object beam'. It has the reverse curvature to the object beam itself, and forms a real image of the object in the space beyond the holographic plate.
Early holograms had both the object and reference beams illuminating the recording medium normally which meant that all the four beams emerging from the holgram were superimposed on one another. The off-axis hologram was developed by Leith and Upatnieks to overcome this problem. The object and reference beams are incident at well-separated angles onto the holographic recording medium and the virtual, real and reference wavefronts all emerge at different angles enabling the re-constructed object beam to be imaged clearly.
File:Holographic recording.jpgPhotograph of a hologram in front of a diffuse light background - 8x8mm
The picture on the right is a photograph, taken against a diffuse light background, of a hologram recorded on photographic emulsion. The area shown is about 8mmx8mm. The holographic recording is the random variation in intensity which is an objective speckle pattern, and not the regular lines which are likely to be due to interference arising from multiple reflections in the glass plate on which the photographic emulsion is mounted. It is no more possible to discern the subject of the hologram from this than it is to identify the music on a gramophone record by looking at the structure of the tracks. When this hologram is illuminated by a divergent laser beam, the viewer will see the object used to make it (in this case, a toy van) because the light is diffracted by the hologram to re-construct the light which was scattered from the object.
When you look at a scene, each eye captures a portion of the light scattered from the scene, and the lens of the eye forms an image of the scene on the retina, in which light from each angular position is focused to a specific angular position in the image plane. Since the hologram reconstructs the whole of the scattered light field which was incident on the hologram, the viewer sees the same image whether this is derived from the light field scattered from the object, or the reconstructed light field produced by the hologram and is unable to tell whether he/she is looking at the real or the virtual object. If the viewer moves about, the object will appear to move in exactly the same way whether he/she is looking at the original light field or the reconstructed light field. If there are several objects in the scene, they will exhibit parallax. If the viewer is using both eyes (stereoscopic vision), he/she will get depth information when viewing the hologram in exactly the same way as when he/she is viewing the real scene.
It should be clear from this why a hologram is not a 3D photograph. A photograph records an image of the recorded scene from a single viewpoint, which is defined by the position of the camera lens. The hololgram is not an image, but an encoding system which enables the scattered light field to be reconstructed. Images can then be formed from any point in the reconstructed beam either with a camera or by eye. It was very common in the early days of holography to use a chess board as the object, and then take photographs at several different angles using the reconstructed light to show how the relative positions of the chess-pieces appeared to change.
Since each point in the hologram contains light from the whole of the original scene, the whole scene can, in principle, be re-constructed from a single point in the hologram. To demonstrate this concept, you can break the hologram into small pieces and you can still see the entire object from each small piece. If you envisage the hologram as a 'window' on the object, then each small piece of hologram is just a part of the window from which you can still view the object even if the rest of the window is blocked off.
You do, however, lose resolution as you decrease the size of the hologram - the image becomes 'fuzzier'. This is a result of diffraction and arises in the same way as the resolution of an imaging system is ultimately limited by diffraction where the resolution becomes coarser as the lens or lens aperture diameter decreases.
The object and the reference beams must be able to produce an interference pattern which is stable during the time in which the holographic recording is made. To do this, they must have the same frequency and the same relative phase during this time, that is, they must be mutually coherent. Many laser beams satisfy this condition, and lasers have been used to make holograms since their invention, though it should be noted that the first holograms by Gabor used 'quasi-chromatic' light sources. In principle, two separate light sources could be used if the coherence condition could be satisfied, but in practice a single laser is always used.
In addition, the medium used to record the fringe pattern must be able to resolve the fringe patterns and some of the more common media used are listed below. The spacing of the fringes depends on the angle between object and reference beam. For example, if this angle is 45o, and the wavelength of the light is 0.5μm, the fringe spacing is about 0.7μm or 1300 lines/mm. A working hologram can be obtained even if all the fringes are not resolved, but the resolution of the image is reduced as the resolution of the recording medium reduces.
Mechanical stability is also very important when making a hologram. Any relative phase change between the object and reference beams due to vibration or air movement will cause the fringes on the recording medium to move, and if the phase changes is greater than π, the fringe pattern is averaged out, and no holographic recording is obtained. Recording time can be several seconds or more, and given that a phase change of π is equivalent to a movement of λ/2 this is quite a stringent stability equirement.
Generally, the coherence length of the light determines the maximum depth in the scene of interest which can be recorded holographically. A good holography laser will typically have a coherence length of several meters, ample for a deep hologram. Certain pen laser pointers have been used to make small holograms (see External links). The size of these holograms is not restricted by the coherence length of the laser pointers (which can exceed several meters), but by their low power of below 5 mW.
The objects which form the scene must, in general, have optically rough surfaces so that they scatter light over a wide range of angles. A specularly reflecting (or shiny) surface reflects the light in only one direction at each point on its surface, so in general, most of the light will not be incident on the recording medium. It should be noted that the light scattered from objects with a rough surface forms an objective speckle pattern which has random amplitude and phase.
The reference beam is not normally a plane wavefront; it is usually a divergent wavefront which is formed by placing a convex lens in the path of the laser beam.
To re-construct the object exactly from a transmission holgram, the reference beam must have the same wavelength, the same curvature, and must illuminate the hologram at the same angle as the original reference beam. Any slight departure from any of these conditions will give a distorted re-construction, and if the difference between the reconstruction and original reference beam is too great, no re-construction is obtained.
Exact re-construction is achieved in holographic interferometry where the holographically re-constructed wavefront interferes with the live wavefront, to map out any displacement of the live object, and gives a null fringe if the object has not moved.
The recording medium must be able to resolve the interference fringes as discussed above. It must also be sufficiently sensitive to record the fringe pattern in a time period short enough for the system to remain optically stable, i.e any relative movement of the two beams must be significantly less than λ/2.
The recording medium has to convert the interference pattern into an optical element which modifies either the amplitude or the phase of a light beam which is incident upon it.
These are known as amplitude and phase holograms respectively. In amplitude holograms the modulation is in the varying absorption of the light by the hologram, as in a developed photographic emulsion which is less or more absorptive depending on the intensity of the light which illuminated it. In phase holograms, the optical distance (i.e. the refractive index or in some cases the thickness) in the material is modulated.
Most materials used for phase holograms reach the theoretical diffraction efficiency for holograms, which is 100% for thick holograms (Bragg diffraction regime) and 33.9% for thin holograms (Raman-Nath diffraction regime, holographic films of typically some μm thickness). Amplitude holograms have a lower efficiency than phase holograms and are therefore used more rarely.
The table below shows the principal materials for holographic recording. Note that these do not include the materials used in the mass replication of an existing hologram. The resolution limit given in the table indicates the maximal number of interference lines per mm of the gratings. The required exposure is for a long exposure. Short exposure times (less than 1/1000th of second, such as with a pulsed laser) require a higher exposure due to reciprocity failure.
It is also possible to make holographic recordings using digital cameras - see digital holography
File:Nokia Battery Hologram.jpgA hologram on a Nokia mobile phone battery. This is intended to show the battery is 'original Nokia' and not a cheaper imitation.
An existing hologram can be replicated, either in an optical way similar to holographic recording, or in the case of surface relief holograms, by embossing. Surface relief holograms are recorded in photoresists or photothermoplastics, and allow cheap mass reproduction. Such embossed holograms are now widely used, for instance as security features on credit cards or quality merchandise. The Royal Canadian Mint even produces holographic gold and silver coinage through a complex stamping process. The first book to feature a hologram on the front cover was The Skook (Warner Books, 1984) by JP Miller, featuring an illustration by Miller.
The first step in the embossing process is to make a stamper by electrodeposition of nickel on the relief image recorded on the photoresist or photothermoplastic. When the nickel layer is thick enough, it is separated from the master hologram and mounted on a metal backing plate. The material used to make embossed copies consists of a polyester base film, a resin separation layer and a thermoplastic film constituting the holographic layer.
The embossing process can be carried out with a simple heated press. The bottom layer of the duplicating film (the thermoplastic layer) is heated above its softening point and pressed against the stamper so that it takes up its shape. This shape is retained when the film is cooled and removed from the press. In order to permit the viewing of embossed holograms in reflection, an additional reflecting layer of aluminium is usually added on the hologram recording layer.
Main article: Holographic memory
Holography can be put to a variety of uses other than recording images. Holographic data storage is a technique that can store information at high density inside crystals or photopolymers. The ability to store large amounts of information in some kind of media is of great importance, as many electronic products incorporate storage devices. As current storage techniques such as Blu-ray reach the denser limit of possible data density (due to the diffraction-limited size of the writing beams), holographic storage has the potential to become the next generation of popular storage media.The advantage of this type of data storage is that the volume of the recording media is used instead of just the surface.
Currently available SLMs can produce about 1000 different images a second at 1024×1024-bit resolution. With the right type of media (probably polymers rather than something like LiNbO3), this would result in about 1 gigabit per second writing speed. Read speeds can surpass this and experts believe 1-terabit per second readout is possible.
In 2005, companies such as Optware and Maxell have produced a 120 mm disc that uses a holographic layer to store data to a potential 3.9 TB (terabyte), which they plan to market under the name Holographic Versatile Disc. Another company, InPhase Technologies, is developing a competing format.
While many holographic data storage models have used "page-based" storage, where each recorded hologram holds a large amount of data, more recent research into using submicrometre-sized "microholograms" has resulted in several potential 3D optical data storage solutions. While this approach to data storage can not attain the high data rates of page-based storage, the tolerances, technological hurdles, and cost of producing a commercial product are significantly lower.
Main article: holographic interferometry
Holographic interferometry (HI)is a technique which enables static and dynamic displacements of objects with optically rough surfaces to be measured to optical interferometric precision (i.e to fractions of a wavelength of light). It can also be used to detect optical path length variations in transparent media, which enables, for example, fluid flow to be visualised and analysed. It can also be used to generate contours representing the form of the surface.
It has been widely used to measure stress, strain, and vibration in engineering structures
Main article: Security hologram
Security holograms are very difficult to forge because they are replicated from a master hologram which requires expensive, specialized and technologically advanced equipment. They are used widely in many currencies such as the Brazilian real 20 note, British pound 5/10/20 notes, Canadian dollar 5/10/20/50/100 notes, Euro 5/10/20/50/100/200/500 notes, South Korean won 5000/10000 notes, Japanese yen 5000/10000 notes, etc. They are also used in credit and bank cards as well as quality products.
Main article: Interferometric microscopy
The hologram keeps the information on the amplitude and phase of the field. Several holograms may keep information about the same distribution of light,
emitted to various directions. The numerical analysis of such holograms allows one to emulate large numerical aperture which, in turn, enables enhancement of the resolution of optical microscopy.
The corresponding technique is called interferometric microscopy. Recent achievements of interferometric microscopy allow one to approach the quarter-wavelength limit of resolution.
The discussion above describes static holography, in which recording, developing and reconstructing occur sequentially and a permanent hologram is produced.
There exist also holographic materials which don't need the developing process and can record a hologram in a very short time. This allows to use holography to perform some simple operations in an all-optical way. Examples of applications of such real-time holograms include phase-conjugate mirrors ("time-reversal" of light), optical cache memories, image processing (pattern recognition of time-varying images), and optical computing.
The amount of processed information can be very high (terabit/s), since the operation is performed in parallel on a whole image. This compensates the fact that the recording time, which is in the order of a µs, is still very long compared to the processing time of an electronic computer. The optical processing performed by a dynamic hologram is also much less flexible than electronic processing. On one side one has to perform the operation always on the whole image, and on the other side the operation a hologram can perform is basically either a multiplication or a phase conjugation. But remember that in optics, addition and Fourier transform are already easily performed in linear materials, the second simply by a lens. This enables some applications like a device that compares images in an optical way.
The search for novel nonlinear optical materials for dynamic holography is an active area of research. The most common materials are photorefractive crystals, but also in semiconductors or semiconductor heterostructures (such as quantum wells), atomic vapors and gases, plasmas and even liquids it was possible to generate holograms.
A particularly promising application is optical phase conjugation. It allows the removal of the wavefront distortions a light beam receives when passing through an aberrating medium, by sending it back through the same aberrating medium with a conjugated phase. This is useful for example in free-space optical communications to compensate for atmospheric turbulence (the phenomenon that gives rise to the twinkling of starlight).
Early on artists saw the potential of holography as a medium and gained access to science laboratories to create their work. Holographic art is often the result of collaborations between scientists and artists, although some holographers would regard themselves as both an artist and scientist.
Salvador Dalí claimed to have been the first to employ holography artistically. He was certainly the first and most notorious surrealist to do so, but the 1972 New York exhibit of Dalí holograms had been preceded by the holographic art exhibition which was held at the Cranbrook Academy of Art in Michigan in 1968 and by the one at the Finch College gallery in New York in 1970, which attracted national media attention.
During the 1970's a number of arts studios and schools were established, each with their particular approach to holography. Notably there was the San Francisco School of holography established by Llyod Cross, The Museum of Holography in New York founded by Rosemary (Possie) H. Jackson, the Royal College of Art in London and the Lake Forrest College Symposiums organised by Tung Jeong (T.J). None of these studios still exist, however there is the Center for the Holographic Arts in New York [1] and the HOLOcenter in Seoul [2] which offer artists a place to create and exhibit work.
A small but active group of artist use holography as their main medium and many more artists integrate holographic elements into their work.
The MIT Museum [3] and Jonathan Ross [4] both have extensive collections of holography and on-line catalogues of art holograms.
File:Contest3.jpg“Peace Within Reach” a Denisyuk DCG hologram by amateur Dave Battin.
Since the beginning of holography experimenters have explored the uses of holography. Starting in 1971 Lloyd Cross started the San Francisco School of Holography and started to teach amateurs the methods of making holograms with inexpensive equipment. This method relied on the use of a large table of deep sand (invented by Jerry Pethic) to hold the optics rigid and dampen vibrations that would destroy the image.
Many of these holographers would go on to produce art holograms. In 1983, Fred Unterseher published the Holography Handbook, a remarkably easy to read description of making holograms at home. This brought in a new wave of holographers and gave simple methods to use the then available AGFA silver halide recording materials.
In 2000 Frank DeFreitas published the Shoebox Holography Book and introduced using inexpensive laser pointers to countless hobbiests. This was a very important development for amateurs as it took the cost for a 5mw laser from $1200 to $5. Now there are hundreds to thousands of amateur holographers worldwide.
In 2006 a large number of surplus Holography Quality Green Lasers (Coherent C315) became available and put Dichromated Gelatin (DCG) within the reach of the amateur holographer. The holography community was surprised at the amazing sensitivity of DCG to green light. It had been assumed that the sensitivity would be non existent. Jeff Blythe responded with the G307 formulation of DCG to increase the speed and sensitivity to these new lasers.
Many film suppliers have come and gone from the silver halide market. While more film manufactures have filled in the voids, many amateurs are now making their own film. The favorite formulations are Dichromated Gelatin, Methelene Blue Sensitised Dichromated Gelatin and Diffusion Method Silver Halide preparations. Jeff Blythe has published very accurate methods for making film in a small lab or garage.
A small group of amateurs are even constructing their own pulsed lasers to make holograms of moving objects.
Jeff Blythe's Film Formulations
In principle, it is possible to make a hologram for any wave.
Main article: Electron holography
Electron holography is the application of holography techniques to electron waves rather than light waves.
Electron holography was invented by Dennis Gabor to improve the resolution and avoid the aberrations of the transmission electron microscope. Today it is commonly used to study electric and magnetic fields in thin films, as magnetic and electric fields can shift the phase of the interfering wave passing through the sample.
The principle of electron holography can also be applied to interference lithography.
Main article: Acoustic holography
Acoustic Holography is the method for registering sound waves.
Atomic holography has evolved out of the development of the basic elements of atom optics. With the Fresnel diffraction lens and atomic mirrors atomic holography follows a natural step in the development of the physics (and applications) of atomic beams. Recent developments including atomic mirrors and especially ridged mirrors have provided the tools necessary for the creation of atomic holograms., although such holograms have not yet been commercialized.
An analogy between the distributed information in holograms and the distributed information in brains gave rise to a speculative idea termed holonomic brain theory.
|
Ovarian_epithelial_cancer | History and Symptoms | Physical Examination | Staging | Laboratory Findings | X Rays | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgical | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Germ cell tumor
Desmoplastic small round cell tumor
Ovarian cyst
Template:WikiDoc Sources
|
Arhinencephaly | Cephalic disorders (from the Greek word κεφάλη, meaning "head") are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic is a term that means "head" or "head end of the body."
Where known, the ICD-10 code is listed below.
Anencephaly (Q00.0)
Colpocephaly (ICD10 unknown)
Holoprosencephaly (Q04.2)
Ethmocephaly (ICD10 unknown)
Hydranencephaly (Q04.3)
Iniencephaly (Q00.2)
Lissencephaly (Q04.3)
Megalencephaly (Q04.5)
Microcephaly (Q02)
Porencephaly (Q04.6)
Schizencephaly (Q04.6)
Acephaly (Q00.0)
Exencephaly (ICD10 unknown)
Macrocephaly (Q75.3)
Micrencephaly (Q02)
Otocephaly (Q18.2)
Craniostenosis (ICD10 unknown), Brachycephaly (ICD10 unknown), Oxycephaly (Q75.0), Plagiocephaly (Q67.3, Scaphocephaly (ICD10 unknown), Trigonocephaly (Q75.0)
Cephalic disorders are not necessarily caused by a single factor, but may be influenced by hereditary or genetic conditions, nutritional deficiencies, or by environmental exposures during pregnancy, such as medication taken by the mother, maternal infection, or exposure to radiation (such disorders are more common in areas of the former Soviet Union affected by nuclear waste disposal problems, such as the area around the Mayak plant in Chelyabinsk, Russia.) Some cephalic disorders occur when the cranial sutures (the fibrous joints that connect the bones of the skull) join prematurely. Most cephalic disorders are caused by a disturbance that occurs very early in the development of the fetal nervous system.
The human nervous system develops from a small, specialized plate of cells on the surface of the embryo. Early in development, this plate of cells forms the neural tube, a narrow sheath that closes between the third and fourth weeks of pregnancy to form the brain and spinal cord of the embryo. Four main processes are responsible for the development of the nervous system: cell proliferation, the process in which nerve cells divide to form new generations of cells; cell migration, the process in which nerve cells move from their place of origin to the place where they will remain for life; cell differentiation, the process during which cells acquire individual characteristics; and cell death, a natural process in which cells die.
Damage to the developing nervous system is a major cause of chronic, disabling disorders and, sometimes, death in infants, children, and even adults. The degree to which damage to the developing nervous system harms the mind and body varies enormously. Many disabilities are mild enough to allow those afflicted to eventually function independently in society. Others are not. Some infants, children, and adults die, others remain totally disabled, and an even larger population is partially disabled, functioning well below normal capacity throughout life.
MOMO syndrome
Positional plagiocephaly
Polycephaly
Encephalocele
Cyclopia
Positional Plagiocephaly information from Seattle Children's Hospital Craniofacial Center
Holoprosencephaly Article from Journal of Postgraduate Medicine
Note 1: http://www.ninds.nih.gov/disorders/cephalic_disorders/cephalic_disorders.htm
Portions of this article were based on the page: http://www.ninds.nih.gov/disorders/cephalic_disorders/detail_cephalic_disorders.htm at the National Institute of Neurological Disorders and Stroke's public domain resource.
|
Oliguria_overview | Oliguria and anuria are the decreased or absent production of urine, respectively.
Oliguria is defined as a urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children, and less than 400 mL or 500 mL per 24h in adults - this equals 17 or 21 mL/hour. For example, in an adult weighing 70 kg it equals 0.24 or 0.3 ml/hour/kg. Alternatively, however, the value of 0.5 mL/kg/h is commonly used to define oliguria in adults as well.
Olig- (or oligo-) is a Greek prefix meaning small or few.
Anuria is defined as less than 50mL urine output per day.
|
Reinfarction | Reinfarction is defined as a recurrence of a myocardial infarction. The rate of reinfarction on angiography (15-20% following fibrinolytic administration) is higher than the clinical rate of reinfarction (2% to 6%) in the setting of ST elevation myocardial infarction.
The frequency, timing, and clinical predictors of in-hospital reinfarction were evaluated in the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations . Reinfarction developed in in 2,258 out of 55, 911 patients (4.3%). Reinfarction was diagnosed a median of 3.8 days after fibrinolytic administration. The specific fibrinolytic agent administered was not associated with the rate of reinfarction: streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55. Multivariate predictors or reinfarction included the following: older age, shorter time to fibrinolytic administration, non-US enrollment, nonsmoking status, prior MI or angina, female gender, anterior MI, and lower systolic blood pressure.
Gibson et al documented that angiographically confirmed reocclusion is observed more frequently among culprit arteries with TIMI grade 2 versus TIMI grade 3 flow (10.4% vs. 2.2%, p = 0.003), in ulcerated lesions (10.7% vs. 3.0%, p = 0.009) and in the presence of collateral vessels (18.2% vs. 5.6%, p = 0.03). Trends toward higher rates of reocclusion were observed among eccentric (7.3% vs. 2.3%, p = 0.06) and thrombotic (8.4% vs. 3.3%, p = 0.06) lesions. Reocclusion was associated with a more severe percent diameter stenosis on quantitative coronary angiography (77.9% vs. 73.9%, p = 0.04).. Pulsatile flow or reversal of flow during systole has been associated with a higher rate of reinfarction .
In the combined GUSTO I and III experience, reinfarction was associated with a higher mortality at 30 days(11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included older age, higher Killip class, lower systolic and diastolic blood pressures, higher heart rate, the presence of an anterior MI, smoking, a history of prior MI, gender, and country of enrollment (all P<0.001) . In contrast, Gibson et al did not find an increase in mortality between 30 days and 2 years in over 20,000 patients in the TIMI trials . Higher mortality at 2 years was found to be due to an early divergence in mortality by 30 days and was not due to a significant increase in late mortality between 30 days and 2 years (4.38% [31/707] vs. 3.76% [685/18,206], p = NS).
Gibson et al reported in their analysis of over 20,000 patients from the TIMI trials that percutaneous coronary intervention performed at the time of the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% vs. 4.5%, p < 0.001) and lower two-year mortality (5.6% vs. 11.6%, p < 0.001). Likewise, coronary artery bypass graft (CABG) surgery was also associated with a lower rate of recurrent MI (0.7% vs. 4.3%, p < 0.001) as well as a lower two-year mortality rate (7.95% vs. 10.6%, p = 0.0008).
The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction |
Familial_syndactyly | In biology, dactyly is the arrangement of digits (fingers and toes) on the hands, feet, or sometimes wings of a tetrapod animal. It comes from the Greek word δακτυλος = "finger".
Sometimes the ending "-dactylia" is used. The derived adjectives end with "-dactyl" or "-dactylous".
Pentadactyly (from Greek pente-="five" plus δακτυλος = "finger") is the condition of having five digits on each limb. It appears that all land vertebrates are descended from an ancestor with a pentadactyl limb, although many species have now lost or transformed some or all of their digits by the process of evolution. Despite the individual variations listed below, the relationship to the original five-digit 'model' can be traced. This phenomenon featured in the work of Charles Darwin who noteably said; "What could be more curious than that the hand of man formed for grasping, that of a mole, for digging, the leg of a horse, the paddle of a porpoise and the wing of a bat, should all be constructed on the same pattern and should include similar bones and in the same relative positions?" Darwin was suggesting that the pentadactyl limb represents some of the strongest evidence for the theory of evolution as it indicates a common ancestry for all land vertebrates.
Tetradactyly (from Greek tetra-="four" plus δακτυλος = "finger") is the condition of having four digits on a limb, as in many amphibians and birds. Some mammals also exhibit tetradactyly (for example the hind limbs of dogs and cats).
Tridactyly (from Greek tri- = "three" plus δακτυλος = "finger") is the condition of having three digits on a limb, as in the Rhinoceros and ancestors of the horse such as Protohippus and Hipparion. These belong to the Perissodactyla. Some birds also have three toes.
Didactyly (from Greek di-="two" plus δακτυλος = "finger") or bidactyly is the condition of having two digits on each limb, as in the Two-toed Sloth, Choloepus didactylus. In humans this name is used for an abnormality in which the middle digits are missing, leaving only the thumb and fifth finger. Cloven-hoofed mammals (such as deer, sheep and cattle - 'Artiodactyla') walk on two digits.
Monodactyly (from Greek monos- = "one" plus δακτυλος = "finger") is the condition of having a single digit on a limb, as in modern horses. These belong to the Perissodactyla.
Syndactyly (from Greek συν- = "together" plus δακτυλος = "finger") is a condition where two or more digits are fused together. It occurs normally in some mammals, such as the siamang. It occurs as an unusual condition in humans.
Syndactyly can be simple or complex. In simple syndactyly, adjacent fingers or toes are joined by soft tissue. In complex syndactyly, the bones of adjacent digits are fused. The kangaroo exhibits complex syndactyly.
Simple syndactyly can be full or partial, and is present at birth (congenital). In early human fetal development, webbing (syndactyly) of the toes and fingers is normal. At about 16 weeks of gestation, apoptosis takes place and an enzyme dissolves the tissue between the fingers and toes, and the webbing disappears. In some fetuses, this process does not occur completely between all fingers or toes and some residual webbing remains. The exact cause is not known. In cases, this condition appears to be hereditary.
In the case of human feet, syndactyly does not affect the function of the foot or toes and does not interfere with walking or swimming or any other activities. Although webbing of the fingers usually does not affect the function of the hand, it can impair function of the fingers. Surgery may be performed to separate webbed fingers or toes. As with any surgery, there are risks of complications. This procedure involves local anesthesia with a sedative and can be done just with a local without the sedative for adults if desired. In addition to the incision between the toes, sometimes it is necessary to remove some skin from elsewhere on the body to graft into the newly exposed space between the toes.
In the case of webbed toes, surgical separation is a purely cosmetic operation with no medical benefits.
Polydactyly (from Greek πολυ- = "many" plus δακτυλος = "finger") (or hyperdactyly, from Greek hyper- = "too many" plus δακτυλος = "finger") is when a limb has more than five digits. This can be:-
As a result of congenital abnormality in a normally pentadactyl animal. Polydactyly is very common among domestic cats.
Normality in some early tetrapod aquatic animals, such as Acanthostega gunnari (Jarvik 1952), which is one of an increasing number of genera of stem-tetrapods known from the Upper Devonian, which are providing insights into the appearance of tetrapods and the origin of limbs with digits. For more information, see polydactyly.
Hypodactyly (from Greek hypo- = "too few" plus δακτυλος = "finger") is having too few digits when not caused by an amputation.
Ectrodactyly is the congenital absence of all or part of one or more fingers or toes. This term is used for a range of conditions from aphalangia (in which some of the phalanges or finger bones are missing), to adactyly (the absence of a digit).
A fusing of almost all digits on all of the hands and feet is ectrodactyly. News anchor Bree Walker is probably the best-known person with this condition, which affects about one in 91,000 people. It is conspicuously more common in the Vadoma in Zimbabwe.
vteCongenital malformations and deformations of musculoskeletal system (Q65-Q79, 754-756)Limbship: Dislocation of hip/Hip dysplasia - Upington disease
feet (Club foot, Flat feet, Pes cavus)
systemic dislocations Larsen syndrome
head, face, spine and chest: skull, face and jaw (Dolichocephaly, Greig cephalopolysyndactyly syndrome, Plagiocephaly) - spine Scoliosis - chest (Pectus excavatum, Pectus carinatum)
any combination head, face, jaw, upper limb, lower limb, pelvis, dactyly Antley-Bixler syndrome - Schmitt Gillenwater Kelly syndrome
dactyly Polydactyly/Syndactyly (Webbed toes) - Cenani Lenz syndactylism
reduction deficits (Acheiropodia, Amelia, Ectrodactyly, Phocomelia)
upper limb (Cleidocranial dysostosis, Madelung's deformity, Sprengel's deformity, Wallis Zieff Goldblatt syndrome)
knee (Genu valgum, Genu varum)
other ArthrogryposisSkull and facial bonesCarpenter syndrome - Craniodiaphyseal dysplasia - Craniosynostosis (Scaphocephaly) - Crouzon syndrome - Hypertelorism - Macrocephaly - Oxycephaly - Platybasia - Saethre-Chotzen syndrome - Treacher Collins syndrome - TrigonocephalySpine and bony thoraxKlippel-Feil syndrome - Spondylolisthesis - Cervical rib - Bifid ribOsteochondrodysplasiadevelopement of cartilage, tubular bones and spine: Achondrogenesis/Hypochondrogenesis - Boomerang dysplasia - Thanatophoric dysplasia - Short rib-polydactyly syndrome - Chondrodysplasia punctata (Rhizomelic chondrodysplasia punctata, Conradi-Hünermann syndrome), Achondroplasia (Hypochondroplasia, Osteosclerosis congenita) - Ellis-van Creveld syndrome - Otospondylomegaepiphyseal dysplasia - Spondyloepiphyseal dysplasia congenita- Osteogenesis imperfecta - McCune-Albright syndrome - Osteopetrosis - Metaphyseal dysplasia - Recessive multiple epiphyseal dysplasia - Hereditary multiple exostoses - Osteopoikilosis - Chondrodystrophy - Osteodystrophy - Atelosteogenesis, type II - Diastrophic dysplasiaOtherabdominal wall (Congenital diaphragmatic hernia, Omphalocele, Gastroschisis, Prune belly syndrome) - Ehlers-Danlos syndromeSee also non-congenital conditions (M, 710-739)
de:Syndaktylie
he:דקטיליה
nl:Syndactylie
sr:Синдактилија
fi:Syndaktylia
sv:Syndaktyli
Template:WikiDoc Sources
|
Euphoria_(emotion) | Euphoria is medically recognized as an emotional and mental state defined as a sense of great (usually exaggerated) elation and well-being. Technically, euphoria is an affect, but the term is often colloquially used to define emotion as an intense,happiness combined with an overwhelming sense of well-being. The word derives from Greek Template:Polytonic, "power of enduring easily, fertility". Euphoria is generally considered to be an exaggerated state, resulting from psychological or pharmacological stressors and not typically achieved during the normal course of human experience, although some natural behaviors, such as activities resulting in orgasm or the winning triumph of an athlete, can induce brief states of euphoria. Euphoria also has spiritual meanings in many belief systems, often being claimed to be a type of connection with some deity. Euphoric experiences from illicit drug use are short-lived and often followed by dysphoria which can be severe. Subsequent dysphoria or the "comedown (drugs)|comedown" can also be much longer in duration than the drug induced euphoria, especially after regular or long term use of certain drugs. On a neurological level, psychoactive drugs that induce states of euphoria typically due so by acting on dopamine, epinephrine, and serotonin neurotransmitters and opioid receptors in the brain. The NMDA and CB1 receptors have also been identified as causing euphoria via the mechanism of action induced by nitrous oxide and marijuana use, respectively.
Drug Side Effect: Betamethasone valerate, Betamethasone dipropionate, Flurazepam, Lorcaserin. |
Romifidine | Romifidine is a drug that is used in veterinary medicine as a sedative mainly in large animals such as horses, although it may be used in a wide variety of species. It is not used in humans, but is closely related in structure to the commonly used drug clonidine.
Romifidine acts as an agonist at the α2 adrenergic receptor subtype. Side effects can include bradycardia and respiratory depression. It is often used alongside other sedative or analgesic drugs such as ketamine or butorphanol. Yohimbine can be used as an antidote to rapidly reverse the effects.
|
Arthrogryposis_like_disorder | vteCongenital malformations and deformations of musculoskeletal system (Q65-Q79
Dislocation of hip/Hip dysplasia - Upington disease
feet (Club foot
Pes cavus)
systemic dislocations Larsen syndrome
head
Plagiocephaly) - spine Scoliosis - chest (Pectus excavatum
Pectus carinatum)
any combination head
dactyly Antley-Bixler syndrome - Schmitt Gillenwater Kelly syndrome
dactyly Polydactyly/Syndactyly (Webbed toes) - Cenani Lenz syndactylism
reduction deficits (Acheiropodia
Phocomelia)
upper limb (Cleidocranial dysostosis
Wallis Zieff Goldblatt syndrome)
knee (Genu valgum
Genu varum)
other ArthrogryposisSkull and facial bonesCarpenter syndrome - Craniodiaphyseal dysplasia - Craniosynostosis (Scaphocephaly) - Crouzon syndrome - Hypertelorism - Macrocephaly - Oxycephaly - Platybasia - Saethre-Chotzen syndrome - Treacher Collins syndrome - TrigonocephalySpine and bony thoraxKlippel-Feil syndrome - Spondylolisthesis - Cervical rib - Bifid ribOsteochondrodysplasiadevelopement of cartilage
Achondrogenesis/Hypochondrogenesis - Boomerang dysplasia - Thanatophoric dysplasia - Short rib-polydactyly syndrome - Chondrodysplasia punctata (Rhizomelic chondrodysplasia punctata
Osteosclerosis congenita) - Ellis-van Creveld syndrome - Otospondylomegaepiphyseal dysplasia - Spondyloepiphyseal dysplasia congenita- Osteogenesis imperfecta - McCune-Albright syndrome - Osteopetrosis - Metaphyseal dysplasia - Recessive multiple epiphyseal dysplasia - Hereditary multiple exostoses - Osteopoikilosis - Chondrodystrophy - Osteodystrophy - Atelosteogenesis
type II - Diastrophic dysplasiaOtherabdominal wall (Congenital diaphragmatic hernia
Prune belly syndrome) - Ehlers-Danlos syndromeSee also non-congenital conditions (M |
Yersinia_enterocolitica_infection_laboratory_findings | Many laboratories do not routinely test for Y. enterocolitica, so it is important to notify laboratory personnel when infection with this bacterium is suspected so that special tests can be done.
|
Chronic_COVID-19 | Shortly after the COVID-19 pandemic onset, emerging studies showed that a considerable proportion of patients with COVID-19 might exhibit sustained postinfection sequelae. This condition has been defined by a variety of names, including long COVID or long-haul COVID, and post-COVID-19 condition. The absence of a universally standardized terminology has made characterization of the epidemiology, risk factors, clinical characteristics, and potential treatments options difficult. Symptoms may occur as an unpredictable combination of respiratory, cardiovascular, urological, neurological, and/or gastrointestinal manifestations. However, the most common symptoms include fatigue, dyspnea, and cognitive dysfunction (known as brain fog by the patients). Symptoms may begin following initial recovery from an acute COVID-19 episode or may persist from the initial acute episode. Symptoms might also fluctuate or relapse over time.
The term ‘Long COVID’ was first used as a Twitter hashtag by a patient who was not recovering from COVID-19. This patient-made term soon became a widely accepted concept by both the public and medical professionals.
Currently, this condition is known by a variety of names, including long COVID, long-haul COVID, post-COVID-19 condition, post-COVID-19 syndrome, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS).
This condition is listed in the ICD-10 classification as post-COVID-19 condition since September 2020.
On October 6, 2021, World Health Organization (WHO) released a clinical case definition of the post-COVID-19 condition through a robust, protocol-based methodology (Delphi consensus), which engaged a diverse group of representative patients, patient-researchers, external experts, WHO staff, and other stakeholders from multiple geographies. It was acknowledged that this definition may change with emerging new evidence and continuously evolving our understanding of the consequences of COVID-19.
According to WHO clinical case definition, the post-COVID-19 condition is defined as: , Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction and generally have an impact on everyday functioning. Symptoms may be new-onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time. A separate definition may be applicable for children. Notes: There is no minimum number of symptoms required for the diagnosis; though symptoms involving different organs systems and clusters have been described.
A summary of some published/available definitions of the post-COVID-19 condition include:
There is no established system for the classification of long COVID.
The exact pathogenesis of long COVID is not fully understood. A controlled study found no unique abnormalities
However, a number of putative pathophysiologic mechanisms have been suggested.
1) Long-term tissue damage: Long-term tissue damage can result in the persistence of symptoms in different organs. For example: Respiratory symptoms, Lung fibrosis may be the cause of respiratory symptoms, such as dyspnea and cough. , Neurologic symptoms, Structural and metabolic abnormalities in the brain and brainstem may be the cause of neurologic symptoms such as headache, delirium, memory loss, anosmia, and fatigue. , Fatigue, Chronic fatigue occurs as a complex syndrome and a few mechanisms have been suggested. These include: , Autonomic nervous system dysfunction, Inflammation, Channelopathies, Inadequate cerebral perfusion, Cardiovascular symptoms, Autonomic symptoms and findings are common in an uncontrolled study, Cardiac injury occurs in a substantial proportion of patients during acute COVID-19 episodes. Resulting cardiac abnormalities (such as impaired contractile function and cardiac remodeling) and myocardial inflammation may account for symptoms such as chest pain, palpitations, and tachycardia. Cardiovascular and respiratory symptoms might also be due to damages of the intrathoracic chemo and mecano-receptors, which are involved in the control and regulation of respiration and heart rate. The SARS-CoV-2 neurotropism (i.e., cell invasion and damage), microcirculation or autoimmune disorders have been suggested as the possible mechanisms for such damages. This hypothesis seems to explain many dysautonomic symptoms which occur due to a dysregulated rate in respiration or heart rate. These symptoms include breathlessness, exercise intolerance, palpitations, or orthostatic malaise.
2) Ongoing inflammation, Several studies have suggested the presence of an unresolved inflammation in patients recovering from COVID-19. This ongoing inflammation may result from a variety of reasons. 1) Viral persistence in the gastrointestinal tract: Studies have shown the persistence of the virus in the gastrointestinal tract (in the gastric and intestinal cells) after recovering from acute COVID-19 episodes due to the high expression of ACE2 receptors in these cells. Increased fecal shedding of the SARS-CoV-2 virus has been shown in some studies. This may trigger a state of immune activation and ongoing inflammation in the body and also may explain the relatively high prevalence (up to 30%) of gastrointestinal manifestations (e.g. appetite loss, nausea, vomiting, diarrhea, and abdominal discomfort) in patients with long COVID. , 2) Lymphopenia: Increased levels of pro-inflammatory markers (e.g. CRP, IL-6, and D-dimer) and lymphopenia occur during acute COVID-19 episodes and have been shown to be associated with long COVID symptoms, particularly myalgia, fatigue, and joint pain. , 3) Autoimmunity: Recently, T-cells and B-cells dysfunction have been suggested to promote long COVID pathophysiology similar to autoimmune diseases. , 4) Other mechanisms, In a recent study using Invasive Cardiopulmonary Exercise Testing (iCPET), the pathophysiologic mechanism of exercise intolerance in post-COVID-19 long-haul syndrome has been investigated. The results of the study showed that patients without cardiopulmonary disease who have recovered from COVID-19 had a marked decrease in peak oxygen consumption and an exaggerated hyperventilation response during exercise. This means that patients who have recovered from COVID-19 had: Reduced peak exercise aerobic capacity, Impaired systemic oxygen extraction, Abnormal ventilatory efficiency slope.
Increased levels of interleukin-17 and interleukin-12, decreased levels of interleukin-4, interleukin-6 and interleukin-10 were observed in the recent study by Queiroz et al.
Neurological manifestations of long COVID were observed to be associated with the presence of ACE2, SLC6A19, TMPRSS4, TMRSS2, interleukin-17, interferon gamma, and zonulin.
IL-17D, IL-17A, TNF-a, PIGF, VCAM-1, KL6, and ICAM-1 were linked with an increased susceptibility risk for pulmonary fibrosis in long COVID.
The reported incidence/prevalence of long COVID varies in different studies mainly due to the absence of single terminology and definition.
A meta-analysis, including 47,910 patients (age 17-87 years), estimated that 80% of the patients with SARS-CoV-2 infections developed one or more long-term (ranging from 14 to 110 days) symptoms.
Women seem to be more commonly affected by long COVID than men.
A cohort study found the COVID alpha variant found:
"Persistent symptoms in COVID-19-positive participants at 90-150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness."
"In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90-150 days after COVID-19 diagnosis or matched timepoint."
There are no established risk factors for long COVID.
However, according to several studies, the most common risk factors for the development of long COVID may include: , Older age, Female gender, Pre-existing comorbidities, such as obesity, asthma, More severity of the acute COVID-19 episode, including a prolonged hospitalization or ICU stay, However, emerging data suggest that even patients with a less severe initial episode of COVID-19, who had not required hospitalization, may also experience persistent symptoms of post-COVID-19 condition, Medical complications during acute COVID-19 episode, such as secondary bacterial pneumonia, venous thromboembolism, Presence of a higher number of symptoms in the acute COVID-19 episode (i.e. an extended spectrum of symptoms) (more than five initial symptoms), Increased levels of C-reactive protein and D-dimer, Decreased lymphocyte count
There is insufficient evidence to recommend routine screening for long COVID.
The natural history, clinical course, long-term complications, and prognosis of long COVID-19 are still not completely understood.
Manifestations of the post-COVID-19 condition vary considerably in terms of organ involvement and severity of symptoms; however, they generally impact the everyday functioning of affected patients.
Symptoms might newly develop following initial recovery from an acute COVID-19 illness or occur as a persist from the initial episode.
Symptoms might also fluctuate or relapse over time.
According to a clinical case definition by WHO, the post-COVID-19 condition is defined as follow: , The post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.
Long COVID can involve almost every organ.
The most common symptoms of long COVID include:
Physical symptoms: Fatigue, Dyspnea, Cough, Chest discomfort, Anosmia
Neurocognitive symptoms: Memory impairment and Cognitive dysfunction: described by patients as “brain fog”, Headache
Psychologic symptoms: Anxiety, Depression, Post-traumatic stress disorder (PTSD)
Other less common symptoms include: Sweating, Myalgias, Diarrhea, Hair Loss (Alopecia), Joint Pain, Sicca Syndrome, Rhinitis, Dysgeusia, Poor Appetite, Dizziness, Vertigo, Insomnia
In patients with cardiopulmonary symptoms, a throughout chest examination may provide a clue to the underlying condition: On pulmonary examination: Coarse crackles: a sign of fibrosis, Dullness on percussion: a sign of pleural effusion or consolidation, Egophony: A sign of consolidation, Fine basilar crackles: A sign of pulmonary edema, On cardiac examination, the following findings may provide a clue to the underlying cardiac complication: Jugular venous distension, Peripheral edema, Orthostasis, Murmurs, Pericardial rub, Third or fourth heart sounds
There are no diagnostic laboratory findings associated with long COVID.
Symptoms do not correlate with the serology of SARS-CoV-2.
In patients with cardiopulmonary symptoms, an ECG may be needed.
A chest x-ray may be helpful in the diagnosis of pulmonary complications of COVID-19 such as lung damage (ie, ground glass opacities, consolidation, interlobular septal thickening) and pleural effusion.
In selected patients with cardiopulmonary symptoms, echocardiography may be necessary.
In patients with cardiopulmonary symptoms, a chest CT scan may be needed.
There are no MRI findings associated with long COVID. However, a cardiac MRI may be helpful in the diagnosis of myocarditis in COVID-19 patients.
There are no other imaging findings associated with long COVID.
In selected patients with cardiopulmonary symptoms, Holter monitoring, cardiopulmonary exercise testing (CPET), and pulmonary function tests may be necessary.
Due to the diversity of symptoms and their severity, the mainstay of long COVID treatment is multidisciplinary and supportive. The management should focus on supporting self-management and individualized rehabilitation.
Dyspnea, Dyspnea in long COVID patients should be treated similar to non-COVID-19 patients. General measures in the management of dyspnea in long COVID patients may include: , Oxygen therapy, Breathing exercises: Pursed lip breathing exercises, Deep breathing exercises, Pulmonary rehabilitation, In the presence of any identified underlying cardiac or pulmonary disease, referral to a cardiologist or pulmonologist and appropriate pharmacotherapy may be required.
Cough, Cough should be managed in a similar to cough in patients with post-viral cough syndrome. Attention should be paid to diagnose and treat other exacerbating or contributing factors such as gastrointestinal reflux disease and asthma. Over-the-counter cough suppressants, including benzonatate, guaifenesin, and dextromethorphan are the mainstay of treatment.
Cardiac injury, Long COVID patients with evidence of cardiac injury should be referred to cardiology services. Patients recovering from cardiac injury with impaired functional status (eg, New York Heart Association class II or higher) should undergo cardiac rehabilitation if no contraindications are present.
Orthostasis, Orthostasis and dysautonomia, such as unexplained sinus tachycardia, dizziness on standing, is initially managed conservatively with compression stockings, abdominal binder, increased intake of fluid and salts, physical therapy/rehabilitation, and behavioral modifications. In patients with postural orthostatic tachycardia syndrome (PoTS) and inadequate response to non-pharmacological therapy, beta-blockers, ivabradine, or fludrocortisone (with blood pressure and response monitoring) might be considered.
Olfactory/gustatory symptoms, In most patients with a loss or decrease in sense of smell or taste, symptoms improve slowly over several weeks and do not require medical intervention. Patients may need education on food and home safety. In patients with persistent symptoms, olfactory training may be appropriate. If conservative management fails, referral to an otolaryngologist and specialized taste and smell clinic may also be considered.
Fatigue, A Consensus Guidance Statement provides practical guidance to clinicians in the treatment of fatigue in postacute sequelae of SARS‐CoV‐2 infection (PASC) patients. Conservative management, 1) Initiation of an individualized and structured, titrated return to activity program (individualized rehabilitation), The goal of such a rehabilitation program should be restoring patients to their previous levels of activity and improve quality of life, The titration approach ensures that patients are engaged in activities at a submaximal level to avoid exacerbation of fatigue. Level of activity should be adjusted according to change in fatigue-related symptoms that develop during or after activity. 2) Educating patients on energy conservation strategies, 3) Encouraging a healthy diet and adequate hydration, 4) Treatment of any underlying medical conditions such as pain, insomnia/sleep disorders (including poor sleep hygiene), and mood problems that may be contributing and/or aggravating fatigue. Pharmacologic therapy and supplements, A number of herbal remedies/supplements and pharmacologic agents have been used in the treatment of chronic fatigue in other causes of chronic illness (eg, multiple sclerosis, fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cancer, brain injury, and Parkinson's disease). These include: , Branched‐chain amino acids, Omega 3 fatty acids, Vitamin B12, Vitamin C, Vitamin D, Magnesium, L‐carnitine, Coenzyme Q10, Ginseng, Echinacea, Amantadine, Modafinil, Methylphenidate, Antivirals/antibiotics/antiparasitics, Antidepressants, Cytokine inhibitors, Galantamine, Glucocorticoids, Immunoglobulins, Rituximab, However, it should be noted that due to limited scientific evidence, currently there is no general consensus on routine administration of these supplements/medications. Thus, they may be considered on a case‐by‐case basis. Other therapeutic interventions such as acupuncture have been suggested in the treatment of fatigue.
Weight loss, In patients with long COVID, weight loss is multifactorial and may occur due to a combination of malnutrition, loss of appetite, catabolic state, swallowing difficulty, and alterations in taste and smell. Patients should be encouraged to eat small, frequent meals with protein and calorie supplementation. Nutrition consultation and referral to a dietician may be required in selected patients with severe weight loss.
Psychological and emotional issues, In patients experiencing emotional distress, mood disturbances, anxiety, or symptoms of post-traumatic stress disorder, mental health assessment and possible referral to a psychiatrist may be required. Cognitive behavioral therapy may benefit patients with anxiety, depression and stress. Neurocognitive concerns may benefit from hyperbaric oxygen
Alopecia, There is no specific therapy for alopecia in COVID-19 patients, and it should be managed similarly to non-COVID-19 patients. In patients with concomitant malnutrition, nutritional deficiencies should be corrected.
Insomnia, All patients with insomnia should be educated on sleep hygiene guidelines, stimulus control instructions, and relaxation techniques. Short-term pharmacologic treatment with benzodiazepines or non-benzodiazepine hypnotics may be needed in selected patients.
The most effective measure to prevent the post-COVID-19 condition is to prevent COVID-19. These primary prevention strategies include:
Vaccination
Masking
Social distancing
Hand hygiene
There are no established measures for the secondary prevention of long COVID.
|
Hepatocellular_Carcinoma | Staging | Diagnostic Study of Choice | History and Symptoms | Physical Examination | Lab Studies | Electrocardiogram | Chest X Ray | MRI | CT | Echocardiography or Ultrasound | Other imaging findings | Other diagnostic studies
Medical Therapy | Surgery | Primary prevention | Secondary prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
|
Farmer%27s_lung_differential_diagnosis | Farmer's lung disease must be differentiated from other diseases that cause cough, dyspnea such as Interstitial lung disease, sarcoidosis and asthma.
Farmer's lung disease should be differentiated from other occupational lung diseases and diseases causing cough and dyspnea, like:
Interstitial Lung disease
Sarcoidosis
Idiopathic pulmonary fibrosis
Lung disease in collagen vascular disease
Pulmonary mycotoxicosis
Asthma
|
Metatarsus | The metatarsus consists of the five long bones of the foot, which are numbered from the medial side (ossa metatarsalia I.-V.); each presents for examination a body and two extremities. These are analogous to the metacarpals of the hand.
Specifically, the bones are:
First metatarsal bone
Second metatarsal bone
Third metatarsal bone
Fourth metatarsal bone
Fifth metatarsal bone
The body is prismoid in form, tapers gradually from the tarsal to the phalangeal extremity, and is curved longitudinally, so as to be concave below, slightly convex above.
The base or posterior extremity is wedge-shaped, articulating proximally with the tarsal bones, and by its sides with the contiguous metatarsal bones: its dorsal and plantar surfaces are rough for the attachment of ligaments.
The head or anterior extremity presents a convex articular surface, oblong from above downward, and extending farther backward below than above.
Its sides are flattened, and on each is a depression, surmounted by a tubercle, for ligamentous attachment.
Its plantar surface is grooved antero-posteriorly for the passage of the flexor tendons, and marked on either side by an articular eminence continuous with the terminal articular surface.
The base of each metatarsal bone articulates with one or more of the tarsal bones, and the head with one of the first row of phalanges.
The first metatarsal articulates with the first cuneiform.
the second with all three cuneiforms.
the third with the third cuneiform.
the fourth with the third cuneiform and the cuboid.
The fifth with the cuboid.
The metatarsal bones are often broken by soccer players. These and other recent cases have been attributed to the modern lightweight design of football boots, which give less protection to the foot.
Stress fractures are thought to account for 16% of injuries related to sports preparation, and the metatarsals are most often involved. These fractures are commonly called march fractures, as they are commonly diagnosed among military recruits after long marches. They are also common among road runners, and even skimboarders. The second and third metatarsals are fixed while walking, thus these metatarsals are common sites of injury. The fifth metatarsal may be fractured if the foot is oversupinated during locomotion.
, , CT 3D human Foot Skin and Bone,
, , Lower extremity,
, , X-ray of foot.
, , Bones of the right foot. Dorsal surface.
, , Skeleton of foot. Medial aspect.
, , Oblique section of left intertarsal and tarsometatarsal articulations, showing the synovial cavities.
Bone terminology
Terms for anatomical location |
Alcoholic_cardiomyopathy_physical_examination |
The patient may have altered mental status due to chronic alcoholism.
Hypertension may be present.
Jugular venous distension may be seen in the presence of right heart failure.
Pedal edema
Cold extremities with decreased pulse
Rales may be heard on lung exam due to pulmonary congestion.
Enlargment of the heart with a laterally displaced and diffused point of maximal impulse.
Abnormal heart sounds, namely third S3 and fourth S4 sounds may be heard.
Apical murmur of mitral regurgitation and the lower parasternal murmur of tricuspid regurgitation may be present secondary to papillary muscle displacement and dysfunction.
Hepatomegaly
Ascites
Other sequelae of alcoholic liver disease may also be noted on physical examination.
Telangiectasia
Spider angiomata |
Group_B_streptococcal_infection | History and Symptoms | Physical Examination | Laboratory Findings
Medical Therapy | Primary Prevention | Secondary Prevention | Future or Investigational Therapies
Template:Bacterial diseases
Template:WikiDoc Sources
|
Lung_cancer_other_diagnostic_studies#PET_scan | Other diagnostic studies include bone scintigraphy, PET scan, and molecular tests.
Bone scan may demonstrate bone metastases.
FDG (18 F fluoro-deoxyglucose) PET scans along with contrast enhanced CT may be helpful in the evaluation of the extent of lung cancer. Findings on FDG-PET/CT suggestive of lung cancer include: Solitary pulmonary nodule
Molecular tests include epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutation.
Specific targeted agents may be administered to patients if these mutations are present. |
Feeling#Gut_feeling | Feeling in psychology is usually reserved for the conscious subjective experience of emotion. Phenomenology and heterophenomenology are philosophical approaches that provide some basis for knowledge of feelings. Many schools of psychotherapy depend on the therapist achieving some kind of understanding of the client's feelings, for which methodologies exist. Some theories of interpersonal relationships also have a role for shared feelings or understanding of another person's feelings.[citation needed]
Perception of the physical world does not necessarily result in a universal reaction among receivers (see emotions), but varies depending on one's tendency to handle the situation, how the situation relates to the receiver's past experiences, and any number of other factors. Feelings are also known as a state of consciousness, such as that resulting from emotions, sentiments or desires.
A gut feeling, or gut reaction, is a visceral emotional reaction to something, and often one of uneasiness. Gut feelings are generally regarded as not modulated by conscious thought.
"Gut feeling" may also be used as a short-hand term for an individual's "common sense" perception of what is "the right thing to do", such as helping an injured passerby, avoiding dark alleys, and other seemingly instinctive feelings about a given situation. It can also refer to common knowledge that some phrases are true no matter when said, such as "The sky is blue," "Fire is hot," and even individual beliefs in quotation like "Allan loves wally more" and other such statements (which may or may not be true, but to the sayer are more true than anything).
Gut feelings, like all reflexive unconscious comparisons, can be re-programmed by practice or experiences.
Affect or Affective
Emotion
Feeling rules
intuition
Myers-Briggs Type Indicator
Qualia
Haptics
Wiktionary: intuition
Wiktionary: qualia
Wiktionary: touch
↑ VandenBos, Gary (2006) APA Dictionary of Psychology. Washington, DC: American Psychological Association
"Feelings" Albert Morris. Video of the Quartet "SKAZ"
A Dictonary of Feelings
ca:Sentiment
cs:Cit
et:Tundmus
ia:Sentimento
it:Sentimento
hu:Érzelem
mk:Чувство
nl:Tastzin
no:Følelser
oc:Sentiment
qu:Kawllay
sk:Cit
sr:Осећање
sv:Känsla
th:ความรู้สึก
uk:Почуття
Template:WH
Template:WS
|
Regonol | Pyridostigmine is a cholinesterase inhibitor that is FDA approved for the treatment of myasthenia gravis. Common adverse reactions include diaphoresis, diarrhea, excessive salivation, increased peristalsis, nausea and vomiting, stomach cramps, muscle fasciculation, asthenia, miosis and excessive bronchial secretion.
Pyridostigmine bromide is available in tablets, each containing 60 mg pyridostigmine bromide.
Dosage: The size and frequency of the dosage must be adjusted to the needs of the individual patient. The average dose is ten 60-mg tablets daily, spaced to provide maximum relief when maximum strength is needed. In severe cases as many as 25 tablets a day may be required, while in mild cases one to six tablets a day may suffice.
There is limited information regarding Off-Label Guideline-Supported Use of Pyridostigmine (patient information) in adult patients.
Dosage: 30 mg q8h
Pyridostigmine bromide is available in tablets, each containing 60 mg pyridostigmine bromide.
Dosage: The size and frequency of the dosage must be adjusted to the needs of the individual patient. The average dose is ten 60-mg tablets daily, spaced to provide maximum relief when maximum strength is needed. In severe cases as many as 25 tablets a day may be required, while in mild cases one to six tablets a day may suffice.
There is limited information regarding Off-Label Guideline-Supported Use of Pyridostigmine (patient information) in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pyridostigmine (patient information) in pediatric patients.
Pyridostigmine bromide is contraindicated in mechanical intestinal or urinary obstruction, and particular caution should be used in its administration to patients with bronchial asthma. Care should be observed in the use of atropine for counteracting side effects, as discussed below.
Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of pyridostigmine bromide may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death. Myasthenic crisis due to an increase in the severity of the disease is also accompanied by extreme muscle weakness, and thus may be difficult to distinguish from cholinergic crisis on a symptomatic basis. Such differentiation is extremely important, since increases in doses of pyridostigmine bromide or other drugs of this class in the presence of cholinergic crisis or of a refractory or "insensitive" state could have grave consequences. *Osserman and Genkins indicate that the differential diagnosis of the two types of crisis may require the use of Tensilon (edrophonium chloride) as well as clinical judgment. The treatment of the two conditions obviously differs radically. Whereas the presence of myasthenic crisis suggests the need for more intensive anticholinesterase therapy, the diagnosis of cholinergic crisis, according to Osserman and Genkins, calls for the prompt withdrawal of all drugs of this type. The immediate use of atropine in cholinergic crisis is also recommended.
Atropine may also be used to abolish or obtund gastrointestinal side effects or other muscarinic reactions; but such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis. For detailed information on the management of patients with myasthenia gravis, the physician is referred to one of the excellent reviews such as those by Osserman and Genkins, Grob or Schwab.
The side effects of pyridostigmine bromide are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Muscarinic side effects can usually be counteracted by atropine, but for reasons shown in the preceding section the expedient is not without danger. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication.
There is limited information regarding Pyridostigmine Postmarketing Experience in the drug label.
There is limited information regarding Pyridostigmine Drug Interactions in the drug label.
Pregnancy Category (FDA): C
The safety of pyridostigmine bromide during pregnancy or lactation in humans has not been established. Therefore, use of pyridostigmine bromide in women who may become pregnant requires weighing the drug's potential benefits against its possible hazards to mother and child.
Pregnancy Category (AUS): C
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pyridostigmine in women who are pregnant.
There is no FDA guidance on use of Pyridostigmine during labor and delivery.
There is no FDA guidance on the use of Pyridostigmine in women who are nursing.
Safety and effectiveness in pediatric patients have not been established.
There is no FDA guidance on the use of Pyridostigmine in geriatric settings.
There is no FDA guidance on the use of Pyridostigmine with respect to specific gender populations.
There is no FDA guidance on the use of Pyridostigmine with respect to specific racial populations.
There is no FDA guidance on the use of Pyridostigmine in patients with renal impairment.
There is no FDA guidance on the use of Pyridostigmine in patients with hepatic impairment.
There is no FDA guidance on the use of Pyridostigmine in women of reproductive potentials and males.
There is no FDA guidance one the use of Pyridostigmine in patients who are immunocompromised.
Pyridostigmine bromide is available in tablets, each containing 60 mg pyridostigmine bromide.
There is limited information regarding Pyridostigmine Monitoring in the drug label.
There is limited information regarding the compatibility of Pyridostigmine and IV administrations.
There is limited information regarding Pyridostigmine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pyridostigmine bromide inhibits the destruction of acetylcholine by cholinesterase and thereby permits freer transmission of nerve impulses across the neuromuscular junction.
Chemically, pyridostigmine bromide is 3-hydroxy-1-methylpyridinium bromide dimethylcarbamate. Its structural formula is:
Pyridostigmine is an analog of neostigmine, but differs from it in certain clinically significant respects; for example, pyridostigmine is characterized by a longer duration of action and fewer gastrointestinal side effects.
There is limited information regarding Pyridostigmine Pharmacokinetics in the drug label.
There is limited information regarding Pyridostigmine Nonclinical Toxicology in the drug label.
There is limited information regarding Pyridostigmine Clinical Studies in the drug label.
There is limited information regarding Pyridostigmine Storage in the drug label.
{{#ask: Page Name::Pyridostigmine
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Pyridostigmine
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
There is limited information regarding Pyridostigmine Patient Counseling Information in the drug label.
Alcohol-Pyridostigmine (patient information) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Mestinon
Mestinon
Timespan
Regonol
There is limited information regarding Pyridostigmine Look-Alike Drug Names in the drug label.
|
Myelodysplastic_syndrome_MRI | Bone marrow MRI is helpful in the diagnosis of myelodysplastic syndrome. On MRI, myelodysplastic syndrome is characterized by low signal on T1-weighted imaging and high signal on T2-weighted imaging |
Type_2_diabetes | Diagnostic Study of Choice |History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X-Ray | CT scan | MRI | Echocardiography and Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Pharmacotherapy (outpatients)
Pharmacotherapy (inpatients)
Glycemic Control
Life Style Modification
Patient education
Surgery
Mobile health
Patient Care Teams
Patient navigators
Shared decision making
Telemedicine
Primary Prevention
Secondary Prevention
List of terms associated with diabetes
.mw-parser-output .refbegin{font-size:90%;margin-bottom:0.5em}.mw-parser-output .refbegin-hanging-indents>ul{list-style-type:none;margin-left:0}.mw-parser-output .refbegin-hanging-indents>ul>li,.mw-parser-output .refbegin-hanging-indents>dl>dd{margin-left:0;padding-left:3.2em;text-indent:-3.2em;list-style:none}.mw-parser-output .refbegin-100{font-size:100%}
Diet, Nutrition and the prevention of chronic diseases (including diabetes) by a Joint WHO/FAO Expert consultation (2003)
Centers for Disease Control Diabetes Section
MedlinePlus Diabetes from the U.S. National Library of Medicine
National Diabetes Education Program
National Diabetes Information Clearinghouse
World Health Organization fact sheet on diabetes
World Health Organization—The Diabetes Programme
National Diabetes Information Clearinghouse
vteEndocrine pathology: endocrine diseases (E00-35, 240-259)ThyroidHypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) - Euthyroid sick syndromePancreasDiabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome - insulin receptor (Rabson-Mendenhall syndrome)ParathyroidHypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)PituitaryHyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH) - Hypopituitarism (Simmonds' disease / Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus) - Adiposogenital dystrophy - Empty sella syndrome - HypophysitisAdrenalCushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - CAH (Lipoid, 3β, 11β, 17α, 21α) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - HypoaldosteronismGonadsOvarian dysfunction (Polycystic ovary syndrome, Premature ovarian failure) - Testicular dysfunction (5-alpha-reductase deficiency) - Testosterone biosynthesis (17-beta-hydroxysteroid dehydrogenase deficiency) - General (Hypogonadism, Delayed puberty, Precocious puberty)OtherAndrogen insensitivity syndrome - Autoimmune polyendocrine syndrome - Carcinoid syndrome - Gigantism - Short stature (Laron syndrome, Psychogenic dwarfism) - Multiple endocrine neoplasia (1, 2) - Progeria - Woodhouse-Sakati syndrome
fi:Aikuistyypin diabetes
sv:Typ 2-diabetes
Template:WikiDoc Sources
Template:WH
Template:WS
|
Hematemesis_other_diagnostic_studies | Endoscopy and biopsy can be used to indicate the diseases in esophagus, stomach and duodenum. Also, bleeding can be stanchedto identify the cause of bleeding.
|
Growth_Hormone_Receptor_Deficiency | History and Symptoms | Physical Examination | Laboratory Findings | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Template:WikiDoc Sources
|
N-3_fatty_acids | ω−3 fatty acids (commonly spelled omega-3 fatty acids) are a family of polyunsaturated fatty acids which have in common a carbon-carbon double bond in the ω−3 position.
Important nutritionally essential ω−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). For a more complete list, see list of ω−3 fatty acids. The human body cannot synthesize ω−3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated ω−3 fatty acids from the eighteen-carbon ω−3 fatty acid, α-linolenic acid. These conversions occur competitively with ω−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the ω−3 α-linolenic acid and ω−6 linoleic acid are essential nutrients which must be obtained from food. Synthesis of the longer ω−3 fatty acids from linolenic acid within the body is competitively slowed by the ω−6 analogues. Thus accumulation of long-chain ω−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of ω−6 analogs do not greatly exceed the amounts of ω−3.
Chemical structure of alpha-linolenic acid (ALA), an essential ω−3 fatty acid, (18:3Δ9c,12c,15c). Although chemists count from the carbonyl carbon (blue numbering), physiologists count from the ω (omega) carbon (red numbering). Note that from the ω end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "ω−3"
For detail on ω (omega) nomenclature and numbering, see EFA Nomenclature.
The term ω−3 (aka "n−3", "omega-3") signifies that the first double bond exists as the third carbon-carbon bond from the terminal methyl end (ω) of the carbon chain.
ω−3 fatty acids which are important in human nutrition are: α-linolenic acid (18:3, ALA), eicosapentaenoic acid (20:5, EPA), and docosahexaenoic acid (22:6, DHA). These three polyunsaturates have either 3, 5 or 6 double bonds in a carbon chain of 18, 20 or 22 carbon atoms, respectively. All double bonds are in the cis-configuration, i.e. the two hydrogen atoms are on the same side of the double bond.
The biological effects of the ω-3 are largely mediated by their interactions with the ω-6 fatty acids; see Essential fatty acid interactions for detail.
A 1992 article by biochemist William E.M. Lands provides an overview of the research into ω−3 fatty acids, and is the basis of this section.
The 'essential' fatty acids were given their name when researchers found that they were essential to normal growth in young children and animals. (Note that the modern definition of 'essential' is more strict.) A small amount of ω−3 in the diet (~1% of total calories) enabled normal growth, and increasing the amount had little to no additional benefit.
Likewise, researchers found that ω−6 fatty acids (such as γ-linolenic acid and arachidonic acid) play a similar role in normal growth. However, they also found that ω−6 was "better" at supporting dermal integrity, renal function, and parturition. These preliminary findings led researchers to concentrate their studies on ω−6, and it was only in recent decades that ω−3 has become of interest.
In 1963 it was discovered that the ω−6 arachidonic acid was converted by the body into pro-inflammatory agents called prostaglandins. By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins and the leukotrienes. The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. However, if the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that ω−3 is also converted into eicosanoids, but at a much slower rate. Eicosanoids made from ω−3 fats often have opposing functions to those made from ω−6 fats (ie, anti-inflammatory rather than inflammatory). If both ω−3 and ω−6 are present, they will "compete" to be transformed, so the ratio of ω−3:ω−6 directly affects the type of eicosanoids that are produced.
This competition was recognized as important when it was found that thromboxane is a factor in the clumping of platelets, which leads to thrombosis. The leukotrienes were similarly found to be important in immune/inflammatory-system response, and therefore relevant to arthritis, lupus, and asthma. These discoveries led to greater interest in finding ways to control the synthesis of ω−6 eicosanoids. The simplest way would be by consuming more ω−3 and fewer ω−6 fatty acids.
September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ω−3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA ω−3 fatty acids may reduce the risk of coronary heart disease." This updated and modified their health risk advice letter of 2001 (see below).
People with certain circulatory problems, such as varicose veins, benefit from fish oil. Fish oil stimulates blood circulation, increases the breakdown of fibrin, a compound involved in clot and scar formation, and it lowers the blood pressure. There is strong scientific evidence, that ω−3 fatty acids significantly reduce blood triglyceride levels and regular intake reduces the risk of secondary and primary heart attack.
Some benefits have been reported in such conditions as rheumatoid arthritis and cardiac arrhythmias.
There is a promising preliminary evidence, that ω−3 fatty acids supplementation might be helpful in cases of depression and anxiety. Studies report highly significant improvement from ω−3 fatty acids supplementation alone and in conjunction with medication.
Some research suggests that fish oil intake reduces the risk of ischemic and thrombotic stroke. However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk. 3 grams of total EPA/DHA daily are considered safe with no increased risk of bleeding involved and many studies used substantially higher doses without major side effects (for example: 4.4 grams EPA/2.2 grams DHA in 2003 study).
Several studies report possible cancer prevention effects of ω−3 fatty acids (particularly breast, colon and prostate cancer). No clear conclusion can be drawn at this time, though.
A 2006 report in the Journal of the American Medical Association concluded that their review of literature covering cohorts from many countries with a wide variety of demographic characteristics demonstrating a link between ω−3 fatty acids and cancer prevention gave mixed results. This is similar to the findings of a review by the British Medical Journal of studies up to February 2002 that failed to find clear effects of long and shorter chain ω−3 fats on total mortality, combined cardiovascular events and cancer.
In 1999, the GISSI-Prevenzione Investigators reported in the Lancet the results of major clinical study in 11 324 patients with a recent myocardial infarction. Treatment with omega-3 fatty acids 1 g/d reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively. These beneficial effects were seen already from three months onwards.
In April 2006, a team led by Lee Hooper at the University of East Anglia in Norwich, UK, published a review of almost 100 separate studies into ω−3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease. This meta-analysis was controversial and stands in stark contrast with two different reviews also performed in 2006 by the American Journal of Clinical Nutrition and a second JAMA review that both indicated decreases in total mortality and cardiovascular incidents (i.e. myocardial infarctions) associated with the regular consumption of fish and fish oil supplements. In addition ω−3 has shown to aid in other mental disorders such as aggression and ADHD (Attention Deficit Hyperactive Disorder).
Several studies published in 2007 have been more positive. In the March 2007 edition of the journal Atherosclerosis, 81 Japanese men with unhealthy blood sugar levels were randomly assigned to receive 1800 mg daily of eicosapentaenoic acid (EPA - an ω−3 essential fatty acid from fish oil) with the other half being a control group. The thickness of the carotid arteries and certain measures of blood flow were measured before and after supplementation. This went on for approximately two years. A total of 60 patients (30 in the EPA group and 30 in the control group) completed the study. Those given the EPA had a statistically significant decrease in the thickness of the carotid arteries along with improvement in blood flow. The authors indicated that this was the first demonstration that administration of purified EPA improves the thickness of carotid arteries along with improving blood flow in patients with unhealthy blood sugar levels.
In another study published in the American Journal of Health System Pharmacy March 2007, patients with high triglycerides and poor coronary artery health were given 4 grams a day of a combination of EPA and DHA along with some monounsaturated fatty acids. Those patients with very unhealthy triglyceride levels (above 500 mg/dl) reduced their triglycerides on average 45% and their VLDL cholesterol by more than 50%. VLDL is a bad type of cholesterol and elevated triglycerides can also be deleterious for cardiovascular health.
There was another study published on the benefits of EPA in the journal The Lancet in March 2007. This study involved over 18,000 patients with unhealthy cholesterol levels. The patients were randomly assigned to receive either 1,800 mg a day of EPA with a statin drug or a statin drug alone. The trial went on for a total of five years. It was found at the end of the study those patients in the EPA group had superior cardiovascular function. Non-fatal coronary events were also significantly reduced in the EPA group. The authors concluded that EPA is a promising treatment for prevention of major coronary events,especially non-fatal coronary events.
Another study regarding fish oil was published in the journal Nutrition in April 2007. Sixty four healthy Danish infants received either cow's milk or infant formula alone or with fish oil from nine to twelve months of age. It was found that those infants supplemented with fish oil had improvement in immune function maturation with no apparent reduction in immune activation.
There was yet another study on ω−3 fatty acids published in the April 2007 Journal of NeuroScience. A group of mice were genetically modified to develop accumulation of amyloid and tau proteins in the brain similar to that seen in people with poor memory. The mice were divided into four groups with one group receiving a typical American diet (with high ratio of ω−6 to ω−3 fatty acids being 10 to 1). The other three groups were given food with a balanced 1 to 1 ω−6 to ω−3 ratio and two additional groups supplemented with DHA plus long chain ω−6 fatty acids. After three months of feeding, all the DHA supplemented groups were noted to have a lower accumulation of beta amyloid and tau protein. It is felt that these abnormal proteins may contribute to the development of memory loss in later years.
Finally, there was a study published regarding ω−3 supplementation in children with learning and behavioral problems. This study was published in the April 2007 edition of the Journal of the Developmental and Behavioral Pediatrics (5), where 132 children, between the ages of seven to twelve years old, with poor learning, participated in a randomized, placebo-controlled, double-blinded interventional trial. A total of 104 children completed the trial. For the first fifteen weeks of this study, the children were given polyunsaturated fatty acids (ω−3 and ω−6, 3000 mg a day), polyunsaturated fatty acids plus multi-vitamins and minerals or placebo. After fifteen weeks, all groups crossed over to the polyunsaturated fatty acids (PUFA) plus vitamins and mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation.
Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of ω−3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefits comparable to those receiving standard NSAIDs. Those who follow a Mediterranean-style diet tend to have less heart disease, higher HDL ("good") cholesterol levels and higher proportions of ω−3 in tissue highly unsaturated fatty acids . Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of ω−3 fatty acids from fatty fish - also tend to have higher proportions of ω−3, increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood) and less heart disease. Eating walnuts (the ratio of ω−3 to ω−6 is circa 1:4 respectively ) was reported to lower total cholesterol by 4% relative to controls when people also ate 27% less cholesterol.
In a letter dated October 31, 2000 entitled Letter Regarding Dietary Supplement Health Claim for omega-3 Fatty Acids and Coronary Heart Disease, the United States Food and Drug Administration Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements noted that the known or suspected risks of EPA and DHA ω−3 fatty acids may include:
There have been reports that increased bleeding can occur if overused (normally over 3 grams per day) by a patient who is also taking aspirin or coumadin (warfarin). However, this is disputed.[2]
The possibility of hemorrhagic stroke (only in case of very large doses, called "Eskimo amounts").
Oxidation of ω−3 fatty acids forming biologically active oxidation products.
Reduced glycemic control among diabetics.
Suppression of immune and inflammation responses, and consequently, decreased resistance to infections and increased susceptibility to opportunistic bacteria.
An increase in concentration of LDL cholesterol in some individuals.
Subsequent advices from the FDA and national counterparts have permitted health claims associated with heart health.
Persons with congestive heart failure, chronic recurrent angina or evidence that their heart is receiving insufficient blood flow are advised to talk to their doctor before taking ω−3 fatty acids. It may be prudent for such persons to avoid taking ω−3 fatty acids or eating foods that contain them in substantial amounts.
In congestive heart failure, cells that are only barely receiving enough blood flow become electrically hyperexcitable. This, in turn, can lead to increased risk of irregular heartbeats, which, in turn, can cause sudden cardiac death. ω−3 fatty acids seem to stabilize the rhythm of the heart by effectively preventing these hyperexcitable cells from functioning by increasing the blood flow, thereby reducing the likelihood of irregular heartbeats and sudden cardiac death. For most people, this is obviously beneficial and would account for most of the large reduction in the likelihood of sudden cardiac death.
Essential fatty acid supplements have gained popularity for children with ADHD, autism, and other developmental differences. A 2004 Internet survey found that 29% of surveyed parents used essential fatty acid supplements to treat children with autism spectrum disorders.
Results from controlled trials are mixed. Fish oils appear to help ADHD-related symptoms in some children. Larger trials are needed. A 2007 double-blind, placebo-controlled trial of small groups of children found that omega-3 fatty acids reduced hyperactivity in children with autism spectrum disorders, suggesting that further research is needed.
In a study of nearly 9,000 pregnant women, researchers found women who ate fish once a week during their first trimester had 3.6 times less risk of low birth weight and premature birth than those who ate no fish. Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. However, attempts by other groups to reverse this increased risk by encouraging increased pre-natal consumption of fish were unsuccessful.
ω−3 fatty acids are known to have membrane-enhancing capabilities in brain cells. One medical explanation is that ω−3 fatty acids play a role in the fortification of the myelin sheaths. Not coincidentally, ω−3 fatty acids comprise approximately eight percent of the average human brain according to Dr. David Horrobin, a pioneer in fatty acid research. Ralph Holman of the University of Minnesota, another major researcher in studying essential fatty acids, who gave it the name, surmised how ω−3 components are analogous to the human brain by stating that "DHA is structure, EPA is function."
A benefit of ω−3 fatty acids is helping the brain to repair damage by promoting neuronal growth. In a six-month study involving people with schizophrenia and Huntington's disease who were treated with EPA or a placebo, the placebo group had clearly lost cerebral tissue, while the patients given the supplements had a significant increase of grey and white matter.
In the prefrontal cortex (PFC) of the brain, low brain ω−3 fatty acids are thought to lower the dopaminergic neurotransmission in this brain area, possibly contributing to the negative and neurocognitive symptoms in schizophrenia. This reduction in dopamine system function in the PFC may lead to an overactivity in dopaminergic function in the limbic system of the brain which is suppressively controlled by the PFC dopamine system, causing the positive symptoms of schizophrenia. This is called the n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia (Ohara, 2007). This mechanism may explain why ω−3 supplementation shows effects against both positive, negative and neurocognitive symptoms in schizophrenia.
Consequently, the past decade of ω−3 fatty acid research has procured some Western interest in ω−3 fatty acids as being a legitimate 'brain food.' Still, recent claims that one's intelligence quotient, psychological tests measuring certain cognitive skills, including numerical and verbal reasoning skills, are increased on account of ω−3 fatty acids consumed by pregnant mothers remain unreliable and controversial. An even more significant focus of research, however, lies in the role of ω−3 fatty acids as a non-prescription treatment for certain psychiatric and mental diagnoses and has become a topic of much research and speculation.
In 1998, Andrew L. Stoll, MD and his colleagues at Harvard University conducted a small double-blind placebo-controlled study in thirty patients diagnosed with bipolar disorder. Over the course of nine months, he gave 15 subjects capsules containing olive oil, and another 15 subjects capsules containing nine grams of pharmaceutical-quality EPA and DHA. In doing so, he was able to make the general distinction between the placebo group failing to improve while the ω−3 group experienced a noticeable degree of recovery. Though Stoll believes that the 1999 experiment was not as optimal as it could have been and has accordingly pursued further research, the foundation has been laid for more researchers to explore the theoretical association between absorbed ω−3 fatty acids and signal transduction inhibition in the brain.
"Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega−3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach." (American Journal of Psychiatry 163:1098-1100, June 2006) In 2004, a study found that 100 suicide attempt patients on average had significantly lower levels of EPA in their blood as compared to controls..
In 2006, a review of published trials in the American Journal of Clinical Nutrition found that "the evidence available provides little support" for the use of fish or the n–3 long-chain polyunsaturated fatty acids contained in them to improve depressed mood. The study used results of twelve randomized controlled trials in its meta-analysis. The review recommended that "larger trials with adequate power to detect clinically important benefits" be performed.
As macronutrients, fats are not assigned recommended daily allowances. Macronutrients have AI (Acceptable Intake) and AMDR (Acceptable Macronutrient Distribution Range) instead of RDAs. The AI for n-3 is 1.6 grams/day for men and 1.1 grams/day for women while the AMDR is 0.6% to 1.2% of total energy.
"A growing body of literature suggests that higher intakes of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) may afford some degree of protection against coronary heart disease. Because the physiological potency of EPA and DHA is much greater than that for α-linolenic acid, it is not possible to estimate one AMDR for all n-3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA." There was insufficient evidence as of 2005 to set a UL (upper tolerable limit) for n-3 fatty acids.
Researchers believe the ideal ω−6 intake should be no more than 4-5 times that of our ω−3 intake. The National Institutes of Health recently published recommended daily intakes of fatty acids, specific recommendations include 650 mg of EPA and DHA, 2.22 g/day of alpha-linolenic acid and 4.44 g/day of linoleic acid.
A perceived risk of fish oil ω−3 supplementation has been heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic and cadmium as well as other contaminants (PCBs, furans, dioxins), which potentially might be found especially in less-refined fish oil supplements. An independent test in 2006 of 44 fish oils on the US market found that all of the products passed safety standards for potential contaminants. The FDA recommends that total dietary intake of ω−3 fatty acids from fish not exceed 3 grams per day, of which no more than 2 grams per day are from nutritional supplements.
Historically, the Council for Responsible Nutrition (CRN) and the World Health Organization (WHO) have published acceptable standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard (IFOS).
Fish oils that typically make this highest grade are those that are molecularly distilled under vacuum, and have virtually no measurable level of contaminants (measured parts per billion and parts per trillion).
ω−3 supplementation in food has been a significant recent trend in food fortification, with global food companies launching ω−3 fortified bread, mayonnaise, pizza, yogurt, orange juice, children's pasta, milk, eggs, confections and infant formula.
Early humans ate inter-tidal shellfish, while living a shoreline existence in Africa. Now, as then, inter-tidal herbivorous shellfish such as mussels and clams can help people reach a healthy balance of ω−3 and ω−6 fats in their diets.
The most widely available source of EPA and DHA is cold water oily fish such as salmon, herring, mackerel, anchovies and sardines. Oils from these fish have a profile of around seven times as much ω−3 as ω−6. Other oily fish such as tuna also contain ω−3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins which may accumulate up the food chain. Some supplement manufacturers remove heavy metals and other contaminants from the oil through various means, such as molecular distillation (see above), which increases purity, potency and safety.
Even some forms of fish oil may not be optimally digestible. Of four studies that compare bioavailability of the triglyceride form of fish oil vs. the ester form, two have concluded that the natural triglyceride form is better, and the other two studies did not find a significant difference. No studies have shown the ester form to be superior although it is cheaper to manufacture.
Although fish is a dietary source of ω−3 fatty acids, fish do not synthesize them; they obtain them from the algae in their diet.
Six times richer than most fish oils in ω−3, Flax (aka linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of ω−3. Flaxseed oil consists of ca. 55% ALA (alpha-linolenic acid). Flax, like chia, contains approximately three times as much ω−3 as ω−6.
15 grams of flaxseed oil provides ca. 8 grams of ALA, which is converted in the body to EPA and then DHA at an efficiency of (2%-15%), and (2%-5%) respectively.
Table 1. ω−3 content as the percentage of ALA in the seed oil.
Table 2. ω−3 content as the percentage of ALA in the whole food.
Eggs produced by chickens fed a diet of greens and insects produce higher levels of ω−3 fatty acids (mostly ALA) than chickens fed corn or soybeans.In addition to feeding chickens insects and greens, fish oils are added to their diet to increase the amount of fatty acid concentrations in eggs.Invalid parameter in <ref> tag
Krill, which are small, shrimp-like zooplankton, also contain the ω−3 fatty acids EPA and DHA. One advantage of extracting ω−3 fatty acids from krill, as opposed to sources higher in the food chain, is that krill contain fewer heavy metals and PCBs harmful to humans. However, in comparison to higher animals, they also contain fewer ω−3 fatty acids per gram.
The ω−6 to ω−3 ratio of grass-fed beef is about 2:1, making it a more useful source of ω−3 than grain-fed beef, which usually has a ratio of 4:1. Commercially available lamb is almost always grass-fed, and subsequently higher in ω−3 than other common meat sources. Milk and cheese from grass-fed cows may also be good sources of ω−3. One UK study showed that half a pint of milk provides 10% of the recommended daily intake (RDI) of ALA, while a piece of organic cheese the size of a matchbox may provide up to 88%".
The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA (22:6 ω-3) and can be produced commercially in bioreactors. Oil from brown algae (kelp) is a source of EPA. Walnuts are one of few nuts that contain appreciable ω−3 fat, with approximately a 1:4 ratio of ω−3 to ω−6. Acai palm fruit also contains ω−3 fatty acids.
Main article: Essential fatty acid interactions
Clinical studies indicate that the ingested ratio of ω−6 to ω−3 (especially Linoleic vs Alpha Linolenic) fatty acids is important to maintaining cardiovascular health.
Both ω−3 and ω−6 fatty acids are essential, i.e. humans must consume them in the diet. ω−3 and ω−6 compete for the same metabolic enzymes, thus the ω−6:ω−3 ratio will significantly influence the ratio of the ensuing eicosanoids (hormones), (e.g. prostaglandins, leukotrienes, thromboxanes etc.), and will alter the body's metabolic function. Generally, grass-fed animals accumulate more ω−3 than do grain-fed animals which accumulate relatively more ω−6. Metabolites of ω−6 are significantly more inflammatory (esp. arachidonic acid) than those of ω−3. This necessitates that ω−3 and ω−6 be consumed in a balanced proportion; healthy ratios of ω−6:ω−3 range from 1:1 to 4:1. Studies suggest that the evolutionary human diet, rich in seafood and other sources of ω−3, may have provided such a ratio. recommend daily intakes of three ω−3 forms: 650 mg of EPA and DHA, and 2.22 grams of ALA, and one ω−6 form: 4.44 grams of LA. This translates to a 3:2 ω−6 to ω−3 ratio. (i.e. 1.5:1)
Typical Western diets provide ratios of between 10:1 and 30:1 - i.e., dramatically skewed toward ω−6. Here are the ratios of ω−6 to ω−3 fatty acids in some common oils: canola 2:1, soybean 7:1, olive 3-13:1, sunflower (no ω−3), flax 1:3 cottonseed (almost no ω−3), peanut (no ω−3), grapeseed oil (almost no ω−3) and corn oil 46 to 1 ratio of ω−6 to ω−3. It should be noted that olive, peanut and canola oils consist of approximately 80% monounsaturated fatty acids, (i.e. neither ω−6 nor ω−3) meaning that they contain relatively small amounts of ω−3 and ω−6 fatty acids. Consequently, the ω−6 to ω−3 ratios for these oils (i.e. olive, canola and peanut oils) are not as significant as they are for corn, soybean and sunflower oils.
It has been reported that conversion of ALA to EPA and further to DHA in humans is limited, but varies with individuals . Women have higher ALA conversion efficiency than men, probably due to the lower rate of utilization of dietary ALA for beta-oxidation. This suggests that biological engineering of ALA conversion efficiency is possible. In the online book of The Benefits of Omega 3 Fatty Acids found in Seal Oil, as Opposed to Fish and Flaxseed Oils, Dr. Ho listed the several factors that inhibit the ALA conversion , which again indicate that the efficiency of ALA conversion could be adjusted by altering one's dietary habits, such as rebalancing the ratio of ω−3 and ω−6 fatty acid intake , , restraining direct alcohol consumptions, and supplementing vitamins and minerals. However, Goyens et al. argues that it is the absolute amount of ALA, rather than the ratio of ω−3 and ω−6 fatty acids, which affects the conversion .
List of ω−3 fatty acids
ω−6 fatty acid
ω−9 fatty acid
Essential fatty acid
Essential fatty acid interactions
Grape seed oil
Camelina sativa
Cod liver oil
Fish oil
Flax
Linseed oil
Chia
Purslane
Resolvins
Wakame |
Fenbufen | Fenbufen is a non-steroidal anti-inflammatory drug used primarily to treat inflammation in osteoarthritis, ankylosing spondylitis, and tendinitis. It can also be used to relieve backaches, sprains, and fractures. Fenbufen is available as a capsule or tablet sold with the brand names Cepal, Cinopal, Cybufen, Lederfen, and Reugast. Fenbufen acts by preventing cyclooxygenase from producing prostaglandins which can cause inflammation.
|
Diabetic_nephropathy_laboratory_findings | The diagnosis of diabetic nephropathy depends mostly on urinalysis. The most important finding is documenting the presence of albumin in the urine
:
Screening for albuminuria is done with a routine dipstick urinalysis.
However, routine dipsticks do not rule out microalbuminuria.
.
However, if the test is negative, a radioimmunoassay for albumin should be done and repeated every year if the initial result is negative.
Conditions such as heart failure, uncontrolled hypertension, UTI and an acute febrile illness increase the albumin excretion in the urine and hence, testing for albuminuria should not be performed during these conditions.
The albumin to creatinine ratio should also be measured in a morning urine sample, a 24-hour or an overnight sample.
|
Mephenoxalone | Mephenoxalone (trade names Dorsiflex, Moderamin, Control-OM) is a muscle relaxant and mild anxiolytic. It inhibits neuron transmission, relaxing skeletal muscles by inhibiting the reflex arc. As the effect of muscle relaxation, mephenoxalone affects mental condition, and is also a treatment for nervousness and anxiety.
|
Alcoholic_fermentation | Ethanol fermentation is the biological process by which sugars such as glucose, fructose, and sucrose, are converted into ethanol and carbon dioxide. Yeasts carry out ethanol fermentation on sugars in the absence of oxygen. Because the process does not require oxygen, ethanol fermentation is classified as anaerobic. Ethanol fermentation is responsible for the rising of bread dough, the production of ethanol in alcoholic beverages, and for much of the production of ethanol for use as fuel.
The chemical equation below summarizes ethanol fermentation, in which one hexose molecule is converted into two ethanol molecules and two carbon dioxide molecules:
C6H12O6 → 2 C2H5OH + 2 CO2
The process begins with a molecule of glucose being broken down by the process of glycolysis into pyruvate:
C6H12O6 → 2 CH3COCOO− + 2 H2O + 2H+
This reaction is accompanied by the reduction of two molecules of Nicotinamide adenine dinucleotide to carbon dioxide and water.
, , Glucose,
, , Pyruvate,
, , Acetaldehyde,
, Error creating thumbnail: File missing, Ethanol,
Ethanol fermentation is responsible for the rising of bread dough. Yeast organisms consume sugars in the dough and produce ethanol and carbon dioxide as waste products. The carbon dioxide forms bubbles in the dough, expanding it into something of a foam. Nearly all the ethanol evaporates from the dough when the bread is baked.
The production of all alcoholic beverages employs ethanol fermentation by yeast. Wines and brandies are produced by fermentation of the natural sugars present in fruits, especially grapes. Beers, ales, and whiskeys employ fermentation of grain starches that have been converted to sugar by the application of the enzyme, amylase, which is present in grain kernels that have been germinated. Amylase-treated grain or amylase-treated potatos is fermented for the production of vodka. Fermentation of cane sugar is the first step in producing rum. In all cases, the fermentation must take place in a vessel that is arranged to allow carbon dioxide to escape, but that prevents outside air from coming in, as exposure to oxygen would prevent the formation of ethanol.
Similar yeast fermentation of various carbohydrate products is used produce much of the ethanol used for fuel.
The dominant ethanol feedstock in warmer regions is sugarcane. In temperate regions, this accessibility has been somewhat replicated by selective breeding of the sugar beet.
In the United States, the main feedstock for the production of ethanol is currently corn. Approximately 2.8 gallons of ethanol (10 liters) are produced from one bushel of corn (35 liters). While much of the corn turns into ethanol, some of the corn also yields by-products such as DDGS (distillers dried grains with solubles) that can be used to fulfill a portion of the diet of livestock. A bushel of corn produces about 18 pounds of DDGS. . Although most of the fermentation plants have been built in corn-producing regions, sorghum is also an important feedstock for ethanol production in the Plains states. Pearl millet is showing promise as an ethanol feedstock for the southeastern U.S.
In some parts of Europe, particularly France and Italy, wine is used as a feedstock due to massive oversupply. Japan is hoping to use rice wine (sake) as an ethanol source.
Main players will be Brazil, USA, EU, and tropical developing countries.
EU can currently (2007) produce ethanol in large quantities with a mineral-oil based chemical process
for 0.57 US$/liter .
USA produces ethanol for circa 0.32 US$/liter, mainly from corn starch.
Brazil produces ethanol for circa 0.27 US$/liter, from sugarcane.
Tropical developing countries do not produce very large amounts of ethanol yet.
Brazil is the largest producer, but it will not be able to meet EU's needs for many years to come,
assuming that it will expand ethanol production at maximum possible rate.
USA is expected to become self-supplying (to avoid high oil prices),
but is not expected to become a major exporter.
EU also wants to avoid high oil prices,
and is starting to require a minimum ethanol percentage in automobile fuels,
so it wants to import ethanol.
Ethanol can be made from mineral oil or from sugars or starches, cheapest of which are starches,
and starchy crop with highest energy content per acre is cassava,
which grows in tropical countries.
Thailand already had a large cassava industry in the 1990s,
for use as cattle food and as cheap admixture to wheat flour;
Nigeria and Ghana are already establishing cassava-to-ethanol plants ; Brazil is doing that too (sugarcane and cassava grow on very different types of soil) ;
and so are many other countries.
EU expects that combined effect of increasing ethanol production will be able to meet it's needs in 2012.
Therefore it is expect that in 2012 price of ethanol will drop from maybe 0.42 US$ to maybe 0.3 US$ (FOB africa).
Production of ethanol from cassava is currently economically feasible when crude oil prices are above 40 US$ per barrel.
New varieties of cassava are being developed, so future situation remains uncertain.
Currently, cassava can yield more than 40 tons per hectare (with irrigation and fertilizer),
and from a ton of cassava roots, circa 200 liter of ethanol can be produced (assuming cassava with 22% starch content),
and a liter of ethanol contains circa 10.7 MJ of energy.
Overall energy efficiency of cassava-root to ethanol conversion is circa 32% .
Cassava plants can grow in poor soils, are drought resistant,
and need a minimum temperature of 17 oC .
They can use solar radiation up to 300 W/m2 (equivalent to lightly clouded tropical sky), and optimum water use is 100 to 150 cm (slightly less than rainfall in rain forest).
For compensating for nutrients taken up, Cassava's fertilizer demand is (in kg nutrient per ton cassava): N:21, P:10, K:42, Ca:7, Mg:4 , so if fertilizer prices go up, so does ethanol price.
Starch price (food-quality starch from Thailand) is circa 0.22 US$/kg ,
and from 1 kg starch , 0.9 liter of ethanol can be produced,
so, producer price would be 0.24 US$/liter plus cost of conversion from starch to ethanol.
A 10 million US$ conversion plant can convert circa 80 million liter per year,
so total cost of ethanol from cassava currently is near USA's production price ;
Due to improvements being made in this relatively new industry, producer price would become lower,
probably near that of Brazil, and maybe even lower than that.
Yeast used for processing cassava is Endomycopsis fibuligera,
sometimes used together with bacterium Zymomonas mobilis.
Most of this information can be found on FAO's website.
Yeast
Zymomonas mobilis
Anaerobic respiration
Cellulose
Cellular respiration
Fermentation (biochemistry)
Fermentation (wine) |
Hypoplasia | Hypoplasia is an incomplete or arrested development of an organ or a part [1]. It is descriptive of many medical conditions such as:
Underdeveloped breasts during puberty.
Underdeveloped testes in Klinefelter's syndrome.
Underdeveloped thymus in DiGeorge syndrome.
Underdeveloped labia majora in popliteal pterygium syndrome.
Underdeveloped cerebellum caused by mutation in the Reelin gene.
Underdeveloped tooth caused by oral pathology, such as Turner's hypoplasia.
Underdeveloped chambers of the heart in hypoplastic left heart syndrome and hypoplastic right heart syndrome
Underdeveloped optic nerve in optic nerve hypoplasia
Underdeveloped sacrum in sacral agenesis
Underdeveloped facial muscle in asymmetric crying facies
Aplasia
Atrophy.
Template:WikiDoc Sources
|
FRS | The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of an individual. The Framingham Risk Score is based on data obtained from the Framingham Heart Study. There are two Framingham Risk Scores, one for men and one for women.
The Framingham Risk Score is available free of charge on the Internet. Everybody can estimate their 10-year cardiovascular risk on the following web page:
http://hp2010.nhlbihin.net/atpiii/calculator.asp
The Framingham Risk Score is one of a number of scoring systems used to determine an individual's chances of developing cardiovascular disease. This means either coronary heart disease or stroke. A number of these scoring systems are available online. Cardiovascular risk scoring systems give an estimate of the probability that a person will develop cardiovascular disease within the next 5 or 10 years. Because they give an indication of who is most likely to develop cardiovascular disease they also indicate who is most likely to benefit from prevention. For this reason cardiovascular risk scores are used to determine who should be offered preventive drugs such as drugs to lower blood pressure and drugs to lower cholesterol levels.
Because the Framingham Risk Score (or another appropriate scoring system) give an indication of the likely benefits of prevention, they are useful for both the individual patient and for the clinician in helping decide whether lifestyle modification and preventive medical treatment, and for patient education, by identifying men and women at increased risk for future cardiovascular events. The CHD risk at 10 years in percent can be calculated with the help of the Framingham Risk Score. Individuals with low risk have 10% or less CHD risk at 10 years, with intermediate risk 10-20%, and with high risk 20% or more. However it should be remembered that these categorisations are arbitrary.
A more useful metric is to consider the effects of treatment. If 100 persons have a 20% ten-year risk of cardiovascular disease it means that 20 of these 100 individuals will develop cardiovascular disease (coronary heart disease or stroke) in the next 10 years. Eighty of them will not develop cardiovascular disease in the next 10 years. If they were to take a combination of treatments (for example drugs to lower cholesterol levels plus drugs to lower blood pressure) that reduced their risk of cardiovascular disease by half it means that 10 of these 100 individuals would develop cardiovascular disease in the next 10 years: 90 of them would not develop cardiovascular disease. This means that 10 of these individuals would have avoided cardiovascular disease by taking treatment for 10 years; 10 would get cardiovascular disease whether or not they took treatment; and 80 would not have got cardiovascular disease whether or not they took treatment.
It is important to recognise that the strongest predictor of cardiovascular risk in any risk equation is age. Almost all persons aged 70 and over are at >20% ten year cardiovascular risk and almost nobody aged under 40 is at >20% ten year cardiovascular risk. Since those who benefit most from treatment are those at highest risk, this means that treatment of patients with raised blood pressure and raised cholesterol levels in their 30ies benefits very few. Whereas treatment of patients with "normal" blood pressure and "normal" cholesterol levels in their 70ies benefits many. This casts doubt on the wisdom of categorising individuals as having high blood pressure or raised cholesterol and treating these individual risk factors without a consideration of both their overall risk of cardiovascular disease and of the probability that they will benefit.
Cardiovascular disease is common in the general population, affecting the majority of adults. It includes: 1) Coronary heart disease (CHD): Myocardial infarction (MI), angina pectoris, heart failure (HF), and coronary death. 2) Cerebrovascular disease, stroke and transient ischemic attack (TIA). 3) Peripheral arterial disease, intermittent claudication and significant limb ischemia. 4) Aortic disease: Aortic atherosclerosis, thoracic aortic aneurysm, and abdominal aortic aneurysm.
An individual’s risk for future cardiovascular events is modifiable, by lifestyle changes and preventive medical treatment. Lifestyle changes can include stopping smoking, healthy diet, regular exercise, etc. Preventive medical treatment can include a statin, mini dose aspirin, treatment for hypertension, etc. It is important to be able to predict the risk of an individual patient, in order to decide when to initiate lifestyle modification and preventive medical treatment.
Multiple risk models for the prediction of cardiovascular risk of individual patients have been developed. One such key risk model is the Framingham Risk Score.
The Framingham Risk Score is based on findings from the Framingham Heart Study.
The Framingham Risk Score has been validated in the USA, both in men and women, both in European Americans and African Americans.. While several studies have claimed to improve on the FRS, there is little evidence for any improved prediction beyond the Framingham risk score
There are two limitations.
The Framingham Risk Score predicts only future coronary heart disease (CHD) events. It does not predict future total cardiovascular events, i.e. it does not also predict risk for stroke, transient ischemic attack (TIA), and heart failure. These also important patient outcomes were included in the 2008 Framingham General Cardiovascular Risk Score. The predicted risk for an individual usually is higher with the 2008 Framingham General Cardiovascular Risk Score than with the 2002 Framingham Risk Score.
The Framingham Risk Score could overestimate (or underestimate) risk in populations other than the US population , and within the USA in populations other than European Americans and African Americans, e.g. Hispanic Americans and Native Americans. It is not yet clear if this limitation is real, or appears to be real because of differences in methodology, etc. As a result, other countries may prefer to use another risk score, e.g. SCORE, which has been recommended by the European Society of Cardiology in 2007.
If possible, a cardiology professional should select the risk prediction model which is most appropriate for an individual patient and should remember that this is only an estimate.
The current version of the Framingham Risk Score was published in 2002. The publishing body is the ATP III, i.e. the «Adult Treatment Panel III», an expert panel of the National Heart, Lung, and Blood Institute, which is part of the National Institutes of Health (NIH), USA.
The original Framingham Risk Score had been published in 1998.
The first Framingham Risk Score included age, gender, LDL cholesterol, HDL cholesterol, blood pressure (and also whether the patient is treated or not for his/her hypertension), diabetes, and smoking. It estimated the 10-year risk for coronary heart disease (CHD). It performed well, and correctly predicted 10-year risk for CHD in American men and women of European and African descent.
The updated version was modified to include dyslipidemia, age range, hypertension treatment, smoking, and total cholesterol, and it excluded diabetes, because Type 2 diabetes meanwhile was considered to be a CHD Risk Equivalent, having the same 10-year risk as individuals with prior CHD. Patients with Type 1 diabetes were considered separately with slightly less aggressive goals; while at increased risk, no study had shown them to be at equivalent risk for CHD as those with previously diagnosed coronary disease or Type 2 diabetes.
Some patients without known CHD have risk of cardiovascular events that is comparable to that of patients with established CHD. Cardiology professionals refer to such patients as having a CHD Risk Equivalent. These patients should be managed as patients with known CHD. Diabetes is accepted as a CHD Risk Equivalent.
The Framingham/ATP III criteria were used to estimate CHD risk in the USA. Data from 11,611 patients from a very large study, the NHANES III, were used. The patients were 20 to 79 years of age, and had no self reported CHD, stroke, peripheral arterial disease, or diabetes.
The results: 82% of patients had low risk (10% or less CHD risk at 10 years). 16% had intermediate risk (10-20%). 3% had high risk (20% or more).
High risk was most commonly found in patients with advanced age, and was more common in men than women.
Framingham Risk Score: The first part of this name, i.e. "Framingham", may be called either "Framingham" or "Framingham/ATP III" by cardiology professionals, and the second part may be called "Score", "Risk Score" or "Cardiac Risk Score". All possible combinations have been used. However, "Framingham Risk Score" is more common than the other variants.
Below are the points of the Framingham Risk Score in detail. However, it is much easier to use the calculator on the Internet.
Age: 20-34 years: Minus 7 points. 35-39 years: Minus 3 points. 40-44 years: 0 points. 45-49 years: 3 points. 50-54 years: 6 points. 55-59 years: 8 points. 60-64 years: 10 points. 65-69 years: 12 points. 70-74 years: 14 points. 75-79 years: 16 points.
Total cholesterol, mg/dL: Age 20-39 years: Under 160: 0 points. 160-199: 4 points. 200-239: 8 points. 240-279: 11 points. 280 or higher: 13 points. • Age 40-49 years: Under 160: 0 points. 160-199: 3 points. 200-239: 6 points. 240-279: 8 points. 280 or higher: 10 points. • Age 50-59 years: Under 160: 0 points. 160-199: 2 points. 200-239: 4 points. 240-279: 5 points. 280 or higher: 7 points. • Age 60-69 years: Under 160: 0 points. 160-199: 1 point. 200-239: 2 points. 240-279: 3 points. 280 or higher: 4 points. • Age 70-79 years: Under 160: 0 points. 160-199: 1 point. 200-239: 1 point. 240-279: 2 points. 280 or higher: 2 points.
If cigarette smoker: Age 20-39 years: 9 points. • Age 40-49 years: 7 points. • Age 50-59 years: 4 points. • Age 60-69 years: 2 points. • Age 70-79 years: 1 point.
All non smokers: 0 points.
HDL cholesterol, mg/dL: 60 or higher: Minus 1 point. 50-59: 0 points. 40-49: 1 point. Under 40: 2 points.
Systolic blood pressure, mm Hg: Untreated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 3 points. 160 or higher: 4 points. • Treated: Under 120: 0 points. 120-129: 3 points. 130-139: 4 points. 140-159: 5 points. 160 or higher: 6 points.
10-year risk in %: Points total: Under 9 points: <1%. 9-12 points: 1%. 13-14 points: 2%. 15 points: 3%. 16 points: 4%. 17 points: 5%. 18 points: 6%. 19 points: 8%. 20 points: 11%. 21=14%, 22=17%, 23=22%, 24=27%, 25=30%
Age: 20-34 years: Minus 9 points. 35-39 years: Minus 4 points. 40-44 years: 0 points. 45-49 years: 3 points. 50-54 years: 6 points. 55-59 years: 8 points. 60-64 years: 10 points. 65-69 years: 11 points. 70-74 years: 12 points. 75-79 years: 13 points.
Total cholesterol, mg/dL: Age 20-39 years: Under 160: 0 points. 160-199: 4 points. 200-239: 7 points. 240-279: 9 points. 280 or higher: 11 points. • Age 40-49 years: Under 160: 0 points. 160-199: 3 points. 200-239: 5 points. 240-279: 6 points. 280 or higher: 8 points. • Age 50-59 years: Under 160: 0 points. 160-199: 2 points. 200-239: 3 points. 240-279: 4 points. 280 or higher: 5 points. • Age 60-69 years: Under 160: 0 points. 160-199: 1 point. 200-239: 1 point. 240-279: 2 points. 280 or higher: 3 points. • Age 70-79 years: Under 160: 0 points. 160-199: 0 points. 200-239: 0 points. 240-279: 1 point. 280 or higher: 1 point.
If cigarette smoker: Age 20-39 years: 8 points. • Age 40-49 years: 5 points. • Age 50-59 years: 3 points. • Age 60-69 years: 1 point. • Age 70-79 years: 1 point.
All non smokers: 0 points.
HDL cholesterol, mg/dL: 60 or higher: Minus 1 point. 50-59: 0 points. 40-49: 1 point. Under 40: 2 points.
Systolic blood pressure, mm Hg: Untreated: Under 120: 0 points. 120-129: 0 points. 130-139: 1 point. 140-159: 1 point. 160 or higher: 2 points. • Treated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 2 points. 160 or higher: 3 points.
10-year risk in %:
Points total:
0 point: <1%.
1 point: 1%.
2 points: 1%.
3 points: 1%.
4 points: 1%.
5 points: 2%.
6 points: 2%.
7 points: 3%.
8 points: 4%.
9 points: 5%.
10 points: 6%.
11 points: 8%.
12 points: 10%.
13 points: 12%.
14 points: 16%.
15 points: 20%.
16 points: 25%.
17 points or more: Over 30%.
Not only coronary heart disease (CHD) events, but also further risks can be predicted. Risk prediction models for cardiovascular disease outcomes other than CHD events have also been developed by the Framingham Heart Study researchers. Amongst others, a risk score for 10-year risk for atrial fibrillation has been developed.
A calculator for 10-year risk for atrial fibrillation is available free of charge on the official website of the Framingham Heart Study:
http://www.mdcalc.com/framingham-coronary-heart-disease-risk-score/#
QRISK |
Subsets and Splits