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Perineal_tear | In obstetrics, a perineal tear is a spontaneous (unintended) laceration of the skin and other soft tissue structures which, in women, separate the vagina from the anus. Perineal tears mainly occur in women as a result of vaginal childbirth, which strains the perineum. Tears vary widely in severity. The majority are superficial and require no treatment, but srounded by a wall, and the anal wall is separated from the vaginal wall by a mass of soft tissue including:
The muscles of the anus (corrugator cutis ani, the internal anal sphincter and the external anal sphincter)
The medial muscles of the urogenital region (the superficial transverse perineal muscle, the deep transverse perineal muscle and bulbocavernosus)
The medial levator ani muscles (puborectalis and pubococcygeus)
The fascia of perineum, which covers these muscles
The overlying skin and subcutaneous tissue
A perineal tear may involve some or all of these structures, which normally aid in supporting the pelvic organs and maintaining faecal continence.
Tears are classified into four categories:
First-degree tear: laceration is limited to the fourchette and superficial perineal skin or vaginal mucosa
Second-degree tear: laceration extends beyond fourchette, perineal skin and vaginal mucosa to perineal muscles and fascia, but not the anal sphincter
Third-degree tear: fourchette, perineal skin, vaginal mucosa, muscles, and anal sphincter are torn; third-degree tears may be further subdivided into three subcategories: 3a: partial tear of the external anal sphincter involving less than 50% thickness, 3b: greater than 50% tear of the external anal sphincter, 3c: internal sphincter is torn
Fourth-degree tear: fourchette, perineal skin, vaginal mucosa, muscles, anal sphincter, and rectal mucosa are torn
In humans and some other primates, the head of the term fetus is so large in comparison to the size of the birth canal that term delivery is rarely possible without some degree of trauma. As the head passes through the pelvis, the soft tissues are stretched and compressed. The risk of severe tear is greatly increased if the fetal head is oriented occiput posterior (face forward), if the mother has not given birth before or if the fetus is large.
The risk of perineal tear is reduced by the use of medio-lateral episiotomy, although this procedure is also traumatic. Epidural anaesthesia and induction of labour also reduce the risk. Instrument been clearly demonstrated. The ‘Epi-no birth trainer’, a relatively recent invention, is a device specifically designed to strengthen and stretch the perineum during pregnancy. In spite of some promising studies, systematic review has shown no effect on the rate of tearing or episiotomy.
Over 85% of women having a vaginal birth sustain some form of perineal trauma, and 60-70% receive stitches. A retrospective study of 8603 vaginal deliveries found a third degree tear had been clinically diagnosed in only 50 women (0.6%). However, when the same authors used anal endosonography in a consecutive group of 202 deliveries, there was evidence of third degree tears in 35% of first-time mothers and 44% of mothers with previous children. These numbers are confirmed by other researchers.
First and second degree tears rarely cause long-term problems. Among women who experience a third or fourth degree tear, 60-80% are asymptomatic after 12 months. Faecal incontinence, faecal urgency, chronic perineal pain and dyspareunia occur in a minority of patients, but may be permanent. The symptoms associated with perineal tear are not always due to the tear itself, since there are often other injuries, such as avulsion of pelvic floor muscles, that are not evident on examination.
A study by the Agency for Healthcare Research and Quality (AHRQ) found that in 2011, first- and second-degree perineal tear was the most common complicating condition for vaginal deliveries in the U.S. among women covered by either private insurance or Medicaid.
Second-degree perineal laceration rates were higher for women covered by private insurance than for women covered by Medicaid.
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Infertility_pelvic_ultrasound | Pelvic ultrasound is a first line diagnostic modality used in the diagnosis of infertility. It can detect changes in endometrium, presence of fibroids etc with great accuracy.
Pelvic ultrasound is used as a first line investigation in the diagnosis of infertility.
Pelvic ultrasound can predict ovulation with higher accuracy than basal body temperature.
It can also detect the cyclical changes in uterine endometrium. These changes are absent in anovulatory cycles.
The position of uterus, presence of fibroids, cystic changes in ovaries, congenital anomalies in the genital tract can be detected via pelvic ultrasound. |
Tacrolimus_(extended_release) | Tacrolimus (extended release) is a calcineurin inhibitor that is FDA approved for the prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate-release formulations in combination with other immunosuppressants. There is a Black Box Warning for this drug as shown here. Common adverse reactions include diarrhea and increased blood creatinine.
Tacrolimus (extended release) is indicated for the prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate-release formulations, in combination with other immunosuppressants.
Take TACROLIMUS (EXTENDED RELEASE) on an empty stomach at the same time of the day, preferably in the morning (to ensure consistent and maximum possible drug exposure).
Swallow TACROLIMUS (EXTENDED RELEASE) whole with fluid (preferably water); do not chew, divide, or crush the tablets.
If a dose is missed, take it as soon as possible within 15 hours after missing the dose; beyond the 15-hour time frame, wait until the usual scheduled time to take the next regular daily dose. Do not double the next dose.
Avoid eating grapefruit or drinking grapefruit juice or alcoholic beverage while taking TACROLIMUS (EXTENDED RELEASE).
African-American patients, compared to Caucasian patients, may need to be titrated to higher TACROLIMUS (EXTENDED RELEASE) dosages to attain comparable trough concentrations.
To convert from a tacrolimus immediate-release product to TACROLIMUS (EXTENDED RELEASE), administer an TACROLIMUS (EXTENDED RELEASE) once daily dose that is 80% of the total daily dose of the tacrolimus immediate-release product.
Monitor tacrolimus whole blood trough concentrations and titrate TACROLIMUS (EXTENDED RELEASE) dosage to achieve target whole blood trough concentration ranges of 4 to 11 ng/mL.
Measure tacrolimus whole blood trough concentrations at least two times on separate days during the first week after initiation of dosing and after any change in dosage, after a change in co-administration of CYP3A inducers and/or inhibitors, or after a change in renal or hepatic function.
When interpreting measured concentrations, consider that the time to achieve tacrolimus steady state is approximately 7 days after initiating or changing the TACROLIMUS (EXTENDED RELEASE) dose.
Monitor tacrolimus whole blood trough concentrations using a validated assay [e.g., immunoassays or high-performance liquid chromatography with tandem mass spectrometric detection (HPLC/MS/MS)].
The immunosuppressive activity of tacrolimus is mainly due to the parent drug rather than to its metabolites.
Immunoassays may react with metabolites as well as the parent drug.
Therefore, whole blood tacrolimus trough concentrations obtained with immunoassays may be numerically higher than concentrations obtained with an assay using HPLC/MS/MS.
Comparison of the whole blood tacrolimus trough concentrations of patients to those described in the prescribing information and other published literature must be made with knowledge of the assay method(s) employed.
There is limited information regarding Off-Label Guideline-Supported Use of Tacrolimus (extended release) in adult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tacrolimus (extended release) in adult patients.
The safety and effectiveness of TACROLIMUS (EXTENDED RELEASE) in pediatric patients have not been established.
There is limited information regarding Off-Label Guideline-Supported Use of Tacrolimus (extended release) in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tacrolimus (extended release) in pediatric patients.
TACROLIMUS (EXTENDED RELEASE) is contraindicated in patients with known hypersensitivity to tacrolimus.
Immunosuppressants, including TACROLIMUS (EXTENDED RELEASE), increase the risk of developing lymphomas and other malignancies, particularly of the skin.
The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.
Examine patients for skin changes and advise to avoid or limit exposure to sunlight and UV light.
Post-transplant lymphoproliferative disorder (PTLD), associated with Epstein-Barr Virus (EBV), has been reported in immunosuppressed organ transplant patients.
The risk of PTLD appears greatest in those individuals who are EBV seronegative. Monitor EBV serology during treatment.
Immunosuppressants, including TACROLIMUS (EXTENDED RELEASE), increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections.
These infections may lead to serious, including fatal, outcomes. Serious viral infections reported include: Polyomavirus-associated nephropathy (especially due to BK virus infection), JC virus-associated progressive multifocal leukoencephalopathy (PML), and, Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease.
Monitor for the development of infection and adjust the immunosuppressive regimen to balance the risk of rejection with the risk of infection.
Medication errors, including substitution and dispensing errors, between tacrolimus immediate-release products and tacrolimus extended-release products were reported outside the U.S.
This led to serious adverse reactions, including graft rejection, or other adverse reactions due to under- or over-exposure to tacrolimus.
TACROLIMUS (EXTENDED RELEASE) is not interchangeable or substitutable with tacrolimus immediate-release products or other tacrolimus extended-release products.
Instruct patients and caregivers to recognize the appearance of TACROLIMUS (EXTENDED RELEASE) tablet.
TACROLIMUS (EXTENDED RELEASE) caused new onset diabetes after transplant (NODAT) in kidney transplant patients, which may be reversible in some patients.
African-American and Hispanic kidney transplant patients are at an increased risk.
Monitor blood glucose concentrations and treat appropriately.
TACROLIMUS (EXTENDED RELEASE), like other calcineurin-inhibitors, can cause acute or chronic nephrotoxicity.
Consider dosage reduction in patients with elevated serum creatinine and tacrolimus whole blood trough concentrations greater than the recommended range.
The risk for nephrotoxicity may increase when TACROLIMUS (EXTENDED RELEASE) is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors).
Monitor renal function and consider dosage reduction if nephrotoxicity occurs.
TACROLIMUS (EXTENDED RELEASE) may cause a spectrum of neurotoxicities.
The most severe neurotoxicities include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremors, paresthesias, headache, mental status changes, and changes in motor and sensory functions.
As symptoms may be associated with tacrolimus whole blood trough concentrations at or above the recommended range, monitor for neurologic symptoms and consider dosage reduction or discontinuation of TACROLIMUS (EXTENDED RELEASE) if neurotoxicity occurs.
Mild to severe hyperkalemia, which may require treatment, has been reported with tacrolimus including TACROLIMUS (EXTENDED RELEASE).
Concomitant use of agents associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) may increase the risk for hyperkalemia.
Monitor serum potassium levels periodically during treatment.
Hypertension is a common adverse reaction of TACROLIMUS (EXTENDED RELEASE) therapy and may require antihypertensive therapy.
Some antihypertensive drugs can increase the risk for hyperkalemia.
Calcium-channel blocking agents may increase tacrolimus blood concentrations and require dosage reduction of TACROLIMUS (EXTENDED RELEASE).
The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection.
In contrast, the concomitant use of strong CYP3A inhibitors may decrease the metabolism of tacrolimus, leading to higher whole blood trough concentrations and greater risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).
Therefore, adjust TACROLIMUS (EXTENDED RELEASE) dose and monitor tacrolimus whole blood trough concentrations when coadministering TACROLIMUS (EXTENDED RELEASE) with strong CYP3A inhibitors (e.g., telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) or strong CYP3A inducers (e.g., rifampin, rifabutin).
TACROLIMUS (EXTENDED RELEASE) may prolong the QT/QTc interval and cause Torsade de Pointes.
Avoid TACROLIMUS (EXTENDED RELEASE) in patients with congenital long QT syndrome.
Consider obtaining electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia).
When coadministering TACROLIMUS (EXTENDED RELEASE) with other substrates and/or inhibitors of CYP3A, a reduction in ENVARSUS XR dosage, monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended.
Whenever possible, administer the complete complement of vaccines before transplantation and treatment with TACROLIMUS (EXTENDED RELEASE).
Avoid the use of live attenuated vaccines during treatment with TACROLIMUS (EXTENDED RELEASE) (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines).
Inactivated vaccines noted to be safe for administration after transplantation may not be sufficiently immunogenic during treatment with TACROLIMUS (EXTENDED RELEASE).
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus.
All of these patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA.
A mechanism for tacrolimus-induced PRCA has not been elucidated. If PRCA is diagnosed, consider discontinuation of TACROLIMUS (EXTENDED RELEASE).
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 addition, the clinical studies were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below.
In an open label, randomized, multinational conversion study, stable kidney transplant patients on a tacrolimus immediate-release product and concomitant immunosuppressants were randomized to treatment with TACROLIMUS (EXTENDED RELEASE) (N=162) or to continued treatment on the tacrolimus immediate-release product (N=162) and treated for a duration of 12 months.
The proportion of patients who discontinued treatment due to adverse reactions was 7.4% and 1.2% in the ENVARSUS XR and tacrolimus immediate-release treatment groups, respectively, through 12 months of treatment.
The most common adverse reactions leading to discontinuation of study drug in the TACROLIMUS (EXTENDED RELEASE) treatment group was cardiac arrest (2 events).
The overall incidence of infections, serious infections, and infections with identified etiology reported in stable kidney transplant recipients treated with TACROLIMUS (EXTENDED RELEASE) or tacrolimus immediate-release product are shown in TABLE 1. Percentage of Stable Patients with Infections Through One Year Post- Treatment in the Conversion Study (a)
This image is provided by the National Library of Medicine.
(a) The stable kidney transplant study was not designed to support comparative claims of TACROLIMUS (EXTENDED RELEASE) compared to tacrolimus immediate-release product for the adverse reactions reported in this table.
(b) BK virus associated nephropathy (BKVAN) occurred in 1.2% (2/162) and 0.6% (1/162) in the TACROLIMUS (EXTENDED RELEASE) and tacrolimus immediate-release treatment groups, respectively.
New onset diabetes after transplantation (NODAT) was defined by the composite occurrence of fasting plasma glucose values ≥126 mg/dL, 2-hour postprandial plasma glucose of at least 200 mg/dL (in oral glucose tolerance test) on 2 or more consecutive occasions post baseline, insulin requirement for ≥31 days, an oral hypoglycemic agent use ≥31 days, or HbA1c ≥6.5% (at least 3 months after randomization) among kidney transplant patients with no medical history of diabetes.
The incidence of NODAT for the stable kidney transplant study through one year post-transplant is summarized in TABLE 2 below.
This image is provided by the National Library of Medicine.
The incidence of adverse reactions that occurred in ≥5% of TACROLIMUS (EXTENDED RELEASE)-treated patients compared to tacrolimus immediate-release product through one year of treatment in the conversion study is shown by treatment group in TABLE 3.
This image is provided by the National Library of Medicine
The following adverse reactions have been reported from marketing experience with tacrolimus in the U.S. and outside the U.S.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Agranulocytosis, decreased blood fibrinogen, disseminated intravascular coagulation, hemolytic anemia, hemolytic uremic syndrome, pancytopenia, prolonged activated partial thromboplastin time, pure red llation, atrial flutter, cardiac arrhythmia, cardiac arrest, electrocardiogram T wave abnormal, flushing, myocardial hypertrophy, myocardial infarction, myocardial ischaemia, pericardial effusion, QT prolongation, supraventricular extrasystoles, supraventricular tachycardia, Torsade de Pointes, deep limb venous thrombosis, ventricular fibrillation.
Ear Disorders: Hearing loss including deafness.
Eye Disorders: Blindness, photophobia, optic atrophy.
Gastrointestinal Disorders: Colitis, dysphagia, gastrointestinal perforation, impaired gastric emptying, intestinal obstruction, mouth ulceration, peritonitis, stomach ulcer.
Hepatobiliary Disorders: Bile duct stenosis, cholangitis, cirrhosis, fatty liver, hepatic cytolysis, hepatic failure, hepatic necrosis, hepatic steatosis, jaundice, hemorrhagic pancreatitis, necrotizing pancreatitis, venoocclusive liver disease.
Hypersensitivity Reactions: Hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.
Immune System Disorders: Graft versus host disease (acute and chronic).
Metabolism and Nutrition Disorders: Glycosuria, increased amylase, pancreatitis.
Musculoskeletal and Connective Tissue Disorders: Myalgia, polyarthritis, rhabdomyolysis.
Neoplasms: Lymphoma including EBV-associated lymphoproliferative disorder, PTLD, leukemia.
Nervous System Disorders: Carpal tunnel syndrome, cerebral infarction, coma, dysarthria, flaccid paralysis, hemiparesis, mental disorder, mutism, nerve compression, posterior reversible encephalopathy syndrome (PRES), progressive multifocal leukoencephalopathy (PML) sometimes fatal, quadriplegia, speech disorder, status epilepticus, syncope.
Renal and Urinary Disorder: Acute renal failure, hemorrhagic cystitis, hemolytic uremic syndrome, micturition disorder.
Respiratory, Thoracic and Mediastinal Disorders: Acute respiratory distress syndrome, interstitial lung disease,lung infiltration, pulmonary hypertension, respiratory distress, respiratory failure.
Skin and Subcutaneous Tissue Disorders: Hyperpigmentation, photosensitivity.
When TACROLIMUS (EXTENDED RELEASE) is prescribed with a given dose of mycophenolic acid (MPA) product, exposure to MPA is higher with TACROLIMUS (EXTENDED RELEASE) coadministration than with cyclosporine coadministration because cyclosporine interrupts the enterohepatic recirculation of MPA while tacrolimus does not.
Monitor for MPA associated adverse reactions and reduce the dose of concomitantly administered mycophenolic acid products as needed.
This image is provided by the National Library of Medicine.
Pregnancy Category (FDA): C
There are no adequate and well-controlled studies in pregnant women.
Tacrolimus is transferred across the placenta.
The use of tacrolimus during pregnancy in humans has been associated with neonatal hyperkalemia and renal dysfunction.
Tacrolimus given orally to pregnant rabbits at 0.7 times the maximum clinical dose and pregnant rats at 1.1 times the maximum clinical dose was associated with an increased incidence of fetal death in utero, fetal malformations (cardiovascular, skeletal, omphalocele, and gallbladder agenesis) and maternal toxicity.
TACROLIMUS (EXTENDED RELEASE) should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
In pregnant rabbits, tacrolimus at oral doses of 0.32 and 1.0 mg/kg (0.7 and 2.3 times the maximum clinical dose based on body surface area, respectively) was associated with maternal toxicity as well as an increased incidence of abortions.
At the 1 mg/kg dose, fetal rabbits showed an increased incidence of malformations (ventricular hypoplasia, interventricular septal defect, bulbous aortic arch, stenosis of ductus arteriosis, interrupted ossification of vertebral arch, vertebral and rib malformations, omphalocele, and gallbladder agenesis) and developmental variations.
In pregnant rats, tacrolimus at oral doses of 3.2 mg/kg (3.7 times the maximum clinical dose) was associated with maternal toxicity, an increase in late resorptions, decreased numbers of live births, and decreased pup weight and viability.
Tacrolimus, given orally to pregnant rats after organogenesis and during lactation at 1.0 and 3.2 mg/kg (1.2 and 3.7 times the maximum recommended clinical dose, respectively) was associated with reduced pup weights and pup viability (3.2 mg/kg only); among the high dose pups that died early, an increased incidence of kidney hydronephrosis was observed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tacrolimus (extended release) in women who are pregnant.
There is no FDA guidance on use of Tacrolimus (extended release) during labor and delivery.
Tacrolimus is present in breast milk. Because of the potential for serious adverse drug reactions in nursing infants from TACROLIMUS (EXTENDED RELEASE)e su end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
There is no FDA guidance on the use of Tacrolimus (extended release) with respect to specific gender populations.
African-American patients may need to be titrated to higher TACROLIMUS (EXTENDED RELEASE) dosages to attain comparable trough concentrations compared to Caucasian patients.
The pharmacokinetics of tacrolimus in patients with renal impairment was similar to that in healthy subjects with normal renal function.
However, due to its potential for nephrotoxicity, monitoring of renal function in patients with renal impairment is recommended; tacrolimus dosage should be reduced if indicated.
The mean clearance of tacrolimus was substantially lower in patients with severe hepatic impairment (mean Child-Pugh score: >10) compared to healthy subjects with normal hepatic function.
With greater tacrolimus whole blood trough concentrations in patients with severe hepatic impairment, there is a greater risk of adverse reactions and dosage reduction is recommended.
For patients with moderate hepatic impairment, monitor tacrolimus whole blood trough concentrations.
For patients with mild hepatic impairment, no dosage adjustments are needed.
There is no FDA guidance on the use of Tacrolimus (extended release) in women of reproductive potentials and males.
There is no FDA guidance one the use of Tacrolimus (extended release) in patients who are immunocompromised.
Take TACROLIMUS (EXTENDED RELEASE) on an empty stomach at the same time of the day, preferably in the morning (to ensure consistent and maximum possible drug exposure).
Swallow TACROLIMUS (EXTENDED RELEASE) whole with fluid (preferably water); do not chew, divide, or crush the tablets.
If a dose is missed, take it as soon as possible within 15 hours after missing the dose; beyond the 15-hour time frame, wait until the usual scheduled time to take the next regular daily dose. Do not double the next dose.
Avoid eating grapefruit or drinking grapefruit juice or alcoholic beverage while taking TACROLIMUS (EXTENDED RELEASE).
African-American patients, compared to Caucasian patients, may need to be titrated to higher TACROLIMUS (EXTENDED RELEASE) dosages to attain comparable trough concentrations.
Measure tacrolimus whole blood trough concentrations at least two times on separate days during the first week after initiation of dosing and after any change in dosage, after a change in co-administration of CYP3A inducers and/or inhibitors, or after a change in renal or hepatic function.
When interpreting measured concentrations, consider that the time to achieve tacrolimus steady state is approximately 7 days after initiating or changing the TACROLIMUS (EXTENDED RELEASE) dose.
Monitor tacrolimus whole blood trough concentrations using a validated assay [e.g., immunoassays or high-performance liquid chromatography with tandem mass spectrometric detection (HPLC/MS/MS)].
The immunosuppressive activity of tacrolimus is mainly due to the parent drug rather than to its metabolites.
Immunoassays may react with metabolites as well as the parent drug.
Therefore, whole blood tacrolimus trough concentrations obtained with immunoassays may be numerically higher than concentrations obtained with an assay using HPLC/MS/MS.
Comparison of the whole blood tacrolimus trough concentrations of patients to those described in the prescribing information and other published literature must be made with knowledge of the assay method(s) employed.
There is limited information regarding the compatibility of Tacrolimus (extended release) and IV administrations.
Postmarketing cases of overdose with tacrolimus have been reported. Overdosage adverse reactions included: Nervous system disorders (tremor, headache, confusional state, balance disorders, encephalopathy, lethargy and somnolence). Gastrointestinal disturbances (nausea, vomiting, and diarrhea). Abnormal renal function (increased blood urea nitrogen and elevated serum creatinine). Urticaria. Hypertension. Peripheral edema, and, Infections [one fatal postmarketing case of bilateral pneumopathy and CMV infection was attributed to tacrolimus (extended-release capsules) overdose].
Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus is not dialyzable to any significant extent; there is no experience with charcoal hemoperfusion.
The oral use of activated charcoal has been reported in treating acute overdoses, but experience has not been sufficient to warrant recommending its use.
General supportive measures and treatment of specific symptoms should be followed in all cases of overdosage.
Tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin (an ubiquitous mammalian intracellular enzyme) is then formed and the phosphatase activity of calcineurin inhibited.
Such inhibition prevents the dephosphorylation and translocation of various factors such as the nuclear factor of activated T-cells (NF-AT) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB).
Tacrolimus inhibits the expression and/or production of several cytokines that include interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor.
Tacrolimus also inhibits IL-2 receptor expression and nitric oxide release, induces apoptosis and production of transforming growth factor-beta that can lead to immunosuppressive activity.
The net result is the inhibition of T-lymphocyte activation and proliferation as well as T-helper-cell-dependent B-cell response (i.e., immunosuppression).
TACROLIMUS (EXTENDED RELEASE), a calcineurin-inhibitor immunosuppressant, is available for oral administration as extended-release tablets containing the equivalent of 0.75 mg, 1 mg, or 4 mg of anhydrous tacrolimus USP.
Inactive ingredients include hypromellose USP, lactose monohydrate NF, polyethylene glycol NF, poloxamer NF, magnesium stearate NF, tartaric acid NF, butylated hydroxytoluene NF, and dimethicone NF.
Tacrolimus is the active ingredient in TACROLIMUS (EXTENDED RELEASE).
Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis.
The chemical structure of tacrolimus is:
This image is provided by the National Library of Medicine
Tacrolimus has an empirical formula of C44H69NO12•H2O and a formula weight of 822.03.
Tacrolimus appears as white crystals or crystalline powder.
It is practically insoluble in water, freely soluble in ethanol, and very soluble in methanol and chloroform.
There is limited information regarding Tacrolimus (extended release) Pharmacodynamics in the drug label.
Table below summarizes the pharmacokinetic (PK) parameters of tacrolimus following oral administration of once-daily TACROLIMUS (EXTENDED RELEASE) in healthy subjects and in kidney transplant patients, under fasted conditions.
Whole blood tacrolimus concentrations in the pharmacokinetic studies were measured using validated HPLC/MS/MS assays.
This image is provided by the National Library of Medicine
In adult kidney transplant patients ≥ 6 months post-transplant switched to TACROLIMUS (EXTENDED RELEASE) at 67% to 80% of the daily dose of tacrolimus immediate-release capsules, the steady state tacrolimus exposures (AUC24) and tacrolimus trough concentrations (C24) were comparable to the AUC24 and C24 measured prior to the switch.
However, the mean Cmax estimate was 30% lower and the median Tmax was more prolonged (6 hours versus 2 hours) following administration of TACROLIMUS (EXTENDED RELEASE) as compared to that of tacrolimus immediate-release capsules.
Absorption of tacrolimus from the gastrointestinal tract after oral administration is incomplete and variable.
In healthy subjects, the oral bioavailability of TACROLIMUS (EXTENDED RELEASE) was approximately 50% higher as compared with both tacrolimus immediate-release and extended-release formulations at steady state.
In healthy subjects who received single TACROLIMUS (EXTENDED RELEASE) doses ranging from 5 mg to 10 mg, the mean AUC and C24 of tacrolimus increased linearly and the elimination half-life did not change with increasing doses.
The presence of a meal affects the absorption of tacrolimus; the rateowing a high-fat breakfast reduced the systemic exposure (AUC) to tacrolimus by approximately 55% and the peak plasma concentration of tacrolimus (Cmax) by 22%, with no effect on the time to reach maximum plasma concentration (Tmax), compared to when TACROLIMUS (EXTENDED RELEASE) was administered under fasted conditions.
In 26 healthy subjects, administration of TACROLIMUS (EXTENDED RELEASE) tablets in the evening resulted in a 15% loweug concentration, and plasma protein concentration.
In a U.S. trial in which tacrolimus was administered as immediate-release formulation, the ratio of whole blood concentration to plasma concentration averaged 35 (range 12 to 67).
The desired pharmacological activity of tacrolimus is primarily due to the parent drug.
Tacrolimus is extensively metabolized by the mixed-function oxidase system, primarily the cytochrome P-450 system 3A (CYP3A).
A metabolic pathway leading to the formation of 8 possible metabolites has been proposed.
Demethylation and hydroxylation were identified as the primary mechanisms of biotransformation in vitro.
The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus.
In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.
In a mass balance study of orally administered rimination accounted for 2.3 ± 1.1% of the total radiolabel administered.
The elimination halEXTENDED RELEASE).
Tacrolimus pharmacokinetics following a single administration of tacrolimus (administered as a continuous IV infusion) were determined in 12 patients (7 not on dialysis and 5 on dialysis, serum creatinine of 3.9±1.6 and 12.0±2.4 mg/dL, respectively) prior to their kidney transplant.
The mean clearance of tacrolimus in patients with renal dysfunction given IV tacrolimus was similar to that in healthy subjects given tacrolimus IV and in healthy subjects given oral tacrolimus immediate-release.
Tacrolimus pharmacokinetics have been determined in 6 patients with mild hepatic impairment (mean Pugh score: 6.2) following single oral administration of tacrolimus immediate-release.
The mean clearance of tacrolimus in patients with mild hepatic impairment was not substantially different from that in healthy subjects.
Tacrolimus pharmacokinetics were studied in 6 patients with severe hepatic impairment (mean Pugh score: >10).
The mean clearance was substantially lower in patients with severe hepatic impairment.
The pharmacokinetics of tacrolimus was studied following single oral administration of tacrolimus immediate-release (5 mg) in 10 African-American, 12 Latino-American, and 12 Caucasian healthy subjects: The mean (±SD) tacrolimus Cmax in African-Americans (23.6±12.1 ng/mL) was lower than in Caucasians (40.2±12.6 ng/mL) and Latino-Americans (36.2±15.8 ng/mL). Mean AUC0-inf tended to be lower in African-Americans (203±115 ng•hr/mL) than Caucasians (344±186 ng•hr/mL) and Latino-Americans (274±150 ng•hr/mL). The mean (±SD) absolute oral bioavailability (F) in African-Americans (12±4.5%) and Lnd/or atimes the AUC at the maximum clinical dose of 0.14 mg/kg/day) and in the rat was 5.0 mg/kg/day (0.24 times the AUC at the maximum clinical dose of 0.14 mg/kg/day).
A 104-week dermal carcinogenicity study was performed in mice with tacrolimus ointment (0.03%-3%), equivalent to tacrolimus doses of 1.1-118 mg/kg/day or 3.3-354 mg/m2/day.
In the study, the incidence of skin tumors was minimal and the topical application of tacrolimus was not associated with skin tumor formation under ambient room lighting.
However, a statistically significant elevation in the incidence of pleomorphic lymphoma in high-dose male (25/50) and female animals (27/50) and in the incidence of undifferentiated lymphoma in high-dose female animals (13/50) was noted in the mouse dermal carcinogenicity study.
Lymphomas were noted in the mouse dermal carcinogenicity study at a daily dose of 3.5 mg/kg (0.1% tacrolimus ointment; 2.5-fold the human exposure in stable adult renal transplant patients converted from tacrolimus immediate-release product to TACROLIMUS (EXTENDED RELEASE).
No drug-related tumors were noted in the mouse dermal carcinogenicity study at a daily dose of 1.1 mg/kg (0.03% tacrolimus ointment).
The relevance of topical administration of tacrolimus in the setting of systemic tacrolimus use is unknown.
The implications of these carcinogenicity studies are limited; doses of tacrolimus were administered that likely induced immunosuppression in these animals, impairing their immune system’s ability to inhibit unrelated carcinogenesis.
No evidence of genotoxicity was seen in bacterial (Salmonella and E. coli) or mammalian (Chinese hamster lung-derived cells) in vitro assays of mutagenicity, the in vitro CHO/HGPRT assay of mutagenicity, or in vivo clastogenicity assays performed in mice; tacrolimus did not cause unscheduled DNA synthesis in rodent hepatocytes.
Tacrolimus given orally at 1.0 mg/kg (1.2 times the maximum clinical dose based on body surface area) to male and female rats, prior to and during mating, as well as to dams during gestation and lactation, was associated with embryolethality and adverse effects on female reproduction.
Effects on female reproductive function (parturition) and embryolethal effects were indicated by a higher rate of pre-implantation loss and increased numbers of undelivered and nonviable pups.
When given at 3.2 mg/kg (3.7 times the maximum clinical dose based on body surface area), tacrolimus was associated with maternal and paternal toxicity as well as reproductive toxicity including marked adverse effects on estrus cycles, parturition, pup viability, and pup malformations.
The conversion study was a randomized, open-label, multinational study evaluating once daily TACROLIMUS (EXTENDED RELEASE) when used to replace tacrolimus immediate-release administered twice daily for maintenance immunosuppression to prevent acute allograft rejection in stable adult kidney transplant patients.
Patients who received a kidney transplant 3 months to 5 years before study entry and on a stable dose of tacrolimus immediate-release of at least 2 mg per day and tacrolimus whole blood trough concentrations between 4 and 15 ng/mL were randomized to 1) switch from twice daily tacrolimus immediate-release to once daily TACROLIMUS (EXTENDED RELEASE) (N=163) or 2) continue tacrolimus immediate-release twice daily (N=163).
MMF or mycophenolate sodium (MPS), or azathioprine (AZA) and/or corticosteroids were allowed as concomitant immunosuppressants during the study period according to the standard of care at the participating site.
The mean age of study population was 50 years; 67% were male; 73% were Caucasian, 22% were African-American, 2% were Asian and 3% were categorized as other races.
Living donors provided 35% of the organs and 65% of patients received a kidney transplant from a deceased donor.
Premature discontinuation from treatment at the end of one year occurred in 13% of TACROLIMUS (EXTENDED RELEASE) patients and 6% of tacrolimus immediate-release patients.
In the conversion study, stable kidney transplant patients converted to TACROLIMUS (EXTENDED RELEASE) at an average daily dose that was 80% of their tacrolimus immediate-release daily dose prior to conversion.
Mean tacrolimus whole blood trough concentrations were maintained within a relatively narrow range throughout the duration of the study for both the TACROLIMUS (EXTENDED RELEASE) conversion group and the tacrolimus immediate-release continuation group.
At Week 1 (after 7 days of stable dosing), the mean ± SD tacrolimus trough concentrations were 7.2 ± 3.1 ng/mL for the TACROLIMUS (EXTENDED RELEASE) conversion group and 7.7 ± 2.5 for the tacrolimus immediate-release continuation group; the baseline values were 7.8 ± 2.3, and 8.0 ± 2.3, respectively.
In the conversion study, the average daily mycophenolate equivalent doses were comparable between the TACROLIMUS (EXTENDED RELEASE) and tacrolimus immediate-release treatment groups.
The efficacy failure rates including patients who developed BPAR, graft failure, death, and/or lost to follow-up at 12 months, as well as the rates of the individual events, are shown by treatment group in the table for the modified intent-to-treat population.
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The mean estimated glomerular filtration rates (eGFR), using the Modification of Diet in Renal Disease 7 (MDRD7) formula, were 61.5 ml/min/1.73 m2 and 60.0 ml/min/1.73 m2 at baseline (Day 0) and 62.0 ml/min/1.73 m2 and 61.4 ml/min/1.73 m2 at 12 months in the ENVARSUS XR and tacrolimus immediate-release treatment groups, respectively.
TACROLIMUS (EXTENDED RELEASE) is supplied in round bottles: the statement ‘ONCE-DAILY’ appears on its label.
This image is provided by the National Library of Medicine
Store at 25 °C (77 °F); excursions permitted to 15 °C-30 °C (59 °F-86 °F) [see USP Controlled Room Temperature].
{{#ask: Page Name::Tacrolimus (extended release)
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This image is provided by the National Library of Medicine
This image is provided by the National Library of Medicine
This image is provided by the National Library of Medicine
This image is provided by the National Library of Medicine
This image is provided by the National Library of Medicine
This image is provided by the National Library of Medicine
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Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Advise patients to:
Inspect their TACROLIMUS (EXTENDED RELEASE) medicine when they receive a new prescription and before taking it. If the appearance of the tablet is not the same as usual, or if dosage instructions have changed, advise patients to contact their healthcare provider as soon as possible to make sure that you have the right medicine. Other tacrolimus products cannot be substituted for TACROLIMUS (EXTENDED RELEASE).
Take once-daily TACROLIMUS (EXTENDED RELEASE) at the same time every day (preferably in the morning) on an empty stomach to ensure consistent and maximum possible drug concentrations in the blood.
Swallow tablet whole with liquid, preferably water. Do not chew, divide or crush tablet.
Avoid alcohol, grapefruit, and grapefruit juice while on TACROLIMUS (EXTENDED RELEASE).
Take a missed dose as soon as possible but not more than 15 hours after the scheduled time. Beyond the 14-hour timeframe, instruct the patient to wait until the usual scheduled time the following morning to take the next regularly scheduled dose. Do not take two doses at the same time.
Inform patients that they are at an increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression.
Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use a sunscreen with a high protection factor.
Inform patients that they are at an increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection.
Inform patients that TACROLIMUS (EXTENDED RELEASE) can cause diabetes mellitus and should be adviss that TACROLIMUS (EXTENDED RELEASE) can have toxic effects on the kidney that should be monfomor.
Advise patients to contact their physician should they develop vision changes, delirium, or tremors.
Inform patients that TACROLIMUS (EXTENDED RELEASE) can cause hyperkalemia.
Monitoring of potassium levels may be necessary, especially with concomitant use of other drugs known to cause hyperkalemia.
Inform patients that TACROLIMUS (EXTENDED RELEASE) can cause high blood pressure which may require treatment with anti-hypertensive therapy.
Instruct patients to tell their health care providers when they start or stop taking any concomitant medications, including prescription and non-prescription medicines, herbal and dietary supplements.
Some medications could alter tacrolimus concentrations in the blood and thus may require adjustment of the dosage of TACROLIMUS (EXTENDED RELEASE). Avoid alcohol, grapefruit.
Inform patients that TACROLIMUS (EXTENDED RELEASE) can interfere with the usual response to immunizations and that they should avoid live vaccines.
Alcohol-Tacrolimus (extended release) interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Envarsus XR
There is limited information regarding Tacrolimus (extended release) Look-Alike Drug Names in the drug label.
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Blood_glucose | Blood sugar is a term used to refer to the amount of glucose in the blood. Glucose, transported via the bloodstream, is the primary source of energy for the body's cells.
Blood sugar concentration, or glucose level, is tightly regulated in the human body. Normally, the blood glucose level is maintained between about 4 and 8 mmol/L (70 to 150 mg/dL). The total amount of glucose in the circulating blood is therefore about 3.3 to 7g (assuming an ordinary adult blood volume of 5 liters). Glucose levels rise after meals and are usually lowest in the morning, before the first meal of the day.
Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) blood sugar. Diabetes mellitus, characterized by persistent hyperglycemia of several causes, is the most prominent disease related to failure of blood sugar regulation.
Though it is called "blood sugar" and sugars besides glucose are found in the blood, like fructose and galactose, only glucose levels are regulated via insulin and glucagon.
Glucose can be measured in whole blood, serum, or plasma. Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report the serum glucose levels. Because RBC (erythrocytes) have a higher concentration of protein (i.e. hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiply the value by 1.15 to give the serum/plasma level.
Collection of blood in clot (red-top) tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells until separated by centrifugation. Higher than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifugation and separation of Plasma/Serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in the blood sample. At room temperature (25°C), a loss of 1 to 2% of glucose per hour should be expected. The loss of glucose levels in aforementioned conditions can be prevented by using Fluoride top (gray-top) as the anticoagulant of choice upon blood collection, as Fluoride inhibits glycolysis. However, this should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples once they have been centrifugated to isolate the serum from cells, this tube would be the most efficient. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, to prevent contamination of the sample with intravenous fluids (IV). Alternatively, blood can be drawn from the same arm with an IV line after the IV was turned off for at least 5 minutes and the arm is elevated to drain the infused fluids away from the vein. As little as 10% contamination with 5% dextrose (D5W) will elevate glucose in a sample by 500mg/dl or more. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual, whereas after meals venous levels are lower than capillary or arterial blood.
There are two different major methods that have been used to measure glucose. The older one is a chemical method that exploits the nonspecific reducing property of glucose in a reaction with an indicator substance that acquires or changes color on its reduction. Since other blood compounds also have reducing properties (e.g., urea, which can build up in uremic patients), this method can have erroneous measurements up to 5 to 15 mg/dl. This is solved by the Enzymatic methods that are highly specific for glucose. The two most common employed enzymes are glucose oxidase and hexokinase.
Fasting Blood Sugar or Glucose test (FBS)
Urine Glucose test
Two-hr Postprandial Blood Sugar Test (2-h PPBS)
Oral Glucose Tolerance test (OGTT)
Intravenous Glucose Tolerance test (IVGTT)
Glycosylated Hemoglobin (HbA1C)
Self-monitoring of Glucose level via Home Kits
The fasting blood glucose (FBG) level is the most commonly used indication of overall glucose homeostasis. Conditions that affect glucose levels are shown in the table below. They reflect abnormalities in the multiple control mechanism of glucose regulation.
The metabolic response to a carbohydrate challenge is conveniently assessed by the postprandial glucose level drawn 2 hours after a meal or a glucose load. In addition, the glucose tolerance test, consisting of serial timed measurements after a standardized amount of oral glucose intake, is used to aid in the diagnosis of Diabetes.
If blood sugar levels drop too low, a potentially fatal condition called hypoglycemia develops. Symptoms may include lethargy, impaired mental functioning, irritability, and loss of consciousness.
If levels remain too high, appetite is suppressed over the short term. Long-term hyperglycemia causes many of the long-term health problems associated with diabetes, including eye, kidney, and nerve damage.
Some people report drowsiness or impvide with 0.055).
John Bernard Henry, M.D.: Clinical diagnosis and Management by Laboratory Methods 20th edition, Saunders, Philadelphia, PA, 2001.
Ronald A. Sacher and Richard A. McPherson: Widmann's Clinical Interpretation of Laboratory Tests 11th edition, F.A. Davis Company, 2001.
Other medical conversions (Albumin, Protein, Creatinine, Creatinine clearance, Cholesterol, Lipid profile, Insulin, Etc..)
Lab Tests Online: Glucose
Alcohol and Blood Sugar |
Limb_Development | Human embryo at six weeks gestational age
9-Week Human Embryo from Ectopic Pregnancy
The vertebrate limb arises out of a general morphogenetic area called aduce the muscle components. The lateral plate mesodermal cells express FGF10 and induce the apical ectodermal ridge (AER) cells to express FGF8 and FGF4 which maintains the FGF10 signal and proliferation in the mesoderm. The position of FGF10 expression is regulated by Wnt8c in the hindlimb and Wnt2b in the forelimb. The forelimb and the hindlimb are specified by their position along the anterior/posterior axis and possibly by two T-box containing transcription factors: Tbx5 and Tbx4 respectively.
Programmed cell death removes the spaces between the digits and joints. BMP signaling induces cell death and Noggin block cell death in the digits.
The limb is made up of three sections: stylopod, zeugopod, and autopod (in order from proximal to distal). Hox genes contribute to the specification of these segments. Mutations in Hox genes lead to proximal/distal losses or abnormalities. There are two competing models for explaining the patterning of these sections.
The AER creates a zone of cell proliferation and lays down the limb from proximal to distal. The time cells leave the AER determines their positional value. Proximal structures are formed earlier than distal structures.
The Progress Zone Model was proposed 30 years ago but recent evidence has conflicted with this model.
Experimental evidence:
Removing the AER at a later period of development results in less disruption of distal structures than if the AER was removed early in development.
Grafting a new bud tip on top of an old bud tip results in a deletion and duplication of structures.
Cells are specified for each segment in the early limb bud and this population of cells expand out as the limb bud grows. This model is consistent with the following cent to the AER when removed--cell death removes some patterning. FGF beads are able to rescue limb development by preventing cell death.
Experimental evidence:
Labeled cells in different position of an early limb bud were restricted to single segments of the limb.
Limbs lacking expression of required FGF4 & FGF8 showed all structures of the limb and not just the proximal parts.
The Zone of Polarizing Activity (ZPA) in the limb bud has pattern-organizing activity by action of a morphogen gradient of Sonic hedgehog (Shh). Shh is both sufficient and necessary to create the ZPA and specify the anterior/posterior pattern in the distal limb (Shh is not necessary for the polarity of the stylopod). Shh is turned on in the posterior through the early expression of Hoxd genes, the expression of Hoxb8, and the expression dHAND. Shh is maintained in the posterior though a feedback loop between the ZPA and the AER. Shh induces the AER to produce FGF4 and FGF8 which maintains the expression of Shh.
Digits 3,4 and 5 are specified by a temporal gradient of Shh. Digit 2 is specified by a long-range diffusible form of Shh and Digit 1 does not require Shh. Shh cleaves the Ci/Gli3 transcriptional repressor complex to convert the transcription factor Gli3 to an activator which activates the transcription of HoxD genes along the anterior/posterior axis. Loss of the Gli3 repressor leads to the formation of generic (unpatterned) digits in extra quantities.
Dorsal/Ventral Patterning arises from Wnt7a signals in the overlying ectoderm not the mesoderm. Wnt7a is both necessary and sufficient to dorsalize the limb. Wnt7a also influences the anterior/posterior axis and loss of Wnt7a causes the dorsal side of limbs to become ventral sides and causes missing posterior digits. Replacing Wnt7a signals rescues this defect. Wnt7a is also required to maintain expression of Shh.
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Suprarenal_vein | The Suprarenal Veins are two in number:
the right ends in the inferior vena cava.
the left ends in the left renal or left inferior phrenic vein.
They receive blood from the adrenal glands and will sometimes form anastomoses with the inferior phrenic veins.
, , Diagram showing completion of development of the parietal veins.
, , Suprarenal glands viewed from the front.
, , Suprarenal glands viewed from behind.
Template:SUNYAnatomyLabs - "Posterior Abdominal Wall: Blood Supply to the Suprarenal Glands"
Template:Dorlands - left
Template:Dorlands - right
Template:Gray's
Template:Veins
Template:WikiDoc Sources
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Dermoid_cyst_classification | Dermoid cysts may be classified according to the mode of occurrence into congenital and aquired types. Dermoid cysts may also be classified into several subtypes based on the anatomical location.
Dermoid cysts may be classified according to the mode of occurrence into: Congenital, Acquired
Dermoid cysts may also be classified into several subtypes based on the anatomical location: Ovarian dermoid cyst, Periorbital dermoid cyst, Spinal dermoid cyst, Intracranial dermoid cyst, Dermoid cysts of the floor of the mouth, Sublingual (median genio-glossal), Submental (median geniohyoid), Submandibular |
Palmar_plantar_erythrodysesthesia_CT_scan | There are no CT scan findings associated with palmar plantar erythrodysesthesia
There are no CT scan findings associated with palmar plantar erythrodysesthesia.
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Immunoproliferative_neoplasm | Immunoproliferative disorders are disorders of the immune system that are characterized by the abnormal proliferation of the primary cells of the immune system, which includes B cells, T cells and Natural Killer (NK) cells, or by the excessive production of immunoglobulins (also known as antibodies). These disorders are subdivided into three main classes, which are lymphoproliferative disorders, hypergammaglobulinemia, and paraproteinemia [5].
Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocyes are B cells and T cells, which are derived from pleuripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to developing a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders, however there are also acquired and Iatrogenic causes [14]
X-linked Lymphoproliferative disorder: There is a mutation on the X chromosome that has been found to be associated with a T and NK cell lymphoproliferative disorder. The mutation is on the long arm of the chromosome, at position 25, which is denoted as Xq25. At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called SLAM-associated protein (SAP).
The term SH2 domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. These domains are present in many signaling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity [1]
The SAP protein is important in the signaling events that activate T and NK cells because it functions as an intracellular adapter that transduces T and NK cell activation. Normally, the SAP protein is expressed in the cytoplasm of T and NK cells, where it binds to the cytoplasmic domain of the surface receptor called Signaling Lymphocyte Activation Molecule (SLAM). This binding initiates a signal transduction pathway, which results in the modulation of IFN-γ. A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, which means it is unable to bind to the SLAM molecule, leading to a lack of modulation of IFN-γ, causing uncontrolled cell proliferation.
Strangely, in boys with X-linked lymphoproliferative disorder there is an overwhelming T-cell mediated response to the Epstein-Barr Virus (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined [14]
Autosomal Lymphoproliferative Disorder: Some children with autoimmune lymphoproliferative disorders are heterozygous for a mutation in the gene that codes for the Fas receptor. Which is located on the long arm of chromosome 10 at position 24.1, denoted 10q24.1 [2]. This gene is member 6 of the TNF-receptor superfamily (TNFSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in apoptosis of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens [1]. As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by Fas receptor, leading to a primitive population of T cells that proliferates in an uncontrolled manner [14].
Other Inherited Causes: Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with EBV infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma. Children with common variable immune deficiency (CVID) are also at a higher risk of developing a lymphoproliferative disorder. Some disorders that predispose a person to lymphoproliferative disorders are severe combined immuno deficiency (SCID), Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome (an X-linked recessive disorder) and Ataxia telar this still have an increased risk of developing a lymphoproliferative disorder [14].
Acquired Causes: Viral infection is a very common cause of lymphoproliferative disorders. The most common is congenial HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders [14].
Iratogenic causes: There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders, however some T cell variations have been described [14]. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus or cyclosporine A [14].
Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglobulin in the blood serum [5]. The name of the disorder refers to the position of the excess of proteins after serum protein electrophoresis (found in the gammaglobulin region). Most hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), because this is the default immunoglobulin type prior to class switching. Some types or hypergammagloinke Tumor Necrosis Factor Super Family memberoted Xq26 [10]. Normally, CD40 ligand is expressed on activated T cells, and is necessary to induce immunoglobulin class switching from IgM to the other immunoglobulin types. It doesgand, and thus the T cells do not induce Ig class switching in B cells, so there are markedly reduced levels of IgG, IgA, and IgE, but ha |
Hepatocellular_carcinoma_primary_prevention | Hepatitis B vaccine is recommended for all children to prevent the development of hepatitis B, which is a major risk factor for hepatocellular carcinoma. Other primary prevention strategies include abstinence from alcohol, avoidance of hepatotoxic drugs, physical exercise, smoking cessation, adequate calorie intake, high doses of certain supplements (vitamin A, copper and iron), screening for wilson's disease and hemochromatosis. Adequate caloric intake, physical activity, prevention of high risk behaviors, screening of blood products may play an important role in primary prevention.
Hepatocellular carcinoma can be prevented by:
Vaccination for Hepatitis B, Alcohol cessation, especially in cirrhotic patients, Avoidance of hepatotoxic drugs, Physical exercise, Smoking cessation, Adequate caloric intake, Avoid excessive consumption of: Vitamin A, Copper, Iron, Education about hepatotoxins such as acetaminophen, Prevention of obesity, Screening of blood donors for Hepatitis B, Hepatitis C, Familial screening for Wilson's disease, hemochromatosis, Reduction of high-risk behaviors such as : Unpr |
Galactosemia_pathophysiology | se.
Abnormalities in any of the enzymes involved in each of the steps of the Leloir pathway can give rise to the pathological condition called galactosemia.
Deficiency or reduced activity of galactose-1-phosphate uridyl transferase enzyme leads to accumulation of galactose-1-phosphate which: Sequesters phosphate essential for energy production in the human body , Inhibits enzymes involved in glucose metabolism, such as pyrophosphorylase , Inhibits galactosyl trasnferase thereby leading to defects in glycosylation
Galactokinase deficiency results in accumulation of galactose which gets converted to galactitol by a minor pathway. This molecule predisposes to cataract by causing: Swelling of the lens, Denaturation of the proteins, Rupture of cell membranes
Epimerase deficiency results in increased UDP-galactose and suppressed UDP-glucose with the ratio changing with the galactose concentration. This can have affects on the glycoprotein and glycolipid synthesis.
Galactose mutarotase enzyme deficiency results in galactose not being able to enter the Le |
Caecitis | mation of the caecum (part of the small intestine) that may be associated with infection.
The condition is usually caused by gram negative enteric commensal bacteria of the gut (gut flora). The most common agent associated with the condition is Pseudomonas aeruginosa.
Caecitis affects immunocompromised patients, such as those undergoing chemotherapy, patients with AIDS, kidney transplant patients, or the elderly.
Signs and symptoms of caecitis include a distended abdomen, fever, chills, nausea, vomiting, abdominal pain and tenderness, and diarrhea.
Inflammation can spread to other parts of the gut in patients with caecitis.
The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis. The mortality rate for caecitis can be as high as 40 to 50%, mostly because it is frequently associated with bowel perforation. Caecitis is diagnosed with a radiograph CT scan showing thickening of the caecum and "fat stranding".
Colitis |
Sclerosing_encapsulating_peritonitis | Sclerosing encapsulating peritonitis (SEP) is a rare benign cause of acute or subacute small bowel obstruction. It is characterized by total or partial encasement of the small bowel within a thick fibrocollagenous membrane.
Sclerosing encapsulating peritonitis can be idiopathic or mainly secondary to chronic ambulatory peritoneal dialysis, peritoneovenous or ventriculoperitoneal shunts, or treatment with practolol.
Various abdominal disorders such as tuberculosis, sarcoidosis, familial mediterranean fever, gastrointestinal malignancy, protein S deficiency, liver transplantation, fibrogenic foreign material and luteinized ovarian thecomas are the other rare causative factors.
Sclerosing encapsulating peritonitis may be confused with congenital peritoneal encapsulation, which is characterized by a thin accessory peritoneal sac surrounding the small bowel. This asymptomtic condition is generally found incidentally during unrelated surgery and does not fit with the clinical or imaging findings in this group of patients.
Radiographs of the abdomen can show air-fluid levels similar to those in patients with any other cause of small-bowel obstruction.
In the appropriate clinical setting, recognition of the entire dilated small bowel at the center of the abdomen and encased within a thick fibrocollageneous membrane, as though it were in a cocoon, on a CT image is diagnostic of sclerosing encapsulating peritonitis.
The other imaging findings may include signs of obstruction, fixation of intestinal loops, ascites or localized fluid collections, bowel wall thickening, peritoneal or mural calcification, and reactive adenopathy.
Patient #1:
CT and gross pathological images demonstrate sclerosing encapsulating peritonitis. The patient was on long term peritoneal dialysis
Images courtesy of RadsWiki
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Horseshoe_kidney_secondary_prevention | There are no established measures for the secondary prevention of horseshoe kidney disease.
There are no established measures for the secondary prevention of horseshoe kidney disease. |
Vitreous_humor | Schematic diagram of the human eye.
The vitreous humour (British spelling) or vitreous humor (U.S. spelling) is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates. It is often referred to as the vitreous body or simply "the vitreous".
The vitreous is 99% water, but has a viscosity two to four times that of pure water, giving it a gelatinous consistency. Other components include salts, sugars, phagocytes, and a network of collagen fibres. Thus, unlike water, it has a refractive index of 1.336. The phagocytic cells in the vitreous serve to remove unwanted debris in the visual field.
Hyaluronic acid was first isolated from vitreous humour.
The primary purpose of the vitreous humour is to provide structural support to the eyeball while offering a clear unobstructed path for light to reach the retina.
The vitreous is also believed to function as a barrier to the forward diffusion of oxygen from the retinal blood supply to the anterior segment of the eye, where it can cause oxidation damage to the lens. Since the vitreous does not regenerate after being removed from the eye (a procedure known as vitrectomy, which is usually performed to allow surgical access to the posterior segment of the eye), early cataract is a frequent complication of retinal surgery.
The collagen fibres of the vitreous are held apart by electrical charges. With aging, these charges tend to reduce, and the fibres may clump together. Similarly, the gel may liquefy, a condition known as syneresis, leading to cells and other organic clusters to float freely within the vitreous humour. These commonly lead to floaters which are perceived in the visual field as spots or fibrous strands. Floaters are generally harmless, but the sudden onset of recurring floaters may signify a posterior vitreous detachment (PVD) or other diseases of the eye.
The metabolic exchange and equilibration between systemic circulation and vitreous humour is so slow that vitreous humour is sometimes the fluid of choice for postmortem analysis of glucose levels or substances which would be more rapidly diffused, degraded, excreted, or metabolised from the general circulation.
http://thebrain.mcgill.ca/flash/i/i_02/i_02_cr/i_02_cr_vis/i_02_cr_vis.html |
Bradycardia_echocardiography | There are no echocardiography/ultrasound findings associated with bradycardia
There are no echocardiography/ultrasound findings associated with bradycardia |
WOSCOPS_Trial | Treatment with pravastatin 40 mg daily in 6595 men with hypercholesterolemia resulted in a significant reduction in the incidence of fatal and non-fatal myocardial infarction and death from cardiovascular causes, without a difference in the deaths due to non-cardiovascular causes in a follow-up period of 4.9 years.
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Papaverine | Papaverine is a phosphodiesterase inhibitor that is FDA approved for the treatment of vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral vascular disease, peripheral and pulmonary embolism. Common adverse reactions include general discomfort, nausea, abdominal discomfort, anorexia, skin rash, malaise, vertigo and headache..
Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.
Dosage
Papaverine Hydrochloride may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.
Parenteral administration of papaverine hydrochloride in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.
There is limited information regarding Off-Label Guideline-Supported Use of Papaverine in adult patients.
Safety and effectiveness in children have not been established.
There is limited information regarding Off-Label Guideline-Supported Use of Papaverine in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Papaverine in pediatric patients.
Intravenous injection of papaverine is contraindicated in the presence of complete atrioventricular heart block. When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.
Papaverine Hydrochloride is not indicated for the treatment of impotence by intracorporeal injection. The intracorporeal injection of papaverine hydrochloride has been reported to have resulted in persistent priapism requiring medical and surgical intervention.
Papaverine Hydrochloride Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.
Papaverine Hydrochloride should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic hypersensitivity with gastrointestinal symptoms, jaundice, or eosinophilia becomes evident or if liver function test values become altered.
Drug dependence resulting from the abuse of many of the selective depressants, including papaverine hydrochloride, has been reported.
The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.
Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.
There is limited information regarding Postmarketing Experience of Papaverine in the drug label.
There is limited information regarding Papaverine Drug Interactions in the drug label.
Pregnancy Category (FDA): C
No teratogenic effects were observed in rats when papaverine hydrochloride was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. *Papaverine Hydrochloride should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Papaverine in women who are pregnant.
There is no FDA guidance on use of Papaverine during labor and delivery.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when papaverine hydrochloride is administered to a nursing woman.
Safety and effectiveness in children have not been established.
There is no FDA guidance on the use of Papaverine with respect to geriatric patients.
There is no FDA guidance on the use of Papaverine with respect to specific gender populations.
There is no FDA guidance on the use of Papaverine with respect to specific racial populations.
There is no FDA guidance on the use of Papaverine in patients with renal impairment.
There is no FDA guidance on the use of Papaverine in patients with hepatic impairment.
There is no FDA guidance on the use of Papaverine in women of reproductive potentials and males.
There is no FDA guidance one the use of Papaverine in patients who are immunocompromised.
Intravenously or Intramuscularly
There is limited information regarding Monitoring of Papaverine in the drug label.
There is limited information regarding IV Compatibility of Papaverine in the drug label.
The symptoms of toxicity from papaverine hydrochloride often result from vasomotor instability and include nausea, vomiting, weakness, central nervous system depression, nystagmus, diplopia, diaphoresis, flushing, dizziness, and sinus tachycardia.
In large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak calcium antagonist.
Following an oral overdose of 15 g, metabolic acidosis with hyperventilation, hyperglycemia, and hypokalemia have been reported. No information on toxic serum concentrations is available.
Following intravenous overdosing in animals, seizures, tachyarrhythmias, and ventricular fibri |
Baber%27s_syndrome | Baber's syndrome is a very rare syndrome characterized by the association of congenital liver cirrhosis with Fanconi syndrome.
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Lovaza | Lovaza al trials of LOVAZA. Safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.
There is no FDA guidance on the use of Lovaza with respect to specific gender populations.
There is no FDA guidance on the use of Lovaza with respect to specific racial populations.
There is no FDA guidance on the use of Lovaza in patients with reimited information regarding IV Compatibility of Lovaza in the drug label.
There is limited information regarding Chronic Overdose of Lovaza in the drug label.
There is limited information regarding Lovaza Pharmacology in the drug label.
The mechanism of action of LOVAZA is not completely understood. Potential mechanisms of action include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal β-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity. LOVAZA may reduce the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids.
LOVAZA, a lipid-regulating agent, is supplied as a liquid-filled gel capsule for oral administration. Each 1-gram capsule of LOVAZA contains at least 900 mg of the ethyl esters of omega-3 fatty acids sourced from fish oils. These are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg).
The empirical formula of EPA ethyl ester is C22H34O2, and the molecular weight of EPA ethyl es t |
Pneumoconiosis_pathophysiology | cticre continues, the elimination system begins to fail, leading to release of reactive oxygen species. These in turn exacerbates the inflammatory response, with the release of more cytokines, such as TNF and interleukins, which subsequently lead to fibrogenesis.
The determinants for the rate of disease progression are the accumulative dose; that is based in duration and intensity of exposure, the fiber type and individual susceptibility.
The underlying pathogenic mechanisms that lead to pulmonary fibrosis in pneumoconiosis remain unclear. Some studies in bronchoalveolar lavage made by Vanhée et al suggest a potential protective effect of TGF- β on the development of pulmonary fibrosis. The alveolar macrophages in coal mr- 1 (IGF-1), whereas, the patients with simple pneumoconiosis secreted transforming- growth factor- β (TGF- β). This suggested a potential protective effect of TGF- β against the development of pulmonary fibrosis.
The risk for pneumoconiosis among constructions workers is evident, but Tjoe et al concluded there is not a clear-cut relationship between exposure and body’s response. This is complex due to the heterogeneity in exposure levels, as well as dust composition and the possible modification of toxicity by other factors present in dust.
Shown below is an image depicting a lung affected with pneumoconiosis.
Pneumoconiosis is caused by environmental exposure. However, acute and more severe forms of the disease do develop in more genetically susceptible people. For example,
a study found polymorphism in IL‐1RA (+ 2018) may iicosis can exacerbate carcinoma and tuberculosis.
Coal worker's pneumoconiosis can increase the risk of tuberculosis.
On gross pathology, pleural plaques are characteristic findings of asbestosis as well as diffuse interstitial pulmonary fibrosis in reticular formation. Coal worker's pneumoconiosis and silicosis both show small interstitial nodules in the upper lung. All pneumoconiosis will present with chronic fibrosis. Silicosis may include eggshell dystrophic calcification.
On microscopic histopathological analysis, anthrocytes, or dust-laden macrophages are characteristic findings of coal worker's pneumoconiosis. Onion skin lesions with concentrically arranged fibers and a central acellular area are typical of silicosis. In asbestosis, asbestosis bodies appear |
Trichinosis_history_and_symptoms | may occur, such as headache, fever, chills, cough, eye swelling, joint pain and muscle pain, and itching. A positive history of gastroenteritis symptoms, muscle pain and fever and recent ingestion of undercooked meat such as pork, wild boar or bear is suggestive of trichinosis.
Trichinosis is mainly caused by eating undercooked meat such as pork wild boar and bear, containing encysted larval Trichinella.
Common symptoms are:
Nausea
Heartburn
Dyspepsia
Diarrhea
Vomiting
Abdominal pain
Muscle pain
Fever
Weakness
Swelling of the face, particularly the eyes
Headache
Chills
Itchy skin or rash
Cough
Diarrhea
Constipation |
Obesity_in_kids | Childhood obesity is a Body Mass Index (BMI) at or above the 95th percentile for children of the same gender and age. It is a serious health problem that can result in health complications. Childhood obesity can be caused by dietary factors, lifestyle factors, underlying medical conditions, genetic causes or certain medications. Obesity may present with high blood pressure, shortness of breath, sleep apnea, gastroesophageal reflux, constipation, insulin resistance, constipation, or irregular menstruation. The presence of polyuria and polydipsia suggests possible diabetes, excess facial hair, insulin resistance and irregular menstruation in adolescent girls may be due to polycystic ovary syndrome (PCOS) and dry skin, constipation and intolerance to cold suggest hypothyroidism. laboratory tests indicated depend on the clinical presentation. Management of obesity includes the treatment of any underlying medical conditions and lifestyle modification.
Obesity was first recognized as a medical disorder by Hippocrates, an ancient Greek physician, in [450 B.C]
In circa 11th century, the complications of obesity including narrowed blood vessels, stroke, and difficulty breathing were described by Avicenna in his book Cannon of Medicine.
Childhood obesity may be classified according to age- and gender- adjusted BMI into two groups:
Obesity: BMI ito an energy imbalance.
This energy imbalance is the result of excess calories intake and/ or decreased calories expenditure.
It has been suggested that a dysfunction in the ghrelin/leptin hormonal pathway may contribute to abnormal appetite control and energy balance.
Gene mutations in single genes including Leptin (LEP), Leptin Receary intake, unhealthy lifestyle , environmental factors, psychological stress , genetic causes , medication-induced or cerebral injury.
Children and adolescents are consuming low nutrient high-calorie foods and beverages at home, school and other places. They are consuming more fast food which is low in nutrients and high in calories, fat and sodium. CDC reports that children and adolescents in the U.S. consumedugar-sweetened beverages which has been directly associated with obesity in multiple reviews.
Physical inactivity, excess use of screen time and inadequate ovegle gene including Leptin (LEP) mutations, Leptin Receptor (LEPR) mutations, Pro-opio melanocortin (POMC) mutations, MC4R deficiency, Proconvertase (PC1/2) deficiency, SIM1 deficiency, NTRK2/BDNF mutations and SH2B1 mutations. Syndromic obesity include Prader Willi Syndrome (PWS), Cohen syndrome, Turner syndrome, down syndrome, and Laurence-Moon-Bardet-Biedl syndrome.
Medications that may cause weight gain in children include second-generation antipsychotics, glucocorticoids, rtiated from other diseases that cause obesity, high blood prld in the USA. This is followed by children aged 6 to 11 years old and then children aged 2 to 5 years of age.
Childhood Obesity prevalence by gender is different depending on the region.
Males are more commonly affected than females 5 to 19 years of age in most high and upper middle-income countries.
There are racial differences for obesity in children.
Obesity prevalence was higher among Hispanics and non-Hispanic blacks than non-Hispanic whites anasthma, obstructive sleep apnea, non-alcoholic fatty liver, gall stones,joint pain and depression.
Common complications of childhood obesity include the progression to adult obesity and increased risk of heart disease, diabetes and cancer risk.
Obese children often suffer from weight stigma, teasing and bullying amongst their p.
The diagnosis ofPhysical examination may be remarkable for:
Stretch marks on hips and abdomen
Acanthosis nigricans
Dry skin, constipation, and fatigability may be signs of hypothyroidism.
Accumulaarly sent girl may suggest polycystic ovary syndrome.
Overweight and obese Children require screening tests:hemoglobin A1C, fasting plasma glucose, 2-hour plasma glucose, and fasting lipids.
The following tests may be indicated for children with obesity depending on the clinical presentation:
TSH, T4, T3, and free T4
Adrenal function tests
Liver function tests
Serum leptin
Serum calcium, phosphorus and parathyroid hormone
Gonadotropin-releasing hormone agonist stimulation test
Free testosterone, total Testosterone, LH, FSH, and dehydroepiandrosterone sulfate.
Management of obesity in children focuses on safely reducing the BMI of the child, preventing and managing complications.
The mainstay of therapy for obesity in children is lifestyle modification through diet, exercise and behavioral modification.
Setmelanotide, a melanocortin-4-receptor agonist was approved by the U.S. Food and Drug Administration (FDA) for children age 6 and older with obesity caused by three rare genetic disorders.
Bariatric surgery are performeths of life, consumption of fruits and vegetables, drinking water, restriction of sweetened drinks and sugary snacks, regular physical activity, limiting scr |
Continuous_variable | used in open sentences. For instance, inc.)
The names of variables used within a discipline often following some naming convention.
In mathematics, very common letters for variables are "x", "y", "n", "a" and "b". "x" and "y" are often used because they correspond to the two axis on a graph, while "a" and "b" are used as the coefficients of x and y in the general form of a linear equation. "n" is often used in statistical analysis, eg, "n" being the number of subjects in a study.
Variables are useful in mathematics because they allow instructions to be specified in a general way. If one were forced to use actual values, then the instructions would only apply in a more narrow set of situations. For example:
Specify a mathematical definition for finding the number twice that of ANY number: double(x) = x + x.
Now, all we need to do to find the double of a number is replace x with any number we want.
double(1) = 1 + 1 = 2
double(3) = 3 + 3 = 6
double(55) = 55 + 55 = 110
etc.
In the aboveer of legs of an animal is a discrete variable. This concept of a variable is widely used in the natural, medical and social sciences.
In causal models, a distinction is made between "independent variables" and "dependent variables", the latter being expected to vary in value in response to changes in the former. In other words, an independent variable is presumed to potentially affect a dependent one. In experiments, independent variables include factors that can be altered or chosen by the researcher independent of other factors.
For example, in an experiment to test whether or not the boiling point of water changes with altitude, the altitude is under direct control and is the independent variable, and the boiling point is presumed to depend upon it and is therefore the dependent variable. The collection of results from an experiment, or information to be used to draw conclusions, is known as data. It is often important to consider which variables to allow for, or to directly control or eliminate, in the design of experiments.
There are also quasi-independent variables, which are those variables that are used by researcher as a grouping mechanism, without manipulating the variable. An example of this would be separating people into groups by their gender. Gender cannot be manipulated, but it is used as a way to group. Another example would be separating people on the amount of coffee they drank before beginning an experiment. The researcher cannot change the past, but can use it to differentiate the groups.
While independent variables can refer to quantities and qualities that are under experimental control, they can also include extraneous factors that influence results in a confusing or undesired manner.
In general, if strongly confounding variables exist that can substantially affect the result, then this makes it more difficult to interpret the results. For example, a study into the incidence of cancer with age will also have to take into account variables such as income (poorer people may have less healthy lives), location (some cancers vary depending on diet and sunlight), stress and lifestyle issues (cancer may be related to these more than age), and so on. Failure to at least consider these factin mathematics and the apparent similarity is source of much confusion. Variables in most of mathematics (those that are extensional and referentially transparent) are time-independent unknowns, while in programming a variable can associate with different values at different times (as they are intensional).
In computer programming a variable is a special value (also often called a reference) that has the property of being able to be associated with another value (or not). What is variable across time is the association. Obtaining the value associated with a variable is often called dereferencing, and creating or changing the association is called assignment.
Variables are usually named by an identifier, but they can be anonymous, and variables can be associated with other variables.
In the computing context, variable identifiers often consist of alphanumeric strings. These identifiers are then used to refer to values in computer memory. This convention of matching identifiers eflection (computer scieat ipectively.
in spreadsheets variables can refer to cells (e.g. $A$2), named ranges, or values in associated source code or functions.
In computer source code, a variable name is one way to bind a variable to a memory location; the corresponding value is stored as a data object in that location so thatence is a kind of variable; its value is the value of the referenced cell (see also: reference (computer science)).
The scope ole itself.
A variable name's scope affects its extent.
Scope is a lexical aspect of a variable. Most languages define a specific scope for each variable (as well as any other named entity), which may differ within a given program. The scope of a variable is the portion of the program code for which the variable's name has meaning and for which the variable is said to be "visible". Entrance into that scope typically begins a variable's lifetime and exit from that scope typically ends its lifetime. For instance, a variable with "lexical scope" is meaningful only within a certain block of statements or subroutine. A "global variable", or one with indefinite scope, may be referred to anywhere in the program. It is erroneous to refer to a variable where it is out of scope. Lexical analysis of a program can determine whether variables are used out of scope. In compiled l value or memory location. A running program may enter and leave a given extent many times, as in the case of a closure.
In portions of code, a variable in scope may never have been given a value, or its value may have been destroyed. Such variables are described as "out of extent" or "unbound". In many languages, it is an error to try to use the value of a variable when it is out of extent. In other languages, doing so may yield unpredictable results. Such a variable may, however, be assigned a new value, which gives it a new extent. By contrast, it is permissible for a variable binding to extend beyond its scope, as occurs in Lisp closures and C static variables. When execution passes back into the variable's scope, the variable may once again be used.
For space efficiency, a memory space needed for a variable may be allocated only when the variable is first used and freed when it is no longer needed. A variable is only needed when it is in scope, but beginning each variable's lifetime when it enters scope may give space to unused variables. To avoid wasting such space, compilers often warn programmers if a variable is declared but not used.
It is considered good programming practice to make the scope of variables as narrow as feasible so that different parts of a program do not accidentally interact with each other by modifying each other's variables. Doing so also prevents action at a distance. Common techniques for doing so are to have different sections of a program use different namespaces, or to make individual variables "private" through either dynamic variable scoping or lexical variable scoping.
Many programming languages employ a reserved value (often named null or nil) to indicate an invalid or uninitialized variable.
In statically-typed languages such as Java or ML, a variable also has a type, meaning that only values of a given class (or set of classes) can be stored in it. A variable of a primitive type holds a value of that exact primitive type. A variable of a class type can hold a null reference or a reference to an object whose type is that class type or any subclass of that class type. A variable of an interface type can hold a null reference or a reference to an instance of any class that implements the interface. A variable of an array type can hold a null reference or a reference to an array.
In dynamically-typed languages such as Python, it is values, not variables, which carry type. In Common Lisp, both situations exist simultaneously: a variable is given a type (if undeclared, it is assumed to be T, the universal supertype) which exists at compile time. Values also have types, which can be checked and queried at runtime. See type system.
Typing of variables also allows polymorphisms to be resolved at compile time. However, this is different from the polymorphism used in object-oriented function calls (referred to as virtual functions in C++) which resolves the call based on the value type as opposed to the supertypes the variable is allowed to have.
Variables often store simple data-like integers and literal strings, but smay determine the length of a list. Such a length function may be parametric polymorphic by including a type variable in its type signature, since the amount of elements in the list is independent of the elements' types.
The formal parameters of functions are also referred to as variables. For instance, in this Python code segment,
<source lang="python">
def addtwo(x):
return x + 2
addtwo(5) # yields 7
</source>
and its equivalent code segment in Lisp,
<source lang="lisp">
(defun addtwo (x)
(+ x 2))
(addtwo 5) ; yields 7
</source>
the variable named x is a parameter because it is given a value when the function is called. The integer 5 is the argument which gives x its value. In most languages, function parameters have local scope [citation needed]. This specific variable named x can only be referred to within the addtwo function (though of course other functions can also have variables called x).
The specifics of variable allocation and the representation of their values vary widely, both among programming languages and among implementations of a given language. Many language implementations allocate space for local variables, whose extent lasts for a single function call on the call stack, and whose memory is automatically reclaimed when the function returns. (More generally, in name binding, the name of a variable is bound to the address of some particular block (contiguous sequence) of bytes in memory, and operations on the variable manipulate that block. Referencing is more common for variables whose values have large or unknown sizes when the code is compiled. Such variables reference the location of the value instead of the storing value itself, which is allocated from a pool of memory called the heap.
Bound variables have values. A value, however, is an abstraction, an idea; in implementation, a value is represented by some data object, which is stored somewhere in computer memory. The program, or the runtime environment, must set aside memory for each data object and, since memory is finite, ensure that this memory is yielded for reuse when the object is no longer needed to represent some variable's value.
Objects allocated from the heap must be reclaimed specially when the objects are no longer needed. In a garbage-collected language (such as C#, Java, and Lisp), the runtime environment automatically reclaims objects when extant variables can no longer refer to them. In non-garbage-collected languages, such as C, the program (and thus the programmer) must explicitly allocate memory, and then later free it, to reclaim its memory. Failure to do so leads to memory leaks, in which the heap is depleted as the program runs, risking eventual failure from exhausting available memory.
When a variable refers to a data structure created dynamically, some of its components may be only indirectly accessed through the variable. In such circumstances, garbage collectors (or analogous program features in languages that lack garbage collectors) must deal with a case where only a portion of the memory reachable from the variable needs to be reclaimed.
A constant is a datum whose value cannot be changed once it is initially bound to a value. In other words, constants cannot be assigned to. In purely functional programming, all data are constant, because there is no assignment.
Although a constant value is specified only once, the constant can be referenced multiple times in a program. Using a constant instead of specifying a value multiple times in the program can not only simplify code maintenance, but it can also supply a meaningful name for it and consolidate such constant assignments to a standard code location (for example, at the beginning).
Programming languages provide one of two kinds of constant variables:
Static constant or Manifest constant
Languages such as Visual Basic allow assigning a fixed value to static constant which will be known at compile time. Such a constant has the same value each time its program runs. Changing the value is accomplished by changing (and possibly recompiling) the code. E.g.: CONST a = 60.
Dynamic constant
Languages such as C++ and Java allow initializing a dynamic constant with a value that is computed at runtime. Thus, unlike static constants, the values of dynamic constants cannot be determined at compile time. E.g.: final int a = b + 20;.
For variables which are references, do not confuse constant references with immutable objects. For example, when a non-constant reference references an immutable object, that reference can be changed so that it references a different object, but the object it originally pointed to cannot be changed (i.e. other references that reference it still see the same information).
Conversely, a constant reference may reference a mutable object. In this case, the reference will always reference the same object (the reference cannot be changed); however, the object that the reference references can still be changed (and other references that also reference that object will see the change), as shown in the following example:
<source lang ="java">
final StringBuffer sampleDynamicConstant = new StringBuffer ("InitialValueOfDynamicConstant");
sampleDynamicConstant.append("_AppendedText");
System.out.println(sampleDynamicConstant);
</source>
The above code produces the following output:
InitialValueOfDynamicConstant_AppendedText
In languages where a variable can be an object (i.e. C++), such a variable being constant is equivalent to the immutability of that object.
Variable interpolation (also variable substitution, variable expansion) is the process of evaluating an expression or string literal containing one or more variables, yielding a result in which the variables are replaced with their corresponding values in memory. It is a specialized instance of concatenation.
Languages that support variable interpolation include Perl, PHP, Ruby, and most Unix shells. In these languages, variable interpolation only occurs when the string literal is double-quoted, but not when it is single-quoted. The variables are recognized because variables start with a sigil (typically "$") in these languages. Ruby uses the "#" symbol for interpolation, and lets you interpolate any expression, not just variables.
For example, the following Perl code:
<source lang="perl">
$name = "Nancy";
print "$name said Hello World to the crowd of people.";
</source>
produces the output:
Nancy said Hello World to the crowd of people.
Template:Wiktionarypar
Template:Wikiversity
Global variable
Local variable
Static variable
Undefined variable
Unreferenced variable
Article giving a general overview of variables in mathematics
bs:Promjenljiva
cs:Proměnná
da:Variabel
de:Variable
et:Muutuja
eo:Variablo
fa:متغیر
gd:Caochladair
ko:변수
it:Variabile
he:משתנה
hu:Változó
nl:Variabele
simple:Variable
sk:Premenná
sl:Spremenljivka
sr:Променљива
fi:Muuttuja (matematiikka)
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Metastasizing | History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | 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
Case #1
Disseminated disease
Q&A: Metastatic Cancer – from the National Cancer Institute
Invasion and Metastases – from Cancer Medicine
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ar:نقيلة
bg:Метастаза
ca:Metàstasi
cs:Metastáza
da:Metastase
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hr:Metastaze
id:Metastasis
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he:גרורה
la:Metastasis
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Meningococcus | Neisseria meningitidis, also simply known as meningococcus, is a gram-negative diplococcal bacterium best known for its role in meningitis. It only infects humans; there is no animal reservoir. It is the only form of bacterial meningitis known to cause epidemics.
There are many strains of meningococcus; the most clinically important are A, B, C, Y and W135:
A - occurs most often in sub-sahara Africa and vaccination is recommended prior to travel with the Men A&C vaccine.
B - is the most lethal form, comprising 40% of UK cases. The changing nature of the B group has prevented formation of a general B vaccine in the UK. However there has been developed the vaccine MeNZB against a specific strain of group B meningococcus, currently being used to control an epidemic in New Zealand. Previously, an earlier neisseria meningitidis vaccine against subtype B was not effective because the sialic acid residues of the capsule are similar to humans.
C - caused approximately 60% of UK cases before the introduction of successful vaccination program for infants. Previously the unconjugated C component of Men A&C was ineffective in those under 2 years. The development of a conjugated form (Men C conj) was needed to provoke infant immunity.
W135 - is particularly a problem for those undergoing annual pilgrimage to Mecca. It is a requirement of Saudi Arabia that all those intending to go on Hajj have a certificate of Men W135 vaccination.
X - A large outbreak of meningitis caused by serogroup X was reported in Niger in 2006. This outbreak is particularly worrying because there is not currently any vaccine against this strain.
Y - In the last decade serogroup Y has emerged as a cause of disease in Northern America
Other strains include 29-E, H, I, K, L, X, and Z.
Though initially a disease with general symptoms like fatigue, meningococcal infections can rapidly progress from fever, headache and neck stiffness to coma and death. Death occurs in approximately 10% of cases. Those with impaired i(ixioup B, although a putative vaccine is curre and Y) meningococcal vaccines available in the US are MCV-4 (a conjugate vaccine Menactra® manufMenrs or less in children aged under 5), because it does not generate memory T-cells. Attempting to overcome this problem by repeated immunisation results in a diminished, not increased antibody response, so boosters are not indicated with this vaccine. In common with all polysaccharide vaccines, Menomune does not produce mucosal immunity, so people can still become colonised with virulent strains of meningococcus, and no herd immunity develops. For this reason, Menomune is eminently suitable for travellers requiring only short term protection, but has no place in national public health prothis formulation will overcome the limitations of Menomune. Menactra is currently licensed only for use in people aged 11 to 55, therefore people outside of this age group can only be offered Menomune.
A study published in March 2006 comparing the two vaccines found that 76% of subjects still had passive protection three years after receiving MCV-4 (63% protective compared with controls), but only 49% has passive protection after receiving MSPV-4 (31% protective compared with controls). This has implications for the timing of recommendations for when meningococcal vaccines should be given, because there is currently no evidence that any of the current vaccines offer continued protection beyond three years.
1. Meningococcal meningitis or meningococcemia, treatment
1.1 Adults
1.1.1 Penicillin MIC < 0.1 mcg/mL
Preferred regimen (1): Penicillin G 4 MU IV q4h for 7 days
Preferred regimen (2): Ampicillin 2 g IV q4h for 7 days
Alternative regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
Alternative regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
Alternative regimen (3): Chloraxime 8-12 g/day IV q4-6h for 7 days
Alternative regimen (1): Cefepime 2 g IV q8h for 7 days
Alternative regimen (2): Chloramphenicol 4y IV q8h for 7 days
Alternative regimen (1): Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
Alternative regimen (2): Chloramphenicol 25 mg/kg/day IV q24h for 7 days
1.2.2 Penicillin MIC 0.1-1.0 mcg/mL
Preferred regimen: Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
Alternative regimen: Chloramphenicol 25 mg/kg/day IV q24h for 7 days
1.3 Neonates (8-28 days old)
1.3.1 Penicillin MIC < 0.1 mcg/mL
Preferred regimen (1): Penicillin G 0.2 MU/kg/day IV q6-8h for 7 days
Preferred regimen (2): Ampicillin 200 mg/kg/day IV q6-8h for 7 days
Alternative regimen (1): Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
Alternative regimen (2): Chloramphenicol 50 mg/kg/day IV q12-24h/kg/day IV q12-24h for 7 days
1.4 Infants and children
1.4.1 Penicillin MICternative regimen (3): Chloramphenicol 75-100 mg/kg/d-24h for 7 days
Preferred regi2): Chloramphenicol 75-100 mg/kg/day q6h for 7 days
Alternative regimen (3): Meropenem 120 mg/kg/den (1): Rif single dose
2.3 Children ≥ 1 month
Preferred regimen: Rifampin 10 mg /kg PO bid for 2 days
2.4 Children < 1 month
Preferred re |
Avidin | ahg.
Avidin has a very strong affinity for biotin with a KD (dissociation constant) of approximately 10-15 M-1, the highest known affinity between any protein and its ligand, and, as such, prevents biotin absorption in the gastrointestinal tract. In biochemical applications, streptavidin or NeutrAvidin, which ng biochemical assays, including western blot, ELISA, ELISPOT and pull-down assays. Avidin immobilized onto solid supports is also used as purification media to capture biotin-labelled protein or nucleic acid molecules. For example, cell surface proteins can be specifically labelled with membrane impermeable biotin reagent, then specifically captured using an avidin-based support.
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Subsets and Splits