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Pyelonephritis_risk_factors | Most risk factors of pyelonephritis are similar to those for cystitis and urethritis, since they themselves predispose the individual to pyelonephritis. Common risk factors in the development of pyelonephritis include renal calculi, urinary tract catheterization, pregnancy, diabetes mellitus, and benign prostatic hyperplasia.
Risk is increased in the following situations:
Any structural abnormalities of the kidneys and the urinary tract can lead to abnormal accumulation of bacteria that can reach the renal parenchyma to cause pyelonephritis.
Kidney stones or calculi
Vesicoureteral reflux (VUR) abnormal backward flow or reflux of urine, can occur post surgically
Posterior urethral valve
Pregnancy
Urinary tract catheterization or stents
Drainage procedures (e.g. nephrostomy)
Prostate disease (e.g. benign prostatic hyperplasia) in men
Polycystic Kidney
Bladder neck obstruction
Horseshoe kidney
Ureterocele
Neuropathic bladder (e.g. spinal cord damage, spina bifida or multiple sclerosis)
Incontinence
Urinary catheters
Calculus
Tumours
Cystitis
Urethritis
Prostatitis
Diabetes mellitus
Immunocompromised states
Sickle cell disease
Transplantation
Pregnancy
HIV
Chemotherapy
Change in sexual partner within the last year
Spermicide use
Decreased expression of CXCR1 (a receptor for IL-8)
Genetic predisposition
Positive family history (close family members with frequent urination)
Young women (reflecting sexual activity in that age group)
Infants with anatomical abnormalities and elderly with hormonal abnormalities |
Spinal_stenosis_x_ray | Narrowed spinal canal, short pedicles of vertebraes, spondylophytes, osteoarthritis of spinal canal.
An x-ray may be helpful in the diagnosis of spinal stenosis. Findings on an x-ray suggestive of spinal stenosis include:
Narrowed spinal canal
Short pedicles of vertebraes
Spondylophytes
Osteoarthritis of spinal canal |
Adrenal_atrophy_other_diagnostic_studies | There are no other diagnostic studies for adrenal atrophy.
There are no other diagnostic studies for adrenal atrophy.
|
Emetine | Emetine is a drug used as both an anti-protozoal and to induce vomiting. It is produced from the ipecac root.
Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuhana. This extract was originally thought to contain only one alkaloid, emetine, but was found to contain several, including cephaeline, emetine, psychotrine and others. Although this therapy was reportedly successful, the extract caused vomiting in many patients which reduced its utility. In some cases, it was given with opioids to reduce nausea. Other suggestions to reduce nausea involved coating the drug to allow it to be released after digestion in the stomach.
The identification of emetine as a more potent agent improved the treatment of amoebiasis. While use of emetine still caused nausea, it was more effective than the crude extract of ipecac root. Additionally, emetine could be administered hypodermically which still produced nausea, but not to the degree experienced in oral administration.
Although it is a potent anti-protozoal, the drug also can interfere with muscle contractions, leading to cardiac failure in some cases. Because of this, in some uses it is required to be administered in a hospital environment so that adverse events can be addressed.
Dehydroemetine is a synthetically produced drug similar to emetine in its anti-amoebic properties, but it produces fewer side effects. In the United States, it is manufactured by Roche andoebiasis in a 7-year old girl with dehydroemetine and metronidazole in Mexico. that dehydroemetine treatment was effective. A total of 60 patients were treated, 20 with dehydroemetine, 20 with Tiberal, and 20 with metronidazole. 25% of patients treated with dehydroemetine reported adverse reactions, compared to 20% with other drugs, but no patient discontinued therapy due to the reaction. that all drug combinations were successful at treating amoebic liver abscesses.
A 1986 in-vitro study compared the effects of dehydroemetine, metronidazole, ornidazole, and secnidazole on Entamoeba histolytica.
A 1980 report described the use of dehydroemetine in treatment of herpes zoster, a condition which can produce painful neurological symptoms. The study involved 40 patients, all of whom were over 60, and compared dehydroemetine treatment to another drug.
Dehydroemetine has been investigated as a treatment for Leishmania infection.
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Typhoid_fever_CT | , bleeding and abscess formation. It may also be helpful in differentiating typhoid fever from other diseases.
CT scans are generally reserved for patients with complications of typhoid fever such as intestinal perforation and bleeding. CT scan findings suggestive on typhoid fever include:
Mesenteric lymphadenopathy
Hepatosplenomegaly
Intestinal perforation or ulceration
Abdominal abscess
Small bowel wall thickening |
Unilateral_neglect | Hemispatial neglect, also called hemineglect, unilateral neglect, spatial neglect or neglect syndrome is a neurological condition in which, after damage to one hemisphere of the brain, a deficit in attention to the opposite side of space is observed.
It most commonly results from brain injury to the right cerebral hemisphere, causing visual neglect of the left-hand side of space. Although most strikingly affecting visual perception ('visual neglect'), neglect in other forms of perception can also be found, either alone, or in combination with visual neglect.
For example, a stroke affecting the right parietal lobe of the brain can lead to neglect for the left side of the visual field, causing a patient with neglect to behave as if the left side of sensory space is nonexistent; although they can still turn left. In an extreme case, a patient with neglect might fail to eat the food on the left half of their plate, even though they complain of being hungry. If someone with neglect is asked to draw a clock, their drawing might show only the numbers 12 and 1 to 6, the other side being distorted or left blank. Neglect patients may also ignore the contralesional side of their body, shaving or adding make-up only to the non-neglected side.
Neglect may also present as a delusional form, where the patient denies ownership of a limb or an entire side of the body. Since this delusion often occurs alone without other signs of mental illness, it is often labeled as a monothematic delusion.
Brain areas in the parietal and frontal lobes are associated with the deployment of attention (internally, or through eye movements, head turns or limb reaches) into contralateral space. Neglect is most closely related to damage to the temporo-parietal junction and posterior parietal cortex. The lack of attention to the left side of space can manifest in the visual, auditory, proprioceptive, and olfactory domains. Although hemispatial neglect often manifests as a sensory deficit (and is frequently co-morbid with sensory deficit), it is essentially a failure to pay sufficient attention to sensory input. This is particularly evident in a related, but separate, condition known as extinction. A patient with extinction following right-hemisphere damage will successfully report the presence of an object in left space when it is the only object present. However, if the same object is presented simultaneously with an object in right space, the patient will only report the object on the right.
Neglect patients can also have problems with "interior" left information, since cases have been reported in which the patient when asked to describe something he knew before his brain damage describes only its right part.
Although hemispatial neglect has been identified following left hemisphere damage (resulting in the neglect of the right side of space), it is most common after damage to the right hemisphere. This disparity is thought to reflect the fact that the right hemisphere of the brain is specialized for spatial perception and memory, whereas the left hemisphere is specialized for language. Hence the right hemisphere is able to compensate for the loss of left hemisphere function, but not vice versa.
Unilateral neglect is a heterogeneous syndrome with several subtypes, and it’s possible that many distinct disorders have been inaccurately lumped together under a single label. There is growing consensus that no single mechanism accounts for the full range of demonstrated symptoms. And it appears that impairments of several different mechanisms converge to result in neglect—each of which could exist singly without causing it. The complexity of attention alone—just one of several mechanisms that may interact—has generated multiple competing hypothetical explanations of neglect. So it’s not surprising that it’s proven difficult to assign particular presentations of neglect to specific neuroanatomical loci. But despite such limitations, we may loosely describe unilateral neglect with four overlapping variables: type, range, axis, and orientation.
Type
We can broadly divide types of neglect into disorders of input and disorders of output. The neglect of input, or “inattention,” includes ignoring contralesional sights, sounds, smells, or tactile stimuli. Surprisingly, this inattention can even apply to imagined stimuli. In what’s termed “representational neglect,” patients may ignore the left side of memories, dreams, and hallucinations.
Output neglect includes motor and pre-motor deficits. A patient with motor neglect does not use a contralesional limb despite the neuromuscular ability to do so. One with pre-motor neglect, or directional hypokinesia, can move unaffected limbs ably in ipsilateral space, but has difficulty directing them into contralesional space. Thus a patient with pre-motor neglect may struggle with grasping an object on the left side even when using the unaffected right arm.
Range
Patients may neglect their own body, the reaching space around them, or the far space beyond their reach. This differentiation is significant because the majority of assessment measures test only for neglect withinin the reaching, or peri-personal, range. But a patient who passes a standard paper-and-pencil test of neglect may nonetheless ignore a left arm or not notice distant objects on the left side of the room.
In extreme cases of personal neglect, patients may deny ownership of contralesional limbs. Sacks (1985) described a patient who fell out of bed after pushing out what he perceived to be the severed leg of a cadaver that the staff had hidden under his blanket. Patients may say things like, “I don’t know whose hand that is, but they’d better get my ring off!” or, “This is a fake arm someone put on me. I sent my daughter to find my real one.”
Axis
Most tests for neglect look for rightward or leftward errors. But patients may also neglect stimuli on one side of a horizontal or radial axis. For example, when asked to circle all the stars on a printed page, they may locate targets on both the left and ride sides of the page while ignoring those across the top or bottom.
In a recent study, researchers asked patients with left neglect to project their midline with a neon bulb and found that they tended to point it straight ahead but position it rightward of their true midline. This shift may account for the success of therapeutic prism glasses, which shift left visual space toward the right. By shifting visual input, they seem to correct the mind's sense of midline. The result is not only the amelioration of visual neglect, but also of tactile, motor, and even representational neglect.
Orientation
An important question in studies of neglect has been left of what? The answer has proven complex. It turns out that subjects may neglect objects to the left of their own midline (egocentric neglect) or may instead see all the objects in a room but neglect the left half of each individual object (allocentric neglect).
These two broad categories may be further subdivided. Patients with egocentric neglect may ignore the stimuli leftward of their trunks, their heads, or their retinae. Those with allocentric neglect may neglect the true left of a presented object or, amazingly, may first correct in their mind’s eye a slanted or inverted object and then neglect the side then interpreted as being on the left. So, for example, if patients are presented with an upside-down photograph of a face, they may mentally flip the object right side up and then neglect the left side of the adjusted image. This also occurs with slanted or mirror-image presentations. A patient looking at a mirror image of a map of the United States may neglect to see California and Oregon despite their inverted placement onto the right side of the map.
Though frequently underappreciated, unilateral neglect can have dramatic consequences. It has more negative effect on functional ability, as measured by the Barthel ADL Index, than age, sex, power, side of stroke, balance, proprioception, cognition, or premorbid ADL status. Its presence within the first 10 days of a CVA is a stronger predictor of poor functional recovery after one year than several other variables, including hemiparesis, hemianopia, age, visual memory, verbal memory, or visuoconstructional ability. Neglect is likely among the reasons that patients with right hemisphere damage are twice as likely to fall as those with left brain damage. Patients with neglect rehabilitate longer and make less daily progress than other patients with similar functional status. And patients with neglect are less likely to live independently than even patients who have both severe aphasia and right hemiparesis.
Treatment consists of finding ways to bring the patient's attention toward the left, usually done incrementally, by going just a few degrees past midline, and progressing from there. Throwing a soft ball from the left, playing a game that involves attending to the left, replying to speakers on the left, or manipulating objects on the left may help. Rehabilitation of neglect is often carried out by neuropsychologists and occupational therapists.
Other forms of treatment that have been tested with variable reports of success include prismatic adaptation, where a prism lens is worn to pull the vision of the patient towards the left, constrained movement therapy where the "good" limb is constrained in a sling to encourage use of the contralesional limb. Eye-patching has similarly been used, placing a patch over the "good" eye. Pharmaceutical treatments have mostly focused on dopaminergic therapies such as bromocriptine, levodopa, and amphetamines, though these tests have had mixed results, helping in some cases and accentuating hemispatial neglect in others.
Blindsight
Brain damage
Anosognosia
Delusion
Monothematic delusion
Hemineglect at Scholarpedia
What is Unilateral Neglect at University of Waterloo
Unilateral Neglect: Clinical and Experimental Studies detailed book review at Monash University |
Desogestrel | Desogestrel and Ethinyl Estradiol is an oral contraceptive that is FDA approved for the prophylaxis of unplanned pregnancy in women who elect to use oral contraceptives as a method of contraception. Common adverse reactions include cholasma, weight variations, bloating, nausea, vomiting, cramps, migraine, depression, amenorrhea, bleeding, nipple discharge, menstruations disorders, vaginal bleeding and breast swelling.
To achieve maximum contraceptive effectiveness, Apri must be taken exactly as directed and at intervals not exceeding 24 hours. Apri is available in the tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided.
The dosage of Apri for the initial cycle of therapy is one rose-colored “active”“Day 1”.
The use of ApriWhen taking Apri, the first rose-colored “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first rose-colored “active” tablet is taken on that day. If switching directly from another oral contraceptive, the first rose-colored “active” tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One rose-colored “active” tablet daily for 21 days, then one white “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a rose-colored “active” tablet is taken the next day (Sunday). When initiating a Sunday sThe use of Apri for contraception may be initiated 4 weeks postpartumIf the patient starts on Apri postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a rose-colored “active” tablet has been taken daily for If the patient misses one (1) rose-colored “active” tablet in Weeks 1, 2, or 3, the rose-colored “active” tablet should be taken as soon as she remembers. If the patient misses two (2) rose-colored “active” tablets in Week 1 or Week 2, the patient should take two (2) rose-colored “active” tablets the day she remembers and two (2) rose-colored “active” tablets the next day; and then continue taking one (1) rose-colored “active”rose-colored “active” tablets in the third week or misses three (3) or more rose-colored “active” tablets in a row, the patient should continue taking one rose-colored “active”There is limited information regarding Off-Label Guideline-Supported Use of Desogestrel and Ethinyl Estraogestrel and Ethinyl Estradiol in adult patientspediatric patients.
Known thrombophilic conditions
Cerebral vascular disease or coronary artery disease (current or history)
Valvular heart disease with complications
Persistent blood pressure values of > 160 mm Hg systolic or > 100 mg Hg diastolicEndometrial carcinoma or other known or suspected estrogen-dependent neoplasia
Undiagnosed abnormal genital bleeding
Cholestatic jaundice of pregnancy or jaundice with prior pill use
Acute or chronic hepatocellular disease with abnormal liver function
Hepatic adenomas or carcinomas
Known or suspected pregnancy
Hypersensitivity to any component of this product
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive For this reason, combination oral contraceptives, including Apri®, should not be used by women who are over 35 years of age and smoke.
obesity and diabete.
The information contained in this package insertof higher doses of estrogens and progestogens than those in common use today. The effect of long term use of the oral contraceptives with formulations of lower doseor case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. (Adapted from refs. 2 and 3 with the author’s permission). For further information, the reader is referred to a text on epidemiological methods.users,and about 4.5 for new cases requiring hospitalization 25. The risk of thromboembolic disease associated with oral contraceptives is not related to length of use and disappears after pill use is stopped. Several epidemiologic studies indicate that third generation oral contraceptives, including those containing desogestrel, are associated with a higher risk of venous thromboembolism than certain second generation oral contraceptives. In general, these studies indicate an approximate 2-fold increased risk, which corresponds to an additional 1 to 2 cases of venous thromboembolism per 10,000 women-years of use. However, data from additional studies have not shown this 2-fold increase in risk.
A two- to four-fold increase in relative risk of post-.4 to 10. The risk is very low in womennd in nonsmokers over the age of 40risk factors.
There is some evidence that the risk of myocardial infarction associated with oral contraceptives is lower when the progestogen has minimal androgenic activity than when the activity is greater. Receptor binding and animal studies have shown that desogestrel or its active metabolite has minimal androgenic activity, although these findings have not been confirmed in adequate and well-controlled clinical trials.strokes and hemorrhagic strokes), although, in general, the risk is greatest among older (> users, for both types of strokes, and smoking interacted to increase the risk of stroke 27 to 29.
In a large study, . The relative risk of hemorrhagic stroke is reported to be 1.2 for non-smokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women.. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents.s used in the contraceptives. Thes for at least 9 years for women 40 to 49 years old In another study in Great Britain, , although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 0.050 mg or higher of estrogens.able 2ow and below that associated with childbirth.
35. Current clinical recommendation involves the use of lower estrogen dose formulations and a careful consideration of risk factors. In 1989, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the use of oral contraceptives in women 40 years of age and over. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are also The Committee recommended that the benefits of low-dose oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks.
Of course, older women, as all womenNumerous epidemiological studies have been performed on the incidence of breast cancer, endometrial cancer, ovarian cancered oral contraceptives (COC). However, this excess risk appears to decrease over time after COC discontinuation and by 10 years after cessation the increased risk disappears. Some studies report an increased risk with duration of use while other studies do not and no consistent relationships have been found with dose or type of steroid. Some studies have found a small increase in risk for women who first use COC before age 20. Most studies show a similar pattern of risk with COC use regardless of a woman’s reproductive history or her family breast cancer history. Breast cancers diagnosed in current or previous oral contraceptive users tend to be less clinically advanced than in nonusers. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormonally-sensitive tumor -and-effect relationship has not been established.
Benign hepatic adenomas are associated with oral contraceptive use,/100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose. Rupture of. O; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediatelyThe majority of recent studies also do not indicateOral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users. This effect has been shown to be directly related to estrogen dose. In general, pIn the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic womenWomen with significant hypertension should not be started on hormonal contraception. extended duration ofprogestational activity and, or renal disease should be encouraged to use another method of contraception. If these women elect to use oral contraceptives, they should be monitored closely and if a clinically significant persistent elevation of blood pressure (BP) occurs (≥ 160 mm Hg systolic or ≥ 100 mm Hg diastolic) and cannot be adequately controlled, oral contraceptives should be discontinued. In general, women who develop hypertension during hormonal contraceptive therapy should be switched to a non-hormonal contraceptive. If other contraceptive methods are not suitable, hormonal contraceptive therapy may continue combined with antihypertensive therapy. Regular monitoring of BP throughout hormonal contraceptive therapy is recommendformer and never users.Ectopic as well as intrauterine pregnancy may occur in contraceptive failur:
Thrombophlebitis and venous thrombosis with or without embolism:
Mesenteric thrombosis
Retinal thrombosis-related:
Nausea
Vomiting
Gastrointestinal symptoms (such as abdominal cramps and bloating)
Breakthrough bleeding
Spotting
Change in menstrual flow
Amenorrhea
Temporary infertility after discontinuation of treatment
Edema
Melasma which may persist
Breast changes: tenderness, enlargement, secretionolestatic jaundice
Migraine
Allergic reaction, including rash, urticaria, and angioedema
Mental depression
Reduced tolerance to carbohydrates
Vaginal candidiasis
Change in corneal curvature (steepening)
Intolerance to contact lenses
The following adverse reactions have been reported in users of oral contraceptives and a causal association has been neither confirmed nor refuted:
re is limited information regarding Desogestrel and Ethinyl Estradiol Postmarketing Experience in the drug label.O to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Coadministration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to administration with HIV protease inhibitors (decrease e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir or increase e.g., indinavir and atazanavir/ritonavir) /HCV protease inhibitors (decrease e.g., boceprevir and telaprevir) or with non-nucleoside reverse transcriptase inhibitors (decrease e.g., nevirapine or increase e.g., etravirine).
Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.
COOtemazepam and lamotrigines with use of COCs.
Pregnancy Category (FDA): X
There is no FDA guidance on usage of Desogestrel and Ethinyl Estradiogestrel and Ethinyl Estradiol in women who are pregnant.
There is no FDA guidance on use of Desogestrel and Ethinyl ESafety and efficacy of ApriThere is no FDA guidance on the use of Desogestrel and Ethinyl Estradiol with respect to specific gender populations.
There is no FDA guidance on the use of Desogestrel and Ethinyl Estradiol with respect to specific racial populations.
There is no FDA guidance on the use of Desogestrel and Ethinyl Estradiol in patients with renal impairment.
There is no FDA guidance on the use of Desogestrel and Ethinyl Estradiol in patients with hepatic impairment.
There is no FDA guidance on the use of Desogestrel and Ethinyl Estradiol in women of reproductive potentials and males.
There is no FDA guidance one the use of Desogestrel and Ethinyl Estradiol in patients who are immunocompromised.
There is limited information regarding Desogestrel and Ethinyl Estradiol Administration in the drug label.
There is limited information regarding Desogestrel and Ethinyl Estradiol Monitoring in the drug label.
There is limited information regarding the compatibility of Desogestrel and Ethinyl E, and withdrawal bleeding may occur in females.There is limited information regarding Desogestrel and Ethinyl Estradiol Structure in the drug label.
Combined, which increase the difficulty of sperm entry into the uterus, and changes in the endometrium which reduce the likelihood of implantation.
Receptor binding studies, as well as studies in animals, have shown that 3-keto-desogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with minimal intrinsic androgenicity 91,92. The relevance of this latter finding in humans is unknown.
Desogestrel is rapidly and almost completely absorbed and converted into 3-keto-desogestrel, its biologically active metabolite. Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of 3-keto-desogestrel, is approximately 84%.
In the third cycle of use after a single dose of Apri, maximum concentrations of 3-keto-desogestrel of 2,805 ± 1,203 pg/mL (mean ± SD) are reached at 1.4 ± 0.8 hours. The area under the curve (AUC0 to ∞) is 33,858 ± 11,043 pg/mL • hr after a single dose. At steady state, attained from at least day 19 onwards, maximum concentrations of 5,840 ± 1,667 pg/mL are reached at 1.4 ± 0.9 hours. The minimum plasma levels of 3-keto-desogestrel at steady state are 1,400 ± 560 pg/mL. The AUC0 to 24 at steady state is 52,299 ± 17,878 pg/mL • hr. The mean AUC0 to ∞ for 3-keto-desogestrel at single dose is significantly lower than the mean AUC0 to 24 at steady state. This indicates that the kinetics of 3-keto-desogestrel are non-linear due to an increase in binding of 3-keto-desogestrel to sex hormone-binding globulin in the cycle, attributed to increased sex hormone-binding globulin levels which are induced by the daily administration of ethinyl estradiol. Sex hormone-binding globulin levels increased significantly in the third treatment cycle from day 1 (150 ± 64 nmol/L) to day 21 (230 ± 59 nmol/L).
The elimination half-life for 3-keto-desogestrel is approximately 38 ± 20 hours at steady state. In addition to 3-keto-desogestrel, other phase I metabolites are 3α-OH-desogestrel, 3ß-OH-desogestrel, and 3α-OH-5α-H-desogestrel. These other metabolites are not known to have any pharmacologic effects, and are further converted in part by conjugation (phase II metabolism) into polar metabolites, mainly sulfates and glucuronides.
Ethinyl estradiol is rapidly and almost completely absorbed. In the third cycle of use after a dose of Apri, the relative bioavailability is approximately 83%.
In the third cycle of use after a single dose of Apri, maximum concentrations of ethinyl estradiol of 95 ± 34 pg/mL are reached at 1.5 ± 0.8 hours. The AUC0 to ∞ is 1,471 ± 268 pg/mL • hr after a single dose. At steady state, attained from at least day 19 onwards, maximum ethinyl estradiol concentrations of 141 ± 48 pg/mL are reached at about 1.4 ± 0.7 hours. The minimum serum levels of ethinyl estradiol at steady state are 24 ± 8.3 pg/mL. The AUC0 to 24, at steady state is 1,117 ± 302 pg/mL • hr. The mean AUC0 to ∞ for ethinyl estradiol following a single dose during treatment cycle 3 does not significantly differ from the mean AUC0 to 24 at steady state. This finding indicates linear kinetics for ethinyl estradiol.
The elimination half-life is 26 ± 6.8 hours at steady state. Ethinyl estradiol is subject to a significant degree of presystemic conjugation (phase II metabolism). Ethinyl estradiol escaping gut wall conjugation undergoes phase I metabolism and hepatic conjugation (phase II metabolism). Major phase I metabolites are 2-OH-ethinyl estradiol and 2-methoxy-ethinyl estradiol. Sulfate and glucuronide conjugates of both ethinyl estradiol and phase I metabolites, which are excreted in bile, can undergo enterohepatic circulation.
There is limited information regarding Desogestrel and Ethinyl Estradiol Nonclinical Toxicology in the drug label.
There is limited information regarding Desogestrel and Ethinyl Estradiol Clinical Studies in the drug label.
Desogestrel and ethinyl estradiol tablets 28 tablets blister cards contain 21 round, film-coated, unscored, biconvex, rose-colored tablets and 7 round, unscored white tablets. Each rose-colored tablet (debossed with “dp” on one side and “575” on the other side) contains 0.15 mg desogestrel and 0.03 mg ethinyl estradiol, USP. Each white tablet (debossed with “dp” on one side and “570” on the other side) contains inert ingredients.
Cartons of 6 blister cards.
Store at 20° to 25°C (68° to 77°F)
{{#ask: Page Name::Desogestrelogestrelogestrel and Ethinyl Estradiol Patient Counseling Information in the drug label.
Alcohol-Desogestrel and Ethinyl Ei
There is limited information regarding Desogestrel and Ethinyl Estradiol Look-Alike Drug Names in the drug label.
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Coronary_artery_revascularization | Hemodynamic Support for Complex PCI
The Angulated or Tortuous Lesion
The Left Internal Mammary Artery
Preparation of the patient for diagnostic catheterization
Technical aspects of the cardiac catheterization laboratory
Obtaining venous and arterial access
Equipment used in diagnostic catheterization
Hemodynamic assessment in the cardiac catheterization laboratory |
Neurotrophic_factor | Neurotrophins, also called "neurotrophic factors", are a family of protein which induce the survival of neurons. They belong to a family of growth factors, secreted proteins usually found in the blood stream which are capable of signaling particular cells to survive, differentiate, or grow. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death - thus allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to form neurons.
The neurotrophin family includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).
There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinases receptors.
p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind.
The Trk family include TrkA, TrkB, and TrkC, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins.
Main article: Nerve growth factor
Nerve growth factor (NGF), the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high affinity receptor TrkA, and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.
Main article: Brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the brain, but also found in the periphery. More specifically, it is a protein which has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized, after NGF and before neurotrophin-3.
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help tin normal neural development.
Despite its name, BDNF is actually found in a range of tissue and cell types, not just the brain. Expression can be seen in the retina, the CNS, motor neurons, the kidneys, and the prostate.Neurotrophin self-production by an individual is described in "Keep Your Brain Alive" Workman Publishing 1999
Neurotrophin-1 (NT-1) is also known as "B cell-stimulating factor-3" (BSF-3) or "cardiotrophin-like cytokine factor 1" (CLCF1), and is a cytokine belonging to the interleukin-6 family. It is a secreted protein, found predominantly in lymph nodes and spleen, which contains 225 amino acids with a molecular mass of 22 kDa in its mature form. It is closely related to other proteins called cardiotrophin-1 and ciliary neurotrophic factor.
NNT-1/BSF-3 induces tyrosine phosphorylation of the IL-6 receptor common subunit glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and the transcription factor STAT3. It has been implicated in the induction of IL-1 (via induction of corticosterone and IL-6) and serum amyloid A, and in B cell hyperplasia. This cytokine is capable of B cell activation via gp130 receptor stimulation.
Main article: Neurotrophin-3
Neurotrophin-3, or NT-3, is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 was the third neurotrophic factor to be characterized, after NGF and BDNF.
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB - see below). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.
Interestingly, anti-depressant drugs produce behavioural changes mainly through gradual effect on BDNF and desensitisement of autoreceptors.
Neurotrophin-4 (NT-4) like BDNF, is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase. It is also known as NT4, NT5, NTF4, and NT-4/5.
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Ovarian_hyperstimulation_syndrome | Ovarian hyperstimulation syndrome (OHSS) is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.
Ovarian hyperstimulation syndrome is usually iatrogenic secondary to ovarian stimulant drug therapy for infertility but may occur as a spontaneous event in pregnancy.
Cetrorelix
Choriogonadotropin alfa
Follitropin beta
Urofollitropin
Symptoms are classified into three categories: mild, moderate, and severe.
Mild symptoms include abdominal bloating and feeling of fullness, nausea, diarrhea, and slight weight gain.
Moderate symptoms include excessive weight gain (weight gain of greater than 2 pounds per day), increased abdominal girth, vomiting, diarrhea, darker urine, reduced urine output, excessive thirst, and dry skin and/or hair.
Severe symptoms are fullness/bloating above the waist, shortness of breath, reduced urine output, calf and chest pains, and lower abdominal pain (in addition to mild and moderate symptoms).
In mild forms of OHSS the ovaries are enlarged, in moderate forms there is additional accumulation of ascites with mild abdominal distension, while in severe forms of OHSS there may be hemoconcentration, thrombosis, abdominal pain and distension, oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing, and late OHSS is seen in early pregnancy.
OHSS may be complicated with ovarian torsion, ovarian rupture, thrombophlebitis and renal insufficiency. Symptoms generally resolve in 1 to 2 weeks, but will be more severe and persist longer if pregnancy is successful. This is likely due to the role of the corpus luteum in sustaining the pregnancy before the placenta has fully developed. Typically, even in severe OHSS with a developing pregnancy, the duration does not extend beyond the first trimester.
OHSS is characterized by the presence of multiple luteinized cysts within the ovariebstance that induces OHSS by making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process by the production of hCG.
Sporadic OHSS is very rare, and may have a genetic component. Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after use of gonadotropin therapy (with administration of FSH), such as Pergonal, and administration of hCG to trigger ovulation, often in conjunction with IVF. The frequency varies and depends on patient factors, management, and methods of surveillance. About 5% of treated patients may encounter moderate to severe OHSS.
Mortality is low, but several fatal cases have been reported.
The imaging findings are similar on ultrasound, CT, and MR imaging.
Ovarian enlargement is present caused by distended corpora lutea cysts of varying sizes.
Because the enlarged follicles are often peripheral in location, a "wheel spoke" appearance has been described, with stromal ovarian tissue located centrally with surrounding cysts.
Familiarity with ovarian hyperstimulation syndrome and the appropriate clinical setting should help avoid the incorrect diagnosis of an ovarian cystic neoplasm.
Images courtesy of RadsWiki
Physicians can reduce the risk of OHSS by monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication. Once OHSS develops, reduction in physical activity, closely monitoring fluid and electrolyte balance, and aspiration of accumulated fluid (ascites) from the abdominal/pleural cavity may be necessary, as well as opioids for the pain. If the OHSS develops within an IVF protocol, it can be prudent to postpone transfer of the pre-embryos since establishment of pregnancy can lengthen the recovery time or contribute to a more severe course. Over time, if carefully monitored, the condition will naturally reverse to normal - so treatment is typically supportive, although patient may need to be treated or hospitalized for pain, paracentesis, and/or intravenous hydration.
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Semi-circular_canal | The semicircular canals are three half-circular, interconnected tubes located inside each ear that are the equivalent of three gyroscopes located in three orthogonal planes.
The vertical canals are positioned at an angle of about 100 degrees relative to one another, while the horizontal canal makes an angle of about 95 degrees with the posterior canal and an angle of about 110 degrees with the anterior canal. Deviations up to 10-15 degrees between individuals are normal. Because the angles between the canals are not perpendicular, movements of the head stimulate horizontal and vertical canals simultaneously.
The three canals are:
Superior semicircular canal
Posterior semicircular canal
Horizontal semicircular canal
Each canal is filled with a fluid called endolymph and contains a motion sensor with little hairs (cilia) whose ends are embedded in a gelatinous structure called the cupula.
The Semicircular canals are a component of the Labyrinth.
, , Transverse section of a human semicircular canal and duct,
, , Illustration of otolith organs,
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Dorzolamide | Dorzolamide is a carbonic anhydrase inhibitor that is FDA approved for the {{{indicationType}}} of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Common adverse reactions include taste alteration, hypersensitivity reaction, punctate keratitis, and visual discomfort.
Dosing Information
One drop in the affected eye(s) three times daily
There is limited information regarding Off-Label Guideline-Supported Use of Dorzolamide in adult patients.
Dosing Information
One drop 1–4 hours after anterior segment laser surgery
Dosing Information
One drop in the affected eye(s) three times daily
There is limited information regarding Off-Label Guideline-Supported Use of Dorzolamide in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dorzolamide in pediatric patients.
Hypersensitivity
Dorzolamide HCl Ophthalmic Solution is contraindicated in patients who are hypersensitive to any component of this product.
Dorzolamide HCl Ophthalmic Solution is a sulfonamide and, although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration with Dorzolamide HCl Ophthalmic Solution. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.
The management of patients with acute angleconside Solution. The concomitant administration of Dorzolamide HCl Ophthalmic Solution and oral carbonic anhydrase inhibitors is not recommended.
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, iloping corneal edema in patients with low endothelial cell counts. Precautions should be used when prescribing Dorzolamide HCl Ophthalmic Solution to this group of patients.
The most frequent adverse events associated withately one-quarter of patients noted a bi the adverse experience profile of Dorzolamide HCl Ophthalmic Solution was comparable to that seen in adult patients.
The following adverse events have occurred either at low incidence (<1%) during clinical trials or have been reported during the use of Dorzolamide HCl Ophthalmic Solution in clinical practice where these events were reported voluntarily from a population of unknown size and frequency of occurrence cannot be determined precisely. They have been chosen for inclusion based on factors such as seriousness, frequency al carbonic anhydrase inhibitors and have, in some instances, resulted in drug interactions (e.g., toxicity associated with high-dose salicylate thetimes the recommended human ophthalmic dose) revealed malformations of the vertebral bodies. These malformations occurred at doses that carecommended human ophthalmic dose). There are no adequate and well-controlled studies in pregnant women. Dorzolamide HCl Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category B3
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dorzolamide in women who are pregnant.
There is no FDA guidance on use of Dorzolamide during labor and delivery.
In a study of dorzolamide hydrochloride in lactating rats, decreases in body weight gain of 5 to 7% in offspring at an oral dose of 7.5 mg/kg/day (94 times the recommended human ophthalmic dose) were seen during lactation. A slight delay in postnatal development (incisor eruption, vaginal canalization and eye openings), secondary to lower fetal body weight, was noted.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the pfectiveness have been observed between elderly and younger patients.
There is no FDA guidance on the use of Dorzolamide with respect to specific gender populations.
There is no FDA guidance on the use of Dorzolamide with respect to specific racial populations.
There is no FDA guidance on the use of Dorzolamide in patients with renal impairment.
There is no FDA guidance on the use of Dorzolamide in patients with hepatic impac state, and possible central nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
There isst active being carbonic anhydrase II (CA-II), found primarily in red blood cells (RB in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP).
Dorzolamide HCl Ophthalmic Solution contains dorzolamide hydrochloride, an inhibitor of human carbonic anhydrase II. Following topical ocular administration, Dorzolamide HCl Ophthalmic Solution reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
Dorzolamide HCl Ophthalmic Solution is a carbonic anhydrase inhibitor formulated for topical ophthalmic use.
Dororide USP is optically actichloride USP has a molecular weight of 360.9 and a melting point of about 264°C. It is a white to off-white, crystalline powder, which is soluble in water and slightly soluble in methanol an. The pH of the solution is approximately 5.6, and the osmolarity is 260-330 mOsM. Each mL of Dorzolamide HCl Ophthalmic Solution 2% contains 20 mg dorzolamide (22.3 mg of dorzolamide hydrochloride USP).
Inactive ingredients are hydroxyethyl cellulose, mannitol, sodium citrate dihydrate, sodium hydroxide (to adjust pH) and water for injection. Benzalkonium chloride 0on. To assess the potential for systemic carbonic annhibition in RBCs were measured.
Dorzolamide accumulates in RBCs during chronic dosing as a result of binding to CA-II. The parent drug forms a single N-desethyl metabolite, which inhibits CA-II less potently than the parent drug but also inhibits CA-I. The metabolite also accumulates in RBCs where it binds primarilyoximates the amount of drug delivered by topical ocular administration of Dorzolamide HCl Ophthalmic Solution 2% t.i.d. Steady state was reached within 8 weeks.
The inhibition of CA-II and totadividuals.
In a two-year study of dorzolamide hydrochloride administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day (250 times the recommended human ophthalmic dose). Papillomas were not seen in rats given oral doses equivalent to approxi doses up to 75 mg/kg/day (~900 times the recommended human ophthalmic dose).
The increased incidence of urinary bladder papillomas seen in the high-dose male rats is a class effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria, and diverse sodium salts.
No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for one year at 2 mg/kg/day (25 times the recommended human ophthalmic dose) or monkeys dosed topically to the eye at 0.4 mg/kg/day (~5 times the recommended human ophthalmic dose) for one year.
The following tests for mutagenic potential were negative: (1) in vivo (mouse) cytogenetic assay; (2) in vitro chromosomal aberration assay; (3) alkaline elution assay; (4) V-79 assay; and (5) Ames test.
In reproduction studies of dorzolamide hydrochloride in rats, there were no adverse effects on the reproductive capacity of males or females at doses up to 188 or 94 times, respectively, thapproximately 3 to 5 mmHg throughout the day and this was consistent in clinical studies of up to one year duration.
The efficacy of Dorzolamide HCl Ophthalal over the one year period.
Dorzolamide HCl Ophthalmic Solution is a slightly opalescent, nearly colorless, slightly viscous solution.
Dorzolamide HCl Ophthalmic Solution is supplied in a white low-density polyethylene (LDPE) bottle with a controlled drop tip and orange polypropylene cap in the following sizes:
5 mL in a 7.5 mL bottle NDC 24208-485-05
10 mL in a 10 mL bottle NDC 24208-485-10
Store Dorzolamide HCl Ophthalmic Solution at 20°-25°C (68°-77°F). Protect from light.
There is limited information regarding Dorzolamide Storage in the drug label.
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be advised tar reactions, particularly conjunctivitis and lid reactions, they should discontinue use and seek their physician's advice.
Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.
Patients should also be instructed that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.
If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.
Patients should be advised that Dorzolamide HCl Ophthalmic Solution contains benzalkonium chloride which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following Dorzolamide HCl Ophthalmic Solution administration.
Alcohol-Dorzolamide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Trusopt Ocumeter
N/A
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Aldolase_A_deficiency | Aldolase A deficiency is a deficiency of the enzyme aldolase A that is found predominantly in muscle and red blood cells.
It may lead to myopathy, exercise intolerance and rhabdomyolysis associated with hemolytic anaemia.
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Familial_hypocalciuric_hypercalcemia_electrocardiogram | The ECG findings associated familial hypocalciuric hypercalcemia are due to cardiac complications of hypercalcemia.
There are no ECG findings associated with familial hypocalciuric hypercalcemia. However, an ECG may be helpful in the diagnosis of cardiac complications of hypercalcemia.
Findings on ECG are due to hypercalcemia and includes:
ST segment - Slcemic patients. This represents an increase in ventricular muscle mass.
T wave - T wave is prolonged in patients with hypercalcemia when compared to normocalcemic patients. |
Dermatofibrosarcoma_protuberans | Dermatofibrosarcoma protuberans (DFSP) is a rare non-hereditary neoplasm of the dermis layer of the skin which is sometimes described as having the tentacles growing into the surrounding fat, muscle and even bone and is therefore, classified as a soft tissue sarcoma. In many respects, the disease behaves as a benign tumor, but in 2-5% of cases it can metastasize, so it should be considered to have a malignant potential. Over 95% of DFSP tumors have the chromosomal translocation t(17;22). The translocation fuses the collagen gene (COL1A1) with the platelet-derived growth factor gene. The fibroblast, the cell of origin of this tumor, expresses the fusion gene in the belief that it is collagen. However, the resulting fusion protein is processed into mature platelet-derived growth factor which is a potent growth factor. Fibroblasts contain the receptor for this growth factor. Thus, the cell "thinks" it is producing a structural protein, but in fact produces a self-stimulatory growth signal. The cell divides rapidly and a tumor forms. In dermatofibrosarcoma protuberans, the tumor has a tendency to return after being removed. However, it does not often metastasize to other parts of the body.
There are several variants of dermatofibrosarcoma protuberans in which different cell types are involved in the tumor.
Dermatofib translocation) between chromosomes 17 and 22
t(17;22)(q21;q13.1) leads to fusion of a part of COL1A1 gene from chromosome 17 with a part of the PDGFB gene from chromosome 22
The translocation is found on one or more extra chromosomes that can be either the normal linear or circu places and the ends of the chromosomal arms fuse together to form a circular structure)
Other genes from chromosomes 17 and 22 can be found on the extra chromosomes, but the role of these genes in the development of this condition is unclear
Translocation is acquired during a person's lifetime and the chromosomes containing the translocation are present only in the tumor cells, this type of genetic change is known as somatic mutation
In normal cells, the COL1A1 gene provides instructions for making part of a large molecule called type I collagen, which strengthens and supports many tissues in the body
The PDGFB gene provides instructions for making one version (isoform) of the platelet derived growth factor (PDGF) protein which by attaching to its receptor, becomes activated and stimulates many cellular processes, including cell growth and division (proliferation) and maturation (differentiation)
The abnormally fused COL1A1-PDGFB gene provides instructions for making an abnormal combined (fusion) protein that ultimately functions like the PDGFB protein
This gene fusion leads to the production of an excessive amount of protein that functions like the PDGFB protein
In excess, this fusion protein stimulates cells to proliferate and differentiate abnormally, leading to the tumor formation as seen in dermatofibrosarcoma protuberans
COL1A1-PDGFB fusion gene is found in more than 90% of the dermatofibrosarcoma protuberans cases
In the remaining 10% of the cases, changes in some other unidentified genes may be associated with this condition such as complex t(5;8) involving the CSPG2 and PTK2B genes
Gross features of dermatofibros growth (seen in some cases)
The early plaque stage may lack the particular storiform pattern
Many non-atypical mitotic figures may be present
Non-polarized, thin collagen
Mild pleomorphism (not significant)
Focal atypia
May coexist with giant cell fibroblastoma
Absent or rare histiocytes
Following cell types are absent: Histiocyte-like cells, Foam cells, Giant cells, Other inflammatory cells
Different variants include: Atrophic (depressed lesion), Collagenous (with central thick collagen bundles), Granular cell (S100 negative), Myxoid, Palisading, Pigmented, Sclerosing
Cytology of dermatofibrosarcoma has following characteristics:
Homogeneous
Isolated spindle cells
Tissue fragments often present with storiform pattern
Fibrillary stromal fragments
Naked nuclei
Slight to moderate atypia (occasionally)
Stellate or spindle cells are present which have long, slender, ramified cell processes which are joined by primitive junctions, often with subplasmalemmal densities
Multivesicular buds are also present commonly
Immunhistochemical staining of dermatofibrosarcoma protuberans shows: Positive staining for: CD34 (strong in 95%), Vimentin, Focal actin, ApoD, Bcl2, NKI-C3, CD99, CD99, Nestin, Tenascin, CD163, Factor XIIIa, CD10, Negative staining for: Factor XIIIa (usually), Keratin, EMA, S100, HMB45, Desmin, CD117
Dermatofibrosarcoma protuberans is estimated to occur in 1 in 100,000 to 1-5 in 1 million people per year
It usually occurs in adults of 20 - 40 years of age
It affects twice more commonly the blacks than whites in US
It can also occur in infants and children
It has a stable incidence which is highest among women
Worse survival is associated with: Increased age, Male sex, Black race, Anatomic location of the limbs and head
Common risk factors for the development of dermatofibrosarcoma include: A scar developing after surgery or a burn, Female sex, Age of 30-50 years, African-American race (Bendar or pigmented variant), Pregnancy
Symptoms include: Flat or a slightly raised skin patch (first sign), 1 to 5 centimeters in diameter, Rubbery (hard to touch), Gives the appearance of a scar or a wrinkled skin patch, Skin-colored, violet or reddish-brown, Soft, depressed skin area (rarely, makes it difficult to diagnose), Grows very slowly over the period of years
Tumors commonly involve the following body parts: Torso/trunk (most common), Arms, Legs, Head, Neck
On physical examination, it can be felt as a small, purplish, reddish, or flesh-colored, flat or raised skin patch or nodule almost 1-5 centimeters in diameter
These include: FNAC , Biopsy, Immunohistochemistry, CD34 staining
MRI, CT scan
Treatment includes:
Dermatofibrosarcoma protuberans must be differentiated must be differentiated from the following:
Neurofibroma
Schwannoma
Ganglioneuroma
Dermal neurotized melanocytic nevus
Myxoid liposarcoma
Solitary circumscribed neuroma/palisaded encapsulated neuroma
Traumatic neuroma
Superficial angiomyxoma
Nerve sheath myxoma
Malignant peripheral nerve sheath tumor (MPNST)/malignant schwannoma
Spindle cell lipoma
Leiomyoma
Inflammatory myofibroblastic tumor
Fibroepithelial polyp/acrochordon (aka skin tag or soft fibroma)
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Diabetes_mellitus#Differential_diagnosis | Diabetes mellitus (DM) refers to a spectrum of disorders with different metabolic changes that result in hyperglycemia as a common feature. It is caused by interaction of environmental agents in a genetically susceptible person. The metabolic disarrangement that may result in hyperglycemia will define the pathologic feature of each type of DM. Decreased insulin secretion, insulin resistance, decreased glucose utilization and increased glucose production are the main metabolic dysregulations that are known to cause hyperglycemia.
Hyperglycemia may cause secondary changes in metabolic arrangement in different systems and it can involve every organ systems. DM is the leading cause of end-stage renal disease (ESRD), non-traumatic lower extremity amputations, and adult blindness worldwide.
Accordingly, early diagnosis and treatment can result in significant decrease in mortality and morbidity. The incidence of diabetes has been increased constantly. According to WHO reports, 346 million people worldwide have diabetes and it is projected to double by 2030. It's prevalence is more in developed countries but the death occurring from DM complications is more common in developing countries.
The prevalence of diabetes type 2 is more common than type 1 diabetes. Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include macrovascular (coronary heart disease, peripheral arterial disease and cerebrovascular disease), microvascular (retinopathy, neuropathy and nephropathy) and other organ involvement (gastrointestinal, genitourinary, dermatologic, infectious, cataracts, glaucoma, periodontal disease and hearing loss). The main goals of treatment are:
Elimination of hyperglycemic symptoms
Control of the long term complications
Improvement of the patient's quality of life
Diabetes mellitus is classified into 3 types based on the pathogenic process that lead to hyperglycemia: Diabetes mellitus type 1, Diabetes mellitus type 2, Gestational diabetes
Complications of diabetes mellitus may be classified as acute or chronic. Acute complications of diabetes mellitus may occur in type 1, type 2, or gestational diabetes. Chronic complications of diabetes mellitus are more likely to occur in long standing type 1 or type 2 diabetes and may be further classified as macrovascular, microvascular, or other (unspecified etiology) as follows:
They include diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycemic state (HHS). DKA could be the presenting feature of type 1 diabetes and it is more common in type 1 diabetes although, it is sometimes seen in type 2 diabetic patients. HHS is mostly seen in the elderly and it is more common in type 2 diabetes.
Coronary heart disease
Peripheral arterial disease
Cerebrovascular disease
Retinopathy (nonproliferative/proliferative)
Macular edema
Sensory and motor (mono- and polyneuropathy)
Autonomic neuropathy
Albuminuria and declining renal function
Gastrointestinal (gastroparesis, diarrhea)
Genitourinary (uropathy/sexual dysfunction)
Dermatologic
Infections
Cataracts
Glaucoma
Periodontal disease
Hearing loss
Complications of gestational diabetes differs from type 1 and type 2 diabetes primarily due to its pregnancy-specific effects on the mother as well as its effects on the fetus.
For more information on maternal complications of gestational diabetes click here.
For more information on fetal complications of gestational diabetes click here.
A fasting plasma glucose (FPG) <5.6 mmol/L (100 mg/dL), a plasma glucose <140 mg/dL (11.1 mmol/L) following an oral glucose challenge and an HbA1c <5.7% are considered normal. Diagnostic criteria for DM are: Symptoms of diabetes plus random blood glucose concentration ≥11.1 mmol/L (200 mg/dL)† OR, Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)‡ OR, Hemoglobin A1c ≥ 6.5% OR, 2-hoursplasma glucose ≥11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test¶
American Diabetes Association Diabetes Diagnostic Criteria 2018 (DO NOT EDIT)
Recommendations for HbA1c: To avoid misdiagnosis or missed diagnosis, the A1C te |
Endocarditis_(patient_information) | Infective endocarditis is an infection of the lining of the heart chambers and heart valves that is caused by bacteria, fungi, or other infectious substances. Having a catheter (tube) or another medical device inserted through your skin, especially for long periods, also can allow bacteria to enter your bloodstream. People who use intravenous (IV) drugs also are at risk for infective endocarditis because of the germs on needles and syringes. Bacteria also may spread to the blood and heart from infections in other parts of the body, such as the gut, skin, or genitals.
Symptoms of endocarditis may develop slowly (subacute) or suddenly (acute). Fever is the classic symptom and may persist for days before any other symptoms appear.
Other symptoms may include:
Abnormal urine color
Blood in the urine
Chills
Excessive sweating
Fatigue
Joint pain
Muscle aches and pains
Nail abnormalities (splinter hemorrhages under the nails)
Night sweats (may be severe)
Paleness
Red, painless skin spots on the palms and soles (Janeway lesions)
Red, painful nodes in the pads of the fingers and toes (Osler's nodes)
Shortness of breath with activity
Swelling of the feet, legs, abdomen
Weakness
Weight loss
Endocarditis is usually a result of a blood infection. Bacteria or other infectious substance can enter the bloodstream during certain medical procedures, including dental procedures, and travel to the heart, where it can settle on damaged heart valves. The bacteria can grow and may form infected clots that break off and travel to the brain, lungs, kidneys, or spleen.
Most people who develop infectious endocarditis have underlying heart disease or valve problems.
However, an organism commonly found in the mouth, Streptococcus viridans, is responsible for about 50% of all bacterial endocarditis cases. This is why dental procedures increase your chances for developing this condition. Such procedures are especially risky for children with congenital heart conditions. As a result, it is common practice for children with some forms of congenital heart disease and adults with certain heart-valve conditions to take antibiotics before any dental work.
Other common culprits include Staphylococcus aureus and enterococcus. Staphylococcus aureus can infect normal heart valves, and is the most common cause of infectious endocarditis in intravenous drug users.
Less common causes of infectious endocarditis include pseudomonas, serratia, and candida.
The following increase your chances for developing endocarditis:
Artificial heart valves
Congenital heart disease (atrial septal defect, patent ductus arteriosus, and others)
Heart valve problems (such as mitral insufficiency)
History of rheumatic heart disease
Intravenous drug users are also at risk for this condition, because unsterile needles can cause bacteria to enter the bloodstream.
Call your health care provider if you note the following symptoms during or after treatment:
Weight loss without change in diet
Blood in urine
Chest pain
Weakness
Numbness or weakness of muscles
Fever
The health care provider may hear abnormal sounds, called murmurs, when listening to your heart with a stethoscope.
A physical exam may also reveal:
Enlarged spleen
Splinter hemorrhages in the fingernails
A history of congenital heart disease raises the level of suspicion. An eye exam may show bleeding in the retina a central area of clearing. This is known as Roth's spots.
The following tests may be performed:
Blood culture and sensitivity (to detect bacteria)
Chest x-ray
Complete blood count (may show mild anemia)
CT scan of the chest
Echocardiogram (ultrasound of the heart)
Erythrocyte sedimentation rate (ESR)
Transesophageal echocardiogram
You will be admitted to the hospital so you can receive antibiotics through a vein. Long-term, high-dose antibiotic treatment is needed to get rid of the bacteria. Treatment is usually given for 4 - 6 weeks, depending on the specific type of bacteria. Blood tests will help your doctor choose the best antibiotic.
Surgery may be needed to replace damaged heart valves.
Patients diagnosed with Endocarditis should avoid using the following medications:
FondaparinuxIf you have been diagnosed with Endocarditis, consult your physician before starting or stopping any of these medications.
Directions to Hospitals Treating Infective Endocarditis
Early treatment of bacterial endocarditis generally has a good outcome. Heart valves may be damaged if diagnosis and treatment are delayed.
Blood clots or emboli that travel to brain, kidneys, lungs, or abdomen
Brain abscess
Congestive heart failure
Glomerulonephritis
Jaundice
Neurological changes |
Congenital_diaphragmatic_hernia_chest_x_ray | Common findings on chest x-ray include cyst like structures representing loops of bowel filling the left hemithorax, mediastinal shift to the right, and varying degrees of gas in the abdomen.
Chest x-ray findings:
Left hemithorax is filled with cystlike structures (loops of bowel).
Mediastinum is shifted to the right.
Abdomen is relatively devoid of gas; visible gas above the diaphragm may be seen.
If the chest radiograph is obtained before any air has entered the herniated bowel, diagnosing this condition with accuracy may be difficult. Similar difficulty arises when the liver alone is in the right hemithorax. In either case, the involved hemithorax is partially or totally opacified.
Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 6351
Case courtesy of Dr Alexandra Stanislavsky, Radiopaedia.org, rID: 15695 |
Capture_beat | A fusion beat occurs when electrical impulses from different sources act upon the same region of the heart at the same time. If it acts upon the ventricular chambers, it is called a ventricular fusion beat, wheres colliding currents in the atrial chambers produce atrial fusion beats.
Ventricular fusion beats can occur when the heart's natural rhythm and the impulse from a pacemaker coincide to activate the same part of a ventricle at the same time, causing visible variation in configuration and height of the QRS complex of an electrocardiogram reading of the heart's activity. This contrasts with the pseudofusion beat wherein the pacemaker impulse does not affect the complex of the natural beat of the heart. Pseudofusion beats are normal. Rare or isolated fusion beats caused by pacemakers are normal as well, but if they occur too frequently may reduce cardiac output and so can require adjustment of the pacemaker.
In some cases of VT with AV dissociation the SA node may transiently "capture" the ventricles, producing a capture beat, which has a normal QRS duration, or a fusion beat, in which the sinus and ventricular beats coincide |
Inclusion_body_myositis | Sporadic inclusion body myositis (sIBM) is an inflammatory muscle disease, characterized by slowly progressive weakness and wasting of the distal and proximal muscles, most aoid-related proteins within the cells and filamentous inclusions (hence the name inclusion body myositis) of abnormal proteins.
sIBM is a rare disease, diagnosed in only about 5 people per million, although not much research exists on the number of cases and some doctors feel the numbers are much higher. sIBM is an age-related disease - its incidence increases with age and symptoms usually begin after 50 years of age. Its prevalence rises to about 35 cases per million in people over 50 (Dalakas 2006). It is the most common acquired muscle disorder seen in older people, although about 20% of cases display symptoms before the age of 50. Weakness comes on slowly (over months or years) and progresses steadily and may lead to severe weakness and wasting of arm and leg muscles. It is slightly more common in men than women. Patients may become unable to perform daily living activities and most require assistive devices within 5 to 10 years of symptom onset. sIBM is not considered a fatal disorder - all things being equal, sIBM will not kill you (but the risk of serious injury due to falls is increased). There is no effective treatment for the disease.
The common type is sIBM - it strikes individuals apparently at random.
There is a type that has been observed in the siblings in several families: termed familial inflammatory sIBM, but is not passed on from generation to generation.
There are also several very rare forms of hereditary inclusion body myopathy (hIBM) that are linked to specific genetic defects and that are passed on from generation to generation, each inherited in different ways. See hereditary inclusion body myopathy.
The causes, of sIBM are currently unknown, though it is likely that it results from the interaction of a number of factors, both genetic and environmental. Our understanding of sIBM is slowly maturing and evolving.
Currently, there are two major theories about how sIBM is caused:
1). Some researchers (e.g., Dr. Dalakas) advocate the theory that the inflammation / immune reaction, caused by an unknown trigger - likely an undiscovered virus or an autoimmune disorder, is the primary, proximal cause of sIBM and that the degeneration of muscle fibres and protein abnormalities are secondary features.
Despite the arguments "in favor of an adaptive immune response in s-IBM, a purely autoimmune hypothesis for s-IBM is untenable because of the disease's resistance to most immunotherapy." (Collins, Inclusion Body Myositis, eMedicine article from WebMD, Last Updated: May 15, 2006, Retrieved March 28, 2007 from http://www.emedicine.com/neuro/topic422.htm#section~introduction)
2). Some researchers (e.g., Dr. Engel and Dr. Askanas) advocate the theory that sIBM is a degenerative disorder related to aging of the muscle fibres and that abnormal, potentially pathogenic protein accumulations in myofibers play a key causative role in s-IBM (apparently before the immune system comes into play). This theory emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum (ER) stress.
Dalakas 2006, says "we can say that two processes, one autoimmune and the other degenerative, occur in the muscle cells in parallel."
Dalakas 2006 suggests that a chain of events causes IBM -- some sort of virus, likely a retrovirus, triggers the cloning of T cells. These T cells appear to be driven by specific antigens to invade muscle fibers. In people with sIBM, the muscle cells display “flags” telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the endoplasmic reticulum (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In IBM, muscle fibers are overloaded with these major histocompatibility complex (MHC) molecules that carry the antigen prote type of autoimmune disorder. One confusing aspect is that medications that lower the immune response do not improve sIBM symptoms, as we would expect in the case of an autoimmune disorder.
When studied carefully, it has not been impossible to detect an ongoing viral infection in the muscles. The new theory is that a chronic viral infection might be the initial triggering factor setting IBM in motion. There have been a handful of IBM cases -- about 15 or so -- that have shown clear evidence of a virus called HTLV-1. This is a complex virus that can cause leukemia but in most cases, lays dormant and people end up being lifelong carriers of the virus. It's too early to say that this is the particular virus directly involved in causing IBM. The Dalakas article says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process (Dalakas, 2006).
As mentioned above, in the past, some researchers have suggested that it is the protein changes that are primary and that precede or trigger the abnormal immune response. From a recent article by Askanas and Engel: "Two hypotheses predominate regarding the key pathogenic mechanisms involved in s-IBM: an amyloid-b-related degenerative process and an immune dysregulation. Ultimately, both may be considered important, and their possible interrelationship may be clarified. An intriguing feature is the accumulation within s-IBM muscle fibers of amyloid-beta (Ab), phosphorylated tau protein, and at least 20 other proteins that are also accumulated in Alzheimer brain. In the s-IBM muscle fibers, there is evidence of misfolding of proteins, pathologic proteinaceous inclusions including aggresomes, abnormalities of the two protein-disposal systems involving the ubiquitin proteasome pathway and the lysosomes, mitochondrial dysfunctions, and oxidative stress. The pronounced T-cell inflammation can be striking, and it is characterized by activated, antigen-driven, cytotoxic CD8+ T-cells."
Askanas V, Dalakas MC, Engel WK. NEUROLOGY 2006;66 (Suppl 1): Si.
amyloid protein
beta amyloid protein
When sIBM was originally described, the major feature noted was muscle inflammation. Two other disorders were also known to display muscle inflammation, and sIBM was classified along with them. They are dermatomyositis (DM) and polymyositis (PM) and all three illnesses were called idiopathic inflammatory myositis or inflammatory myopathies (idiopathic means they don’t know what causes it).
It appears that sIBM and polymyositis share some common features, especially the initial sequence of immune system activation, however, polmyositis comes on over weeks or months, does not display the subsequent muscle degeneration and protein abnormalities as seen in IBM, and as well, polymyositis tends to respond well to treatments, IBM does not. IBM is often confused with (misdiagnosed as) polymyositis and polymyositis that does not respond to treatment is likely IBM.
Dermatomyositis appears to be a different disease altogether with different root causes unrelated to either PM or sIBM.
There are genetic features that do not directly cause IBM but that appear to predispose a person to getting IBM - having this particular combination of gene the MHC class II region (Dalakas 2006). sIBM is not passed on from generation to generation, although the susceptibility region of genes may be.
There are also several very rare forms of hereditary inclusion body myopathy (myopathies) that are linked to specific genetic defects and that are passed on from generation to generation. Because these forms do not show inflammation, they are classified as myopathies and not myositis types. Because they do not display inflammation as a primary symptom, they may in fact be similar, but different diseases than sporadic inclusion body myositis. There are several different types, each inherited in diffeeness by doctors and because of improved diagnostic tests. In spite of much progress, sIBM is still often difficult to diagnose and many patients are initially misdiagnosed, often with polymyositis.
The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as for manipulating pens, keys, buttons, and zippers, pulling handles, and firmly grasping handshakes. Arising from a chair becomes difficult. Walking becomes more precarious. Sudden falls, sometimes resulting in major injury to the skull or other bones, can occur, even from walking on minimally-irregular ground or from other minor imbalances outside or in the home, due to weakness of quadriceps and gluteus muscles depriving the patient of automatic posture maintenance. A foot-drop can increase the likelihood of tripping. Dysphagia can occur, usually caused by upper esophageal constriction that often can be symptomatically improved, for several months to years, by bougie dilation per a GI or ENT physician. Respiratory muscle weakness can sometimes eventuate." W. King Engel, and Valerie Askanas NEUROLOGY 2006;66 (Suppl 1): S20–S29
Dalakas (2006) says: "If a patient has the typical clinical phenotype of sIBM, but the muscle biopsy shows only features of a chronic inflammatory myopathy (inflammation, large fibers, splitting, and increased connective tissue, but no vacuoles), the diagnosis is probable sIBM. If, however, there is also strong upregulation of major histocompatibility complex (MHC) class I antigens (see below), and amyloid deposits and cytochrome-oxidase-negative fibers are present, the diagnosis of sIBM is rather more certain. . . . Shaking hands with a patient can provide the first indication of sIBM, because of the weak grip. If the patient complains of falls due to weakness at the knees and feet, has atrophic thighs, and does not report paresthesias or cramps, sIBM is very likely. Diagnostic dilemmas arise when the weakness and atrophy are slightly asymmetric or limited to the lower extremities, raising the possibility of a lower motor neuron disease. Motor neuron disorders, however, can be distinguished from IBM by the presence of hyperreflexia, cramps, fasciculations and large motor units on EMG."
This is an enzyme in the blood produced when muscle cells are damaged, normally by the ordinary wear and tear of everyday life. Elevated levels indicate that abnormal muscle damage has occurred, or is occurring. Typically, in sIBM, CK values are about 10 times normal levels but may fall during the course of the disease (Dalakas 2006).
The best test to diagnose sIBM is a muscle biopsy (MBx). A small piece of muscle is surgically removed and then is studied in the laboratory. Several major changes in the muscle cells are usually visible that are characteristic of sIBM:
Inflammation is present and inflammatory cells are seen invading the muscle cells
Holes ("vacuoles") appear in the muscle fibers ("vacuolar degeneration")
Inclusions ("clumps" of material) are found inside the muscle fibers, these are associated with the build-up of several different abnormal proteins, including tau protein and beta amyloid.
There are twisted, abnormal filamentous protein strands called "paired-helical filaments" (PHFs). PHFs contain a protein called phosphorylated tau that shows up when the muscle is tested with a stain called SMI-31 monoclonal antibody – this test recognizes p-tau of the PHFs within s-IBM muscle fibers and also in the AD brain.
Another abnormal protein is called ubiquitin. Inclusions containing ubiquitin can usually be seen in the muscle biopsies of sIBM patients, but they do not appear in any other muscle illnesses (e.g., not in polymyositis).
An electromyography (EMG) is often done and shows characteristic abnormalities. In this test, a small electric current is put into a muscle and a machine records how the muscle responds.
There have been several attempts to use different medications (immunotherapies) to treat sIBM but in clinical trials, although some have produced minor short term improvements, none has been shown to be effective in the long term. These include the common immunotherapeutic agents, such as corticosteroids, azathioprine, methotrexate, cyclosporine, cyclophosphamide and total lymphoid irradiation. Why this is so is a mystery because based on the theory presented here these drugs should have a better effect in helping IBM. The response of dysphagia to intravenous immunoglobulin can be significant (Dalakas, 2006). No medication has yet been developed specifically for sIBM.
New treatments called Biologic agents (Biologics) are being developed to treat immune disorders -- these are not drugs as we commonly understand them, made from chemicals, they are developed from proteins taken from the cell. One study by Dalakas is now under way is using an agent called Campath (alemtuzumab) to treat IBM (see below).
Currently (October 2006) a study is being done to examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). See: [2]
Published online before print October 31, 2006
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0603386103
MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle.
Roberta Morosetti *, Massimiliano Mirabella *, Carla Gliubizzi *, Aldobrando Broccolini *, Luciana De Angelis ¶, Enrico Tagliafico ||, Maurilio Sampaolesi **, Teresa Gidaro *, Manuela Papacci *, Enrica Roncaglia ||, Sergio Rutella , Stefano Ferrari ||, Pietro Attilio Tonali *, Enzo Ricci *, and Giulio Cossu **
,*Department of Neurosciences and Interdisciplinary Laboratory for Stem Cell Research and Cellular Therapy, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy; Fondazione Don Carlo Gnocchi, 00194 Rome, Italy; Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park, 00128 Rome, Italy; ¶Department of Histology and Embriology, University "La Sapienza," 00161 Rome, Italy; ||Department of Biomedical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy; **Stem Cell Research Institute, San Raffaele Hospital, 20132 Milan, Italy; Institute of Hematology, Catholic University, 00168 Rome, Italy; and Department of Biology, University of Milan, 20133 Milan, Italy
Edited by Tullio Pozzan, University of Padua, Padua, Italy, and approved September 19, 2006 (received for review April 28, 2006)
This is a highly selective layman's translation and synopsis. Please refer to the original article for confirmation of the information presented here.
Synopsis:
This research reports the isolation and characterization of mesoangioblasts, [ME - so - angie - OH - blasts] vessel-associated stem cells, obtained from the diagnostic muscle biopsies of patients with inflammatory myopathies (IM). Mesoangioblasts represent a distinct type of mesoderm progenitor cells that eventually develop (differentiate) into a variety of mesoderm tissues including skeletal, cardiac and smooth muscle. The number of mesoangioblast cells isolated, their rate of growth and lifespan, their marker expression, and their ability to differentiate into smooth muscle do not differ between mesoangioblasts from normal patients and IM mesoangioblasts. IBM mesoangioblasts show the same ability to divide that is observed in normal muscle suggesting that the disease has not reduced their proliferation potency. Nevertheless, although IBM mesoangioblasts can normally differentiate into smooth muscle cells (SMCs), their differentiation into skeletal muscle seems markedly impaired, because no skeletal myotubes are seen arising from IBM mesoangioblasts after laboratory stimulation. Thus, mesoangioblasts isolated from IBM, fail to differentiate into skeletal myotubes (developing skeletal muscle fibers characterized by their tubular appearance).
IBM mesoangioblasts were found to express high levels of genes known to inhibit the generation of new muscle (myogenesis) such as TGFbeta-1, SFRP-2 (secreted frizzled-related protein 2), and BHLHB3 (basic helix-loop-helix domain containing class B3 transcription factor).
In IBM mesoangioblasts, BHLHB3, is highly over active and this in turn inhibits MyoD function, thus preventing the creation of new muscle (myogenesis). IBM mesoangioblasts did not give rise to differentiated myotubes and did not display any MyoD genetic activity (no MyoD mRNA), and MyoD could not be induced by the researcher's laboratory techniques.
The problem of reduced MyoD function in IBM can be addressed in two ways. First, through cell transplantation. Using a mouse model, the researchers treated [human] IBM mesoangioblasts in the laboratory with a virus (an adenoviral vector) carrying with it the full-length mouse MyoD. So, the researchers took the genetic code for MyoD from mice and used the virsus to put it into these IBM mesoangioblast cells. These treated cells were then transplanted into the muscle of special research mice, significantly restoring normal muscle function. This introduction of MyoD overcomes the BHLHB3 inhibition. It also activates the MyoD that is already present in the cells, irreversibly making the cells generate new muscle.
Second, the researchers examined the effect of using a genetic method to block out the function of the BHLHB3 gene. The IBM mesoangioblasts display increased levels of BHLHB3 messenger RNA (mRNA), the inhibitor of MyoD. Therefore, the researchers used small interfering RNA (siRNA) created specifically to block the action of BHLHB3 in mesoangioblasts from three IBM patients. The siRNA treated cells were able to differentiate into muscle, giving rise to muscle myotubes after 7 days.
Therefore, either by silencing the overactive BHLHB3 gene or by transplanting modified cells in order to over express MyoD, we should be able to restore muscle genesis in the IBM mesoangioblasts, opening the way for new cell-based therapeutic strategies to treat IBM.
Page by a patient (the creator of this page) [3]
Online IBM patient support group: [4] |
Swelling_of_the_feet | History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | 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
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Procaine | Procaine is a local anesthetic that is FDA approved for the {{{indicationType}}} of local Anesthetic for local infiltration and peripheral nerve block. Common adverse reactions include myocardial depression, hypotension, hypertension, bradycardia, ventricular arrhythmias, cardiac arrest,nausea / vomiting, cutaneous lesions of delayed onset, urticaria, edema related to allergic reactions , nervousness, dizziness, blurred vision, tremors may occur due to systemic toxicity, drowsiness or convulsions with subsequent unconsciousness and respiratory arrest..
Procaine 0.25% to 0.5% solutions in doses of 350 to 600 milligrams may be used for Infiltration Anesthesia. Epinephrine may be added for vasoconstrictive effect to give a final concentration of 1:200,000.
For, Procaine 0.5% solution (up to 200 milliliters), 1% solution (up to 100 milliliters), or 2% solution (up to 50 milliliters) is recommended. The 2% solution is generally limited to procedures requiring a small volume of anesthetic, ie, 10 to 25 milliliters (mL). An anesthetic solution of 0.5 mL to 1 mL of Epinephrine 1:1,000 per 100 mL may be used to promote vasoconstriction (1:200,000 or 1:100,000).
To prepare 60 milliliters (mL) of a 0.5% solution (5 milligrams/mL), dilute 30 mL of the 1% solution with 30 mL sodium chloride 0.9% injection. To prepare 60 mL of a 0.25% solution (2.5 milligrams/mL), dilute 15 mL of the 1% solution with 45 mL sodium chloride 0.9% injection .
A dose of procaine 50 milligrams of a 10% solution mixed with an equal amount of diluent may be used for Anesthesia of the perineum; 100 milligrams (1 milliliter) diluted with an equal amount of diluent for the perineum and lower extremities; and up to 200 milligrams (2 milliliters) with 1 milliliter of diluent for anesthesia of the costal margin.
Usual total dose of Procaine during one treatment should not exceed 1000 milligrams.
The serum half-life of Procaine has been prolonged in some uremic patients.
The serum half-life of Procaine has been prolonged in patients with liver disease; dosage reductions are recommended.
Patient response to Procaine varies, and reduced doses should be given to elderly or acutely ill patients (Prod Info Procaine(R), 1990a).
Procaine doses should be reduced in patients with cardiac disease.
Reduced doses of procaine may be necessary for obstetric delivery and in patients with increased intra-abdominal pressure.
There is limited information regarding Off-Label Guideline-Supported Use of Procaine in adult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Procaine in adult patients.
For Infiltration Anesthesia, the maximum recommended Procaine dose is 15 milligrams/kilogram of a 0.5% solution in pediatric patients.
There is limited information regarding Off-Label Guideline-Supported Use of Procaine in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Procaine in pediatric patients.
Procaine is contraindicated in patients with a known hypersensitivity to procaine, drugs of a similar chemical configuration, or para-aminobenzoic acid or its derivatives.
It is also contraindicated in patients with a known hypersensitivity to other components of solutions of Procaine.
Contains acetone sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Local anesthetics should only be employed by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies which might arise from the block to be employed, and then only after insuring the immediate availability of oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies. (see also adverse reactions and precautions.) delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.
It is essential that aspiration for blood or cerebrospinal fluid, where applicable, be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.
Reactions resulting in fatality have occurred on rare occasions with the use of local anesthetics, even in the absence of a history of hypersensitivity. Large doses of local anesthetics should not be used in patients with heartblock.
Procaine with epinephrine or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur. Likewise, solutions of Procaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension or disturbances of cardiac rhythm may occur.
Local anesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection.
Mixing or the prior or intercurrent use of any local anesthetic with Procaine cannot be recommended because of insufficient data on the clinical use of such mixtures.
Reactions to procaine are characteristic of those associated with other ester-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels which may be due to overdosage, rapid absorption, inadvertent intravascular injection, or slow metabolic degradation.
A small number of reactions may result from hypersensitivity, idiosyncrasy, or diminished tolerance to normal dosage.
The most commonly encountered acute adverse experiences which demand immediate countermeasures are related to the central nervous system and the cardiovascular system. These adverse experiences are generally dose related and due to high plasma levels which may result from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of nerve blocks near the vertebral column (especially in the head and neck region), may result in underventilation or apnea (“Total or High Spinal”). Factors influencing plasma protein binding, such as acidosis, systemic diseases which alter protein production, or competition of other drugs for protein binding sites may diminish individual tolerance.
Plasma cholinesterase deficiency may also account for diminished tolerance to ester-type local anesthetics.
These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest.
The incidence of convulsions associated with the use of local anesthetics varies with the procedure used and the total dose administered.
High doses or inadvertent intravascular injection may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock, hypotension (or sometimes hypertension), bradycardia, ventricular arrhythmias, and cardiac arrest. (See Warnings, Precautions, and Overdosage sections.)
Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients, such as the antimicrobial preservative chlorobutanol contained in multiple-dose vials. These reactions are characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and, possibly, anaphylactoid-like symptomatology (including severe hypotension). Cross sensitivity among members of the ester-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established.
The incidences of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered, and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient. Many of these effects may be related to local anesthetic techniques, with or without a contribution from the drug.
There is limited information regarding Procaine Postmarketing Experience in the drug label.
The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.
Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.
The clinical observation has been made that despite adequate sulfonamide therapy, local infections have occurred in areas infiltrated with procaine hydrochloride prior to diagnostic punctures and drainage procedures. Therefore, Procaine should not be used in any condition in which a sulfonamide drug is being employed since para-aminobenzoic acid inhibits the action of the sulfonamide.
Pregnancy Category (FDA): C
Animal reproduction studies have not been conducted with Procaine. It is not known whether procaine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Procaine should be given to a pregnant woman only if clearly needed and the potential benefits outweigh the risk. This does not exclude the use of procaine hydrochloride at term for obstetrical anesthesia or analgesia. (See Labor and Delivery.)
Pregnancy Category (AUS):
There is no Australian Druperformed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function.
Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.
Paracervical or pudendal anesthesia may alter the forces at parturition through changes in uterine contractility or maternal expulsive efforts. In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. The use of obstetrical anesthesia may increase the need for forceps assistance.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. The long-term significance of these observations is unknown.
Fetal bradycardia which frequently follows paracervical block may be indicative of high fetal blood concentrations of procaine with resultant fetal acidosis. Fetal heart rate should be monitored prior to and during paracervical block. Added risk appears to be present in prematurity, toxemia of pregnancy, and fetal distress. The physician should weigh the considering paracervical block in these conditions. Careful adherence to recommended dosage is of the utmost importance in paracervical block. Failure to achieve adequate analgesia with these doses should arouse suspicion of intravascular or fetal injection.
Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and usually manifest seizures within six hours. Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication.
Case reports of maternal convulsions and cardiovascular collapse following use of some local anesthetics for paracervical block in early pregnancy (as anesthesia for ele dose of the local anesthetic should not be exceeded. Injection should be made slowly and with frequent aspiration. Allow a five-minute ius position or a blanket roll or sandbag may be placed beneath the right hip and the gravid uterus displaced to the left.
It is not known whether local anesthetic drugs are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when local anesthetics are administered to a nh plasma levels encountered during therapeutic use of local anesthetics or to unins, and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.
The first step in the management of systemic toxic reactions, as well as underventilation oconmg to 100 mg bolus IV injection of succinyl pevous system, respiratory and cardiac function, add to postictal depression, and may result in apnea. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should he evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a ons demonstrated rapid development of hypoxia, hypercarbia, and acidosis within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions, and emphasize the importance of immediate and effective ventilation with oxygen which may avoid e local anesthetic may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arr injection of local anesthetic solution may produce these same signs and also lead to cardiac a instituted and maintained gerous in pregnant women at term because of aortocaval compression by the gravid uterus. Therefore, during treatment of systemic toxicity, maternal hypotensione, or manual displacement of the uterus off the great nd bySwing structural formula:
This image is provided by the National Library of Medicine.
The solutions are made isotonic with sodium chloride and the pH is adjusted between 3 and 5.5 with sodium hydroxide and/or hydrochloric acid.
Procaine hydrochloride is related chemically and pharmacologically to the ester-type local anesthetics. It contains an ester linkage between the aromatic nucleus and the amino group.
Procaine is available as sterile solutions in concentrations of 1% and 2% for injection via local infiltration and peripheral nerve block.
Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block and ultimately to cardiac arrest. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.
Following systemic absorption, local anesthetics can prodrestlessness, tremors and shivering, progressing to convulsions, followed by depression, and coma progressing ultimately to respiratory arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher ceninistration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.he individual. Procaine will normally provide anesthesia whund drug is available for placental transfer. The extent of placental transfer is also determined by the degree of ionization and lipid solubility of the drug. Lipid, soluble nonionized drugs readily enter the fetalblood from the maternal circulation.
Depending upon the route of administration, local anesthetics are distributed to some ain.
Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic o.
Procaine is readily absorbed following parenteral adminis following initial use.
This image is provided by the National Library of Medicine.
There is limited information regarding Procaine Storage in the drug label.
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When appropriate, patients should be informed, in advance, that they may experience temporary loss of sensation and motor activity following proper administration of regional anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions in the package insert.
Alcohol-Procaine interaction has not been established. Talk to your doctor about the effects of taking alcoh |
Primary_stem_villi | Chorionic villi are villi that sprout from the chorion in order to give a maximum areateagrammatic. |
Subarachnoid_hemorrhage_physical_examination | eout ipsilateral mydriasis, which results from rupture of a posterior communicating artery aneurysm.
Abducens nerve palsy is usually due to increased ICP rather than a true localizing sign
Monocular vision loss can be caused by an ophthalmic artery aneurysm compressing the ipsilateral optic nerve
Hemiparesis results from middle cerebral artery (MCA) aneurysm, ischemia or hypoperfusion in the vascular territo |
Carcinoma_of_lung | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
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Nutritional_supplement | A dietary supplement (also known as food supplement) is intended to supply nuperson's diet. This category may also include herbal supplements which may have added health benefits.
In the United States, a dietary supplement is defined under the Dietary Supplement Health and Education Act of 1994 (DSHEA) as a product that is intended to supplement the diet and bears or contains one or more of the following dietary ingredients:
a vitamin
a mineral
an herb or other botanical (excluding tobacco)
an amino acid
a dietatbelieved that the federal government should review the safety of dietary supplements and approve them before they can be marketed to consumers.
Similar confusion about the implications of DSHEA was noted in an October 2002 nationwide Harris poll. Here, 59% of respondents believed that supplements had to be approved by a government agency before they could be marketed; 68% believed that supplements had to list potential side effects on their labels; and 55% believed that supplement labels could not make study, published in Archives of Internal Medicine, found broad public support for greater governmental regulation of dietary supplements than is currently permitted by DSHEA. The researchers found that a majority of Americans supported pre-marketing approval by the FDA, increased oversight of harmful supplements, and greater scrutiny of the truthfulness of supplement label claims.
The claims that a dietary supplement makes are essential toa treatment or cure for a specific disease or condet a specific product.
Dietary supplements are permitted to make structure/function claims. These are broad claims that the product can support the structure or function of the body (e.g., "glucosamine helps support healthy joints"). The FDA must be notified of these claims within 30 days of their first use, and there is a requirement that these claims be substantiated.
Other claims that required approval from FDA include health claims and qualified health claims. Health claims are permitted to be made if they meet the requirements for the claims found in the applicable regulations. Qualified health claims can be made through a petition process, including scientific information, if FDA has not approved a prior petition.
The Food Supplements Directive requires that supplements be demonstrated to be safe, both in quantity and quality. Some vitamins are essential in small quantities but dangerous in large quantities, notably Vitamin A. Consequently, only those supplements that have been proven to be safe may be sold without prescription. In practice, the number of reported incidents with food supplements is nevertheless low.
In Europe, it is also an established view that food supplements should not be labeled with drug claims but can bear health claims, although to a degree that differs from one member state to the other.
The umers throughout Europe, including over one million in r manufacturers to add vitamins and minerals to the list of ingredients of a food supplement, that refusal must be on scientifas of 15 April, 1997, underminology:
As a rule, BADSs are foodstuffs with clinically proven effectiveness. BADSs are recommended not only for prophylactics, but can be included into a complex therapy for the relpplements (Press release)
↑ Bjelakovic, G. (2007). "Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention". Journal of the American Medical Association. 297: 842–857. Retrieved 2007-04-23. Unknown parameter |coauthors= ignored (help)
Dietary Supplement Information from the U.S. Food and Drug Administration
What's in the Bottle? An Introduction to Dietary Supplements, from the U.S. National Center for Complementary and Alternative Medicine
Safety information on herbal supplements, from the U.S. National Institutes of Health
Use of Complementary and Alternative Medicine (CAM) by the American Public: A report of the Institute of Medicine
Botanical Medicines: The Need for New Regulations, from the New England Journal of Medicine
vteDietary supplementsTypesAmino acids • Fatty acids • Herbal Supplements • Minerals • Probiotics • Vitamins • Whole food supplementsVitamins and mineralsRetinol (Vitamin A) • B vitamins: Thiamine (B1) • Riboflavin (B2)• Niacin (B3)• Pantothenic acid (B5)• Pyridoxine (B6)• Biotin (B7)• Folic acid (B9) • Cyanocobalamin (B12) • Ascorbic acid (Vitamin C) • Ergocalciferol and Cholecalciferol (Vitamin D) • Tocopherol (Vitamin E) • Naphthoquinone (Vitamin K) • Calcium • Choline • Chlorine • Chromium • Cobalt • Copper • Fluorine • Iodine • Iron • Magnesium • Manganese • Molybdenum • Phosphorus • Potassium • Selenium • Sodium • Sulfur • ZincOther common ingredientsCarnitine • Chondroitin sulfate • Cod liver oil • Copper gluconate • Creatine • Dietary fiber • Elemental calcium • Ephedra • Fish oil • Folic acid • Ginseng • Glucosamine • Glutamine • Iron supplements • Japanese Honeysuckle • Krill oil • Lactobacillus • Lingzhi • Linseed oil • Melatonin • Red yeast rice • Royal jelly • Saw palmetto • Spirulina • Taurine • Wheatgrass • Wolfberry • Yohimbine • Zinc gluconateRelated articlesCodex Alimentarius • Enzyte • Metabolife • Hadacol • Nutraceutical • Multivitamin
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Filiform_papilla | Template:Infobox Anatomy
The filiform papillae are thin, long papillae "V"-shaped cones that don't contain taste buds but are the most numerous. These papillae are mechanical and not involved in gustation covering most of the dorsal (top). Characterized increased keratinization. papillae (projections)
They are small and arranged in lines parallel to the V-shaped row of circumvallate papillae, except at the tip of the tongue where they are aligned transversely.
Close-up view of a tongue with visible fungiform papillae (large bumps) scattered among filiform papillae (small bumps).
Projecting from their apices are numerous filamentous processes, or secondary papillae. These are of a whitish tint, owing to the thickness and density of the epithelium of which they are composed. This epithelium has undergone a peculiar modification as the cells have become cornified and elongated into dense, imbricated, brush-like processes.
They contain also a number of elastic fibers, which render them firmer and more elastic than the papillae of mucous membrane generally.
The larger and longer papillae of this group are sometimes termed papillae conicae.
Fungiform papillae are found dispersed throughout the filiform papillae.
Papilla
Tongue
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Thyroid_adenoma_classification | Thyroid adenoma may be classified based on FNA cytology into 6 groups include macrofollicular, adenomatoid, colloid adenomas, nodular goiter, lymphocytic thyroiditis and granulomatous thyroiditis.
Thyroid adenoma may be classified based on Fine needle aspiration (FNA) cytology into 6 groups (known as The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)) : Macrofollicular, Adenomatoid/hyperplastic nodules, Colloid adenomas, Nodular goiter, Lymphocytic thyroiditis, Granulomatous thyroiditis
For information on the classification of thyroid nodules, click here.
↑ Cibas ES, Ali SZ (2009). "The Bethesda System for Reporting Thyroid Cytopathology". Thyroid. 19 (11): 1159–65. doi:10.1089/thy.2009.0274. PMID 19888858.
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Hinge_joint | In the hinge joint (ginglymus), the articular surfaces are moulded to each other in such a manner as to permit motion only in one plane, forward and backward, the extent of motion at the same time being considerable.
The direction which the distal bone takes in this motion is seldom in the same plane as that of the axis of the proximal bone; there is usually a certain amount of deviation from the straight line during flexion.
The articular surfaces are connected together by weak collateral ligaments, which form their chief bond of union.
The best examples of ginglymus are the interphalangeal joints and the joint between the humerus and ulna; the knee- and ankle-joints are less typical, as they allow a slight degree of rotation or of side-to-side movement in certain positions of the limb.
Interphalangeal articulations of hand
Interphalangeal articulations of foot
Diagram at ntu.edu.tw
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Myositis | Myositis is a general term for inflammation of the muscles. Many such conditions are considered likely to be caused by autoimmune conditions, rather than directly due to infection (although autoimmune conditions can be activated or exacerbated by infections.)
Elevation of creatine kinase (CK) in blood is indicative of myositis. The MM and not the MB or BB fraction of the CK will be elevated.
Myositis must be differentiated from the following conditions causing muscle weakness, hypotonia, or flaccid paralysis:
The following drugs or conditions may additionally need to be differentiated from myositis:
Atorvastatin
Cellulitis
Deep vein thrombosis
Dermatomyositis
Dolutegravir
Hematoma
Idiopathic inflammatory myopathies
Inclusion body myositis
Influenza myositis
Juvenile dermatomyositis
Lovastatin
Lyme myositis
Myositis ossificans
Neuromuscular complications accompanying AIDS
Osteoarthritis
Osteomyelitis
Paraneoplastic neuropathy
Peripheral vascular disease
Polymyositis
Pravastatin (less likely than other statins)
Pyomyositis
Rheumatoid arthritis
Simvastatin
Statin therapy
Systemic lupus erythematosus
Toxoplasma myositis
Trichinosis
Trypanosomiasis
Tuberculous pyomyositis
Viral myositis (including following an episode of influenza)
Wasting syndrome
Pembrolizumab
Pergolide
Zidovudine
(Images courtesy of RadsWiki)
, Myositis, Myositis ,
, Myositis, Myositis ,
, Myositis, Myositis ,
, Myositis, Myositis ,
, Myositis, Myositis ,
myopathy (muscle disease)
myalgia (muscle pain)
The Myositis Association
NIH
FAQ
Arthritis.org
The Johns Hopkins Myositis Center
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↑ 1.0 1.1 Kira R (February 2018). "[Acute Flaccid Myelitis]". Brain Nerve (in Japanese). 70 (2): 99–112. doi:10.11477/mf.1416200962. PMID 29433111.CS1 maint: Unrecognized language (link)
↑ Hopkins SE (November 2017). "Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations". Curr Treat Options Neurol. 19 (12): 48. doi:10.1007/s11940-017-0480-3. PMID 29181601.
↑ Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR (September 2016). "Acute flaccid myelitis: A clinical review of US cases 2012-2015". Ann. Neurol. 80 (3): 326–38. doi:10.1002/ana.24730. PMC 5098271. PMID 27422805.
↑ Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K (February 2018). "Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015". Clin. Infect. Dis. 66 (5): 653–664. doi:10.1093/cid/cix860. PMC 5850449. PMID 29028962.
↑ Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters H, Tyler KL, Abzug MJ, Dominguez SR (August 2018). "Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality". Lancet Infect Dis. 18 (8): e239–e247. doi:10.1016/S1473-3099(18)30094-X. PMID 29482893. Vancouver style error: initials (help)
↑ Chen IJ, Hu SC, Hung KL, Lo CW (September 2018). "Acute flaccid myelitis associated with enterovirus D68 infection: A case report". Medicine (Baltimore). 97 (36): e11831. doi:10.1097/MD.0000000000011831. PMC 6133480. PMID 30200066.
↑ "Botulism | Botulism | CDC".
↑ McCroskey LM, Hatheway CL (May 1988). "Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract". J. Clin. Microbiol. 26 (5): 1052–4. PMC 266519. PMID 3290234.
↑ Lindström M, Korkeala H (April 2006). "Laboratory diagnostics of botulism". Clin. Microbiol. Rev. 19 (2): 298–314. doi:10.1128/CMR.19.2.298-314.2006. PMC 1471988. PMID 16614251.
↑ Brook I (2006). "Botulism: the challenge of diagnosis and treatment". Rev Neurol Dis. 3 (4): 182–9. PMID 17224901.
↑ Dimachkie MM, Barohn RJ (May 2013). "Guillain-Barré syndrome and variants". Neurol Clin. 31 (2): 491–510. doi:10.1016/j.ncl.2013.01.005. PMC 3939842. PMID 23642721.
↑ Walling AD, Dickson G (February 2013). "Guillain-Barré syndrome". Am Fam Physician. 87 (3): 191–7. PMID 23418763.
↑ Gilhus NE (2011). "Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy". Autoimmune Dis. 2011: 973808. doi:10.4061/2011/973808. PMC 3182560. PMID 21969911.
↑ Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA (May 2004). "Transverse Myelitis: pathogenesis, diagnosis and treatment". Front. Biosci. 9: 1483–99. PMID 14977560.
↑ Amato AA, Greenberg SA (December 2013). "Inflammatory myopathies". Continuum (Minneap Minn). 19 (6 Muscle Diing. Rochester-Toronto Magnetic Resonance Study Group". Arch Neurol. 51 (1): 61–6. PMID 8274111.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑ Riva N, Agosta F, Lunetta C, Filippi M, Quattrini A (2016). "Recent advances in amyotrophic lateral sclerosis". J Neurol. 263 (6): 1241–54. doi:10.1007/s00415-016-8091-6. PMC 4893385. PMID 27025851.CS1 maint: Multiple names: authors list (link)
↑ Michelle EH, Mammen AL (2015). "Myositis Mimics". Curr Rheumatol Rep. 17 (10): 63. doi:10.1007/s11926-015-0541-0. PMID 26290112.
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Endodontology | If decay progresses to the first stage, a small filling will be required. If decay develops to the third stage depicted, root canal therapy will be required.
Endodontics is a specialty of dentistry, that deals with the tooth pulp and tissues surrounding the root of a tooth. The pulp (containing nerves, arterioles and venules as well as lymphatic tissue and fibrous tissue) can become diseased or injured and thus is unable to repair itself. The pulp then dies and endodontic treatment is required. The word comes from the Greek words endo meaning inside and odons meaning tooth. Literally taken, it means study of that which is "inside the tooth".
Endodontists are dentists who have specialized in this field. Typically they have completed an additional 2-3 years of training following dental school. Many endodontic residents do original research and earn a Master's degree as well as a specialty certificate. They specialize and limit their practice to root canal therapy and root canal surgery. Patients requiring root canal therapy are either referred by their general dentists to the endodontist or are self referred. Root canal therapy is also a standard procedure for general dentists.
The most common procedure done in endodontics is root-canal therapy. This procedure aims to save a tooth that would otherwise be extracted (pulled) due to infection caused by decay (a cavity in the tooth), a large filling, or trauma to the tooth. Root canal therapy involves the removal of diseased pulp tissue inside the tooth (the area inside the tooth that becomes infected due to the aforementioned reasons). The aim of treatment is to remove irreversibly inflamed, or necrotic pulp tissue before infection sets in (or after it has already set in). When the pulp tissue becomes infected, caused by bacteria from inside the tooth, the infection can leak out of the tooth's root and make the surrounding bone ill and painful or cause an abscess to form. Once the diseased pulp tissues are removed, the body's defense system can then repair the damage created by disease. Usually, this will require 2-3 visits to your dentist. The dentist will use a local anesthetic to make the procedure pain-free. In most places, it is considered a standard of care to use a rubber dam in order to isolate the tooth and provide a clean environment. An opening is made on the top of the tooth. Then the pulp chamber and root canals are cleaned and shaped for filling and sealing. Often, an intra-pulpal medicament to inhibit bacterial growth is placed and the tooth is filled with a temporary restoration until the second appointment, where the temporary restoration and medicament are removed and the canal(s) are sealed with gutta-percha--thus completing the procedure. Increasingly, however, endodontic treatment is being performed in one appointment as clinicians are finding fewer incidents of infection and pain with one-appointment vs. two appointment treatment.
Other procedures practiced in endodontics include incision for drainage and periradicular surgery. These treatments are needed in cases of abscesses, root fractures, and problematic tooth anatomy.
Root canal
Journal of Endodontics
Oral surgery
Dental dam
American Association of Endodontists
American Board of Endodontics
International Endodontic Journal
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Pheochromocytoma_surgery#cite_note-pmid25188716-3 | Surgery is the mainstay of treatment for pheochromocytoma. Adrenalectomy, laparoscopic transabdominal and retroperitoneal approaches have been used successfully for non-metastatic abdominal pheochromocytomas.
The mainstay of treatment for pheochromocytoma is surgery. Surgical resection is usually done for patients with either: Benign localized tumor, Unilateral pheochromocytoma- Unilateral adrenalectomy, Bilateral pheochromocytomas- cortical-sparing adrenalectomy.
Surgery is the mainstay of treatment for pheochromocytoma.
Two approaches have been used successfully for non-metastatic abdominal pheochromocytomas: Laparoscopic transabdominal, Retroperitoneal
There are less complications associated with laparoscopic surgery than with open surgery.
Major intraoperative complications include: Intraoperative tumor capsule rupture, Hypertensive crisis, Myocardial infarctions, Cerebrovascular hemorrhages, Hemodynamic instability after tumor resection. Hypoglycemia , Severe hypotension
Surgery is the mainstay of treatment for pheochromocytoma, even if it is asymptomatic.
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Mucosa-associated_lymphoid_tissue_(MALT)_lymphoma | Staging | History and Symptoms | Physical Examination | Laboratory Findings | Upper GI Endoscopy | CT | MRI | Endoscopic Ultrasound | Biopsy | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
vteMyeloid Hematological malignancy/leukemia histology (ICD-O 9590-9989, C81-C96, 200-208)CFU-GM/and other granulocytesTemplate:Navbox subgroupMEPTemplate:Navbox subgroupCFU-MastMastocytoma (Mast cell leukemia, Mast cell sarcoma, Systemic mastocytosis)Multiple/unknownAML (Acute panmyelosis with myelofibrosis, Myeloid sarcoma) · MP (Myelofibrosis) · Acute biphenotypic leukaemiaSee also hematology, lymphoid malignancy
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Palmar_plantar_erythrodysesthesia_causes | Several different chemotherapeutic agents have been associated with palmar plantar erythrodysesthesia (PPE). Most frequently associated drugs include cytarabine, docetaxel, doxorubicin, liposomal-encapsulated doxorubicin, 5-fluorouracil, and capecitabine.
Chemotherapy drugs that can cause this syndrome include:
Most Frequently Associated:
Cytarabine (Cytosar-U)
Docetaxel (Docefrez, Taxotere)
Doxorubicin (Adriamycin) and liposomal-encapsulated doxorubicin (Doxil)
5-Fluorouracil (5-FU, Adrucil)
Capecitabine (Xeloda)
Less Frequently Associated:
Cisplatin
Cyclophosphamide
Daunorubicin and liposomal daunorubicin
Doxifluridine
Etoposide
Floxuridine (FUDF)
Hydroxyurea (hydroxycarbamide)
6-Mercaptopurine
Methotrexate
Mitotane
Paclitaxel (Taxol)
Tegafur
Vinorelbine
Idarubicin (Idamycin)
Vemurafenib (Zelboraf)
6-thioguanine
Targeted Therapy Drugs Causing PPE:
Axitinib (Inlyta)
Cabozantinib (Cabometyx, Cometriq)
Regorafenib (Stivarga)
Sorafenib (Nexavar)
Sunitinib (Sutent)
Pazopanib (Votrient) |
Omega-3_fatty_acid#Botanical_sources | ω−3 fatty acids (commonly spelled omega-3 fatty acids) are a family of polyunsaturated fatty acids which have in common a carbon-carbon double bond in the ω−3 position.
Important nutritionally essential ω−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). For a more complete list, see list of ω−3 fatty acids. The human body cannot synthesize ω−3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated ω−3 fatty acids from the eighteen-carbon ω−3 fatty acid, α-linolenic acid. These conversions occur competitively with ω−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the ω−3 α-linolenic acid and ω−6 linoleic acid are essential nutrients which must be obtained from food. Synthesis of the longer ω−3 fatty acids from linolenic acid within the body is competitively slowed by the ω−6 analogues. Thus accumulation of long-chain ω−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of ω−6 analogs do not greatly exceed the amounts of ω−3.
Chemical structure of alpha-linolenic acid (ALA), an essential ω−3 fatty acid, (18:3Δ9c,12c,15c). Although chemists count from the carbonyl carbon (blue numbering), physiologists count from the ω (omega) carbon (red numbering). Note that from the ω end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "ω−3"
For detail on ω (omega) nomenclature and numbering, see EFA Nomenclature.
The term ω−3 (aka "n−3", "omega-3") signifies that the first double bond exists as the third carbon-carbon bond from the terminal methyl end (ω) of the carbon chain.
ω−3 fatty acids which are important in human nutrition are: α-linolenic acid (18:3, ALA), eicosapentaenoic acid (20:5, EPA), and docosahexaenoic acid (22:6, DHA). These three polyunsaturates have either 3, 5 or 6 double bonds in a carbon chain of 18, 20 or 22 carbon atoms, respectively. All double bonds are in the cis-configuration, i.e. the two hydrogen atoms are on the same side of the double bond.
The biological effects of the ω-3 are largely mediated by their interactions with the ω-6 fatty acids; see Essential fatty acid interactions for detail.
A 1992 article by biochemist William E.M. Lands provides an overview of the research into ω−3 fatty acids, and is the basis of this section.
The 'essential' fatty acids were given their name when researchers found that they were essential to normal growth in young children and animals. (Note that the modern definition of 'essential' is more strict.) A small amount of ω−3 in the diet (~1% of total calories) enabled normal growth, and increasing the amount had little to no additional benefit.
Likewise, researchers found that ω−6 fatty acids (such as γ-linolenic acid and arachidonic acid) play a similar role in normal growth. However, they also found that ω−6 was "better" at supporting dermal integrity, renal function, and parturition. These preliminary findings led researchers to concentrate their studies on ω−6, and it was only in recent decades that ω−3 has become of interest.
In 1963 it was discovered that the ω−6 arachidonic acid was converted by the body into pro-inflammatory agents called prostaglandins. By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins and the leukotrienes. The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. However, if the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that ω−3 is also converted into eicosanoids, but at a much slower rate. Eicosanoids made from ω−3 fats often have opposing functions to those made from ω−6 fats (ie, anti-inflammatory rather than inflammatory). If both ω−3 and ω−6 are present, they will "compete" to be transformed, so the ratio of ω−3:ω−6 directly affects the type of eicosanoids that are produced.
This competition was recognized as important when it was found that thromboxane is a factor in the clumping of platelets, which leads to thrombosis. The leukotrienes were similarly found to be important in immune/inflammatory-system response, and therefore relevant to arthritis, lupus, and asthma. These discoveries led to greater interest in finding ways to control the synthesis of ω−6 eicosanoids. The simplest way would be by consuming more ω−3 and fewer ω−6 fatty acids.
September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ω−3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA ω−3 fatty acids may reduce the risk of coronary heart disease." This updated and modified their health risk advice letter of 2001 (see below).
People with certain circulatory problems, such as varicose veins, benefit from fish oil. Fish oil stimulates blood circulation, increases the breakdown of fibrin, a compound involved in clot and scar formation, and it lowers the blood pressure. There is strong scientific evidence, that ω−3 fatty acids significantly reduce blood triglyceride levels and regular intake reduces the risk of secondary and primary heart attack.
Some benefits have been reported in such conditions as rheumatoid arthritis and cardiac arrhythmias.
There is a promising preliminary evidence, that ω−3 fatty acids supplementation might be helpful in cases of depression and anxiety. Studies report highly significant improvement from ω−3 fatty acids supplementation alone and in conjunction with medication.
Some research suggests that fish oil intake reduces the risk of ischemic and thrombotic stroke. However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk. 3 grams of total EPA/DHA daily are considered safe with no increased risk of bleeding involved and many studies used substantially higher doses without major side effects (for example: 4.4 grams EPA/2.2 grams DHA in 2003 study).
Several studies report possible cancer prevention effects of ω−3 fatty acids (particularly breast, colon and prostate cancer). No clear conclusion can be drawn at this time, though.
A 2006 report in the Journal of the American Medical Association concluded that their review of literature covering cohorts from many countries with a wide variety of demographic characteristics demonstrating a link between ω−3 fatty acids and cancer prevention gave mixed results. This is similar to the findings of a review by the British Medical Journal of studies up to February 2002 that failed to find clear effects of long and shorter chain ω−3 fats on total mortality, combined cardiovascular events and cancer.
In 1999, the GISSI-Prevenzione Investigators reported in the Lancet the results of major clinical study in 11 324 patients with a recent myocardial infarction. Treatment with omega-3 fatty acids 1 g/d reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively. These beneficial effects were seen already from three months onwards.
In April 2006, a team led by Lee Hooper at the University of East Anglia in Norwich, UK, published a review of almost 100 separate studies into ω−3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease. This meta-analysis was controversial and stands in stark contrast with two different reviews also performed in 2006 by the American Journal of Clinical Nutrition and a second JAMA review that both indicated decreases in total mortality and cardiovascular incidents (i.e. myocardial infarctions) associated with the regular consumption of fish and fish oil supplements. In addition ω−3 has shown to aid in other mental disorders such as aggression and ADHD (Attention Deficit Hyperactive Disorder).
Several studies published in 2007 have been more positive. In the March 2007 edition of the journal Atherosclerosis, 81 Japanese men with unhealthy blood sugar levels were randomly assigned to receive 1800 mg daily of eicosapentaenoic acid (EPA - an ω−3 essential fatty acid from fish oil) with the other half being o mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation.
Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of ω−3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefits comparable to those receiving standard NSAIDs. Those who follow a Mediterranean-style diet tend to have less heart disease, higher HDL ("good") cholesterol levels and higher proportions of ω−3 in tissue highly unsaturated fatty acids . Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of ω−3 fatty acids from fatty fish - also tend to have higher proportions of ω−3, increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood) and less heart disease. Eating walnuts (the ratio of ω−3 to ω−6 is circa 1:4 respectively ) was reported to lower total cholesterol by 4% relative to controls when people also ate 27% less cholesterol.
In a letter dated October 31, 2000 entitled Letter Regarding Dietary Supplement Health Claim for omega-3 Fatty Acids and Coronary Heart Disease, the United States Food and Drug Administration Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements noted that the known or suspected risks of EPA and DHA ω−3 fatty acids may include:
There have been reports that increased bleeding can occur if overused (normally over 3 grams per day) by a patient who is also taking aspirin or coumadin (warfarin). However, this is disputed.[2]
The possibility of hemorrhagic stroke (only in case of very large doses, called "Eskimo amounts").
Oxidation of ω−3 fatty acids forming biologically active oxidation products.
Reduced glycemic control among diabetics.
Suppression of immune and inflammation responses, and consequently, decreased resistance to infections and increased susceptibility to opportunistic bacteria.
An increase in concentration of LDL cholesterol in some individuals.
Subsequent advices from the FDA and national counterparts have permitted health claims associated with heart health.
Persons with congestive heart failure, chronic recurrent angina or evidence that their heart is receiving insufficient blood flow are advised to talk to their doctor before taking ω−3 fatty acids. It may be prudent for such persons to avoid taking ω−3 fatty acids or eating foods that contain them in substantial amounts.
In congestive heart failure, cells that are only barely receiving enough blood flow become electrically hyperexcitable. This, in turn, can lead to increased risk of irregular heartbeats, which, in turn, can cause sudden cardiac death. ω−3 fatty acids seem to stabilize the rhythm of the heart by effectively preventing these hyperexcitable cells from functioning by increasing the blood flow, thereby reducing the likelihood of irregular heartbeats and sudden cardiac death. For most people, this is obviously beneficial and would account for most of the large reduction in the likelihood of sudden cardiac death.
Essential fatty acid supplements have gained popularity for children with ADHD, autism, and other developmental differences. A 2004 Internet survey found that 29% of surveyed parents used essential fatty acid supplements to treat children with autism spectrum disorders.
Results from controlled trials are mixed. Fish oils appear to help ADHD-related symptoms in some children. Larger trials are needed. A 2007 double-blind, placebo-controlled trial of small groups of children found that omega-3 fatty acids reduced hyperactivity in children with autism spectrum disorders, suggesting that further research is needed.
In a study of nearly 9,000 pregnant women, researchers found women who ate fish once a week during their first trimester had 3.6 times less risk of low birth weight and premature birth than those who ate no fish. Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. However, attempts by other groups to reverse this increased risk by encouraging increased pre-natal consumption of fish were unsuccessful.
ω−3 fatty acids are known tup had clearly lost cerebral tissue, while the patients given the supplements had a significant increase of grey and white matter.
In the prefrontal cortex (PFC) of the brain, low brain ω−3 fatty acids are thought to lower the dopaminergic neurotransmission in this brain area, possibly contributing to the negative and neurocognitive symptoms in schizophrenia. This reduction in dopamine system function in the PFC may lead to an overactivity in dopaminergic function in the limbic system of the brain which is suppressively controlled by the PFC dopamine system, causing the positive symptoms of schizophrenia. This is called the n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia (Ohara, 2007). This mechanism may explain why ω−3 supplementation shows effects against both positive, negative and neurocognitive symptoms in schizophrenia.
Consequently, the past decade of ω−3 fatty acid research has procured some Western interest in ω−3 fatty acids as being a legitimate 'brain food.' Still, recent claims that one's intelligence quotient, psychol |
Cardiac_resynchronization_therapy_complications | Bleeding, infection and lead dislodgement are not uncommon complications of cardiac resynchronization therapy.
Bleeding and Hematomas: The incidence in clinical trials is 2.4%; in routine clinical practice, the actual incidence of pocket hematomas is probably higher as the trials only reported those hematomas, which needed surgical intervention. It is important to note that early re-intervention of pocket hematomas is associated with a 15-fold increase in infection.
Infection
Lead dislodgement. (CRT trials demonstrated a rate verying from 2.9% to 10.6%; the MIRACLE-ICD study demonstrated a higher occurence of lead dislodgement with left ventricular lead than right atrial and right ventricular leads-6.8%, 15 and 0.6% respectively).
Pneumothorax (0.9% in CRT trials, Medicare registry reported 1.2%),
Myocardial injury
Coronary sinus dissection (1.3%) or perforation (1.3%)(complication rate related to coronary veins has been reported i |
Pulmonary_edema_CT | Thoracic CT scan may be helpful in the diagnosis of pulmonary edema. Findings on CT scan diagnostic of hydrostatic pulmonary edema include cardiomegaly, vascular engorgment, pleural effusions.
Thoracic CT scan may be helpful in the diagnosis of pulmonary edema. Findings on CT scan diagnostic o |
Sickle-cell_disease_CT | CT scan may be helpful in rule out infarction or hemorrhage for patients who present with neurological deficits or altered mental status.
There are no CT scan findings associated with sickle cell disease. However, a CT scan may be helpful in the diagnosis of complications of sickle cell disease, which include:
Autosplenectomy
Rule out infarction or hemorrhage for patients who present with neurological deficits or altered mental status
CT scan showing autosplenectomy source:Case courtesy of Dr Gagandeep Singh, Radiopaedia.org, rID: 7731
CT scan showing autosplenectomy source:Case courtesy of Dr Gagandeep Singh, Radiopaedia.org, rID: 7731
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Dyspepsia_screening | There is insufficient evidence to recommend routine screening for dyspepsia.
There is insufficient evidence to recommend routine screening for dyspepsia.
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Erythema_Nodosum | Erythema nodosum (EN) (red nodules) is an inflammation of the fat cells under the skin (panniculitis). It causes tender, red nodules that are usually seen on both shins. EN is an immunologic response to a variety of different causes.
Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
[Disease name] may be classified according to [classification |
Collateral | ling of a major epicardial segment.
For more images, see Coronary collaterals case studies.
Images below depict collateral anastomoses between the RCA and the LAD.
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Otalgia_medical_therapy | Treatment of otalgia lies in identifying the pathology, whether it exists within the ear or elsewhere. Antibntivirals can be used for viral causes such as herpes zoster oticus, and antifungals can be used for oral thrush. NSAIDs are used if myalgias and neuralgias are suspected. The patient should be re-examined after a 2 week trial on the NSAIDs. Appropriate consultation with a neurologist, dentist, gastroenterologist etc., should be done.
Antibiotics are the mainstay of treatment of uncomplicated acute otitis media (AOM) in adults. The preferred antibacterial drug for the patient with AOM must be active against Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. Amoxicillin remains the drug of choice for initial therapy of AOM. Mild to moderate disease: 500 mg every 12 hours, or 250 mg every 8 hours for 5 - 7 days. Severe disease: 875 mg every 12 hours, or 500 mg every 8 hours for 10 days.
Alternatives to amoxicillin in case of penicillin allergy include Cefdinir (300 mg twice a day or 600 mg once daily), Cefpodoxime (200 mg twice a day), Cefuroxime (500 mg every 12 hours), and Ceftriaxone (2 g IM or IV once).
Treatment of otitis externa includes: Pain management using NSAIDs. Gently cleansing the debris from the external auditory canal with irrigation or by using a soft plastic curette or cotton swab under direct visualization. Topical medical therapy which includes a combination of mild acid, corticosteroids and either an antibiotic or antifungal. Mild disease can be treated by using an acidifying agent and a corticosteroid. As an alternative a 2:1 mixture of 70% isopropyl alcohol and acetic acid can be used. More severe disease requires addition of an antibacterial or antifungal to the above. Oral antistaphylococcal and IV antipseudomonal antibiotics are generally preferred in patients with fevers, immunosuppression, diabetes, adenopathy, or in those individuals with extension of the infection outside of the ear canal. Chronic, noninfectious, therapy-resistant external otitis can be treated using 0.1% Tacrolimus cream according to a prospective study by Caffier et al.
Cholesteatomas are preferably treated by surgery. If the patient refuses surgery or if the medical condition of the patient contraindicates use of general anesthesia, then routine cleaning will help control infection and growth of cholesteatoma, but it does not stop further expansion and does not eliminate risk.
Antibiotics are the main stay of treatment for mastoiditis. Ceftriaxone is used as the initial drug of choice. Further choice of an antibiotic depends on culture studies and Grams staining. If open mastoid surgery is not undertaken, use of single, high-dose, intravenous steroids is warranted to decrease mucosal swelling and to promote natural drainagea solution known as a cerumenolytic agent which is introduced into the ear canal. The common agents used are: Carbamide peroxide (6.5%) and glycerine, Sodium bicarbonate B.P.C. (sodium bicarbonate and glycerine), Various organic liquids (glycerol, almond oil, mineral oil, baby oil), Cerumol (arachis oil, turpentine and dichlorobenzene), Cerumenex (Triethanolamine, polypeptides and oleate-condensate), Urea, hydrogen peroxide and glycerine, Docusate, a detergent,an active ingredient found in laxatives
Syringing and curette methods are other alternatives for cerumen removal.
Furunculosis of the external ear can be treated by: 10% Ichthammol in glycerine wick pack, Polymyxin B, Neomycin, or hydrocortisone ear drops causes, obtained thorough a history followed by systemic examination.
NSAIDs, throat lozenges, mouth gargling and antibiotics are the main stay of treatment for acute pharyngitis.
Pain killers and antibiotics form the main stay of treatment for tonsillitis.
Temporomandibular joint disorderaser therapy, Wearing a splint or night guard, Undergoing corrective dental treatments, Avoiding extreme jaw movements, Not resting chin on hand, Learning relaxation techniques
Some novel techniques include Transcutaneous electrical nerve stimulation (TENS), trigger-point injections, and radio wave therapy.
Decongestants, antihistamines and steroids for barotrauma.
Neuralgias can be treated using NSAIDs, lation |
Meningitis#treatment | o protect the central nervous system. Meningitis is the inflammation of these protective membranes. Meningitis may have been described in the Middle Ages, but it was first accurately identified by the Swiss Vieusseux (a scientific-literary association) during an outbreak in Geneva, Switzerland in 1805. In 1661, Thomas Willis first described the inflammation of meninges and an epidemic of meningitis. In the 17th century, Robert Whytt provided a detailed explanation of tuberculous meningitis and its stages. This was further elaborated by John Cheyne in the same century. Meningococcal meningitis was than described by Gaspard Vieusseux, Andre Matthey in Geneva and Elisa North in Massachussetes. Meningitis may develop in response to a number of causes, including infectious agents (bacteria, viruses, fungi, or other organisms) or non-infectious causes, such as systemic illnesses that may necessitates prompt medical attention and evaluation. The common presenting features of meningitis are, fever, neck stiffness and headache. Other symptoms include, photophobia (inability to tolerate bright light), phonophobia (inability to tolerate loud noises), irritability, altered mental status (in small children), and seizure. Physical examination of meningitis may vary in adults and infants. In adults, physical examination findings may include bradycardia, disorientation, papilledema, neck stiffness, positive brudzinski's and kernig's sign. However, petechial rash, bulging fontanelle, neck stiffness, jaundice, and convulsions are physical examination findings in infants. Diagnosis is based on clinical findings and CSF analysis. Treatment options are based on etiology and varies from supportive care and observing the patient (viral meningitis) to antibiotic therapy for bacterial meningitis or chemotherapy and/or irradiation for neoplastic meningitis.
Bacterial meningitis can be community acquired or health care associated.
The major causes of community-acquired bacterial meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, primarily in patients over 50 years of age or those who have deficiencies in cell-mediated immunity, Listeria monocytogenes
The major causes of health care-associated ventriculitis and meningitis are different (usually staphylococci and aerobic gram-negative bacilli) and occur more commonly after neurosurgical procedures (eg, post-craniotomy, ventriculoperitoneal shunts, lumbar shunts, external ventricular drains or following head trauma such as basilar skull fracture with or without clinical evidence of leak of cerebrospinal fluid)
A more detailed discussion of the epidemiology of and risk factors for bacterial meningitis is presented elsewhere.
Meningitis could be classified to two main groups based on etiology:
Infectious
Non-infectious
Infectious meningitis may be classified as the following algorithm based on chronicity of symptoms.
Systemic illnesses, such as malignancies and connective tissue diseases (e.g. sarcoidosis, SLE, and wegener's) may involve meninges in their course and present as chronic meningitis.
Certain drugs may cause meningeal irritation and resemble as meningitis including:
Nonsteroidal antiinflammatory drugs (NSAIDs)
Intravenous immunoglobulin
Inted on clinical presentation in combination with CSF analysis. CSF analysis has major role for diagnosis and rule out other possibilities. The following table summarizes the CSF findings in different types of meningitis.
Empiric therapy for meningitis must be initiated after CSF obtained.
The choice of empiric antibiotic therapy is depend on patient age and underlying comorbid disease.
Adapted from IDSA guidlines.
Recommendations for antimicrobial therapy in adult patients with presumptive pathogen identification by positive Gram stain.
Adapted from IDSA guidlines.
Surgical intervention is not recommended for the management of meningitis.
Adapted from the recommendations of the United States Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) for the use of meningococcal vaccines.
The quadrivalent meningococcal conjugate vaccines (MenACWY) are Menactra (MenACWY-DT) and Menveo (MenACWY-CRM); these have replaced the quadrivalent meningococcal polysaccharide vaccine Menomune (MPSV4). MenHibrix (HibMenCY), a combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b, was discontinued in 2017. Trumenba (MenB-FHbp) and Bexsero (MenB-4C) are meningococcus serogroup B vaccines.
Secondary prevention with Antimicrobial chemoprophylaxis is necessary for individuals who have close contact with patients with invasive meningococcal disease. Close contacts include:
1.household members , 2.child-care center contacts ,3.anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management) in the 7 days before symptom onset. Health-care personnel should receive chemoprophylaxis if they were managing an airway or exposed to respiratory secretions of a patient with meningococcal disease. For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index-patient or for anyone seated dir |
Eosinophilic_pneumonia_differential_diagnosis | Acute eosinophilic pneumonia may be differentiated from other causes of pulmonary eosinophilia such as acute eosinophilic pneumonia, the transpulmonary passage of helminth larvae (Löffler syndrome), tropical pulmonary eosinophilia, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, and drugs and toxins.
Acute eosinophilic pneumonia may be differentiated from other causes of pulmonary eosinophilia.
The cause of acute eosinophilic pneumonia is unknown.
Some investigators have suggested that AEP is an acute hypersensitivity reaction to an unidentified inhaled antigen in an otherwise healthy individual.
Three types of helminths, Ascaris (A. lumbricoides, A. suum), hookworms (Ancylostoma duodenale, Necator americanus), and Strongyloides stercoralis, have larvae that reach the lungs, penetrate into alveoli, and ascend the airways then reach the gastrointestinal tract.
Ascaris is the most common cause of Löffler syndrome worldwide.
Tropical pulmonary eosinophilia is immune response to the bloodborne microfilarial stages of the lymphatic filariae and Wuchereria bancrofti.
The typical symptoms are cough, breathlessness, wheezing, fatigue, and fever. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity.
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is a vasculitic disorder often characterized by sinusitis, asthma, and prominent peripheral blood eosinophilia.
It is the s |
Swelling | my xp22 pter
X chromosome, monosomy xq28
X chromosome, trisomy 26-28
X chromosome, trisomy xp3
X chromosome, trisomy xpter xq13
X chromosome, trisomy xq
X chromosome, trisomy xq25
Yellow nail syndrome
Edema of specific organs (cerebral edema, pulmonary edema, macular edema, pedal edema) may also occur, each with different specific causes to peripheral edema, but all based on the same principles. Ascites is effectively edema within the peritoneal cavity, as pleural effusions are effectively edema in the pleural cavity. Causes of edema which are generalized to the whole body can cause edema in multiple organs and peripherally. For example, severe heart failure can cause peripheral edema, pulmonary edema, pleural effusions and ascites.
Common and usually harmless appearances of cutaneous edema are observed with mosquito bites and skin contact with certain plants (urticaria).
Edema may be found in the eyes after corrective surgery or procedures of that nature.
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Headache,_cluster | Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | CT | MRI | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Primary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
American Council for Headache Education
Headache
Tension headache
Migraine
Rebound headache
Hemicrania continua
Trigeminal neuralgia
Chronic Paroxysmal Hemicrania
Template:Diseases of the nervous system
Template:WikiDoc Sources
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Fetal_hypogastric_artery | The umbilical artery is a paired artery (with one for each half of the body) that is found in the abdominal and pelvic regions. In the fetus, it extends into the umbilical cord.
Umbilical arteries carry deoxygenated blood from the fetus to the placenta in the umbilical cord. There are usually two umbilical arteries present together with one umbilical vein in the cord. The umbilical arteries are actually the latter of the internal iliac arteries that supply the hind limbs with blood in the fetus. The umbilical arteries surround the urinary bladder and then carry all the deoxygenated blood out of the fetus through the umbilical cord.
The umbilical artery is the only artery present in the human body, aside from the pulmonary arteries, which carries deoxygenated blood.
Occasionally, there is only the one single umbilical artery (SUA) present in the cord. This abnormality is typically more common in multiple births, but can appear with singletons as well. Babies with SUA may have a higher likelihood of having other congenital abnormalities. However, additional testing (high level ultrasound scans) can rule out these abnormalities prior to birth and alleviate parental anxiety. Genetic counseling may be useful, too, especially when weighing the pros and cons of more invasive procedures such as chorionic villus sampling and amniocentesis.
It is important to note that a diagnosis of SUA, while anxiety provoking, is in no way a guarantee that a fetus is at risk for other problems in utero or after birth. Especially encouraging are cases in which no other soft markers for congenital abnormalities are visible via ultrasound. In fact, medical literature suggests that 1 in 100 newborns have it, making it the most common umbilical abnormality. Prior to ultrasound technology, the only method for determining the presence of such a cord was at birth, following an examination of the placenta. Given that the vast majority of expectant mothers do not receive the kind of advanced ultrasound scanning required to confirm SUA in utero, most cases may never detected antenatally even today.
In the United States, doctors and midwives typically encourage parents to take the added precaution of having regular growth scans near term to rule out intrauterine growth restriction, which can happen on occasion and warrant intervention. Yet the majority of growth restricted infants with the abnormality also have other defects. Echocardiograms may be advised late in the pregnancy to ensure the heart is functioning properly. Finally, neonates with the finding may also have a higher occurrence of kidney problems, so close examination of the infant may be warranted shortly after birth. Among SUA infants, there is a slightly elevated risk for post-natal urinary infections.
The umbilical artery is a branch of the anterior division of the internal iliac artery and represents the patent (open) part of the embryonic umbilical artery. (The non-patent obliterated part of the artery is the medial umbilical ligament.) The umbilical artery is found in the pelvis, and gives rise to the superior vesical arteries. In males, it also gives rise to the artery to the ductus deferens.
, , Model of human embryo 1.3 mm. long.
, , Transverse section of human embryo eight and a half to nine weeks old. ,
, , Tail end of human embryo twenty-five to twenty-nine days old.
, , Inguinal fossae,
Template:GPnotebook
Templ |
Camillo_Golgi | Camillo Golgi (July 7, 1843 – January 21, 1926) was an Italian physician and scientist.
Camillo Golgi was born in Corteno (Brescia). His father was a physician and district medical officer. Golgi studied at University of Pavia, where he worked in the experimental pathology laboratory under Giulio Bizzozero, who elucidated the properties of bone marrow. He graduated in 1865. He spent much of his career studying the central nervous system. Tissue staining techniques in the latter half of the 19th century were inadequate for studying nervous tissue. While working as chief medical officer in a psychiatric hospital, he experimented with metal impregnation of nervous tissue, using mainly silver (silver staining). He discovered a method of staining nervous tissue which would stain a limited number of cells at random, in their entirety. This enabled him to view the paths of nerve cells in the brain for the first time. He called his discovery the "black reaction" (in Italian, reazione nera), which later received his name (Golgi's method) or Golgi stain. The reason for the random staining is still not understood.
The black reaction consisted in fixing silver chromate particles to the neurilemma (the neuron membrane) by reacting silver nitrate with potassium dichromate. This resulted in a stark black deposit on the soma as well as on the axon and all dendrites, providing an exceedingly clear and well contrasted picture of neuron against a yellow background. The ability to visualize separate neurons led to the eventual acceptance of the neuron doctrine.
In addition to this discovery, Golgi discovered a tendon sensory organ that bears his name (Golgi receptor). He studied the life cycle of Plasmodium falciparum and related the timing of fevers seen in malaria with the life cycle of this organism. Using his staining technique, Golgi identified the intracellular reticular apparatus in 1898 which bears his name, the Golgi apparatus.
In renal physiology Golgi is renown for being the first to show that the distal tubulus of the nephron returns to its originating glomerulus (nerve ending of the Bombula) a finding that he published in 1889 ("Annotazioni intorno all'Istologia dei reni dell'uomo e di altri mammifieri e sull'istogenesi dei canalicoli oriniferi". Rendiconti R. Acad. Lincei 5: 545-557, 18 |
Children%27s_Claritin | f Loratadine in women who are pregnant.
There is no FDA guidance on use of Loratadine during labor and delivery.
Ask a health professional before use.
In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222)
There is no FDA guidance on the use of Loratadine in geriatric settings.
There is no FDA guidance on the use of Loratadine with respect to specific gender populations.
There is no FDA guidance on the use of Loratadine with respect to specific racial populations.
There is no FDA guidance on the use of Loratadine in patients with renal impairment.
There is no FDA guidance on the use of Loratadine in patients with hepatic impairment.
There is no FDA guidance on the use of Loratadine in women of reproductive potentials and males.
There is no FDA guidance one the use of Loratadine in patients who are immunocompromised.
Oral
There is limited information regarding Loratadine Monitoring in the drug label.
There is limited information regarding the compatibility of Loratadine and IV administrations.
There is limited information regarding Loratadine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Loratadine is a tricyclic antihistamine, whf the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others. Loratadine is almost totally (97–99%) bound to plasma proteins. Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.
There is limited information regarding Loratadine Nonclinical Toxicology in the drug label.
There is limited information regarding Loratadine Clinical Studies in the drug label.
Supplied as tablets of 10 mg in 30 taugPageImaDrugLabelImages
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Coronary_heart_disease_secondary_prevention_target_population | Patients who should be treated with secondary prevention are those with established atherosclerosis including peripheral artery
disease; carotid artery disease; atherosclerotic aortic disease; diabetes and those with a Framingham Risk Score of > 20%.
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Caplans_syndrome_medical_therapy | There is no treatment for Caplan Syndrome; the mainstay of therapy is supportive care.
Supportive therapy for Caplan Syndrome includes treatment of Rheumatoid arthritis, Steroid. Lung transplant for irreversible pulmonary fibrosis..
Pharmacologic medical therapies for Caplan Syndrome include steroid therapy, Disease modifying antirheumatic drugs(DMARDS) for Rheumatoid arthritis. Irreversible lung fibrosis requires lung transplantation. |
Continuous_murmur | A continuous murmur begins in systole and continues into diastole. They are caused by blood flow from high pressure chambers into low pressure chambers. The most common causes of continuous murmurs are patent ductus arteriosus, arteriovenous fistula and arterial stenosis.
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
Abdominal aortic aneurysm
Pulmonary embolism
Anemia
Aortic coarctation
Arteriovenous fistula
Cervical venous hum
Patent ductus arteriosus
Pericardial friction rub
Pregnancy
Pulmonary arteriovenous fistula
Renal artery stenosis
Valvular heart disease
Abdominal aortic aneurysm
Anemia
Aortic coarctation
Aortic-atrial fistulas
Arteriovenous fistula
Arteriovenous malformation
Atrial septal defect with mitral stenosis
Carotid artery stenosis
Celiac artery stenosis
Cervical venous hum
Cholangiocarcinoma
Cimino fistula
Cirrhosis
Coronary artery fistula
Fistula between an internal mammary graft and the pulmonary vasculature
Hepatic hemangioma
Hepatic hum
Hepatoma
Hyperthyroidism
Liver metastasis
Lutembacher's syndrome
Mammary souffle
Mitral stenosis with a persistent left superior vena cava
Paget's disease
Pulmonary embolism
Patent ductus arteriosus
Pericardial friction rub
Pregnancy
Pulmonary arteriovenous fistula
Pulmonary artery stenosis
Pulmonary atresia with ventricular septal defect
Renal artery stenosis
Renal cell carcinoma
Ruptured aneurysm of sinus of valsalva
Takayasu arteritis
Total anomalous pulmonary venous drainage
Tricuspid atresia
Tricuspid regurgitation
Truncus arteriosus
Valvular heart disease
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Fever_of_unknown_origin_resident_survival_guide | Management of fever of unknown origin should generally be withheld until the etiology is ascertained so that treatment can be targeted toward a specific pathology.
Fever of unknown origin (FUO) may be considered providing all the following criteria are fulfilled:
Fever higher than 38.3°C (100.9°F) on several occasions
Persisting without diagnosis for at least 3 weeks
At least 1 week's investigation in hospital
Minimum diagnostic evaluation to qualify as FUO includes:
Comprehensive history
Repeated physical examination
Complete blood count, including differential and platelet count
Routine blood chemistry, including lactate dehydrogenase, bilirubin, and liver enzymes
Urinalysis, including microscopic exmination
Chest radiograph
Erythrocyte sedimentation rate
Antinuclear antibodies
Rheumatoid factor
Three or more sets of blood cultures while not receiving antibiotics
Cytomegalovirus IgM antibodies or virus detection in blood
Heterophile antibody test in children and young adults
Tuberculin skin test
CT of abdomen or radionuclide scan
HIV antibodies or virus detection assay
Further evaluation tles, pustules, subcutaneous nodules, or cellulitis may be present in cryptococcosis.
Sister Mary Joseph nodule (palpable nodule bulging into the umbilicus) may be present in metastasis of a malignant tumor in the pelvis or abdomen.
Multiple purplish papules, nodules, and plaques may be present on the scalp, face, and neck in lymphoma.
Multiple erythematous, painful plaques with small bumps, pustules, and vesicles may be present in Sweet's syndrome.
Palpable purpura may be present on the lower extremities and other areas of dependency in cutaneous vasculitis.
Head
Temporal artery tenderness with weak pulse may be present in temporal arteritis.
Sinus tenderness may be present in sinusitis.
Eyes
Roth's spots or conjunctival hemorrhage may be present in infective endocarditis.
Photophobia or ocular pain on palpation suggestive of uveitis may be present in Wegener's granulomatosis, Behcet syndrome, Vogt-Koyanagi-Harada syndrome, or infections.
Mouth
Oral thrush caused by candidiasis may be present in patients with HIV/AIDS.
Oral ulcers may be present in systemic lupus erythematosis, disseminated histoplasmosis, and Behcet syndrome.
Tenderness with a palpable abscess may be present in periodontal disease.
Petechiae on the palate may be present in infective endocarditis.
Parotid gland enlargement and tenderness may be present in infections (e.g., Staphylococcus aureus, tuberculosis, mumps, HIV), Sjogren's syndrome, or sarcoidosis.
Neck
Cervical lymph nodes may be present in inflammation, infection, lymphoma, or Kikuchi disease.
Enlargement of the thyroid gland may be present in thyroiditis.
Lungs
Rales or rhonchi may be present in pneumonia.
Fremitus with diminished breath sounds may be present in pneumonia.
Heart
Heart murmurs may be present in endocarditis secondary to infections (infective endocarditis), systemic lupus erythematosus (Libman-Sacks endocarditis), or chronic diseases (marantic endocarditis).
Abdomen
Abdominal tenderness may be present in intra-abdominal infections.
Rebound tenderness may be present in intra-abdominal infections.
An acute abdomen may be present in intra-abdominal infections.
Guarding may be present in intra-abdominal infections.
Flank pain may be present in psoas muscle abscess, perinephric abscess, or pyelonephritis.
An inguinal mass may be present in psoas muscle abscess.
Splenomegaly may be present in infectious mononucleosis, splenic abscess, or hepatitis.
Genitourinary
Prostatic enlargement may be present in prostatic abscess.
Epididymal nodule may be present in epididymitis.
Testicular nodule may be present in polyarteritis nodosa.
Extremities
Osler's nodes may be present in infective endocarditis.
Swollen joints with effusion may be present in infectious arthritis or rheumatic diseases.
Splinter hemorrhage in the nail beds may be present in infective endocarditis.
Limb tenderness along deep veins may be present in deep vein thrombosis or thrombophlebitis.
Neurologic
Altered mental status may be present.
Cranial nerve deficits may be present in cerebral vasculitis associated with systemic lupus erythematosus.
Laboratory Workup
CBC with DC
SMA-7
AST, ALT, LDH, bilirubin, and ALP
Creatine kinase
Blood cultures, at least 2 sets
Urinalyl transferase
Coombs test
Cold agglutinins
Ferritin
Angiotensin-converting enzyme
Thyroid peroxidase and anti-thyroglobulin antibodies
Antinuclear antibodies
Rheumatoid factor
Cryoglobulins
CMV serology and heterophile antibody test if ⊕ atypical lymphocytes
Q fever serology if ⊕ exposure etiology is ascertained so that treatment can be directed toward a specific pathology.
Empiric corticosteroids may be appropriate in patients with suspected temporal arteritis to prevent vascular complications.
Patients with febrile neutropenia should receive broad-spectrum antipseudomonal antibiotics immediately after specimens for cultures have been obtained.
FUO
D/C nonessential Rx
Defervescence in 72h Fever persists
Drug fever CT or nuclear scan
Focus identified Focus undetermined
Verify with tissue biopsy IE suspected?
Duke criteria fulfilled IE unlikely
Treat as IE GCA suspected?
GCA likely GCA unlikely
Treat as GCA ANC < 500?
Febrile neutropenia Normal ANC
Antipseudomonal abx Follow up
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R-ICE_regimen | ICE-R regimen refers to a chemoimmunotherapy regimen consisting of rituximab, ifosfamide, carboplatin and etoposide used to treat indolent and aggressive forms of non-Hodgkin's lymphoma; also used to treat relapsed and refractory non-Hodgkin's lymphoma.
RRituximab
IIfosfamide
CCarboplatin
EEtoposide
Relapsed and refractory non-Hodgkin's lymphoma. |
Tricuspid_stenosis_surgery | Surgical tricuspid valve replacement in tricuspid stenosis (TS) is recommended among patients undergoing surgical intervention for left valvular disease as well as among patients with severe symptomatic isolated tricuspid stenosis (TS).
Surgery is the mainstay of treatment for tricuspid stenosis (TS), which includes the following:
Valvotomy
Valvotomy in tricuspid stenosis (TS) patients is done by using 1, 2, or 3 balloons.
By undergoing balloon valvotomy the tricuspid valve area increase from less than 1 to almost 2 cm2.
In cases of severe rheumatic tricuspid stenosis using a inoue balloon is much more useful and a simplified approach.
With valvotomy there is significant change in transvalvular pressure gradient across tricuspid valve and there is a decrease in right atrial pressure.
Balloon Valvuloplasty for Bioprosthetic Tricuspid Valve Stenosis. Case courtesy by Emmanouil Petrou, MD et al
Valve surgery
In tricuspid stenosis (TS) patients valve surgery include either valve repair or valve replacement.
Consider repair of the tricuspid valve if its feasible.
If tricuspid valve repair not an option consider valve replacement.
Patients who are undergoing tricuspid valve replacement the mortality rate is little higher when compared to patients who are undergoing tricuspid valve repair.
While considering tricuspid valve replacement it can be done in 2 ways: Open tricuspid valve replacement, Transcatheter replacement
Surgeon can choose either a bioprosthetic valve or an mechanical valve, the outcome is same using either of the valves with some conditions as an exception.
Survival in patients with bioprosthetic va |
Moxatag | al therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Mucocutaneous candidiasis.
Nausea
Vomiting
Diarrhea
Black hairy tongue
Hemorrhagic/pseudomembranous colitis
Anaphylaxis
Serum sickness-like reactions
Erythematous maculopapular rashes
Erythema multiforme
Stevens-Johnson syndrome
Exfoliative dermatitis
Toxic epidermal necrolysis
Acute generalized exanthematous pustulosis
Hypersensitivity vasculitis
Urticaria
NOTE: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxicillin therapy.
Rise in AST (SGOT) and/or ALT (SGPT)
Cholestatic jaundice
Hepatic cholestasis
Acute cytolytic hepatitis
Crystalluria
Anemia, including hemolytic anemia
Thrombocytopenia
Thrombocytopenic purpura
Eosinophilia
Leukopenia
Agranulocytosis
NOTE: These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.
Hyperactivity
Agitation
Anxiety
Insomnia
Confusion
Convulsions
Behavioral changes
Dizziness
Tooth discoloration: brown, yellow, or gray staining.
In clinical trials using combination therans were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxicillin, clarithromycin, or lansoprazole.
Amoxicillin/Clarithromycin/Lansoprazole:The most frequently reported adverse events for patients who received triple therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly %). No Amoxicillin Postmarketing Experience in the drug label.
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.
Pregnancy Category or harm to the fetus due to amoxicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS): A
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amoxicillin in women who are pregnant.
Oral ampicillin-class antibiotics are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of ampicillin slightly decreased the uterine tone and frequency of contractions but moderately increased the height and duration of contractions. However, it is not known whether use of amoxicillin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.
Penicillins have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.
Becain was conducted to determine whether subes between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken iicillin with respect to specific gender populations.
There is no FDA guidance on the use of Amoxicillin with respect to specific racial populations.
There is no FDA guidance on the use of Amoxicillin in patients with renal impairment.
There is no FDA guidance on the use of Amoxicillin in patients with hepatic impairment.
Amoxicillin and potassium clavulanate was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test, and was negative in each of these assays. In a multi-generation reproduction study in rats, no impairment of fertility or other adverse reproductive effects were seen at doses up to 500 mg/kg (approximately 3 times the human dose in mg/m2).
There is no FDA guidance one the use of Amoxicillin in patients who are immunocompromised.
oral
As with any potent drug, periodic assessment of renal, hepatic, and hematopoietic function should be made during prolonged therapy. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with amoxicillin should have a follow-up serologic test for syphilis after 3 months.
There is limited information regarding the compatibility of Amoxicillin and IV administrations.
In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.
Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin may be removed from circulation by hemodialysis.
Amoxicillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide.
Chemically it is (2S,5R,6R)-6-[(R)-(-)-2- amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid trihydrate. The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45.
There is limited information regarding Amoxicillin Pharmacodynamics in the drug label.
Amoxicillin is stable in the presence of gastric acsion has been partially investigated. The 400 mg and 875 mg formulations have been studied only when administered at the start of a light meal. However, food effect studies have not been performed with the 200 mg and 500 mg formulations. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxicillin is approximately 20% protein-bound.
Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 3.5 mcg/mL to 5 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.
Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of amoxicillin with 875 mg of amoxicillin/ clavulanate potassium showed that the 875 g tablet of amoxicillin produces an AUC0-∞ of 35.4 ±8.1 mcg•hr/mL and a Cmax of 13.8 ±4.1 mcg/mL. Dosing was at the start of a light meal following an overnight fast.
Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.
There is limited information regarding Amoxicillin Nonclinical Toxicology in the drug label.
Randomized, double-blind clinical studies performed in the United States in patients with H. pylori and duodenal ulcer disease of 2ombllin as the trihydrate.
250 mg yellow opaque cap and yellow opaque body, size 2, printed “RX654” on both cap and body. NDC 63304-654-20 bottles of 20, NDC 63304-654-30 bottles of 30, NDC 63304-654-01 bottles of 100, NDC 63304-654-05 bottles of 500, NDC 63304-654-77 Unit-dose 100s
500 mg maroon opaque cap and yellow opaque body, size 0-el, printed “RX655” on both cap and body. NDC 63304-762-82 bottles of 12, NDC 63304-762-20 bottles of 20, NDC 63304-762-01 bottles of 100, NDC 63304-762-13 bottles of 120, NDC 63304-762-05 bottles of 500
Each tablet contains 500 mg or 875 mg amoxicillin as the trihydrate.
500 mg pink colored, film coated, capsule shaped tablets; debossed with “RX762” on one side and plain on the other side. NDC 63304-762-82 bottles of 12, NDC 63304-762-20 bottles of 20, NDC 63304-762-01 bottles of 100, NDC 63304-762-13 bottles of 120, NDC 63304-762-05 bottles of 500
875 mg pink colored, film coated, capsule shaped tablets; debossed withottles of 500
200 mg light pink colored, strawberry flavored, circular, flat faced, beveled edge tablets, with mottled appearance; debossed with “RX760” on one side. NDC 63304-760-20 bottles of 20, NDC 63304-760-01 bottles of 100, NDC 63304-760-05 bottles of 500
250 mg pink colored, strawberry flavored, circular, flat faced, beveled edge tablets, with mottled appearance; debossed with “RX515” on one side. NDC 63304-515-30 bottles of 30, NDC 63304-515-01 bottles of 100, NDC 63304-515-04 bottles of 250
400 mg light pink colored, strawberry flavored, circular, flat faced, beveled edge tablets, with mottled appearance; debossed with “RX716” on one side. NDC 63304-761-20 bottles of 20, NDC 63304-761-01 bottles of 100, NDC 63304-761-05 bottles of 500
The 200 mg per 5 mL oral suspension is off white to light orange granular powder forming a light orange to orange suspension on constitution with water. The resulting suspension has a characteristic fruity flavor and is available as follows: NDC 63304-969-03 50 mL bottles, NDC 63304-969-01 75 mL bottles, NDC 63304-969-04 100 mL bottles
The 400 mg per 5 mL oral suspension is off white to light orange grae tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration preferable, but not required.
Store amoxicillin capsules 250 mg and 500 mg, amoxicillin tablets 500 mg and 875 mg, amoxicillin chewable tablets 125 mg, 200 mg, 250 mg and 400 mg and amoxicillin unreconstituted powder 200 mg/5 mL and 400 mg/5 mL at controlled room temperature 15° – 30° C (59° – 86° F) (see USP).
{{#ask: Page Name::Amoxicillin
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|?Drug Name
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There is limited information regarding Amoxicillin Patient Counseling Information in the drug label.
Alcohol-Amoxicillin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Amoxil
Trimox
Wymox
Moxatag
There is limited information regarding Amoxicillin Look-Alike Drug Names in the drug label.
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Osteoarthritis_screening | Routine screening for osteoarthritis is not indicated unless the patient is symptomatic.
Accurate data about the prevalence of OA can be useful for the health care system to have appropriate plans for management of OA patients. Nowadays, the OA screening in general population depends on the self-reported symptoms recorded during the clinical evaluation. An approved screening algorithm OA with sufficient sensitivities and specificities is necessary for OA management. Due to the lack of a reliable screening test for OA, the assessments of the prevalence of OA in a general population is difficult. Meanwhile, some scientist have worked on the screening questionnaires for identifying the knee or hip OA. Using only a questionnaire to identify OA cases without the physical examinations and radiographs would be non-verifiable.
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Hypercoagulable_state | History and Symptoms | Physical Examination | Laboratory Findings | X Ray | CT | MRI | Ultrasound | Other Imaging Studies | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Future or Investigational Therapies | Cost Effectiveness of Therapy
Case #1
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Hypolipoproteinemia_pathophysiology#Primary_Lipoprotein_Disorders | Multiple mechanisms have been described in different diseases and clinical conditions that are found to be associated with hypolipidemia. Secondary causes are far more common than primary causes and include anemia, hyperthyroidism, critical illness, malignancy, malabsorption, infection, Chronic liver disease, and Chronic inflammation.
Shown below is a table summarizing the primary hypolipoproteinemia along with the involved gene and main lipoprotein.
Hypolipedemia has been found in association with different clinical conditions.
Anemia: Hypolipedemia has been identified in association with different types of anemia e.g.congenital dyserythropoietic anemia, congenital spherocytosis, sickle cell anemia, beta-thalassemia, aplastic anemia, and sideroblastic anemia. The exact etiology of hypolipidemia in anemic patients is not known, some studies outlined different mechanisms, another study suggest that hypolipidemia might be the cause rather than the consequence of anemia, which is explained by that cholesterol deficiency leads to rigidity of the erythrocytes,e common in dyslipial screening for thyroid dysfunction in all dyslipidemic patients.
Critical illness: Cholesterol levels drop at the onset of acute illness, and normalize after recovery. This ntrol recommended to accelerate the recovery of the cholesterol levels.
Malignancy: Several epidemiological studies suggested an inverse relation between serum cholesterol level and cagenous source of body lipids. Brar et al demonstrated that celiac disease is associated with hypocholesterolemia and a gluten-free diet will result in rising of total cholesterol, bacterial, viral, and parasitic infections all might induce hypocholesterolemia.
Chronic liver disease: Hypolipidemia is frequently observed in severe chronphase response to inflammation, reduction in plasma lipid levels is a well known phenomenon, it is explained by the chronic effect of proinflammatory cytokines on lipoprotein me |
Neosar | mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 day for both initial and maintenance dosing.
Dosing Information
Single agent: 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Single agent: 1 to 5 mg/kg/day ORALLY, for both initial and maintenance dosing.
Dosing Information
Single agent: 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Single agent: oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic lymphoid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic lymphoid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Chronic myeloid leukemia: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Chronic myeloid leukemia: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant histiocytosis (clinical): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant histiocytosis (clinical): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - mixed small and large cell: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - mixed small and large cell: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Multiple myeloma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Multiple myeloma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mycosis fungoides, Advanced: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Neuroblastoma, Dis 5 mg/kg IV twice weekly.
Neuroblastoma, Disseminated disease: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Non-Hodgkin's lymphoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Non-Hodgkin's lymphoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Ovarian carcinoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Ovarian carcinoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Retinoblastoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Rmideto 50R kin's disease, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Hodgkin's disease, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant histiocytosis (clinical): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant histiocytosis (clinical): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - mixed small and large cell: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - mixed small and large cell: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Malignant lymphoma - small lymphocytic, Nodular or diffuse: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Mantle cell lymphoma, Stages III and IV (Ann Arbor staging system): (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatrics patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy.
Dosing Information
Minimal change disease, In patients who fail to respond to or are unable to tolerate adrenocorticosteroid therapy: 2 mg/kg ORALLY every day for 8 to 12 weeks; MAX cumulative dose 168 mg/kg; treatment beyond 90 days in males increases probability of sterility.
Limitations of Use:
The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established.
Dosing Information
Multiple myeloma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twin th fungoides, Advanced: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Neuroblastoma, Disseminated disease: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Neuroblastoma, Disseminated disease: (single agent) oral cyclophosphamide to 5 mg/kg IV twice weekly.
Non-Hodgkin's lymphoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Ovarian carcinoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Ovarian carcinoma: (single agent) oral cyclophosphamide is usually administered at dosages in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosing Information
Retinoblastoma: (single agent) 40 to 50 mg/kg IV in divided doses over 2 to 5 days OR 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV twice weekly.
Retinoblastoma: (single agphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur.
Urinary Outflow Obstruction
Cyclophosphamide is contraindicated in patients with urinary outflow obstruction.
Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections
Cyclophosphamide can cause myelosuppression (leukopenia, neutropenia, thrombocytopenia and anemia), bone marrow failure, and severe immunosuppression which may lead to serious and sometimes fatal infections, including sepsis and septic shock. Latent infections can be reactivated.
Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. In case of neutropenic fever, antibiotic therapy is indicated. Antimycotics and/or antivirals may also be indicated.
Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed. Cyclophosphamide should not be administered to patients with neutrophils ≤1,500/mm3 and platelets <50,000/mm3. Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. G-CSF may be administered to reduce the risks of neutropenia complications associated with cyclophosphamide use. Primary and secondary prd to normalize after approximately 20 days. Bone marrow failure has been reported. Severe myelosuppression may be expected particularly in patients pretreated with and/or receiving concomitant chemotherapy and/or radiation therapy.
Urinary Tract and Renal Toxicity
Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Medical and/ or surgical supportive treatment may be required to treat protracted cases of severe hemorrhagic cystitis. Discontinue cyclophosphamide therapy in case of severe hemorrhagic cystitis. Urotoxicity (bladder ulceration, necrosis, fibrosis, contracture and secondary cancer) may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Urotoxicity can occur with short-term or long-term use of cyclophosphamide.
Before starting treatment, exclude or correct any urinary tract obstructions. Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of urotoxicity and/or nephrotoxicity. Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections. Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity. Mesna has been used to prevent severe bladder toxicity.
Cardiotoxicity
Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy.
Supraventricular arrhythmias (including atrial fibrillation and flutter) and ventricular arrhythmias (including severe QT prolongation associated with ventricular tachyarrhythmia) have been reported after treatment with regimens that included cyclophosphamide.
The risk of cardiotoxicity may be increased with high doses of cyclophosphamide, in patients with advanced age, and in patients with previous radiation treatment to the cardiac region and/or previous or concomitant treatment with other cardiotoxic agents.
Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with pre-existing cardiac disease.
Monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease.
Pulmonary Toxicity
Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with increased mortality. Pneumonitis may develop years after treatment with cyclophosphamide.
Monitor patients for signs and symptoms of pulmonary toxicity.
Secondary Malignancies
Cyclophosphamide is genotoxic. Secondary malignancies (urinary tract cancer, myelodysplasia, acute leukemias, lymphomas, thyroid cancer, and sarcomas) have been reported in patients treated with cyclophosphamide-containing regimens. The risk of bladder cancer may be reduced by prevention of hemorrhagic cystitis.
Veno-occlusive Liver Disease
Veno-occlusive liver disease (VOD) including fatal outcome has been reported in patients receiving cyclophosphamide- containing regimens. A cytoreductive regimen in preparation for bone marrow transplantation that consists of cyclophosphamide in combination with whole-body irradiation, busulfan, or other agents has been identified as a major risk factor. VOD has also been reported to develop gradually in patients receiving long-term low-dose immunosuppressive doses of cyclophosphamide. Other risk factors predisposing to the development of VOD include preexisting disturbances of hepatic function, previous radiation therapy of the abdomen, and a low performance status.
Embryo-Fetal Toxicity
Cyclophosphamide can cause fetal harm when administered to a pregnant woman. Exposure to cyclophosphamide during pregnancy may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn. Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys.
Advise female patients of reproductive potential to avoid becoming pregnant and to use highly effective contraception during treatment and for up to 1 year after completion of therapy.
Infertility
Male and female reproductive function and fertility may be impaired in patients being treated with cyclophosphamide. Cyclophosphamide interferes with oogenesis and spermatogenesis. It may cause sterility in both sexes. Development of sterility appears to depend on the dose of cyclophosphamide, duration of therapy, and the state of gonadal function at the time of treatment. Cyclophosphamide-induced sterility may be irreversible in some patients. Advise patients on the potential risks for infertility [see Use in Specific Populations (8.4 and 8.6)].
Impairment of Wound Healing
Cyclophosphamide may interfere with normal wound healing.
Hyponatremia
Hyponatremia associated with increased total body water, acute water intoxication, and a syndrosed in more detail in other sections of the labeling.
Hypersensitivity.
Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections
Urinary Tract and Renal Toxicity
Cardiotoxicity
Pulmonary Toxicity
Secondary Malignancies
Veno-occlusive Liver Disease
Embryo-Fetal Toxicity
Reproductive System Toxicity
Impaired Wound Healing
Hyponatremia
Common Adverse Reactions
Hematopoietic system:
Neutropenia occurs in patients treated with cyclophosphamide. The degree of neutropenia is particularly important because it correlates with a reduction in resistance to infections. Fever without documented infection has been reported in neutropenic patients.
Gastrointestinal system:
Nausea and vomiting occur with cyclophosphamide therapy. Anorexia and, less frequently, abdominal discomfort or pain and diarrhea may occur. There are isolated reports of hemorrhagic colitis, oral mucosal ulceration and jaundice occurring during teceiving the drug. Pigmentation of the skin and changes in nails can occur.
The following adverse reactions have been identified from clinical trials or post-marketing surveillance. Because they are reported from a population from unknown size, precise estimates of frequency cannot be made.
Cardiac: cardiac arrest, ventricular fibrillation, ventricular tachycardia, cardiogailure (including fatal outcomes), cardiomyopathy, myocarditis, pericarditis, carditis, atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, bradycardia, tachycardia, palpitations, QT prolongation.
Congenital, Familial aion, gastroenteritis).
Ear and Labyrinth: deafness, hearing impaired, tinnitus.
Endocrine: water intoxreatitis, colitis, enteritis, cecitis, stomatitis, constipation, parotid gland inflammation.
General Disorders and Administrative Site Conditions: multiorgan failure, general physical deterioration, influenza-like illness, injection/infusion site reactions (thrombosis, necrosis, phlebitis, inflammation, pain, swelling, erythema), pyrexia, edema, chest pain, mucosal inflammation, asthenia, pain, chills, fatigue, malaise, headache.
Hematologic: myelosuppression, bone marrow failure, disseminated intravascular coagulation and hemolytic uremic syndrome (with thrombotic microangiopathy).
Hepatic: veno-occlusive liver disease, cholestatic hepatitis, cytolytic hepatitis, hepatitis, cholestasis; hepatotoxicity with hepatic ns ha (including fatal outcomes), other bacterial, fungal, viral, protozoal and, p herpes zoster, Strongyloides, sepsis and septic shock.
Investigations: blood lactate dehydrogenase increased, C-reactive protein increased.
Metabolism and Nutrition: hyponatremia, fluid retention, blood glucose increased, blood glucose decreased.
Musculoskeletal and Connective Tissue: rhabdomyolysis, scleroderma, muscle spasms, myalgia, arthralgia.
Neoplasms: acute leukemia, myelodysplastic syndrome, lymphoma, sarcomas, renal cell carcinoma, renal pelvis cancer, bladder cancer, ureteric cancer, thyroid cancer.
Nervous System: encephalopathy, convulsion, dizziness, neurotoxicity has been reported and manifested as reversible posterior leukoencephalopathy syndrome, myelopathy, peripheral neuropathy, polyneuropathy, neuralgia, dysesthesia, hypoesthesia, paresthesia, tremor, dysgeusia, hypogeusia, parosmia.
Pregnancy: premature labor.
Psychiatric: confusional state.
Renal and Urinary: renal failure, renal tubular disorder, renal impairment, nephropathy ryncluding fatal outcomes), obliterative bronchiolitis, organizing pneumonia, alveolitis allergic, pneumonitis, pulmonary hemorrhage; respiratory distress, pulmonary hypertension, pulmonary edema, pleura.
Skin and Subcutaneous Tissue: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, palmar-plantar erythrodysesthesia syndrome, radiation recall dermatitis, toxic skin eruption, urticaria, dermatitis, blister, pruritus, erythema, nail disorder, facial swelling, hyperhidrosis.
Tumor lysis syndrome: like other cytotoxic drugs, cyclophosphamide may induce tumor-lysis syndrome and hyperuricemia in patients with rapidly growing tumors.
Vascular: pulmonary embolism, venous thrombosis, vasculitis, peripheral ischemia, hypertension, hypotension, flushing, hot flush.
Cyclophosphamide is a pro-drug that is activated by cytochrome P450s.
An increase of the concentration of cytotoxic metabolites may occur with:
Protease inhibitors: Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. Use of protease inhibitor-based regimens was found to be associated with a higher incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regi
Increased hemnhibitors: ACE inhibitors can cause leukopenia.
Natalizumab
Paclitaxel: Increased hematotoxicity has been reported when cyclophosphde and, for example:
Anthracyclines
Cytarabine
Pentostatin
Radiation therapy of the cardiac region
Trastuzumab
Increased pulmonary toxicity may result from a combined effect of cyclophosphamide and, for example:
Amiodarone
G-CSF, GM-CSF (granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor): Reports suggest an increased risk of :*pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF or GMCSF.
Increased nephrotoxicity may result from a combined effect of cyclophosphamide and, for exampl |
Hyperfocus | Hyperfocus is an intense form of mental concentration or visualization that focuses consciousness on a narrow subject, or beyond objective reality and onto subjective mental planes, daydreams, concepts, fiction, the imagination, and other objects of the mind.
From a neurodiversity perspective, hyperfocus is a mental ability that is a natural expression of personality. However, hyperfocus can also be regarded as a psychiatric diagnosis, as a distraction from reality and a symptom of attention deficit hyperactivity disorder (ADHD), adult attention-deficit disorder (AADD), or autistic spectrum disorders.
Some people say that hyperfocus is an important element of meditation. In common parlance, hyperfocus is sometimes referred to as "zoning out." In sports, it is sometimes referred to as "being in the zone".
The term hyperfocus is not in common use among academics, and seldom appears in peer-reviewed articles. However, related terms such as concentration, absorption and 'focused attention' are widely used.
A positive aspect of hyperfocus might be the ability to use detachment from ordinary mentality to create new approaches to familiar situations. It may also improve learning speed and comprehension.
On the other hand, it sometimes presents a challenge to common teaching and parenting techniques. Schools and parents generally expect obedience from children and reward them for it, but hyperfocused children do not always cooperate under these circumstances. This can be overcome with investments of time and effort by the teacher or parent, but it is not always possible to spend a lot of time focusing on one child in a typical classroom situation.
Psychiatry describes only the distraction aspect of hyperfocus, referring to ADHD as 'inattentiveness and impulsiveness'. Hyperfocus is not recognised by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), and no article using the term appears in PubMed.
Besides hyperfocus, various special abilities have been suggested to occur in ADHD, i |
Kawasaki_disease_natural_history,_complications_and_prognosis | If left untreated, the symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction. If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short. Patients with Kawasaki disease may progress to develop long term cardiovascular illness such as coronary artery disease, and pre-mature atherosclerosis. Common complications of Kawasaki disease include vasculitis and coronary artery aneurysms. Prognosis is generally excellent and the mortality rate of patients with Kawasaki disease is approximately 2%.
If left untreated, the symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction.
If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short.
Patients with Kawasaki disease may progress to develop long ter |
Ebstein%27s_anomaly_of_the_tricuspid_valve_differential_diagnosis | Disorders that Ebstein's anomaly must be distinguished from include:
Accessory pathway-mediated WPW syndrome and SVT
Atrial septal defect (ASD)
Cyanotic congenital heart diseases
Isolated, severe tricuspid regurgitation
L-transposition of the great vessels
Severe right heart failure with dilation of the anulus
Ebstein's anomaly should be differentiated from other cynotic diseases and others
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Gastrointestinal_perforation_screening | There is insufficient evidence to recommend routine screening for gastrointestinal perforation
There is insufficient evidence to recommend routine screening for gastrointestinal perforation |
Congenital_chloride_diarrhea | Congenital chloride diarrhea (CCD, also congenital chloridorrhea) is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins. More than 20 mutations in the gene are known to date. A rare disease, CCD occurs in all parts of the world but is more common in some populations with genetic founder effects, most notably in Finland.
CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.
CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.
An important feature in this diarrhea that helps in the diagnosis, is that its the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.
Available treatments address the symptoms of CCD, not the underlying defect. Early diagnosis and aggressive salt replacement therapy result in normal growth and development, and generally good outcomes. Replacement of NaCl and KCl has been shown to be effective in children.
A potential treatment is butyrate.
Observations leading to the characterization of the SLC26 family were based on research on rare human diseases. Three rare recessive diseases in humans have been shown to be caused by genes of this family. Diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome are caused by the highly related genes SLC26A2 (first called DTDST), SLC26A3 (first called CLD or DRA), and SLC26A4 (first called PDS), respectively. Two of these diseases, diastrophic dysplasia and congenital chloride diarrhea, are Finnish heritage diseases.
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Verapamil_hydrochloride_tablet_nonclinical_toxicology | Verapamil is a calcium channel blocker rofile of both drugs and the clinical experience suggest beneficial interactions
The interaction between cimetidine and chronically administered verapamil has not been studied
Variable results on clearance have been obtained in acute studies of healthy volunteers
clearance of verapamil was either reduced or unchanged
Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil-lithium therapy
lithium levels have been observed sometimes to increase
and sometimes to be unchanged
Patients receiving both drugs must be monitored carefully
Verapamil therapy may increase carbamazepine concentrations during combined therapy
This may produce carbamazepine side effects such as diplopia
Therapy with rifampin may markedly reduce oral verapamil bioavailability
Phenobarbital therapy may increase verapamil clearance
Verapamil therapy may increase serum levels of cyclosporine
Verapamil may inhibit the clearance and increase the plasma levels of theophylline
Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward move cardiovascular depression
Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing)
It may be necessary to decrease the dose of verapamil and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly
Hypotension and bradyarrhythmias have been observed in patients receiving concurrent telithromycin
an antibiotic in the ketolide class
Sinus bradycardia resulting in hospitalization and pacemaker insertiog/kg/day) times the human oral daily dose
and have revealed no evidence of teratogenicity
this multiple of the human dose was embryocidal and retarded fetal growth and development
probably because of adverse maternal effects reflected in reduced weight gains of the dams
This oral dose has also been shown to cause hypotension in rats
There are no adequate and well-controlled studies in pregnant women
Because animal reproduction studies are not always predictive of human response
this drug should be used during pregnancy only if clearly needed
Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Verapamil in women who are pregnant
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus
or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention
Such adverse experiences have not been reported in the literature
despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor
Verapamil is excreted in human milk
Because of the potential for adverse reactions in nursing infants from verapamil
nursing should be discontinued while verapamil is administered
Safety and effectiveness in pediatric patients have not been established
There is no FDA guidance on the use of Verapamil in geriatric settings
There is no FDA guidance on the use of Verapamil with respect to specific gender populations
There is no FDA guidance on the use of Verapamil with respect to specific racial populations
About 70% of an administered dose of verapamil is excreted as metabolites in the urine
Verapamil is not removed by hemodialysis
Until further data are available
verapamil should be administered cautiously to patients with impaired renal function
These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage
Since verapamil is highly metabolized by the liver
it should be administered cautiously to patients with impaired hepatic function
Severe liver dysfunction prolongs the elimination half-life of verapamil to about 14 to 16 hours
approximately 30% of the dose given to patients with normal liver function should be administered to these patients
Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects should be carried out
There is no FDA guidance on the use of Verapamil in women of reproductive potentials and males
There is no FDA guidance one the use of Verapamil in patients who are immunocompromised
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy
prolongs recovery from the neuromuscular blocking agent vecuronium
and causes a worsening of myasthenia gravis
It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission
FDA Package Insert for Verapamil contains no information regarding drug monitoring
FDA Package Insert for Verapamil contains no information regarding IV compatibility
Treat all verapamil overdoses as serious and maintain observation for at least 48 hours (especially Verapamil SR)
preferably under continuous hospital care
Deutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil
In a few reported cases
overdose with calcium channel blockers has been associated with hypotension and bradycardia
initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride
Verapamil cannot be removed by hemodialysis
Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing
Asystole should be handled by the usual measures including cardiopulmonary resuscitation
The precise mechanism of action of VerapaoVerapamil in vasospastic (Prinzmetal's or variant) as well as unstable angina at rest
Whether this effect plays any role in classical effort angina is not clear
but studies of exercise tolerance have not shown an increase in the maximum exercise rate–pressure product
a widely accepted measure of oxygen utilization
relief of spasm or dilation of coronary arteries is not an important factor in classical angina
Verapamil regularly reduces the total peripheral resistance (afterload) against which the heart works both at rest and at a given level of exercise by dilating peripheral arterioles
This unloading of the heart reduces myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of Verapamil in chronic stable effort angina
Electrical activity through the AV node depends
upon calcium influx through the slow channel
By decreasiel sinus rhythm is usually not affected
but in patients with sick sinus syndrome
Verapamil may interfere with sinus-node impulse generation and may induce sinus arrest or sinoatrial block
Atrioventricular block can occur in patients without preexisting conduction defects
Verapamil decreases the frequency of episodes of paroxysmal supraventricular tachycardia
Verapamil does not alter the normal atrial action potential or intraventricular conduction time
but in depressed atrial fibers it decreases amplitude
Verapamil may shorten the antegrade effective refractory period of the accessory bypass tract
Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway following administration of verapamil
Verapamil has a local anesthetic action that is 1
6 times that of procaine on an equimolar basis
It is not known whether this action is important at the doses used in man
Verapamil exerts antihypertensive effects by decreasing systemic vascular resistance
usually without orthostatic decreases in blood pressure or reflex tachycardialf-life in single-dose studies ranged from 2
the half-life increased to a range from 4
0 hours (after less than 10 consecutive doses given 6 hours apart)
Half-life of verapamil may increase during titration
Aging may affect the pharmacokinetics of verapamil
Elimination half-life may be prolonged in the elderly
orally administered Verapamil undergoes extensive metabolism in the liver
Twelve metabolites have been identified in plasma
all except norverapamil are present in trace amounts only
Norverapamil can reach steady-state plasma concentrations approximately equal to those of verapamil itself
The cardiovascular activity of norverapamil appears to be approximately 20% that of verapamil
Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days
About 3% to 4% is excreted in the urine as unchanged drug
Approximately 90% is bound to plasma proteins
In patients with hepatic insufficiency
metabolism is delayed and elimination half-life prolonged up to 14 to 16 hours
the volume of distribution is increased and plasma clearance reduced to about 30% of normal
Verapamil clearance values suggest that patients with liver dysfunction may attain therapeutic verapamil plasma concentrations with one third of the oral daily dose required for patients with normal liver function
After four weeks of oral dosing (120 mg q
verapamil and norverapamil levels were noted in the cerebrospinal fluid with estimated partition coefficient of 0
06 for verapamil and 0
An 18-month toxicity study in rats
at a low multiple (6-fold) of the maximum recommended human dose
and not the maximum tolerated dose
did not suggest a tumorigenic potential
There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10
and 120 mg/kg/day or approximately 1
the maximum recommended human daily dose (480 mg/day or 9
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation
Studies in female rats at daily dietary doses up to 5
5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility
Effects on male fertility have not been determined
In chronic animal toxicology studies
verapamil caused lenticular and/or suture line changes at 30 mg/kg/day or greater
and frank cataracts at 62
5 mg/kg/day or greater in the beagle dog but not in the rat
Development of cataracts due to verapamil has not been reported in man
FDA Package Insert for Verapamil contains no information regarding clinical studies
USP 120 mg are supplied as ivory
film-coated tablet |
Xanthogranulomatous_cholecystitis | Xanthogranulomatous cholecystitis (XGC) is a rare form of gallbladder disease which mimics gallbladder cancer although it is not cancerous. It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and colleagues.
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Malignant_fibrous_histiocytoma | Fibrosarcoma (fibroblastic sarcoma) is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. Fibrosarcoma is classified |
Phenovarm | It is commonly used as an intermediate chemical in the manufacture of various antipsychotic neuroleptic psychotropic drugs. It originally was developed as a synthetic dye in 1883, and it was introduced by DuPont as an insecticide in 1935.
It is sometimes used as an antihelminthic in livestock. It is used as an industrial chemical in the manufacture of rubber additives.
Phenothiazine pesticides work by affecting the nervous system of insects, inhibiting the breakdown of acetylcholine by disabling the en |
Adventitia_externa | The tunica externa, also known as the tunica adventitia, is the outermost layer of a blood vessel, surrounding the tunica media. It is mainly composed of collagen. The collagen serves to anchor the blood vessel to nearby organs, giving it stability.
A common pathological disorder concerning the tunica externa is scurvy, also known as vitamin C deficiency. Scurvy occurs because vitamin C is essential for the synthesis of collagen, and without it, the faulty collagen cannot m |
Choledocholithiasis_(patient_information) | Choledocholithiasis is the presence of a gallstone in the common bile duct. The stone may consist of bile pigments or calcium and cholesterol salts.
Symptoms usually do not occur unless the stone blocks the common bile duct. Symptoms that may occur include:
Abdominal pain in the right upper or middle upper abdomen that may: Come and go, Be sharp, cramping, or dull, Spread to the back or below the right shoulder blade, Get worse after eating fatty or greasy foods, Occurs within minutes of a meal
Fever
Loss of appetite
Jaundice (yellowing of skin and whites of eyes)
Nausea
Vomiting
While stones can frequently pass through the common bile duct into the duodenum, some stones may be too large to pass through the CBD and will cause an obstruction.
Risk Factors include:
A previous medical history of gallstones
Choledocholithiasis can occur in people who have had their gallbladder removed
Tests that show the location of stones in the bile duct include the following:
Abdominal CT scan
Abdominal ultrasound
Endoscope retrograde cholangiography (ERCP)
Endoscopic ultrasound
Magnetic resonance cholangiopancreatography (MRCP)
Percutaneous transhepatic cholangiogram (PTCA)
Your doctor may order the following blood tests:
Bilirubin
Liver function tests
Pancreatic enzymes
Cholecystitis
Perforated peptic ulcer
Acute peptic ulcer exacerbation
Amoebic liver abscess
Acute amoebic liver colitis
Acute pancreatitis
Acute intestinal obstruction
Renal colic
Acute retrocolic appendicitis
Call for an appointment with your health care provider if abdominal pain with or without fever develops that is not attributable to other causes, if jaundice develops, or if other symptoms suggestive of choledocholithiasis occur.
The goal of treatment is to relieve the blockage.
Treatment may involve:
Surgery to remove the gallbladder and stones
ERCP and a procedure called a sphincterotomy, which makes a surgical cut into the muscle in the common bile duct.
Directions to Hospitals Treating Choledocholithiasis
Blockage and infection caused by stones in the biliary tract can be life threatening. However, with prompt diagnosis and treatment, the outcome is usually very good.
Biliary cirrhosis
Cholangitis
Pancreatitis
http://www.nlm.nih.gov/medlineplus/ency/article/000274.htm
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Nefazodone | Nefazodone is a 5-HT2 Antagonists that is FDA approved for the {{{indicationType}}} of major depressive disorder. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cardiovascular: orthostatic hypotension (2.8% to 4), gastrointestinal: constipation (10% to 17% ), nausea (14% to 23% ), xerostomia (25% ), neurologic: asthenia (7% to 13% ), confusion (7% ), dizziness (11% to 22% ), headache (26% to 52% ), lightheadedness (10% ), somnolence (16% to 32% ),ophthalmic: blurred vision (3% to 9% ).
Major depressive disorder
There is limited information about Off-Label Guideline-Supported Use of Nefazodone in adult patients.
There is limited information about Off-Label Non–Guideline-Supported Use of Nefazodone in adult patients.
There is limited information about FDA-labeled indications and dosage information of Nefazodone in pediatric patients.
There is limited information about Off-Label Guideline-Supported Use of Nefazodone in pediatric patients.
There is limited information about Off-Label Non–Guideline-Supported Use of Nefazodone in pediatric patients.
Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see Warnings and Precautions).
Nefazodone hydrochloride tablets are contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury (see Boxed Warning). Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.
The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see Warnings and Precautions), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and nefazodone should be avoided for most patients, including the elderly.
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
This image is provided by the National Library of Medicine.
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for nefazodone hydrochloride tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that nefazodone hydrochloride tablets is not approved for use in treating bipolar depression.
(See Boxed Warning.)
Cases of life-threatening hepatic failure have been reported in patientsand lovastatin or simvastatin (see Precautions); serotonin syndrome; and Stevens-Johnson syndrome; and thrombocytopenia.
Drugs Highly Bound to Plasma Protein
Because nefazodone is highly bound to plasma protein (see Clinical Pharmacology, Pharmaclt from displacement of nefazodone by other hhe pharmacokinetics of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had binical significance. Therefore, no dosage adjustment of either lithium or nefazodone is required when they are coadministered.
Carbamazepine – The coadministration of nefazodone (200 mg BID) for 5 days to 12 healthy subjects on carbamazepine who had achieved steady state (200 mg BID) was found to be well tolerated. Steady-state conditions for carbamazepine, nefazodone, and several of their metabolites were achieved by day 5 of coadministration. With coadministration of the two drugs there were significant increases id.
Theophylline
When nefazodone (200 mg BID) was given to patients being treated with theophylline (600 to 1200 mg/day) for chronic obstructive pulmonary disease, there was no change in the steady-state pharmacokinetics of either nefazodone or theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). Therefore, dosage adjustment is not necessary for either drug when coadAU name
1-(3-[4-(3-chlorophenyl)piperazin-1-yl]propyl)-3-ethyl-4-(2-phenoxyethyl)-1H-1,2,4-triazol-5(4H)-one
Identifiers
CAS number
83366-66-9
e:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass
470.01 g/mol
SMILES
eMolecules & PubChem
Pharmacokinetic data
Bioavailability
20% (variable)
Protein binding
>99%
Metabolism
Hepatic (active metabolites, including mCPP)
Half life
2–4 hours
Excretion
Urine (55%), Feces (20–30%)
Therapeutic considerations
Pregnancy cat.
C
Legal status
Prescription Only (S4)(AU) Template:Unicode Prescription only
Routes
Oral
Mechanism of Action
The mechanism of action of nefazodone, as with other antidepressants, is unknown.
Structure
Nefazodone hydrochloride tablets USP are an antidepressant for oral adphenylpiperazine antidepressant. The chemical name for nefazodone hydrochloride is 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one monohydrochloride. The structural formula is:
This image is provided by the National Library of Medicine.
C25H32CIN5O2•HCl M.W. 506.5
Nefazodone hydrochloride is a nonhygroscopic, white crystalline solid. It is freely soluble in chloroform, soluble in propylene glycol, and slightly soluble in polyethylene glycol and water.
Nefazodone hydrochloride tablets USP are supplied as capsule-shaped tablets containing 50 mg, 100 mg, 150 mg, 200 mg, or 250 mg of nefazodone hydrochloride and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium starch glycolate and povidone. Additionally, the 50 mg tablets include ferric oxide red as a colorant, the 150 mg tablets incacodynamics
Preclinical studies have shown that nefazodone inhibits neuronal uptake of serotonin and norepinephrine.
Nefazodone occupies central 5-HT2 receptors at nanomolar concentrations, and acts as an antagonist at this receptor. Nefazodone was shown to antagonize alpha1-adrenergic receptors, a property which may be associated with postural hypotension. In vitro binding studies showed that nefazodone had no signifiic, or benzodiazepine.
Pharmacokinetics
Nefazodone is rapidly and completely absorbed but is subject to extensive metabolism, so that its absolute bioavailability is low, about 20%, and variable. Peak plasma concentrations occur atabolite, hydroxynefazodone, exhibit nonlinear kinetics for both dose and time, with AUC and Cmax increasing more than proportionally with dose increases and more than expected upon multiple dosing over time, compared to single dosing. For example, in a multiple-dose study involving BID dosing with 50, 100, and 200 mg, the AUC for nefazodone and hydroxynefazodone increased by about 4 fold with an increase in dose from 200 to 400 mg per day; Cmax increased by about 3 fold with the same dose increase. In a multiple-dose study involving BID dosing with 25, 50, 100, and 150 mg, the accumulation ratios for nefazodone and hydroxynefazodone AUC, after 5 days of BID dosing relative to the first dose, ranged from approximately 3 to 4 at the lower doses (50 to 100 mg/day) and from 5 to 7 at the higher doses (200 to 300 mg/day); there were also approximately 2 to 4 fold increases in Cmax after 5 days of BID dosing relative to the first dose, suggesting extensive and greater than predicted accumulation of nefa measures: 17 Item Hami possible age-related differences in response.
Since its initial marketing as an antidepressant drug product, additional clinical investigations of nefazodone have been conducted. These studies explored nefazodone’s use under conditions not evaluated fully at the time initial marketing approval was granted.
Studies in “Inpatients”
Two studies were conducted to evaluate nefazodone’s effectiveness in hospitalized depressed patients. These were 6 week, dose-titration trials comparing nefazodone (up to 600 mg/day) and placebo, on a BID schedule. In one study, nefazodone was superior to placebo. In this study, the mean modal dose of nefazodone was 503 mg/day, and 85% of these inpatients were melancholic; at baseline, patients were distributed at the higher end of the 7 point CGI Severity scale, as follows: 4 = moderately ill (17%); 5 = markedly ill (48%); 6 = severely ill (32%). In the other study, the differentiation in response rates between nefazodone and placebo was not statistically significant. This result may be explained by the “high” rate of spontaneous improvement among the patients randomized to placebo.
Studies of “Relapse Prevention in Patients Recently Recovered (Clinically) From Depression”
Two studies were conducted to assess nefazodone’s capacity to maintain a clinical remission in acutely depressed patients who were judged to have responded adequately (HDRS total score ≤ 10) after a 16 week period of open treatment with nefazodone (titr 18) for patients taking nefazodone compared to those on placebo. The second study was of appropri nefazodone’s efficacy for this use.
Comparisons of Clinical Trial Results
Highly variable results have been seen in the clinical development of all antidepressant drugs. Furthermore, in those circumstances when the drugs have not been studied in the same controlled clinical trial(s), comparisons among the findings of studies evaluating the effectiveness of different antidepressant drug products are inherently unreliable. Because conditions of testing (e.g., patient samples, investigators, doses of the treatments administered and compared, outcome measures, etc.) vary among trials, it is virtually impossible to distinguish a difference in drug effect from a difference due to one or more of the confounding factors just enumerated.
Nonclinical Toxicology
There is limited information regarding Nefazodone Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Nefazodone Clinical Studies in the drug label.
How Supplied
Nefazodone hydrochloride tablets USP, 50 mg, are light-pink to pink (mottled), capsule-shaped, beveled-edged tablets, debossed “7178” on one side and debossed “93” on the other side. They are available in bottles of 100.
Nefazodone hydrochloride tablets USP, 100 mg, are white to off-white, capsule-shaped tablets, debossed “1024” on one side and scored on the other side with a debossed “93” on one side of the score. They are available in bottles of 60.
Nefazodone hydrochloride tablets USP, 150 mg, are peach (mottled), capsule-shaped tablets, debossed “7113” on one side and scored on the other side with a debossed “93” on one side of the score. They ed tablets, debossed “1025” on one side and debossed “93” on the other side. They are available in bottles of 60.
Nefazodone hydrochloride tablets USP, 250 mg, are white to(68° to 77°F) There may be new information. This leaflet provides a summary about nefazodone and does not include everything there is to know about your medicine. This information is not meant to take the place of talking with your doctor.
What is the most important information that I should know about nefazodone?
Rarely, people who take nefazodone can develop serious liver problems. If you get any of the following symptoms while taking nefazodone, call your doctor right away because you may be developing a liver problem:
Yellowing of the skin or whites of eyes (jaundice)
Unusually dark urine
Loss of appetite that lasts several days or longer
Nausea
Abdominal (lower stomach) pain
People who currently have liver problems should not take nefazodone.
What is nefazodone?
Nefazodone is a medicine used to treat depression. Nefazodone is thought to treat depression by correcting an imbalance in the amounts of certain natural chemicals, such as serotonin and norepinephrine, which are in your brain.
Who should not take nefazodone?
Do not take nefazodone if you
Are allergic to nefazodone or the related medicine Desyrel® (trazodone).
Are taking Seldane® (terfenadine), an antihistamine; Hismanal® (astemizole), an antihistamine; Propulsid® (cisapride), used for heartburn; Halcion® (triazolam), used for insomnia; Orap® (pimozide), used to treat Tourette’s syndrome; or Tegretol® (carbamazepine), used to control seizures.
Currently have liver problems.
Are taking or have taken within the last 14 days one of the medicines for depression known as monoamine oxidase inhibitors (MAOIs), such as Nardil® or Parnate®.
Be sure to tell your doctor if you
Have ever had liver problems;
Are taking any other medicine, vitamin supplement, or herbal remedy, including those sold without a prescription (over-the-counter);
Have heart problems or have had a heart attack or stroke;
Have had manic episodes (extreme agitation or excitability);
Have ever attempted suicide;
Have had convulsions (seizures);
Are pregnant or breast-feeding.
How should I take nefazodone?
Take nefazodone at the same time every day exactly as prescribed by your doctor. You may take nefazodone with or without food.
It may take a while for you to feel that nefazodone is working. You may not feel the full effect for several weeks. Once you feel better, it is important to keep taking nefazodone as directed by your doctor.
If you miss a dose of nefazodone, skip that dose and continue with your regular schedule. Never take 2 doses at the same time.
If you think that you have taken more nefazodone than prescribed, contact your doctor, local poison control center, or emergency room right away.
What should I avoid while taking nefazodone?
Do not drive or operate possibly dangerous machinery (such as an automobile, power mower, or power tool) or participate in any hazardous activity that requires full mental alertness until you know how nefazodone affects you.
Before taking nefazodone, tell your doctor about any medicines you are taking, imay affect how nefazodone works and should not be used in combination without talking to your doctor.
Do not drink alcoholic beverages while taking nefazodone.
Tell your doctor if you are pregnant, planning to become pregnant, or become pregnant while taking nefazodone. It is not known whether nefazodone can harm your unborn baby.
Talk with your doctor before taking nefazodone if you are breast-feeding. It is not known whether nefazodone can pass through your breast milk to the baby.
What are the possible side effects of nefazodone?
The most common side effects of nefazodone are sleepiness, dry mouth, nausea, dizziness, constipation, weakness, lightheadedness, problems with visior has prescribed nefazodone for you and you alone. Do not give nefazodone to other people even if they have the same condition. It may harm them.
This leaflet provides a summary of the most important information about nefazodone. If you would like more information, talk with your doctor or pharmacist. You can ask for information about nefazodone that is written for healthcare professionals.
Seldane® is a registered trademark of Hoechst Marion Roussel Inc. (now Aventis Pharmaceuticals).
Hismanal® and Propulsid® are registered trademarks of Janssen Pharmaceutica Products, L.P.
Nardil® is a registered trademark of Parke-Davis.
Parnate® is a registered trademark of SmithKline Beecham Pharmaceuticals.
Halcion® is a registered trademark of Pharmacia & Upjohn.
Orap® is a registered trademark of Gate Pharmaceuticals, a di with your or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member’s, healthcare provider about:
all risks and benefits of treatment with antidepressant medicines
all treatment choices for depression or other serious mental illness
What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?
1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
thoughts about suicide or dying
attempts to commit suicide
new or worse depression
new or worse anxiety
feeling very agitated or restless
panic attacks
trouble sleeping (insomnia)
new or worse irritability
acting aggressive, being angry, or violent
acting on dangerous impulses
an extreme increase in activity and talking (mania)
other unusual changes in behavior or mood
What else do I need to know about antidepressant medicines?
Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
Antidepressant medicines have other side effects. Talk to the healthcare provider about the sidePA 18960
Rev. E 5/2008
Precautions with Alcohol
Alcohol-Nefazodone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Nefazodone Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Nefazodone Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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Lactose_intolerance_historical_perspective | Lactose intolerance was first discovered by Hippocrat pigs, and rats. The association between the ethnicity and lactose intolerance was discovered in 1966 by Bayless and Rosensweig. In 1978, breath hydrogen test was used by Levitt to diagnose lactose intolerance.
Lactose intolerance was first discovered by Hippocrate, the ancient Greek physician 2500 years ago.
In 1906, Pimmer was the first scientist to discover lactase enzyme in the intestine of infant dogs, pigs, and rats. He also found that this enzyme decreased in the adult intestine of these animals.
In 1959, Durand and Holzei et al decribed congenital lactase deficiency
The association between the ethnicity and lactose intolerance was discovered in 1966 by Bayless and Rosensweig and in 1968 by Neale.
In the early 1970s, lactase-phlorizin hydrolase (LPH) gene mutations were first implicated in the pathogenesis of lactose intolerance.
In 1978, breath hydrogen test was used by Levitt to diagnose lactose intolerance
|
Infantile_hemangioendothelioma | Infantile hemangioendothelioma is a rare benign vascular tumour arising from mesenchymal tissue and is usually located in the liver. It often presents in infancy with cardiac failure because of extensive arteriovenous shunting within the lesion. It is the third most common liver tumor in children, the most common benign vascular tumor of the liver in infancy, and the most common symptomatic liver tumor during the first 6 months of life.
Infantile hemangioendotheliomas have a variable sonographic appearance and may be either hypoechoic or hyperechoic or may have mixed echogenicity.
Color Doppler US evaluation will show increased flow.
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Melanoma_electrocardiogram | There are no ECG findings associated with melanoma.
There are no ECG findings associated with melanoma.
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Strongyloidiasis_laboratory_findings | The diagnosis of strongyloidiasis is made by presence of clinical signs and symptoms, eosinophilia, and posf larvae in the stool. Sputum examination may rarely be used to identify organisms in cases of hyperinfection. Agar tracking (detection of larval tracks on agar culture plates) has been shown to be more sensitive than the conventional stool e demonstrated by repeated examinations of stool. Enzyme immunoassay (EIA) is currently recommended because of its greater sensitivity (90%). Antibody test results cannot be used to differentiate between the past and current infection. In disseminated cases of strongyloidiasis, larvae can be detected in sputum by simple wet-mount in fluid from a bronchoalveolar lavage (BAL).
Eosinophilia is generally present during the acute and chronic stageserial stool examination.
The diagnosis rests on the microscopi of cases.
Repeated examinations of stool specimens increase the chances of detecting larvae.
The diagnostic sensitivity increases to 50% with three stool examinations and can approach 100% if seven serial stool samples are examined
Specialized stool examinations techniques include Baermann concentration, Horadi-Mori filter paper culture, quantitative acetate concentration technique, and nutrient agar plate cultures.
Diagnostic characteristics: length 200 to 250 µm (up to 380 µm), Short buccal cavity, Prominent genital primordium.
Strongyloides stercoralis:The prominent genital primordium in the mid-section of the larva (black arrow) is readily evident. Note also the Entamoeba coli cyst (white arrow) near the posterior end of the larva. Source:https://commons.wikimedia.org/w/index.php?curid=219824
Immunodiagnostic tests for strongyloidiasis are indicated when the infection is suspected and the organism cannot be demonstrated by duodenal aspiration, string tests, or by repeated examinations of stool.
Antibody detection tests should use antigens derived from Strongyloides stercoralis filariform larvae for the highest sensitivity and specificity.
Although indirect fluorescent antibody (IFA) and indirect hemagglutination (IHA) tests have been used,
Immunocompromised persons with disseminated strongyloidiasis usually have detectable IgG antibodies despite their immunosuppression.
Cross-reactions in patients with filariasis and other nematode infections can occur.
Antibody test results cannot be used to differentiate between the past and current infection.
A positive test warrants continuing efforts to establish a parasitological diagnosis followed by antihelminthic treatment.
Serologic monitoring may be useful in the follow-up of immunocompetent treated patients: antibody levels decrease markedly within 6 months after successful chemotherapy.
More sensitive and specific serologic tests using recombinant antigens have been and are being developed, and are available at specific laboratories.
An additional advantage of these serologic tests is that there is typically a significant drop in titer by 6 months after parasite eradication, which may make it possible to use these tests as a check the response to medical therapy.
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Serology can be useful but is not commonly available and can give false-negative results.
Results for ELISA should be used in conjunction with clinical history and geographical data |
Simvastatin_use_in_specific_populations | Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the {{{indicationType}}} of reductions in risk of CHD mortality and cardiovascular events, hyperlipidemia, adolescent patients with heterozygous familial hypercholesterolemia (HeFH). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection.
The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
Patients taking Verapamil, Diltiazem, or Dronedarone
The dose of simvastatin should not exceed 10 mg/day.
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin should not exceed 20 mg/day.
The recommended dosage is 40 mg/day in the evening. simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin should be reduced by 50% if initiating lomitapide. simvastatin dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.
Because simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin is administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored.
Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in adult patients.
Dosing Information
40 mg/day for 1 month followed by 80 mg/day thereafter
Dosing Information
40 mg
Dosing Information
10 to 20 mg/day
Dosing Information
5 mg
Dosing information
80 mg/day
Dosing information
20 mg twice daily
Dosing information
80 mg/day
Dosing information
80 mg/day
Dosing information
20 mg daily
Dosing Information
The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products).
Concomitant administration of gemfibrozil, cyclosporine, or danazol.
Hypersensitivity to any component of this medication.
Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
Women who are pregnant or may become pregnant
Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.
Nursing mothers
It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin should not breastfeed their infants.
Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.
The risk of myopathy, including rhabdomyolysis, is dose related. In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively. The incidence of myopathy with 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvatatin 8is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potto report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: prox muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing simvastatin. simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspectetin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.
Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. simvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. simvastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Drug Interactions
The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or grapefruit juice. Combination of these drugs with simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
The combined use of simvastatin with gemfibrozil, cyclosporine, or danazol is contraindicated.
Caution should be used when prescribing other fibrates with simvastatin, as these agents can cause myopathy when given alone and the risk is increased when they are co-administered.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
The benefits of the combined use of simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/dnistered with lipid-modifying doses of a niacin-contered wi doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
Prescribing recommendations for interacting agents are summarized in the table below.
This image is provided by the National Library of Medicine.
Persistent increases (to more than 3X the ULN) in serum transaminases have occurred in The increases were notatients with more than one transaminase elevation to >3X ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 [0.7%] vs. 12 [0.6%]). Elevated transaminases resulted in the discontinuation of 8 patients from therapy in the simvastatin group (n=2,221) and 5 in the placebo group (n=2,223). Of the 1,986 simvastatin treated patients in 4S with normal liver function tests (LFTs) at baseline, 8 (0.4%) developed consecutive LFT elevations to >3X ULN and/or were discontinued due to transaminase elevations during the 5.4 years (median follow-up) of the study. Among these 8 patients, 5 initially developed these abnormalities within the first year. All of the patients in this study received a starting dose of 20 mg of simvastatin; 37% were titrated to 40 mg.
In 2 controlled clinical studies in 1,105 patients, the 12-month incidence of persistent hepatic transaminase elevation without regard to drug relationship was 0.9% and 2.1% at the 40- and 80-mg dose, respectively. No patients developed persistent liver function abnormalities following the initial 6 months of treatment at a given dose.
It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin. If serious liver injury with clinical symptoe etiology is not found do not restart simvastatin. Note that ALT may emanate from muscle, therefore ALT rising with CK may indicate myopathy.
The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin.
As with other lipid-lowering agents, moderate (less than 3X ULN) elevations of serum transaminases have been reported following therapy with simvastatin. These changes appeared soon after initiation of therapy with simvastatin, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.
Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia(0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).
Scandinavian Simvastatin Survival Study
In 4S involving 4,444 (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of simvastatin (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.
This image is provided by the National Library of Medicine.
Heart Protection Study
In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simvastatin compared with 5.1% in patients treated with placebo. The incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.
Other Clinical Studies
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.
Laboratory Tests
Marked persistent increases of hepatic transaminases have been noted. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK.
Adolescent Patients (ages 10-17 years)
In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or simvastatin(10-40 mg daily), the most common adverse reactions observed in both groups were upper respiratory infection, headache, abdominal pain, and nausea.
Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during postapproval use of simvastatin: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting, anemia, erectile dysfunction, interstitial lung disease, rhabdomyolysis, hepatitis/jaundice, fatal and non-fatal hepatic failure, and depression.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1)].
An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4.
Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [SeeWarnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs iscribing with simvastatin.
The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day Niacin) of Niacin-containing products. In particular, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of Niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of Niacin-containing products.
In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in digoxin concentrations in plasma. Patients taking digoxin should be monitored appropriately when simvastatin is initiated.
In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
Pregnancy Category (FDA): X
simvastatin is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term oes increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. If simvastatin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
There are rare reports of congenital anomalies following intrauterine exposure to statins. In a review3 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related statin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the gg treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified.
Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed idiscontinuation of simvastatin should be consideimvastatin during labor and dass is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother
Safety and effectiveness of simvastatin in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with simvastatin had an adverse reaction profile similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on menstrual cycle length in girls. Adolescent females should be counseled on appropriate contraceptive methods while on simvastatin therapy. Simvastatin has not been studied in patients younger than 10 years of age, nor in pre-menarchal girls.
Of the 2,423 patients who received simvastatin in Phase III clinical studies and the 10,269 patients in the Heart Protection Study who received simvastatin, 363 (15%) and 5,366 (52%), respectively were ≥65 years old. In HPS, 615 (6%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, simvastatin should be prescribed with caution in the elderly.
A pharmacokinetic study with simvastatin showed the mean plasma level of statin activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age. In 4S, 1,021 (23%) of 4,444 patients were 65 or older. Lipid-lowering efficacy was at least as great in elderly patients compared with younger patients, and simvastatin significantly reduced total mortality and CHD mortality in elderly patients with a history of CHD. In HPS, 52% of patients were elderly (4,891 patients 65-69 years and 5,806 patients 70 years or older). he relative risk reductions of CHD death, non-fatal MI, coronary and non-coronary revascularization procedures, and stroke were similar in older and younger patients. In HPS, among 32,145 patients entering the active run-in period, there were 2 cases of myopathy/rhabdomyolysis; these patients were aged 67 and 73. Of the 7 cases of myopathy/rhabdomyolysis among 10,269 patients allocated to simvastatin, 4 were aged 65 or more (at baseline), of whom one was over 75. There were no overall differences in safety between older and younger patients in either 4S or HPS.
Because advanced age (≥65 years) is a predisposing factor for myopathy, including rhabdomyolysis, simvastatin should be prescribed with caution in the elderly. In a clinical trial of patients treated with simvastatin 80 mg/day, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.
There is no FDA guidance on the use of Simvastatin with respect to specific gender populations.
There is no FDA guidance on the use of Simvastatin with respect to specific racial populations.
Caution should be exercised when simvastatin is administered to patients with severe renal impairment
Simvastatin is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels
There is no FDA guidance on the use of Simvastatin in women of reproductive potentials and males.
There is no FDA guidance one the use of Simvastatin in patients who are immunocompromised.
Oral
There is limited information regarding motoringtions.
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesiss 3.6 g. All patients recovered without sequelae. Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-5H38O5 and its molecular weight is 418.57. Its structeely soluble in chloroform, methanol and ethanol.
Simvastatin talets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of simvastatin and the followin, tnstrated that elevated levels of total-C, LDa lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-owing base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus 14C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (<5%).
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.
The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. While the recommended therapeutic dose range is 5 to 40 mg/day, there was no substantial de hwas administered immediately before an American Heart Association recommended low-fat meal.
e mea 18-30 years of age. Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and principal route of elimination, have suggesmyopathy is increased by high levels of HMG-CoA reincrease the risk of myopathy.
This image is provided by the National Library of Medicine.
In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a singred daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day.
In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).
In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC).
A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose.
No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of don study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
There was decreased fertility in male rats treated with simvastatin for 34 weeks at 25 mg/kg body weight (4 times the maximum human exposure level, based on AUC, in patients receiving 80 mg/day); however, this effect was not observed during a subsequent fertility study in which simvastatin was administered at this same dose level to male rats for 11 weeks (the entire cycle of spermatogenesis including epididymal maturation). No microscopic changes were observed in the testes of rats from either study. At 180 mg/kg/day, (which produces exposure levels 22 times higher than those in humans taking 80 mg/day based on surface area, mg/m2), seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. In dogs, there was drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation at 10 mg/kg/day, (approximately 2 times the human exposure, based on AUC, at 80 mg/day). The clinical significance of these findings is unclear.
CNS Toxicity
Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.
A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.
CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.
There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).
Reductions in Risk of CHD Mortality and Cardiovascular Events
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol 212-309 mg/dL (5.5-8.0 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20-40 mg/day (n=2,221) |
Phosphates | A phosphate, in inorganic chemistry, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Phosphates are important in biochemistry and biogeochemistry or ecology.
The general chemical structure of a phosphate
This is the structural formula of the phosphoric acid functional group as found in a weakly acidic aqueous solution. In more basic aqueous solutions, the group will donate the two hydrogen atoms and ionize as a phosphate group with a negative charge of 2.
The phosphate ion is a polyatomic ion with the empirical formula PO43− and a molar mass of 94.97 g/mol; it consists of one central phosphorus atom surrounded by four identical oxygen atoms in a tetrahedral arrangement. The phosphate ion carries a negative three formal charge and is the conjugate base of the hydrogenphosphate ion, HPO42−, which is the conjugate base of H2PO4−, the dihydrogen phosphate ion, which in turn is the conjugate base of H3PO4, phosphoric acid. It is a hypervalent molecule (the phosphorus atom has 10 electrons in its valence shell). Phosphate is also an organophosphorus compound with the formula OP(OR)3.
A phosphate salt forms when a positively charged ion attaches to the negatively charged oxygen atoms of the ion, forming an ionic compound. Many phosphates are insoluble in water at standard temperature and pressure, except for the alkali metal salts.
In dilute aqueous solution, phosphate exists in four forms. In strongly basic conditions, the phosphate ion (PO43−) predominates, while in weakly basic conditions, the hydrogen phosphate ion (HPO42−) is prevalent. In weakly acid conditions, the dihydrogen phosphate ion (H2PO4−) is most common. In strongly acid conditions, aqueous phosphoric acid (H3PO4) is the main form.
, , H3PO4,
, , H2PO4−,
, , HPO42−,
, , PO43−,
More precisely, considering the following three equilibrium reactions:
H3PO4 ⇌ H+ + H2PO4−
H2PO4− ⇌ H+ + HPO42−
HPO42− ⇌ H+ + PO43−
the corresponding constants at 25°C (in mol/L) are (see phosphoric acid):
<math> K_{a1}=\frac{[\mbox{H}^+][\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^{-3}</math>
<math>K_{a2}=\frac{[\mbox{H}^+][\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^{-8}</math>
<math> K_{a3}=\frac{[\mbox{H}^+][\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-13}</math>
For a strongly basic pH (pH=13), we find
<math>\frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^{10} \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^5 \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14</math>
showing that only PO43− and HPO42− are in significant amounts.
For a neutral pH (for example the cytosol pH=7.0), we find
<math> \frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 7.5\times10^4 \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 0.62 \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-6}</math>
so that only H2PO4− and HPO42− ions are in significant amounts (62% H2PO4−, 38% HPO42−). Note that in the extracellular fluid (pH=7.4), this proportion is inverted (61% HPO42−, 39% H2PO4−).
For a strongly acid pH (pH=1), we find
<math>\frac{[\mbox{H}_2\mbox{PO}_4^-]}{[\mbox{H}_3\mbox{PO}_4]}\simeq 0.075 \mbox{ , }\frac{[\mbox{HPO}_4^{2-}]}{[\mbox{H}_2\mbox{PO}_4^-]}\simeq 6.2\times10^{-7} \mbox{ , } \frac{[\mbox{PO}_4^{3-}]}{[\mbox{HPO}_4^{2-}]}\simeq 2.14\times10^{-12}</math>
showing that H3PO4 is dominant with respect to H2PO4−. HPO42− and PO43− are practically absent.
Phosphate can form many polymeric ions, diphosphate (also pyrophosphate), P2O74−, triphosphate, P3O105−, et cetera. The various metaphosphate ions have an empirical formula of PO3− and are found in many compounds.
Phosphate deposits can contain significant amounts of naturally occurring uranium. Subsequent uptake of such soil amendments can lead to crops containing uranium concentrations.
Elemental phosphorus and phosphides are not found (rare phosphide minerals may be found in meteorites).
Phosphates are the naturally occurring form of the element phosphorus, found in many phosphate minerals. In mineralogy and geology, phosphate refers to a rock or ore containing phosphate ions.
The largest rock phosphate deposits in North America lie in the Bone Valley region of central Florida, United States, the Soda Springs region of Idaho, and the coast of North Carolina. Smaller deposits are located in Montana, Tennessee, Georgia and South Carolina near Charleston along Ashley Phosphate road. The small island nation of Nauru and its neighbor Banaba Island, which used to have massive phosphate deposits of the best quality, have been mined excessively. Rock phosphate can also be found on Egypt, Israel, Morocco, Navassa Island, Tunisia, Togo and Jordan have large phosphate mining industries as well.
In biological systems, phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate, to distinguish it from phosphates bound in various phosphate esters. Inorganic phosphate is generally denoted Pi and can be created by the hydrolysis of pyrophosphate, which is denoted PPi:
P2O74− + H2O → 2HPO42−
However, phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. Similar reactions exist for the other nucleoside diphosphates and triphosphates. Phosphoanhydride bonds in ADP and ATP, or other nucleoside diphosphates and triphosphates, contain high amounts of energy which give them their vital role in all living organisms. They are generally referred to as high energy phosphate, as are the phosphagens in muscle tissue. Compounds such as substituted phosphines, have uses in organic chemistry but do not seem to have any natural counterparts.
In ecological terms, because of its important role in biological systems, phosphate is a highly sought after resource. Consequently, it is often a limiting reagent in environments, and its availability may govern the rate of growth of organisms. Addition of high levels of phosphate to environments and to micro-environments in which it is typically rare can have significant ecological consequences. For e |
Ellis_Tonic_Sherry | A multivitamin is a preparation intended to supplement a human diet with vitamins
dietary minerals and other nutritional elements
Such preparations are available in the form of tablets
which are only available and administered under medical supervision
multivitamins are recognized by the Codex Alimentarius Commission (the United Nations' highest authority on food standards) as a category of food
Many multivitamins are formulated and/or labelled to differentiate consumer sectors e
Consumer multivitamin formulas are available as tablets
Once and twice per day multivitamin formulas dominate common usage
although some formulas are designed for consumption 3 - 7 times per day or even allow hourly use
Compositional variation amongst brands and lines allows substantial consumer choices
Modern multivitamin products roughly classify into RDA centric multivitamins with or without iron
RDA centric multivitamin/multimineral formulas with or without iron
higher potency formulas with mostly above RDA components with or without iron
and more specialized formulas by condition
such as for diabetics or by less common components
herbal extracts or premium vitamin and mineral forms
the US FDA allows a multivitamin to be called "high potency" if at least two-thirds of its nutrients have at least 100 percent of the DV
"high potency" usually means substantially increased vitamin C and Bs with some other enhanced vitamin and mineral levels
but some minerals may still be much less than DV
Some components are typically much lower than RDA amounts
usually the most expensive vitamin component
at over $4000 per active pound
is typically added in at only 5%-30% of RDA in many one per day formulations
Sometimes low content composition is for population subgroups
where the RDA would be inappropriate
such often occurs with iron
where the original population intake calculation was ca 12-13 mg iron per day by including menstruating females but some percentage of HFE gene bearing males
may only need as little as ~1 mg iron per day including the normal dietary contribution
Basic commercial multivitamin supplement products often contain the following ingredients
Other formulas may include additional ingredients such as other carotenes (e
higher than RDA amounts of B
C or E vitamins including gamma-tocopherol
citrus bioflavinoids or nutrient forms variously described as more easily absorbable
By supplementing the diet with additional vitamins and minerals
multivitamins can be a valuable tool for those with dietary imbalances or different nutritional needs
People with dietary imbalances may include those on restrictive diets and those who can't or won't eat a nutritious diet
Pregnant women and elderly adults have different nutritional needs than other adults
and a multivitamin may be indicated by their physicians
RDA centric multivitamins are not to be confused with the basic orthomolecular medicine daily recommendations
The proponents of that also generally recommend individually optimized
They also recommend more absorbable forms of vitamins and minerals
in inexpensive but higher potency formulas
While multivitamins can be a valuable tool to correct dietary imbalances
it is worth exercising basic caution before taking them
especially if any medical conditions exist
pregnant women should generally consult their doctors before taking any multivitamins
Because high doses of vitamin A are believed to cause birth defects
special multivitamin formulations exist for pregnant women that do not contain this nutrient
Severe vitamin and mineral deficiencies require medical treatment and can be very difficult to treat with common over-the-counter multivitamins
special vitamin or mineral forms with much higher potencies are available
either as individual components or as specialized formulations
Multivitamins in bottle related quantites may risk acute overdosage if taken in large amounts
due to the slight toxicity of certain components
other components at extraordinary levels in high potency forms include (but are not limited to) vitamin A
Total iron content of the whole bottle is the primary concern for child safety
There also are strict limits on the retinol content for vitamin A during pregnancies that are specifically addressed by prenatal formulas
various medical conditions and medications may adversely interact with multivitamins
For normal adults taking a multivitamin for general health purposes
conventional medicine and government authorities recommend that a multivitamin should contain 100% DRI/RDA or less for each ingredient
many common brand supplements in the United States contain above-DRI amounts for some vitamins or minerals
Many brands offer low iron or iron-free versions of their multivitamin supplements
Some analyses have suggested that high potency synthetic beta-carotene
without adequate other redox antioxidants such as vitamin C
may shorten life rather than extend it in cases of oxidative stress (e
liver disease and liver stressing chemicals (e
suggest that there appears to be little risk to supplement users of experiencing adverse side effects due to excessive intakes of micronutrients
the Journal of the American Medical Association stated that "it appears prudent for all adults to take vitamin supplements
which examined the clinical applications of vitamins for the prevention of chronic diseases in adults
Fairfield from the Harvard School of Medicine
examined English-language articles about vitamins in relation to chronic diseases published between 1966 and 2002
and concluded that inadequate intake of several vitamins has been linked to the development of diseases including coronary heart disease
1998 issue of the New England Journal of Medicine featured an editorial entitled "Eat Right and Take a Multivitamin" that was based on studies that showed health benefits resulting from the consumption of nutritional supplements
professor of Biochemistry and Molecular Biology at the University of California
and a senior scientist at Children's Hospital Oakland Research Institute (CHORI)
suggests that "to maximize human health and lifespan
scientists must abandon outdated models of micronutrients" and that "a metabolic tune-up through an improved supply of micronutrients is likely to have great health benefits
In 2006 the National Institutes of Health convened an expert panel to examine the available evidence on nutrient supplements
This review concluded that "Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly
or in combinations of three |
Volvulus_pathophysiology | Regardless of cause, volvulus causes symptoms by two mechanisms: One is bowel obstruction, manifested as abdominal distension and vomiting. The other is ischemia (loss of blood flow) to the affected portion of intestine. This causes severe pain and progressive injury to the intestinal wall, with accumulation of gas and fluid in the portion of the bowel obstructed. Ultimately, this can result in necrosis of the affected intestinal wall, acidosis, and death. Acute volvulus therefore requires immediate surgical intervention to untwist the affected segment of bowel and possibly resect any unsalvageable portion.
In western society, chronic constipation can lead to an overloaded sigmoid colon.
In developing nations, a high fiber diet leads to sigmoidal overload.
When the bowel loop is overloaded with material, it becomes susceptible to torsion along the axis of an elongated mesentery.
A large pelvic mass or a large gravid uterus can alter the position of the intra-abdominal organs, predisposing to the formation of volvulus.
With recurrent attacks of torsion, the base of the mesentery can become chronically inflammed and eventually shortens.
This leads to recurrent volvulus.
The twisting of a mobile loop of bowel can happen spontaneously and may be congenital or acquired.
Acquired causes of volvulus include: Adhesions, Iatrogenic e.g. lower GI endoscopy, Bowel atony, Hirschsprung's disease, Pregnancy
Congenital causes are discussed below.
Malrotation occurs when there is arrest of the normal rotation of the embryonic gut.
During weeks 4-8 of development, the embryonic coelom, or cavity, normally cannot accommodate the rapidly expanding gastrointestinal (GI) tract.
Consequently, the primary intestinal loop pushes back into the yolk stalk, and will become the future umbilicus.
The direction in which the loop grows takes the axis of the future superior mesenteric artery.
As the primary intestinal loop grows out of the abdomen, it begins to rotate by twisting 90 degrees counterclockwise.
There are two factors that force this rotation: The proximal bowel (gastroduodenal) grows faster than the dist |
Anagen | A hair follicle is part of the skin that grows hair by packing old cells together. Attached to the follicle is a sebaceous gland, a tiny sebum-producing gland found everywhere except on the palms, lips and soles of the feet. The thicker density of hair, the more sebaceous glands are found.
Also attached to the foll |
Pediatric_inflammation_of_heart_muscle | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Endomyocardial Biopsy | Chest X Ray | MRI | Echocardiography | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
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Criteria_for_Renal_Stenosis | Diagnostic Criteria | History and Symptoms | Physical Examination | X Ray | CT | MRI | Echocardiography or Ultrasound
Medical Therapy | Angioplasty and Stenting | Surgery
Case #1
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Malarial_parasite | A plasmodium is also the macroscopic form of the protist known as a slime mould.
Plasmodium is a genus of parasitic protozoa. Infection with this genus is known as malaria. The parasite always has two hosts in its life cycle: a mosquito vector and a vertebrate host. At least ten species infect humans. Other species infect other animals, including birds, reptiles and rodents.
The genus Plasmodium was created in 1885 by Marchiafava and Celli and there are over 175 species currently recognized. New species continue to be described.
The genus is currently (2006) in need of reorganization as it has been shown that parasites belonging to the genera Haemocystis and Hepatocystis appear to be closely related to Plasmodium. It is likely that other species such as Haemoproteus meleagridis will be included in this genus once it is revised.
Host range among the mammalian orders is non uniform. At least 29 species infect non human primates; rodents outside n |
Dermatitis_herpetiformis_history_and_symptoms | Dermatitis Herpetiformis (also called Duhring's disease), is a chronic itchy rash which is frequently associated with Celiac Disease. The rash is made |
Complex_regional_pain_syndrome_epidemiology_and_demographics | Complex regional pain syndrome is more common between the ages of 40 and 60, and it affects women more frequently.
CRPS can strike at any age, but is more common between the ages of 40 and 60.The number of reported CRPS cases among adolescents and young adults is increasing.
It affects both men and women, but is more frequently seen in women.
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Cavernous_sinus_thrombosis_classification | The Jefferson classification and Ishikawa classification has been used to localize cavernous sinus lesions. According to the the location of the intracranial orifice of the optic canal and the entry of the maxillary nerve into the cavernous sinus, lesions may be classified in Ishikawa and Jefferson classification into three groups: Anterior lesions, middle lesions and posterior lesions. Although more number of patients could be classified in Ishikawa classification, there is no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of cavernous sinus lesions.
The Jefferson classification and Ishikawa classification has been used to localize cavernous sinus lesions.
According to the the location of the intracranial orifice of the optic canal and the entry of the maxillary nerve into the cavernous sinus, lesions may be classified in Ishikawa and Jefferson classification into three groups: Anterior lesions, Middle lesions, Posterior lesions
Although more number of patients could be classified in Ishikawa classification, there is no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of cavernous sinus lesions. |
Pulmonary_embolism_support_group | In a support group, members provide each other with various types of nonprofessional, nonmaterial help to pulmonary embolism patients. The help may take the form of providing relevant information, relating personal experiences, listening to others' experiences, providing sympathetic understanding, and establishing social networks. A support group may also provide ancillary support, such as serving as a voice for the public or engaging in advocacy.
PE, due to its sudden appearance in an otherwise healthy person, comes as a surprise and disbelief for most of the patients. The support group helps patients deal with that feeling of anxiety and shock. Various non-profit organizations have been developed, and they are helping patients cope with the emotional trauma. One such non-profit organizations is North American Thrombosis Forum.
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Left_main_artery | The origin of the left main coronary artery (LMCA) is from the left sinus valsalva (LSV). Prior to entry into the coronary sulcus, it travels between the left auricle and the main pulmonary artery (PA). The left circumflex (LCX) and left anterior descending (LAD) arteries arise from the bifurcation of the LMCA, which does not have any significant branches. It is 1 to 25 mm long, and is normally 3 to 5 mm wide. Severe narrowing of the left main coronary artery can result in death due to coronary ischemia, and is an indication for coronary artery bypass grafting or coronary stenting.
Left main artery bifurcates into the left anterior descending artery and the left circumflex artery.
Shown below is an image depicting the left main artery.
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Anomalous origin of LCA from PA (ALCAPA) is also known as Bland-White-Garland syndrome was described in 1956.
ALCAPA is a very rare and a serious congenital coronary artery anomaly (0.008%).
In this anomaly RCA is often dilated and provides an extensive collateral circulation to the LMCA territory.
The specific findings are dilated collateral arteries and coronary veins in imaging.
Additional components have been demonstrated in this syndrome as aortic coarctation and patent ductus arteriosus.
The suggested method of the treatment is reimplantation surgery of LMCA onto the aorta.
This anomaly is characterized by the absence of LMCA. In this case, the LCX and LAD are normal in their distribution pattern but arise from adjacent, separate ostia in the LSV.
Absent LMCA is a common benign anomaly, occurring in 0.41%-0.67% of cases.
Cases of left system dominance and aortic valve disease have been found to have increased incidence.
This condition is associated with no hemodynamic impairment. However, lack of identification of this anomaly may lead to clinical consequences during coronary catheterization or surgery.
There are often prominent right-to-left collateral vessels between the coronary arteries, although these vessels are usually inadequate to meet the oxygen requirements of left ventricle.
A large conus collateral branch supplying the LAD may mimic a pre-pulmonic vessel.
Atresia of the LMCA is associated with formation of a fibrous connection between the left sinus valsalva and the LCX-LAD arterial junction.
It usually affects patients in first year of life, but has also been described in elderly patients.
The lumen may not be identifiable or may be abnormal and nearly obliterated. Right-to-left collateral circulation may exist between coronary arteries to compensate for oxygen requirements, but may still be inadequate to meet the oxygen demand. A large conus collateral branch supplying the LAD may resemble a pre pulmonic vessel.
Shown below are an animated and a static angiography images depicting the left main artery in the RAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO cranial view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the RAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO cranial view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
Shown below are an animated and a static angiography images depicting the left main artery in the LAO caudal view.
LAD= Left anterior descending artery; LCX= Left circumflex artery; LM= Left main artery.
In carefully selected patients, percutaneous left main intervention can safely and effectively treat patients in whom coronary artery bypass graft surgery is a suboptimal option. Data from the SYNTAX trial supports such an approach.
Careful selection of patients for PCI is critical.
Fractional Flow Reserve (FFR) may be helpful in determining if a lesion is critical.
Mortality and procedural results vary depending upon whether the lesion is ostial and/or in the shaft versus distal and involves the bifurcation.
Thus, careful and meticulous angiography in multiple views is critical to fully assess the left main at it's ostium and bifurcation. Optimal views include but are not limited to the AP caudal and the LAO Caudal.
Coronary Artery Bypass Grafting (CABG) is currently the standard of care for patients with left main disease. However, this recommendation may be modified as data emerge regarding:
Very low in-hospital mortality among patients treated with left mainnting, or Y, Culotte; in double barrel V or crush stenting LCX limer |
Superior_mediastinal_syndrome | History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Radiation Therapy | Primary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Pemberton's sign
Cough causes
Oncologic emergencies
Mediastinal tumor
vteCardiovascular disease (heart)IschaemicCoronary disease
Coronary artery dise |
Asphyxiant | s of chest compression include the knee-on-stomach position, or techniques such as leg scissors (also referred to as body scissors and in budo referred to as do-jime, 胴絞, "trunk strangle") where you wrap the legs around the opponent's midsection and squeeze them together.
Pressing is a form of torture or execution which works through asphyxia.
Asphyxia is used to maim or kill in capital punishment, suicide, torture, and warfare. It is also used non-fatally in martial arts, combat sports, BDSM and during sex as erotic asphyxia. Because the need to breathe is triggered by the level of carbon dioxide in the blood, some victims may not experience an urgent need to breathe and may remain unaware of the onset of hypoxia.
Various chemical and physiological situations can interfere with the body's ability to absorb and use oxygen or regulate blood oxygen levels:
Carbon monoxide inhalation, such as from a car exhaust, carbon monoxide has a higher affinity than oxygen to the hemoglobin in the blood's red blood corpuscles bonding with it tenaciously, displacing oxygen and preventing the blood from transporting it around the body.
Contact with certain chemicals, including pulmonary agents (such as phosgene) and blood agents (such as hydrogen cyanide).
Self-induced hypocapnia by hyperventilation, as in shallow water or deep water blackout and the choking game.
A seizure which stops breathing activity.
Sleep apnea.
Drug overdose.
Ondine's curse, central alveolar hypoventilation syndrome, or primary alveolar hypoventilation, a disorder of the autonomic nervous system in which a patient must consciously breathe. Although it is often said that persons with this disease will die if they fall asleep, this is not usuall the case.
Acute respiratory distress syndrome |
Levo-transposition_of_the_great_arteries_natural_history,_Complications_%26_Prognosis | The prognosis on simple levo-TGA depends mainly on the presence of cardiac shunts such as fossa ovalis, atrial septal defect, ventricular septal defect, and ductus arteriosus. With complex l-TGA, the infant will fail to thrive and is unlikely to survive longer than a year if corrective surgery is not performed.
Simple l-TGA
The prognosis on simple l-TGA depends mainly on the presence of cardiac shunts such as fossa ovalis, atrial septal defect, ventricular septal defect, and ductus arteriosus.
If one or more of these defects are present, blood will be mixed, allowing a small amount of oxygen to be delivered to the body, giving an opportunity to the newborn to survive long enough to receive corrective surgery.
With simple l-TGA, if the foramen ovale and ductus arteriosus are allowed to close naturally, the newborn will likely not survive long enough to receive corrective surgery.
While the foramen ovale and ductus arteriosus are open after birth, some mixing of red and blue blood occurs allowing a small amount of oxygen to be delivered to the body; if ASD, VSD, PFO, and/or PDA are present, this will allow a higher amount of the red and blue blood to be mixed, therefore delivering more oxygen to the body, but can complicate and lengthen the corrective surgery and/or be symptomatic.
Complex
With complex l-TGA, the infant will fail to thrive and is unlikely to survive longer than a year if corrective surgery is not performed.
Generally, if the defect (levo-TGA) is not corrected during the first year of life, the patient's condition will deteriorate to the point of inoperability.
Modern repair procedures within the ideal time-frame and without additional complications have a very high success rate. |
Inferior_peduncle | The upper part of the posterior district of the medulla oblongata is occupied by the inferior peduncle, a thick rope-like strand situated between the lower part of the fourth ventricle and the roots of the glossopharyngeal and vagus nerves.
The inferior peduncles connect the medulla spinalis and medulla oblongata with the cerebellum, and are sometimes named the restiform bodies.
The inferior cerebellar peduncle carries many types of input and output fibers that are mainly concerned with integrating proprioceptive sensory input with motor vestibular functions such as balance and posture maintenance.
Proprioceptive information from the body is carried to the cerebellum via the posterior spinocerebellar tract.
This tract passes through the inferior cerebellar peduncle and synapses within the paleocerebellum.
Vestibular information projects onto the archicerebellum.
This peduncle also carries information directly from the Purkinje cells to the vestibular nuclei in the dorsal brainstem located at the junction between the pons and medulla.
Superior cerebellar peduncles
Middle cerebellar peduncles
Cerebral peduncle
, , Upper part of medulla spinalis and hind- and mid-brains; posterior aspect, exposed in situ.
, , Superficial dissection of brain-stem. Lateral view.
, , Dissection of brain-stem. Lateral view.
, , Deep dissection of brain-stem. Lateral view.
, , Dissection of brain-stem. Dorsal view. ,
, , Diagram showing the course of the arcuate fibers.
, , Dissection showing the course of the cerebrospinal fibers.
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Cerebellum
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Hirsutism_case_studies | A 19-year-old woman complains of slowly progressive hair growth. Since high school, she has shaved her upper lip weekly and waxed her abdomen and thighs monthly. Her menstrual periods are regular. Physical exami |
Hybrid_coronary_revascularization | and coronary stenting during the same operation. It is not to be confused with a MIDCAB procedure, which uses the smaller thoracotomy incision but does not involve coronary stenting. Hybrid bypass offers all the benefits of a MIDCAB:
A much smaller incision (made through the rib cage as opposed to cutting the sternum and opening the rib cage) than with traditional bypass surgery.
Less pain for the patient and quicker recovery time.
Less risk of complications, infections etc and also decreases the necessity for two separate cardiac procedures (bypass and stenting).
Not all hospitals and/or surgeons offer this procedure and it requires a specially equipped OR. As such, it is worth inquiring to determine which hospitals do and whether or not a patient can benefit from this procedure.
Coronary artery bypass surgery
Percutaneous coronary intervention |
Esophageal_web | Esophageal webs are mucosal folds that partially obstructs the esophageal lumen. The exact pathogenesis of esophageal webs is not known but it is thought to be due to either esophageal inflammation, congenital anomaly, or iron deficiency. They can be classified into type A, B, and C according to their site and extent; type B being the most common. The most common causes are Plummer-Vinson syndrome, celiac sprue and Zenker’s diverticulum. Esophageal webs most commonly present with dysphagia that has a slow onset and is rarely complicated with weight loss. Esophageal webs must be differentiated from other causes of dysphagia such esophageal strictures and achalasia. In barium esophagogram, esophageal webs appear as a uniform narrowing of the esophagus and on endoscopy, esophageal webs appear as a smooth narrowing of the esophagus that is not present in the whole circumference of the lumen. Esophageal dilation is the cornerstone of treatment and it is effective in relieving the symptoms but with high recurrence rate.
In 1944, esophageal webs were first described by Templeton and it was thought to be a congenital disease because most of the patients were children.
In 1953, a series of case reports of patients having dysphagia and radiological signs denoting esophageal narrowing made the diagnosis of esophageal rings not confined to the pediatric population.
In 1968, histological examination of specimens from the esophageal rings proved that none of them had muscle involvement.
Esophageal webs can be classified according to their site and extent in three categories
Type A esophageal rings describe webs that involve the muscle layer of the esophageal wall and lies in close proximity to the squamo-columnar junction.
It is less common than type B esophageal webs.
Type B esophageal rings describe the webs that involve only the mucosa and submucosa of the esophagus.
It is often named “Schatzki ring”.
It is located exactly at the squamo-columnar junction.
Type C esophageal rings refer to wall invaginations due to pressure from the diaphragm.
It is rare with no clinical significance.
There are multiple theories explaining the origin of esophageal webs.
Esophageal webs are thought to be due to the chronic damage to the esophageal mucosa.
This is supported by the presence of inflammatory cells in the wall of the web.
In eosinophilic esophagitis, eosinophils were found while in cases of chronic inflammation as GERD, lymphocytes prevailed.
Esophageal webs are thought to be due to failure of the esophagus to recanalize.
Specimens showed that the esophageal webs contained respiratory epithelium supporting this theory.
The webs mostly remain asymptomatic for long times and that is why it is not correlated with being congenital.
The esophageal webs of Plummer-Vinson syndrome have been associated with iron deficiency anemia in many studies.
The exact mechanism by which iron deficiency causes esophageal webs is not known, but it was hypothesized that iron deficiency starts a sequence of events in the esophageal epithelium that ends in its damage and formation of a web.
Moreover, treatment of iron deficiency in Plummer-Vinson syndrome patients leads to resolution of dysphagia even before the laboratory results become normal.
Esophageal webs appear as an eccentric narrowing of the esophageal lumen (while rings cause circumferential narrowing).
Esophageal webs are covered normally by mucosa and submucosa.
It is characterized by the presence of basal cell hyperplasia.
The tissue is often heavily infiltrated with chronic inflammatory cells.
Eosinophilic esophagitis is characterized by the presence of eosinophil infiltration.
Iron deficiency anemia
Plummer-Vinson syndrome
Celiac sprue
Zenker’s diverticulum
Epidermolysis bullosa
Bullous pemphigoid
Graft versus host disease
Pemphigus Vulgaris
Esophageal webs must be differentiated from other causes of dysphagia such as achalasia and esophageal carcinoma.
Webs are diagnosed in 5-15% of patients doing barium esophagogram for diagnosing the cause of dysphagia.
Congenital esophageal webs are estimated to be 1 in 25,000 to 1 in 50,000 live births.
Esophageal webs affects the whites more than other population.
Esophageal webs tend to be more common in females.
This may be due to the increased prevalence of iron deficiency anemia.
Esophageal has no predilection for an age group, however, it is usually not symptomatic until after the age of 40.
According to USPSTF, there are no screening measures recommended for esophageal webs.
The disease can start at any age but symptoms usually start in the fifth decade of life.
The dysphagia is usually to soli |
Chronic_pancreatitis_(patient_information) | Chronic pancreatitis is swelling (inflammation) of the pancreas that leads to scarring and loss of function. The pancreas is an organ located behind the stomach that produces chemicals needed to digest food. It also produces the hormones insulin and glucagon.
Symptoms of Chronic pancreatitis include
Abdominal pain, Greatest in the upper abdomen, May last from hours to days, Eventually may be continuous, May be worsened by eating or drinking, May be worsened by drinking alcohol, May spread (radiate) to the back
Digestive problems
Fatty stools
Nausea and vomiting
Pale or clay-colored stools
Unintentional weight loss
The symptoms may become more frequent as the condition gets worse. The symptoms may mimic pancreatic cancer. Sitting up and leaning forward may sometimes relieve the abdominal pain of pancreatitis.
Chronic pancreatitis causes inflammation and scarring of tissue in the pancreas. This makes the pancreas unable to produce the right amount of chemicals (enzymes) needed to digest fat. It also interferes with insulin production, which may lead to diabetes.
The condition is most often caused by alcoholism and alcohol abuse. Sometimes the cause cannot be determined, however. Genetic causes have become more common. Other conditions have also been linked to chronic pancreatitis, such as:
Chronic blockage of the pancreatic duct
Injury
Hyperlipidemia
Hyperparathyroidism
Chronic pancreatitis occurs more frequently in men than in women. This may be because alcohol-use disorders are more common in men.
Chronic pancreatitis is often confused with acute pancreatitis because the symptoms are similar. As with acute pancreatitis, the doctor will conduct a thorough medical history and physical examination. Blood tests may help the doctor know if the pancreas is still making enough digestive enzymes, but sometimes these enzymes appear normal even though the person has chronic pancreatitis.
In more advanced stages of pancreatitis, when malabsorption and diabetes can occur, the doctor may order blood, urine, and stool tests to help diagnose chronic pancreatitis and monitor its progression.
After ordering x rays of the abdomen, the doctor will conduct one or more of the tests used to diagnose acute pancreatitis—abdominal ultrasound, CT scan, EUS, and MRCP.
Call for an appointment with your health care provider if:
You develop symptoms of pancreatitis
You have pancreatitis and your symptoms worsen or do not improve with treatment
Treatment for chronic pancreatitis may require hospitalization for pain management, IV hydration, and nutritional support. Nasogastric feedings may be necessary for several weeks if the person continues to lose weight.
When a normal diet is resumed, the doctor may prescribe synthetic pancreatic enzymes if the pancreas does not secrete enough of its own. The enzymes should be taken with every meal to help the person digest food and regain some weight. The next step is to plan a nutritious diet that is low in fat and includes small, frequent meals. A dietitian can assist in developing a meal plan. Drinking plenty of fluids and limiting caffeinated beverages is also important.
People with chronic pancreatitis are strongly advised not to smoke or consume alcoholic beverages, even if the pancreatitis is mild or in the early stages
Acute pancreatitis
Cholelithiasis
Diabetes mellitus
Pancreatic cancer
Irritable bowel syndrome
Directions to Hospitals Treating Chronic pancreatitis
Determining the cause of acute pancreatitis and treating it promptly may help to prevent chronic pancreatitis. Avoiding heavy consumption of alcohol dramatically reduces the risk of developing this condition.
This is a serious disease that may lead to disability and death. You can reduce the risk by avoiding alcohol.
Ascites
Blockage (obstruction) of the small intestine or bile ducts
Blood clot in the vein of the spleen
Fluid collections in the pancreas (pancreatic pseudocysts) that may become infected
Poor function of the pancreas, Diabetes, Fat malabsorption
http://www.nlm.nih.gov/medlineplus/ency/article/000221.htm
http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis/#chronic
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Staphylococcal | Staphylococcus (from the Template:Lang-el, staphylē, "grape" and κόκκος, kókkos, "granule") is a genus of Gram-positive bacteria. Under the microscope, they appear round (cocci), and form in grape-like clusters.
The Staphylococcus genus includes at least 40 species. Of these, nine have two subspecies and one has three subspecies. Most are harmless and reside normally on the skin and mucous membranes of humans and other organisms. Found worldwide, they are a small component of soil microbial flora.
The taxonomy is based on 16s rRNA sequences, and most of the staphylococcal species fall into 11 clusters:
S. aureus group – S. aureus, S. simiae
S. auricularis group – S. auricularis
S. carnosus group – S. carnosus, S. condimenti, S. massiliensis, S. piscifermentans, S. simulans
S. epidermidis group – S. capitis, S. caprae, S. epidermidis, S. saccharolyticus
S. haemolyticus group – S. devriese |
Holography | m of curves of decreasing separation with increasing distance from the centre.
The photographic plate is developed giving a complicated pattern which can be cons into the plate from the other side will 'see' a point source of light whether the original source of light is there or not.
This sort of hologram is effectively a concave lens, since it 'converts' a plane wavefront into a divergent wavefront. It will also increase the divergence of any wave whicable to produce an interference pattern which is stable during the time in which the holographic recording is made. To do this, they must have the same frequency and the same relative phase during this time, that is, they must be mutually coherent. Many laser beams satisfy this condition, and lasers have been used to make holograms since their invention, tl some of the more common media used are listed below. The spacing of the fringes depends on the angle between object and reference beam. For example, if this angle is 45o, and the wavelength of the light is 0.5μm, the fringe spacing is about 0.7μm or 1300 lines/mm. A working hologram can be obtained even if all the fringes are not resolved, but the resolution of the image is reduced as the resolution of the recording medium reduces.
Mechanical stability is also very important when making a hologram. Any relative phase change between the object and reference beams due to vibration or air movement will cause the fringes on the rhase clly, the coherence length of the light determines the maximum of several meters, ample for a deep hologram. Certain pen laser pointers have been used to make small holograms (see External links). The size of these holograms is not restricted by the coherence length of the laser pointers (which can exceed several meters), but by their low power of below 5 mW.
The objects which form the scene must, in general, have optically rough surfaces so that they scatter light over a wide range of angles. A specularly reflecting (or shiny) surface reflects the light in only one direction at each point on its surfac |
Arhinencephaly | Cephalic disorders (from the Greek word κεφάλη, meaning "head") are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic is a term that means "head" or "head end of the body."
Where known, the ICD-10 code is listed below.
Anencephaly (Q00.0)
Colpocephaly (ICD10 unknown)
Holoprosencephaly (Q04.2)
Ethmocephaly (ICD10 unknown)
Hydranencephaly (Q04.3)
Im.
The human nervous system develops from a small, specialized plate of cells on the surface of the embryo. Early in development, this plate of cells forms the neural tube, a narrow sheath that closes between thdevelopment of the nervous system: cell proliferation, the process in which nerve cells divide to form new generations of c |
Subsets and Splits