Gene/Protein Disease Symptom Drug Enzyme Compound
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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Availability of a drug regimen that eradicates the hepatitis C virus (HCV) in more than half of treated patients provides the medical community with a powerful new weapon to diminish the anticipated future wave of HCV-related liver disease and cancer. Clinicians must understand the benefits, risks, and costs associated with the combination of peginterferon alfa and ribavirin. Major clinical trials with this new standard of HCV therapy have demonstrated sustained virologic responses of 54% and 56% with 48 weeks of combination therapy. Response is highest in those with genotype 2/3, with early virologic response by week 12, in patients with high adherence, and in patients receiving weight-appropriate ribavirin dosages. The most common side effects are manageable and include fatigue, headache, myalgia, rigors, fever, nausea, insomnia, and depression. Neutropenia associated with interferon and anemia associated with ribavirin are more serious side effects that can cause discontinuation or dose reduction. Clinicians can maximize results and reduce costs with a regimen of peginterferon alfa plus ribavirin by choosing patients carefully, educating patients thoroughly, stopping therapy early in those patients who do not respond by week 12 of therapy, and enhancing adherence by managing side effects with appropriate dose reductions and/or selective use of antidepressants or hematopoietic colony stimulators.
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PMID:Managing hepatitis C. 1508 65

Headache is regarded by patients as a disturbing (or unpleasant) symptom. It can be produced by either organic diseases or functional head abnormalities. Twenty-five years ago headache was supposed to be a psychosomatic angiospastic algia. Certain unusual forms were thought to be caused by triggers like anger, cough, exertion, and sexual activity. Experimental research explored the role of circulating serotonin, prostaglandin, estrogen levels, and platelet abnormalities. As computed tomography, helical computed tomography, and scanning or magnetic resonance imaging evolved, new data became available. None of the newer reports have demonstrated liver involvement as a cause of headache. This minireview intends to cover the spectrum of brain alteration in liver disease. It describes some of the pathophysiological characteristics of hepatic encephalopathy and, also, the relationship among migraine, constipation, and liver disease.
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PMID:Headache and liver disease: is their relationship more apparent than real? 1530 94

It is possible to identify renal cysts in several subjects by ultrasonography imaging techniques. Among the inherited polycystic kidney diseases we include autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic diseases such as von Hippel-Lindau disease, tuberous sclerosis complex (TSC1 and TSC2), and autosomal dominant polycystic kidney disease (ADPKD). ARPKD is a rare disease, related to PKHD1 gene, located on chromosome 6p21, that encodes a protein named polyductin/fibrocystin. Pathoanatomical features are bilateral kidney involvement with multiple microcysts, and invariably liver involvement with portal and interlobular fibrosis. A single genetic defect leads to different degrees of renal and hepatic involvement with very different phenotypes and different clinical outcome, in the same family too. ARPKD clinically may show 4 different forms: perinatal, neonatal, infantile, and juvenile. ADPKD is much more frequent (1: 400-1000 live births), and can arise from mutations in 2 different genes, named PKD1 located on chromosome 16p13.3, and PKD2 located on chromosome 4q21-23. The proteins encoded by the PKD1 and PKD2 genes are named polycystins which play crucial roles in several biologic processes. To explain the focal lesions that affected different organs and tissues the "double hit" theory has been proposed (germinal mutation plus somatic mutation on PKD1 or PKD2). Recently, biologic evidence documented the crucial role of the renal primary cilia on the formation of polycystins to induce cystogenesis. ADPKD may be clinically characterized by abdominal pain, hypertension, episodes of gross hematuria, headache, renal stones, aortic and cerebral aneurysms, mitral valve prolapse, and polycystic liver disease. ADPKD is slowly progressive disease responsible for up 10% of end stage renal failure (ESRF) in every country of the world. Male sex, PKD1 gene, episodes of gross hematuria, and the precocity and severity of hypertension play an important role in the progression of renal disease to ESRF.
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PMID:Autosomal recessive and dominant polycystic kidney diseases. 1578 25

There is an evidence that increased capillary permeability in the standing position is related to a deficit in the sympathetic nervous system. The leakage of this fluid leads to various clinical conditions which frequently puzzle the consulting physician because despite the frequency of this condition intelligent physicians and patients are unaware of the cause of their condition. One of the most common manifestations is the inability to lose weight despite proper dieting. A randomized study comparing the efficacy of a diuretic, a converting enzyme inhibitor, spironolactone and a sympathomimetic amine on weight loss in diet refractory women found that only the latter in the form of dextroamphetamine sulfate demonstrated significant weight reduction over a six month time span. In fact, the dextroamphetamine sulfate proved effective when given in the next 6 months to the three groups failing to respond for the first 6 months. The diagnosis of a deficit in sympathomimetic amines is established by demonstrating an abnormal clearance of a water load in the erect position and exclusion of other conditions that are associated with an abnormal free water clearance, e.g., hypothyroidism, renal or liver disease or congestive heart failure. The original definition of an abnormal water load test was excretion of <55% of a 1500 ml water load in 6h but we found that <75% defines a greater population who suffer from this problem. There are several conditions that have proven refractory to conventional theory that respond quickly and effectively to sympathomimetic amines. There have been many anecdotal reports of relieving interactable pain syndromes quickly and efficiently with sympathomimetic amine theory, despite failure with a multitude of other therapies. These include interstitial cystitis and pelvic pain that was attributed to endometriosis, gastrointestinal pain including esophagitis and gastroparesis, headaches, joint pain, fibromyalgia, and carpal tunnel syndrome. It is not clear if the improvement in pain is related to a decrease in fluid retention or a direct effect of the sympathomimetic amines on the sympathetic nervous system. Sympathomimetic amine theory has helped other conditions besides pain, e.g., chronic fatigue, vasomotor symptoms in young women not associated with decreased ovarian egg reserve, and chronic urticaria resistant to all other therapies. Thus, these studies strongly suggest that physicians be aware of this condition involving a deficit in the sympathetic nervous system when faced with various enigmatic complaints especially if standard therapy has not proven effective.
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PMID:A disorder of sympathomimetic amines leading to increased vascular permeability may be the etiologic factor in various treatment refractory health problems in women. 1776 3

We report the case of a 26-year-old woman who developed thrombophlebitis in her left leg in 2002, followed by fever, asthenia and headache in 2004. Antinuclear antibodies, antimitochondrial antibodies, anti-liver kidney microsome, anti-Smith, antiphospholipid (aPL) and antineutrophil cytoplasmic antibodies, as well as lupus- anticoagulant activity were positive. Systemic lupus erythematosus (SLE) with aPL syndrome was diagnosed and the patient was treated with azathioprine and heparin. Symptoms persisted and itching arose in the following months. The patient was admitted to our department in January 2005 for jaundice and skin rash. Elevated levels of acute phase proteins and cholestasis and liver necrosis indexes were present. Antinuclear antibodies, aPL and antimitochondrial antibodies (M5) antibodies were positive. Liver histology showed minimal focal hepatocyte necrosis, intrahepatic biliary stasis and intralobular inflammatory cell infiltrate. The absence of clinical signs that are characteristic of SLE as well as the failure to confirm antiSmith antibody positivity led us to rule out a diagnosis of SLE. On the basis of clinical, immunological and histological data, autoimmune intrahepatic cholangiopathy associated with primary aPL syndrome was diagnosed. The patient was treated with intravenous methylprednisolone followed by oral prednisone, warfarin and ursodeoxycholic acid. Liver necrosis and cholestasis indexes rapidly improved within 1 month and progressively reached the normal range. To our knowledge, this is the first description of a patient with an association of intrahepatic cholangiopathy and aPL, thus suggesting that autoimmune liver disease might associate with aPL syndrome.
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PMID:Autoimmune intrahepatic cholangiopathy associated with antiphospholipid antibody syndrome. 1787 18

Living donor liver transplantation has become an alternative therapy for patients with end-stage liver disease. Donors are healthy individuals and donor safety is the primary concern. The objective of this study was to evaluate the anesthetic complications and outcomes for our donor cases; we report one death. The charts of the patients who underwent donor hepatectomy from February 1997 to June 2007 were retrospectively reviewed. Right hepatectomy (resection of segments 5-8) was done in 101 donors, left lobectomy (resection of segments 2-3) in 11 donors, and left hepatectomy (resection of segments 2-4) in one donor. Minor anesthetic complications were shoulder pain, pruritus and urinary retention related to epidural morphine, and major morbidity included central venous catheter-induced thrombosis of the brachial and subclavian vein, neuropraxia, foot drop and prolonged postdural puncture headache. One of 113 donors died from pulmonary embolism on the 11th postoperative day. This procedure has some major risks related to anesthesia and surgery. Although careful attention will lower complication rate, we have to keep in mind that the risks of donor surgery will not be completely eliminated.
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PMID:Anesthesia-related complications in living liver donors: the experience from one center and the reporting of one death. 1882 70

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although mainly metabolized in the liver, abnormal liver function tests were a rare adverse effect during clinical trials and we found no literature about albendazole-induced hepatitis requiring admission. This patient had a previous history of albendazole ingestion in 2002 resulting in increase of liver function tests. And in 2005, the episode repeated. We evaluated the patient for viral hepatitis, alcoholic liver disease, and autoimmune hepatitis, but no other cause of hepatic injury could be found. Liver biopsy showed periportal steatosis and periportal necrosis. The initial abnormal liver function test improved only with supportive care. These findings and the Roussel Uclaf Causality Assessment Method of the Council for International Organizations of Medical Sciences (RUCAM/CIOMS) score of 9 are compatible with drug-induced hepatitis so we report the case of this patient with a review of the literature.
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PMID:Acute drug-induced hepatitis caused by albendazole. 1895 2

Evidence is accumulating for the early sustained usage of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis. Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998. Postmarketing surveillance, case reports and observational studies have highlighted less common or unexpected adverse events. Therefore, it is appropriate that we review the benefit-risk profile of leflunomide after 10 years of widespread usage. A wide-based search of relevant literature was performed to formulate this assessment. The improvements in rheumatoid arthritis shown by double-blind, randomized controlled trials (RCTs) of leflunomide have now been shown to be maintained beyond 4 years in open-label extension studies. Leflunomide is comparable to methotrexate, but better than sulfasalazine at 24 months in only one study. However, tolerance in clinical practice research shows higher than expected withdrawal rates due to both toxicity and lack of efficacy when compared with methotrexate and placebo. Adverse events reported include gastrointestinal upset, hypertension, headache, hepatotoxicity and hair loss, as well as predisposition to infection and peripheral neuropathy. The incidence of gastrointestinal adverse effects for leflunomide is similar to sulfasalazine but higher than those seen with methotrexate. Serious drug-induced hepatotoxicity leading to hospitalization is rare (0.02%), but isolated fatalities from liver failure have been documented. It is considered likely, but not yet proven, that there may be an increased incidence of weight loss and interstitial lung disease with leflunomide. Leflunomide in combination with methotrexate or sulfasalazine is an effective regimen in RCTs utilizing placebo controls, but more research is needed to confirm its effectiveness in combination with other DMARDs, particularly biologicals. The active metabolite of leflunomide is teratogenic in animal studies and is also found in breast milk. Therefore, contraception is advised in both males and females of child-bearing potential. There are genetic, pharmacokinetic and biochemical reasons to explain variation in both patient response and adverse event profile. Hence, blood and blood pressure monitoring are recommended and therapeutic drug monitoring should be considered in clinical nonresponders. Leflunomide is an effective DMARD that sustains a clinical and radiological response comparable to sulfasalazine and methotrexate. However, adverse effects necessitate frequent monitoring. It should be used with caution in those of child-bearing potential and with pre-existing lung and liver disease.
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PMID:Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing. 2048 33

Fibromyalgia syndrome (FMS) is a widespread pain condition associated with a wide range of additional symptoms including fatigue, insomnia, depression, anxiety and stiffness. Duloxetine is one of three medications currently FDA approved for use in FMS management. Duloxetine is a mixed serotonin and norepinephrine reuptake inhibitor (SNRI) that functions by increasing central nervous system levels of serotonin and norepinephrine. This review is a primer on use of duloxetine in FMS management and includes information on pharmacology and pharmacokinetics, a review of the three duloxetine FMS treatment trials currently in publication, a discussion of the safety and tolerability of duloxetine, and patient-focused perspectives on duloxetine use in FMS management. Duloxetine has proven efficacy in managing pain and mood symptoms in adult FMS patients with and without major depressive disorder. However, due to side effects, duloxetine must be used with caution in patients with fatigue, insomnia, gastrointestinal complaints, headache, cardiovascular disease, bleeding-risk, and in those 24 years of age and younger due to risk of suicidality. Duloxetine use should be avoided in patients with liver disease or alcoholics. As with all medications, duloxetine is best used as part of an individualized regimen that includes nonpharmacologic modalities of exercise, education and behavioral therapies.
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PMID:Duloxetine for the management of fibromyalgia syndrome. 2119 98

Hepatocellular carcinoma rarely metastasizes to the pituitary gland and this site is very rarely the initial site of disease presentation. When it does, it may mimic a far more common pituitary adenoma. Metastatic hepatocellular carcinoma should be suspected in any individual with known liver disease or significant risk factors. The most common clinical sign of metastatic HCC to the skull is a subcutaneous mass followed by neurological deficits including visual disturbances, headache and seizure. The diagnosis can be made based on the histopathologic and immunohistochemical findings. When metastatic HCC is present in the skull base, appropriate work up should be done to rule out other metastatic sites, most commonly present in the spine.
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PMID:A 50-year-old man with back pain and a sellar mass. Metastatic hepatocellular carcinoma. 2358 45


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