Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S-adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S-adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome.
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PMID:Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. 218 71

The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty-five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody-positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty-nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable.
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PMID:The demography of primary biliary cirrhosis in Ontario, Canada. 219 12

Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy.
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PMID:Effects of plasma exchange (PE) in primary biliary cirrhosis (PBC). A pilot study. 231 37

Primary biliary cirrhosis (PBC) or chronic non-suppurative destructive cholangiohepatitis is rare in southern Africa. Eight patients with this diagnosis were identified and fully investigated at Groote Schuur Hospital between 1980 and 1988. Seven patients were female, all were white or coloured, and their ages ranged from 49 years to 80 years. All patients presented with a history of malaise, fatigue, night sweats and pruritus, which had been present for 3 months--12 years before diagnosis of PBC. Initial misdiagnosis had resulted in unnecessary invasive investigations including laparotomies. Signs of chronic liver disease, such as xantholasmas, evidence of pruritus, the sicca syndrome or hepatomegaly, were invariably present. Marked elevation of serum alkaline phosphatase level and IgM were present in all cases. Antimitochondrial antibodies were positive in significant titre in 7 of the 8 patients. Liver biopsies demonstrated stage II-III disease in all patients. Therapy was chiefly supportive and symptomatic although most patients received immunosuppressive agents. Despite the late presentation, the subsequent course was similar to that seen elsewhere where patients are recognised earlier.
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PMID:Primary biliary cirrhosis. A retrospective survey at Groote Schuur Hospital, Cape Town. 236 77

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.
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PMID:A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss. 277 3

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.
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PMID:Opioid peptides and primary biliary cirrhosis. 314 46

Primary sclerosing cholangitis and primary biliary cirrhosis are chronic cholestatic syndromes that may be difficult to differentiate clinically. Destructive cholangitis occurs in both diseases and leads to similar clinical and biochemical abnormalities. Therefore, we compared the clinical, biochemical, immunologic, radiologic, and hepatic histologic features of these syndromes in two large groups of patients prospectively selected by predefined criteria. Primary biliary cirrhosis (n = 258) occurred predominantly in middle-aged women who were usually symptomatic with fatigue and pruritus, commonly had keratoconjunctivitis sicca, and often were hyperpigmented. Tests for antimitochondrial antibodies were always positive, usually in very high titer. Although the extrahepatic bile ducts were normal radiographically, smooth tapering and narrowing of the intrahepatic bile ducts was occasionally noted. Hepatic histology was diagnostic when a florid duct lesion was present. In contrast, primary sclerosing cholangitis (n = 60) occurred primarily in young men who were usually symptomatic with fatigue and pruritus and frequently had chronic ulcerative colitis. Tests for antimitochondrial antibodies were nearly always negative and cholangiography demonstrated abnormalities of the extrahepatic and intrahepatic bile ducts in all cases. Although hepatic histology was often compatible with the diagnosis, it was usually not diagnostic, and considerable overlap existed with the abnormalities seen in primary biliary cirrhosis. Likewise, biochemical tests of copper metabolism were similar in both syndromes. These results call attention to the differences and similarities in the clinicopathologic features of these two cholestatic syndromes and provide a basis for a rational diagnostic strategy.
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PMID:Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. 388 May 53

Five patients with primary biliary cirrhosis and prolonged cholestasis underwent intensive plasmapheresis. The indications for plasmapheresis included intractable pruritus or hypercholesterolemia and xanthomatous neuropathy. Patients noted a rapid improvement of pruritus and fatigue which was sustained as long as plasmapheresis was continued. Cholesterol levels were lowered an average of 10.3 mmol/l and xanthomata were reduced in three of four patients. Two patients with painful neuropathy caused by xanthomata experienced relief of this symptom. The liver and spleen size were not affected by plasmapheresis, and activities of aminotransferases, alkaline phosphatase and titres of mitochondrial antibody remained unchanged. We conclude that plasmapheresis has a role in the therapeutic management of patients with advanced primary biliary cirrhosis who are disabled by the complications of pruritus, xanthomatous neuropathy, or hypercholesterolemia with xanthoma formation.
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PMID:Role of plasmapheresis in primary biliary cirrhosis. 397 76

A standardized clinical, laboratory, and histological assessment was carried out on 85 patients with primary biliary cirrhosis within 1 year of developing symptoms. Presenting symptoms included pruritus (n = 30), jaundice (n = 9), variceal bleeding (n = 6), ascites (n = 5), fatigue (n = 4), and abdominal pain (n = 4). Ten patients had symptoms not immediately suggestive of hepatic etiology and a further 17 were asymptomatic, the diagnosis being made fortuitously. Eighty four percent were not incapacitated and 52 were anicteric. Less than half were pigmented, 22% had xanthoma, and only 12% were deeply jaundiced. In contrast, all had significant laboratory abnormalities with alkaline phosphatase activity greater than 400 IU/L in 60% and IgM greater than 2.5 g/L in 75%. Mitochondrial antibody was detectable in 83% with a titer greater than 1:160 in 70%. Cirrhosis was present in 24 patients, nine of whom were anicteric and a further 11 had fibrosis or scarring.
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PMID:Early features of primary biliary cirrhosis: an analysis of 85 patients. 400 76

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. 403 Jul 9


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