Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Since the introduction of fenofibrate to European clinical practice in 1975, some 6.5 million patient-years of experience in the treatment of hyperlipidemia have been accumulated. A review of results of clinical trials shows fenofibrate to have a broad spectrum of lipid-lowering activity, reducing the total cholesterol level by 20-25% in type IIa patients and triglycerides by 40-60% in type IIb and IV patients. High levels of low-density lipoprotein cholesterol are reduced and, where low at baseline, high-density lipoprotein levels are increased. An associated activity is a 10-28% reduction in serum uric acid levels. Adverse reactions in the mostly open clinical trials ranged from 2-15%; mild gastrointestinal problems dominated, and occurred with much the same frequency in the placebo-treated groups of controlled trials. There are also reports of fatigue, headache, loss of libido, dizziness, and insomnia. Some excess of skin rash emerged as the only statistically significant unwanted clinical effect in one placebo-controlled trial. Biochemically, there are occasional fluctuations in serum transaminase values, while gamma-glucuronyl transferase and alkaline phosphatase are often decreased, all without apparent clinical significance. Lithogenicity of the bile is often increased above pretreatment levels, but there is no evidence from trials or postmarketing surveillance that the use of fenofibrate is associated with an increase of gallstone formation.
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PMID:Review of European clinical experience with fenofibrate. 265 20

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

To further define the clinicopathologic features and determinants of survival, we reviewed the cases of 110 patients with primary hepatic malignancy managed surgically between 1975 and 1986. Presenting signs of symptoms were pain (57%), fatigue (48%), abdominal mass (40%), and weight loss (33%). Twenty-six percent of patients had a history of hepatitis or cirrhosis. Histopathologically, tumors were hepatocarcinoma (72%), fibrolamellar variant (7%), cholangiocarcinoma (9%), mixed (7%), and other (5%). Resectability rate with curative intention was 67%. Exploration and biopsy alone was performed in 27% and palliative resection in 6%. Hospital mortality was 9%, and serious morbidity was 22%. Perioperative morbidity and mortality were significantly associated with operative blood loss. Median survival was 12.6 months, with a 5-year survival of 18%. Median survival after curative resection was 22.8 months, and 5-year survival was 27%. Univariate analysis showed that female sex, normal performance status, well-differentiated tumor, and curative resection were associated with increased survival; cholangiocarcinoma, nodal metastases, cirrhosis, hypocalcemia, prolonged prothrombin time, and increased serum transaminase and alkaline phosphatase were associated with decreased survival. Cox multivariate analysis showed that curative resection, normal performance status, and well-differentiated tumors were associated with increased survival, and prolonged prothrombin time and hypocalcemia were associated with decreased survival.
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PMID:Primary hepatic malignancy: surgical management and determinants of survival. 279 50

A case report is presented of a 43-year-old woman with generalized peliosis hepatitis that developed during longterm use of oral contraceptives (OCs). The patient had been in good health until the last 2 years when she began to experience vague epigastric pains and a feeling of abdominal distension. Several months prior to admission, she had started to complain of itching and fatigue. There was no history of dark urine, white stools, or hepatitis. On physical examination, no jaundice or cutaneous stigmata of chronic liver disease were observed. Laboratory studies showed a normal erythrocyte sedimentation rate and hematological blood count. A radionuclide study of the liver showed hepatomegaly; especially the left lobe was enlarged. A computerized tomographic scan of the liver showed multiple areas of decreased density in both of the enlarged lobes. There was no evidence of a tumor. Selective transfemoral angiography of the celiac artery also showed hepatic enlargement but no signs of a space-occupying lesion. At laparoscopy, the liver was grossly enlarged and had a lumpy appearance, but again there were no signs of a tumor. No evidence of veno-occlusive disease or hepatocellular adenoma was found. The diagnosis was peliosis hepatitis. The OCs were withdrawn, and the patient was discharged. Regular follow-up in the outpatient department showed no decrease in the size of the liver. The alkaline phosphatase level rose. The fatigue became worse, and cholestyramine was prescribed for progressive itching. In September 1980, the patient was admitted for reevaluation. A repeated CT scan and angiography of the liver again yielded no evidence of a tumor. Esophagoscopy showed the presence of varices grade 2. The liver at laparoscopy had the same appearance as it had in 1976. Histological examination of a biopsy specimen showed occasional dilated sinusoids and locally marked periportal and intralobular fibrosis. No regeneration nodules were found. The diagnosis was liver fibrosis. The patient's condition deteriorated gradually in the following years. She experienced increasing fatigue. Steatorrhea developed, and the patient lost weight. She needed increasing doses of cholestyramine and oral supplementation of vitamins A, D, and K. She was admitted for a 3rd time in February 1985. Esophagoscopy revealed varices grade 4. A CT scan of the liver showed no change. The patient successfully underwent an orthotopic liver transplantation in January 1987. The diagnosis of peliosis hepatis was well documented in this patient.
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PMID:Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives. 312 33

The quianazoline antifolate N10-propargyl-5,8-dideazafolic acid (ICI 155,387), an inhibitor of thymidylate synthetase (TS), was evaluated for clinical toxicity in a phase I trial. The compound was given once every week as a bolus injection. Fourteen patients with advanced cancer were treated at doses of 10-30 mg/m3. Four patients from the lowest to the highest dose developed severe renal toxicity, detected by a reversible decrease in the Cr-EDTA clearance. Hepatotoxicity was observed with transient elevations of alanine aminotransferase (ALT) in 10 patients and alkaline phosphatase in nine patients. Neither the incidence nor the severity of these toxicities was dose related. Two patients developed feelings of fatigue, which in one patient coincided with a decrease in Cr-EDTA clearance. No myelotoxicity, dermatological, gastrointestinal toxicity or mucositis was seen. No tumour responses due to ICI 155,387 occurred. The severity and the erratic nature of the renal side-effects suggest that this schedule cannot be recommended for further development of this compound in Phase II trials.
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PMID:A phase I evaluation of N10-propargyl-5,8-dideazafolic acid. 335 7

The mortality and morbidity in abdominal surgery were investigated in two groups of patients, one with empty (N = 228) and the other with normal (N = 220) iron stores before operation. The estimation of body iron stores by measurements of serum ferritin concentration assumes that the only reason for a low ferritin value is an empty iron store. The results showed that the period of hospital treatment was shorter and the number of complications, especially infections, fewer, in patients with normal as compared to empty iron stores before the operation (p less than 0.001). These differences were especially striking in patients subjected to gastric or large bowel surgery. The results were not explained by differences in sex, age, serum albumin, or clinical anemia. The complications were not predictable from preoperative serum albumin, alkaline phosphatase, or alanine amino transferase levels. Among patients with postoperative complications those with preoperative empty iron stores also had a lower preoperative blood hemoglobin concentration (127 +/- 10 g/liter) than those with normal preoperative iron stores (136 +/- 9 g/liter). Thus it is speculated that the mechanisms behind postoperative complications due to preoperative empty iron stores might be a decrease in tissue oxygenation, resulting in an increased fatigue while working, decreased contractile capacity of the respiratory muscles, and a decrease in immune function. Thus a measurement of serum ferritin concentration and correction of empty iron stores is recommended before abdominal surgery.
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PMID:Empty iron stores as a significant risk factor in abdominal surgery. 339 23

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.
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PMID:Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-alpha A (rIFN alpha A). 363 19

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


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