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)

Case records of 177 patients admitted with Hodgkin's disease were reviewed to assess the frequency and significance of coagulation abnormalities. Prolongation of the prothrombin time, activated partial thromboplastin time, or thrombin time occurred in 56 patients, 32 percent of all evaluable cases. The most frequent clotting abnormalities involved the prothrombin time, which was increased in 43 patients (24 percent). Prothrombin time prolongation correlated with bulky or advanced disease as defined by stage (p = 0.001), constitutional symptoms (p less than 0.0001), massive mediastinal involvement (p = 0.02), and elevated alkaline phosphatase levels (p less than 0.0001). Abnormal coagulation test results followed the course of disease, normalizing with tumor regression and reappearing during relapse. Despite the surprising incidence of abnormal coagulation results, bleeding complications were reported in only two cases. Patients undergoing invasive procedures in the presence of clotting abnormalities fared no worse than those in whom procedures were cancelled. There is no evidence that complete staging evaluation should be comprised because of these abnormal test values. Extensive hematologic testing revealed no single mechanism to explain the coagulation factor disorders found in Hodgkin's disease.
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PMID:Abnormal coagulation results in patients with Hodgkin's disease. 316 Feb 35

The purpose of this pilot study was to determine whether daily administration of cyclosporin A to symptomatic patients with primary biliary cirrhosis for 1 yr would lead to a significant and sustained improvement in liver enzyme abnormalities. Twelve adult patients (11 female, 1 male; aged 52.6 +/- 8.9 yr, mean +/- SD) with serologic and histologically defined primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. Cyclosporin A was administered at sufficient dosages to maintain serum radioimmunoassay trough levels between 100 and 200 ng/ml (starting dosage, 2.5 mg/kg.day). After 1 yr of therapy, significant changes from pretreatment values were seen only in recipients of cyclosporin A. These included a 37% decrease in mean serum alkaline phosphatase and a 43% decrease in gamma-glutamyltransferase (controls +3% and -14%, respectively). Mean serum bilirubin and albumin levels and prothrombin times remained unaltered in the two groups, as did the extent of inflammation and fibrosis and the histologic staging of liver biopsy specimens. Although mean serum creatinine levels increased by 51% in recipients of cyclosporin A (+2% in controls), there were no associated changes in diastolic blood pressure or creatinine clearance values. Other side effects including thrombocytopenia, hirsutism, headaches, tremor, and parasthesiae were common in the treated group but not of sufficient severity to warrant adjustment in the dosage or discontinuation of therapy. The observed changes in hepatic, renal, and hematologic tests tended to return to baseline after discontinuation of therapy. Two patients, both placebo recipients, died of liver failure during the study period. The results of this study indicate that in symptomatic primary biliary cirrhosis, cyclosporin A administration is associated with a significant improvement in cholestatic liver enzyme abnormalities that persists for the duration of therapy. A progressive rise in serum creatinine levels and a high incidence of side effects raise concerns regarding the long-term safety of this agent in primary biliary cirrhosis.
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PMID:Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis. 316 99

In alimentary deficiency of vitamin K in rats, accompanied by an increase in the prothrombin time by 30%, activity of kidney creatine kinase and of blood serum alkaline phosphatase was unaltered, while the activity of alkaline phosphatase in small intestinal mucose was decreased by 20% and that of creatine kinase from skeletal muscles--by 10%. In vitamin K-deprived animals the rate of coupling between respiration and mitochondrial phosphorylation was decreased, which might be due to alteration in the NADH-dehydrogenase complex. Menadion reductase activity and cyanide-resistant respiration of mitochondria were unaltered in presence of menadion. Palmitic acid effectively activated of mitochondrial respiration in vitamin K-deprived animals (contrary to the control rats). This effect appears to occur as a result of structural alterations in mitochondria depending on vitamin K level in the organelles.
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PMID:[The effect of vitamin K deficiency in rats on various enzyme systems participating in energy metabolism]. 319 31

The effects of a new synthetic steroid Org OD 14 on the haemostatic mechanism were investigated in 60 post-menopausal women, randomly allocated to 12 weeks of treatment with either 2.5 mg/day of Org OD 14 or a placebo in a double-blind, group-comparative study. Assessments were made 2 weeks before and just prior to the start of treatment, at weeks 6 and 12 during treatment, and 2 weeks after its cessation. No significant differences between the two groups were found with regard to prothrombin time, kaolin cephalin clotting time (KCCT), clotting factors VII, VIII and X, white blood count (WBC) or transaminases (ASAT, ALAT). The following statistically significant differences were seen in the Org OD 14 group: higher plasminogen, antithrombin III, haemoglobin, haematocrit and platelet count, and increased fibrinolytic activity on fibrin plates, as well as lower fibrinogen and alkaline phosphatase values. These findings indicate that Org OD 14 displays no adverse effects on coagulation, while changes in fibrinolysis seem to be beneficial for post-menopausal women.
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PMID:Coagulation and fibrinolysis in post-menopausal women treated with Org OD 14. 330 92

A multivariate Cox regression analysis with time-dependent variables has been performed on the data of 415 patients with cirrhosis included in a controlled clinical trial of 10-15 mg prednisone daily versus placebo. The analysis showed that a poor prognosis was associated with a low prothrombin index, marked ascites, GI bleeding, high age, high daily alcohol consumption, high bilirubin and alkaline phosphatase and low albumin values, little liver connective tissue inflammation, and poor nutritional status. Prothrombin index and ascites showed significant interaction with the treatment in such a manner that high prothrombin index and absence of ascites were associated with a beneficial effect of prednisone, whereas low prothrombin index and presence of ascites were associated with a harmful effect of prednisone treatment. The final model was validated in independent patients by comparing their actual survival with that predicted from the model, using a split-sample testing technique. The prognostic factors were combined with an index that can be used to update prognosis whenever changes occur in the clinical status of a patient during the course of the disease. The probability of surviving the next 3 or 6 months can be estimated from the prognostic index at any time during the course. The index may be of value for the correct timing of special therapeutic procedures such as liver transplantation.
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PMID:Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables. 352 Jul 95

Patients with alcoholic hepatitis with plasma B12 levels above 800 pg/ml have overt clinical manifestations of liver disease including severe hepatocellular damage. High plasma B12 levels significantly correlate (P less than 0.0001) with standard liver function tests, e.g. bilirubin, cholylglycine, alkaline phosphatase, AST and prothrombin time as an index of the severity of hepatic damage. Decrease in plasma B12 to normal titres implies a decrease in the severity of alcoholic liver disease, whereas increased plasma B12 levels relate to increased severity and mortality.
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PMID:Plasma vitamin B12 titres as indicators of disease severity and mortality of patients with alcoholic hepatitis. 359 79

Hepatic metabolism is the primary process of elimination of propafenone. It therefore is important to understand the effect of altered liver function on the disposition and elimination kinetics of this drug. Patients with abnormal liver function probably will require treatment with propafenone for cardiac arrhythmias; an understanding of the relationship between liver function and the pharmacokinetics of propafenone will provide a rational basis for optimal dosage adjustments in these individuals. Our results demonstrate that both systemic clearance and bioavailability of propafenone are sensitive to variability in liver function. The bioavailability of propafenone is inversely related to the clearance of indocyanine green (ICG), whereas a direct relationship exists between systemic clearance of propafenone and ICG clearance. Comparisons of clinical parameters with the propafenone data yielded interesting results. An overall clinical grading of severity of liver disease based on the presence or absence of portal hypertension (i.e., varices and/or splenomegaly), prior encephalopathy, and ascites did not correlate well with propafenone results. However, albumin, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT) concentrations and prothrombin time values correlated strongly with the overall results. No definite relationships with subjects' age; weight; and hemoglobin, alkaline phosphatase, lactic acid dehydrogenose, cholesterol, blood urea nitrogen, or creatinine levels were detected. These results demonstrate that moderate to severe liver disease significantly affects the absorption and disposition of propafenone. In patients with cirrhosis, and presumably other forms of hepatic dysfunction, careful adjustments of propafenone doses are needed to optimize therapy.
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PMID:Influence of hepatic dysfunction on the pharmacokinetics of propafenone. 369 82

To investigate the natural history of compensated cirrhosis, 293 consecutive patients without previous major complications (ascites, jaundice, encephalopathy or gastrointestinal hemorrhage) were studied in terms of morbidity (probability of developing decompensated cirrhosis during follow-up) and survival. Patients were diagnosed by liver histology between 1968 and 1980. Median follow-up was 63 months. Decompensation of cirrhosis was considered when a patient first developed one of the major complications of the disease. Ten years after diagnosis, the probability of developing decompensated cirrhosis and the survival probability rate were 58 and 47%, respectively. A multivariate survival analysis (Cox's regression model) using clinical, biochemical and histological data obtained at diagnosis disclosed seven factors that predicted prognosis: serum bilirubin; serum gamma-globulin concentration; hepatic stigmata; prothrombin time; sex; age, and alkaline phosphatase. According to the contribution of each one of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. The predicting value of this index was validated by a split sample testing technique.
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PMID:Compensated cirrhosis: natural history and prognostic factors. 380 91

The pharmacokinetics of mezlocillin were investigated in 26 patients with alcoholic liver disease. Serum concentrations of mezlocillin were measured following intravenous administration of 3 g doses over 30 min. The mean peak serum concentration (+/- standard deviation) of mezlocillin at the end of infusion was 138.8 +/- 55.7 mg/l and the mean terminal half-life (T 1/2 beta) was 2.10 +/- 0.9 h. The 24 h urinary recovery of mezlocillin was 35.4 +/- 12.4% of the administered dose. Serum clearance was found to be inversely correlated with alkaline phosphatase and with total bilirubin. The T 1/2 beta was related to the following clinical measurements: age, SGOT and prothrombin time. This relationship suggests it may be prudent to adjust the dosage and the dosage interval of mezlocillin in patients with hepatobiliary dysfunction.
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PMID:Pharmacokinetics of mezlocillin in patients with hepatobiliary dysfunction. 381 96

Quantitative and qualitative measures of liver function were investigated in rabbits with chronic renal failure (CRF) induced 3 months earlier by surgical reduction of renal mass, and compared with a sham-operated control group. In the CRF group the galactose elimination capacity (GEC) was significantly decreased by 25%, but when related to liver weight the difference was not statistically significant. The clearance of antipyrine was unaffected. The serum activities of alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase were similar in the two groups. The prothrombin index was increased by 20%, and the serum albumin concentration decreased by 9%. By light microscopy no significant morphological changes were found in the livers of the CRF rabbits. The results do not indicate significant changes of the hepatic functional status during moderate chronic renal insufficiency.
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PMID:Functional status of the liver during chronic renal failure: an experimental study in the rabbit. 393 5


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