Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cysteinyl leukotrienes, comprising leukotriene C4 and its metabolites, are biologically most active mediators, eliminated from the blood circulation by the liver and the kidneys. The urine of normal subjects and of patients with hepatic and/or renal failure was analysed for endogenous cysteinyl leukotrienes. The leukotriene metabolites were separated by reversed-phase high-performance liquid chromatography and subsequently quantified by radioimmunoassay. Leukotriene E4 was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol l-1 in healthy subjects to 0.8 nmol l-1 in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4 averaged 7.8 nmol l-1; in addition, N-acetyl-leukotriene E4 was detected in an average amount of 1.5 nmol l-1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 mumol leukotriene E4 mol-1 creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease.
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PMID:Analysis of cysteinyl leukotrienes in human urine: enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome. 249 62

The development of hepatic encephalopathy and coma hepaticum in patients with acute gastrointestinal bleeding and hepatic cirrhosis is a serious problem. Since 1983 we perform a whole gut irrigation with mannite for cleansing the bowel via naso-gastric tube. The aim of this therapy is to reduce the severity of hepatic encephalopathy. The first 20 patients with the new therapeutic concept were compared with the last 20 patients with the prevailing therapy. We studied the effect of the new therapeutic concept as to reduction of hepatic encephalopathy and possible electrolyte loss. None of the patients in the mannite group had hepatic encephalopathy stage III or IV, whereas 75% of the patients without mannite showed clinical signs of stage III or IV. Serum potassium, sodium and chloride were not significantly different between both groups. In the group with mannite application no change in serum creatinine was observed, whereas in the other group a minute increase of serum creatinine was seen.
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PMID:[Orthograde intestinal irrigation with a mannitol solution in reducing hepatic encephalopathy in patients with liver cirrhosis and gastrointestinal hemorrhage]. 250 57

We determined human and canine plasma clearance of atrial natriuretic factor (ANF) by lung, liver, and kidney from arteriovenous differences in plasma ANF and measured organ plasma flow. Human subjects had lower plasma ANF concentrations in the pulmonary vein or the pulmonary capillary wedge position when compared with the pulmonary artery, and both sites yielded pulmonary ANF extraction ratios of 24%. Canine lung ANF extraction was 19 +/- 3% and pulmonary ANF clearance was 328 +/- 78 ml/min per m2 vs. 357 +/- 53 ml/min per m2 in man. Hepatic plasma ANF clearance was 216 +/- 26 ml/min with an extraction ratio of 30 +/- 3% in humans and 199 +/- 89 ml/min and 36 +/- 6% in the dog. Renal plasma ANF clearance in human subjects was 78 +/- 12 ml/min per kidney and correlated well with each kidney's creatinine clearance (r = 0.58, P less than 0.05). The mean renal ANF extraction ratio was 35 +/- 4% in human subjects and 42 +/- 6% in the dog. These data quantitate the specific organ ANF clearances by lung, liver, and kidney in human subjects and in dogs and provide a rationale for elevated plasma ANF levels in cirrhosis, renal failure, and diseases accompanied by reduced perfusion of these organs. These findings support the conclusion that plasma ANF concentrations are dependent upon both the stimuli for ANF secretion as well as the specific organ clearances of ANF.
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PMID:Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog. 252 90

Hepatic encephalopathy and gastrointestinal (GI) bleeding are the most serious complications in cirrhosis. The purpose of this study was to examine survival after the first episode of GI bleeding or coma, or both, and to identify variables associated with the subsequent survival in 284 consecutive patients with cirrhosis admitted to one division of hepatology over a period of 81 months. Patients who only bled had markedly longer survival than those who only had coma, whereas those who had both bleeding and coma had by far the poorest survival, only 15% being alive 1 year later. Several other variables showed a significant association with survival. In a Cox multiple regression analysis the following four variables showed significant association with a short survival: coma and bleeding at the episode, ascites, low prothrombin index, and high serum creatinine. The prognostic index derived from the Cox model, which was validated by a split-sample testing technique, may be used to refine prognostic estimation in this subgroup of severely ill cirrhotic patients.
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PMID:Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognostic factors. 259 62

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach. 270 9

Following chronic oral administration of digitoxin 0.1 mg day-1 the pharmacokinetics of this glycoside were studied in seven patients with hepatorenal insufficiency and were compared with those of seven healthy volunteers. Liver cirrhosis of the patients was confirmed by liver biopsy. Mean creatinine clearance of the healthy subjects was 129.7 +/- 3.3 ml min-1 (mean +/- SEM), that of the patients was 25.6 +/- 20.4 ml min-1. Mean antipyrine clearance (parameter of oxidative liver function) was 49.7 +/- 6.0 ml min-1 in the volunteers and 22.0 +/- 2.9 ml min-1 in the patients. Plasma protein binding of digitoxin (PPB) was 95.0 +/- 1.1% in the patients and 96.7 +/- 0.6% in the healthy subjects (n.s.). Total body clearance of digitoxin (Cltot) was 0.0728 +/- 0.0120 ml min-1 kg-1 in the patients and 0.0615 +/- 0.0027 ml min-1 kg-1 in normals (n.s.]. Mean steady state plasma levels (Css) of the patients were 18.3 +/- 4.7 ng ml-1 and 15.8 +/- 1.3 ng ml-1 in the normals (n.s.). Our data obtained from chronic oral administration do not indicate a reduced total body clearance of digitoxin in patients with hepatorenal insufficiency.
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PMID:Digitoxin in patients with hepatorenal insufficiency after repeated oral administration. 270 65

To determine the effects of liver disease on the disposition of ciramadol, an analgesic that undergoes ether glucuronidation, we studied its plasma pharmacokinetics in 10 patients with stable cirrhosis, 8 with acute viral hepatitis, and 16 age-matched healthy controls. Renal excretion of the glucuronides was also determined. In healthy controls given a single intravenous dose of the drug the t 1/2 was 3.4 +/- 0.3 hrs and the systemic clearance was 668 +/- 109 ml/min of which renal clearance was 320 +/- 73 ml/min and non-renal clearance 349 +/- 74 ml/min. The corresponding values after an oral dose were similar. Renal clearance was related directly to the estimated creatinine clearance. Moreover, the renal clearance of ciramadol exceeded creatinine clearance, suggesting that the drug was excreted not only by glomerular filtration but also by tubular secretion. The systemic clearance of intravenous ciramadol was diminished by 40% in cirrhosis, P less than 0.05, due to a reduction in renal clearance, while non-renal clearance remained normal. Renal clearance of the inactive glucuronides, on the other hand, was not affected. In patients with acute viral hepatitis, systemic clearance was unchanged, but renal clearance of ciramadol tended to increase during the acute phase of the disease and to return toward normal after recovery. Renal excretion of the inactive glucuronides was decreased by 48% (P less than .05). These findings suggest that the non-renal ether glucuronidation of ciramadol remains intact in patients with stable cirrhosis or acute viral hepatitis. However, the renal clearance of the drug may be impaired in cirrhosis, but tends to be enhanced in acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of liver disease on the disposition of ciramadol in humans. 272 8

It is known that chronic alcoholics and type II diabetics show hyperlipidemia, characterized by hypertriglyceridemia and in a minor degree by hypercholesterolemia. The mechanisms underlying the effect of ethanol and carbohydrates on plasma lipids seem to be different; therefore in diabetic subjects chronic alcohol consumption could produce a more severe hyperlipidemia and so accelerate atherosclerotic events. In order to verify it we have measured plasma cholesterol, HDL-cholesterol, and triglycerides and investigated the presence of micro- and macroangiopathy in two groups of non-insulin-dependent diabetics, differing each other for daily alcohol intake (18 chronic male alcoholics and 30 male subjects consuming respectively more than 150 g and less than 50 g of alcohol daily). In alcoholics, no clinical features, laboratory and echographic findings of cirrhosis and pancreatic disease were present. In order to avoid a possible interference of other factors on the metabolism of plasma lipids, in our study patients were selected with the following criteria: 1) only male subjects; 2) age 40-60 years; 3) nonsmokers; 4) moderate coffee drinkers; 5) average physical activity; 6) with BMI less than 28; 7) in good diabetic control (HbA1c less than 6%, n.v. 4.4%-5.6%); 8) normal kidney function (plasma creatinine less than 1.3 mg%) and 24 hr proteinuria absent;) 9) in treatment with diet alone or diet plus low doses of sulphonylureas or biguanides. The data were analyzed by Student's "t" and chi-squared tests. No significant differences could be detected (alcoholics/occasional drinkers, means +/- 1 SD) either in the plasma levels of cholesterol (181.7 +2- 39.3/198.2 +/- 32.5), HDL-cholesterol (43.4 +/- 12.7/38.5 +/- 11.9), and triglycerides (105.5 +/- 56.4/159.7 +/- 114.8) and in the frequency of micro (22.2%/16.6%) and macroangiopathy (16.6%/26.6%) between the two studied groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of chronic alcohol consumption on blood lipid levels and angiopathy in diabetics]. 274 71

The effect of encainide administration on steady-state plasma digoxin levels was evaluated in 17 patients receiving stable doses of digoxin. A paired t test, comparing plasma digoxin levels (mean +/- standard error) before encainide therapy (1.05 +/- 0.14 ng/ml) and after 2 weeks of encainide, 100 mg/day (1.03 +/- 0.11 ng/ml) or 200 mg/day (1.2 +/- 0.2 ng/ml), indicates no significant (p greater than 0.05) change in digoxin levels. These results were confirmed in a second study of 10 patients with severe congestive heart failure. Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required. Plasma concentrations of encainide and its 2 major metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide, significantly increased by 31.6%, 43.1% and 35.6% after concomitant cimetidine administration in 13 healthy adult men receiving 75 mg/day of encainide. However, a retrospective evaluation of 33 patients receiving both drugs did not reveal any clinically significant interactions. Retrospective evaluation of patients enrolled in clinical studies who received concomitant digoxin (268), antiarrhythmics (118), anticoagulants (78), antidiabetics (40), antipsychotics (23), beta blockers (88), calcium-channel blockers (24) or diuretics (229) did not reveal any clinically significant interactions with encainide. Similarly, in vitro protein binding studies did not reveal any clinically significant interactions with encainide or its major metabolites. Six patients with moderate to severe renal impairment (creatinine clearance 10 to 38 ml/min) received 25 mg of encainide, 3 times/day, for 7 doses. Plasma encainide, ODE and 3-methoxy-O-demethyl concentrations were similar to those observed in normal subjects who had received twice the dose of encainide, and steady-state apparent oral clearance of encainide was reduced by 66% with renal impairment. Based on these data it is recommended that in patients with moderate to severe renal impairment encainide be initiated at one-third the normal dose, or 25 mg once a day. Doses may be elevated in small increments at 1-week intervals if needed for efficacy. The effect of hepatic impairment on the pharmacokinetics of encainide was studied in 7 patients with clinically documented cirrhosis. Compared with normal subjects studied using a similar protocol, the plasma concentrations of encainide were elevated significantly due to a 6-fold decrease in oral clearance. However, since plasma concentrations of the active metabolite ODE were correspondingly lower, specific encainide dosing instructions for patients with hepatic impairment are not indicated.
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PMID:Drug interaction studies and encainide use in renal and hepatic impairment. 287 43

To investigate the pharmacokinetics of benazepril hydrochloride in special populations, single or multiple doses between 5 and 20 mg of the new drug were given, and the pharmacokinetics of unchanged benazepril and its pharmacologically active metabolite benazeprilat were compared with those in healthy male volunteers. In elderly subjects and patients with mild and moderate renal insufficiency, there was little change in the kinetics of benazepril or benazeprilat. In patients with severe renal impairment (creatinine clearance less than 30 ml/min), benazeprilat elimination was slowed, which resulted in greater accumulation after repeated dosing. In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected. Therefore dose adjustment is unnecessary because of the patient's age, mild or moderate renal impairment, or hepatic cirrhosis. Dose reduction is necessary in patients with creatinine clearance less than 30 ml/min.
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PMID:Pharmacokinetics of a new angiotensin-converting enzyme inhibitor, benazepril hydrochloride, in special populations. 291 53


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