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)

Several authors have suggested that the risk of developing aminoglycoside nephrotoxicity is greater in cirrhotic patients than in the noncirrhotic population. However, this has not been confirmed by other investigators. To compare the intensity and characteristics of aminoglycoside nephrotoxicity in cirrhotic and normal rats, 31 rats with carbon tetrachloride-induced cirrhosis with ascites and 35 control rats were treated with gentamicin. Each group of rats was divided into two subgroups in order to receive 10 or 40 mg per kg per day of gentamicin, and different subsets of animals were killed on Days 4, 8 and 12 of treatment for renal histological examination and determination of renal tissue gentamicin concentration. Urine volume, osmolality, sodium excretion and N-acetyl-beta-D-glucosaminidase activity were measured daily throughout the study. Creatinine clearance and trough plasma concentration of gentamicin were determined in each animal immediately before killing. There were no significant differences between cirrhotic and control rats in relation to the magnitude of changes in urine volume, osmolality, sodium excretion and N-acetyl-beta-D-glucosaminidase activity and creatinine clearance during gentamicin administration. The values of a histopathological score semiquantitatively assessing the renal morphological changes observed by light microscopy were not significantly different in cirrhotic and control rats. In addition, similar trough plasma and renal cortical tissue concentrations of gentamicin were observed in both groups of animals. These results suggest that, in this experimental model, cirrhosis does not increase the risk for aminoglycoside nephrotoxicity.
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PMID:Comparative study of aminoglycoside nephrotoxicity in normal rats and rats with experimental cirrhosis. 339 10

Great importance has been given to nutritional evaluation concerning either diagnosis or prognosis, and also involving nutritional support as therapeutic approach. Nutritional evaluation of 32 cirrhotic patients was performed using anthropometric measures as triceps skinfold and arm muscular circumference, and laboratory data: creatinine/height index, serum albumin transferrin; and lymphocyte number in peripheral blood. Non-caloric stores, evaluated by triceps skinfold were extremely low in 81% of the cases studied, while muscular stores, evaluated by arm muscular circumference and creatinine/height index were depleted in respectively 37.5% and 43.7%. Visceral stores evaluated by serum levels of albumin and transferrin, as well as immunological state, measured by peripheral lymphocytes counts, showed severe depletion in 10 to 15% of the patients. The increasing importance of nutrition in hepatic cirrhosis is stressed and interpretation of the different methods used for nutritional evaluation in chronic liver disease is discussed.
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PMID:[Nutritional evaluation in cirrhotic patients]. 344 8

Changes in urinary PGE2 and PGF2 alpha excretion in chronic liver diseases were observed in relation to renal hemodynamics and sodium balance. After equilibration on a 110-170-meq sodium diet, daily urine collections were analyzed for PGE2 and PGF2 alpha by a new extraction and radioimmunoassay method. PGE2 was significantly greater in cirrhotics than in healthy subjects and in chronic hepatitis. The value was greater in cirrhotics with ascites than in those without ascites (p less than 0.05). PGF2 alpha did not differ among the groups. In cirrhotics PGE2 was correlated negatively with creatinine clearance (Ccr)(r = -0.76, p less than 0.001). After administration of 200 mg indomethacin, a significant fall in Ccr was seen only in cirrhotics with ascites. The percentage fall in PGE2 after indomethacin correlated with that in Ccr (r = 0.89, p less than 0.05) and with that in urinary sodium excretion (r = 0.68, p less than 0.02). These results suggest that PGE2 is essential in the maintenance of renal function in liver cirrhosis with ascites.
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PMID:Urinary prostaglandins and renal function in chronic liver diseases. 345 30

It has been postulated that diminished renal prostaglandin E2 (PGE2) production, whether basal or in response to stimulation by diuretic treatment, determines the intensity of sodium retention in cirrhosis. Urinary PGE2 excretion (as an index of renal PGE2 production) as well as urine volume, urinary sodium and potassium excretion, and creatinine clearance were examined in 19 patients with cirrhosis and either no ascites, diuretic-responsive ascites, or diuretic-resistant ascites. Measurements were made both before (all patients) and after (ascitic patients) stimulation of renal PGE2 synthesis by 80 mg of furosemide intravenously. Urinary PGE2 excretion was similar in the three groups both before and after furosemide. Baseline urine volume and creatinine clearance were similar in all groups but were significantly less after furosemide in patients with diuretic-resistant ascites as compared to the other two groups. The natriuretic response to intravenous furosemide was significantly less in patients with diuretic-resistant ascites. Insertion of the peritoneovenous shunt to aid in the management of diuretic-resistant ascites resulted in a marked, immediate increase in urine volume and urinary PGE2 excretion in the four patients who were serially evaluated, but natriuresis occurred in only two. Overall, urinary PGE2 excretion correlated with urine volume but not with sodium excretion or creatinine clearance. Diminished renal PGE2 production, as reflected by urinary PGE2 excretion, does not appear to be a determinant of the severity of renal sodium retention in cirrhosis.
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PMID:Urinary prostaglandin E2 excretion, sodium retention, and diuretic responsiveness in patients with chronic liver disease. 347 Oct 82

Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta-adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.
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PMID:Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis. 347 23

Urinary excretion of two prostacyclin metabolites was investigated in 48 subjects: 8 controls and 40 cirrhotics (9 without ascites, 22 with ascites and preserved renal function, and 9 with functional renal failure). Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), believed to reflect renal prostacyclin production, was significantly increased in patients without ascites and in ascitic patients with preserved renal function, but cirrhotics with renal failure showed rates similar to controls. Excretion of 2,3-dinor-6-keto-PGF1 alpha (PGI-M), the major urinary metabolite of systemic prostacyclin, was increased in all groups of patients, including those with renal failure. A single dose of sulindac, a renal-sparing prostaglandin synthesis inhibitor, reduced PGI-M but not 6-keto-PGF1 alpha in 5 cirrhotic patients. This would be consistent with the predicted renal origin of the latter and the systemic origin of the former. Ascitic patients with high urinary excretion of PGI-M (above the median value) showed significantly lower mean arterial pressure and higher plasma renin activity and aldosterone than patients with excretion below the median. Urinary 6-keto-PGF1 alpha was higher in patients with low PGI-M. Finally, creatinine clearance corrected excretion of PGI-M, as an estimation of relative plasma levels correlates both with plasma renin activity and plasma aldosterone in the 31 subjects who presented with ascites. It is suggested that enhanced synthesis of systemic prostacyclin may influence hemodynamic changes in patients with liver cirrhosis. Overproduction of systemic prostacyclin in the absence of increased renal prostacyclin synthesis appears to be characteristic of patients with functional renal failure.
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PMID:Increased synthesis of systemic prostacyclin in cirrhotic patients. 351 Sep 38

In a series of studies, peritoneovenous shunting (PVS) has been used to dissect out some of the many factors involved in salt and water retention associated with hepatic ascites. Careful metabolic studies showed that, immediately following PVS, diuresis and natriuresis were associated with a marked rise in cardiac output, renal plasma flow and creatinine clearance, and a significant fall in the elevated serum aldosterone and plasma renin activity to within the normal range. Despite these changes, sodium excretion in these patients remained abnormal when challenged with a high salt diet. In contrast, an immediate increase in water excretion was not associated with a reduction in the elevated antidiuretic hormone (ADH) levels which do, however, decrease to some extent after 2 weeks. Thus, in the long term, these cirrhosis patients will have improved systemic and renal hemodynamics and function and normalization of the renin-aldosterone axis and ADH, yet will still have a "sodium-retaining lesion," the nature of which still needs to be elucidated.
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PMID:The use of peritoneovenous shunting in unravelling the pathogenesis of ascites in cirrhosis. 351 75

Urinary prostaglandin excretion was studied in 42 patients with liver cirrhosis and in nine control subjects on restricted sodium intake and on bed rest. Creatinine clearance (CCr), sodium excretion (UNaV), plasma renin activity (PRA) and plasma aldosterone were also evaluated. Patients without ascites and ascitic patients without renal failure showed increased urinary excretion of immunoreactive 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha), prostaglandin E2 (iPGE2) and thromboxane B2 (iTXB2) when compared with controls, while immunoreactive PGF2a (iPGF2 alpha) levels did not differ from those in the control group. Patients with functional renal failure (FRF) presented a significant reduction of vasodilator prostaglandins but urinary excretion of iTXB2 was higher than in controls. On the whole, cirrhotic patients with higher urinary excretion of prostaglandins had normal or nearly normal PRA and aldosterone levels. i6-keto-PGF1 alpha and iPGE2 inversely correlated with PRA and aldosterone. The relationship between i6-ketoPGF alpha alpha and CCr was found to be highly significant in cirrhotic patients but not in the control group. On the other hand, iPGE2 significantly correlated with UNaV and with the fractional excretion of sodium (FENa). We concluded that: (a) enhanced renal prostaglandin synthesis in cirrhosis, inversely related to PRA and aldosterone, may be dependent on volume status; and (b) preserved renal function in these patients is associated with the ability to synthesize prostacyclin and PGE2.
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PMID:Renal prostaglandins in cirrhosis of the liver. 351 33

Urinary antithrombin III (AT III) related antigen was analyzed by SDS-polyacrylamide gel electrophoresis and Western blotting, and the nitrocellulose membrane was scanned with a 2-wavelength TLC scanner. The urinary AT III related antigen was found to be located in three different molecular weight regions: the AT III region, and molecular weight regions higher and lower than that of AT III. The ratio of the higher molecular weight region to the AT III region divided by the urinary creatinine, was taken as an "index" and was analyzed in liver cirrhosis patients as well as in normal controls. The "index" in liver cirrhosis was higher than that in the controls. Further, the "index" revealed a significant proportional correlation with the total bilirubin and direct bilirubin, and also a significant inversely proportional correlation with the plasma AT III, suggesting that the "index" tends to become higher as liver function decreases. The pathophysiological significance of the "index" is briefly discussed.
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PMID:Molecular analysis of urinary AT III related antigen in liver cirrhosis. 352 65

Tertatolol is rapidly (tmax: 1.25 h) and totally absorbed by the gastro-intestinal tract with a low presystemic metabolism, and the bioavailability (60%) is not affected by food intake. Although clearance is low (130 ml/min), half-life is short (3 h) due to a restricted volume of distribution. Tertatolol is extensively metabolized (99%) to 9 metabolites with three equally important pathways, sulfoxidation, hydroxylation and conjugation. The half-life is not altered in hypertensive patients. It is increased in the elderly (7 h) and in patients with renal failure (9 h, irrespective of creatinine levels). However, considering the once-daily regimen, the recommended dose (5 mg/24 h) does not need to be altered in these patients. In hepatic disease, the modifications of pharmacokinetic parameters correlate with the severity (t1/2 = 14.5 h in the severe group). Taking into account the extensive metabolism of the drug, this justifies halving the dose in patients with cirrhosis and prothrombin time less than 70%. The kinetics are linear over a 10-fold dosage range and, after repeated dosing, there is no accumulation. Despite the short half-life, and because of a flat plasma level response curve, beta-blockade continues for 24 h following a 5-mg dose.
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PMID:Biodisposition of tertatolol in man: a review. 354 11


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