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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV-absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid. In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration (= clearance equivalent) was about 2.2 ml.min-1.kg-1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml.min-1.kg-1 and 0.59 ml.min-1.kg-1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy. The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites.
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PMID:Urinary caffeine metabolites in man. Age-dependent changes and pattern in various clinical situations. 142 75

Serum concentrations of caffeine (CA) and its three major dimethylmetabolites (theobromine; TB: paraxanthine; PX: theophylline; TP) were measured in fifteen patients with cholelithiasis, in ten patients with cirrhosis and in ten healthy subjects after the oral CA (2 mg/kg) loading. The correlations of total body clearance (CL) between three-point study (sampling times 1, 2 and 4 h) and nine-point study (sampling times 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h) were highly significantly correlated (r = 0.988, p less than 0.001). The elimination half-life (t1/2) of CA was significantly longer in cirrhotic patients than in the other two groups. Cirrhosis had no effect on the apparent volume of distribution (Vd) of CA, but CL of CA was substantially reduced in these patients. Production of the three metabolites of CA, but mainly PX, was reduced in patients with cirrhosis. There were significant correlations between the serum PX/CA (r = 0.911, p less than 0.001) and (PX + TB + TP)/CA (r = 0.905, p less than 0.001) ratios and CL of CA at 4 h after CA administration in the three groups. These findings suggest that CA pharmacokinetic parameters can be estimated using a simplified three-point blood sampling procedure following a single oral load and that the serum PX/CA or (PX + TB + TP)/CA ratio in a single blood sample taken 2 or 4 h after dosing provides a useful indicator for the assessment of hepatic drug-oxidizing capacity, N-demethylation, in decompensated liver cirrhosis. However, CA test was unable to distinguish the difference of liver function between the control subjects and in patients with cholelithiasis.
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PMID:A simple useful method for the determination of hepatic function in patients with liver cirrhosis using caffeine and its three major dimethylmetabolites. 142 97

Less complex methods of measuring hepatic metabolic capacity are needed. A simplified caffeine clearance test was evaluated in 23 patients with stable alcoholic liver disease. First, saliva caffeine concentrations were measured over a 24-h caffeine-free interval. Clearance was calculated from the rate of elimination of caffeine and an assumed volume of distribution and compared with the results of a formal clearance test using sequential plasma and saliva samples following a 300 mg oral dose. The simplified method was then assessed in 11 hospitalized patients with cirrhosis. Saliva caffeine concentrations remained measurable over the interval of study in 82% of patients. Caffeine clearance as determined by the simplified method did not differ from plasma caffeine clearance after an oral dose. Application of this method was achieved in 11 of 12 patients hospitalized for complications of severe liver disease, and revealed markedly diminished clearance. Thus, caffeine clearance can be accurately estimated in patients with severe liver disease using two or more samples of either saliva or plasma. This simplified determination of caffeine elimination rate provides a more practical assessment of hepatic metabolic capacity than a formal clearance test.
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PMID:Caffeine clearance in cirrhosis. The value of simplified determinations of liver metabolic capacity. 834 Jun 6

Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory.
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PMID:The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function. 151 59

We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C). Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Cardiac output was measured by using Doppler echocardiography. Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively). Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14). Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance. However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.
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PMID:Plasma glucagon concentration in cirrhosis is related to liver function but not to portal-systemic shunting, systemic vascular resistance, or urinary sodium excretion. 198 11

Previous studies strongly suggest that adenosine receptors on juxtaglomerular cells function to restrain the secretion of renin induced by a variety of stimuli. The clinical significance of this is that caffeine, a widely consumed adenosine receptor antagonist, could augment renin release responses to diseases such as renovascular hypertension, liver cirrhosis and heart failure and to therapeutic maneuvers such as salt restriction, diuretics and vasodilators. Caffeine may be particularly troublesome in this regard because this methylxanthine has central nervous system effects and intracellular actions that also might contribute to the overall ability of caffeine to potentiate renin secretion. The purpose of this study was to document the effects of caffeine on renin release responses to a vasodilator and to investigate what mechanisms were responsible for any augmentation of vasodilator-induced renin secretion. Accordingly, we compared the effects of caffeine vs. 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX; a xanthine that we documented in this study not to significantly enter the brain or penetrate cell membranes) on base-line and hydralazine-induced renin release in both normal and beta adrenoceptor-blocked (propranolol, 15 mg/kg) rats. Both xanthines (at a dose of 10 mg/kg plus 150 micrograms/min) attenuated adenosine-mediated hypotension and bradycardia, and DPSPX was at least as effective as caffeine in antagonizing peripheral adenosine receptors. Caffeine and DPSPX increased base-line plasma renin activity to a similar extent regardless of whether the animals were pretreated with propranolol. In rats with an intact beta adrenergic system, caffeine, but not DPSPX, increased the renin release response to low-dose hydralazine (1 mg/kg). Although both xanthines augmented the renin release response to high-dose hydralazine (10 mg/kg), caffeine was more efficacious in this regard. In beta adrenoceptor-blocked rats, neither caffeine nor DPSPX augmented the renin release response to low-dose hydralazine, whereas both xanthines equally potentiated the renin release response to high-dose hydralazine. These data demonstrate that caffeine increases base-line renin release primarily by blocking peripheral (most likely renal), cell-surface adenosine receptors; however, caffeine potentiates vasodilator-induced renin secretion in part by blocking peripheral (most likely renal), cell-surface adenosine receptors and in part by additional central nervous system and/or intracellular mechanism(s) that involve the beta adrenergic system.
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PMID:Caffeine potentiates vasodilator-induced renin release. 200 84

In 56 patients with various liver diseases and in 15 healthy controls fasting serum concentrations of caffeine (HPLC method) and total endogenous bile acids (enzymatic-spectrophotometric assay) were determined. Serum caffeine concentrations were significantly higher in patients with chronic hepatitis or liver cirrhosis than in controls but no differences was found between patients with obstructive jaundice and controls. Contrary to caffeine, fasting serum bile acids concentrations were higher in all patients groups than in controls. In all studied groups there was no correlation between caffeine and serum bile acids estimations. In patients with liver cirrhosis there was correlation between caffeine test and the Child's classification score. However, no correlation existed between the Child's classification and the serum bile acids concentration. Our data suggest that fasting serum caffeine concentration is more usefull indicator of liver injury than determination of total endogenous serum bile acids.
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PMID:[Comparison of the value of serum caffeine and bile acid concentrations as indicators of liver injury]. 207 20

Female Uje: WIST rats received thioacetamide (TAA) in the tap water (0.3 g/l) from the 4th to 6th months of life to produce experimental liver cirrhosis. Immediately, 2 and 7 days after TAA cessation it was investigated by means of in vivo (caffeine and metamizol elimination) and vitro methods (cytochrome P-450, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation), whether this animal model represents the restricted cytochrome P-450-dependent biotransformation comparable to human liver cirrhosis. The total capacity of the liver was diminished immediately and 2 days after TAA cessation. After 7 days the capacity was unchanged compared to the controls or partly even enhanced. Therefore, this animal model reflects rather a short time than a stable alteration of biotransformation after TAA cessation comparable to human liver cirrhosis.
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PMID:[Effect of 3 months of thioacetamide treatment on liver biotransformation in vivo and in vitro (various times after discontinuation)]. 209 75

Effect of smoking cigarettes on hepatic metabolizing capacity of caffeine in respect to the extent of liver damage was studied among 46 patients with chronic liver disease and 6 healthy, nonsmoking subjects. The rates of hepatic elimination in cirrhosis (68 +/- 35 ml/min) and chronic extrahepatic cholestasis (60 +/- 32 ml/min) were lower in comparison to steatosis (132 +/- 38 ml/min), chronic active hepatitis (115 +/- 35 ml/min) and healthy control group (115 +/- 46 ml/min). Generally, the patients smoking cigarettes (n = 21) metabolized caffeine more rapidly than nonsmoking patients (107 +/- 42 ml/min vs 71 +/- 41 ml/min, p less than 0.01). In cirrhotics we observed the 9% difference of caffeine clearance between smokers and non-smokers, whereas in ++ groups of patients showing no significant impairment of caffeine elimination rate (steatosis, hepatitis) the tobacco induced the 33% change in caffeine clearance. Healthy nonsmoking subjects metabolized caffeine more rapidly than smoking cirrhotics (115 +/- 46 ml/min vs 71 +/- 26 ml/min, p less than 0.05). It may be concluded that smoking cigarettes increase hepatic elimination rate of caffeine in chronic liver disease, however the range of this effect depends upon the extent of liver damage.
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PMID:[Effect of smoking on caffeine elimination by the liver in patients with chronic liver diseases]. 209 23

Hepatic microsomal function was assessed by a caffeine clearance test at night and during the day using saliva and serum samples obtained simultaneously. In 26 patients with cirrhosis, 21 patients with noncirrhotic liver disease and 15 control subjects caffeine elimination correlated well during the day and at night (r = 0.915 for serum and 0.917 for saliva). The correlation coefficients for caffeine clearance in saliva and serum were 0.940 during the day and 0.963 overnight. In the cirrhotic patients, clearance differed significantly from noncirrhotic liver disease and controls in saliva samples overnight: 0.51 +/- 0.45 ml/min per kg versus 0.91 +/- 0.44 and 1.41 +/- 0.56, respectively. Comparable results were obtained for serum clearance overnight and clearances during the day. Serum and saliva clearances at night correlated well with the aminopyrine breath test (rs = 0.884 and 0.907, respectively). Overnight caffeine clearance in saliva might be a simple useful method for assessing progression and prognosis of liver disease.
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PMID:Assessment of hepatic function. Comparison of caffeine clearance in serum and saliva during the day and at night. 218 97


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