Total effective vascular compliance in patients with cirrhosis: a study of the response to acute blood volume expansion.

Although arterial vasodilation is a well-known feature in patients with cirrhosis, the venous system remains unexplored. To measure total effective vascular compliance, a reflection of the properties of the venous system, rapid volume expansion (300 ml of a gelatin solution in 3 min) was performed in 23 patients. Eleven patients had compensated cirrhosis (Child-Pugh grade A or B), and eight had decompensated cirrhosis (Child-Pugh grade C). Four control patients had mild chronic hepatitis, normal hepatic venous pressure and normal liver architecture. Cardiac index, hepatic venous pressures, hepatic and azygos blood flow and renal plasma flow were measured before and immediately after volume expansion. Right atrial pressure was recorded during volume expansion. This allowed the calculation of total effective vascular compliance, which was higher in patients with decompensated cirrhosis than in those with compensated cirrhosis (4.65 +/- 4.21 vs. 1.34 +/- 0.63 ml.mm Hg-1.kg-1; p less than 0.05). In response to volume expansion, renal vascular resistance decreased significantly in patients with compensated cirrhosis, but not in those with decompensated cirrhosis (-30% +/- 33% vs. +2% +/- 23%; p less than 0.05). No change was seen in glomerular filtration rate. Systemic oxygen consumption increased in patients with compensated cirrhosis, but not in those patients with decompensated cirrhosis (25% +/- 33% vs. -4% +/- 9%; p less than 0.05). Although in all patients with cirrhosis volume expansion increased central venous pressures, azygos blood flow and the hepatic venous pressure gradient did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Energy metabolism in patients with acute and chronic liver disease

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis.

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.     

Increased production of cysteinyl leukotrienes in hepatorenal syndrome

The cysteinyl leukotrienes C4 and D4 are potent renal vasoconstrictors which may modulate glomerular function in vivo, and may therefore be important in the pathogenesis of hepatorenal syndrome. Urinary leukotriene E4, the major metabolite of leukotrienes C4 and D4, was elevated in patients with hepatorenal syndrome (17.8 ng/h) when compared with normal controls (5.1 ng/h) or subjects with renal failure alone (1.9 ng/h). Urinary leukotriene E4 was also elevated in subjects with decompensated liver disease (cirrhosis with ascites 28.6 ng/h, severe hepatocellular dysfunction 57.5 ng/h), but normal in compensated liver disease (6.7 ng/h). In the early stages of hepatorenal syndrome, leukotriene E4 excretion rate was up to 100-fold higher (560 ng/h) than in normals, and fell in parallel with creatinine clearance, indicative of the glomerular filtration rate-dependent renal excretion. Following correction for creatinine clearance, leukotriene E4, excretion was considerably higher in hepatorenal syndrome (54.1 pg/ml creatinine clearance) compared with normals (1.0 pg/ml creatinine clearance), chronic renal failure (3.2 pg/ml creatinine clearance), decompensated liver disease (ascites 7.7 pg/ml creatinine clearance, and severe hepatocellular dysfunction 11.0 pg/ml creatinine clearance), and compensated liver disease (1.9 pg/ml creatinine clearance). To interpret the significance of these findings, we determined renal clearance and endogenous metabolism of the cysteinyl leukotrienes by infusion of [3H]leukotriene C4 into a single subject with hepato-renal syndrome and two control subjects. Renal clearance of leukotriene E4, was reduced in hepatorenal syndrome (2.4 ml/min) compared with controls (greater than 17 ml/min) which together with the increased excretion rate of leukotriene E4 demonstrates that there is increased cysteinyl leukotriene production in hepatorenal syndrome. This may be one of the factors involved in its pathogenesis.     

Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency

Following administration of digitoxin, 1 mg intravenously, the pharmacokinetics of this glycoside were studied in eight healthy volunteers and in eight patients with hepatorenal insufficiency (mean creatinine clearance 19.6 +/- 2.9 ml/min; antipyrine clearance 25.6 +/- 3.2 ml/min; means +/- SEM). Liver cirrhosis of the patients was confirmed by liver biopsy. Plasma protein binding of digitoxin (means +/- SEM) was 95.1 +/- 0.7% in the patients and 95.6 +/- 1.2% in the volunteers (NS). Total body clearance of digitoxin was 0.0530 +/- 0.0040 ml/min/kg of body weight in the patients and 0.0547 +/- 0.0043 ml/min/kg of body weight in the healthy subjects (NS). When elimination half-lives of the patients and the volunteers were compared, there was also no significant difference (7.0 +/- 0.77 days in the patient group and 7.8 +/- 0.8 days in the volunteers). Our data concerning digitoxin kinetics in patients with hepatorenal insufficiency do not indicate an accumulation of the drug in these patients.     

A comparison between antipyrine and aminopyrine blood clearances.

The purpose of this study was to investigate the relationship between two quantitative liver functions, that is, antipyrine blood clearance and aminopyrine blood clearance, in normal subjects and in patients with liver cirrhosis. The mean blood clearances of antipyrine and aminopyrine in cirrhotic patients (0.220 +/- 0.085 ml/min/kg and 1.13 +/- 0.56 ml/min/kg; n = 64) was 50% and 38% of that of normal subjects (0.440 +/- 0.110 ml/min/kg and 2.95 +/- 0.59 ml/min/kg; n = 11). While no significant correlation was demonstrated between these two values in normal subjects (n = 11, r = -0.107, p greater than 0.10), a strong positive correlation was observed between antipyrine and aminopyrine blood clearances in cirrhotic patients (n = 64, r = 0.846, p less than 0.001). These results suggest that both antipyrine and aminopyrine blood clearances may be valuable indicators for assessing the total hepatic functioning mass in cirrhotics.     

Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system

When renal perfusion pressure is reduced in experimentally induced low-output states, glomerular filtration rate is preserved by angiotensin II-mediated efferent arteriolar vasoconstriction, but available evidence in man suggests that angiotensin II supports renal function only to the extent that it preserves systemic blood pressure. We performed simultaneous assessments of cardiac and renal function in 56 patients with severe chronic heart failure before and after 1 to 3 months of converting-enzyme inhibition. Among the 29 patients with a pretreatment renal perfusion pressure under 70 mm Hg, patients with preserved renal function (creatinine clearance greater than 50 ml/min/1.73 m2) had markedly elevated values for plasma renin activity (11.8 +/- 3.8 ng/ml/hr) and showed a significant decline in creatinine clearance after converting-enzyme inhibition (61.1 +/- 3.0 to 45.9 +/- 5.3 ml/min/1.73 m2; p less than .05). In contrast, although similar with respect to all pretreatment demographic, hemodynamic, and clinical variables, patients with a creatinine clearance under 50 ml/min/1.73 m2 had low values for plasma renin activity (3.4 +/- 0.8 ng/ml/hr) and, despite similar drug-induced decreases in systemic blood pressure, showed no change in creatinine clearance after therapy with captopril or enalapril (32.6 +/- 2.5 to 41.4 +/- 3.8 ml/min/1.73 m2). Changes in creatinine clearance varied linearly and inversely with pretreatment values for plasma renin activity (r = - .64, p less than .001); converting-enzyme inhibition effectively abolished the pretreatment difference in renal function seen in the high- and low-renin subgroups. In the 27 patients with a renal perfusion pressure of 70 mm Hg or greater, creatinine clearance did not vary significantly with plasma renin activity and was not altered by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethambutol kinetics in patients with impaired renal function

The pharmacokinetics of ethambutol (EMB) were investigated in 13 hospitalized patients with varying degrees of compromised renal function. Each patient was administered 15 mg/kg EMB by a constant-rate, 1-h infusion. Plasma and urine samples were collected for as long as 24 and 96 h, respectively, for analysis of EMB by electron capture gas-liquid chromatography. Plasma EMB concentrations appeared to decline multi-exponentially, with a terminal phase half-life of 7.4 to 11.8 h. Total body clearance of EMB ranged from 2.0 to 9.6 ml/min/kg and the steady-state volume of distribution from 0.80 to 3.60 L/kg. The fraction of EMB dose excreted unchanged in the urine varied from 0.03 to 0.26, and renal clearance varied from 0.07 to 0.57 ml/min/kg. The results of this study clearly indicate that renal failure decreases total body clearance and renal clearance and prolongs elimination half-life of EMB when compared with that in normal volunteers. The terminal phase elimination rate constant correlated significantly with creatinine clearance and the reciprocal of serum creatinine (y = 0.037 X +0.060, r = 0.795, p less than 0.05; y = 0.042 X +0.061, r = 0.783, p less than 0.05, respectively). Either creatinine clearance or serum creatinine of an individual patient would thus serve as a useful predictor for his or her capacity to eliminate EMB. Dosage adjustment is mandatory for EMB in patients with compromised renal function in order to achieve optimal therapy and to avoid undesirable side effects.     

Antipyrine clearance as a measure of drug metabolism in patients with diabetes mellitus

Antipyrine-clearance calculated from a single 24 hrs blood sample following i. v. injection of 1 g was determined in insulin dependent diabetics (n = 20), patients with liver cirrhosis (n = 8), with fatty liver + hepatitis (n = 5) and alcoholics with normal liver morphology (n = 3). Antipyrine-clearance values in normal subjects amounted to 58,7 +/- 4,8 ml/min (means +/- s), in cirrhotics to 11,8 +/- 10,1 ml/min (p less than 0.01), in patients with fatty liver to 43,3 +/- 10,1 ml/min (p less than 0.01), and in alcoholics to 62,5 +/- 18,6 ml/min. In diabetics, diseased for many years, also a decrease in the clearance values was seen (41 +/- 17,5 ml/min; p less than 0.05). 15 out of them were below the 2 s range of normal subjects. Thus, the drug-metabolizing capacity in diabetics seems to be markedly reduced, and drug dosage might have to take account of this fact.     

Evaluation of plasma thrombomodulin (TM) levels in patients with liver disease]

Plasma TM levels in patients with various liver diseases were determined by using EIA. In normal subject (n = 58), it's concentration was 15.9 +/- 3.5 ng/ml (mean +/- SD). In liver diseases, the level increased: Acute hepatitis (n = 16), 23.0 +/- 6.5, chronic active hepatitis (n = 21) 22.2 +/- 6.6, compensated liver cirrhosis (n = 20) 27.8 +/- 10.1, decompensated liver cirrhosis (n = 14) 47.6 +/- 17.5, compensated liver cirrhosis with hepatocellular carcinoma (n = 7) 26.3 +/- 7.9, decompensated liver cirrhosis with hepatocellular carcinoma (n = 4) 46.0 +/- 11.8, and fulminant hepatitis (n = 9) 42.0 +/- 20.4. The percentages of abnormal values higher than 22.9 ng/ml, which is mean + 2SD in control subject was 38-100% in liver diseases, especially 100% in patients with liver cirrhosis or with fulminant hepatitis. There was little correlation between plasma TM levels and conventional liver function tests in various liver diseases. Immunohistochemical study of liver tissue showed that an increase of plasma TM level was partially caused by damage and regeneration of endothelial cell. Based on these results the measurement of plasma TM concentration could be an useful marker for detection of hepatic failure.     

Urinary concentrations of bile acid glucuronides and sulfates in hepatobiliary diseases

Urinary bile acids in normal subjects and patients with obstructive jaundice and liver cirrhosis were quantitated by mass fragmentography after separation into nonglucuronidated-nonsulfated, glucuronidated and sulfated fractions. Mean values of total bile acids in urine were as follows: Control subjects (n = 7), 1.90 +/- 0.67; obstructive jaundice (n = 9), 77.90 +/- 40.39; liver cirrhosis, compensated (n = 6), 15.14 +/- 8.97, and decompensated (n = 6), 11.84 +/- 9.32 (mean +/- SD, mg/day). The percentages of each conjugate was 19-29% in the non-glucuronidated-nonsulfated fraction, 6-14% in the glucuronidated fraction and 60-74% in the sulfated fraction. Bile acids in urine and serum correlated well in each fraction (r = 0.82-0.84, p less than 0.001). The clearance of the three conjugates was the highest in the sulfates, and the clearance of glucuronides was higher than that of non-esterified bile acids. The glucuronidation and sulfation of bile acids play an important role in the detoxication of bile acids by excreting them into urine, especially in patients with elevated serum bile acids.     

Plasma endotoxin measured by the combination of new perchloric acid pretreatment method and endotoxin specific assay in liver cirrhosis]

Using with the newly modified perchloric acid pretreatment method and endotoxin specific assay (Endospecy), the plasma endotoxin in the patients with liver cirrhosis was investigated. The mean value of plasma endotoxin in control (n = 20) was below 9.8 pg/ml. The plasma endotoxin level in liver cirrhosis was 5.7 +/- 5.3 pg/ml (n = 70, mean +/- SD), and 20% of the patients (15 cases) showed above 9.8 pg/ml. Endotoxin level significantly correlated with the severity of liver function based on the Child-Turcotte classification (p less than 0.01). Plasma endotoxin positively correlated with total bilirubin (r = 0.417) and ICG clearance test (r = 0.298) and negatively correlated with prothrombin time (%) (r = 0.497) and HDL-cholesterol (r = 0.578) in the patients with liver cirrhosis. There was no correlation between esophageal varices and plasma endotoxin level. Plasma endotoxin was slightly detected in the patients with decompensated cirrhosis, and these data suggest that plasma endotoxin level in cirrhosis is not so elevated.     

Metabolism of 15N-ammonia in patients with cirrhosis: a three-compartmental analysis.

Urinary 15N-ammonia and 15N-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of 15N-ammonia (0.2 mumol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary 15N-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p less than 0.001). The percentage of ammonia reutilization of a given dose of 15N-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p less than 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p less than 0.001) and correlated positively with ammonia reutilization (p less than 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure.     

阿德福韦酯治疗慢性乙型肝炎、肝硬化代偿期和失代偿期患者2年疗效比较

目的观察慢性乙型肝炎（乙肝）、乙肝肝硬化代偿期和失代偿期患者接受阿德福韦酯（ADV）抗病毒治疗2年的疗效。方法对初治的慢性乙肝32例（慢性乙肝组）、乙肝肝硬化代偿期10例（肝硬化代偿期组）和失代偿期14例（肝硬化失代偿期组）应用ADV治疗2年,治疗前和治疗后每3个月检测Au等生化指标及HBVDNA等病毒学指标。结果3组患者在治疗前各项指标基线水平无显著差异,具有可比性。ADV治疗1年和2年时,3组ALT的复常率和HBeAg血清学转换率之间差异无统计学意义（P〉0．05）。治疗2年时慢性乙肝组HBVDNA水平下降的中位数为5．9log10 U／ml,肝硬化代偿期组为6．2log10 U／ml,肝硬化失代偿期组为2．9log U／ml。肝硬化失代偿期组在治疗6个月后的病毒学应答比慢性乙肝组和肝硬化代偿期组差。结论接受ADV治疗2年的慢性乙肝、肝硬化代偿期和失代偿期患者中,肝硬化失代偿期患者病毒学应答差。     

Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis

The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.     

Digitoxin in patients with hepatorenal insufficiency after repeated oral administration

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.     

Colchicine clearance is impaired in alcoholic cirrhosis

Colchicine may have benefit in primary biliary cirrhosis and alcoholic liver disease. It is currently used in patients with impaired liver function, yet little is known about its elimination in such patients. Colchicine clearance in the rat is significantly impaired in various models of liver disease. To study this in human beings, colchicine pharmacokinetics were compared in normal subjects and patients with alcoholic cirrhosis. Colchicine clearance was impaired in the cirrhotic patients. Normal subjects had a mean clearance of 10.65 +/- 1.82 ml/min.kg, whereas cirrhotic patients had a mean clearance of 4.22 +/- 0.45 ml/min.kg (p less than 0.01). The half-life was 57.4 +/- 14.2 min in control subjects vs. 114.4 +/- 19.7 min in cirrhotic patients (p = 0.054). Volume of distribution was not different in the two groups (0.718 +/- 0.1 L/kg in control subjects; 0.716 +/- 0.158 L/kg in cirrhotic patients, p greater than 0.99). No correlation was seen between colchicine clearance and bilirubin, albumin, prothrombin time or Child-Pugh classification, but this may be the result of the small number of patients studied. Based on the values measured, it is estimated that colchicine steady state would change from an average 1.12 ng/ml in normal individuals to 2.82 ng/ml in the cirrhotic patients if 0.6 mg were taken every 12 hr. It is unknown whether this change would be clinically significant. These data show that cirrhosis impairs colchicine clearance and demonstrates that the liver is a major route of colchicine elimination.     

Renal clearance of pancreatic and salivary amylase relative to creatinine in patients with chronic renal insufficiency.

Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.     

Effects of ranitidine on plasma clearance of indocyanine green in patients with liver cirrhosis

The effects of ranitidine on plasma clearance of ICG were investigated in 68 cirrhotic patients (9 were positive for HBsAg, 33 were alcoholics and 26 had cryptogenic cirrhosis). The ICG clearance test was performed before and after ranitidine administration. In 31 patients treated with ranitidine (150 mg perorally), the plasma ICG clearance were 233.6 +/- 20.4 ml/min (mean +/- S.E.) and 239.2 +/- 20.5 ml/min before and after ranitidine, respectively. In the 37 treated with intravenous ranitidine 50 mg, the corresponding values were 205.4 +/- 17.7 ml/min and 206.4 +/- 17.9 ml/min. There was no significant change in the plasma clearance of ICG or the elimination rate constant after ranitidine administration. Even in patients with decompensated liver cirrhosis, no significant change was demonstrated in the plasma ICG clearance after ranitidine. These results led to the conclusions that ranitidine does not reduce the hepatic blood flow and that it is a safe and useful drug for the treatment of gastrointestinal tract bleeding in patients with liver cirrhosis.     

Effects of diet-therapy on urinary protein excretion albuminuria and renal haemodynamic function in obese diabetic patients with overt nephropathy

Twenty-four type 1 and type 2 diabetic patients with obesity and overt nephropathy were studied for 12 months after hypocaloric diet change from 1870 to 1410 kcal/day (without changes of protein:carbohydrate ratio). Several parameters were evaluated: arterial blood pressure, blood glucose, fructosamine, HbA1c, proteinuria, albuminuria, glomerular filtration rate (GFR), creatinine clearance, triglycerides, HDL and total cholesterol. A significant reduction of body weight (body mass index from 33 +/- 1.6 to 26 +/- 1.8 kg/m2, P less than 0.001), concomitantly with a decrease of blood pressure levels (P less than 0.002) was demonstrated at the end of the study. Triglyceride (P less than 0.002), HDL (P less than 0.002), HDL (P less than 0.05) and total cholesterol (P less than 0.01) levels were reduced after diet-therapy, while a mild improvement of glycometabolic profile was observed in the same period. A marked decrease of proteinuria (from 1280 +/- 511 to 623 +/- 307 mg/24 h, P less than 0.01) and albuminuria (from 723 +/- 388 to 492 +/- 170 micrograms/min, P less than 0.01), and an improvement of GFR (from 66 +/- 13 to 81 +/- 11 ml/min/1.73 m2, P less than 0.01) and creatinine clearance (from 79 +/- 14 to 91 +/- 13 ml/min, P less than 0.01) was demonstrated after 12 months of diet-treatment. Our data suggest that body weight reduction by hypocaloric diet may delay the progression of clinical nephropathy in obese diabetic patients.