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Biomedical subjects

C Merkel

Publications and source records attributed to C Merkel.

At least 19 recordsLinked to original sources
PubMed1992

Variability of atrial natriuretic peptide plasma levels in ascitic cirrhotics: pathophysiological and clinical implications.

Ascitic cirrhotic patients are a heterogenous population with respect to factors that may affect plasma human atrial natriuretic peptide levels (such as degree of plasma volume and plasma levels of angiotensin II, vasopressin and norepinephrine). Thus the proven variability of plasma human atrial natriuretic peptide values in ascitic cirrhotic patients may be due also to the selection of patients, not only to the study conditions. The response to standardized stepped-care medical treatment of ascites makes it possible to characterize ascitic cirrhotic patients with different patterns of renal sodium excretion, intrarenal sodium handling, plasma renin activity, plasma aldosterone and thus, probably, effective circulating volume. Consequently, we evaluated human atrial natriuretic peptide plasma levels in controls (n = 23), in ascitic cirrhotic patients who underwent spontaneous diuresis (group A, n = 7) and in cirrhotic patients who required diuretic treatment (group B, n = 44). The last group was then divided into two subgroups. Subgroup B-R (n = 25) included patients who responded to spironolactone alone, whereas subgroup B-NR (n = 19) included patients who did not respond to 500 mg/day spironolactone. All patients were maintained on identical normocaloric restricted sodium intake (80 mEq/day) throughout the study. Ascitic cirrhotic patients, as a whole, had higher values of human atrial natriuretic peptide than did controls (70.8 +/- 46.6 pg/ml vs. 41.7 +/- 16.3 pg/ml, p < 0.025). No difference was found in human atrial natriuretic peptide/plasma renin activity between the two groups (87 +/- 160 pg/ng/hr vs. 44 +/- 73 pg/ng/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Cox's regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.

Adolescent↗
PubMed1992

Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients.

Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.

Adult↗
PubMed1992

Aminopyrine breath test in the prognostic evaluation of patients with cirrhosis.

This prospective study assessed the role of aminopyrine breath test in the prognosis of patients with cirrhosis, and evaluated whether the test provided useful information not included in the Pugh score. During a period of 36 months, 125 patients with biopsy proven liver cirrhosis were included, and followed for up to 48 months (median 17 months). During follow up 43 patients died (20 of liver failure). Survival was univariately related to aminopyrine breath test (p less than 0.02), Pugh score (p less than 0.01), presence of ascites (p less than 0.01), and sex (p less than 0.05). Using Cox's regression analysis, Pugh score, aminopyrine breath test, and sex, were independent significant predictors of survival. From the Cox's model a prognostic index was computed. According to a receiver operating characteristic curve analysis, the prognostic index predicting death showed an improvement in area under the curve when compared with a prognostic index calculated excluding aminopyrine breath test, but the improvement did not reach statistical significance (p = 0.12). A similar prognostic index was calculated to predict death from liver failure. Cox's regression analysis selected aminopyrine breath test, Pugh score, and aetiology as the best set of predictor covariates. According to a receiver operating characteristic curve analysis, a prognostic index cut off value of 2.6 had a 94% sensitivity and a 88% specificity. The prognostic index significantly improved prognostic accuracy when compared with a prognostic index calculated from Pugh score and aetiology, but excluding aminopyrine breath test (p = 0.05). These data disclose that the aminopyrine breath test offers additional prognostic information to the Pugh score, and the prognosis of patients with cirrhosis.

Adult↗
PubMed1992

Effect of triglycyl-lysin-vasopressin on quantitative liver function tests in patients with cirrhosis.

The effects of vasopressin and of its analogues on liver function, and their possible mechanisms of action, are poorly understood. This study was designed to assess the effect of triglycyl-lysin-vasopressin on liver function, evaluated by two quantitative tests independent of liver blood flow, i.e., indocyanine green intrinsic hepatic clearance and galactose elimination capacity. Indocyanine green intrinsic hepatic clearance and galactose elimination capacity were determined before and after administration of 2 mg triglycyl-lysin-vasopressin to (respectively) 10 and 12 patients with cirrhosis. Eighteen additional patients with cirrhosis were studied before and after infusion of placebo. No significant variation in either test was observed in placebo-treated patients. A significant decrease in indocyanine green intrinsic hepatic clearance, averaging 22%, was observed in patients receiving the drug (p = 0.04). Conversely, galactose elimination capacity remained unchanged after the drug. These results are compatible with the hypothesis that the drug produced a preferential decrease in perfusion in functioning areas of the liver, with relative maintenance of blood flow in non-functioning areas.

Adult↗
PubMed1991

Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score.

Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification.

Aminopyrine↗
PubMed1991

Hypophosphatemia and renal tubular dysfunction in alcoholics. Are they related to liver function impairment?

The study was designed to evaluate (a) the role of reduced renal phosphate reabsorptive capacity assessed as the ratio of maximum capacity for renal phosphate reabsorption (TmPO4) to glomerular filtration rate (GFR) in the pathogenesis of hypophosphatemia in alcoholics, (b) possible mechanisms leading to reduced TmPO4/GFR, and (c) the effect of liver function impairment on TmPO4/GFR. The TmPO4/GFR, its major extrarenal determinants, ratios of urinary excretion gamma-glutamyl transpeptidase and of alpha-glucosidase to GFR (uGGT/GFR and uAGL/GFR), indices of structural damage of renal tubular cells, and fractional clearance of lysozyme, an index of proximal renal function, were evaluated in 31 alcoholics with alcohol-related liver disease, 24 alcoholics without alcohol-related liver disease, 14 patients with non-alcohol-related liver disease, and 25 control subjects. Hypophosphatemia was found in 35% of alcoholics with alcohol-related liver disease, 29% of alcoholics without alcohol-related liver disease, and no patients with non-alcohol-related liver disease. A reduced TmPO4/GFR was the major determinant of hypophosphatemia in both groups of alcoholics. No difference in extrarenal determinants of TmPO4/GFR was found between alcoholics with and without hypophosphatemia. Alcoholics with and without alcohol-related liver disease had increased uGGT/GFR and normal uAGL/GFR regardless of serum phosphate level. Fractional clearance of lysozyme, instead, was increased only in hypophosphatemic alcoholics with and without alcohol-related liver disease. The TmPO4/GFR correlated inversely with the fractional clearance of lysozyme in both groups of alcoholics (P less than 0.01). The TmPO4/GFR and urinary enzymes were normal in patients with non-alcohol-related liver disease. It was concluded that a reduced TmPO4/GFR is involved in the pathogenesis of hypophosphatemia in alcoholics. A proximal tubular dysfunction seems to be responsible for the reduced TmPO4/GFR. Liver function impairment is not required for the expression of this tubular dysfunction.

Adult↗
PubMed1991

Theophylline pharmacokinetics and liver function indexes in chronic liver disease.

Since patients with chronic liver disease present with greatly varying theophylline disposal reductions, in cirrhotics the acute theophylline dose schedule must be guided by an index of liver function that predicts theophylline pharmacokinetics. We therefore studied 26 patients with severe chronic liver disease to ascertain the efficacy of the routinely used clinical and biochemical liver function tests in predicting theophylline pharmacokinetics. The prealbumin plasma level, recently proposed as a valuable index of liver function, was also considered. With respect to 10 controls, theophylline clearance was found to be significantly reduced (30 +/- 2 vs. 75 +/- 11 ml/kg/h, mean +/- SD, p less than 0.01). However, only 7 patients had a reduction great enough to require a reduced intravenous theophylline dose schedule. An analysis of clinical utility, made on the basis of ROC curves, showed that the albumin/globulin ratio was the most effective index for identifying patients requiring lower doses of theophylline. Prealbumin and albumin were also useful, whereas bilirubin, prothrombin time, pseudocholinesterase, the presence of ascites and Pugh-Child's classification of the severity of liver disease were found to be worthless.

Adult↗
PubMed1991

Evaluation of splanchnic angiography as a prognostic index of survival in patients with cirrhosis.

Prognostic evaluation of advanced liver disease is usually made on the basis of the common clinical and biochemical data included in the Child-Turcotte classification. The aim of this study was to evaluate the contribution of data from splanchnic angiography as a guide to prognosis in patients with cirrhosis. Over an 8-year period 219 patients with cirrhosis were investigated by splanchnic angiography and followed up prospectively. At the end of the study 95 patients had died (43.4%). Median survival time was 68 months. In addition to several clinical and biochemical data, hepatic portal venous perfusion and the presence of caudad hepatofugal veins as assessed by angiography were significant predictors of survival. Incorporating all nonangiographic variables in a Cox's multiple regression analysis, a clinicobiochemical set of prognostic covariates (ascites, s-albumin, gammaglobulins, s-alkaline phosphatase, and sex) was selected. When adding to this model each of the angiographic variables, only portal perfusion resulted in an independent predictor of survival. In conclusion, in cirrhotics the angiographic evaluation of portal perfusion improved the prognostic information obtained from clinical and biochemical data.

Adult↗
PubMed1991

A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients.

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial.

Sublingual captopril (25 mg) was compared with sublingual nifedipine (10 mg) to determine their effectiveness and safety in the treatment of hypertensive emergencies. In nine of 10 patients who received sublingual captopril, mean (+/- SD) systolic blood pressure and diastolic blood pressure dropped from 245 +/- 39 to 190 +/- 25 mm Hg (P less than .0025) and from 144 +/- 8 to 115 +/- 8 mm Hg (P less than .001) at 50 minutes, respectively. The hypotensive effect of the drug was maintained for a mean of 4 hours. In six of nine responders to sublingual captopril, blood pressure-lowering effect was associated with a clear improvement of end-organ failure within 60 minutes. There were no side effects, including a dangerous fall in blood pressure or reflex tachycardia. Sublingual nifedipine lowered diastolic blood pressure and systolic blood pressure in eight of 10 patients. The hypotensive effect of nifedipine was more rapid than that of captopril (10 vs 20 minutes for diastolic blood pressure and 20 vs 30 minutes for systolic blood pressure, respectively), but no difference was observed in the time or in the magnitude of peak hypotensive effect between the two treatments, nor was a difference observed in the duration of hypotensive effect. In six of eight responders to nifedipine therapy, a clear improvement of symptoms and signs of end-organ failure was observed within 60 minutes. In three patients, minor side effects were observed. We conclude that sublingual captopril effectively and safely lowers arterial blood pressure in patients with hypertensive emergencies.

Administration, Sublingual↗
PubMed1990

Substrate availability other than glucose in the brain during euglycemia and insulin-induced hypoglycemia in dogs.

Alternative substrates other than glucose could be used by the brain. In this study we hypothesized that lactate and ketone bodies can provide a significant portion of oxidative brain substrates in insulin-dependent diabetes mellitus (IDDM). Six control (C) and six insulin-treated streptozotocin diabetic (IDDM) dogs were studied during euglycemia (EU) and acute insulin induced hypoglycemia (HYPO). During EU for similar plasma glucose concentration (5.5 +/- 0.4 v 5.2 +/- 0.2 mmol/L in IDDM dogs showed a higher baseline lactate concentration (1.5 +/- 0.25 v 0.74 +/- 0.10 mmol/L; P less than .05). The ketone body concentrations were also increased in IDDM dogs but this increase was not statistically significant. The brain glucose uptake was 6.9 +/- 0.6 mumol/kg/min in C and 5.4 +/- 0.7 in IDDM. Lactate was released by the brain both in IDDM dogs (11.36 +/- 1.8 mumol/kg/min) and in C dogs (3.87 +/- 0.9; P less than .05). The brain ketones rate of disappearance (Rd) was 0.3 +/- 0.05 mumol/kg/min in IDDM dogs and 0.19 +/- 0.08 in C dogs. During HYPO the glucose uptake across the brain was 2.88 +/- 0.7 mumol/kg/min in IDDM and 3.12 +/- 0.5 in C dogs. We observed an overall brain lactate release (3.21 +/- 1.7 mol/kg/min) in C dogs and a net uptake (13.44 +/- 1.1; P less than .01) in IDDM (P less than .01). The brain ketones Rd was 0.1 +/- 0.2 mumol/kg/min in IDDM and 0.1 +/- 0.1 in C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Clinical significance of cholelithiasis in patients with decompensated cirrhosis.

There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis, severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1-91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients.

Adult↗
PubMed1990

Lack of effect of verapamil and isosorbide dinitrate on the hepatic clearance of indocyanine green in cirrhosis.

1. Vasodilators are currently under investigation as possible therapeutic agents in the treatment of portal hypertension. Among them calcium-channel antagonists and organic nitrates have been of particular interest. Few and conflicting data, however, have been reported on their effect on liver function. 2. Twenty patients with biopsy-proven alcoholic cirrhosis were studied before and 25-35 min following the acute administration of 5 mg verapamil i.v. (eight patients) or 5 mg isosorbide dinitrate sublingually (12 patients). The plasma clearance of indocyanine green (ICG) and its intrinsic hepatic clearance were used as indices of liver function. Seven further patients were investigated before and after a placebo infusion according to the same methodology. 3. No significant change in ICG kinetics was found after verapamil or isosorbide dinitrate.

Adult↗
PubMed1990

Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance.

Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldosterone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 +/- 0.11 vs. 1.29 +/- 0.12%, P less than 0.001; 12529 +/- 677 vs. 15707 +/- 796 microEq min-1 1.73 m-2 BSA, P less than 0.005; 2384 +/- 135.2 vs. 3685 +/- 219.3 microEq min-1 1.73 m-2 BSA, P less than 0.001; 19.5 +/- 1.0 vs. 24.2 +/- 1.3%, P less than 0.01; 2299 +/- 127 vs. 3485 +/- 214 microEq min-1 1.73 m-2 BSA, P less than 0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; P less than 0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 +/- 1.0 vs. 22.4 +/- 1.2%, P less than 0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 +/- 0.4 vs. 94.4 +/- 0.5%, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗