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Biomedical subjects

C Merkel

Publications and source records attributed to C Merkel.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1990

Plasma carnitine levels in liver cirrhosis: relationship with nutritional status and liver damage.

The plasma level of carnitine, a co-factor involved in many metabolic reactions, is high in alcoholic liver cirrhosis, due to an increased amount of esterified carnitine. To determine if this alteration is linked to alcoholic liver disease or to liver cirrhosis per se. total carnitine, free carnitine, total esterified carnitine, short chain acylcarnitine and long chain acylcarnitine were measured in 41 patients suffering from liver cirrhosis of different aetiology and severity. In 19 of these patients, acetylcarnitine was also measured. Moreover, multivariate analysis was performed to assess the association of carnitine plasma levels with nutritional and liver disease indices. Of the nutritional indices (creatinine/height ratio, mid upper arm muscle circumference and triceps skinfold) only triceps skinfold appeared to be weakly correlated with carnitine (with long chain acylcarnitine). Significantly high levels of acetylcarnitine, short chain acylcarnitine, total esterified carnitine and total carnitine were found in cirrhotics independently of the aetiology of cirrhosis, even though a trend towards higher levels of acetylcarnitine was evident in heavy drinkers. Direct correlations of gamma-glutamyltransferase with acetylcarnitine, acetylcarnitine/free carnitine, short chain acylcarnitine/free carnitine and total esterified carnitine/free carnitine were found. Carnitine plasma levels did not differ in the three Pugh-Child's classes; however, a trend towards higher levels of acetylcarnitine was found in Pugh-Child's class C. In conclusion, the high levels of acetylcarnitine, short chain acylcarnitine, total esterified carnitine and total carnitine found in cirrhosis were linked to liver disease. Alcohol abuse seemed only to be an exacerbating factor.

Adult↗
PubMed1990

Pharmacokinetics of iloprost in patients with hepatic dysfunction.

In the present experiment the pharmacokinetics of iloprost was studied in eight hospitalized patients suffering from liver cirrhosis (mean age: 56 years, 3 females, 5 males, child-classification: A [n = 1], B [n = 5], C [n = 2]/mean 14C-aminopyrine breath test: 3.9% dose/2 h). Iloprost was administered as a 1 h-i.v. infusion with 1 ng/kg/min to all the test subjects. Steady state plasma levels of 93 +/- 31 pg/ml were observed at the end of infusion. The terminal half-life of iloprost was 28 +/- 24 min. From AUC values of 126 +/- 60 pg.h/ml a total clearance of 10 +/- 5 ml/min/kg was calculated. The study demonstrated that iloprost clearance was reduced by a factor of 2 in patients suffering from hepatic dysfunction compared with healthy subjects. Individual dose titration is the recommended dose regimen for iloprost therapy in all patients. Therefore, apart from a reduction of the starting dose (of approximately 50%) for titration, special recommendations are not necessary for patients with impaired liver function.

Adult↗
PubMed1989

Indocyanine green intrinsic hepatic clearance as a prognostic index of survival in patients with cirrhosis.

The prognostic value of quantitative liver function tests in patients with cirrhosis is not clearly established. Indocyanine green intrinsic hepatic clearance (ICG-IHC) is a quantitative liver function parameter independent of liver blood flow, which was shown to correlate strictly with the Child-Turcotte-Pugh (CTP) classification of severity of liver disease. Few data are available on its prognostic value. One hundred and five patients with cirrhosis were studied. ICG-IHC was measured according to the 'sinusoidal perfusion' model. Median ICG-IHC in the whole series was 374 ml/min (interquartile range: 214-496 ml/min). During follow-up (mean 31 months; max. 48 months) 38 patients died. The probability of survival was lower in patients with ICG-IHC lower than 300 ml/min (35% at 48 months) than in patients with ICG-IHC between 300 and 1000 ml/min (70%), or with ICG-IHC over 1000 ml/min (80%) (P = 0.02). Also s-albumin (P less than 0.01), ascites (P = 0.001) and CTP class (P less than 0.001) were significant predictors of survival. On incorporation of age, sex, etiology of cirrhosis, ICG-IHC, s-albumin, s-bilirubin, prothrombin index, ascites and encephalopathy, into a multiple regression analysis according to the Cox's model, the results showed only ascites and s-albumin to be independent significant predictors of survival, while ICG-IHC was not among the covariates independently predictive of survival. When CTP class was added to the investigated covariates, the results showed it as the only independent predictor of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Fat emboli in bilateral total knee arthroplasty. Predictive factors for neurologic manifestations.

Fat embolism after bilateral total knee arthroplasty (TKA) occurred in 12% of the authors' patients having bilateral TKA with intramedullary instrumentation. Usually embolism was manifested as neurologic changes, most often changes of mental status. Death is a potential consequence, and this occurred in one patient. The present authors believe that fat embolism is not predictable preoperatively and propose that intraoperative guidelines can be used to reduce risk of this complication. Intraoperative monitoring by a Swan-Ganz catheter will permit measurement of the pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure. A sustained rise of any of these would be an indication to abort the second knee operation. If Swan-Ganz catheter is not available, a sustained fall of oxygen saturation to 90% or lower can be used as a criterion. The risk for fat embolism is increased with the use of intramedullary instrumentation, and the above guidelines are recommended for operations with this type of instrumentation. A fluted intramedullary rod and vent holes should be used.

Catheterization, Swan-Ganz↗
PubMed1989

Prognostic indicators of survival in patients with cirrhosis and esophageal varices, without previous bleeding.

Sixty-one patients with cirrhosis with varices without previous bleeding were admitted to our Department over a period of 2 yr. Fifty had alcoholic cirrhosis. Child-Turcotte-Pugh class was A in 11 patients, B in 30, and C in 20. Varices were F1 in 18, and F2-F3 in 43. During follow-up of up to 40 months, one patient was lost to follow-up and 22 patients died, seven of gastrointestinal bleeding and 15 of liver failure. The probability of death from any cause was significantly related to Child-Turcotte-Pugh class, ascites, encephalopathy, s-albumin, s-bilirubin, prothrombin index, and galactose elimination capacity. Independent prognostic variables according to Cox's model resulted s-albumin, s-bilirubin, encephalopathy, and varices. Considering only patients who died from liver failure, survival was univariately related to the same determinants, whereas the Cox's model individuated s-bilirubin, s-albumin, ascites, and galactose elimination capacity as independent prognostic indicators. Considering only patients who died from gastrointestinal bleeding no Cox model could be performed due to the small number of deaths. In patients with F1 varices, the probability of death from liver failure was 5 times higher than that from gastrointestinal bleeding; in patients with F2-F3 varices, liver failure and gastrointestinal bleeding each accounted for approximately half of the deaths. These data could become useful when programming a clinical trial of prophylaxis which considers reduction in mortality as the main end-point.

Adult↗
PubMed1988

Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis.

Nadolol, a non-cardioselective beta adrenoreceptor blocking agent, has been reported to decrease portal pressure without affecting liver function in cirrhotic patients treated for 1 month. There were no data about the long-term effects of nadolol on liver function. In 11 patients with cirrhosis and portal hypertension galactose eliminating capacity, aminopyrine metabolic capacity, ICG clearance and IGC intrinsic hepatic clearance according to the "parallel tube" model were measured before and after 6 months of treatment with nadolol at a dose reducing resting heart rate by approximately 25%. No significant variation in any of these parameters was found. Thus 6 months of continuous oral administration of nadolol did not further impair liver function in cirrhotics.

Adult↗
PubMed1988

Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis.

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20-40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.

Adult↗
PubMed1988

Effects of iloprost, a prostacyclin analog derivative, on renal plasma flow, renal function, and renin-aldosterone system in humans.

The effects of iloprost, a stable analog derivative of prostacyclin, on heart rate, blood pressure, renal plasma flow (RPF), glomerular filtration rate, filtration fraction, urine flow, fractional excretion of sodium (FENa), proximal fractional sodium reabsorption (PFRNa), fractional sodium resorption at the ascending limb of Henle's loop (HFRNa), plasma renin activity (PRA), and plasma aldosterone concentration (PA) were evaluated in patients with peripheral vascular disease and normal renal function. In 10 patients the drug was administered intravenously for 6 hours daily for 6 days at a rate of 1 ng/kg/min. In 7 patients iloprost was also administered at a dose of 2 ng/kg/min for the same time. There was no significant change in heart rate and blood pressure at both iloprost doses. At the dose of 1 ng/kg/min the drug had no effect on renal hemodynamics and function, PRA, and PA. At the dose of 2 ng/kg/min iloprost significantly increased RPF (p less than 0.025) and FENa (p less than 0.025) and significantly decreased HFRNa (p less than 0.025) without affecting glomerular filtration rate, filtration fraction, urine flow, PFRNa, PRA, and PA. No correlation was found between the increase in RPF and FENa (r = 0.01). We conclude that at a dose of 2 ng/kg/min, but not 1 ng/kg/min, iloprost has a natriuretic effect secondary to inhibition of sodium reabsorption at the ascending limb of the Henle's loop and not related to the renal hemodynamic effect.

Aged↗
PubMed1988

The calcium-channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

1. Recently the calcium-channel blocker, verapamil, has been reported to decrease portal pressure in rats with experimental cirrhosis and in patients with liver cirrhosis. 2. In eight patients with alcoholic cirrhosis the effect of verapamil (5 mg i.v.) on systemic and splanchnic haemodynamics was investigated. 3. Mean arterial pressure, wedged hepatic venous pressure, hepatic venous pressure gradient, and verapamil plasma concentrations were measured before and at 10, 20, 30 min following 5 mg i.v. administration of verapamil. At 30-40 min cardiac output, systemic vascular resistance and hepatic blood flow were also measured. 4. Verapamil plasma concentrations averaged 47.9 +/- 52.0, 36.5 +/- 36.3, 31.3 +/- 33.9 ng ml-1 at 10, 20, 30 min respectively: mean arterial pressure and systemic vascular resistance decreased significantly (-9% and -14% respectively), and cardiac index increased significantly (+8%). Wedged hepatic venous pressure and hepatic venous pressure gradient remained unchanged, variations never exceeding 0.2 kPa. Hepatic blood flow increased significantly by 12%. 5. These results show that i.v. administration of 5 mg verapamil does not decrease portal pressure in alcoholic cirrhosis. This lack of effect is probably the consequence of a balance between decrease in porto-hepatic vascular resistance and increase in splanchnic blood inflow.

Adult↗
PubMed1988

Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach.

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.

Adolescent↗
PubMed1988

Impaired renal water excretion in liver cirrhosis. The role of reduced distal delivery of sodium.

The study was aimed to assess the relationships between distal sodium delivery and renal diluting ability in liver cirrhosis. Renal response to maximal water load was evaluated in 18 cirrhotic patients without ascites, 12 with mild or moderate ascites, and 26 controls. Distal sodium delivery was derived from clearance calculations during the hypotonic diuresis induced by maximal water load. Although ascitic patients showed a greater impairment in free-water excretion, the pattern of the renal response to maximal water load was similar in ascitic and non-ascitic patients; it was characterized by reduced free-water clearance and reduced distal delivery of sodium. Free-water clearance corrected for distal sodium delivery was normal in non-ascitic patients and in the majority (75%) of decompensated cirrhotics, indicating a primary role of an increased proximal sodium resorption in the pathogenesis of the impaired water excretion of these patients. Renal diluting capacity did not correlate with the severity of liver functional impairment, as evaluated by single liver function tests or by Child's criteria.

Adult↗
PubMed1988

Tissue plasminogen activator in cultured human trabecular meshwork cells. Predominance of enzyme over plasminogen activator inhibitor.

Maintenance of patency of the trabecular meshwork, the major outflow channel of the anterior chamber of the eye, is necessary to prevent an excessive rise in intraocular pressure. Obstruction of flow due to clot formation results in severe glaucoma and damage to the optic nerve. We have found that human trabecular meshwork cells which have been passaged in tissue culture synthesize large amounts of tissue plasminogen activator (t-PA), based on functional, immunologic and molecular weight analysis. Trabecular cells express substantially more t-PA activity than vascular endothelium which produces t-PA for clot dissolution in the systemic circulation. Vascular cells produce excess t-PA inhibitor while trabecular cells make comparatively little. Trabecular meshwork cells are the first normal cell type reported in which the balance between t-PA and inhibitor is weighted towards the activator, indicating that fibrinolysis may be more important than clotting in the anterior chamber of the eye.

Cells, Cultured↗
PubMed1988

[Liver metabolism of indocyanine green and aminopyrine in liver cirrhosis: relations with functioning liver cell mass].

Hepatic clearance of indocyanine green, a drug with a high hepatic extraction rate, and breath tests with aminopyrine, a drug with a low hepatic extraction ratio, were calculated in 26 patients with liver cirrhosis. In addition galactose elimination capacity was calculated as an index of functional liver cell mass. All these parameters resulted significantly correlated with each other. These results confirm the view that during liver cirrhosis, metabolism of drugs with high and low hepatic extraction rates can be described according to the intact hepatocyte theory.

Adult↗