Motor performance during and following acute alcohol intoxication in healthy non-alcoholic subjects.

Chronic alcohol abuse has adverse effects on skeletal muscle, and reduced muscle strength is frequently seen in chronic alcoholics. In this study the acute effects of moderate alcohol intoxication on motor performance was evaluated in 19 non-alcoholic healthy subjects (10 women, 9 men). A randomised double-blinded placebo controlled design was applied to subjects receiving alcohol in juice and pure juice at two separate test periods. Isokinetic and isometric muscle strength and endurance were determined before, during, 24 and 48 h after the ingestion of alcohol in juice and juice (placebo). To detect a reduced activation of the central motor pathways superimposed external electrical stimulations during voluntary contractions were applied. Creatine kinase (CK) was measured to detect any alcohol-induced changes in sarcolemmal integrity. No change was seen in isokinetic as well as in isometric muscle performance during or following the alcohol intoxication as compared to the non-alcoholic condition. Also, no central activation failure was observed. No significant difference in CK increment was observed comparing the alcoholic- and non-alcoholic condition. In conclusion, a single episode of moderate alcohol intoxication (1,4 g/l) does not impair motor performance, and no accelerated exercise-induced muscle damage is seen.

Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis.

BACKGROUND AND AIM: Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient's water balance. RESULTS: Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day v 0.021 (0.017); p<0.05). Stratification according to clinical manifestations (Child- Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p<0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho=-0.57, p<0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment. CONCLUSIONS: Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.

Decreased muscle strength and contents of Mg and Na,K-pumps in chronic alcoholics occur independently of liver cirrhosis.

OBJECTIVES: To evaluate the influence of established liver cirrhosis on muscle strength and muscle contents of magnesium (Mg), potassium (K) and sodium, potassium pumps (Na,K-pumps) in chronic alcoholic patients. DESIGN: An open cross-sectional study. SETTING AND SUBJECTS: Forty consecutive chronic alcoholics (18 with cirrhosis and 22 without cirrhosis) admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, or to a collaborating alcoholism treatment centre, and 36 healthy control subjects. MAIN OUTCOME MEASURES: Evaluation of participant's subjective physical ability and measurement of maximum isokinetic muscle strength and muscle mass, as well as measurements of Mg, K and Na,K-pumps in skeletal muscle. RESULTS: Maximum isokinetic muscle strength and muscle mass were equally reduced in patients with and without cirrhosis (P < 0.01 all). In keeping with this, both groups of patients felt equally physically restricted. Muscle Mg was reduced to the same extent in the two groups of patients (by 12 and 9%, P < 0.001, both), whereas the muscle K content was only significantly lower in the cirrhotic patients (10%, P < 0.001). The muscle content of Na,K-pumps was reduced by 14%, (P < 0.01) in the cirrhotic patients and by 8% (P < 0.05) in the noncirrhotic patients. CONCLUSION: Our alcoholic patients complained of physical disability, had reduced skeletal muscle mass, isokinetic muscle strength, content of muscle Mg and content of Na,K-pumps. There was no difference between patients with and without cirrhosis. It appears that it is the heavy alcohol intake, and not the cirrhosis per se, that is responsible for the observed defects.

Muscle strength, Na,K-pumps, magnesium and potassium in patients with alcoholic liver cirrhosis -- relation to spironolactone.

OBJECTIVES: To evaluate the muscle strength in relation to muscle contents of magnesium (Mg), potassium (K) and sodium, potassium (Na,K)-pumps in patients with alcoholic cirrhosis. DESIGN: An open cross-sectional study. SETTING AND SUBJECTS: Fifty-one consecutive patients with liver cirrhosis admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, and 28 age- and sex-matched healthy control subjects. MAIN OUTCOME MEASURES: Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K, and Na,K-pumps. Furthermore, maximum isokinetic knee extension and skeletal muscle mass were evaluated. RESULTS: Muscle mass, muscle strength, muscle Mg and muscle K were substantially reduced in the patients (P < 0.01, all), and fell with increasing severity of the liver disease reflected in the Child-Pugh (C-P) class. Patients treated with spironolactone for 2 weeks or more, had increased muscle strength, muscle Mg and content of Na,K-pumps, compared with the rest of the patients (P < 0.05, all). In a multivariate analysis of the patients, skeletal muscle mass, muscle Mg and daily alcohol consumption (g) were independent predictors of isokinetic muscle strength (P < 0.05, all). CONCLUSIONS: Patients with alcoholic liver cirrhosis showed considerably reduced muscle strength and muscle Mg was an independent predictor of muscle strength. Surprisingly, in the spironolactone treated patients, muscle weakness was less pronounced, possibly because of the action of spironolactone on muscle Mg, K and Na,K-pump content.

Plasma cystatin C as a marker of renal function in patients with liver cirrhosis.

Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial.

Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension.

[Amyl nitrite poisoning]. / Amylnitritforgiftning.

Two cases of amylnitrite poisoning are presented. In both cases, severe methaemoglobinemia developed after ingestion of approximately 10 ml of amylnitrite. When admitted to hospital, both patients were deeply cyanosed, and arterial blood samples were noticed to be chocolate brown. They were intravenously treated with methylene blue. Within one hour the condition of both patients had improved dramatically, and blood gas-samples had normalised. In cases of cyanosis with no obvious genesis, poisoning with amylnitrite should be considered.