Alcohol and liver injury: dose-related or permissive effect?

Studies addressing the risk of development of cirrhosis of the liver in relation to alcohol consumption have been based on comparisons at the aggregate population level and, at the individual level, on case-control studies and cohort studies, and on retrospective and prospective assessment of alcohol consumption. The ideal, but unfeasible, study design for estimation of the risk function is a prospective monitoring of alcohol consumption and recording of the rate of development of cirrhosis per unit of time. Two recent studies, approaching this design, suggested that above a rather low, but not precisely determined, level of alcohol consumption the risk of development of cirrhosis is not further influenced by the amount of alcohol consumed. A critical analysis of previous studies suggests that this risk function is actually compatible with their findings. The contention that alcohol abuse has a permissive rather than a dose-dependent role in the development of alcoholic liver injury encourages research into the additional factors that must act before the liver injury occurs.     

Anomalies in perifascicular muscle fibers as an differential-diagnostic criterion. II. Perifascicular hypertrophies in primary myopathies

In order to compare a group of patients with a polymyositis (PM) to a control group, 28 cases of primary myopathies were examined by morphometry with regard to differences between central and peripheral muscle fibers in muscle fascicles. A significant difference in favor of peripheral muscle fibers, i.e., a peripheral hypertrophy was found in 22 out 28 cases (significantly in 14 cases). Therefore, histometry is a valuable additional method for discrimination between PM and primary myopathies.     

Pharmacokinetics of a new macrolide, roxithromycin, in infants and children

The pharmacokinetics of roxithromycin was investigated after oral administration of 2.5 mg/kg doses given 12 hours apart during 6 days in infants and children. These 18 subjects suffering from a respiratory tract infection were divided into three age groups: group I less than 18 months, group II less than 5 years, group III less than 13 years. At day 6, the elimination plasma half-life had an average value (mean +/- SD) of 19.8 +/- 9.7 h (group I), 21.0 +/- 9.4 h (group II) and 20.8 +/- 6.9 h (group III), respectively. The maximum concentration of roxithromycin (Cmax) was attained between 1 and 2 hours after dosing with mean values of 10.1 +/- 3.0 mg/l (group I), 8.7 +/- 4.9 mg/l (group II), 8.8 +/- 7.0 mg/l (group III). All the calculated pharmacokinetic parameters did not significantly differ from one group to another. The kinetics of roxithromycin in infants and children seemed to be age independent and showed no accumulation after repeated doses. During 12 hours, the plasma concentrations were above MIC of microorganisms generally present in respiratory tract infections. Two daily doses of 2.5 mg/kg of roxithromycin 12 hours apart may be proposed in infants and children.     

Effect of the calcium antagonist nimodipine on hemodynamics, gas exchange and endocrine parameters in opiate anesthesia

During opiate anesthesia (standardized dosage of fentanyl) for operation of cerebral aneurysms after subarachnoid hemorrhage, different hemodynamic, respiratory, metabolic, and endocrine parameters were determined before (1 in Fig. 1-4), after (6), and during consecutive stages of induced hypotension (systolic blood pressure 100 mmHg (2), 90 mmHg (3), 80 mmHg (4, 5) during an interval of 20 min), comparing two groups with different vasodilating drugs. In the first group (nimo/NNP in Figs. 2-4) a constant infusion of nimodipine was applied (1.2 micrograms/kg b.w. X min-1), while sodium nitroprusside (NNP) was added in small amounts as necessary to achieve the respective values of systolic blood pressure. In the second group (NNP in Figs. 2-4) induced hypotension was done with NNP alone (maximal dosage: 8 micrograms/kg X min-1). Each group consisted of 11 patients. Additional nimodipine (in the first group), a calcium antagonist commonly recommended for preventing vasospasm and consequent neurologic deficits after subarachnoid hemorrhage, not only reduced the need for NNP, a vasodilating drug with potential toxicity, by 70%-80% as compared to the second group (Table 1). In addition, the cardiovascular situation was more stable in patients with nimodipine infusion: rapid variations of blood pressure and heart rate as well as tachyphylaxis and rebound, typical for NNP-induced hypotension, were avoided. Nevertheless, comparing the hemodynamic data at fixed stages of hypotension, there were only minor differences between both groups (Fig. 2). Reduction of blood pressure was due to a decrease in vascular resistance and was accompanied by an increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)