Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers.

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors.

Forty-seven consecutive patients were prospectively evaluated to study the incidence of hepatic encephalopathy as well as modifications in the PSE index after TIPS. Various clinical, laboratory, and angiographic parameters were also recorded to identify risk factors for the development of post-TIPS hepatic encephalopathy (HE). Mean follow-up was 17 +/- 7 months. During follow-up, six patients died and one underwent transplantation. All other patients were followed for at least a year. Fifteen patients (32%) experienced 20 acute episodes of precipitated HE (hospitalization was necessary in 10 instances), and five patients (11%) presented a continuous alteration in mental status with frequent spontaneous exacerbation during follow-up. Both precipitated and spontaneous HE occurred more frequently during the first three months of follow-up. Moreover the PSE index was significantly worse than basal values one month after TIPS, thereafter returning to near basal values. HE was successfully treated in all patients but one who required a reduction in the stent/shunt diameter. Increasing age (>65 years) and low portacaval gradient (<10 mm Hg) were predictors of HE after TIPS. A gradual dilation of the stent/shunt should be performed to obtain a portacaval gradient >10 mm Hg to avoid an unacceptable rate of HE after TIPS.

Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.

Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.

Increased energy expenditure in cirrhotic patients with hepatocellular carcinoma.

Basal energy expenditure was measured by indirect calorimetry in 12 cirrhotic patients with hepatocellular carcinoma. Values were compared to those observed in 12 cirrhotic patients without hepatocellular carcinoma but with similar nutrition status. Energy expenditure was also predicted in each patient by the Harris-Benedict equation. Basal energy expenditure, whether expressed as kilocalorie per day or corrected for kilogram body weight or for kilogram fat-free mass, was found increased in cirrhotic patients with hepatocellular carcinoma. These patients expended an average of 250 kcal/day more than was expected given their body size. The highest values were observed in the patients who experienced a recent significant weight loss. Our study demonstrates that the presence of hepatocellular carcinoma on liver cirrhosis increases the metabolic rate of patients. This factor could contribute to progressive malnutrition in patients with hepatocellular carcinoma and should be taken into consideration when these patients are given nutritional support.

Zinc and other trace elements in liver cirrhosis.

Alterations in trace element concentrations may be observed in patients with chronic liver disease. Notably, selenium and zinc levels are reduced both in serum and in liver tissue of cirrhotic patients. Low selenium levels have been involved in the pathogenesis of liver damage as this element is important in controlling the levels of toxic oxygen radicals in the cells. Zinc deficiency has been involved in the pathogenesis of a number of clinical findings in chronic liver disease. These include the possible role of zinc deficiency in the pathogenesis of hepatic encephalopathy, by inducing alterations in urea metabolism. In CC14 cirrhotic rats oral zinc supplementation reduces ammonia levels and increases OCT activity in the liver. Oral zinc supplementation has been also proposed in the treatment of cirrhotic patients with chronic hepatic encephalopathy, the results however are not yet conclusive.

Pulmonary hypertension, hypoxemia, and death in a patient with scleroderma.

Pulmonary hypertension in systemic sclerosis is usually secondary to pulmonary fibrosis or vascular changes. We have described a patient with systemic sclerosis who had pulmonary hypertension as a result of unsuspected thromboembolic disease.