Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 µm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 µm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 µm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

Optical spectroscopy of lanthanide ions in ZnO-TeO2 glasses.

Zinc tellurite glasses of compositions 19ZnO-80TeO2-1Ln2O3 with Ln = Eu, Er, Nd and Tm were prepared by melt quenching. The absorption spectra were measured and from the experimental oscillator strengths of the f-->f transitions the Judd-Ofelt parameters ohm(lambda) were obtained. The values of the ohm(lambda) parameters are in the range usually observed for oxide glasses. For Nd3+ and Er3+, luminescence spectra in the near infrared were measured and the stimulated emission cross sections sigma(p) were evaluated for some laser transitions. The high values of sigma(p), especially for Nd3+, make them possible candidates for optical applications. Fluorescence line narrowing (FLN) spectra of the Eu3+ doped glass were measured at 20 K, and the energies of the Stark components of the 7F1 and 7F2 states were obtained. A crystal field analysis was carried out assuming a C2v site symmetry. The behaviour of the crystal field ratios B22/B20 and B44/B40 agrees reasonably well with the values calculated using the geometric model proposed by Brecher and Riseberg. The crystal field strength at the Eu3+ sites appears to be very low compared to other oxide glasses.

The effect of metoclopramide and haloperidol on plasma renin activity and aldosterone levels in rats.

To gain further information on dopaminergic inhibition of renin release and aldosterone secretion, we studied the effect of 0.1, 1.0, or 5.0 mg metoclopramide or haloperidol/kg body weight i.p. on plasma renin activity (PRA) and aldosterone concentration in serum, and of furosemide pretreatment or dietary sodium restriction (14 days) on PRA and aldosterone responses to 1.0 and 5.0 mg haloperidol/kg b.wt. i.p. in groups of eight male Sprague-Dawley rats. Aldosterone levels in serum were increased very similarly by 0.1 and 1.0 mg metoclopramide and haloperidol/kg. Whereas PRA and aldosterone were unaffected by 5.0 mg metoclopramide/kg, both were maximally stimulated by 5.0 mg haloperidol/kg. Furosemide pretreatment increased PRA and aldosterone concentration and blunted the aldosterone response to haloperidol. PRA response to 5.0 mg haloperidol/kg was not changed. After sodium restriction, aldosterone concentration as inappropriately high and did not respond to 1.0 mg haloperidol/kg. However, PRA and aldosterone response to 5.0 mg haloperidol/kg was magnified. Our study confirms both dopaminergic inhibition of PRA and stimulation of aldosterone secretion by dopamine antagonists in rats. A feedback regulatory mechanism becomes conceivable which comprises aldosterone secretion, sodium turnover, volume homeostasis, and dopaminergic activity.

Prevalence of GB virus C/hepatitis G virus RNA and anti-E2 glycoprotein antibodies in homosexual men with HIV coinfection.

BACKGROUND: The objective of this cross-sectional, nonrandomized, prospective study was to generate data on the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) in a cohort of HIV-infected homosexuals from Munich. PATIENTS: A total of 71 HIV-infected homosexual men were analyzed for prevalence of GBV-C RNA and antibodies to the E2 envelope glycoprotein (E2Ab). 475 healthy volunteer blood donors in southern Bavaria served as a control group. RESULTS: The prevalence of GBV-C RNA was 27% (control group: 2.3%) and the prevalence of E2Ab was 35% (control group: 6%). The total prevalence for present and past infection was 62%. The differences between the HIV-infected patients and the control group were significant (p < 0.0001). GBV-C RNA and E2Ab were not detected simultaneously in any serum sample. The E2Ab positive patients were older than the GBV-C RNA positives (mean 46 years versus 39 years, p = 0.0350). The GBV-C RNA and E2Ab negative patients were older than the GBV-C RNA positives (mean 47 years versus 39 years, p = 0.0236). The E2Ab positive patients had suffered sexually transmitted diseases more frequently than the patients negative for markers of GBV-C infection (p = 0.0308). E2Ab positive patients also had higher mean levels of alanine aminotransferase compared to patients without evidence of GBV-C infection (p = 0.0164). 59.4% of all individuals were anti-HBc IgG positive. CONCLUSION: The data can be interpreted as indirect evidence for sexual transmission of GBV-C.

Carbohydrate-deficient transferrin is not a useful marker for the detection of chronic alcohol abuse.

BACKGROUND: The role of carbohydrate-deficient transferrin (CDT) as a reliable marker for the detection of chronic alcohol abuse has been discussed controversially. METHODS: Therefore, we investigated CDT in the sera from 405 subjects with different alcohol intake. Besides healthy control subjects (n = 42), inpatients and outpatients in a department of gastroenterology (n = 325) and patients admitted to a department of otorhinolaryngology (n = 38) were studied. A total of 213 patients suffered from various forms of liver diseases, and 89 patients had liver transplantation. CDT values were determined by a double-antibody radioimmunoassay. RESULTS: In the 241 alcohol-abstinent subjects, CDT levels ranged from 3 to 90 units L-1 (median = 12); the 92 moderate drinkers (20-60 g of alcohol per day) showed values from 3 to 40 units L-1 (median = 12), and the 72 subjects with chronic alcohol abuse (> 60 g per day) revealed CDT levels from 3 to 100 units L-1 (median = 16). The diagnostic specificity for alcohol abuse was 86.8% for men (sensitivity 36.9%) and 95% for women (sensitivity 0%). CONCLUSION: Our data indicate that measurement of CDT does not reach clinical use in the detection of chronic alcohol abuse in an unselected population because of its insufficient specificity and sensitivity.

Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection.

Cytokines that are secreted as a response to viral antigen not only have direct antiviral properties but also crucially influence immune reactions determining the outcome of infection. As an advantageous alternative to the study of cytokines present in the supernatants of antigen-specific T cell clones and lines, we have used ELISPOT assays to determine the number of interferon-gamma (IFN-gamma)- and IL4-producing cells generated by peripheral blood mononuclear cells from patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB) infection in response to HBcAg in a short-term culture (48 h). In response to HBcAg IFN-gamma was predominantly produced. In contrast to the results obtained in acute hepatitis B, the typical lymphokine pattern in CHB was characterized by a weak or absent antigen-specific IFN-gamma production. A predominance of IL-4-producing cells was not observed in either AHB or CHB. A significant number of IFN-gamma-producing cells was usually detectable during phases of viral elimination and the quality of the lymphokine response seemed to be epitope independent. Comparison of the results obtained in proliferation assays and ELISPOT assays clearly shows that lymphokine production upon stimulation with viral protein is totally independent of T cell proliferation and more sensitively reflects antiviral reactivity.