Randomised clinical trial: the efficacy of treatment, guided by a shorter duration of response, using peginterferon alfa-2a plus ribavirin for hepatitis C virus other than genotypes 2 or 3.

BACKGROUND: The efficacy of individualised antiviral treatment durations for chronic hepatitis C remains unclear. AIM: To evaluate treatment durations based on virological responses at week 4, 8 and 12 of peginterferon alfa-2a plus ribavirin therapy. METHODS: Previously untreated patients with HCV genotypes, other than 2 or 3, initiated therapy with peginterferon alfa-2a 180 µg/week plus ribavirin 1000-1400 mg/day. HCV-RNA-negative patients at week 4 rapid virological response (RVR) were randomised to 24 or 48 weeks of treatment; those negative at week 8 were randomised to 36 or 48 weeks; and those who were negative or had a ≥ 2-log drop at week 12 were randomised to 72 or 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV-RNA after 24 weeks of follow-up. RESULTS: The study was terminated prematurely due to lagging enrollment. Of 236 patients who started treatment, 195 were randomised at week 4 (n = 50), 8 (n = 61) or 12 (n = 84). Ninety-five per cent of patients had genotype 1. SVR rates were not significantly different between patients randomised to 24 (84%) or 48 weeks (84%) at week 4, to 36 (73%) or 48 weeks (74%) at week 8, or to 48 (49%) or 72 weeks (40%) at week 12. CONCLUSIONS: In this predominantly genotype 1 cohort, shortening therapy to 24 weeks in patients with a week-4 response and 36 weeks in those with a week-8 response produced SVR rates that were similar to a 48-week regimen. Lengthening treatment to 72 weeks did not improve SVR rates. Genotype 1 patients with RVR can be treated for 24 weeks.

On the suitability of fiberglass reinforced polyester as building material for mesocosms.

Gel- and topcoat surface layers on fiberglass [glass-reinforced plastic (GRP)] made of unsaturated resin based on isophthalic acid polyester and neopentyl glycol (ISO-NPG) were tested for leaching, ecotoxicity of water eluates, and abrasion by river sediments at a current speed of 0.5 m * s-1. Leaching from topcoat tempered at low temperature was significant, whereas it was negligible from highly tempered gelcoat. Water eluates from both gel-and topcoat were nontoxic in routinely employed biotests (bacteria, algae, daphnids). No abrasion by river sediments was detectable. Based on these results, GRP with gelcoat made of ISO-NPG is considered a suitable building material for mesocosms.

Sublethal effects of prolonged exposure to disulfoton in rainbow trout (Oncorhynchus mykiss): cytological alterations in the liver by a potent acetylcholine esterase inhibitor.

Mature male rainbow trout (Oncorhynchus mykiss) were exposed for 28 days to 0, 1, 5, and 20 micrograms/liter disulfoton, i.e., to concentrations well below any macroscopically visible effect due to the primary acute toxic mechanism of acetylcholine esterase inhibition. In an attempt to reveal sublethal injury of disulfoton in rainbow trout, ultrastructural and stereological parameters were recorded in the liver as the central organ of xenobiotic metabolism in fish. Quantitative methods were definitely not able to replace qualitative techniques because, except for mitochondria, peroxisomes, and hepatocellular lipid inclusions, stereological analysis revealed only insignificant variations of hepatocellular components, whereas hepatocytes displayed a complex pattern of numerous delicate qualitative alterations. Effects were most evident within cisternae of the rough endoplasmic reticulum (RER), thus suggesting modifications of protein metabolism. Structural alterations included degenerative effects such as dilation and vesiculation of RER cisternae, formation of concentric RER arrays and augmentation of smooth endoplasmic reticulum, dilation of Golgi cisternae, and the development of cytoplasmic myelinated bodies as well as stacks of membranous material within mitochondria. Structural integrity and augmentation of peroxisomes and mitochondria as well as increased activity of the Golgi system were indicative of adaptive/compensative reactions following disulfoton treatment. In fact, adaptive effects seemed more pronounced than degenerative phenomena resulting in only minor disturbances in hepatocyte structure following disulfoton exposure. Because most effects had to be classified as unspecific responses to environmental or xenobiotic stressors, no distinct mode of sublethal action can be suggested for disulfoton.

Long-term results of total abdominal colectomy for chronic idiopathic constipation. Value of preoperative assessment.

PURPOSE: A small proportion of patients with chronic idiopathic constipation are incapacitated by the problem. We have assessed 1) the efficacy of total abdominal colectomy, and 2) the predictive value of preoperative testing. METHODS: Preoperative testing included complete history and physical examination, appropriate biochemical and hematologic assessment, psychiatric interview, colon transit studies using ingested radiopaque pellets, anorectal manometry, colonic intraluminal manometry, and measurement of colon diameters and length on barium enema examination. All patients were followed for 65 +/- 40 months. RESULTS: Seventy-one percent had excellent or very good results. Twenty-one percent were satisfied, had improved the quality of their life, and felt the operation was worthwhile despite frequent residual or new symptoms. Two (8 percent) patients did not improve. Patients with a psychiatric history or physiologic evidence of an afferent nerve defect had poorer results (P < 0.05). CONCLUSIONS: Total abdominal colectomy with ileorectal anastomosis is highly effective in alleviating symptoms in patients with chronic idiopathic constipation.