Attenuation of acetaminophen hepatitis by prostaglandin E2. A histopathological study.

Acute acetaminophen hepatitis was produced in three groups of five rats given 1600 mg/kg by gavage. The protective effect of 16,16-dimethyl prostaglandin E2, 200 micrograms/kg administered subcutaneously 30 min later, was compared to the protective effect of N-acetylcysteine 1 g/kg similarly administered. All animals were killed at 24 hr, and liver tissues were compared histologically to the damage found in acetaminophen-treated controls and untreated anatomic controls. Serum transaminase values at 24 hr exceeded 1000 units in the acetaminophen control group, averaged 658 units in the acetylcysteine treated group, and were near normal (75 units) in the prostaglandin treated group (P < 0.02). Liver samples (1 cm3) were removed terminally at 24 hr. Liver damage was assessed without reference to precedent history. Histopathologically, damage was most severe in the acetaminophen control group, mainly in pericentral lobular zones. The prostaglandin-treated group showed considerably less damage, which was confined to the hepatic vein area. The acetylcysteine-treated group showed an intermediate degree of damage. We conclude that dmPGE2, given 30 min after ingestion of acetaminophen was found to be more effective in limiting liver damage than NAC in this rat model.

Prediction of Helicobacter pylori in gastric specimens by inflammatory and morphological histological evaluation.

Statistical correlations and predictive values were calculated for 330 gastrointestinal biopsies and tissues, of which 248 were from the stomach from 115 patients in this retrospective study, which graded 10 inflammatory and 14 morphological mucosal and submucosal abnormalities and compared them with the presence of Helicobacter pylori. Analysis revealed that 78 (31.5%) of the 248 stomach biopsies and tissues showed H. pylori, and 21 (8.5%) had non-Helicobacter-like bacteria, such as rods and cocci. Inflammatory components had high correlations, with specimens containing polymorphonuclear leukocytes (PMNs) showing high specificities and predictive values for a positive test, whereas the chronic inflammatory components had high sensitivities and predictive values for a negative test. Positive morphological correlations existed for mucus depletion, degeneration, regeneration, and ulceration, but intestinal metaplasia and adenocarcinoma had negative correlations. The antrum was most commonly infected, suggesting that intact healthy antral morphology and the neutral mucin in the surface epithelial cells represents the optimal environment for infection. Also, 8.5% of the gastric biopsies and tissues showed non-Helicobacter bacteria associated with inflammation, thus raising the question of colonization versus pathogenesis.

Clinical experience with cytomegalovirus isolation using conventional cell cultures and early antigen detection in centrifugation-enhanced shell vial cultures.

A total of 1,915 clinical samples was inoculated by low-speed centrifugation into shell vials (Bartels Immunodiagnostics, Bellvue, Wash.) containing cover slip monolayers of MRC-5 fibroblasts. At 1 and 2 days postinoculation, one cover slip was stained by an indirect immunofluorescence technique using a monoclonal antibody (Biotech Research Laboratories for Dupont, Billerica, Mass.) to cytomegalovirus (CMV) early antigen (EA). Clinical samples were also inoculated into three MRC-5 or MRHF cell cultures which were observed for 30 days for the appearance of a cytopathic effect (CPE). Of 157 CMV-positive samples, 92 (59%) were identified by centrifugation-enhanced EA (CE-EA) and 131 (83%) produced a CPE. CE-EA was less sensitive than CPE for all types of samples, although 17% of CMV-positive samples were detected by CE-EA alone. Evaluation of the CMV status of patients with CE-EA-positive-CPE-negative samples indicated that these samples likely represented true CMV-positive results. The average elapsed time between culture inoculation and identification of CMV decreased as follows when both CE-EA and CPE, rather than CPE alone, were used: urines, 15 to 7 days; buffy coats, 18 to 9 days; lung samples, 13 to 8 days; throat samples, 18 to 7 days. Although CE-EA was less sensitive than 30-day cell culture, both CE-EA and CPE were identified as valuable in CMV detection, and neither could be discontinued without a decrease in the CMV isolation rate or an increase in the turnaround time.

The role of metabolic energy in the lethal action of basic proteins on Candida albicans.

Comparative studies were made on the destructive effects of certain basic proteins on a strain of Candida albicans and two of its respiration-impaired mutants. Both by direct plate counts of survivors and by quantitative ultraviolet spectrophotometric analyses of released cellular constituents, the respiration-impaired mutants were less vulnerable to the destructive actions of the basic proteins than were ordinary wild-type cells. The lethal incidence and the ultraviolet absorbing cellular substances released from wild-type cells by the proteins were markedly decreased in the presence of the oxidative phosphorylation uncouplers sodium azide, 2,4-dinitrophenol, and salicylanide and approximately equal to the effects produced on an oxidative phosphorylation mutant not treated with the uncouplers. The heightened resistance of a culture through mutational or chemical impairment of its respiratory system suggests a role of metabolic energy in the destructive action of various basic proteins on yeast cells.