Extrapulmonary Pneumocystis carinii infections.

A case of disseminated infection with Pneumocystis carinii is presented, and the English-language literature is reviewed for cases of documented extrapulmonary infection with this organism. In this case--with P. carinii diffusely replacing the bone marrow and causing hepatic, adrenal, and glomerular tuft necrosis--the clinical illness and multiple-organ dysfunction attributed to disseminated P. carinii were more severe than had previously been described. Because the rate of extrapulmonary P. carinii infection found at autopsy in patients with AIDS is at least 2.5% at our institution, we caution against the routine use of aerosol rather than parenteral pentamidine for treatment of P. carinii pneumonia until additional data are available.

AIDS-related lymphoid neoplasia. The Memorial Hospital experience.

The clinical features and laboratory results of 63 patients with or at risk for AIDS with lymphoid neoplasias seen from November 1980 through November 1986 are reviewed. Forty-three had systemic non-Hodgkin's lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkin's disease (HD), and one had plasmacytoma evolving to myeloma. Those with systemic NHL included 40 (93%) with intermediate or high-grade histologies, 35 (81%) with advanced stage (III, IV), and 28 (65%) with extranodal disease at presentation (predominantly marrow and meninges). Overall survival was short (median, 10.5 months from diagnosis) with the majority of deaths attributable to AIDS-related opportunistic infections (OI). However, 17 patients with diffuse NHL achieved a complete clinical remission, and nine now have been disease-free for more than 1 year (median follow-up, 28 months; range, 12 to 73 months). Early stage and lack of systemic symptoms were features associated with prolonged disease-free survival. Primary brain NHL was a uniformly lethal manifestation of AIDS, being diagnosed at postmortem in seven of nine severely immunosuppressed homosexual men. As with NHL, a propensity towards advanced disease and extranodal involvement was also observed in HD, suggesting that the atypical clinical behavior of HD may be an additional epiphenomenon of AIDS. This experience tends to argue for the use of intensive therapy in at least some patients with AIDS-related systemic NHL since it has resulted in a proportion of long-term disease-free survivors.

Effect of vitamin A deficiency on hepatic microsomal and colon mucosal mixed function oxidase. IV--Influence on aflatoxin B1 metabolism, ethylmorphine and epoxide hydrase activity.

Male, weanling rats, divided into two groups were maintained for 45 days on a corn-based diet containing 5 mg vitamin A palmitate per kg diet (Group 1, normal animals) and without the vitamin (Group 2, dificient animals). Fifteen hours after the last feeding, the animals were decapitated and liver microsomes and colon mucosal epithelial homogenates were prepared and used to investigate the relative activities of the mixed function oxidase (MFO) and epoxide hydrase (EH) enzyme systems. The sequential metabolism of aflatoxin B1 (AFB1) and its epoxide AFBepox) product, respectively, were also estimated by measuring apparent maximal velocities (Vmax) and Michaelis constants (Km) for ethylmorphine (EM) N-demethylase and styrene oxide hydratase. The Vmax data indicated that MFO activity in the liver and colon was not rate-limiting in the two groups of animals but the reverse were observed with calculated reaction rates at concentrations above (0,03 mM) for EM N-demethylase only. In both organs, styrene oxide hydratase depict calculated reaction rates which are not rate-limiting for all the concentration range (0,001 to 3,00 mM). If these reaction rates are applied to AFB1 metabolism, it may be concluded that MFO and not epoxide hydrase (EH) activity is a critical agent under vitamin A deficiency in AFB1 toxicity and/or carcinogenesis. Measurements of AFT1 metabolism both in terms of substrate disappearance and product formation do not confirm this observation except for the production of AFR0 and compounds of unknown structure at the origin which may embody the critical factor(s) that promotes colon carcinogenesis under vitamin A deficiency.