Adverse reactions to cotrimoxazole in HIV-infected patients: predictive factors and subsequent HIV disease progression.

The relationship between the onset of adverse events to cotrimoxazole in HIV-infected patients and the subsequent development of toxoplasmosis, other AIDS-defining events and survival was studied in 592 French patients who first received cotrimoxazole during the Delta trial. Low CD4+ cell count at cotrimoxazole introduction was the only factor associated with the onset of adverse reactions. The occurrence of toxoplasmosis and first AIDS-defining events were significantly and independently linked to a low CD4+ cell count at cotrimoxazole introduction (p < 0.0001) and to previous cotrimoxazole withdrawal for adverse events (p = 0.004 and p < 0.0001, respectively), but not to previous cotrimoxazole withdrawal for reasons other than adverse events, as compared to patients who did not discontinue taking cotrimoxazole during this survey. The survival rate was significantly shorter among both patients who stopped taking cotrimoxazole for adverse events and for other reasons (p = 0.03 and p = 0.0001, respectively), as compared to patients who continued to take cotrimoxazole.

Isoproterenol, endotoxin shock, and the generalized shwartzman reaction.

Adult hybrid albino rabbits were divided into seven groups. Three groups were given two respective intravenous doses of 10 mug, 25 mug, or 100 mug of endotoxin at an interval of 24 hours. Three other groups were given endotoxin as above, and, in addition, were given 0.5 mg of isoproterenol hydrochloride (Isuprel) by subcutaneous injections at eight-hour intervals beginning at the time of the first injection of endotoxin. A single group was given isoproterenol only. The animals were observed for clinical signs of shock beginning at the time of the first injection of endotoxin. The mortality during the course of the experiment was noted. At the time of death, the animals were studied grossly, and sections were taken for light microscopy. Results showed no meaningful enhancement of endotoxin toxicity as manifested by shock, generalized Shwartzman reaction, or mortality.

PIP: This report concerns the effects of a pure beta-adrenergic compound, isoproteronal hydrochloride, on endotoxin toxicity. 2 experimental models were used: endotoxin shock and the generalized Schwartzman reaction. 70 albino rabbits were divided into 7 groups of 10 animals and were treated as follows: Group 1, endotoxin (100 mcg) and saline; Group 2, endotoxin (100 mcg) and isoproterenol (.5 mg); Group 3, endotoxin (25 mcg) and saline; Group 4, endotoxin (25 mcg) and isoproterenol (.5mg); Group 5, endotoxin (10 mcg) and saline; Group 6, endotoxin (10 mcg) and isoproterenol (.5 mg); and Group 7, saline and isoproterenol (.5 mg). Isoproterenol was administered subcutaneously at 8-hour intervals beginning at the time of the 1st injection of endotoxin. The animals were observed for clinical signs of shock and mortality was noted. Isoproterenol treatment did not alter the mortality of endotoxin shock. At the time of death, the animals were studied grossly, and sections were taken for light microscopy. An increase in the incidence of gross renal cortical necrosis was noted only at the 100-mcg endotoxin level, where 40% of animals exhibited renal cortical necrosis compared with 10% of controls. There were no gross renal lesions in animals given isoproterenol alone. Injections of .5 mg of isoproterenol at 8-hour intervals did not alter the total number of microscopical lesions at the 3 dosage levels of endotoxin. No microscopical renal lesions were observed in those given only isoproterenol.