Perinatal pharmacokinetics of zidovudine.
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Biomedical subjects
Publications and source records attributed to A Waldner.
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UNLABELLED: Since anatomopathological lesions of the adrenal gland have been frequently observed at autopsy in AIDS, we investigated the glucocorticoid function in 63 patients (51 men, 12 women) infected by the human immunodeficiency virus (HIV) in order to determine the incidence and the nature of any adrenocortical abnormalities at various stages of HIV infection. The patients were classified according to the Centers for Disease Control (CDC) recommendations into group II (asymptomatic; N = 13), group III (lymphadenopathy; N = 27) and group IV (clinical manifestations; N = 23). Plasma ACTH and cortisol before and after an exogenous ACTH stimulation test were measured in patients as in 30 age-matched controls. Plasma renin activity and plasma aldosterone before and after ACTH stimulation were also measured in 31 patients (group II: 12; group III: 10; group IV: 9). Compared with controls patients from group II-III had higher levels of ACTH (39.11 +/- 17.01 vs 29.73 +/- 8.53 ng/l; p = 0.003) and basal cortisol (232 +/- 91.2 vs 184.3 +/- 30.9 micrograms/l; p = 0.03). No significant differences were noted between group IV patients and controls as to ACTH and basal and stimulated cortisol levels. Among the 63 patients, only one from group IV had a blunted cortisol response after ACTH stimulation test. Plasma renin activity, and basal and stimulated aldosterone levels in the 3 groups of patients were not different from control values. IN CONCLUSION: 1. Adrenal insufficiency does not seem very frequent in group IV patients and is likely to be a late complication in AIDS. 2. The increased ACTH and basal cortisol levels found in group II and group III patients argue for an early dysregulation of the adrenocortical axis in HIV infection. The exact physiopathological mechanism is not yet known, but an enhanced CRH production by interleukin 1 and/or a direct role of the HIV envelope glycoprotein (gp 120) may explain the high ACTH level in HIV patients.
To assess subclinical involvement of the peripheral nervous system and its relationship to the immunological status of human immunodeficiency virus (HIV)-infected patients, we prospectively studied the peripheral nerve conductions and the subsets of peripheral blood lymphocytes of HIV patients. Fifty-seven patients, aged 20-54 years, 28 homosexuals and 29 heterosexuals, classified as CDC II-III (40 patients) and CDC IV (17 patients) were studied. No neurological symptoms or signs were present on bedside examination or questioning for all of the CDC II-III patients. For each conduction measured (H-reflex, sural and sciatic velocities, sural amplitude), the geometric mean was below normal values (p less than 0.05). Among the 57 HIV-infected patients, 20 (35%) had a significant decrease of at least one electrophysiologic measurement: 10/17 CDC IV patients vs. 10/40 CDC II-III patients (p less than 0.05). Two or more simultaneous abnormalities were more often observed in the CDC IV than in the CDC II-III group (9/10 vs. 4/10) (p less than 0.01). In the CDC II-III group, patients with subclinical neuropathies had higher T-helper and lower T-suppressor cell counts and higher T-helper/T-suppressor ratios than random patients without any neurologic abnormalities (1,057 vs. 657 cells/microliters, p less than 0.05, and 757 vs. 1,304 cells/microliters, p less than 0.01, 1.55 vs. 0.68, p less than 0.01, respectively). We conclude that (a) the peripheral nervous system is precociously and subclinically involved in the HIV disease; (b) the patients with infraclinical neuropathies have a significantly higher T-helper cell count than those without any neurologic involvement. The mechanism and the prognostic value of these two findings remain to be more precisely examined, and further studies are required.
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The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.