Aetiology and presentation of HIV/AIDS-associated pulmonary infections in patients presenting for bronchoscopy at a referral hospital in northern Tanzania.

OBJECTIVES: To determine the aetiological agents of pulmonary infections in HIV-infected Tanzanians and to correlate the causative agents with clinical, radiographic features, and mortality. DESIGN: A prospective study. SETTING: Kilimanjaro Christian Medical Centre (KCMC), Tanzania. SUBJECTS: Bronchoalveolar lavage fluid (BAL) were obtained from 120 HIV infected patients with pulmonary infections. BAL for causative agents was analysed and correlated with clinical and radiographic features, and one-month outcome. RESULTS: Causative agents were identified in 71 (59.2%) patients and in 16 of these patients, multiple agents were found. Common bacteria were identified in 35 (29.2%) patients, Mycobacterium tuberculosis in 28 (23.3%), Human Herpes Virus 8 (HHV8) in 12 (10%), Pneumocystis jiroveci in nine (7.5%) and fungi in five (4.2%) patients. Median CD4 T cell count of the patients with identified causes was 47 cells/microl (IQR 14-91) and in the 49 patients with undetermined aetiology was 100 cells/ microl (IQR 36-188; p = 0.01). Micronodular chest radiographic lesions were associated with presence of M. tuberculosis (p = 0.002). The one-month mortality was 20 (16.7%). The highest mortality was associated with HHV8 (41.7%) and M. tuberculosis (32.1%). Mortality in patients with undetermined aetiology was 11.3%. No death occurred in patients with PCP. CONCLUSION: In this population of severely immunosuppressed HIV-infected patients with pulmonary infection a variety of causative agents was identified. Micronodular radiographic lesions were indicative of TB. High mortality was associated with M. tuberculosis or HHV8. No death occurred in patients with P. jiroveci infection.

Nonstationary disposition of valproic acid during prolonged intravenous infusion: contributions of unbound clearance and protein binding.

Circadian variations in disposition have been observed for a variety of agents, including anticonvulsants. Valproic acid (VPA), an anticonvulsant used to control generalized and partial seizures, has exhibited diurnal oscillations in steady-state concentrations during long-term administration to humans and non-human primates. The present study was conducted to assess potential diurnal changes in the disposition of VPA during prolonged i.v. infusion in rats. Animals, maintained on a strict 12-h per day light cycle, were equipped with venous cannulae and an arterial microdialysis probe. VPA was administered as a 50-mg/kg loading dose followed by a 42 mg/kg/h infusion for 70 h. Blood and microdialysate samples were obtained at timed intervals after establishment of steady-state throughout two complete light/dark cycles; and total (serum) and unbound (microdialysate) VPA was determined by gas chromatography. Modest oscillations (6-7 h period) in total and unbound VPA were observed; clearance and binding parameters were not different between light and dark periods. However, unbound clearance increased, and unbound fraction decreased, with time over the course of the infusion. These results suggest that time-dependent changes in VPA disposition occur in rats, although oscillations in steady-state concentrations do not appear to be diurnal in nature.

Angiotensin-converting enzyme inhibitors and AT1-receptor antagonist restore nitric oxide synthase (NOS) activity and neuronal NOS expression in the adrenal glands of spontaneously hypertensive rats.

During development of hypertension in spontaneously hypertensive (SHR) rats, the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3-4, 7-8 and 12-13 weeks after birth. Basal NOS activity was measured by the ability of homogenate to convert [3H]-L-arginine to [3H]-L-citrulline. At all ages, SHR rats exhibited 50-60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12-13 weeks) were treated chronically with the angiotensin I-converting enzyme inhibitors (ACE-I) captopril or enalapril, or the AT1-receptor antagonist losartan (2 x 25, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activity and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was significantly increased in treated SHR rats when compared to control rats. The isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribute to the onset and maintenance of hypertension. The upregulation of nNOS protein in the adrenal glands may be one of the mechanisms by which ACE inhibitors and AT1-receptor antagonists by restoring the NO synthesis, mediate their antihypertensive effects.

Lactose malabsorption and giardiasis in Basotho school children.

The prevalence of primary, adult-type, lactose malabsorption was assessed by means of the hydrogen breath test after intake of 360 ml of full cream milk (approximately 18 g lactose) in 96 randomly selected Basotho school children, aged 5-15 years. Of 86 children who did not have diarrhoea in the previous week 82 (85%) were lactose malabsorbers, while 4 (5%) could not be classified because of undetectable hydrogen excretion. Milk intolerance presenting as diarrhoea was significantly (p less than 0.01) more common in children who associated previous abdominal complaints with milk intake and/or did not like milk. A negative hydrogen breath test was significantly (p less than 0.05) more often observed in children who had diarrhoea in the previous week. Giardia was present in 18 (19%) of 93 children. The incidence of giardiasis did not correlate with the presence of lactose malabsorption in children without diarrhoea in the previous week. However, milk intolerance presenting as diarrhoea was significantly (p less than 0.05) more common in children with giardiasis. The findings support the use of physiological quantities of milk in Basotho school children.