Prevalence and clinical characteristics of pulmonary TB among pregnant and post-partum women.

SETTING: Antenatal care (ANC) and postpartum care (PPC) clinic in Manhiça District, Mozambique.OBJECTIVE: To estimate the prevalence of TB among pregnant and post-partum women and describe the clinical characteristics of the disease in a rural area of Southern Mozambique.METHODS: We conducted a cross-sectional TB prevalence study among pregnant and post-partum women recruited from September 2016 to March 2018 at the Manhiça Health Care Center (MHC). We recruited two independent cohorts of women consecutively presenting for routine pregnancy or post-partum follow-up visits.RESULTS: A total of 1,980 women from the ANC clinic and 1,010 from the PPC clinic were enrolled. We found a TB prevalence of 505/100,000 (95% CI: 242-926) among pregnant women and 297/100,000 (95% CI: 61-865) among post-partum women. Among HIV-positive pregnant women, TB prevalence was 1,626/100,000 (95% CI: 782-2,970) and among postpartum HIV-positive women, TB prevalence was 984/100,000 (95% CI: 203-2,848).CONCLUSIONS: The burden of TB was not higher in postpartum women than in pregnant women. Most TB cases were detected in HIV-positive women. TB screening and diagnostic testing among pregnant and postpartum women attending ANC and PPC clinics in Manhiça District is acceptable and feasible.

Plasma porphyrins in the porphyrias.

BACKGROUND: As an aid in the diagnosis and management of porphyria we have developed a method to fractionate and quantify plasma porphyrins and have evaluated its use in various porphyrias. METHODS: We used HPLC with fluorometric detection to measure plasma concentrations of uroporphyrin I and III, heptacarboxyl III, hexacarboxyl III, pentacarboxyl III, and coproporphyrin I and III. We studied 245 healthy subjects, 32 patients with classical porphyria cutanea tarda (PCT), 12 patients with PCT of renal failure, 13 patients with renal failure, 8 patients with pseudoporphyria of renal failure, 3 patients with acute intermittent porphyria, 5 patients with variegate porphyria, 5 patients with hereditary coproporphyria, and 4 patients with erythropoietic protoporphyria. RESULTS: Between-run CVs were 5.4-13%. The recoveries of porphyrins added to plasma were 71-114% except for protoporphyrin, which could not be reliably measured with this technique. Plasma porphyrin patterns clearly identified PCT, and its clinical sensitivity equaled that of urine porphyrin fractionation. The patterns also allowed differentiation of PCT of renal failure from pseudoporphyria of renal failure. CONCLUSIONS: The assay of plasma porphyrins identifies patients with PCT and appears particularly useful for differentiating PCT of renal failure from pseudoporphyria of renal failure.

Biochemical differentiation of the porphyrias.

OBJECTIVES: To differentiate the porphyrias by clinical and biochemical methods. DESIGN AND METHODS: We describe levels of blood, urine, and fecal porphyrins and their precursors in the porphyrias and present an algorithm for their biochemical differentiation. Diagnoses were established using clinical and biochemical data. Porphyrin analyses were performed by high performance liquid chromatography. RESULTS AND CONCLUSIONS: Plasma and urine porphyrin patterns were useful for diagnosis of porphyria cutanea tarda, but not the acute porphyrias. Erythropoietic protoporphyria was confirmed by erythrocyte protoporphyrin assay and erythrocyte fluorescence. Acute intermittent porphyria was diagnosed by increases in urine delta-aminolevulinic acid and porphobilinogen and confirmed by reduced erythrocyte porphobilinogen deaminase activity and normal or near-normal stool porphyrins. Variegate porphyria and hereditary coproporphyria were diagnosed by their characteristic stool porphyrin patterns. This appears to be the most convenient diagnostic approach until molecular abnormalities become more extensively defined and more widely available.

Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection.

BACKGROUND: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease. OBJECTIVE: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease. DESIGN: Parallel study. SETTING: Two hospital outpatient clinics. PARTICIPANTS: 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea. MEASUREMENTS: Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy. INTERVENTION: Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea. CONCLUSIONS: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.

Effects of the antacids in didanosine tablets on dapsone pharmacokinetics.

OBJECTIVE: To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV). DESIGN: Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments. SETTING: Clinical investigation unit of a university hospital. PARTICIPANTS: Six healthy men and six HIV-positive men. MEASUREMENTS: Serial dapsone plasma concentrations were measured when dapsone, 100 mg, was administered alone and with either the third of four doses of didanosine placebo tablets (group 1) or the 27th of 28 doses of active didanosine tablets (group 2). In each study, pharmacokinetic variables were determined using noncompartmental methods and compared by analysis of variance. RESULTS: When dapsone was administered alone, pharmacokinetic variables did not significantly differ from those with dapsone given in either combination (P > 0.10 for all comparisons). CONCLUSIONS: Didanosine, antacids, and other excipients in the currently used didanosine chewable tablets did not significantly affect plasma concentrations of dapsone.

Effect of bismuth subsalicylate on ciprofloxacin bioavailability.

A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had no significant effect on the plasma pharmacokinetics of a single oral dose of 750 mg of ciprofloxacin administered to 12 healthy volunteers (six men and six women). These results suggest that ciprofloxacin bioavailability will not be significantly decreased by single doses of bismuth subsalicylate when the two medications are administered simultaneously.

Effects of alfentanil on the hemodynamic and catecholamine response to tracheal intubation.

A randomized, placebo-controlled study was conducted in 60 ASA Class I, II, and III patients to determine the dose response of alfentanil in moderating the cardiovascular and catecholamine response to tracheal intubation (INT). Patients were randomly allocated into one of four groups to receive either 15 micrograms/kg alfentanil (A15), 30 micrograms/kg alfentanil (A30), 45 micrograms/kg alfentanil (A45), or normal saline (control), given intravenously (i.v.) before induction of anesthesia. One minute after administration of 4.0 mg/kg thiopental and 1.5 mg/kg succinylcholine i.v., tracheal intubation was performed using direct laryngoscopy. In response to INT, increases in heart rate, systolic blood pressure, and systemic vascular resistance occurred in the control group. These changes were significantly more than corresponding changes of heart rate, systolic blood pressure, and systemic vascular resistance in all three alfentanil groups (P < 0.05). In contrast, cardiac index and ejection fraction decreased moderately in every group during the study period, but there were no differences among groups with respect to either cardiac index or ejection fraction at corresponding times following INT. In the control group, epinephrine and norepinephrine serum concentrations increased by 152 +/- 52% and 58 +/- 62%, respectively, following INT (different from A30 and A45, P < 0.05). However, up to a dose of 30 micrograms/kg (A30), a dose-dependent decrease in the maximum percent changes of both epinephrine and norepinephrine occurred in response to INT. A larger dose of alfentanil was no more efficacious as the catecholamine response to tracheal intubation was not significantly different when comparing the A45 and A30 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cations in the didanosine tablet reduce ciprofloxacin bioavailability.

The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone. In the didanosinecation regimen, subjects received two didanosine-placebo tablets every 12 hours for two doses. On day 2, they received two didanosine-placebo tablets immediately followed by a single 750 mg ciprofloxacin tablet. Serial blood samples were collected for 24 hours after administration of each ciprofloxacin dose. The average maximum concentration of ciprofloxacin alone was 3.38 +/- 0.63 (SD) micrograms/ml compared with 0.25 +/- 0.21 (SD) micrograms/ml when ciprofloxacin was administered with the didanosine placebo (p < 0.0001). The mean (+/- SD) area under the plasma drug concentration-time curve from time 0 to the last measurable concentration for ciprofloxacin alone was 15.50 +/- 2.69 micrograms.hr/ml compared with 0.26 +/- 0.21 micrograms.hr/ml when ciprofloxacin was coadministered with the didanosine-placebo (p < 0.0001). The mean time to maximum concentration of ciprofloxacin alone decreased from 1.56 +/- 0.62 to 0.75 +/- 0.38 hours with buffer administration (p = 0.0012). The simultaneous administration of ciprofloxacin and didanosine should be avoided.