Epidemiology of congenital malaria in Nigeria: a multi-centre study

Objective To determine the burden of congenital malaria in newborns in Nigeria. Methods In a prospective multi‐centre study, 1875 consecutive mother–baby pairs were enrolled over a continuous 12‐month period. Blood smears were prepared from mothers, neonates, placental aspirates and cord blood within 4 h of delivery. Outcome variables were patent parasitaemia in the mother, placenta, cord and neonate in addition to maternal and neonatal haematocrit. Results Patent parasitaemia was detected in 95 neonates (5.1%). The occurrence varied between study centres, but was found year round in all sites. The mean parasite density among infected neonates was low (48 asexual forms per μl, range 8–200/μl). Maternal and placental parasitaemia were the most important risk factors for patent neonatal parasitaemia (P < 0.0001). Spontaneous clearance of parasitaemia occurred in 62.1% of neonates before day 2. 33.7% were symptomatic within 3 days of birth. Conclusion Congenital malaria is often asymptomatic, clears spontaneously and may not warrant treatment. However, newborns with unexplained fever and refusal to feed in malaria endemic areas should be tested for malaria.     

An assessment of cardiovascular risk among the people of a Nigerian university community.

BACKGROUND: The purpose of this study was to assess the level of cardiovascular disorder risk among the staff and students of Obafemi Awolowo University, Ile-Ife, Nigeria. METHODS: Six hundred apparently healthy subjects voluntarily participated in this study. They consisted of 200 students, 200 junior workers and 200 senior staff. Subjects' weight, height and blood pressures were taken. Subsequently, the questionnaire used for the Framingham Heart Study was given for completion. The questionnaire sought information on cardiovascular risk factors including smoking habits, sedentary lifestyle, diet, personality trait, age and sex. RESULTS: Students had a mean risk score of 10.24, junior staff 11.38, and senior staff 12.42. Significant differences were found between the level of risk for the students and that of the senior staff. However, no significant difference existed between the junior and senior staff and no significant difference existed between the level of risk for the students and the junior staff. Further, there was no significant difference in the level of risk for males compared to females. CONCLUSION: We concluded that the level of cardiovascular risk was low among the subjects selected for this study.     

Pattern of congenital malformations in Nigerian children

A series of 252 abortuses, stillbirths and neonates at the University of Ilorin Teaching Hospital and ECWA Hospital, Egbe, in Nigeria, were examined by autopsy dissection between 1983 and 1985. Their clinical cohorts in the nurseries, pediatric wards and those subjected to operations were also reviewed. Primary school children volunteers in two Ilorin schools were also examined in 1987 for cardiopulmonary malformations and umbilical hernia. Incident rates for congenital malformations ranged from 0.08 to 38.27% for congenital groin hernia, 2.39 to 8.73% for umbilical hernia, and 0.21 to 21.05% for the entire gastrointestinal tract. Other incident rates are 0.10 to 7.14% for genitourinary tract, 0.33 to 6.69% for CNS, 0.16 to 5.55% for musculoskeletal system, 0.26 to 4.76% for cardiovascular and 0.06 to 3.9% for bronchopulmonary malformations. The scope of the study is expected to make it adaptable in other developing countries.     

Plasma concentration-response relationship for cimetidine inhibition of drug metabolism in the rat

Cimetidine inhibition of antipyrine elimination has been studied in the rat over a range of steady state cimetidine concentrations. Cimetidine is a potent inhibitor of antipyrine metabolism with a concentration of about 1.25 mg/liter causing a 50% decrease in the total plasma clearance of antipyrine. The degree of inhibition of antipyrine clearance caused by cimetidine is dependent upon its plasma concentration, but the relationship is not linear. The formation clearances of all antipyrine metabolites measured--3-hydroxymethylantipyrine, 4-hydroxyantipyrine, and norantipyrine--are inhibited by cimetidine at all concentrations used. The susceptibility of the different metabolites to cimetidine inhibition does vary. The renal clearance of antipyrine was also decreased by cimetidine by an unknown mechanism. Analysis of the individual formation clearances suggests that the inhibition of oxidative metabolism due to cimetidine is caused by its binding to two classes of enzyme sites--a high affinity, low capacity and a low affinity, high capacity site. These two different sites would appear to be responsible for the production of different metabolites of antipyrine. The true nature of the selectivity of cimetidine inhibition of antipyrine metabolism is apparent from the formation clearances but not from the urinary metabolite patterns.     

Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies.

Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood measurements of AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.     

A pharmacokinetic study of amphotericin B lipid complex injection (Abelcet) in patients with definite or probable systemic fungal infections

This study describes a pharmacokinetic evaluation of amphotericin B (AMB) lipid complex injection (ABLC or Abelcet) in 17 patients with systemic fungal infection administered 5 mg/kg of body weight/day by infusion for 10 to 17 days. The results showed that AMB exhibited multiexponential disposition with high clearance, large volume of distribution at steady state, and long apparent elimination half-life but no evidence of accumulation in the blood after multiple daily doses. The results confirm previous observations and further reinforce the suggestion that ABLC may exist as a depot in the tissues from which free AMB is slowly released to limit exposure.     

Complementary anti-inflammatory effects of a β-blocker and a corticosteroid in an asthma model

Glucocorticosteroids are the mainstay treatment for chronic asthma; however, adverse effects can limit their usefulness. We previously determined in experimental asthma that chronic administration of β₂-adrenoceptor inverse agonists reduced airway hyperresponsiveness and indexes of inflammation. However, the effect of co-administration of glucocorticosteroids with β₂-adrenoceptor inverse agonists is unknown. Therefore, we evaluated the anti-inflammatory effect of co-administration of dexamethasone, a glucocorticosteroid, and nadolol, a β₂-inverse agonist, in a murine asthma model. We measured eosinophils and cytokines in bronchoalveolar lavage fluid and mucin content in epithelial cells after exposure to different concentrations of dexamethasone and nadolol. Dexamethasone was administered for 3 days and nadolol for 24 days prior to ovalbumin challenge. Both drugs were continued during five daily intranasal challenges with ovalbumin. Independent administration of dexamethasone (0.4 mg/kg/day) or nadolol (25 ppm) reduced bronchoalveolar lavage eosinophils by 58% and 36%, respectively (P < 0.05). Co-administration of both drugs yielded an additive reduction in eosinophils (81%, P < 0.05). Co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) also yielded a greater reduction in mucin volume density (83%) than either drug alone (18% for dexamethasone and 62% for nadolol) and greater than high-dose dexamethasone (71%) alone (P < 0.05). Similarly, co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) yielded an additive effect on the reduction of type 2 cytokines in bronchoalveolar lavage fluid equivalent to the administration of a 10-fold higher dose of dexamethasone. In Summary, the simultaneous administration of a glucocorticosteroid and a β₂-adrenoceptor inverse agonist was more effective at reducing indexes of airway inflammation than either drug given alone; suggesting nadolol may possess “glucocorticoid-sparing” properties.