Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)     

Regional differences in the vasorelaxant effects of nicorandil and amlodipine on isolated porcine coronary arteries

Summary— The vasorelaxant effects of nicorandil, a K⁺-channel opener, and amlodipine, a dihydropyridine-type Ca²⁺-channel blocker, were investigated on partially and maximally K⁺-depolarized ring preparations from the porcine left anterior descending coronary artery. By comparing vascular responses in the proximal and distal parts of the epicardial segment, the scope of the study was to evaluate regional differences in the action of nicorandil and amlodipine. Nicorandil (10 ⁷- 10^-4 M) shifted the K⁺ concentration-response curves to the right and depressed the maximal contractile responses in a concentration-dependent manner, consistent with K⁺-channel opening and secondary non-K⁺-channel opening mechanisms of action. Nicorandil had a significantly more potent relaxant effect in the proximal compared to the distal arterial rings contracted with 85 mM K⁺. Pretreatment with methylene blue (10^-5 M) did not significantly influence the regional difference in the action of nicorandil. Amlodipine (10⁹- 10^-6 M) had a significantly more potent and effective inhibitory and relaxant effect than nicorandil under the same conditions. In contrast to nicorandil, the effect of amlodipine was more prominent in the distal compared to the proximal vessel rings. The cumulative addition of extracellular Ca²⁺ exhibited a more potent contractile response in the distal rather than in the proximal rings. Nicorandil totally and amlodipine partly eliminated the contractile responses to the lowest concentration of Ca²⁺. The inhibitory effect of amlodipine on the contractile responses to higher Ca²⁺ concentrations was more pronounced than that of nicorandil. The results show that there are regional differences in the responsiveness of porcine coronary arteries to Ca²⁺, nicorandil and amlodipine. Our findings indicate that the regional difference in nicorandil-induced vasodilation was caused neither by the K⁺-channel opening nor by the nitrate-like mechanism of action, but could be due to a direct Ca²⁺-influx blocking effect of the drug.     

The role of men in family planning decision-making in rural and urban Nigeria.

OBJECTIVES: To determine the role of men in family planning decision-making in both rural and urban areas of Nigeria. METHODS: A total number of 370 married men (244 rural and 126 urban) were interviewed using a pre-tested, semi-structured interviewer based questionnaire. The study was conducted in the Iwaro community in Atakumosa West Local Government area (rural men) and the Oranfe Community in Ife East Local government area (urban men), both in Osun State, South West Nigeria. RESULTS: The results showed a high level of awareness of family planning among both study groups (98.3% rural and 98.4% urban). Most men in both groups believe that a decision about family planning should be made jointly by the spouses instead of being the prerogative of either. This contrasts with the generally held belief that men are opposed to family planning and a take predominant role in contraceptive decision-making. The condom was the most commonly known and used method with a preponderance among urban (81.1%) over rural men (69.4%). Many men would use family planning if their wives demanded it. However, most respondents in both study groups believed that men should not accompany their wives to the family planning centre to obtain contraceptive supplies and advice. CONCLUSION: Deciding about contraception should be done jointly by men and women in South West Nigeria.     

Noma (cancrum oris): questions and answers

Noma (cancrum oris) is an infectious disease which destroys the oro-facial tissues and other neighboring structures in its fulminating course. It affects predominantly children aged 2-16 years in sub-Saharan Africa where the estimated frequency in some communities may vary from one to seven cases per 1000 children. The key risk factors are poverty, malnutrition, poor oral hygiene, deplorable environmental sanitation, close residential proximity to livestock, and infectious diseases, particularly measles. Malnutrition acts synergistically with endemic infections in promoting an immunodeficient state, and noma results from the interaction of general and local factors with a weakened immune system as the common denominator. Acute necrotizing gingivitis (ANG) is considered the antecedent lesion. Current studies suggest that evolution of ANG to noma requires infection by a consortium of microorganisms with Fusobacterium necrophorum and Prevotella intermedia as the suspected key players. Without appropriate treatment, mortality rate is 70-90%. Survivors suffer the two-fold affliction of oro-facial disfigurement and functional impairment. Reconstructive surgery of the resulting deformity is time-consuming and financially prohibitive for the victims who are poor.     

Diet restriction by pregnant women in Nigeria

The reasons for food aversions given by selected low income, illiterate women during pregnancy fell into four categories: health, tradition, economy and religion. More than two thirds of these mothers strongly avoided milk, cowpea seeds and bournvita for fear of having big babies which they thought would lead to difficult labor and cesarean section. Only one of the respondents associated infantile rickets with nutrition. Nutritional counseling, coupled with a fear-mechanism technique for a minimum of four months, served to correct these erroneous assumptions. The effects of the counseling sessions were evaluated by monitoring patterns of maternal weight gain and the baby's weight. The experimental group had a significant pattern of monthly weight gain (P less than 0.02) and heavier babies (P less than 0.01) than the control group. The authors conclude that diet restrictions of this nature can be modified positively through regular nutritional counseling and, in extreme cases, by the use of a fear-mechanism technique.     

In vitro and in vivo MMP gene expression localisation by In Situ -RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts

Background  

Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult.