This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)
Despite studies of the pathologic and microbiologic aspects of the lung in cystic fibrosis (CF), there is a lack of information on the lung localization of bacterial pathogens. Bacteriologic data come from cultures of sputum or accessible lung effluent from bronchoscopy. Our objective was to localize Pseudomonas aeruginosa (PA) in situ in order to provide descriptive data on the relationship between the presence of PA and disease of the surrounding tissue. Using stored, uncut blocks of preserved lung, we deparaffinized, cut, mounted, and reacted them with high-titer rabbit sera made to a mucoid strain of PA. The tissues were then reacted with a second antibody, biotinylated goat antirabbit immunoglobulin, developed using a peroxidase technique and counterstained with hematoxylin. PA organisms stained with heavy brown deposits and this was species-specific. In five patients with CF chronically colonized with PA, the organisms could easily be localized in multiple sections. Microscopic study demonstrated that location was generally endobronchiolar and associated with bronchiolar obliterative changes, mainly in small (less than 1 mm) airways. Extraluminal PA organisms were rare even when there was chronic interstitial inflammation. This study demonstrated the presence of PA at the location where physiologic damage in CF is most severe--the small bronchioles--strengthening the association between PA and pulmonary deterioration in CF.
Background: The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000-2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship.
Empyema rarely complicates pneumonia. In a 361-bed regional pediatric hospital, 50 pleural empyemas were identified from 1988 through 1994; 17 (34%) occurred in the last 12 months of this period, for which the incidence was 3.3 per 100,000 of the population aged < or = 18 years (P < .05, chi 2 test). A significant seasonal prevalence was observed: 50% of cases occurred in the winter (P < .001, chi 2 test). In contrast with the findings of previous studies, in which empyemas predominantly occurred in infants, the median age of our patients was 7 years; underlying illnesses were present in only 10%, and all had community-acquired disease. Eighty-two percent had chest tubes inserted, 56% required a thoracotomy with pleural decortication, and 2% had a lobectomy. There were no deaths. Streptococcus pneumoniae was isolated in 40% of the cases; specimens in 44% of the cases were sterile. None of the empyemas were associated with Staphylococcus aureus or Haemophilus influenzae type b, and only one was caused by group A streptococcus. Among 13 S. pneumoniae isolates, the rate of resistance to penicillin was 15%; to erythromycin, 15%; to chloramphenicol, 31%; and to cefotaxime, 23%. The penicillin-resistance rate among blood and cerebrospinal fluid pneumococcal isolates was 17% during 1993-1994. Drug-resistant S. pneumoniae is now a recognized cause of pleural empyemas in children.
Expression of HLA-B57 is associated with restricted replication of human immunodeficiency virus (HIV), but the mechanism for its protective effect remains unknown. If this advantage depends upon CD8 T-cell recognition of B57-restricted epitopes, mother-to-child transmission of escape mutations within these epitopes could nullify its protective effect. However, if the B57 advantage is largely mediated by selection for fitnessattenuating viral mutations within B57-restricted epitopes, such as T242N in TW10-Gag, then the transmission of such mutations could facilitate viral control in the haploidentical infant. We assessed the consequences of B57-associated mutations on replication capacity, viral control, and clinical outcome after vertical transmission in 13 mother-child pairs. We found that expression of HLA-B57 was associated with exceptional control of HIV during infancy, even when mutations within TW10 and most other B57-restricted epitopes were transmitted, subverting the natural immunodominance of HLA-B57. In contrast, most B57-negative infants born to B57-positive mothers progressed rapidly to AIDS. The presence of T242N led to a reproducible reduction in viral fitness, as demonstrated by in vitro assays using NL4-3 constructs encoding p24 sequences from individual mothers and infants. Associated compensatory mutations within p24-Gag were observed to reverse this impairment and to influence the propensity of T242N to revert after transmission to B57-negative hosts. Moreover, primary failure to control viremia was observed in one infant to whom multiple compensatory mutations were transmitted along with T242N. These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag.
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