Unsuccessful validation of 2004 model for predicting academic or behavioural limitations after childhood bacterial meningitis.

AIM: In 2004, a model identifying children at risk of academic or behavioural limitations after bacterial meningitis (BM) was presented. Risk factors were male gender, low birthweight, lower educational level of the father, Streptococcus pneumoniae, lower cerebrospinal fluid (CSF) leucocyte count, delay between admission and start of antibiotics, dexamethasone <2 days, seizures and prolonged fever. The aim of this study was to validate that prediction model in an independent cohort. METHODS: Academic or behavioural limitations were determined in 93 Dutch school-age BM survivors. Risk factors for limitations were obtained from medical files. Validation was performed by applying the model in the cohort, then assessing discrimination and goodness of fit. Multiple imputation techniques were used to deal with missing values. RESULTS: Although fit of the model appeared good when it came to similarity of expected and observed cases (p-value of the Hosmer-Lemeshow test 0.24-0.57), discrimination was poor. Area under the curve (AUC) of the receiver operated characteristics (ROC) curve of the model was 0.83 (95% CI: 0.77-0.89) in the development cohort and 0.53 (95% CI: 0.41-0.65) in the validation cohort. CONCLUSION: External validation of the model was unsuccessful. It is not suitable for implementation in practice.

Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis.

The susceptibility, severity and prognosis of infectious diseases depend on the ability of the host immune system to respond to pathogens. Genetic variation of immune response genes is associated with susceptibility to and severity of infectious diseases. Bacterial meningitis (BM) is a serious and life-threatening infectious disease of the central nervous system (CNS). Despite adequate antibiotic treatment and immunization strategies, mortality remains high, especially in developing countries. Streptococcus pneumoniae and Neisseria meningitidis are the two most common causative microorganisms of BM worldwide. The pathogenesis of BM starts with mucosal bacterial colonization, followed by invasion and survival of bacteria in the bloodstream, crossing of the blood-brain barrier, finally causing infection in the CNS, where host defense is less adequate. Host defense to BM starts with a complex cascade of pathogen recognition and subsequent intracellular signaling causing transcription of genes leading to the production of inflammatory mediators. Although this immune reaction is essential for killing microbes, it is also associated with damage to healthy cells and thus adverse disease outcome. This review provides an overview of the pathogenesis of invasive pneumococcal disease and invasive meningococcal disease related to the influence of genetic variation in genes involved in innate immunity, focusing on BM.

The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women.

The purpose of this study was to determine the effect of 8 wk of bovine colostrum supplementation on body composition and exercise performance in active men and women. Subjects were randomly assigned to a placebo (whey protein) and colostrum group (20 g/d in powder form). Each subject participated in aerobic and heavy-resistance training at least three times per wk. Body composition was assessed via dual x-ray absorptiometry analysis. Treadmill time to exhaustion, one repetition maximum strength (bench press), and the total number of repetitions performed during one set to exhaustion at a submaximal load for the bench press (50% and 100% of body weight for women and men, respectively) were ascertained. The whey protein group experienced a significant increase (P < 0.05) in body weight (mean increase of 2.11 kg), whereas the colostrum group experienced a significant (P < 0.05) increase in bone-free lean body mass (mean increase of 1.49 kg). There were no changes in any of the other parameters measured. Thus, supplementation with bovine colostrum (20 g/d) in combination with exercise training for 8 wk may increase bone-free lean body mass in active men and women.

Effects of exercise training and amino-acid supplementation on body composition and physical performance in untrained women.

The purpose of this study was to determine the effects of 6 wk of essential amino acid (EAA) supplementation on body composition and exercise performance in untrained women (n = 21). Subjects were randomly assigned to a placebo (cellulose) or an EAA (average daily dose of 18.3 g of EAAs in pill form) group. Each subject participated in aerobic and heavy-resistance training three times per week. Body composition was assessed via dual x-ray absorptiometry analysis. Muscular endurance was determined via treadmill time to exhaustion, and strength was assessed by the total amount of weight lifted for one set to exhaustion at an estimated 12 repetitions maximum. No changes occurred in either group for body weight, lean body mass, fat mass, or bone mineral content. Treadmill time to exhaustion (TTE) improved significantly (P < 0.05) in the EAA group (mean +/- SD; pre-TTE = 13.15 +/- 3.67 min, post-TTE = 14. 73 +/- 4.26 min), whereas the placebo group did not change significantly. The total weight lifted at the subject's maximum 12 repetitions did not significantly change in either group. In previously untrained individuals, the ingestion of EAAs combined with aerobic and heavy-resistance training for 6 wk did not have a significant effect on body composition or muscular strength; however, aerobic muscular endurance increased significantly.

Immunohistochemical localization of transforming growth factor-beta 1 in the nonnecrotizing granulomas of pulmonary sarcoidosis.

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha 5 beta 1 fibronectin receptor. The role of TGF-beta 1 in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta 1 in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta 1, the TGF-beta 1 binding proteoglycan decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta 1. We further demonstrated decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta 1 staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta 1 and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta 1 may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.

Obstetric forceps pad designed to reduce infant trauma.

The use of the standard obstetric forceps has been associated with varying degrees of maternal and fetal trauma. To reduce the degree of skin markings, a pliable polyurethane pad with selfadherent backing has been designed, which can be applied to each blade of the forceps. One hundred five neonates who required forceps-assisted deliveries were observed for evidence of skin trauma immediately after delivery and again at 24 hours. Padded forceps significantly reduced craniofacial visible skin markings when compared with the skin markings produced by the unpadded forceps. The addition of the pad to the forceps blade had no adverse effect on the mother, and obstetricians encountered no problems in the application and use of the pads.

The indusium griseum in the mouse: architecture, Timm's histochemistry and some afferent connections.

The Indusium griseum (IG) is an enigmatic cortical field classically felt to be a part of the hippocampus (HC). In the mouse, IG lies just dorsal to the corpus callosum at the base of the anterior half of cingulate cortex. In coronal sections the field is small but constitutes a fairly long rostro-caudal strip. The connections of the IG are poorly understood. The Timm's staining pattern of the IG is reminiscent of a mini-dentate gyrus (DG) comprising a layer of granule cells with two bands of staining in the molecular layer. In the DG there are three bands which correspond to inputs from the lateral and medial entorhinal area (LEA and MEA) and the ipsi- and contralateral association systems. Using anterograde transport of HRP we have found that the LEA and MEA also terminate in the molecular layer of the IG. This suggests that the IG is a displaced portion of the DG. The olfactory system is known to have a strong indirect influence on the HC via primary and secondary bulbar projections to the LEA. Wheat germ agglutinin-HRP injections confined to the main olfactory bulb (MOB) show a direct projection from the MOB to IG. Both the olfactory bulb itself and retrobulbar structures such as the piriform cortex (PC) convey olfactory information to the LEA; the LEA supplies a major input to the DG. Our results suggest that there is a more direct pathway whereby olfactory information may influence a cortical region, IG, whose histochemistry and direct afferents from the entorhinal cortex suggest that it is part of or closely related to the DG. Thus, IG may represent a phylogenetically old olfacto-recipient outpost of the hippocampus.