Association study of Glutathione S-transferase P1 (GSTP1) with asthma and bronchial hyper-responsiveness in two German pediatric populations

Glutathione S-Transferase P1 ( GSTP1 ) is an important enzyme in the detoxification of products of oxidative stress. Several studies have shown an association of the amino acid variant Ile105Val with bronchial asthma and the reaction of the lung to inhalant pollutants. The aim of this study was to test the two known amino acid variants in GSTP1 for association with bronchial asthma and airway hyper-responsiveness in two German pediatric populations. We genotyped Ile105Val and Ala114Val in the Multicenter Allergy Study cohort (85 children with asthma, 123 controls) and asthmatic children from Freiburg (n = 178). We did not find association of either polymorphisms with bronchial asthma or airway hyper-responsiveness. We conclude from our data that polymorphisms within GSTP1 do not play a major role in the development of bronchial asthma in German children.     

Non-synaptic Localization of the Glutamate Transporter EAACI in Cultured Hippocampal Neurons

It has been postulated for several years that the high affinity neuronal glutamate uptake system plays a role in clearing glutamate from the synaptic cleft. Four different glutamate transporter subtypes are now identified, the major neuronal one being EAAC1. To be a good candidate for the reuptake of glutamate at the synaptic cleft, EAAC1 should be properly located at synapses, either at pre- or postsynaptic sites. We have investigated the distribution of EAAC1 in primary cultures of hippocampal neurons, which represent an advantageous model for the study of synaptogenesis and synaptic specializations. We have demonstrated that EAAC1 immunoreactivity is segregated in the somatodendritic compartment of fully differentiated hippocampal neurons, where it is localized in the dendritic shaft and in the spine neck, outside the area facing the active zone. No co-localization of EAAC1 immunoreactivity with the stainings produced by typical presynaptic and postsynaptic markers was ever observed, indicating that EAAC1 is not to be considered a synaptic protein. Accordingly, the developmental pattern of expression of EAAC1 was found to be different from that of typical synaptic markers. Moreover, EAAC1 was expressed in the somatodendritic compartment of hippocampal neurons already at stages preceding the formation of synaptic contacts, and was also expressed in GABAergic interneurons with identical subcellular distribution. Taken together, these data rule against a possible role for EAAC1 in the clearance of glutamate from within the cleft and in the regulation of its time in the synapse. They suggest an unconventional non-synaptic function of this high-affinity glutamate carrier, not restricted to glutamatergic fibres.     

No association of histamine- N-methyltransferase polymorphism with asthma or bronchial hyperresponsiveness in two German pediatric populations

Histamine plays an important role in the allergic inflammation. Histamin N-Methyltransferase (HNMT) catalyses the major pathway of histamine metabolism in the human lung. A common functional single nucleotide polymorphism (SNP) within the HNMT gene (C314T) was recently related to asthma. We tested this SNP for associations with asthma and asthma associated traits in two German pediatric populations (1. MAS-cohort, n=888, 85 children with asthma; 2. asthmatic children from Freiburg, n=176). Non-asthmatic (n=515) and non-atopic (n=211) children from the MAS-cohort were used as controls. For genotyping melting curve analyses (Light Cycler System) were applied. In contrast to a previous study, no association of the HNMT 314T allele with asthma, bronchial hyperresponsiveness (BHR) or other asthma related phenotypes could be observed in either study population. We conclude that this SNP might not play a major role in the pathogenesis of asthma or BHR in German children.     

A Model of Consequences of Need-Driven, Dementia-Compromised Behavior

PURPOSE: To extend the original need-driven, dementia-compromised behavior (NDB) model by explaining the consequences of behavioral symptoms for the person with dementia. ORGANIZING CONSTRUCT AND METHODS: Literature is reviewed and the consequences of expressing needs through need-driven, dementia-compromised behaviors are posited. The consequences of need-driven, dementia-compromised behavior (C-NDB) theory is proposed as a framework to improve understanding of the person with dementia and the consequences of behavioral symptoms and unmet needs. FINDINGS: Instead of normative verbal communication, people with significant dementia commonly communicate need via non-normative behaviors, making it difficult for caregivers to know that the person has a need and the extent of such need. Not meeting needs of people with dementia affects the person with dementia, care factors, and contextual factors. Cascading effects occur in which not meeting the original need results in new needs and behavioral symptoms. CONCLUSIONS: This framework indicates the consequences of expressing need behaviorally rather than verbally and shows that caregiver actions might moderate the events that lead to many needs being unresolved. Suggestions are made regarding future research questions deduced from the model.     

Profile of Postdischarge Rehospitalizations and Acute Care Visits for Seven Patient Groups

Abstract The study's purpose was to examine postdischarge rehospitalizations and acute care visits in seven high risk, high volume, high-cost patient groups. Subjects were drawn from an urban tertiary teaching hospital. The total sample ( N = 764) consisted of seven patient groups (drawn from five randomized clinical trials): very low birthweight (VLBW) infants ( n = 79); women post-unplanned cesarean birth ( n = 122) and their infants ( n = 123); pregnant women with diabetes ( n = 55); women post-hysterectomy surgery ( n = 109); and elderly with medical cardiac Diagnostic Related Groups (DRGs) ( n = 142) and elderly with surgical cardiac DRGs ( n = 134). The VLBW infant and pregnant diabetic groups were predominantly African American, the elderly and hysterectomy groups predominantly Caucasian, and the cesarean group almost equally distributed. The lowest rate of rehospitalization (2%) occurred in the cesarean group, the highest (35%) in the pregnant diabetics. In four groups (cesarean and infants, hysterectomy and surgical elderly), 60%-100% of the rehospitalizations occurred within 4 weeks of discharge. Subjects requiring acute care visits ranged from 13% (hysterectomy) to 82% (VLBW infants). Acute care visits demonstrated greater distribution throughout the follow-up periods but also tended to concentrate in the first 4 weeks postdischarge.     

Sexually Active Adolescents and Young Adults: A High-Risk Group for Chlamydia trachomatis Infection

Background: The importance of travel as a risk factor for Chlamydia trachomatis infection was evaluated among a series of young people consecutively tested.
Methods: We studied 130 sexually active young subjects, aged 14–25 years, all living in the Rome, Italy, urban area. Ninety-eight females and 32 males attended hospital-based clinics or were the partners of an infected female. About half of these subjects had traveled abroad either for pleasure or for work, mostly to Europe, but also to North America or to Asia, where they admitted to having had casual sex. We used two "gold standard" methods to diagnose infection with C. trachomatis : culture on McCoy cells grown in shell vial, and direct immunofluorescence with monoclonal antibodies. Subjects were considered infected when at least one test was positive.
Results: Thirty-nine of 130 (30%) subjects were asymptomatic, and 27/130 (20.8%) subjects were infected with Chlamydia trachomatis , of whom 6/25 (24%) asymptomatic females and 3/14 (21.4%) asymptomatic males were infected. Among teen-aged (ages 14–19) youngsters with more than one sex partner, international travel was an additional significant risk factor for C. trachomatis infection (p <.02; OR 20; 95% Cl 1.47–40%). Urethritis/cystitis and vaginal pathology/discharge were the prevalent manifestations of illness among the females, while urethritis was the only clinical condition found in the males.
Conclusion: In a series of young subjects, travel abroad, sex with more than one partner, and teen age, combined together, were significant risk factors for the acquisition of Chlamydia trachomatis genitourinary infection.     

Locomotor Strategies Preceding Independent Walking: Prospective Study Of Neurological And Language Development In 424 Cases

Locomotor strategies used before the acquisition of independent walking were studied in 424 infants. 270 were survivors of neonatal intensive care (the index group); the other 154 (controls) had had no perintal complications. Five forms of locomotion were distinguished: crawling on hands and knees, creeping on the stomach, bottom-shuffling, other, and none before independent walking. Crawling was the most common form of locomotion in both groups. A higher percentage in the index group were late crawlers (greater than 10 months), but similar proportions in both groups were bottom-shufflers or simply stood up and walked. One of the most important factors influencing locomotor strategies was asymmetry. Analysis of the influence of locomotor strategies on psychomotor and linguistic outcome up to five years showed no significant relationships within the index group. However, within the control group, infants who crawled had a statistically greater incidence of later motor delay, which is in contrast to the findings of other studies.     

IL-6 Expression in Neurons of Transgenic Mice Causes Reactive Astrocytosis and Increase in Ramified Microglial Cells but no Neuronal Damage

Growing evidence suggests that aberrant production of inflammatory cytokines within the central nervous system (CNS) contributes to the development of pathological conditions. To test the cause—effect relationship between the overproduction of interleukin-6 (IL-6) in the CNS and the onset of neuropathological changes, we have generated transgenic mice in which human IL-6 expression has been targeted to the neurons by using the rat neuron-specific enolase promoter. These mice develop reactive astrocytosis and an increase in ramified microglial cells but do not show histological or behavioural signs of neuron damage at the light microscope level. We thus conclude that a constant release of human IL-6 by neuronal subpopulations in mice is sufficient to activate cells potentially capable of modulating the local immune response, but at the same time is compatible with normal neuron functions.