Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due to Bordetella pertussis in a Murine Model

The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.     

Eradication of 'ooHelicobacter pylori'ox : an objective assessment of current therapies

The purpose of the present review was to determine objectively the optimal treatment for the eradication of H. pylori amongst the currently used regimens. A comprehensive literature search provided a data-base relating to the following treatments: dual therapy with an anti-secretory drug plus either amoxycillin or clarithromycin; standard triple therapy, with or without additional anti-secretory drugs; proton pump inhibitor triple therapy; and H₂-receptor antagonist triple therapy. Emphasis was placed on intention-to-treat analyses of eradication rates using all of the available evidence. The criteria used to select the optimal treatment were efficacy (eradication rates), frequency of side-effects, simplicity of the regimen (number of tablets per day and duration of treatment) and cost. The analysis showed that proton pump inhibitor triple therapy (that is, a proton pump inhibitor plus any two of amoxycillin, clarithromycin or a nitroimidazole) was the preferred treatment for the eradication of H. pylori . In particular, the 1-week, low-dose regimen with omeprazole plus clarithromycin plus tinidazole produced the highest eradication rates (>90%) with the lowest frequency of side-effects and at only modest cost.     

Mentoring in inservice training for child care workers

A model for training the trainers of child care providers that employs Vygotsky's framework of the Zone of Proximal Development is described. This efficient training mechanism proposes mentoring relationships as a means to meet the developmental needs of experienced child care professionals and improve the quality of existing child care programs.The authors would like to thank Dr. Bille Thomas and the satellite resource center directors and staff members for their work on the project.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Regulation of major histocompatibility complex (MHC) products in fresh and cultured human fetal pancreata aged 9–16 gestational weeks by gamma-interferon

Immunological data on the human fetal pancreas (HFP) are mainly confined to its constitutive expression of the MHC antigens. However, cytokines, such as gamma-interferon (g-IFN), released by lymphocytes during immune reactions, can induce or upregulate the expression of MHC products in allografts and alter their immunological behaviour. We investigated the effects of g-IFN on fresh and cultured HFPs aged 9–16 gestational weeks (gw). Following g-IFN stimulation of fresh HFPs, there was class I hyperexpression by the ductal cells, and some of the ductal, endothelial and islet cells also became class II⁺. Conventional tissue culture (5% CO₂ in air at 37°C) reduced the number of interstitial class II⁺ cells within the HFP after 1 week but was associated with de novo class I expression by some of the ductal cells. Remarkably, the changes in major histocompatibility complex (MHC) antigen expression by the ductal cells occurred earlier and were markedly enhanced when the HFPs were cultured beforehand. The number of interstitial class II⁺ cells in fresh and cultured HFPs was not influenced by g-IFN. The significance of these observations with regard to clinical HFP transplantation is discussed.     

Congential dislocation of the hip and adult low back pain: a report of three cases

Congenital dislocation of the hip (CDH) in an adult can accompany or cause mechanical low-back pain. This in turn, can create confusion in making the proper diagnosis. The mechanical alterations caused by CDH create an added strain to the lumbosacral spine. Manipulative treatment for back pain in these patients must not subject the dislocated hips to undue torque.     

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.     

Spinal dysraphism and cavovarus foot deformity: a case report

Neurological impairment secondary to spinal dysraphism most commonly presents as unilateral cavovarus foot in children. The deformity usually develops in the growing child around the age of five or six. The presence of a cavovarus foot of unknown origin in a child should lead to a complete neurological examination, including an assessment of the spine for spinal dysraphism. The early recognition of pathology may prevent severe neurological sequelae. A case of lipomyelomeningocele is presented to illustrate that cord damage in children with spinal dysraphism can present initially as a cavovarus foot.