NHS Direct usage in a GP population of children under 5 years: is NHS Direct used by people with the greatest health need?

This study compares health status, demographic and socioeconomic characteristics of users and non-users of NHS Direct in order to establish whether the service is being used by people with the greatest need for healthcare services. It suggests that use of NHS Direct is widespread among carers of children under 5 years old, but there is evidence that it may not be accessed equitably by those from ethnic minorities, lower socioeconomic groups and those with established ill health.     

A longitudinal study of vergence adaptation in incipient presbyopia

BACKGROUND: To investigate vergence adaptation during the incipient phase of presbyopia, when the amplitude of accommodation approaches the level where the first reading addition is required. The study aimed to assess the ability of the vergence system to counteract changes in the component contributions to the overall vergence response with the decline in the amplitude of accommodation in presbyopia, although previous reports on the nature of changes in accommodative, tonic and proximal vergence are equivocal. METHODS: Using a 'flashed' Maddox rod technique, an assessment of vergence adaptation to 6delta base-out and 6delta base-in prism was made for 28 subjects (aged 35-45 years at the commencement of the study). The measurements were taken four times over a 2-year period. RESULTS: Using a repeated measures analysis of variance, the results show that with the decline in amplitude of accommodation, there is a statistically significant reduction in the magnitude of vergence adaptation to both base-out (p < 0.05) and base-in prism (p < 0.01). CONCLUSIONS: This study shows that with ageing, there is a decrease in the ability of the slow vergence mechanism to overcome a change in fusional vergence demand and would suggest that either the fast component of fusional vergence must cope with any change in fusional vergence demand or that the sum of the accommodative, tonic and proximal vergence responses are virtually stable with age.     

A preventive intervention for enhancing resilience among highly stressed urban children

Describes the development and evaluation of a pilot 12-session, school-based preventive intervention designed to enhance resilience among inner-city children who have experienced major life stress. Thirty-six 4th–6th grade children participated in the intervention in groups of 5–8 co-led by school personnel. The curriculum focussed on understanding feelings in oneself and others, perspective-taking, social problem-solving, dealing with solvable and unsolvable problems, and building self-efficacy and esteem. Pre-post evaluation showed significant improvement among participants on teacher-rated indices of learning problems and task orientation and on child ratings of perceived self-efficacy, realistic control attributions and anxiety. Program limitations and factors that restrict generalization are considered and new directions for program development and research are proposed.     

Effects of ethmoidal nerve stimulation on respiration-related neurones in the dorsal medulla of the cat

Stimulation of the nasal mucosa produces a number of respiratory reflexes the afferent limb of which is provided by the ethmoidal nerve, a branch of the trigeminal nerve. In the cat this nerve terminates within the trigeminal nucleus. It has no direct projection to brainstem respiratory centres. This study examines the response of respiratory-related neurones in the nucleus of the solitary tract (NTS) to ethmoidal stimulation. It demonstrates that these neurones show both excitatory and inhibitory responses to ethmoidal stimulation. Thus, the NTS appears to be involved in respiratory reflexes initiated by stimulation of the nasal mucosa.     

CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation

We report the capacity of CD40 ligand (CD40L)-negative T cell clones to activate human B cells. CD40L-negative T cells induce a level of B cell proliferation 10–20% of that seen with normal T cells. The signal provided by the negative clones is synergistic with that derived from a CD40L transfectant, and restores B cell proliferation to normal levels, showing that CD40L-negative T cell clones are not inherently inhibitory for B cells. Although their capacity to induce proliferation was much reduced, CD40L-negative T cell clones were still strong inducers of B cell differentiation to plasma cells. This differentiation to plasma cells was inhibited by a CD40L transfectant. The data are discussed with regard to the normal in vivo mechanism for maintaining B cell memory and memory antibody responses to T-dependent antigens.     

Impaired Microvascular Function in Normal Children: Effects of Adiposity and Poor Glucose Handling

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat ( r =−0.20, P < 0.05 and r =−0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l⁻¹) showed significantly lower vasodilatation to both ACh (   P < 0.005  ) and SNP (   P < 0.02  ) than those in the lower quintile (range 3.9-4.9 mmol l⁻¹). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile ( P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin ( r = 0.59, P < 0.001) and with the fasting insulin resistance index ( r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated ( r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.     

Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation

To facilitate study of alveolar macrophages in vivo, we developed a method to rapidly and efficiently replace resident alveolar macrophages with macrophages of a different (donor) genotype. Chimeric mice were generated by lethal irradiation followed by fetal liver transplantation (FLT) using green fluorescent protein (GFP) transgenic reporter mice as donors. Kinetics of peripheral blood monocyte (PBM) and alveolar macrophage reconstitution was determined 4 and 10 weeks post-FLT by quantifying the percentage of GFP+ cells. To enhance the recruitment of donor monocytes into the lung after FLT, mice were treated with intratracheal administration of liposomal clodronate to deplete host alveolar macrophages at 6 weeks post-FLT. PBM reconstitution occurred by 4 weeks after FLT (85.7+/-1.6% of CD11b+/Gr-1+ monocytes were GFP+), and minimal alveolar macrophage repopulation was observed (9.5% GFP+). By 10 weeks following FLT, 48% of alveolar macrophages were GFP+ by immunostaining of macrophages on lung tissue sections, and 55.1 +/- 1.6% of lung lavage macrophages were GFP+ by fluorescein-activated cell sorter analysis. Clodronate treatment resulted in a significant increase in GFP+ alveolar macrophages 10 weeks after FLT. By immunostaining, 90% of macrophages were GFP+ on lung tissue sections and 87.5 +/- 1.1% GFP+ in lung lavage (compared with GFP-transgenic controls). The ability of newly recruited alveolar macrophages to clear Pseudomonas aeruginosa and activate nuclear factor-kappaB in response to Eschericia coli lipopolysaccharide demonstrated normal macrophage function. Optimizing this methodology provides an important tool for the study of specific genes and their contribution to alveolar macrophage function in vivo.     

Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.