Care of diabetic patients in hospital clinics and general practice clinics: a study in Dudley.

A five year retrospective casenote review was undertaken of 452 patients attending 11 different general practice diabetic clinics, and 506 patients attending a diabetic clinic at hospital A and 210 patients attending a diabetic clinic at hospital B. The populations attending the clinics, the degree of glycaemic control achieved and the monitoring for the development of diabetic complications were investigated. Insulin dependent patients comprised 57.9% of patients attending the diabetic clinic at hospital A, 35.7% at hospital B and 25.0% of patients attending the diabetic clinics at general practices. Of these 55.6%, 37.3% and 30.1% respectively received multiple daily insulin injections. Hospital A had a higher proportion of patients under 40 years old than hospital B or the general practice clinics. The ages of diabetic patients attending the general practice diabetic clinics were broadly similar to those attending hospital B. Significantly more general practice patients, both insulin and non-insulin dependent, had a mean blood glucose level of less than 11 mmol l-1 compared with patients attending clinics at hospitals A and B (P < 0.001). Glycosylated haemoglobin levels did not differ between patients attending hospital A and the general practice clinics. More non-insulin dependent and insulin dependent diabetic patients attending the general practice clinics and hospital A had been monitored satisfactorily for diabetic retinopathy (general practice clinic 68.8% and 39.7% respectively, hospital A 61.7% and 43.5%) than at hospital B (43.0% and 19.4%). Referral rates among all groups for ophthalmological assessment were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).     

Binding of gluten-derived peptides to the HLA-DQ2 (α1*0501, β1*0201) molecule,assessed in a cellular assay

The nature of the immunopathogenic relationship underlying the very strong association of coeliac disease (CD) to the HLA-DQ (A1*0501, B1*0201) genotype is not known, but probably relates to binding of gluten-derived epitopes to the HLA-DQ (α1*0501, β1*0201) heterodimer (DQ2). These epitopes have not yet been defined. In this study we have tested the binding of various gluten-derived peptides to DQ2 in a cellular assay using Epstein–Barr virus (EBV)-transformed B lymphocytes and murine fibroblast transfectants. One of these peptides (peptide A), which has previously been shown to exacerbate the CD lesion in vitro and in vivo, was found to bind to DQ2, albeit only moderately, lending further credence to its possible role in the pathogenesis of CD. The nature of peptide A's binding to DQ2 was explored with truncated and conservative point substituted analogues and compared with the published DQ2 binding motif, the results of which explain the observed level of binding.     

Recombinant mouse monoclonal antibodies with single amino acid substitutions affecting Clq and high affinity Fc receptor binding have identical serum half-lives in the BALB/c mouse.

The serum half-lives of three recombinant mouse monoclonal antibodies, differing radically in their ability to bind to Clq or FcRI but only minimally in structure, were determined in the BALB/c mouse following intravenous administration. The wild-type antibody, a chimaeric antibody comprising variable domains binding 3-iodo-4-hydroxy-5-nitrophenylacetate and constant domains of the mouse IgG2b isotype, was eliminated from the bloodstream with biphasic kinetics: alpha-phase, 0.5 days; beta-phase, 7.0 days. The alpha- and beta-phase half-lives of mutant recombinant antibodies with single amino acid substitutions, either Glu 235-Leu allowing binding to the mouse FcRI, or Lys 322-Ala reducing Clq binding 30-fold, were indistinguishable from those of the wild-type antibody demonstrating that the biological half-life of intact mouse IgG is independent of the ability to bind Clq or FcRI. The major implication of the present study is that IgG molecules which have been genetically engineered to eliminate interaction with other components of the immune system should retain the long half-life typical of natural antibodies.     

Dietary Patterns in Runners with Gastrointestinal Disorders

Individuals with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and reflux frequently experience gastrointestinal symptoms (GIS), potentially enhanced by high-intensity running. Food avoidances, food choices, and GIS in runners with IBS/IBD (n = 53) and reflux (n = 37) were evaluated using a reliability and validity tested questionnaire. Comparisons to a control group of runners (n = 375) were made using a Fisher’s Exact test. Runners with IBS/IBD experienced the greatest amount of exercise-induced GIS followed by those with reflux. Commonly reported GIS were stomach pain/cramps (77%; 53%), bloating (52%; 50%), intestinal pain/cramps (58%; 33%), and diarrhea (58%; 39%) in IBS/IBD and reflux groups respectively. In the pre-race meal, those with IBS/IBD frequently avoided milk products (53%), legumes (37%), and meat (31%); whereas, runners with reflux avoided milk (38%), meat (36%), and high-fibre foods (33%). When considering food choices pre-race, runners with IBS/IBD chose grains containing gluten (40%), high fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) fruits (38%), and water (38%). Runners with reflux chose water (51%), grains containing gluten (37%), and eggs (31%). In conclusion, while many runners with IBS/IBD and reflux are avoiding trigger foods in their pre-race meals, they are also consuming potentially aggravating foods, suggesting nutrition advice may be warranted.