Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow- up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.      

High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

Characterization of the epitope recognized by a monoclonal antibody highly specific for blood group M antigen

The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used.     

Head-Up Tilt Test in Patients with High Pretest Likelihood of Neurally Mediated Syncope: An Approximation to the "Real Sensitivity" of this Testing

This study was designed to examine the "true sensitivity" of a specific head-up tilt (HUT) testing protocol using clinical findings. The HUT protocol used 45 minutes at 60 degrees for the baseline portion and intermittent boluses of 2, 4, and 6 micrograms of isoproterenol in the second phase. Eighty-eight patients (40 men and 48 women; mean age of 33.8 +/- 16 years) with recurrent syncope and high pretest likelihood of neurally mediated syncope were included. The following were considerated as high pretest likelihood criteria: (1) at least two syncopal episodes; (2) no structural heart disease and normal baseline ECG; (3) age < 65 years; (4) a typical history of neurally mediated syncope, triggering factors plus premonitory signs; and (5) short duration of symptoms and fast recovery without neurological sequelae. Fifty-four patients (61%) had a positive tilt test (34/88 baseline [39%] and 20/50 with isoproterenol [40%]). The shorter time interval between the last syncopal episode and baseline HUT test was the only predictor for a positive response (P < 0.003). Conversely, this time interval was not predictor of positive responses during isoproterenol-tilt testing. In conclusion: (1) we claim a "sensitivity" for this combined protocol of 61%; and (2) our results indicate that patients with syncope of unknown origin must be tilted nearest as possible to the last syncope to increase the positive responses of HUT test.     

Knowledge of pressure ulcer prevention: a cross-sectional and comparative study among nurses

Background  

Pressure ulcers are a common, painful and costly condition. Results of a 1991 study into the knowledge among Dutch hospital nurses on the usefulness of measures to prevent pressure ulcers showed moderate knowledge. Results were confirmed by subsequent studies. In recent years, Dutch guidelines have been updated and the attention given to pressure ulcer care has been increased. This was expected to improve pressure ulcer care and to increase nurses' knowledge. The aims of the current study were to investigate (1) how much nurses employed in Dutch hospitals know about the usefulness of 28 preventive measures considered in the most recent national pressure ulcer guideline; (2) whether differences in knowledge exist between nurses working in hospitals that audit pressure ulcers and those employed in hospitals that do not; and (3) to study whether knowledge among Dutch hospital nurses regarding the usefulness of preventive measures had changed between 1991 and 2003.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

相似文献   

Diabetes mellitus in India: The modern scourge

India has a high prevalence of diabetes mellitus and the numbers are increasing at an alarming rate. In India alone, diabetes is expected to increase from 40.6 million in 2006 to 79.4 million by 2030. Studies have shown that the prevalence of diabetes in urban Indian adults is about 12.1%, the onset of which is about a decade earlier than their western counterparts and the prevalence of Type 2 diabetes is 4–6 times higher in urban than in rural areas. The risk factors peculiar for developing diabetes among Indians include high familial aggregation, central obesity, insulin resistance and life style changes due to urbanization. Screening for gestational diabetes and impaired glucose tolerance among pregnant women provides a scope for primary prevention of the disease in mothers as well as in their children. The problems of obesity and impaired glucose tolerance (IGT) (important predisposing factors) are not confined to adults alone but children are also increasingly getting affected. Most long standing macro and micro vascular complications are also more common among Indian diabetics as compared to other races and ethnic groups. A strong familial clustering of diabetic nephropathy among Indian Type 2 diabetics has also been noted. Clustering of cardiovascular risk factor like Syndrome X is common among urban Indians. The rising incidence of diabetes and its complications are going to pose a grave health care burden on our country. Timely effective interventions/measures and screening tests for complications at the time of diagnosis becomes imperative not only for early detection, but also to prevent progression to end stage disease. Screening for gestational diabetes among pregnant women would also go a long way in primary prevention of the disease. Life style changes/interventions and drugs like rosiglitazone are the current strategies that can prevent and/or delay the onset of diabetes. Simple interventional strategies like “Eat less, Eat on time and Walk more” can go a long way in preventing these chronic disorders among present as well as in the future generations.