Human T-cell receptor V alpha gene polymorphism.

Polymorphism in the germline repertoire of T-cell receptor (TCR) variable alpha and beta (V alpha and V beta) genes could alter the relative abilities of individuals in a population to respond to particular antigens. Variation in the number of germline V alpha and V beta gene segments has been reported in wild mice and in different inbred mouse strains. A previous study of the human V beta gene germline repertoire failed to reveal a similar degree of polymorphism in the numbers of V beta gene segments. We have now carried out a survey of 10 different V alpha gene segment subfamilies containing approximately 23 V alpha gene segments in a panel of 120 unrelated individuals by hybridization and failed to find any evidence for V alpha repertoire polymorphism. To determine if significant germline polymorphism does occur in humans at the level of individual V gene segments, we determined the nucleotide sequences of eight copies of the V alpha 21 gene segment derived from seven unrelated individuals. Polymorphic differences between these sequences defined three different alleles. One of these alleles contains a frameshift mutation which would cause premature termination of the protein product. The presence of this null allele among the eight sequences determined suggests that functionally relevant germline polymorphism of human TCR V gene segments may occur by mechanisms other than gene duplication or deletion.     

Challenging the world: patient safety and health care-associated infection.

Improving the safety of patient care is an issue which affects health systems in both developed and developing countries. To co-ordinate and accelerate improvements in patient safety, the World Health Organization (WHO) has supported the creation of the World Alliance for Patient Safety which was launched in October 2004. The six action areas of the Alliance are Patients for Patient Safety, Taxonomy, Research, Solutions for Patient Safety, Reporting and Learning, and a biennial Global Patient Safety Challenge. The first Challenge covering 2005-2006 was launched in October 2005 under the banner 'Clean Care is Safer Care'. The Challenge addresses health care-associated infection, a major, patient safety problem affecting hundreds of millions of people worldwide.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.     

Topical treatments for seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy and effectiveness

BACKGROUND: Evidence for the effectiveness of topical treatments, in providing symptomatic relief from ocular allergy, remains uncertain. AIMS: To assess the effectiveness and relative efficacy of topical treatments for the management of seasonal allergic conjunctivitis. DESIGN OF STUDY: A systematic review and meta-analysis. SETTING: A literature search of the Cochrane Library, Medline, and EMBASE bibliographic databases. METHOD: Double-masked randomised controlled trials were identified, that compared the use of topical mast cell stabilisers (sodium cromoglycate, nedocromil, lodoxamide) with placebo, topical antihistamines with placebo, and topical mast cell stabilisers with topical antihistamines. RESULTS: A meta-analysis of six trials showed that patients using sodium cromoglycate were 17 times (95% confidence interval [CI] = 4 to 78) more likely to perceive benefit compared with those using a placebo, although this estimate may be partially influenced by publication bias. Five trials indicated that those patients using nedocromil were 1.8 times (95% CI = 1.3 to 2.6) more likely to perceive their allergy to be moderately or totally controlled than those using a placebo. Four trials showed that those using antihistamines were 1.3 times (95% CI = 0.8 to 2.2) more likely to perceive a 'good' treatment effect than those using mast cell stabilisers, although this beneficial effect was not statistically significant. Limited evidence suggests that antihistamines might have a faster therapeutic effect compared to mast cell stabilisers. CONCLUSION: Overall, these findings confirm the benefit of topical mast cell stabilisers and antihistamines over placebo for the treatment of allergic conjunctivitis. There is, however, insufficient evidence to recommend the use of one type of medication over another. Treatment preferences should therefore be based on convenience of use (with reduced frequency of instillation for some preparations), patient preference, and costs, especially as important side effects were not reported with any medication.