Results of Duchenne muscular dystrophy family screening in practice: leaks rather than cascades?

McGowan R, Challoner BR, Ross S, Holloway S, Joss S, Wilcox D, Holden ST, Tolmie J, Longman C. Results of Duchenne muscular dystrophy family screening in practice: leaks rather than cascades? Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations in the gene that encodes the protein dystrophin. Approximately 2 of 3 affected boys inherit their mutation from their carrier mother whereupon other female relatives are at risk of carrying the mutation. Female carriers are also at risk of developing cardiomyopathy and regular cardiac screening is recommended. Clinical genetics services offer genetic counselling and carrier tests for consenting relatives of DMD patients known as ‘cascade screening’. We retrospectively analysed data from two genetics centres, West of Scotland and South East Thames where the latter centre operated a computer‐held DMD register. Over the period, 1971–2008, a total of 843 potential carriers, in 195 West of Scotland families, were tested: 16% of 1st degree relatives and 48% of 2nd degree and more distant relatives were not tested. In South East Thames, a total of 1223 potential carriers in 349 families were tested: 49% of 1st degree and 65% of 2nd degree and more distant relatives were not tested. These data are similar to Becker muscular dystrophy/DMD carrier screening results recently reported from the Netherlands. Retrospective results from three countries indicate that despite efforts to offer extended cascade screening, significant numbers of potential carriers of DMD remain unaware of their reproductive and health risks.     

Mechanisms underlying the antireflux action of fundoplication.

The effect of fundoplication on patterns of gastro-oesophageal reflux and the underlying motor mechanisms were investigated in 18 patients with symptomatic reflux. Oesophageal motility and pH were recorded concurrently after a standard meal. Studies were performed preoperatively and from 5 to 27 months after surgery. Fundoplication virtually eliminated reflux in all but three patients. Control of reflux was associated with a 50% fall in the number of transient lower oesophageal sphincter relaxations, a fall in the proportion of transient lower oesophageal sphincter relaxations accompanied by reflux from 47% to 17%, and an increase in the mean residual pressure at the gastro-oesophageal junction during swallow induced lower oesophageal sphincter relaxation from 0.7 mm Hg to 6.0 mm Hg. Basal pressure at the gastro-oesophageal junction rose from 10.9 mm Hg to 14.5 mm Hg, however, there was no correlation between postoperative reflux and basal gastro-oesophageal junction pressure. These findings suggest that the anti-reflux effects of fundoplication result from changes in the mechanical behaviour of the gastro-oesophageal junction that result in incomplete abolition of the high pressure zone during lower oesophageal sphincter relaxation, and reduced triggering of transient lower oesophageal sphincter relaxations.     

Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.     

Acceptability of Smartphone Application-Based HIV Prevention Among Young Men Who Have Sex With Men

Young men who have sex with men (YMSM) are increasingly using mobile smartphone applications (“apps”), such as Grindr, to meet sex partners. A probability sample of 195 Grindr-using YMSM in Southern California were administered an anonymous online survey to assess patterns of and motivations for Grindr use in order to inform development and tailoring of smartphone-based HIV prevention for YMSM. The number one reason for using Grindr (29 %) was to meet “hook ups.” Among those participants who used both Grindr and online dating sites, a statistically significantly greater percentage used online dating sites for “hook ups” (42 %) compared to Grindr (30 %). Seventy percent of YMSM expressed a willingness to participate in a smartphone app-based HIV prevention program. Development and testing of smartphone apps for HIV prevention delivery has the potential to engage YMSM in HIV prevention programming, which can be tailored based on use patterns and motivations for use.