Publics and biobanks: Pan-European diversity and the challenge of responsible innovation

This article examines public perceptions of biobanks in Europe using a multi-method approach combining quantitative and qualitative data. It is shown that public support for biobanks in Europe is variable and dependent on a range of interconnected factors: people''s engagement with biobanks; concerns about privacy and data security, and trust in the socio-political system, key actors and institutions involved in biobanks. We argue that the biobank community needs to acknowledge the impact of these factors if they are to successfully develop and integrate biobanks at a pan-European level.     

Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor

A boy whose chronic granulomatous disease (CGD) manifested in infancy, and whose elder brother had died at 7 years of age, had phagocytes with complete lack of functional cytochrome B-245 and which could not be induced by interferon gamma to achieve adequate staphylococcal killing. He underwent an elective displacement bone marrow transplant from a volunteer unrelated donor at the age of 8 months. This has achieved 100% replacement of the CGD granulocytes by those of the normal volunteer and the boy has since had a normal childhood for 3 years. Six previous transplants for CGD are briefly reviewed and illustrate that the host abnormal marrow must be completely displaced using an adequate dose of busulphan to ensure 100% stable engraftment of the donor's marrow and that this is best done under elective conditions before septic foci and irreversible organ damage have occurred. Criteria need to be developed to identify early those patients likely to have severe morbidity.     

Colposcopic genital findings in prepubertal girls assessed for sexual abuse

After the introduction of the colposcope for the examination of children suspected of being sexually abused in Leeds, a study was undertaken to describe the findings in detail. A total of 109 consecutive prepubertal girls, mean age 70.4 months were assessed including colposcopic genital and anal examination, and peer group review of reports and photographs. Fifty nine children had signs consistent with blunt force penetrating trauma (hymenal transection/major notch, scar, or hymenal attenuation). Transections were encountered most commonly at 6 o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh abduction only and in 47 the hymenal orifice transverse diameter was greater than 4 mm on labial separation. Overall, physical findings were commonly present and in only two cases were no signs recorded. Non-specific and frequent findings included patterns of labial and introital reddening. Supportive hymenal signs including swelling, rounding of edge, thickening, distortion, and loss of symmetry were common. Labial fusion was present in 20. Urethral dilatation with labial separation was noted in 14. Physical findings including normality are consistent with abuse and even minor anogenital signs as well as negative findings should be documented. Colposcopy and photography are valuable tools in peer review, teaching, and case management.     

Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years

OBJECTIVE: To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years. DESIGN: Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months. SUBJECTS: 290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis. MAIN OUTCOME MEASURES: Age and sex standardised z scores for height, weight, and body mass index. RESULTS: 459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height. CONCLUSIONS: Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years.     

Outcome of Displacement Bone Marrow Transplantation for Inborn Errors of Metabolism

The concept of displacement bone marrow transplantation arose from our work at Westminster 1970–1973, by which time we had extended the donors from matched siblings to other family and unrelated donors. DBMT is not a panacea, but can be applied to about 7% of understood inborn errors, where it is possible to devise in vitro tests to predict in vivo donor effects. Its use to install donor bone marrow as a component factory for the life of the recipient, and the importance of immunoprophylaxis are summarised. Worthwhile correction has been achieved for 48 previously fatal genetic diseases, partial correction for another five, but there has been failure for three diseases. Some 80% of our patients were not found in known families and could not have been prevented.     

6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists

Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.