Focal Dermal Hypoplasia Due to a Novel Mutation in a Boy with Klinefelter Syndrome

A boy was born with multiple anomalies, including right hemifacial microsomia, eye abnormalities, syndactyly, right hand ectrodactyly, hypoplastic nails, omphalocele, bladder exstrophy, renal dilatation, and splayed symphysis pubis. The skin was also abnormal, with atrophic skin plaques and areas of telangiectasia along the lines of Blaschko. The karyotype was 47,XXY (Klinefelter syndrome). He was found to have a heterozygous mutation in the PORCN gene. He exhibited the classical features of focal dermal hypoplasia. Fewer than 15% of reported cases are male when it is thought to be due to postzygotic mutation and thus mosaic. This is the first reported boy to have heterozygous mutation for Goltz syndrome who survived due to the extra X chromosome.     

Effect of a GP desktop resource on smoking cessation activities of general practitioners

Objectives To evaluate an intervention aimed at increasing the quantity and quality of brief opportunistic general practitioner (GP) advice to smokers encouraging and supporting quit attempts. Design Randomized controlled trial with two groups: (1) control and (2) GP desktop resource (GDR). Smoking cessation activities of GPs were assessed by an independent postal survey 1 month after distribution of resource. Subjects and setting One hundred and seven GPs in West Dorset. Main outcome measures GPs’ self‐reported rates of advising and counselling smokers on cessation over the previous week. Results The rate of opportunistic advice per week in the GDR group was 4.9 (SD = 4.1), compared with 2.8 (SD = 1.8) in the control group, F = 8.2, p = 0.0025, one‐tailed. The rate of giving counselling was also higher 2.2 (SD = 3.2) in the intervention group versus 1.0 (SD = 1.4) in the control group, F = 4.0, p = 0.025, one‐tailed. The proportion who had recommended or prescribed NRT was greater, although not significantly (54% versus 46%, Fisher’s exact p = 0.1, one‐tailed). Conclusions The findings indicate that the GDR can increase the rate of delivery of opportunistic advice and provision of counselling. Given the importance of this activity, a larger trial appears to be warranted to examine the long‐term effect and the effect on cessation rates in patients.     

Improving the prevention and management of chronic disease in low-income and middle-income countries: a priority for primary health care

The burden of chronic diseases, such as heart disease, cancer, diabetes, and mental disorders is high in low-income and middle-income countries and is predicted to increase with the ageing of populations, urbanisation, and globalisation of risk factors. Furthermore, HIV/AIDS is increasingly becoming a chronic disorder. An integrated approach to the management of chronic diseases, irrespective of cause, is needed in primary health care. Management of chronic diseases is fundamentally different from acute care, relying on several features: opportunistic case finding for assessment of risk factors, detection of early disease, and identification of high risk status; a combination of pharmacological and psychosocial interventions, often in a stepped-care fashion; and long-term follow-up with regular monitoring and promotion of adherence to treatment. To meet the challenge of chronic diseases, primary health care will have to be strengthened substantially. In the many countries with shortages of primary-care doctors, non-physician clinicians will have a leading role in preventing and managing chronic diseases, and these personnel need appropriate training and continuous quality assurance mechanisms. More evidence is needed about the cost-effectiveness of prevention and treatment strategies in primary health care. Research on scaling-up should be embedded in large-scale delivery programmes for chronic diseases with a strong emphasis on assessment.     

Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence

Background:

Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D₂-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D₂/D₃ receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.

Methods:

Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [¹⁸F]fallypride.

Results:

MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D₂/D₃ receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D₂/D₃ receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).

Conclusions:

These results provide the first direct evidence of a link between deficient D₂/D₃ receptor availability and steep temporal discounting. This finding fits with reports that low striatal D₂/D₃ receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.