Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation-induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.

Reapplix ApS.

Bilateral inferior petrosal sinus sampling for ACTH with corticotrophin releasing hormone stimulation has become an established test in differentiating pituitary Cushing's disease from Cushing's syndrome due to ectopic ACTH secretion. We report two patients with Cushing's disease who developed thromboembolic complications soon after inferior petrosal sinus sampling. We discuss the possible mechanisms leading to this complication in a syndrome in which thromboembolic complications are well recognized and highlight the need for consideration of prophylactic anticoagulation.

Objective-To audit the standards of secondary prevention of coronary heart disease in postmyocardial infarction patients. Design-Follow up audit, one year after acute admission with myocardial infarction. Setting-University Hospital. Subjects-For the initial admission, 153 patients were audited, with 84 patients contacted one year later. Demographic data, treatment status, and cholesterol levels were analysed both on admission and at follow up. Interventions-Total cholesterol was checked at the audit time either in the hospital or in the doctor's surgery. Main outcome measures-Statin doses and cholesterol levels. Results-Ninety six per cent of patients had their lipid profile performed on admission. Eighty three per cent of the patients with total cholesterol > 5 mmol/l were discharged from the hospital on lipid lowering medication. Forty five per cent of the subjects who were followed up had cholesterol levels > 5 mmol/l at 1 year. There was a disproportionate use of low doses of statins (lower than those shown in eVective trials: simvastatin 20 to 40 mg, pravastatin 40 mg) with a third of all patients on medication not achieving the targets at one year. Conclusion-There was a major improvement in the proportion of patients started on treatment compared with figures reported by previous studies. However, the titration of the statin doses to achieve the targets is still unsatisfactory. (Heart 2000;84:e3)

Peutz±Jeghers syndrome, an autosomal dominant condition in which hyperpigmented macules involving the perioral area of the face, mucous membranes, hands and feet are associated with polyps of the gastrointestinal tract and an increased risk of malignancies. The differential diagnosis also includes leopard syndrome, centrofacial lentiginosis and Carney's syndrome, all of which have associated internal abnormalities such as obstructive cardiomyopathy, cardiac myxomas, deafness, mental retardation and bone defects. These abnormalities need to be excluded by clinical examination and non-invasive tests such as electrocardiography and echocardiography. In 1989 O'Neill and James reported ten patients of black colour with autosomal dominant transmission of hyperpigmented macules on the face, hands, feet and buttocks but sparing mucous membranes with no associated internal abnormalities 1. Our patient has all the features of the described inherited patterned lentiginosis in blacks.