[Anti TNF-alpha treatment of a refractory polymyositis]. / Traitement d'une polymyosite réfractaire par anti TNF-alpha.

INTRODUCTION: Anti TNF-alpha agents may represent a possibility of treatment in cases of refractory polymyositis. CASE REPORT: We report a case of polymyositis refractory to corticosteroids and immunosuppressive agents in whom adjunction of infliximab led to a mild and transient improvement, and a secondary improvement after discontinuation of the treatment. DISCUSSION: In the reported cases of polymyositis treated with infliximab or etanercept a short-term response was seen in 9 out of 11 cases. Adverse events of the treatment are mentioned, and should be taken into account in the decision of treatment.

[Hypercalcemia of double origin: association of multiple myeloma and ectopic parathyroidal adenoma]. / Une hypercalcémie d'origine double: association myélome et adénome parathyroïdien ectopique.

INTRODUCTION: Multiple myeloma and primary hyperparathyroidism are two causes of hypercalcemia. This association has already been described to be not casual, despite their link is still unknown. OBSERVATION: We describe a 68 years old woman, without notable background, was admitted for low back pain. Biology showed an IgG Kappa multiple myeloma (stade 3) and an hypercalcemia without renal failure. Hypercalcemia was difficult to control with bisphosphonate and calcitonin. At first, there was also an hypophosphoremia and a high parathormone level (287 pg/ml). Imaging showed spread myeloma impairment and a right paramediastinal tissular mass. Biopsy diagnosed an ectopic parathyroidal adenoma. DISCUSSION: Multiple myeloma and primary hyperparathyroidism can be associated. They are often revealed by an hypercalcemia difficult to control or refractory to the treatment. Hypophosphoremia can suggest the diagnosis of hyperparathyroidism. Both this observation and litterature (about twenty case reports) suggest that this double diagnosis should be systematicly evoked and explored by an assay of parathormone and a seric proteins electrophoresis in all hypercalcemia. CONCLUSION: Multiple myeloma and parathyroidal adenoma should be both explored in all hypercalcemia, because they can be associated.

Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes).

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.

Pathways for the oxidation of sarin in urban atmospheres.

The nerve agent sarin has recently been deployed by terrorists in a major city. The molecule is volatile and made its way to many victims by passing as vapor through a highly reactive medium. Here we estimate rates and pathways for the removal of gas phase sarin from a generalized urban atmosphere. Only information from the open scientific literature is used. By structure reactivity comparisons with the organophosphorus pesticides, hydroxyl radical hydrogen abstraction may occur in as little as one hour. Decomposition of side chains after hydroxyl attack leads to organic oxygenates which preserve the phosphonofluoridate and so toxicity. The aqueous aerosol surface is contacted in minutes and offers access to a range of dissolved nucleophiles. Substitution displaces the fluoride leaving group, giving safe phosphoric acid analogs. Because of uncertainties in the electron distribution and in aqueous decay mechanisms, the time constants must be viewed as lower limits.

Improved metabolic control decreases platelet activation markers in patients with type-2 diabetes.

BACKGROUND: Cardiovascular disease is associated with platelet dysfunction in patients with diabetes. Hyperglycaemia is known as an independent risk factor for micro- and macrovascular complications, and improvement of metabolic control has shown beneficial effects on diabetic late complications. Our study attempts to clarify the effect of improved metabolic control on platelet activation markers in patients with type-2 diabetes. MATERIALS AND METHODS: Thirty patients were studied at baseline and 3 months after improvement of metabolic control and compared with an age-matched nondiabetic control group. Platelet activation markers (CD31, CD36, CD49b, CD62P and CD63) were assessed by flow cytometry analysis. RESULTS: Significantly more activated platelets were detected in patients with diabetes compared with controls. After 3 months' improvement of metabolic control, a significant decline of all platelet activation markers except CD36 was noted. Furthermore a significant correlation between CD62P, CD63 and HbA(1c) levels was observed. CONCLUSIONS: We conclude therefore that improvement of metabolic control has a beneficial effect on platelet activation. This may have an implication in the pathogenesis of vascular disease in patients with type-2 diabetes.

Effects of losartan on cerebral and ocular circulation in healthy subjects.

AIMS: The introduction of specific inhibitors of AT1 receptors, such as losartan, has enabled the investigation of the renin-angiotensin-system (RAS) in humans in vivo. We studied the role of the RAS in the cerebral and ocular circulation in healthy subjects. Haemodynamic effects of orally administered losartan were investigated with non-invasive methods. METHODS: In a placebo-controlled randomized, double-blind two way crossover design losartan (100 mg orally) or placebo was administered in 10 healthy subjects. The effect of losartan was studied at hourly intervals for 8 h. In addition, the effect of losartan on haemodynamic changes induced by exogenous angiotensin II (Ang II) was assessed. Blood flow velocities in the ophthalmic and the middle cerebral artery (OA, MCA) were measured with Doppler sonography. Pulsatile choroidal blood flow was estimated with laser interferometric measurement of fundus pulsation. RESULTS: Losartan significantly increased fundus pulsation amplitude (+11%, 95% CI: 5 to 16% P<0.0001), tended to increase resistive index in the ophthalmic artery (+12%, 95% CI: 0 to 23%) and tended to decrease mean arterial pressure (-15%, 95% CI: -23 to -1%). Ang II induced effects on cerebral, ocular and systemic haemodynamics were prevented by preceding administration of losartan. CONCLUSIONS: The present data suggest that Ang II is not a major determinant of cerebral and ocular blood flow in vivo. The observed changes in cerebral and ocular haemodynamic parameters after losartan administration reflect effects on systemic blood pressure.