Anti-pm/scl antibodies in connective tissue disease: Clinical and biological assessment of 14 patients

INTRODUCTION: Anti-PM/Scl antibodies (Anti-PM/Scl) represent a rarely encountered type of antinuclear antibodies. They have mainly been reported in association with idiopathic inflammatory myositis - systemic sclerosis overlap syndromes (also called scleromyositis or sclerodermatomyositis) but also with polymyositis, dermatomyositis and systemic sclerosis without features of overlap syndromes. Studies concerning characteristics of patients with anti-PM/SCl are rare and include small numbers of patients. PATIENTS AND METHODS: Retrospective review of clinical and biological characteristics of 14 patients with anti-PM/Scl in two University Hospitals: one in Belgium (Erasme Hospital, Bruxelles) and one in France (Hautepierre Hospital, Strasbourg). RESULTS: Seven patients were identified in Erasme and 7 in Strasbourg: 5 with systemic sclerosis-(dermato)myositis overlap syndromes, 4 with dermatomyositis, 1 with polymyositis, 3 with systemic sclerosis, 1 with primary Sj?gren's syndrome. The most frequently observed clinical characteristics (85% of patients) were: pulmonary interstitial disease and arthralgia or arthritis. No patient of our series died or developed cancer (mean follow-up:6.1 years). CONCLUSIONS: Our study failed to identify an homogeneous clinical pattern in patients with anti-PM/Scl, except for 2 characteristics shared by 85% of the patients. This lack of homogeneity is in agreement with preceding literature. We confirm the favourable prognosis associated with the presence of anti-PM/Scl, despite the high incidence of interstitial pulmonary disease. The absence of cancer associated with presence of anti-PM/Scl represents a partial explanation. Finally, we report herein the second case of primary Sj?gren's syndrome associated with anti-PM/Scl.     

In vivo evidence that cGMP is the second messenger for atrial natriuretic factor.

cGMP generation has been associated with many of the vascular and endocrine actions of atrial natriuretic factor (ANF) in vitro. To examine the role of cGMP as a second messenger for the renal hemodynamic action of ANF in vivo, we measured glomerular filtration rate (GFR) and cGMP concentration in systemic artery, renal vein, and urine as well as in Bowman's space and end-proximal tubule (by free-flow micropuncture) after administration of ANF. ANF increased GFR by 45% and simultaneously induced a greater than 5-fold increase of cGMP concentration in glomerular ultrafiltrate (Bowman's space) when compared to controls. There was no significant increase in either systemic artery or renal vein cGMP concentration. Thus, the source of increased Bowman's space cGMP is not from the blood via filtration but rather from either glomerular mesangial or epithelial cells, which are not in direct contact with the circulation. Although a small amount of tubular handling of cGMP occurred along the length of the nephron, the augmented cGMP production from the glomerulus accounted for most of the 10- to 12-fold higher urinary cGMP excretion observed after ANF administration. Intrarenal arterial infusion of dibutyryl cGMP, but not dibutyryl cAMP, increased GFR in a dose-dependent fashion (from 10 to 1000 microM) by a mechanism similar to that of ANF--an increase in glomerular hydraulic pressure. Thus, ANF markedly stimulated glomerular production of cGMP, which coincided with a marked increase in GFR. Since dibutyryl cGMP itself was capable of increasing GFR, cGMP is the likely second messenger for ANF in vivo.     

An abnormal platelet membrane lipid composition in patients with low and high blood cholesterol

Platelet lipid composition was determined in subjects with hypercholesterolemia (HC) (9.17 ± 2.15 mmol/L), hypocholesterolemia (HYPOC) (3.29 ± 1.01 mmol/L), and normocholesterolemic controls (NC) (5.29 ± 0.82 mmol/L). Lipid composition was quantitated in washed platelets by measuring platelet cholesterol (C) and phospholipid (PL) content, C/PL molar ratio and platelet PL phosphatidylcholine (PC) to sphingmyelin (SM) ratio. There was a significant increase and a significant decrease in C/PL molar ratio in subjects with HC and HYPOC compared to normals (0.74 ± 0.06 and 0.53 ± 0.06 vs 0.59 ± 0.04, p<0.01, respectively). These alterations were due to a significant change in platelet C content, whereas, platelet PL content was stable. PC/SM ratio was markedly decreased in HYPOC compared to NC (0.80 ± 0.18 vs 2.03 ± 0.18, p<0.01, respectively). These results indicate that blood cholesterol is a major determinant of platelet membrane lipid composition. This effect may be of concern in relation to a possible excess morbidity in patients not only with HC, but also with a low blood cholesterol.     

Transient hyperthyroxinemia in symptomatic hyponatremic patients

Twenty-two patients with severe hyponatremia were divided into 12 patients with and ten without associated neurologic manifestations (groups 1 and 2, respectively). Marked hyperthyroxinemia was demonstrated in seven patients in group 1 but in none in group 2. The triiodothyronine concentration was also higher than normal in two patients in group 1. All serum iodothyronine concentrations in group 1 were significantly higher than in group 2. Thyrotropin and thyroxine-binding globulin levels were normal in both groups. The differences between groups were apparent only in the acute phase, and there were no clinical manifestations of hyperthyroidism. All iodothyronine concentrations returned to normal within two weeks after the correction of the hypo-osmolar disorder. Our results indicate that a transient asymptomatic increase in serum iodothyronine levels occurs during hyponatremia. Thus, thyroid test results should be interpreted cautiously in patients with acute, severe, symptomatic hyponatremia.     

Relapse of a renal inflammatory pseudotumour associated with Wegener's granulomatosis

We report the case of a 32-year-old patient with Wegener's granulomatosis (WG) associated with a (biopsy - proven) renal inflammatory pseudotumour (IPT) of the left kidney treated by a partial nephrectomy, glucocorticoids and immunosuppressive drugs, in whom a relapse of renal IPT was found 6 years after the diagnosis of the first IPT. The originality of this observation lies in the fact that a relapse of IPT has never been described and also in the fact that complete regression of the IPT relapse was obtained with immunosuppressive treatment, while renal IPTs are currently treated by total or partial resection of the kidney. Finally, we discuss the potential benefits of an integrated 18fluorodeoxyglucose PET/CT for the follow-up of WG, since this imaging technique contributed to the management of the present case.     

Sputtered iridium oxide films for neural stimulation electrodes

Sputtered iridium oxide films (SIROFs) deposited by DC reactive sputtering from an iridium metal target have been characterized in vitro for their potential as neural recording and stimulation electrodes. SIROFs were deposited over gold metallization on flexible multielectrode arrays fabricated on thin (15 microm) polyimide substrates. SIROF thickness and electrode areas of 200-1300 nm and 1960-125,600 microm(2), respectively, were investigated. The charge-injection capacities of the SIROFs were evaluated in an inorganic interstitial fluid model in response to charge-balanced, cathodal-first current pulses. Charge injection capacities were measured as a function of cathodal pulse width (0.2-1 ms) and potential bias in the interpulse period (0.0 to 0.7 V vs. Ag|AgCl). Depending on the pulse parameters and electrode area, charge-injection capacities ranged from 1-9 mC/cm(2), comparable with activated iridium oxide films (AIROFs) pulsed under similar conditions. Other parameters relevant to the use of SIROF on nerve electrodes, including the thickness dependence of impedance (0.05-10(5) Hz) and the current necessary to maintain a bias in the interpulse region were also determined.     

Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction

Cytosolic phospholipase A2alpha (cPLA2alpha) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as prostaglandins and leukotrienes. Considerable understanding of cPLA2alpha function has been derived from investigations of the enzyme and from cPLA2alpha-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B4 released from calcium ionophore-activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient's cPLA2alpha genes (p.[Ser111Pro]+[Arg485His; Lys651Arg]). The total PLA2 activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E2, prostaglandin D2, and thromboxane A2 were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA2.     

The risks of a quick fix: a case against mandatory body mass index reporting laws

As the United States addresses obesity, a number of state legislatures are considering laws that require schools to track and report students' body mass index (BMI), a measurement of body weight (weight/height²). This article describes the state level activity on mandatory BMI reporting, offers numerous arguments against this practice, and suggests an alternative approach to promoting health in youth. Mandatory BMI reporting laws place a new and inappropriate responsibility on the schools. Proponents of such laws imply that BMI reporting will have positive outcomes, yet there is virtually no independent research to support this assumption. The authors argue that these laws could do significant harm, including an increased risk for children to develop eating disorder symptoms.