Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk

It has recently been suggested that the low-frequency c.136-14_136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14_136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14_136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease.     

Added value of early 18F-FDOPA PET/CT acquisition time in medullary thyroid cancer

The aim of this study was to determine whether early acquisition of F-fluorodihydroxyphenylalanine (F-FDOPA) PET/CT could improve the detection of medullary thyroid cancer (MTC). We retrospectively compared early (median time: 15 min) and delayed (median time: 94 min) acquisitions, positive on at least one of the two phases, in 15 dual-phase F-FDOPA PET/CT examinations performed on 14 patients referred for initial staging (one examination), suspected recurrence (eight examinations) or restaging of MTC (six examinations). Among the 14 true-positive (TP) examinations, more lesions (51 vs. 43) or more intense uptake (mean SUVmax=4 vs. 2.4, P<0.05) was observed on early versus delayed phases, regardless of the anatomical site of disease (lymph node, liver or bone). The only false-positive case, a reactive lymph node, was visible only on the delayed acquisition. Early acquisition appeared to be more appropriate in the detection of MTC lesions compared with acquisition at 60 min or later.     

Development and Evaluation of a Dipstick Diagnostic Test for Neisseria meningitidis Serogroup X

The emergence of Neisseria meningitidis serogroup X (NmX) in the African meningitis belt has urged the development of diagnostic tools and vaccines for this serogroup, especially following the introduction of a conjugate vaccine against N. meningitidis serogroup A (NmA). We have developed and evaluated a new rapid diagnostic test (RDT) for detecting the capsular polysaccharide (cps) antigen of this emerging serogroup. Whole inactivated NmX bacteria were used to immunize rabbits. Following purification by affinity chromatography, the cpsX-specific IgG antibodies were utilized to develop an NmX-specific immunochromatography dipstick RDT. The test was validated against purified cpsX and meningococcal strains of different serogroups. Its performance was evaluated against that of PCR on a collection of 369 cerebrospinal fluid (CSF) samples obtained from patients living in countries within the meningitis belt (Cameroon, Côte d''Ivoire, and Niger) or in France. The RDT was highly specific for NmX strains. Cutoffs of 10⁵ CFU/ml and 1 ng/ml were observed for the reference NmX strain and purified cpsX, respectively. Sensitivity and specificity were 100% and 94%, respectively. A high agreement between PCR and RDT (Kappa coefficient, 0.98) was observed. The RDT gave a high positive likelihood ratio and a low negative likelihood (0.07), indicating almost 100% probability of declaring disease or not when the test is positive or negative, respectively. This unique NmX-specific test could be added to the available set of RDT for the detection of meningococcal meningitis in Africa as a major tool to reinforce epidemiological surveillance after the introduction of the NmA conjugate vaccine.     

Cyclic AMP-phosphodiesterases inhibitor improves sodium excretion in rats with cirrhosis and ascites.

BACKGROUND: The mechanisms responsible for renal dysfunction and sodium retention in cirrhosis remain unclear. Cyclic AMP (cAMP) regulates sodium reabsorption in the proximal nephron. This study investigates the role of cAMP metabolism in renal dysfunction in cirrhosis. METHODS: Renal function was studied by the clearance technique in anesthetized control and cirrhotic rats with or without ascites. cAMP phosphodiesterase (PDE) activity was measured in the renal cortex in vitro. Moroever, the effects on renal function of the intravenous administration of cAMP and rolipram, a powerful and specific cAMP-PDE4 inhibitor, were evaluated. RESULTS: In control and in non-ascitic cirrhotic rats, cAMP administration significantly increased sodium and phosphate excretions, but did not change these excretions in cirrhotic rats with ascites. cAMP-PDE activity was higher in ascitic than in control rats (P < 0.05). Rolipram infusion significantly increased sodium and phosphate excretion only in cirrhotic rats with ascites. CONCLUSION: These results suggest that increased renal cAMP-PDE activity is responsible for resistance to the natriuretic effects of cAMP in cirrhosis and plays a role in the development of ascites.     

Adherence to nCPAP in patients with coronary disease and sleep apnea without sleepiness

Many patients with obstructive sleep apnea (OSA) do not have sleepiness and adherence to nasal continuous positive airway pressure (nCPAP) is unknown when this treatment is primarily recommended for a cardiovascular concern. The aim of this study was to determine the adherence to nCPAP in patients with coronary artery disease (CAD) and OSA without sleepiness. nCPAP was recommended in 75 patients with CAD and OSA, 29 without and 46 with sleepiness. The daily use of nCPAP and changes in sleepiness (Epworth Sleepiness Scale), in other OSA symptoms and in SF-36 quality-of-life questionnaires were evaluated at 1 yr of follow-up. Sixty-seven patients (89%) were still using nCPAP at the end of follow-up. The absence of sleepiness at diagnosis did not imply a greater number of nCPAP refusals and nCPAP adherence was similar in both groups, 5.1 (1.5) h in patients without versus 5.4 (1.6) h in patients with sleepiness. In patients with sleepiness at diagnosis, the use of nCPAP was associated with reduced sleepiness and improvement in the OSA symptoms and quality-of-life questionnaires; in contrast, only the symptoms questionnaire improved in patients without sleepiness. In conclusion, in our experience adherence to nCPAP treatment in patients with CAD and OSA is not influenced by the absence of sleepiness.     

Acute respiratory failure after interferon-gamma therapy of end-stage pulmonary fibrosis

Interferon (IFN)-gamma was recently proposed as a treatment for idiopathic pulmonary fibrosis. We report on four patients who developed acute respiratory failure with new alveolar opacities after 2 (two patients), 6, and 35 injections of IFN-gamma-1b. All four patients had advanced idiopathic pulmonary fibrosis (total lung capacity less than 45% predicted or carbon monoxide diffusion capacity less than 30% predicted), and two patients had familial pulmonary fibrosis. No other cause of deterioration was found. Refractory hypoxemia led to death in three cases and to lung transplantation in one case. Pathologic studies in two patients showed diffuse alveolar damage lesions with preexisting usual interstitial pneumonia. These cases suggest that IFN-gamma therapy can induce an acute respiratory failure in patients with end-stage idiopathic pulmonary fibrosis.