Genetic and environmental factors influencing fasting serum adiponectin in Hispanic children

CONTEXT: Because of its antiinflammatory and insulin-sensitizing properties, adiponectin may play a role in the development of cardiovascular disease and type 2 diabetes. OBJECTIVES: The aims of these analyses were: 1) to estimate the heritability of fasting serum adiponectin; 2) to evaluate the effects of age, sex, and body composition on fasting serum adiponectin; 3) to test for associations between fasting serum adiponectin and diet, fitness, energy expenditure, and fat oxidation; and 4) to determine the relationships between fasting serum adiponectin, insulin and lipids, and blood pressure in Hispanic children. DESIGN: Genetic and environmental factors influencing fasting serum adiponectin were investigated in a cohort of children participating in the VIVA LA FAMILIA Study in 2000-2005. SETTING: This study was performed at the Children's Nutrition Research Center. PARTICIPANTS: The study participants were 805 Hispanic nonoverweight and overweight children, ages 4-19 yr. MAIN MEASURE: The main measure of the study was fasting serum adiponectin. RESULTS: The heritability of serum adiponectin was 0.93 +/- 0.10 (P = 2.4 x 10(-40)). Adiponectin differed by age (P = 0.001), sex (P = 0.04), and weight (P = 0.001) status. Adiponectin levels declined with age, in association with changes in sex hormones and growth factors. Adiponectin was not associated with macronutrient intake, fitness, 24-h energy expenditure, or fat oxidation. Controlling for age, sex, and percent fat mass, adiponectin was inversely associated with homeostasis model of insulin resistance, triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (P = 0.001). Significant positive genetic correlations were detected between adiponectin and total cholesterol (rho(G) = 0.19), HDL-C (rho(G) = 0.32), low-density lipoprotein cholesterol (rho(G) = 0.24), and IGF-binding protein-1 (rho(G) = 0.39), and negative genetic correlations were detected between adiponectin and leptin (rho(G) = -0.30), TG (rho(G) = -0.21), TG/HDL-C (rho(G) = -0.33), and IGF-binding protein-3 (rho(G) = -0.32), indicating shared genetic components in their expression. CONCLUSION: The high heritability of adiponectin and pleiotropy seen between adiponectin and leptin, growth factors, and lipids may play a role in the pathogenesis of cardiovascular disease and type 2 diabetes in overweight Hispanic children.     

Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging.

AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery.     

Value of automated segmental motion analysis in the assessment of aortic stenosis severity

BACKGROUND AND AIMS OF THE STUDY: Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity. METHODS: Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated. RESULTS: A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p <0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve area < or =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index >0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively. CONCLUSION: The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.     

Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.     

The spectrum of computerized tomography (CT) findings in central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii in immunocompetent children

Cranial CT scans of eleven immunocompetent children with central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii were retrospectively reviewed. These children had an average age of 8.8 years and positive culture for C. n. var. gattii in cerebrospinal fluid. The most common signs and symptoms were headache, fever, nuchal rigidity, nausea and vomiting. No normal cranial CT was detected in any patient. Hypodense nodules were observed in all patients. The remaining scan abnormalities were as follows: nine had diffuse atrophy, six had hydrocephalus, and five had hydrocephalus coexistent with diffuse atrophy.     

The first record of American visceral leishmaniasis in domestic cats from Rio de Janeiro, Brazil

This paper is the first to report visceral leishmaniasis in domestic cats (Felis catus domesticus) from an endemic area in Rio de Janeiro state, Brazil. A relatively high seroprevalence of 25% was observed although none of them have presented any symptom. Our results support the observation of previous authors, suggesting that cats may be considered as alternative domestic hosts of visceral leishmaniasis and should be included in serological investigations performed in endemic areas.     

A soluble mouse brain splice variant of type 2alpha corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity

Peptides of the corticotropin-releasing factor (CRF) family signal through the activation of two receptors, CRF receptor type 1 (CRFR1) and type 2 (CRFR2), both of which exist as multiple splice variants. We have identified a cDNA from mouse brain encoding a splice variant, soluble CRFR2alpha (sCRFR2alpha), in which exon 6 is deleted from the gene encoding CRFR2alpha. Translation of this isoform produces a predicted 143-aa soluble protein. The translated protein includes a majority of the first extracellular domain of the CRFR2alpha followed by a unique 38-aa hydrophilic C terminus resulting from a frame shift produced by deletion of exon 6. By using RT-PCR and Southern hybridization, the relative mRNA expression levels of full-length (seven transmembrane domains) CRFR2alpha and the soluble form (sCRFR2alpha) in the mouse brain were measured with a single reaction. The results demonstrate high levels of expression of sCRFR2alpha in the olfactory bulb, cortex, and midbrain regions. A rabbit antiserum raised against a synthetic peptide fragment encoding the unique C terminus revealed specific sCRFR2alpha immunoreactivity in mouse brain slices by immunohistochemistry and in extracts of brain regions by RIA. Interestingly, the sCRFR2alpha immunoreactivity distribution closely approximated that of CRFR1 expression in rodent brain. A protein corresponding to sCRFR2alpha, expressed and purified from either mammalian or bacterial cell systems, binds several CRF family ligands with low nanomolar affinities. Furthermore, the purified sCRFR2alpha protein inhibits cellular responses to CRF and urocortin 1. These data support a potential role of the sCRFR2alpha protein as a possible biological modulator of CRF family ligands.     

Blood pressure-lowering efficacy of amiloride versus enalapril as add-on drugs in patients with uncontrolled blood pressure receiving hydrochlorothiazide

A large proportion of patients with hypertension need a second drug to reach satisfactory control of blood pressure (BP), but there are few well-designed controlled trials comparing the efficacy of drugs added as a second option. In a double-blind randomized clinical trial, 82 patients with uncontrolled BP, receiving hydrochlorothiazide 25 mg daily, were selected to receive amiloride 2.5-5 mg/day (n = 39) or enalapril 10-20 mg/day (n = 43). Ambulatory blood pressure monitoring (ABPM) was done before and after 12-weeks of treatment. Office BP was measured in the 4(th), 8(th), and 12(th) weeks. The doses of amiloride and enalapril were doubled in the fourth week, and propranolol was added in the 8th week if office BP was above 140/90 mm Hg. There was a greater BP reduction in patients treated with enalapril. The ABPM delta values between the groups were 3.6 +/- 2.2, 3.9 +/- 2.2, and 1.1 +/- 2.7 mmHg for 24-h, daily, and nightly systolic blood pressure, respectively, favoring enalapril. For diastolic blood pressure (DBP), the deltas were 1.7 +/- 2.0, 3.2 +/- 1.5, and 1.2 +/- 1.9 mmHg, respectively (p = 0.039 for daily DBP). Office SBP decreased more and sooner in patients allocated to enalapril (p = 0.003). More patients taking amiloride required propranolol to control BP (p = 0.035). Potassium increased 0.3 mEq/L on the average in both groups. Cough, albeit predominantly mild, was reported more frequently by participants treated with enalapril. We conclude that enalapril is more effective than amiloride to lower BP of patients on hydrochlorothiazide with uncontrolled BP.     

The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya,western Kenya

In spite of increasing resistance, chloroquine remains the primary drug for treatment of malaria in most sub-Saharan African countries. We evaluated the effect of drug treatment policy on the case-fatality rates of children, adjusting for differing distributions of malaria and severe anemia. In 1991, 63% of children were treated with chloroquine while the remaining 37% were treated with a regimen that would eliminate and clear parasitemia. Case-fatality rates were 13% and 4.1%, respectively; the proportion of deaths attributable to chloroquine treatment was 69%. The trend in case-fatality rates for malaria decreased as an increasing proportion of children received an effective treatment regimen; adjusted malaria case-fatality rates were 5.1%, 3.6%, and 3.3% in 1992, 1993, and 1994, respectively, when 85% of children in 1992 and 97% of children in 1993-1994 received effective therapy. These 4 years of data provide strong evidence that continued use of chloroquine in areas with resistance is contributing to excess Plasmodium falciparum-related deaths.     

Complete atrioventricular block in a woman with systemic lupus erythematosus

The complete atrioventricular (AV) heart block is a rare complication in the course of systemic lupus erythematosus. We describe a case of a young woman with systemic lupus erythematosus and lupus cardiomyopathy who was admitted into our hospital with a syncopal attack showing on the electrocardiogram a paroxysmal complete AV heart block. The syncopal attack was resolved with a pacemaker implantation.