Cardiac 123I-MIBG scintigraphy and arrhythmic risk in left ventricular noncompaction

Left ventricular noncompaction is an unusual but increasingly recognized cardiomyopathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhythmias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC.     

History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia

Protein C (PC) deficiency is an autosomal dominant inherited disorder associated with spontaneous and recurrent thrombotic events. Factor V Leiden (FVL) increases the risk of thrombosis in PC-deficient type I families. We have investigated the relationship between PC deficiency genotype and clinical phenotype in a large four-degree Italian family followed since 1988. Methods: PC activity and antigen levels were quantified; sequencing of PC DNA was performed to identify polymorphism. FVL and factor II (G20210A) polymorphism were screened. Results: PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type. Of 15, eight were heterozygous for FVL. The two subjects with PC < 6%, homozygous for Arg32Cys and heterozygous for FVL, suffered from thrombosis during childhood. Of 11, six subjects with PC deficiency and heterozygous for FVL showed the first thrombosis at an age between 21 and 54. None of the five PC-deficient subjects, who were wild type for FVL, showed thrombosis. Two subjects with PC > 70%, both heterozygous for FVL developed thrombosis in the presence of another risk factor. This study suggests that FVL and PROC mutations increase the risk of thrombosis in subjects with PC deficiency, which could be considered as a 'variable' risk factor. The thrombosis-prone PC-deficient families carry additional risk factors for thrombosis.     

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.     

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.     

Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review

Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg^-1 day^-1 with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren’s syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.     

Predictors of right ventricle dysfunction after anterior myocardial infarction

Background

Regardless significant therapeutic advances, mortality and morbidity after myocardial infarction (MI) are still high. For a long time, the importance of right ventricle (RV) function has been neglected. Recently, RV dysfunction has also been associated with poor outcomes in the setting of heart failure. The shape, location, and contraction conditions make the RV chamber assessment technically challenging.

Methods

Our study identified clinical characteristics and left ventricle (LV) echocardiographic data performed 3-5 days after MI that could be associated with RV dysfunction (RV fractional area change [FAC] < 35%) 6 months after MI.

Results

The RV dysfunction group consisted of 11 patients (RV FAC 29.4% ± 5.2) and the no RV dysfunction group of 71 patients (RV FAC 43.7% ± 5.1); (P < 0.001). Both groups presented the same baseline clinical characteristics. Left atrium (LA), interventricular septum (IVS), and left ventricular posterior wall (LVPW) were larger in RV dysfunction than in no RV dysfunction. Conversely, E wave deceleration time (EDT) was lower in RV dysfunction when compared with no RV dysfunction. Left atrium_adj (adjusted by gender, age, infarct size, and body mass index) (odds ratio [OR], 1.22; confidence interval [CI], 1.016-1.47; P = 0.032), interventricular septum_adj (OR, 1.49; CI, 1.01-2.23; P = 0.044), and E wave deceleration time_adj (OR, 0.98; CI, 0.97-0.98; P = 0.029) assessed soon after MI predicted RV failure after 6-months.

Conclusions

LV diastolic dysfunction, resulting from anterior MI and assessed 3-5 days after the event, may play an important role in predicting RV dysfunction 6 months later.     

Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells

Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3?h) and long term (24?h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO₂ increased in 1?h and the conversion of glucose to lipids increased at 3?h. In addition, glycine oxidation to CO₂ and conversion of glycine to lipids increased at 1?h, whereas the incorporation of glycine in proteins decreased at 1 and 3?h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24?h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.