Management of patent ductus arteriosus in preterm infants.

OBJECTIVE: To evaluate the incidence of symptomatic patent ductus arteriosus (PDA) in preterm infants, and the results of the intravenous indomethacine treatment and surgery. METHODS: Among 394 preterm infants (<37 weeks), symptomatic PDA was diagnosed by echocardiography in 51 babies and they were examined retrospectively. All infants were managed conservatively and then IV indomethacine was given to non-responders (n=30). Surgical closure was performed in 12 babies. RESULTS: The incidence of symptomatic PDA in preterm infants was 12.9%: median age: 3 days, mean birth weight: 1434+/-540 g (540-2900g) and mean gestational age (GA) 30.9+/-3.3 weeks (23-37 weeks). With indomethacine, ductal closure was achieved in 70% infants. Early clinical improvement was observed in all cases that underwent surgery and most of them had a low birth weight (<1500 g) and an early gestational age (<32 weeks). None of them died due to operation. CONCLUSION: The incidence of symptomatic PDA is high in preterm infants. Treatment with indomethacine improves ductal closure and is associated with few reversible adverse effects. In the other hand, early clinical improvement and high success rate were achieved after surgery. If indomethacine fails to achieve ductal closure, decision of surgery must be made immediately.     

Antiarrhythmic effect of magnesium sulfate after open heart surgery: effect of blood levels

BACKGROUND: Arrhythmias following cardiac surgery is still a difficult complication to treat. Magnesium sulfate is an effective antiarrhythmic agent with negligible side effects. In this study, effects of magnesium sulfate as a first line antiarrhythmic agent was compared with results of two different well-accepted antiarrhythmic agents. METHODS: One hundred patients with arrhythmia were prospectively randomized to a study and a control group. Lidocaine and amiodarone were accepted as standard antiarrhythmic agents. Patients in study group were received magnesium sulfate routinely as a first line antiarrhythmic agent. Unresponsive arrhythmias were treated with standard antiarrhythmic agents. Control group patients received only standard antiarrhythmics. RESULTS: Magnesium sulfate alone was effective in 56% of the study group whereas 74% of the control group were responsive to standard antiarrhythmics (P=n.s.). In study group, a subgroup analysis according to blood levels of Mg2+ revealed that magnesium sulfate was more effective in patients with low Mg2+ levels (63% for low Mg2+ levels, 55% for normal Mg2+ levels, 36% for high Mg2+ levels) and ventricular arrhythmias (60% for ventricular and 40% for supraventricular arrhythmias), without statistical significance. CONCLUSIONS: Magnesium sulfate is an effective and safe antiarrhythmic agent for arrhythmias developed after open-heart surgery. Its antiarrhythmic effect may relate to its pharmacological properties and unrelated to normalization of the circulating magnesium concentrations. We recommend its use as a first line antiarrhythmic agent without routine measurement of blood levels.     

Clinical features and diagnostic approach to sarcoidosis according to stages

Seventy-seven patients with sarcoidosis followed in our department evaluated retrospectively and the study continued prospectively. Depending on the radiologic findings, 26 (33.8%) of these cases were considered to be in stage 1, 47 (61.0%) were in stage 2 and 4 (5.2%) were in stage 3. Erythema nodosum was found in 29 (37.7%) cases; 15 (51.7%) of whom were stage 1, 13 (44.8%) were stage 2 and 1 (3.4%) was stage 3. There was peripheral lymphadenopathy in 8 (10.4%) cases. Bronchoscopy was performed in 68 cases and 55 found to be normal. BAL was determined in 50 of those to whom bronchoscopy had been performed. Mean BAL lymphocyte rate was found to be 32.2% and it was 36.1% in stage 1, 31.1% in stage 2 and 22.2% in stage 3. Diagnosis of sarcoidosis was confirmed with histopathologic examination in 48 cases and with BAL and other clinical signs in the others. It was confirmed with parenchymal biopsy in 15 cases, with scalene lymph node biopsy in 8 cases, with bronchial mucosa biopsy in 5, with transcranial needle aspiration biopsy in 5, with video-assisted thoracoscopic surgery in 4, with right supraclavicular lymph node biopsy in 3 and with skin biopsy in 2 cases. Tuberculin skin test was performed in 67 cases and was found to be negative in 51 (76.1%). Serum ACE levels were checked in 11 cases and found to be high in 7 of them (63.6%) (mean: 21.9). Two of 55 cases who had neurologic examination, 3 of 60 cases who had fundoscopy were found to have pathologic findings.     

Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis

OBJECTIVE: The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes. METHODS: Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls. RESULTS: In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period. CONCLUSION: Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.     

Microdeletions of ELP4 Are Associated with Language Impairment,Autism Spectrum Disorder,and Mental Retardation

Copy‐number variations (CNVs) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared the presence of small CNVs disrupting the ELP4‐PAX6 locus in 4,092 UK individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridization, with WTCCC controls (n = 4,783). The phenotypic analysis was then extended using the DECIPHER database. We followed up association using an autism patient cohort (n = 3,143) compared with six additional control groups (n = 6,469). In the clinical discovery series, we identified eight cases with ELP4 deletions, and one with a partial duplication of ELP4 and PAX6. These cases were referred for neurological phenotypes including language impairment, developmental delay, autism, and epilepsy. Six further cases with a primary diagnosis of autism spectrum disorder (ASD) and similar secondary phenotypes were identified with ELP4 deletions, as well as another six (out of nine) with neurodevelopmental phenotypes from DECIPHER. CNVs at ELP4 were only present in 1/11,252 controls. We found a significant excess of CNVs in discovery cases compared with controls, P = 7.5 × 10^?3, as well as for autism, P = 2.7 × 10^?3. Our results suggest that ELP4 deletions are highly likely to be pathogenic, predisposing to a range of neurodevelopmental phenotypes from ASD to language impairment and epilepsy.     

Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway

We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.     

Increased soluble FAS suggests delayed apoptosis in familial Mediterranean fever complicated with amyloidosis

OBJECTIVE: Interactions of the FAS with FAS ligand have been proposed as a major regulatory mechanism of immune homeostasis. Soluble FAS (sFAS) acts as a competitive antagonist to FAS, thereby inhibiting FAS mediated apoptosis. sFAS concentrations have been studied in various autoimmune diseases, with controversial results. In this cross sectional study, we investigated the role of sFAS protein in attack-free patients with familial Mediterranean fever (FMF) with and without amyloidosis. METHODS: Twelve FMF patients without amyloidosis (male/female: 7/5; median age 23.5 yrs, range 17-38), 10 FMF patients with amyloidosis (male/female: 5/5; median age 41.5 yrs, range 33-51), and 14 controls (male/female: 6/8; median age 46 yrs, range 38-57) were enrolled in the study. Serum sFAS concentrations were studied by ELISA. RESULTS: Median serum sFAS concentrations were 4630 (2580-12,270), 1338 (453-3240), and 3430 (2110-5960) pg/ml in FMF patients without amyloidosis, FMF patients with amyloidosis, and controls, respectively. Intergroup differences were all statistically significant (p < 0.05). CONCLUSION: Elevated serum sFAS concentrations in attack-free FMF patients might be due to dysregulated apoptosis of polymorphonuclear leukocytes together with the ongoing subclinical inflammatory activity. On the other hand, decreased sFAS concentrations could contribute to the augmented apoptosis together with the alterations in immune response leading to the amyloidosis.     

Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders

Objectives. Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804–815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412–1418) and BDNF regulates the expression of the dopamine D₃ receptor. Objective. We examined the role of the BDNF and DRD3 genes in suicide. Methods. We analysed four tag single-nucleotide polymorphisms (SNPs) in BDNF and 15 SNPs in the D₃ receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of European ancestry (N = 188). Results. In this sample, we found a possible interaction between the BDNF Val66Met and DRD3 Ser9Gly SNPs in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66Met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (Bonferroni P < 0.05). However, we could not replicate this finding in samples from other psychiatric populations. Conclusions. Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.