Effect of weight loss on QTc dispersion in obese subjects.

OBJECTIVE: Increased QTc dispersion is a predictor for ventricular arrhythmias. The aim of this study was to investigate whether QTc dispersion decreases after weight loss program with diet and medical treatment. METHODS: Total 30 (24 women and 6 men, mean age: 44+/-8 years) obese subjects who lost at least 10% of their original weight after 12 week weight loss program were included in present study. Obesity was defined as > or =30 kg/m(2) of body mass index (BMI). Normal weight was defined as < or = 25 kg/m(2) of BMI. RESULTS: After 12 week weight loss program, BMI decreased from 42+/-5 kg/m(2) to 36+/-4 kg/m(2) (p<0.001) and mean weight of obese subjects decreased from 110+/-17 kg to 95+/-15 kg (p<0.001). The mean amount of weight loss was 14.5+/-5.0 kg (range 9-32 kg). The average percent of weight loss was 13% (10.0%-20.3%). Maximum QTc interval (from 446+/-19 ms to 433+/-27 ms, p=0.024) and QTc dispersion (from 66+/-18 ms to 52+/-25 ms, p=0.024) significantly decreased after weight loss program. A statistically significant correlation was found between decrease in level of QTc dispersion and amount of weight loss (r=0.487, p=0.007). CONCLUSION: Substantial weight loss in obese subjects is accompanied by significantly decreased QTc dispersion. The degree of QTc dispersion reduction is associated with amount of weight loss.     

Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin

Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. I/R injury is believed to be a consequence of free radical generation in the heart especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and pharmacological concentrations have been shown to reduce the I/R-induced cardiac damage in isolated rat hearts. However, the physiological role of melatonin in the prevention of this damage is unknown. Rats were pinealectomized or sham-operated (control) 2 months before the I/R studies. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct size, expressed as the percentage of the risk zone, was found significantly higher in pinealectomized rats (49+/-3.4%) than in the control group (34+/-3.6%). Melatonin administration (4 mg/kg, either before ischemia or reperfusion) to pinealectomized rats significantly reduced the infarct size values and returned them to the control values. On the other hand, melatonin administration (4 mg/kg) to sham-operated rats failed to attenuate significantly the I/R-induced infarct size. These results suggest that physiological melatonin concentrations are important in reducing the I/R-induced myocyte damage, while pharmacological concentrations of melatonin did not add to the beneficial effect. As melatonin levels have been reported to decrease with age, melatonin replacement therapy may attenuate I/R-induced myocardial injury, especially in older patients.     

Purification and in vitro toxicity of gamma amanitin

We aimed to obtain gamma amanitin with high purity through a purification process and compare toxic effects of alpha, beta, and gamma amanitin. Specific concentrations of the toxins (25, 10, 1, and 0.1?μg/mL) were applied to the C3A human hepatocytes. A MTT test was performed to determine the level of toxicity. Alpha amanitin showed a higher toxicity in 48?h while the lowest toxicity was observed in beta amanitin. The toxicity level of gamma amanitin was found between the alpha and beta amanitin toxicity. Our method is suitable for obtaining gamma amanitin with high purity (>99%) as well as for obtaining alpha amanitin and beta amanitin. Gamma amanitin has been shown to have equal responsibility for toxicity as alpha amanitin in amanita poisoning.     

Sildenafil Citrate Does Not Alter Ventricular Repolarization Properties: Novel Evidence from Dynamic QT Analysis

Background: Sildenafil citrate may have direct cardiac electrophysiological effects, and is possibly responsible for some cardiac events. The aim of our study was to investigate the effects of sildenafil citrate on QT dynamicity properties with a new QT analysis program showing even small changes in ventricular repolarization. Methods: Twenty‐four‐hour Holter electrocardiographic recordings were used to obtain the data in the predrug phase (1‐hour rest position before drug administration), and in the postdrug phase (1‐hour rest position, which began 60 minutes after 50 mg oral sildenafil citrate administration). With the special QT analysis program (Verda, Reynolds Medical Ltd., UK); mean values of RR, QT, QT_o (corrected QT), J (the exponent of correction formula) and S (QT/RR plots slope) parameters together with QT variability indexes (QTVI) were calculated for study phases. Results: Mean ± SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR: 845 ± 42 ms vs 816 ± 46 ms, P < 0.05; QT: 371 ± 8 ms vs 361 ± 9 ms, P < 0.05). However, sildenafil did not induce any significant change in mean ± SEM values for QT_o, J, and S in postdrug phase compared with predrug phase (408 ± 10 ms vs 406 ± 8 ms, 0.474 ± 0.030 vs 0.433 ± 0.025, 0221 ± 0.020 vs 0.198 ± 0.017, respectively; P > 0.05). QTVIs were also not different in each phase (predrug: ?0.874 ± 0.071 vs postdrug: ?0.997 ± 0.067, P = 0.109). Conclusions: Fifty milligrams sildenafil does not affect QT dynamicity properties. The cardiac events associated with sildenafil could not be explained with ventricular arrhythmias.     

Arch-first technique via clamshell incision: successful surgical reoperation for aortic arch dissection

We report a case of successful reoperation for aortic arch dissection with use of the "arch-first" technique in a patient who had Marfan syndrome. Extracorporeal circulation was initiated via right subclavian artery cannulation, and the chest was entered through a clamshell incision for the best exposure. When the patient was cooled to 18 degrees C, the perfusion was stopped. After the 1st aortic arch anastomosis to a 30-mm Dacron graft, cerebral perfusion was reestablished via the right subclavian artery. The aortic repair was then completed. The cerebral ischemic time was 18 minutes, the aortic cross-clamp time was 69 minutes, and the total extracorporeal circulation time was 334 minutes. The patient was discharged from the hospital on postoperative day 10 with no neurologic impairment. The arch-first technique shortens the duration of brain ischemia. When combined with a clamshell incision, the technique is particularly helpful for reoperation of the aortic arch and thoracic aorta.     

Inducible nitric oxide synthase expression in chronic viral hepatitis and its relation with histological severity of disease

summary . The role of nitric oxide in the pathogenesis of chronic viral hepatitis is not known. Elevated nitric oxide production is assumed to be responsible for the pathological changes in many inflammatory conditions, mainly via peroxynitrite, a potential oxidant that is produced by the reduction of superoxide anion with nitric oxide. The intensity and the distribution of the immunohistochemical staining of intrahepatic inducible nitric oxide synthase were studied in the biopsy specimens obtained from 63 patients with viral hepatitis and 13 patients with elevated transaminase levels of various aetiologies. Hepatic inducible nitric oxide synthase staining was significantly more intense in the viral hepatitis group ( P  = 0.000). Inducible nitric oxide synthase staining levels correlated well with the severity of the viral hepatitis using the Knodell's liver histological activity index ( r  = 0.393, P  = 0.002) Among the viral hepatitis group, the pathological distribution of the inducible nitric oxide synthase staining favoured the periportal hepatocytes (zone 1) whereas less staining was observed in parenchymal hepatocytes zone of 2 and 3 and bile duct epithelium. As nitric oxide mediated nitration of hepatocellular proteins is elevated in inflamed hepatic tissues and is correlated with the severity of the disease, we suggest that inducible nitric oxide synthase can possibly have a critical role in the pathogenesis of chronic viral hepatitis.     

Is there any relationship between adverse pregnancy outcome and first trimester nuchal translucency measurements in normal karyotype fetuses?

Aim: This study aims to research whether there is a relationship between first trimester nuchal translucency (NT) measurements and pregnancy complications such as gestational diabetes mellitus (GDM), gestational hypertension (GHT), intrauterine growth restriction (IUGR) and oligohydramnios.

Method: This study included 225 singleton pregnancies attending Canakkale Onsekiz Mart University Obstetrics and Gynecology clinic for all monitoring and examinations, and gave birth at our clinic between January 2011 and December 2012. Data sources were clinical records and the hospital's automation system, and the study was planned as retrospective cohort. NT measurement was made between 10 weeks 3 days and 13 weeks 6 days gestation. For data analysis, the chi-square, Mann–Whitney U test and Spearman correlation were used.

Results: Of pregnancies, in the study, 5 (2.2%) developed GDM, 6 (2.6%) developed GHT, 2 (0.89%) developed IUGR and 10 (4.4%) developed oligohydramnios. There was no correlation identified between NT measurements and development of GDM, GHT, IUGR and oligohydramnios.

Conclusion: There was no relationship found between first trimester NT measurements and complications that could develop in pregnancy. For the first time in the literature, NT and oligohydramnios were studied and no relationship was observed.     

Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis‐related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well‐established cancer gene lysine (K)‐specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome‐sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D‐mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

Sonographic assessment of subacromial bursa distension during arm abduction: establishing a threshold value in the diagnosis of subacromial impingement syndrome

Purpose

In this study, we aimed to establish a quantitative threshold value in the diagnosis of subacromial impingement syndrome by measuring the thickness of the subacromial bursa during abduction and adduction.

Materials and methods

Forty-five patients with subacromial impingement syndrome and 54 healthy individuals underwent dynamic shoulder ultrasonography. The subacromial bursa, between the supraspinatus tendon margin and peribursal adipose tissue, was measured between the acromion and humeral head at its widest part. The subacromial impingement ratio was calculated by dividing the subacromial bursa thickness during abduction to the subacromial bursa thickness during adduction. Shapiro–Wilk test was used in the assessment of normal distribution of parameters.

Results

The mean subacromial bursa thickness in the abduction position was 1.8 ± 1.1 mm in the study group and 0.9 ± 0.3 mm in the control group. The mean subacromial bursa thickness in the adduction position was 0.9 ± 0.5 mm in the study group and 0.8 ± 0.3 mm in the control group. The subacromial impingement ratio showed a statistically significant difference between groups (p < 0.0001), and the ratio being 2.0 ± 0.5 in the study group and 1.2 ± 0.1 in the control group. For measurements performed in the abduction position, the best cut-off value was calculated as 1.3 mm, and sensitivity and specificity were 70.6 and 85.2%, respectively. The best cut-off value was 1.4 for the subacromial impingement ratio, and sensitivity and specificity were 88.2 and 96.3%, respectively.

Conclusion

Subacromial impingement ratio is a very practical and reliable method in subacromial impingement syndrome diagnosis.