Substrate and procedural predictors of outcomes after catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) due to diastolic dysfunction, elevated left atrial pressure, and enlargement. Although catheter ablation for drug‐refractory AF is an effective treatment, the efficacy in HCM remains to be established. Methods: Thirty‐three consecutive patients (25 male, age 51 ± 11 years) with HCM underwent pulmonary vein (PV) isolation (n = 8) or wide area circumferential ablation with additional linear ablation (n = 25) for drug‐refractory AF. Twelve‐lead and 24‐hour ambulating ECGs, echocardiograms, event monitor strips, and SF 36 quality of life (QOL) surveys were obtained before ablation and for routine follow‐up. Results: Twenty‐one (64%) patients had paroxysmal AF and 12 (36%) had persistent/permanent AF for 6.2 ± 5.2 years. The average ejection fraction was 0.63 ± 0.12. The average left atrial volume index was 70 ± 24 mL/m 2 . Over a follow‐up of 1.5 ± 1.2 years, 1‐year survival with AF elimination was 62%(Confidence Interval [CI]: 66‐84) and with AF control was 75%(CI: 66‐84). AF control was less likely in patients with a persistent/chronic AF, larger left atrial volumes, and more advanced diastolic disease. Additional linear ablation may improve outcomes in patient with severe left atrial enlargement and more advanced diastolic dysfunction. Two patients had a periprocedureal TIA, one PV stenosis, and one died after mitral valve replacement from prosthetic valve thrombosis. QOL scores improved from baseline at 3 and 12 months. Conclusion: Outcomes after AF ablation in patients with HCM are favorable. Diastolic dysfunction, left atrial enlargement, and AF subtype influence outcomes. Future studies of rhythm management approaches in HCM patients are required to clarify the optimal clinical approach.     

Inhibition of leukemic HL60 cell growth by transferrin-gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea [see comments]

Cellular requirements for iron during DNA synthesis are related to the increased activity of the iron-containing M2 subunit of ribonucleotide reductase, the enzyme responsible for the reduction of ribonucleotides to deoxyribonucleotides. We have previously shown that transferrin- gallium (Tf-Ga) inhibits cellular iron incorporation. In the present study, Tf-Ga-induced inhibition of HL60 cell growth and upregulation of Tf receptor density was reversed with hemin. Cells exposed to 2 mumol/L Tf-Ga for six hours or longer displayed a diminution in the electron spin resonance (ESR) spectroscopy signal of the tyrosyl radical of the M2 subunit of ribonucleotide reductase. The effect of Tf-Ga on the ESR signal was reversed by hemin. Tf-Ga decreased the incorporation of 14C- adenosine into DNA and decreased intracellular deoxyribonucleotide pools, with the maximum diminution seen in deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP) pools. Exposure of cells to combinations of Tf-Ga and hydroxyurea (a known inhibitor of ribonucleotide reductase) resulted in a marked inhibition of cell growth that was consistent with drug synergy. Our studies suggest that Tf-Ga inhibits DNA synthesis through action on the M2 subunit of ribonucleotide reductase and that combinations of Ga and hydroxyurea should be further evaluated in in vivo tumor models.     

Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study

Introduction

Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.

Methods

Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients’ temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn’s multiple comparisons test was used for comparison of individual time points.

Results

The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.

Conclusions

Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.     

Nutritional factors and hypospadias risks

Carmichael SL, Ma C, Feldkamp ML, Munger RG, Olney RS, Botto LD, Shaw GM, Correa A. Nutritional factors and hypospadias risks. Paediatric and Perinatal Epidemiology 2012; ?? : ??–??. Background: We examined whether hypospadias was associated with several aspects of the diet, including intake of animal products, intake of several nutrients and food groups related to a vegetarian diet and oestrogen metabolism, and diet quality. Methods: The study included deliveries from 1997 to 2005 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews, and two diet quality indices were developed based on existing indices. Analyses included 1250 cases with second‐ or third‐degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 3118 male, liveborn, non‐malformed controls. All odds ratios (OR) and 95% confidence intervals [CI] were estimated from logistic regression models that included several potential confounders, including energy intake. Results: Intake of animal products was not associated with hypospadias; for example, the adjusted OR for any vs. no intake of meat was 1.0 [95% CI 0.6, 1.6]. Frequency of intake of meat or other animal products was also not associated with hypospadias, nor was intake of iron or several nutrients that are potentially related to oestrogen metabolism. Diet quality was also not associated with hypospadias; the OR for diet quality in the highest vs. lowest quartile for the two diet quality indices were 1.0 [95% CI 0.6, 1.6] and 0.9 [95% CI 0.7, 1.1]. Conclusion: This large study does not support an association of a vegetarian diet or worse diet quality with hypospadias.     

不同诱导方法诱导家蝇幼虫血淋巴中抗菌肽差异性的SDS-PAGE检测

目的 检测不同诱导方法(针刺,紫外,热诱导)诱导家蝇三龄幼虫血淋巴中的抗茵肽的差异性.方法 用不同诱导方法诱导家蝇三龄幼虫,提取血淋巴后,采用梯度乙腈洗脱,应用SDS-PAGE检测抗菌肽的差异性.结果 针刺与未诱导组无明显差异,热诱导组中30%乙腈洗脱组分中在30～71 KD中出现3个差异条带,紫外诱导组50%乙腈洗脱组分在16～20 KD中出现2个差异条带,60%乙腈洗脱组分中在16-20 KD中出现2个差异条带.结论 综合幼虫的成活率及操作的方便性,最佳的诱导方法为热诱导.     

Short-interval recanalization after gelfoam occlusion

Gelfoam® is a temporary embolization agent often used in trauma where permanent arterial occlusion is not desired. Gelfoam occlusions have been shown to resolve by 2 weeks, but shorter intervals have not been studied. We report a case of spontaneous arterial hemorrhage due to ruptured hepatic malignancy where treatment was Gelfoam slurry occlusion of the right hepatic artery. Repeat hemorrhage resulted in repeat CT and hepatic arteriography, which showed that recanalization of the occluded artery had occurred in less than 48 hours. Gelfoam arterial occlusion in some cases may last less than 2 weeks.     

注射用尤瑞克林治疗急性脑梗死的临床疗效观察

目的 观察尤瑞克林治疗急性脑梗死的临床疗效.方法 将符合入选条件的60例急性脑梗死惠者分为治疗组和对照组,每组30例.两组基础治疗相似,治疗组患者加用尤瑞克林,每日1次;分别给予治疗前后神经功能缺损评分和临床疗效比较,同时检测血常规、尿常规、肝肾功能及凝血功能等.结果 治疗组神经功能缺损评分较治疗前差异有统计学意义(P<0.05),疗效明显优于对照组,且无不良反应.结论 尤瑞克林治疗急性脑梗死疗效确切,安全可靠.