Left Septal Atrial Tachycardias: Electrocardiographic and Electrophysiologic Characterization of a Paraseptal Focus

Left Septal Atrial Tachycardias. Objective: The objective was to characterize the electrocardiographic and electrophysiological features of focal atrial tachycardia (FAT) originating from the left septum (LS). Background: FAT is recognized to occur at predefined anatomic locations rather than randomly throughout the atria. We describe the ECG and EP features of ATs originating from the LS as an important site for apparent perinodal tachycardias. Methods: Nine patients presenting with LS FAT from a consecutive series of 384 underwent EP/RFA for symptomatic FAT. Results: The mean age was 56 ± 12 years; 7 female with symptoms for 36 ± 28 months. P wave morphology (PWM) was negative/positive in lead V1 and across the precordial leads and negative or negative/positive in inferior leads in all patients. Tachycardia was incessant in 6 out of 9 patients with a mean tachycardia cycle length 421 ± 56 milliseconds. His A was ahead of P wave in all patients (mean ?15 ± 5 milliseconds) and earlier than CS proximal (mean 4 ± 9 milliseconds). Successful acute focal ablation achieved at a mean of 31 ± 12 milliseconds ahead of P wave with no recurrences at a mean follow‐up of 30 ± 28 months. Conclusion: Although the left septum is an uncommon site for focal AT an awareness of this location for harboring foci is particularly important when mapping apparently right‐sided septal tachycardias. (J Cardiovasc Electrophysiol, Vol. 24, pp. 413‐418, April 2013)     

耐一线药物及注射药物对耐多药结核病治疗效果的影响

背景和目的:最近的研究结果表明,对其他一线药物和注射类药物(如卡那霉素、卷曲霉素)等耐药是影响耐多药结核病(MDR-TB)患者治疗效果的独立危险因素.本研究旨在明确耐其他一线药物和注射类药物对韩国不合并人免疫缺陷病毒(HIV)感染的MDR-TB患者临床疗效的影响.方法:采用回顾性队列研究分析1996年1月至2005年12月首尔国家大学附属医院治疗的211例MDR-TB患者治疗效果,排除7例丢失和7例迁出,对197例患者进行了最终分析.     

Aven‐mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma

Conventional high‐grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis‐free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti‐apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G₂ cell‐cycle arrest; Chk1 protein levels were attenuated and ATR–Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven‐depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven‐controlled ATR–Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix‐embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR–Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

败血症病人死亡危险性预评估方法的探讨

目的:探索可早期预测严重败血症病人死亡的临床和实验室指标或系统模型。方法:对ICU连续收治的26例严重败血症病人行前瞻性观察28天,分析其死亡的相关临床和实验室指标。结果:共有14人(54％)死亡,多死于第1周内(74％)。根据循环中的细胞间粘附分子-1水平能早期预测其脏器衰竭和死亡。一些临床指标水平在死亡病人与生存病人之间差别较大,其中包括血总胆红素、pH值、红细胞压积、氧合指数、动静脉血氧差、四项SIRS指标和一些血流动力学指标等。结论:综合上述指标可以尝试建立起了一个能够早期评估病人死亡可能性的积分系统。     

Free testosterone levels in umbilical‐cord blood predict infant head circumference in females

Aim Fetal androgens influence fetal growth as well as postnatal neurocognitive ability. However, to our knowledge, no published study has prospectively examined the impact of early‐life androgens on infant brain growth. We report the association between circulating fetal androgen levels, measured from umbilical‐cord blood at birth, and a proxy measure of brain growth: head circumference. Method Participants were 82 unselected female infants from a large representative birth cohort (mean gestational age 39.4wks, SD 1.7). Umbilical‐cord blood was obtained at birth and analysed for androgen concentrations (total testosterone, androstenedione, dehyrdroepiandrosterone, and its sulphated metabolite). Head circumference and two other measures of growth – weight (mean 3311.4g, SD 461.3) and length – were measured within 3 days of birth and again at approximately 1 year of age (mean age 13.1mo, SD 1.1). Results Multivariate linear regressions found an inverse association between levels of free testosterone and growth in head circumference (correlation=?.24), even when adjusting for sociodemographic/obstetric covariates and head size at birth. Growth in weight and length could not be predicted by free testosterone concentration. Interpretation This is the first report of an association between prenatal androgen levels and postnatal growth in head circumference. These findings suggest that early‐life androgens may impact brain development during infancy.     

The Renin–Angiotensin System Mediates the Effects of Stretch on Conduction Velocity,Connexin43 Expression,and Redistribution in Intact Ventricle

Effect of Stretch on Conduction and Cx43 . Introduction: In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin–angiotensin system (RAS). Methods and Results: In an open‐chest canine model, a device was used to stretch part of the right ventricle (RV) by 22% for 6 hours. Activation mapping using a 312‐electrode array was performed before and after stretch. Regional stretch did not change longitudinal conduction velocity (post‐stretch vs baseline: 51.5 ± 5.2 vs 55.3 ± 8.1 cm/s, P = 0.24, n = 11), but significantly reduced transverse conduction velocity (28.7 ± 2.5 vs 35.4 ± 5.4 cm/s, P < 0.01). It also reduced total Cx43 expression, by Western blotting, compared with nonstretched RV of the same animal (86.1 ± 32.2 vs 100 ± 19.4%, P < 0.02, n = 11). Cx43 labeling redistributed to the lateral cell borders. Stretch caused a small but significant increase in the proportion of the dephosphorylated form of Cx43 (stretch 9.95 ± 1.4% vs control 8.74 ± 1.2%, P < 0.05). Olmesartan, an angiotensin II blocker, prevented the stretch‐induced changes in Cx43 levels, localization, and conduction. Conclusion: Myocardial stretch in vivo has opposite effects to that in neonatal myocytes in vitro. Stretch in vivo causes conduction changes associated with Cx43 remodeling that are likely caused by local stretch‐induced activation of the RAS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1276‐1283, November 2010)     

Predictors of Mortality in Patients with Lower Extremity Peripheral Arterial Disease: 5‐Year Follow‐up

Background: Peripheral arterial disease (PAD) is associated with increased mortality. Lower extremity (LE) revascularization improves symptoms, but less is known about long‐term survival benefits of LE arterial revascularization. Methods: Two hundred and eighty‐three patients with an ankle brachial index (ABI) ≤0.9 were identified at the Veterans Administration Hospital, Danville, Illinois, and rates of LE arterial revascularization and all‐cause mortality were measured at 5 years. Results: Of 283 patients identified, 42 (15%) underwent LE revascularization including 39 surgical procedures and 18 percutaneous interventions for symptomatic PAD. Eleven (26%) patients underwent repeat procedures over the 5 years of follow‐up. Those undergoing revascularization were more often Caucasian (95% vs. 79%, P = 0.01) and had lower ABIs (ABI ≤ 0.4, 45% vs. 17%, P = <0.001). At 44 ± 19 months follow‐up, there were fewer deaths in patients that underwent revascularization compared to patients who did not undergo revascularization; 10/42 (24%) versus 107/241 (44%) patients, P = 0.012. In a multivariate model LE arterial revascularization was associated with a trend toward lower all‐cause mortality (HR 0.51 [95% CI 0.26–1.02], P = 0.056). Independent predictors of mortality were age ≥65 years (HR 2.42 [95% CI 1.52–3.85], P < 0.001), history of coronary artery disease (HR 1.67 [95% CI 1.13–2.46], P = 0.010), chronic kidney disease (HR 1.75 [95% CI 1.15–2.67], P = 0.010), and an ABI ≤ 0.4 (HR 1.88 [95% CI 1.19–2.96], P = 0.006). Conclusion: Few patients at this center with LE‐PAD underwent arterial revascularization. After adjusting for baseline differences, there is a trend toward lower 5‐year mortality in those undergoing LE arterial revascularization when compared to those who do not.     

Analysis of the relationship between age and treatment response in migraine

In migraine, headache severity varies with age. As a consequence, the effectiveness of medication may also depend on a patient's age. The purpose of this study was to assess the combined effect of age and drug treatment on headache characteristics. Using data from clinical trials of sumatriptan in adolescents and adults, we show how the interaction between age and drug exposure can be parameterised as a covariate on a Markov model that describes the decline of headache severity over three clinically defined stages (no relief, relief and pain-free status). The model explains important clinical observations: (i) the rates at which the pain relief and pain-free status were attained were found to be inversely related to age; (ii) in placebo-treated patients, the mean transit time from 'no relief' to 'relief' is 3 h for young adolescents and increases to 6 h for patients aged ≥ 30 years; and (iii) sumatriptan reduces the transit time to 2 h, irrespective of age. These findings indicate that the therapeutic gain over placebo increases with age. Prospective studies of antimigraine drugs should take this relationship into account when extrapolating efficacy data from adults to adolescents.