DSpace community: 臨床醫學研究所

Brugada Syndrome - an under-Recognized Electrical Disease in Patients with Sudden Cardiac Death

Wed, 09 Sep 2009 06:46:39 GMT

title: Brugada Syndrome - an under-Recognized Electrical Disease in Patients with Sudden Cardiac Death abstract: In 1992, Brugada and Brugada described 8 patients with a history of aborted sudden death and a distinct ECG pattern of right bundle-branch block with ST segment elevation in leads V1-V3 and normal QT interval in the absence of any structural heart disease. It is called Brugada syndrome now and is believed to be responsible for 4-12% of all sudden deaths and around 20% of deaths in patients with structurally normal hearts. Although this syndrome is observed worldwide and the exact prevalence is unknown, it is more common in the Southeast Asian countries. Repeated syncope, ventricular fibrillation, and sudden cardiac death have been reported in patients with Brugada syndrome. The clinical presentation of Brugada syndrome is distinguished by a male predominance and the appearance of arrhythmic events at an average age of 40 years. The Brugada syndrome is inherited in an autosomal dominant manner with incomplete penetrance and an incidence ranging between 5 and 66 per 10 ,000. The surface ECG manifestations of the syndrome can transiently disappear, but can be unmasked by potent sodium channel blockers in some cases. Mutations of the cardiac sodium channel SCN5A have been detectable in <20% of patients with Brugada syndrome. Recent genetic studies have confirmed the genetic heterogeneity of the disorder. Antiarrhythmic drugs appear to be of little use in prolonging survival and in preventing recurrences of ventricular arrhythmias. To date, implantable cardioverter defibrillator remains the best therapy to prevent sudden death in these patients. Copyright (C) 2004 S. Karger AG, Basel.

Ingested Arsenic, Cigarette Smoking, and Lung Cancer Risk: A Follow-up Study in Arseniasis-Endemic Areas in Taiwan

Wed, 09 Sep 2009 06:43:42 GMT

title: Ingested Arsenic, Cigarette Smoking, and Lung Cancer Risk: A Follow-up Study in Arseniasis-Endemic Areas in Taiwan abstract: CONTEXT: Arsenic has been documented as a lung carcinogen in humans in only a few follow-up studies, which were limited by a small number of cases or the lack of information on cigarette smoking. OBJECTIVES: To elucidate the dose- response relationship between ingested arsenic and lung cancer and to assess the effect of cigarette smoking on the arsenic- lung cancer association. DESIGN, SETTING, AND PARTICIPANTS: A total of 2503 residents in southwestern and 8088 in northeastern arseniasis-endemic areas in Taiwan were followed up for an average period of 8 years. Information on arsenic exposure, cigarette smoking, and other risk factors was collected at enrollment through standardized questionnaire interview. MAIN OUTCOME MEASURES: The incidence of lung cancer was ascertained through linkage with national cancer registry profiles in Taiwan (January 1985-December 2000). The joint effect of arsenic and cigarette smoking was estimated by both etiologic fraction and synergy index. RESULTS: There were 139 newly diagnosed lung cancer cases during a follow-up period of 83 ,783 person -years. After adjustment for cigarette smoking and other risk factors, there was a monotonic trend of lung cancer risk by arsenic level in drinking water of less than 10 to 700 microg/L or more (P<.001). The relative risk was 3.29 ( 95% confidence interval, 1.60-6.78) for the highest arsenic level compared with the lowest. The etiologic fraction of lung cancer attributable to the joint exposure of ingested arsenic and cigarette smoking ranged from 32% to 55%. The synergy indices ranged from 1.62 to 2.52, indicating a synergistic effect of ingested arsenic and cigarette smoking on lung cancer. CONCLUSIONS: There was a significant dose- response trend of ingested arsenic on lung cancer risk, which was more prominent among cigarette smokers. The risk assessment of lung cancer induced by ingested arsenic should take cigarette smoking into consideration.

Kinetics of Perrhenate Uptake and Comparative Biodistribution of Perrhenate, Pertechnetate, and Iodide by Nai Symporter-Expressing Tissues in Vivo

Wed, 09 Sep 2009 06:42:50 GMT

title: Kinetics of Perrhenate Uptake and Comparative Biodistribution of Perrhenate, Pertechnetate, and Iodide by Nai Symporter-Expressing Tissues in Vivo abstract: Pertechnetate (as (TcO4-)-Tc-99m), I-123(-), and I-131(-) have a long and successful history of use in the diagnosis and therapy of thyroid cancer, with uptake into thyroid tissue mediated by the sodium-iodide symporter ( NIS). NIS has also emerged as a potential target for radiotherapy of nonthyroid malignancies that express the endogenous or transfected symporter. Perrhenates (as (ReO4-)-Re-188 and ( ReO4-)-Re-186) are promising therapeutic substrates of NIS, although less is known about their behavior in vivo. In this study, we endeavored to characterize the biologic behavior of perrhenate, especially in relation to iodide and pertechnetate, to better explore its possible therapeutic role. Methods: We describe the simultaneous biodistribution and uptake in vivo of iodide, pertechnetate, and perrhenate in groups of healthy CD1 mice, either with or without coadministration of perchlorate (ClO4-), a potent NIS inhibitor . Animals administered single radiopharmaceuticals were imaged as a means of illustrating these findings. Kinetic properties of perrhenate were compared with those of iodide in a stably transfected NIS-bearing Madin- Darby canine kidney (MDCK) cell line. Results: Biodistributions of iodide, pertechnetate, and perrhenate in live mice were remarkably similar. Activity in salivary gland and stomach was severalfold greater than in blood, remained elevated over the initial 2 h, and subsequently washed out . A similar pattern characterized pertechnetate and perrhenate uptake by the thyroid, in which the 2-h concentration was slightly more elevated than at the 20-min time point. However, uptake subsequently decreased by 19 h. In contrast, iodide continued to increase through the 19-h time point, presumably as a result of organification. The addition of perchlorate sharply decreased uptake of all 3 radiopharmaceuticals by the stomach, salivary glands, and thyroid and resulted in their rapid clearance, paralleling blood-pool clearance. In tissues that do not express NIS ( liver, muscle, spleen), uptake of all 3 radiopharmaceuticals was low and rapidly decreased over time, paralleling blood- pool clearance. Similar findings were seen in kidney, where only minimal amounts of NIS are expressed in tubular cells. In stably transfected MDCK cells, steady-state accumulation of iodide was approximately 4-fold higher than that of perrhenate at 30 min. No active transport was demonstrated in nontransfected MDCK cell lines or after perchlorate administration. Uptake values measured at different concentrations of substrate demonstrated saturation kinetics . Apparent maximal velocity values for perrhenate and iodide were 25.6 1.4 and 106 3.2 pmol/mug, respectively, and corresponding affinity constant values were 4.06 0.87 and 24 .6 1.81 mumol/L. Conclusion: Perrhenate is avidly taken up by NIS in a manner similar to iodide and pertechnetate in vivo, with the exception of organification of iodide by the thyroid. By more fully appreciating the behavior of perrhenate, especially in relation to iodide and pertechnetate , we can better realize its potential role in the diagnosis and therapy of NIS-bearing tissues.

On the Tail Probability of the Longest Well-Matching Run

Wed, 09 Sep 2009 06:41:56 GMT

title: On the Tail Probability of the Longest Well-Matching Run abstract: The distribution of the length of the longest run has wide applications in regard to reliability and DNA sequencing. Statistical tests based on the longest well-matching run are usually considered to be more reasonable than tests based on the perfect-matching run. In this paper, a method adopted from Fu and Koutras (J. Amer. Statist. Assoc. 89 (1994) 1050) is proposed to improve the efficiency of computing the exact distribution of length. We used the result to investigate the accuracy of some approximations of the distribution. (C) 2003 Elsevier Science B.V. All rights reserved.