Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.

PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3, or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to 60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a modest in vitro effect, Bcl-2 ASO alone caused the regression of established xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days in a C15 model. The survival times for mice treated with both Bcl-2 ASO and radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This combination resulted in a more-than-additive effect in C666-1 tumors. Less impressive gains observed in C15 tumors might be attributable to higher expression of antiapoptotic Bcl-2 family proteins and limited drug distribution in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation combination, however, was effective, resulting in mice surviving for >80 days relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO and radiation combination is a highly potent therapy for nasopharyngeal cancer. Further examination of combination therapy with radiation and other Bcl-2 family-targeted anticancer agents in both preclinical and clinical settings is definitely warranted.     

不同多焦视网膜电图系统在评估视网膜功能上的比较

目的 评估VERIS mfERG （EDI Inc）和Espion multifocal imager （Diagnosys）两种不同系统测量正常眼多焦视网膜电图（mfERG）的电位波反应的差异及其相关性,并用两个不同系统分别测量黄斑前膜患眼的mfERG并进行分析.方法 这是一项横断面研究,在VERIS系统使用Burian-Allen （BA）电极,Espion系统使用BA和DTL电极分别测量25只正常眼的mfERG,将3次测得的一阶反应的相应数据进行配对t检验及Pearson相关分析.两个系统用BA电极分别测量19只黄斑前膜患眼的mfERG,对一阶反应的相应数据进行Fisher＇s exact test分析.结果 VERIS BA测得正常眼N1波、P1波振幅密度值最大,其次为Espion BA,Espion DTL最小;VERIS BA测得N1波、P1波潜伏期最长,Espion BA与Espion DTL差异无统计学意义.Espion BA与VERIS BA测得的P1波振幅密度、潜伏期皆有明显的相关性.黄斑前膜患眼中,VERIS BA比Espion BA能检测到更多P1波振幅密度和P1波潜伏期的异常.结论 不论VERIS或Espion系统都能成功记录多焦视网膜电图,当两种系统都使用Burian-Allen电极时,两者mfERG一阶反应P1波振幅密度及潜伏期有着良好的相关性.     

Altitude and childhood growth

To assess the possible influence of altitude on childhood growth in the United States, we used data collected by the Centers for Disease Control Pediatric Nutrition. Surveillance System from eight mountain states to determine the height and weight status of children aged 5 years or younger enrolled in various public health programs between 1982 and 1984. The mean birth weight, height-for-age, weight-for-age, and weight-for-height indicators were found to decline significantly with increasing altitude, starting at an elevation greater than 1500 m (p less than 0.001, ANOVA). The reduction in growth was observed for all age groups and all birth weight groups studied. Part of the observed reduction in growth could be attributed to the lower birth weight of children born at higher altitude. However, the reduced growth status persisted after controlling for birth weight, suggesting the presence of an extrauterine growth retardation effect related to altitude.     

Two-year clinical outcomes following lower limb endovascular revascularisation for chronic limb-threatening ischaemia at a tertiary Asian vascular centre in Singapore

INTRODUCTIONPercutaneous transluminal angioplasty (PTA) is commonly used to treat patients with chronic limb-threatening ischaemia (CLTI). This study aimed to examine the mortality and functional outcomes of patients with CLTI who predominantly had diabetes mellitus in a multi-ethnic Asian population in Singapore.METHODSPatients with CLTI who underwent PTA between January 2015 and March 2017 at the Vascular Unit at Singapore General Hospital, Singapore, were studied. Primary outcome measures were 30-day unplanned readmission, two-year major lower extremity amputation (LEA), mortality rates, and ambulation status at one, six and 12 months.RESULTSA total of 221 procedures were performed on 207 patients, of whom 184 (88.9%) were diabetics. The one-, six- and 12-month mortality rate was 7.7%, 16.4% and 21.7%, respectively. The two-year LEA rate was 30.0%. At six and 12 months, only 96 (46.4%) and 93 (44.9%) patients were ambulant, respectively. Multivariate analysis revealed that preoperative ambulatory status, haemoglobin, Wound Ischaemia and foot Infection (WIfI) score, and end-stage renal failure (ESRF) were independent predictors of one-year ambulatory status. Predictors of mortality at one, six and 12 months were ESRF, preoperative albumin level, impaired functional status and employment status.CONCLUSIONPTA for CLTI was associated with low one-year mortality and two-year LEA rates but did not significantly improve ambulation status. ESRF and hypoalbuminaemia were independent predictors of mortality. ESRF/CKD and WIfI score were independent predictors of loss of ambulation at six months and one year. We need better risk stratification for patients with CLTI to decide between initial revascularisation and an immediate LEA policy.     

High-resolution computed tomography in patients with atypical ‘cardiac‘ chest pain: a study investigating patients at 10-year cardiovascular risks defined by the Framingham and PROCAM scores

Background and objective Atypical ‘cardiac‘ chest pain (ACCP) is not usually caused by myocardial ischaemia. Current noninvasive investigations for these symptoms are not yet as accurate as invasive coronary angiography. The latest 64-row multi-detector computed tomography (MDCT) technology is non-invasive, has high specificity and negative predictive values for the detection of significant coronary disease. Our aim was to investigate if this modality can provide more information in the assessment of outpatients with ACCP in addition to established cardiovascular risk scores. Methods Seventy consecutive patients presenting to the outpatient clinic with ACCP underwent 64-row MDCT scan of the coronary arteries. They were categorized into low, medium or high risk groups based upon the Framingham and PROCAM scores. We defined a clinically abnormal MDCT scan as coronary stenosis =50% or calcium score ＞400 Agatston. Results Fifty-three (75.7%) patients did not have clinically abnormal scans. Framingham score classified 43 patients as low-risk while PROCAM classified 59 patients as low-risk. MDCT scans were abnormal for 18.6% and 22.0% of the respective low-risk group of patients. For patients with medium-to-high risk, 33.3% and 36.4% of Framingham and PROCAM patient groups respectively had abnormal MDCT scans. Conclusion MDCT adds valuable information in the assessment of patients with ACCP by identifying a significant proportion of patients categorized as low-risk to have underlying significant coronary stenosis and coronary calcification by established cardiovascular risk scores.     

Feasibility and accuracy of coronary imaging in elderly patients using the 64-row multi-detector computed tomography: a correlation study with conventional coronary angiography

Background Elderly patients generally have higher occurrence of coronary calcification, increased heart rate and difficulty with prolonged breath-holding. The aim of our study was to investigate the feasibility and accuracy of using 64-row multi-detector computed tomography (MDCT) in the assessment of coronary artery stenoses in elderly patients. Methods One hundred and fifty two patients with suspected or known coronary artery disease were divided into 4 groups according to their age (Group A: 40-49 years, n=34; Group B: 50-59 years, n=57; Group C: 60-69 years, n=48; Group D: 70 years and above; n=13). Coronary CT angiography (CTA) using a 64-row MDCT was performed and the findings were compared with that of conventional coronary angiography (CCA). Using axial images, multi-planar reconstructions (MPR) and maximum intensity projections (MIP), coronary segments of lumen diameter = 1.5mm were analyzed for the presence of significant stenosis (= 50% ). Results Percentages of poor image quality from coronary CTA preventing reliable correlations with CCA were 21%, 14%, 19% and 62% in Groups A to D respectively. Patients in Group D had significantly higher calcium scores compared with the other groups (P<0.001). In patients where CTA images were of acceptable quality, percentages of accurate correlations with CCA were 89.8%, 93.4%, 86.6% and 78.0% for Groups A to D respectively. There were no significant difference in serum creatinine, heart rate and contrast volume between the 4 groups. Conclusions The 64-row MDCT coronary angiography was less accurate and feasible for patients aged 70 years or above due to heavy coronary calcification and inability to perform a satisfactory breath-hold. However, a high diagnostic accuracy with the MDCT is possible in patients aged less than 70 years.(J Geriatric Cardiol 2006;3(1):9-14)     

Assessment of left ventricular ejection fraction: comparison of two dimensional echocardiography, cardiac magnetic resonance imaging and 64-row multi-detector computed tomography

Objectives To compare left ventricular ejection fraction (LVEF) determined from 64-row multi-detector computed tomography (64-row MDCT) with those determined from two dimensional echocardiography (2D echo) and cardiac magnetic resonance imaging (CMR). Methods Thirty-two patients with coronary artery disease underwent trans-thoracic 2D echo, CMR and contrast-enhanced 64-row MDCT for assessment of LVEF within 48 hours of each other. 64-row MDCT LVEF was derived using the Syngo Circulation software; CMR LVEF was by Area Length Ejection Fraction (ALEF) and Simpson method and 2D echo LVEF by Simpson method. Results The LVEF was 49.13±15.91 % by 2D echo, 50.72±16.55% (ALEF method) and 47.65±16.58%(Simpson method) by CMR and 50.00±15.93% by 64-row MDCT. LVEF measurements by 64-row MDCT correlated well with LVEF measured with CMR using either the ALEF method (Pearson correlation r = 0.94, P <0.01) or Simpson method (r = 0.92, P<0.01). It also correlated well with LVEF measured using 2D echo (r = 0.80, P < 0.01). Conclusion LVEF measurements by 64-row MDCT correlated well with LVEF measured by CMR and 2D echo. The correlation between 64-row MDCT and CMR was better than the correlation between 2D echo with CMR. Standard data set from a 64-row MDCT coronary study can be reliably used to calculate the LVEF. (J Geriatr Cardiol 2006;3(1): 2-8)