FDA’S Perspectives on Cardiovascular Devices

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, §903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 ). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA’s review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.     

100例性病患者心理健康状况调查分析

目的：探讨性病患者的心理健康状况,为临床治疗和护理提供依据。方法：采用症状自评量表（SCL-90）对100例性病患者的心理健康状况进行测验。结果：100例性病患者SCL-90检测的阳性率为51%,阳性样本因子分居前的是敌对、强迫症状、抑郁、人际敏感。结论：性病患者广泛存在的心理问题,在药用治疗的同时应注意心理方面的治疗和疏导。     

West Nile virus preferentially transports along motor neuron axons after sciatic nerve injection of hamsters

Prior findings led us to hypothesize that West Nile virus (WNV) preferentially transports along motor axons instead of sensory axons. WNV is known to undergo axonal transport in cell culture and in infected hamsters to infect motor neurons in the spinal cord. To investigate this hypothesis, WNV was injected directly into the left sciatic nerve of hamsters. WNV envelope-staining in these hamsters was only observed in motor neurons of the ipsilateral ventral horn of the spinal cord, but not in the dorsal root ganglion (DRG). To evaluate the consequence of motor neuron infection by WNV, the authors inoculated wheat germ agglutinin—horseradish peroxidase (WGA-HRP) 9 days after WNV sciatic nerve injection, and stained the spinal cord and the DRG for HRP activity 3 days later. The degree of HRP-staining in DRG was the same in WNV- and sham-infected animals, but the HRP-staining in the motor neuron in the ventral horn was considerably less for WNV-infected hamsters. To investigate the mechanism of WNV transport, hamsters were treated with colchicine, an inhibitor of membranous microtubule-mediated transport. The intensity of the WNV-stained area in the spinal cord of colchicine-treated hamsters at 6 days after WNV infection were significantly reduced (P≤.05) compared to the placebo-treated hamsters. These data suggest that WNV is preferentially transported through the motor axons, but not the sensory axons, to subsequently infect motor neurons and cause motor weakness and paralysis.     

Hyperemic Islets: A Possible Explanation for Poor Yields in Human and Porcine Islet Isolation

When studying histological characteristics of human and porcine pancreata in relation to islet isolation, we encountered a remarkably high number of hyperemic islets. The abnormalities observed in these islets ranged from a single dilated vessel through multiple widely dilated vessels to hemorrhages extending into the surrounding exocrine tissue. We determined their possible relevance for outcomes of islet isolation. This study involved a histological examination of 143 porcine pancreata (72 juvenile and 71 adult) and islet isolation from 48 adult pancreata. Human pancreata obtained from 71 multiple organ donors yielded islet isolation in 24 cases. To determine their endocrine content, tissue samples were stained with Aldehyde Fuchsin. The presence of hyperemic islets was scored semiquantitatively with pancreata allotted to categories based on the severity. In humans and pigs we observed hyperemic islets in 48% of pancreata, but only 4.0 ± 2.4% of the islets were hyperemic. In both humans and pigs, significantly higher endocrine content was found in the most severely affected pancreata. When the higher endocrine content was taken into account and isolation results were expressed as ratios of yield and content, we observed significantly lower yields in the most affected pancreata in pigs with a trend toward lower yields in humans. A substantial proportion of human and porcine pancreata contain hyperemic islets. Although the results in humans are preliminary, our data suggest that this phenomenon may contribute to the unpredictable, highly variable islet yields in pigs and humans.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

广西边远少数民族学生体型及体质量指数3年追踪**

背景: 前期研究表明广西18~22岁少数民族学生体质量偏轻。 目的：拟进一步了解广西2645名少数民族学生体型及体质健康状况，寻找影响的关联因子。 设计、时间及地点：追踪调查，于2004-12/2007-12在广西民族大学完成。 对象：广西民族大学2003/2005三次体质健康测试的全体学生2 645人。男1 337人，女1308人，年龄为18~20岁，共15个民族。 方法：根据2003年教育部、体育总局《学生体质健康标准（试行方案）》和实施方法分为形态指标、技能指标和身体素质指标3大类。对2 645名少数民族身体机能与体质量指数变化的跟踪调查。 主要观察指标：身高、体质量、肺活量、立定跳远、坐位体前屈、体质量指数。 结果：①广西民族大学2003级学生大学3年期间男生身高、体质量增长率比全国同期多2.45%，身体形态发育正处于高峰期，女生成偏瘦型体型，身体形态发育情况总体欠佳。②男女学生在刚入校时肺活量机能较差，远远低于同期全国平均水平。3年后男生肺活量增长率为11.55%、女生肺活量增长率为27.72%，分别高于全国同期肺活量增长率。③坐位体前屈机能高于同期全国平均水平，男生呈逐年上升趋势，同期全国男性呈下降趋势；同期全国乡村女生均呈逐年上升趋势。④立定跳远机能提高较大，3年后增长率为18.15%，明显高于全国同期立定跳远增长率水平的2.61%。女生立定跳远机能总体不如全国同期水平。⑤体质量指数总体与同期全国乡村男女学生体质量指数比较稍低一些(P < 0.01)。 结论：2 645名少数民族学生发育正处于高峰期；肺活量机能不及全国同期平均水平。男女体质量指数分布有所不同，体质量偏轻者女生多于男生，表明学生营养状况总体欠佳。