Reducing unintentional injuries on the nation's highways: research and program policy to increase seat belt use

Death, disability, and injury from motor vehicle accidents constitute a public health crisis. The goal of this paper is to describe how Meharry Medical College's Center for Community Based Research plans to address this problem. A model of how high-risk groups are influenced to engage in behaviors that increase risk for traffic crashes is articulated. Five strategies for reducing risk for motor vehicle morbidity and mortality are identified: 1) influencing the individual at the point of decision; 2) mobilizing communities and coalitions to support individual and systems changes; 3) modifying environmental factors to modify behaviors; 4) changing laws and public policy; and 5) working towards the elimination of underlying causes. The Center for Community Based Research's promotion of seat belt use, based on each of these five strategies, is described. Addressing the public health crisis resulting from death and injury on the nation's roads and the excess risk faced by minority groups in this country will require the coordinated efforts of many groups. This work must be driven by research, the outcome of which will be a reduction in preventable injury, disability and premature death.     

Host response to autologous endothelial seeding

Dacron and expanded polytetrafluoroethylene grafts, seeded with autologous venous endothelial cells at the time of implantation, subsequently develop endothelial linings. However, it has not been shown whether the endothelial cells in these linings are derived from the seeded cells, or whether the seeding process itself stimulates host endothelial cells to proliferate and cover the grafts. As a first step in testing this hypothesis, bilateral end-to-side aortoiliac expanded polytetrafluoroethylene grafts with an internal diameter of 6 mm, an internodal distance of 22 microns, and an average length of 9.2 cm were placed in 10 adult mongrel dogs weighing 20 to 25 kg; the aorta was ligated just distal to the origin of the grafts. The graft on one side, chosen at random, was seeded with autologous endothelium that was harvested by enzyme single-stage technique from external jugular veins; the other side was not seeded. After 4 weeks the animals were anesthetized and heparinized, and the grafts were fixed by perfusion in vivo with 2.5% glutaraldehyde solution before they were removed. Both grafts occluded in two animals, and both grafts were patent in five animals. In two animals the seeded grafts were open and the unseeded grafts were occluded. In one the seeded graft was occluded and the unseeded graft was patent. There was no significant difference in clot-free surface area between seeded (29% +/- 18%) and unseeded (31% +/- 11%) grafts. Scanning electron microscopy showed the presence of an endothelial monolayer that averaged 39% +/- 20% and 36% +/- 26% coverage, respectively, in the clot-free midgraft portions of all seeded and unseeded patent grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thoracoscopic Radiofrequency Ablation of the Myocardium

Radiofrequency (RF) catheter ablation has been used for the treatment of ventricular tachycardia (VT), however, in some patients VT might result from subepicardiai macroreentry that could be successfully terminated by epicardial approach. This study examined the feasibility of thoracoscopic RF ablation of myocardium from epicardium using a custom made electrode. In five mongrel dogs, the thoracoscope was introduced through the 7th intercostal space. A 500-kHz continuous wave RF energy was connected to a custom made multiple electrode probe. Under thoracoscopic guidance, the heart was exposed and the RF probe was introduced. RF ablation was performed on the nonvascular ventricular wall of the beating heart. The left ventricular free wall and right ventricular outflow tract were satisfactorily visualized and ablated. The total dose of RF energy ranged from 50 to 500 J. and the estimated volume of ablated lesions ranged from 41.0–799 mm³. There were significant correlations between the RF discharge output and the irradiated lesion volume (P < 0.01), and the depth of the lesions (P < 0.01). Grossly, after RF ablation the ventricular myocardium demonstrated a circular, well-demarcated area of thermal injury. Volume and depth of the lesion depended upon the total dose of delivered RF energy. Thoracoscopic RF ablation appears to be a minimally invasive and useful method for creating irradiated myocardial lesions from epicardial surface. This method could he technically feasible for the treatment of Vts for which endocardial RF ablation is ineffective.     

人骨髓间质干细胞体外扩增和向内皮细胞定向诱导分化的研究

目的：体外分离、扩增成人骨髓间质干细胞（MSCs）和向内皮细胞（ECs）定向诱导分化，开辟心血管组织工程种子细胞的新来源。 方法： 采用Percoll(1 073 g/L)从正常成人骨髓中分离出MSCs，纯化和扩增后流式细胞仪鉴定其纯度；用血管内皮生长因子(VEGF)诱导MSCs向ECs分化，Ⅷ因子(vWF)免疫组化和透射电镜(TEM)鉴定细胞性质。 结果： 5.0×105个MSCs在体外扩增15代后，获得8.0×1012个MSCs，扩增了约1.6×107倍；MSCs在加入VEGF诱导培养大约14-21 d，80%-90%的诱导细胞对Ⅷ因子相关抗原呈阳性反应；TEM可观察到胞浆内有Weible-palade小体，证实为ECs。 结论： 成人骨髓MSCs在体外具有定向诱导分化为ECs的潜能，这为心脏组织工程瓣体外构建, 尤其是在小儿先天性心脏病组织工程研究中种子细胞的来源提供了可能性。     

Abnormalities of iron metabolism and erythropoiesis in vitamin E- deficient rabbits

Rabbits fed a vitamin E-deficient diet developed severe muscular dystrophy in 3-4 wk, but they did not become anemic. Nevertheless, reticulocyte counts increased in deficient rabbits (3.2%) compared to control rabbits (0.9%), and erythroid hyperplasia was evident in the bone marrow. Comparing deficient rabbits to controls, the plasma iron concentration was lower (134.4 versus 206.6 microgram/dl); the TIBC was higher (335.9 versus 228.3 microgram/dl); the whole blood protoporphyrin concentration was higher (131.6 versus 81.7 microgram/dl); and the total iron content was lower in spleen (71 versus 153 microgram), higher in skeletal muscle (4956 versus 3054 microgram), and unchanged in bone marrow, liver, and heart. Studies of iron absorption and excretion using 59Fe showed no abnormalities in deficient rabbits. There were abnormalities of ferrokinetics, however. The half-time of disappearance of 59Fe was shorter (100.6 versus 169.4 min), the plasma iron turnover was greater (1.25 versus 0.95 mg/dl blood/day), and the reappearance of 59Fe in circulating erythrocytes at day 9 was greater (77.2% versus 57.2%) in deficient rabbits. Anemia induced by phlebotomy accentuated the abnormal iron metabolism of deficient rabbits, and the animals were unable to correct the anemia. These findings show that vitamin E deficiency in rabbits causes abnormal erythropoiesis associated with abnormal iron metabolism and sequestration of iron in skeletal muscle.     

A phase II, double-blind, randomized, placebo-controlled, dose comparative study of the efficacy, tolerability, and safety of MCC-135 in subjects with chronic heart failure, NYHA class II/III (MCC-135-GO1 study): rationale and design

BACKGROUND: Chronic heart failure (CHF) can be caused either by a predominant abnormality in systolic function (systolic heart failure) or a predominant abnormality in diastolic function (diastolic heart failure). Randomized clinical trials have identified a number of pharmaceutical agents that can reduce morbidity and mortality in patients with systolic heart failure. Despite significant therapeutic advances, systolic heart failure continues to result in high rates of morbidity and mortality. In contrast to systolic heart failure, no randomized clinical trials have been performed in patients with diastolic heart failure. Common to the mechanisms causing both systolic and diastolic heart failure are abnormalities in calcium homeostasis. Mitsubishi Pharma Corporation has developed a compound (MCC-135, INN; caldaret) whose mechanism of action is proposed to be modulation of calcium homeostasis at the sarcoplasmic reticulum and cellular membrane. The purpose of this study was to test the safety, tolerability, and efficacy of MCC-135 in patients with mild to moderate heart failure. METHODS: This was a phase II, multicenter, randomized, double-blind study of parallel group design comparing 3 oral dose regimens of MCC-135 (5 mg, 25 mg, 50 mg, twice daily) with a placebo control. The treatment period was 24 weeks. A total of 511 patients were recruited from 69 centers in the United States and Europe. One hundred and twenty-five patients were recruited in each of the 4 treatment groups. Patients in each treatment group were divided into 2 cohorts: those with an ejection fraction < or = 40%, and those with an ejection fraction >40% as determined by core laboratory analysis of echocardiographic studies. CONCLUSION: Patient recruitment was completed in September 2002. Patient follow-up was completed by February 2003; the results will be available for release in 2004.