A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

Effectiveness of exercise in patients with osteoarthritis of hip or knee: nine months' follow up

OBJECTIVE: To determine whether the effects of an exercise programme in patients with osteoarthritis of hip or knee are sustained at six and nine months' follow up. METHODS: A randomised, single blind, clinical trial was conducted in a primary care setting. Patients with osteoarthritis of hip or knee (ACR criteria) were selected. Two intervention groups were compared. Both groups received treatment from their general practitioner, including patient education and drug treatment if necessary. The experimental group also received exercise treatment from a physiotherapist in primary care. The treatment period was 12 weeks, with an ensuing 24 week follow up. The main outcome measures were pain, drug use (non-steroidal anti-inflammatory drugs), and observed disability. RESULTS: 201 patients were randomly allocated to the exercise or control group, and 183 patients completed the trial. At 24 weeks exercise treatment was associated with a small to moderate effect on pain during the past week (difference in change between the two groups -11.5 (95% CI -19.7 to -3.3). At 36 weeks no differences were found between the groups. CONCLUSIONS: Beneficial effects of exercise decline over time and finally disappear.     

A STD/HIV prevention trial among adolescents in managed care

OBJECTIVE: To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors. DESIGN: A randomized intervention trial with 3- and 9-month follow-up. SETTING: Five staff-model managed care sites in Washington, DC (n = 19 pediatricians). PATIENTS: Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%). INTERVENTION: Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence). MAIN OUTCOME MEASURES: Adolescent-reported sexual intercourse and condom use. RESULTS: More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94). CONCLUSIONS: STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.     

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.     

A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial

Background  

Because of a high cardiovascular disease (CVD) risk in people with Familial Hypercholesterolemia (FH), early prevention of cardiovascular disease is important for health gain and cost reduction. This project focuses on the development and evaluation of an innovative intervention aiming to reduce CVD risk by promoting a healthy lifestyle among people with FH.     

乙稀雌酚肌注致心房纤颤1例

1　病例报告　男 ,71岁 ,因排尿困难于 1999- 0 9- 0 4入院 .B超确诊前列腺增生 5 a,既往无高血压、心脏病及心率失常史 .查体 :Bp17/ 10 k Pa,心界不大 ,心率 6 2次· min- 1 ,心律齐 .下腹部可触及涨大的膀胱 ,约耻骨上 4指 .入院时 ECG正常 .肝肾功能无异常 ,确诊前列腺增生伴急性尿潴留 .首先予导尿 ,导出尿液约 90 0 m L,之后 im乙稀雌酚 1mg,2 h后患者突发心慌、胸闷、气短、心前区疼痛 .发现患者大汗BP12 /6 k Pa,P110次· min- 1 ,R2 8次· min- 1 ,心率绝对不齐 ,脉搏明显短促 ,两肺底可闻及湿性罗音及哮鸣音 ,ECG示房颤 ,心…     

Internet网上细胞凋亡研究的信息资源及其利用

0　引言　 Internet网上含有丰富的信息资源 ,科研人员可以通过 Internet网了解其所研究领域的最新发展动态 ,获取全面和系统的科研信息 ,有利于进行学术交流[1 ] .然而网上信息浩如烟海 ,当检索某一专门领域的资料时 ,有时无从下手 .我们在科研实践中对 Internet网上主要的细胞凋亡研究信息资源及其查找方法进行了归纳 .1　细胞凋亡专业网站1. 1　 The Cell death society (http:/ / www.celldeath-apoptosis.org)　为美国细胞死亡学会主办 ,概括了细胞凋亡和程序性细胞死亡研究的各个领域 ,包括与细胞凋亡有关的各种疾病 .可以免费注册…     

Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy

The radiopharmaceutical iodine 131 metaiodobenzylguanidine (I-131 MIBG) has been shown to locate pheochromocytomas scintigraphically with a false-negative rate of approximately 13%. To improve image quality and reduce the false-negative rate, I-123 was examined as a radioactive label for MIBG, as it has many advantages over I-131, including superior dosimetry and better detection efficiency. Diagnostic doses of 0.5 mCi (18.5 MBq) I-131 MIBG and 10.0 mCi (370.0 MBq) I-123 MIBG with nearly equivalent radiation dosimetries were compared in 18 patients with known or suspected pheochromocytomas. Images of superior quality were obtained with I-123 MIBG in 18 of 18 patients, and in eight cases lesions not visualized on I-131 MIBG scintigraphy were portrayed. A further advantage of I-123 MIBG is that it permits single photon emission computed tomography (SPECT). This was performed in six cases and provided additional information in three cases. The adrenal medullae were definitely visualized using I-123 scintigraphy in eight of 14 patients still possessing adrenal glands, whereas I-131 MIBG images portrayed the adrenal medulla in only one of 14 cases. Five remaining patients had multiple abdominal tumor deposits that were difficult to differentiate from normal adrenal medullae.     

胫后血管逆行皮瓣修复足部肿瘤性软组织缺损

目的探讨足部软组织肿瘤扩大切除术后出现缺损的修复方法.方法自1989年10月～2001年10月,应用胫后血管逆行岛状皮瓣修复15例足部软组织肿瘤扩大切除术后的缺损.结果15例患者随访12～84个月,平均38个月.胫后血管逆性岛状皮瓣完全成活,并且无局部复发.结论小腿内侧胫后血管逆行岛状皮瓣修复足部肿瘤性软组织缺损是理想的选择.具有就近取材、皮肤色泽结构相似,操作简单的特点.