防治成人呼吸窘迫综合征的人工重组肺泡表面活性剂研制II.生物发光法筛选制剂处方

在前期用表面化学方法进行防治成人呼吸窘迫综合征的药物制剂处方筛选基础上，通过建立尘肺动物模型，用生物发光技术从清除自由基能力角度对制剂进行处方筛选，获到了有良好表面性能和一定自由基清除能力的人工重组肺泡表面活性剂制剂处方。该制剂有待经模型动物防治试验评价。     

SARS: prognosis, outcome and sequelae

Severe acute respiratory syndrome (SARS) is associated with considerable morbidity and mortality in the acute phase. Worldwide case fatality rate is 11% (range 7 to 27%) for the most severely affected regions. Several adverse prognostic factors have been identified, including advanced age, presence of comorbidity, higher lactose dehydrogenase levels and initial neutrophil count, but the impact of viral and other host factors on outcome is unknown. Published data on sequelae of SARS are limited. Clinical follow-up of patients who recovered from SARS has demonstrated radiological, functional and psychological abnormalities of varying degrees. In the early rehabilitation phase, many complained of limitations in physical function from general weakness and/or shortness of breath. In a small series of subjects who underwent CT scan of the chest, over half showed some patchy changes consistent with pulmonary fibrosis. Lung function testing at 6–8 weeks after hospital discharge showed mild or moderate restrictive pattern consistent with muscle weakness in 6–20% of subjects. Mild decrease in carbon monoxide diffusing capacity was detected in a minority of subjects. Preliminary evidence suggests that these lung function abnormalities will improve over time. Psychobehavioural problems of anxiety and/or depression were not uncommon in the early recovery phase, and improved over time in the majority of patients. Avascular necrosis of the hip has been reported as another complication. The long-term sequelae of SARS are still largely unknown. It is important to follow up these patients to detect and appropriately manage any persistent or emerging long-term sequelae in the physical, psychological and social domains.     

The abnormal response of polycystic ovarian disease patients to exogenous pulsatile gonadotropin-releasing hormone: characterization and management

Pulsatile GnRH administration for induction of ovulation is often ineffective in polycystic ovarian disease (PCOD) patients. To clarify and correct the endocrine mechanisms underlying this deranged response we gave pulsatile GnRH (5 micrograms, iv, every 60 min) to idiopathic hypogonadotropic hypogonadism (IHH) patients with primary amenorrhea for 19 cycles and to PCOD patients for 24 cycles before (pre-A) and for 25 cycles after (post-A) GnRH analog suppression. Compared to IHH, pre-A cycles were characterized by elevated LH, estradiol, and testosterone; reduced luteal phase progesterone; and low ovulatory (38%) and pregnancy rates (8%). Conversely, LH, estradiol, and follicular phase testosterone levels were lower in post-A than in pre-A cycles, while luteal phase progesterone was higher; the endocrine pattern of post-A cycles closely resembled the one of IHH cycles. The ovulatory and pregnancy rates of PCOD patients improved remarkably in post-A cycles (90% and 38%, respectively). Excessive body weight was associated with a lower incidence of ovulation in both pre-A (15%) and post-A cycles (75%). A worse endocrine pattern and a lower ovulatory rate (50%) were obtained when a second consecutive post-A cycle occurred without repeating GnRH analog suppression. No signs of even mild ovarian hyperstimulation and no multiple pregnancies were recorded in the post-A cycles. We conclude that in PCOD 1) deranged pituitary sensitivity, excessive ovarian androgen secretion, and obesity critically affect folliculogenesis and ovulation; 2) pituitary-gonadal suppression with a GnRH analog markedly improves the endocrine and clinical responses to pulsatile GnRH ovulation induction; 3) optimal results can be achieved only when each pulsatile GnRH cycle is preceded by GnRH analog suppression; and 4) pulsatile GnRH is highly effective and safe for ovulation induction, provided that PCOD subjects are pretreated with a GnRH analog.     

The Effectiveness of Loyalty Rewards to Promote the Use of an Internet-Based Heart Health Program

Background

Internet-based health programs have been shown to be effective in reducing risk for cardiovascular disease. However, their rates of enrollment and engagement remain low. It is currently unclear whether rewards from established loyalty programs can serve as a conditioned stimulus to improve the use of a freely available Internet-based program.

Objective

The objectives of the study were to (1) examine enrollment rates and levels of engagement with the My Health eSupport program between a Conditioned Reward group and a Control group, and (2) investigate the influence of loyalty rewards and participant characteristics on levels of enrollment and program engagement.

Methods

The study sample (n=142,726) consisted of individuals who were offered enrollment in an Internet-based health intervention (My Health eSupport) after completing the Heart&Stroke Risk Assessment on the Heart and Stroke Foundation website. My Health eSupport programs provided encouragement and tips for lifestyle change. This is a free, self-guided, fully automated program that proactively delivers tailored email messages at 2-week intervals based on the participant’s stage of motivational “readiness” and priority for lifestyle change. Participants in the Conditioned Reward group were offered a single exposure of 20 loyalty reward points from the Air Miles loyalty program for completing the Heart&Stroke Risk Assessment (10 reward points) and enrolling in the Internet-based program (10 reward points). Meanwhile, no rewards were given to the Control group participants. All data were collected between February 1, 2011 and February 10, 2012.

Results

In total, 51.38% (73,327/142,726) of individuals in the Conditioned Reward group and 48.62% (69,399/142,726) of individuals in the Control group completed the Heart&Stroke Risk Assessment. Subsequently, significantly more individuals from the Conditioned Reward group (52.96%, 38,835/73,327) enrolled in the My Health eSupport program than Controls (4.07%, 2826/69,399). Regression analyses indicated that individuals were 27.9 times (95% CI 26.4-29.4; P<.001) more likely to join the My Health eSupport program when presented with loyalty rewards controlling for gender, age, education, ethnicity, employment, and number of modifiable risk factors. However, ongoing engagement level was low in both groups and it was not influenced by loyalty rewards. Instead, individuals were more likely to engage with the My Health eSupport program if they were greater than 60 years of age (OR 12.56, 95% CI 5.66-27.8; P<.001), were female (OR 1.27, 95% CI 1.09-1.46; P=.002), or had one or more modifiable risk factors (OR 1.38, 95% CI 1.31-1.45; P<.001).

Conclusions

Our findings suggest that a single exposure of loyalty rewards may be used to encourage individuals to enroll in an Internet-based preventative health program, but additional strategies are required to maintain engagement level. Future studies need to examine the schedules of loyalty reward reinforcement on the long-term engagement level of Internet-based health programs.     

Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry

Synchronous video tape fluoroscopy and manometry of the esophagus was performed in 11 subjects (seven men and four women; mean age, 49 years). Four had normal and seven had abnormal esophageal motility (diffuse esophageal spasm, n = 4; nonspecific esophageal motility disorder, n = 3) that was shown by previous manometry. A digital timer appeared on the video tape recording and marked the manometric tracing synchronously. Alternate 5-mL and 10-mL barium boluses were recorded for a total of 10 swallows per patient. Video tape examinations were reviewed prospectively, and the status of primary peristalsis and presence and severity of tertiary activity were noted. A total of 98 swallows (58 normal, 40 abnormal) were correlated, and a 96% agreement was found in assessing primary peristalsis. Overall results of fluoroscopic examinations of each subject during all swallows showed complete agreement with those of manometry; segregating the swallows into groups of five showed 92% concordance. Severe tertiary activity was invariably seen with abnormal primary peristalsis at fluoroscopy.     

前路减压及深低温冷冻异体腓骨移植改善上胸段严重结核性后凸畸形患者脊髓功能

目的:观察前路经胸减压,深低温冷冻同种异体腓骨移植对上胸段(顶椎位于T2￣6)陈旧性结核所致的严重后凸畸形患者脊髓功能的影响。方法:选择1999-01/2005-01四川大学华西医院收治的陈旧性结核所致上胸段严重后凸畸形(后凸角>60°)合并不全截瘫的手术患者7例,3例患者在15岁以下,患者或其家属都理解并同意手术方案。均行前路(旋肩胛切口)经胸减压,深低温冷冻异体腓骨支撑植骨融合 /-后路自体骨植骨融合手术以治疗严重后凸畸形,手术均不矫正后凸,准备植骨床后,稍撑开融合节段的上下固定椎约5mm,前方放置深低温冷冻同种异体腓骨条(华西医院骨库提供,来源是捐献尸体和因外伤截除的肢体。异体腓骨经过常规脱脂、脱细胞、浸泡消毒和深低温冷冻后已极大地降低了其免疫原性),后方放肋骨条做支撑植骨,并将剩余自体骨剪成小条填充在植骨空隙间。术后需石膏(支具)辅助外固定8￣10个月。记录评估手术的并发症、植骨融合情况以及手术前和随访期末时脊髓功能(Frankel脊髓损伤分级A￣E:全瘫￣基本正常或无瘫痪)、背部疼痛情况(0￣3:无￣严重)和活动能力(1￣4:卧床￣无需辅助)。结果:7例患者全部得到随访,术后平均随访3.4年(1.5￣5年)。①所有患者的植骨均获融合,有1例患者术后复查时发现植入的异体腓骨轻度移位,未见植骨块骨折,术后后凸畸形无加重。②无术后脊髓功能恶化者,有2例FrankelC级恢复至E级,2例C级恢复至D级,以上4例中3例为青少年,且均无需辅助即能行走;其余3例成人术前后Frankel分级无变化。所有患者的背痛均缓解。结论:冷冻异体腓骨可有效用于治疗陈旧性结核所致的上胸段严重后凸畸形患者,前路减压和融合可以缓解疼痛,改善活动能力,尤其有利于青少年患者脊髓功能恢复。     

安定在家兔体内的肠胃循环药代动力学分析

6只家兔iv安定5 mg·kg^-1后,浓度—时间数据呈现双峰形。本文提出肠胃循环动力学模型,用于分析实测数据,得到了一般动力学参数:T_1/2(α)=0.21±=0.15 h,T_1/2(β)=2.2+0.6 h,K_e=1.5±0.6 h^-1,K₁₂=2.0±1.0 h^-1,K₂₁=1.0±0.4 h^-1,V₁=3.1±1.6 L·kg^-1,AUC=1.7±0.5μg·h^-1·ml^-1。此外,还求得有关肠胃循环的参数,即:重吸收滞后时间T′=0.25±0.24h,重吸收速率常数K_A=3.5±1.4 h^-1,重吸收率R_A=24±7%。