FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Pudendal Thigh Fasciocutaneous Flaps for Vaginal Reconstruction in Gynecologic Oncology

The pudendal thigh is a sensate fasciocutaneous flap supplied by the posterior labial artery. We report on the results of pudendal thigh flaps used for vaginal reconstruction in eight patients at the time of pelvic exenteration (6) and radical vaginectomy (2). Patients were interviewed and results were assessed 5 to 19 months after surgery. The flaps were raised in the thigh creases just lateral to the hair bearing area of the labia majora and included skin, subcutaneous tissues, deep fascia of the thigh, and the epimysium of the adductor muscles. Flap sizes varied from 9 × 4 cm to 15 × 6 cm. Bilateral flaps were used in seven patients. The flaps were technically easy to perform. Partial (apical) flap necrosis occurred in four patients. One patient developed complete necrosis of bilateral flaps, followed by an enterovaginal fistula. One patient whose flaps did not necrose developed a rectovaginal fistula at the site of rectal reanastomosis. The functional results are disappointing. The only patient having successful vaginal intercourse had a unilateral flap reconstruction following lower vaginectomy in a nonirradiated pelvis. No patient with bilateral flaps or prior pelvic irradiation has had successful coitus. Other long-term sequelae include vulvar pain (2), chronic vaginal discharge (2), hair growth (4), and protrusion of the flaps (2). These vulvovaginal symptoms discourage patients and their partners from genital contact. Breaching the integrity of the vulva to construct a neovagina that is likely to be unsuitable for sexual intercourse may deprive women of their only potential for normal genital sexual responsiveness. Techniques of vaginoplasty require continued assessment.     

Effect of budesonide on pulmonary hyperinflation in young asthmatic children.

In 19 asthmatic children, aged 2-6 years, the effect of six weeks' treatment with inhaled budesonide or placebo on functional residual capacity (FRC--helium dilution) and bronchodilator responsiveness was assessed in a double blind, randomised crossover trial. FRC was increased in most children at the start of treatment. Treatment with budesonide was associated with a reduction in FRC by comparison with placebo (median change 9% v 0%; p less than 0.05). There was a trend towards a greater response to a bronchodilator after budesonide. The results suggest that inhaled corticosteroids reduce hyperinflation in young asthmatic children.     

The physiological regulation of toll-like receptor expression and function in humans

Eleven mammalian toll-like receptors (TLRs 1–11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14⁺ monocytes following activation with specific TLR ligands was greater ( P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34°C). Strenuous exercise resulted in a decrease ( P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14⁺ monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14⁺ monocytes following activation with specific TLR ligands was decreased ( P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.     

溴莫尼定对视网膜缺血性损伤神经保护作用的实验研究

目的：探讨溴莫尼定(brimonidine)对视网膜缺血性损伤神经的保护作用。方法：新西兰大耳白兔32只，随机分为正常对照组、生理盐水治疗组、噻吗心安(timolol)治疗组、brimonidine治疗组，每组8只。后3组为损伤治疗组，通过生理盐水前房高压灌注的方法，制成视网膜缺血动物模型，在视网膜缺血前lh其结膜囊内分剐给予生理盐水、0．5％timolol眼液或0．2％brimonidine眼液局部治疗。在灌注后7d，观察图形视网膜电图(P-ERG)b波振幅变化，并进行组织形态学观察和视网膜神经节细胞(RGC)计数分析。结果：灌注后7d，3个损伤治疗组相对b波振幅恢复率为：7％、11％和64％，RGC标准丢失率为：43％、38％和12％，brimori-die治疗组视网膜组织形态结构接近正常对照组，而生理盐水治疗组和timolol治疗组视网膜内层组织结构损伤明显。结论：Brimonidine局部治疗对缺血诱导的视网膜结构和功能的损害有明显的神经保护作用。