Isoxazolines as potent antagonists of the integrin alpha(v)beta(3)

Starting with lead compound 2, we sought to increase the selectivity for alpha(v)beta(3)-mediated cell adhesion by examining the effects of structural changes in both the guanidine mimetic and the substituent alpha to the carboxylate. To prepare some of the desired aminoimidazoles, a novel reductive amination utilizing a trityl-protected aminoimidazole was developed. It was found that guanidine mimetics with a wide range of pK(a)'s were potent antagonists of alpha(v)beta(3). In general, it appeared that an acylated 2-aminoimidazole guanidine mimetic imparted excellent selectivity for alpha(v)beta(3)-mediated adhesion versus alpha(IIb)beta(3)-mediated platelet aggregation, with selectivity of approximately 3 orders of magnitude observed for compounds 3g and 3h. It was also found in this series that the alpha-substituent was required for potent activity and that 2,6-disubstituted arylsulfonamides were optimal. In addition, the selective alpha(v)beta(3) antagonist 3h was found to be a potent inhibitor of alpha(v)beta(3)-mediated cell migration.     

Myofibers in tongues of Down's syndrome

Muscle samples from the anterior part of the tongue in 15 patients with Down's syndrome (undergoing partial glossectomy), and 6 post-mortem controls, were examined histochemically. In most cases there was a Type 2 myofiber hypertrophy and preponderance, with frequent type 'grouplet' formation. In four cases examined ultrastructurally, hyperplastic, disorganized and atrophic neuromuscular junctions were seen. These preliminary ultrastructural findings suggest that synaptic morphometry could be a rewarding method of studying neuromuscular deficits in Down's syndrome.     

Effect of quinolone antimicrobials on theophylline pharmacokinetics

The purpose of the research was to ascertain the comparative differences of quinolone antibiotics on theophylline pharmacokinetics. Eight healthy male volunteers were randomly assigned to four treatments. Each was administered norfloxacin (NOR) 800 mg/d, ciprofloxacin (C) 1 g/d, nalidixic acid (NAL) 2 g/d and placebo (P) for 7 days. On the seventh day of each treatment, theophylline (5 mg/kg) iv was administered. The elimination half-life (T 1/2), total body clearance (CL) and volume of distribution at steady state (Vss) of theophylline were calculated using model-independent methods. ANOVA for repeated measures was used for data comparisons. The mean (SD) theophylline results were: CL l/kg/h--NOR .038 (.006), C .033 (.006), NAL .045 (.008), P .044 (.007); T 1/2 h--NOR 9.2 (1.8), C 10.6 (1.8), NAL 8.3 (1.8), P 7.5 (1.4). Theophylline Vss differences by treatment were not significant. NOR and C significantly decreased theophylline's clearance and the clearance change can be of clinical significance.     

Stitch removal from hair-bearing areas: a simple method

A simple method to ease the removal of stitches in hair-bearing areas is presented. The method consists of applying a depilatory cream to remove the masking hair.     

Life satisfaction, self-esteem, and perceived health status among elder Korean women: focus on living arrangements.

The purpose of this study was to examine whether living arrangements significantly affect life satisfaction, self-esteem, and perceived health status of elder Korean women. A total of 121 women aged 65 to 89 was interviewed in an urban community senior center in Korea. The convenience sample was obtained by face-to-face interviews using a structured questionnaire. Life satisfaction, self-esteem, and perceived health status were strongly correlated with each other. Living arrangements significantly affected life satisfaction, self-esteem, and perceived health status. Women who live with their married son had the highest life satisfaction and self-esteem and perceived themselves to be healthier in comparison to their counterparts. Therefore, government programs need to be developed to assist children in caring for their parents to improve their overall well-being.     

检查前用药可降低乳腺钼钯X线检查中的不适

目的验证乳腺钼钯X线检查前给予对乙酰氨基酚、布洛酚和(或)4%利多卡因凝胶能否减轻检查不适或提高普查中有恐惧感妇女的满意度。方法本前瞻性研究为     

Symptoms of depression prospectively predict poorer self‐care in patients with Type 2 diabetes

Aims To examine prospectively the association of depression symptoms with subsequent self‐care and medication adherence in patients with Type 2 diabetes mellitus. Methods Two hundred and eight primary care patients with Type 2 diabetes completed the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) and the Summary of Diabetes Self‐Care Activities (SDSCA) at baseline and at follow‐up, an average of 9 months later. They also self‐reported medication adherence at baseline and at a follow‐up. Results Baseline HANDS scores ranged from 0 to 27, with a mean score of 5.15 ± 4.99. In separate linear regression models that adjusted for baseline self‐care, patients with higher levels of depressive symptoms at baseline reported significantly lower adherence to general diet recommendations and specific recommendations for consumption of fruits and vegetables and spacing of carbohydrates; less exercise; and poorer foot care at follow‐up (β ranging from ?0.12 to ?0.23; P < 0.05). Similarly, each one‐point increase in baseline HANDS score was associated with a 1.08‐fold increase in the odds of non‐adherence to prescribed medication at follow‐up (95% confidence interval 1.001, 1.158, P = 0.047). Increases in depression scores over time also predicted poorer adherence to aspects of diet and exercise. Conclusions Depressive symptoms predict subsequent non‐adherence to important aspects of self‐care in patients with Type 2 diabetes, even after controlling for baseline self‐care. Although the relationship between symptoms of depression and poorer diabetes self‐care is consistent, it is not large, and interventions may need to address depression and self‐care skills simultaneously in order to maximize effects on diabetes outcomes.     

Pull-through approach to percutaneous angioplasty of totally occluded common iliac arteries

A method has been developed to increase the probability of success of percutaneous transluminal balloon angioplasty of total occlusions of the common iliac artery when conventional methods have failed. In 10 patients with a totally obstructed iliac artery, a guide wire was passed through a catheter placed from the contralateral side around the aortic bifurcation and antegrade through the total obstruction. The end of the wire was either snared by a retrieval basket or guided through a sheath in the ipsilateral common femoral artery, thus providing a firmly anchored pathway for subsequent manipulations. Balloons were then inserted retrograde through both common femoral arteries and dilated. In the first five patients, ipsilateral retrograde passage of a guide wire had failed despite multiple attempts with a variety of devices. In the other five patients, the contralateral antegrade approach was used initially. The new method was successful in all 10 patients with totally obstructed common iliac arteries.