Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers

Study Objective . To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. Design . Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. Setting . A university medical center. Patients . Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions . Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. Conclusions . Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

An Assessment of Recent Pharmacy Graduates' Knowledge and Competency,Professional Practice Functions,and Involvement in Pharmacy Teaching Programs

Study Objectives . To determine self-evaluated professional knowledge and competency, functions, demographic information, lifelong learning, degree and training status, practice sites, involvement in pharmacy teaching programs, and salary for recent pharmacy graduates. Design . A survey of recent Bachelor of Science (B.S.) pharmacy graduates of the University of Wisconsin School of Pharmacy. Measurements and Main Results . A total of 371 B.S. pharmacy graduates (55% response rate) provided information. Graduates who had an advanced degree or training (from many programs) after completing their B.S. pharmacy degree, and those who were teaching in pharmacy programs generally had higher self-rated levels of knowledge and competencies. Hospital pharmacists spent less of their work time in dispensing activities (33.82% ± 30.39%) than community pharmacists (61.04% ± 19.97%; t =8.78, df = 288, p<0.001); community pharmacists spent twice as much of their work time counseling and educating patients (16.65% ± 10.47% vs 7.13% ± 7.39%; t = 9.06, df = 288, p<0.001). The amount of time pharmacists spent in dispensing functions had a negative association with knowledge and competencies in the sections on pharmacokinetic and disease process (r=−0.277, p<0.01), patient communications (r=−0.272, p<0.01), and administrative and economic aspects of practice (r=−0.210, p<0.01) for all respondents. Pharmacists reported that they spent 13.78 ± 14.06 hours per month outside work in professional lifelong learning. There was a negative association between the time pharmacists spent dispensing and the time they spent in professional lifelong learning (r=−0.239, p<0.001), and a positive relationship between the time spent in such learning and the time providing information to prescribers and other health care professionals (r=0.214, p<0.001), monitoring patients (r=0.216, p<0.001), and performing primary care activities (r=0.176, p<0.001). Graduates reported a mean yearly salary of $46,879 ± $8183. More hospital pharmacists were involved in teaching (48, 37%) than those practicing in a community setting (19, 12%). Conclusions . Practice site, advanced degree or training, lifelong learning, involvement in teaching programs, and time spent in various professional functions were associated with pharmacists' self-rated knowledge and competencies. (Pharmacotherapy 1994;14(6):712–723)     

Ampicillin-Sulbactam versus Cefoxitin for Prophylaxis in High-Risk Patients Undergoing Abdominal Surgery

This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p>0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p>0.05). Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.     

钕钇铝石榴石激光治疗后囊混浊（353例）

采用钕钆铝石榴石激光切除白内障囊外摘除术后１０１例后房人工晶体植入后２５２例的后囊混浊共３５３例，激光治疗疗后视力均明显提高，矫正视力＞１．０者占８２．４％，无１例＜０．５。无明显并发症。     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

细胞内钙信号的变化调节血管平滑肌细胞增殖

目的探讨细胞内钙信号的变化对大鼠血管平滑肌细胞(VSMC)增殖作用的影响及其对细胞内信号转导机制的变化。方法以培养的大鼠VSMC为模型,用雷尼丁(RY)剌激VSMC内贮Ca2 释放入胞浆,用3H亮氨酸及3H胸腺嘧啶掺入量作为反应VSMC增殖的指标,加入不同的细胞内信号转导阻断剂,观察对RY效应的影响。结果与对照组相比,RY浓度依赖性地促进细胞内游离钙浓度的增高,差异显著(P<0.05或0.01)。RY剌激组蛋白核酸合成速率明显增高,与对照组相比差异显著(P<0.01);尼卡地平(Nicardipine),蛋白激酶C抑制剂(H7),钙调素激酶(CaMPK)抑制剂(W7)和丝裂素活化蛋白激酶(MAPK)抑制剂(PD98059)能明显抑制RY介导的VSMC蛋白核酸合成速率增高,与RY剌激组相比差异显著(P<0.01)。结论细胞内钙信号的变化明显促进VSMC增殖,但其效应可能通过Ca2 、PKC、MAPK来介导。钙离子拮抗剂可抑制血管平滑肌细胞增殖。     

前颌中缝牵张修复牙槽裂的实验研究

目的　探索用缝牵张成骨技术以组织再生的原理修复牙槽裂。方法　采用犬牙槽裂模型 ,牙槽裂形成术后 2周 ,于前颌中缝处安置缝牵张器 ,外张力 2 0 0g。牵张 2～ 3周 ,裂隙侧的前颌骨向侧方移动贴紧远中裂缘 ,用局部黏骨膜瓣修复牙槽裂隙。保持 2周后去除缝牵张器。临床观察、连续X线、头颅干骨和组织学检查评价治疗结果。结果　所有对照动物形成规则的牙槽裂 ,无自发骨性愈合。前颌中缝牵张后 ,裂隙侧前颌缓慢向裂侧上颌靠拢 ,2～ 3周与远中裂缘密切贴合。X线片示前颌中缝呈现由窄渐宽的三角形 ,三角形的尖端指向后方 ,三角区域的骨密度逐渐增加。骨膜成形术后 3个月 ,原牙槽嵴缺损处骨质连续性完全恢复 ,且牙槽骨段在三维方向上均与对侧相同。前颌中缝恢复正常直线形态。结论　该牙槽裂模型稳定性和重复性好 ;前颌中缝牵张诱导缝区新骨形成 ,一侧前颌向裂隙移位和局部骨膜成形可达到完善的牙槽裂修复。     

避孕

Theresa Carroll,40岁,是一位有两个孩子的离异母亲,今天来诊所进行年度体格检查.Theresa是Re-becca Thompson的家庭医生,已经有5年了.