Cyclosporine in glomerular disease

Cyclosporine was introduced in 1981 as an immunosuppressive agent in renal transplantation. Its use was soon extended to the treatment of various glomerular disorders. In light of its known immunomodulating effects, the use of cyclosporine has been most prominent in those glomerular diseases thought to have an immune basis. The most careful studies of cyclosporine in glomerular diseases have been performed in the pediatric population with idiopathic nephrotic syndrome (i.e., minimal change disease and focal segmental glomerulosclerosis), although data are accumulating regarding efficacy and safety in adults with idiopathic nephrotic syndrome. In patients who are steroid-dependent, cyclosporine therapy can induce complete or partial remission in a significant proportion of cases; success rates in patients with steroid-resistant nephrotic syndrome are less encouraging. Treatment with cyclosporine allows for dose reduction or elimination of corticosteroids, and the consequent salutary effect on growth in the child and glucose and bone metabolism in all patients. Studies that suggest a potential benefit of cyclosporine in recurrent nephrotic syndrome in renal allografts and in other glomerular diseases are also discussed.     

Preferred strategies for secondary infrainguinal bypass: lessons learned from 300 consecutive reoperations

PURPOSE: To determine the optimal surgical strategies in reoperative infrainguinal bypass, we reviewed our results in 300 consecutive secondary bypasses in 251 patients operated on between Jan. 1, 1975, and Nov. 1, 1993. METHODS: There were 168 men (67%) and 83 women (33%), with a mean age of 64.8 years and a typical distribution of risk factors including smoking (76.4%), diabetes (33.7%), and coronary artery disease (47.1%). The indications for surgery were limb-threatening ischemia in 83.5% and severe claudication in 16.5% of patients. The majority of conduits (n = 213) were autogenous vein and were composed of a single segment of greater saphenous vein in 121 bypasses (57%) and various alternative veins including composite, arm, and lesser saphenous vein in 92 bypasses (43%). Prosthetic conduits included 69 polytetrafluoroethylene, 16 umbilical vein, and two Dacron grafts. RESULTS: There was one perioperative death (0.3%) and a 25% total morbidity rate including a 1.7% myocardial infarction rate. There was a 28.6% early (< 30 days) graft failure and 10.7% early amputation rate for prosthetic bypass grafts compared with 13.6% early graft failure and 5.6% early amputation rates for vein grafts. Autogenous vein bypasses had higher 5-year secondary patency rates than had prosthetic grafts (51.5% +/- 4.6% vs 27.4% +/- 6.1%, p < 0.001). Results with autogenous vein bypass improved significantly from the 1975 to 1984 to the 1985 to 1993 interval with 5-year secondary patency rates increasing from 38.3% +/- 6.9% to 59.1% +/- 5.8% (p = 0.017) and 5-year limb-salvage rates increasing from 40.4% +/- 7.6% to 72.4% +/- 6.6% (p < 0.001). Vein grafts to the popliteal and tibial outflow levels had equivalent long-term results. Vein grafts completed for claudication demonstrated results superior to those for limb salvage, with a 5-year secondary patency rate of 75.8% +/- 8.1% versus 52.3% +/- 7.9% (p = 0.048). Secondary autogenous vein bypass grafting performed after early primary graft failure (< 3 months) did particularly poorly, with only a 27.2% +/- 7.7% 4-year secondary patency rate. Greater saphenous veins tended to perform better than alternative vein bypasses, with a 5-year secondary patency rate of 68.5% +/- 6.0% compared with 48.3% +/- 10.5% (p = 0.09) and a 5-year limb-salvage rate of 77.8% +/- 7.4% versus 54.2% +/- 11.8% (p = 0.046). CONCLUSIONS: When patients suffer a recurrence of limb-threatening ischemia at the time of infrainguinal graft failure, aggressive attempts at secondary revascularization with autogenous vein are warranted based on the low surgical morbidity and mortality rates and the improved patency and limb salvage rates that are currently attainable.     

Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.     

Hidden Implementation Dependencies in High Assurance and Critical Computing Systems

Critical and catastrophic failures in high assurance and critical computing systems can arise from unfounded assumptions of independence between system components, requirements, and constraints (work product sections), which can stem from misunderstandings and miscommunication between system engineers, managers, and operators and from inadequate or incomplete traceability between system work products. In this article, we propose a formal framework for the effective implementation of traceability between work product sections along with a technique for discovering potential causes of critical failures in high assurance and critical computing system models. We introduce a new abstraction of interrelated work product sections called implementation meta-work product and describe how our technique finds these meta-work products. We also demonstrate how this technique can be used to help analysts discover potential causes of safety-related errors in high assurance and critical computing systems by applying it to one case study of a known critical error and to one case study where we anticipate potential safety hazards     

Benefits of collecting local data on breast cancer and mammography practices in northwestern Pennsylvania

OBJECTIVES: A randomized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking. METHODS: Thirty-two work sites were randomized to treatment or no treatment for 2 years. Treatment consisted of health education classes combined with a payroll-based incentive system. Evaluation was based on cohort and cross-sectional surveys. RESULTS: Of 10,000 total employees in treatment work sites, 2041 and 270 participated in weight control and smoking cessation programs, respectively. Weight losses averaged 4.8 lbs, and 43% of smoking participants quit. Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0% and 2.1% in cross-sectional and cohort surveys, respectively. No treatment effect was found for weight. Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs (r = .45 for smoking and r = .55 for weight). CONCLUSIONS: This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile.     

Activation of auditory cortex during silent lipreading

Watching a speaker's lips during face-to-face conversation (lipreading) markedly improves speech perception, particularly in noisy conditions. With functional magnetic resonance imaging it was found that these linguistic visual cues are sufficient to activate auditory cortex in normal hearing individuals in the absence of auditory speech sounds. Two further experiments suggest that these auditory cortical areas are not engaged when an individual is viewing nonlinguistic facial movements but appear to be activated by silent meaningless speechlike movements (pseudospeech). This supports psycholinguistic evidence that seen speech influences the perception of heard speech at a prelexical stage.