Pharmacologic C5-complement suppression reduces blood loss during on-pump cardiac surgery

BACKGROUND: Inflammation contributes to morbidity following on-pump cardiac surgery. Complement activation during cardiopulmonary bypass has been associated with the postoperative bleeding and tissue injury. This study examines the pharmacology and impact on blood loss of complement C5 suppression with pexelizumab in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Pexelizumab, a humanized monoclonal antibody single-chain fragment that binds to the human C5 complement component, was studied in a Phase II multicentered clinical trial. CABG (n = 800) and CABG with concomitant valve surgery (n = 114) patients were evaluated. Patients were randomized to either: pexelizumab bolus (2.0 mg/kg) + placebo infusion; pexelizumab bolus (2.0 mg/kg) + pexelizumab infusion (0.05 mg/kg/hour for 24 hours); or placebo bolus + placebo infusion. Pharmacology, chest tube drainage, and transfusion requirements were assessed. RESULTS: Mean maximum pexelizumab serum concentration was similar for bolus and bolus + infusion-treated patients. Complement-dependent serum hemolytic activity was completely suppressed within 1 hour following pexelizumab bolus, however, suppression was maintained for a longer duration in the bolus + infusion compared to the bolus-only treated patients. A reduction in chest tube drainage was observed for all pexelizumab-treated patients, although transfusion of blood products was similar across all study groups. CONCLUSION: Pexelizumab administration inhibits complement-dependent hemolytic activity and is associated with a reduction in postoperative chest tube drainage in patients undergoing cardiac surgery requiring cardiopulmonary bypass. Further, clinical studies are needed to assess the value of complement attenuation in this setting.     

First prize: ureteral segmental replacement revisited

BACKGROUND AND PURPOSE: Long strictures of the proximal ureter are difficult to manage, and circumferential replacement with various natural and synthetic materials has been unsuccessful. We sought to use cultured autologous cells seeded onto graft material for proximal-ureteral replacement. Additionally, we wished to determine if urothelial cell-seeded de-epithelialized small bowel would generate adequate ureteral replacement. MATERIALS AND METHODS: Three sets of experiments were performed. First, autologous pig-bladder smooth-muscle and urothelial cells were expanded in culture on large sheets of multilayer small-intestinal submucosa (SIS). These sheets were then tubularized and used to replace a 5-cm segment of proximal ureter in pigs. Second, autologous cells harvested from the bladders of Beagle dogs were cultured and seeded on porcine ureteral acellular matrix, which was used to replace a 3-cm segment of ureter in dogs. Segments were wrapped in omentum to enhance vascularity. Third, a de-epithelialized small-bowel segment seeded with autologous bladder-epithelial cells was transversally retubularized (Monti) into a 4-cm ureteral replacement. Follow-up studies consisted of retrograde pyelography, serum chemistry assays, hematoxylin/eosin studies, and immunohistopathologic examination using antibodies against alpha-smooth-muscle actin and pancytokeratin AE1-AE3. RESULTS: Coculture of urinary-tract cells on large segments of SIS failed to create adequate ureteral replacement. All grafts were contracted and stenotic, with complete obstruction of the ipsilateral renal unit. Similar results were seen in the Beagles. Despite clinical obstruction and gross contraction of the graft, a circumferential muscular ureteral wall lined with multilayer transitional epithelium was present. Urotheliumseeded de-epithelialized Monti bowel segments resulted in patent ureteral replacement without hydroureteronephrosis and with normal renal function, serum electrolytes, and acid-base balance. However, bowel mucosa fully regenerated, with multilayer transitional epithelium growing adluminally in continuity with the proximal and distal anastomotic sites. CONCLUSIONS: Seeding of ureteral grafts with autologous bladder cells does not promote success in two largeanimal models using different xenogenic acellular matrices. However, muscle and urothelium regeneration occurs with ureteral acellular matrix in the dog. Urothelium-seeded de-epithelialized Monti bowel segments may be an acceptable substitute for long proximal ureteral segments. Further technical refinements are required to replace the bowel mucosa completely with normal urothelium.     

Changes in disease specific and generic quality of life related to changes in lower urinary tract symptoms: the Krimpen study

PURPOSE: We determined if and to what extent longitudinal changes in lower urinary tract symptoms are related to disease specific and generic quality of life in men. MATERIAL AND METHODS: A longitudinal, population based study with a followup of 4.2 years was done in 1,688 who were 50 to 79 years old. Data were collected through self-administered questionnaires, including the Sickness Impact Profile (3 domains), Inventory of Subjective Health, International Prostate Symptom Score (I-PSS) and Benign Prostatic Hyperplasia Impact Index. Moreover, they completed various physical and urological measurements. Mean I-PSS and quality of life scores at baseline and followup were analyzed for certain subgroups. Multiple linear regression was used to determine the change in quality of life in relation to baseline I-PSS, I-PSS changes between baseline and followup, and age. RESULTS: Although mean I-PSS increased with time, the average generic quality of life improved and almost a third of the men reported better disease specific quality of life. Multiple linear regression revealed that disease specific quality of life was associated with I-PSS at baseline, changes in I-PSS between baseline and followup, and age. However, generic quality of life scores were not associated with these parameters. CONCLUSIONS: Changes in lower urinary tract symptoms severity had little impact on disease specific quality of life in 50 to 79-year-old men or on generic quality of life during the 4.2-year followup.     

Cross-training hospital nurses to reduce staffing costs

There are advantages and disadvantages of cross-training hospital nurses. The financial benefit of reducing reliance on supplemental agency staff can be quantified. Cross-training policies can be compared. Simulation shows that the strategic cross-training principle of chaining performs particularly well. Practical formulas (that can be solved in a spreadsheet) are provided for quickly evaluating the economic performance of staffing and cross-training scenarios.     

Evaluation of microbial inoculation and vegetation to enhance the dissipation of atrazine and metolachlor in soil

Four greenhouse studies were conducted to evaluate the effects of native prairie grasses and two pesticide-degrading bacteria to remediate atrazine and metolachlor in soils from agricultural dealerships (Alpha site soil, northwest Iowa, USA; Bravo site soil, central Iowa, USA). The Alpha soil contained a low population of atrazine-degrading microorganisms relative to the Bravo soil. Each soil freshly treated with atrazine or metolachlor was aged for a short or long period of time, respectively. An atrazine-degrading bacterium, Agrobacterium radiobacter strain J14a; a metolachlor-degrading bacterium, Pseudomonas fluorescens strain UA5-40; and a mixture of three native prairie grasses-big bluestem (Andropogon gerardii Vitman), yellow Indian grass (Sorghastrum nutans [L.] Nash), and switchgrass (Panicum virgatum L.)-were added to the soils after the soils were aged for long periods of time. The soils aged for short periods of time were treated with J14a, the prairie grasses, or both after aging. The J14a and the grasses significantly reduced the concentration of atrazine in Alpha soil when the soil was aged for a short period of time. However, these treatments had no statistically significant effect when the soil was aged for a long period of time or on atrazine in Bravo soil. Inoculation with UA5-40 did not enhance metolachlor dissipation in either soil, but vegetation did increase metolachlor dissipation. Our results indicate that the dissipation of atrazine by J14a is affected by the presence of indigenous atrazine-mineralizing microorganisms and probably by the bioavailability of atrazine in the soil.     

An alternative method of determining standard of care in alleged cases of malpractice

BACKGROUND: Physician experts hired and prepared by litigants provide most information on standard of care for medical malpractice cases. Because this information may not be objective or accurate, we examined the feasibility and potential value of surveying peer physicians to assess standard of care. METHODS: The survey method was evaluated for a medical malpractice case involving a patient hospitalized with abdominal pain. An abstract of the medical record was created that included the patient characteristics and physician decisions most likely to influence patient outcome. The abstract and questionnaire were sent to 16 academic family physicians and to 20 randomly chosen primary care physicians in Iowa who practiced in communities of similar size to the defendant's community. RESULTS: All 16 academic and 18 (90%) community physicians completed the survey. All respondents judged the patient as presenting with an acute abdomen, and 89% of the community physicians and 100% of the academic physicians judged the care as below standard. More than half the physicians surveyed listed the autopsy diagnosis (perforated ulcer) in their differential. CONCLUSION: Surveys of randomly selected physicians are feasible to perform for medical malpractice cases. A pro-physician bias has little if any influence on the results.     

Oncolyn对温石棉所致大鼠氧化损伤影响的实验研究

目的探讨温石棉对实验大鼠氧化损伤的影响以及Oncolyn的缓解作用。方法Wistar大鼠随机分为对照组、石棉组和Oncolyn组,应用支气管灌注的方法给予大鼠温石棉5mg/ml,同时经口给入Oncolyn40d,剂量为1.5g/(kg·d),检测肺泡巨噬细胞中DNA损伤状况以及血液和肺脏中NO、NOS和抗氧化酶SOD、CAT、GSHPx、GST的活性。结果石棉组肺泡巨噬细胞DNA链断裂增加,表现为彗星出现率和DNA迁移长度增加;血液中NO和NOS水平和SOD、GSHPx活性增加,而GST活性下降;而肺组织中NOS、SOD、GSHPx和GST的活性均下降,MDA含量增加。应用Oncolyn预防后,肺泡巨噬细胞DNA损伤下降;血液中NO、NOS的水平以及SOD活性下降,而GSHPx、GST、CAT活性上升;肺组织中抗氧化酶活性增加,MDA含量下降。结论Oncolyn对温石棉所致机体氧化损伤有一定的缓解作用。     

Monitor-to-monitor temporal correlation of air pollution in the contiguous US

Numerous studies have reported short-term associations between ambient air pollution concentrations and mortality and morbidity. Particulate matter (PM) was often implicated as the most significant predictor of the health outcomes among the various air pollutants. However, a question remains as to the potential role played by the relative error of exposure estimation associated with each pollutant in defining their relative strengths of association. While most of the recent studies on PM exposure measurements have focused on the temporal correlation between personal exposures and the concentrations observed at ambient air quality monitors (within a few miles from the subjects), there have been few studies that systematically evaluated spatial uniformity of temporal correlation of air pollution within the scale of a city (several tens of miles) for which mortality or morbidity outcomes are aggregated in time-series studies. In this study, spatial uniformity of temporal correlation was examined by computing monitor-to-monitor correlation using available multiple monitors for PM(10) and gaseous criteria pollutants (NO(2), SO(2), CO, and O(3)) in the nationwide data between 1988 and 1997. For each monitor, the median of temporal correlation with other monitors within the Air Quality Control Region (AQCR) was computed. The resulting median monitor-to-monitor correlation was modeled as a function of qualitative site characteristics (i.e., land-use, location-setting, and monitoring-objective) and quantitative information (median separation distance, longitude/latitude or regional indicators) for each pollutant. Generalized additive models (GAM) were used to fit the smooth function of the separation distance and regional variation. The intercepts of the models across pollutants showed the overall rankings in monitor-to-monitor correlation on the average to be: O(3), NO(2), and PM(10), (r approximately 0.6 to 0.8)>CO (r<0.6)>SO(2) (r<0.5). Both the separation distance and regional variation were important predictors of the correlation. For PM(10), for example, the correlation for the monitors along the East Coast was higher by approximately 0.2 than western regions. The qualitative monitor characteristics were often significant predictors of the variation in correlation, but their impacts were not substantial in magnitude for most categories. These results suggest that the apparent regional heterogeneity in PM effect estimates, as well as the differences in the significance of health outcome associations across pollutants, may in part be contributed to by the differences in monitor-to-monitor correlations by region and across pollutants.     

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.