PET physiological measurements using constant infusion

A wide range of study designs can be used with positron emission tomography methods to provide quantitative measurements of physiological parameters. While bolus injection of tracer is the conventional approach, use of combined bolus plus constant infusion provides a number of advantages for receptor-binding tracers. Of recent interest is the use of this approach to dynamically follow the displacement of tracer during in vivo changes in neurotransmitter concentrations. This paper provides an overview of the tradeoffs in using bolus/infusion methods versus conventional bolus injection for receptor binding studies.     

Stigma, discrimination, and HIV/AIDS knowledge among physicians in Barbados.

OBJECTIVE: To determine the extent of clinical knowledge of HIV/AIDS that physicians in Barbados have and their attitudes towards persons living with HIV/AIDS. METHODS: In 2000 the Barbados Association of Medical Practitioners conducted a survey in order to assess its members' views on HIV/AIDS issues. Over a two-month period 203 physicians (76% of all those practicing in the country) were interviewed. The survey included physicians working in private practice and the public sector. They were surveyed individually concerning their attitudes towards counseling as well as their clinical knowledge, perception of safe practices, fear of occupational exposure, views on ethical issues, experience treating HIV/AIDS patients, and background with HIV/AIDS continuing education. RESULTS: In comparison to physicians who had graduated in later years, physicians who had graduated in 1984 or earlier had seen fewer HIV/AIDS clients, had lower levels of knowledge about the disease, were more likely to test for HIV/AIDS without informed consent, and were less likely to have ever attended a continuing education training course on HIV/AIDS. Overall, knowledge of the clinical indications of HIV/AIDS was low, and 76% of the physicians did not think they had adequate counseling skills. Over 80% of the physicians were comfortable looking after HIV/AIDS patients. While 95% of the physicians would not release HIV test results without a patient's consent, 33% would test, without consent, a seriously ill patient, and 15% would test without consent a patient upon whom they had to perform an invasive procedure if they perceived the patient to be from a high-risk population such as gay men or commercial sex workers. Only 53% of the physicians had attended an HIV/AIDS in-service training program between 1995 and 1999. CONCLUSIONS: Physician training in Barbados should focus on all aspects of HIV/AIDS care, including clinical and emotional factors. Attendance at such training should be mandatory for public sector physicians, and medical school curricula need to be examined to ensure their HIV/AIDS content is current and comprehensive.     

Epidemic parenteral exposure to volatile sulfur-containing compounds at a hemodialysis center.

OBJECTIVE: To determine the cause of acute illness on August 30, 2000, among patients at an outpatient dialysis center (center A). DESIGN: We performed a cohort study of all patients receiving dialysis on August 30, 2000; reviewed dialysis procedures; and analyzed dialysis water samples using microbiologic and chemical assays. SETTING: Dialysis center (center A). PATIENTS: A case-patient was defined as a patient who developed chills within 5 hours after starting hemodialysis at center A on August 30, 2000. RESULTS: Sixteen (36%) of 44 patients at center A met the case definition. All case-patients were hospitalized; 2 died. Besides chills, 15 (94%) of the case-patients experienced nausea; 12 (75%), vomiting; and 4 (25%), fever. Illness was more frequent on the second than the first dialysis shift (16 of 20 vs 0 of 24, P < .001); no other risk factors were identified. The center's water treatment system had received inadequate maintenance and disinfection and a sulfurous odor was noted during sampling of the water from the reverse osmosis (RO) unit. The water had elevated bacterial counts. Volatile sulfur-containing compounds (ie, methanethiol, carbon disulfide, dimethyldisulfide, and sulfur dioxide) were detected by gas chromatography and mass spectrometry in 8 of 12 water samples from the RO unit and in 0 of 28 samples from other areas (P < .001). Results of tests for heavy metals and chloramines were within normal limits. CONCLUSIONS: Parenteral exposure to volatile sulfur-containing compounds, produced under anaerobic conditions in the RO unit, could have caused the outbreak. This investigation demonstrates the importance of appropriate disinfection and maintenance of water treatment systems in hemodialysis centers.     

比较亮脯利特与醋酸甲孕酮注射剂皮下注射治疗子宫内膜异位症相关疼痛

目的：与亮脯利特比较，醋酸甲孕酮皮下注射（DMPA-SC104）治疗子宫内膜异位症的有效性和安全性。设计：3期多中心、随机、评价者盲法、对照比较试验。机构：加拿大和美国的临床试验点。患者：274例手术诊断的子宫内膜异位症妇女。干预：每3个月肌注DMPA-SC（104mg）或亮脯利特（11．25mg），共6个月。治疗后随访12个月。主要观察指标：5种子宫内膜异位症症状或体征的减轻（痛经、性交困难、盆腔痛、盆腔触痛、盆腔硬化）；骨密度（BMD）改变、低雌激素的症状、出血及体重的变化。结果：DMPA-SC104，在治疗末（6个月）减轻5种子宫内膜异位症症状或体征的4种，在12个月随访末（18个月）减轻全部5种症状，与亮脯利特统计学上效果相当。DMPA-SC104组患者显示在6个月较亮脯利特有更少的BMD损失，在随访的12个月又回到基线水平。     

In-hospital mortality after transurethral resection of the prostate in Victorian public hospitals

BACKGROUND: The purpose of the present paper was (i) to identify trends in in-hospital mortality after transurethral resection of the prostate (TURP) in Victorian public hospitals; and (ii) to explore associations between in-hospital mortality after TURP and age, adverse events, type of admission (emergency/planned), location of the hospital (metropolitan/rural), teaching status of the hospital and length of stay. METHODS: Trends in in-hospital mortality after TURP and the associations between in-hospital mortality and the aforementioned variables were studied using International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) coded Victorian hospital morbidity data from public hospitals between 1987-88 and 1994-95. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were based on univariate and multivariate logistic regression, respectively. RESULTS: After adjustment for age, comorbidity, and other confounding variables, the trend in mortality reduction over time was highly significant (P for trend < 0.0001, 95% CI for trend: 0.84-0.95). Highly significant associations with mortality were observed for emergency admissions (OR = 1.99, P < 0.0001), presence of adverse events (OR = 2.69, P < 0.0001), length of hospital stay (P for trend < 0.0001, 95% for trend: 1.88-2.15) and age (P for trend < 0.0001; 95% CI for trend: 1.26-1.48). CONCLUSIONS: Routinely collected data from hospitals can provide tentative evidence of improved effectiveness of a surgical treatment, provided analysis takes careful account of potential sources of bias, especially those related to possible changes in case selection over time. These kinds of data should stimulate a joint effort between clinicians, quality assurance experts and epidemiologists to confirm this attribution, and to locate the causative factors.     

The effect of anesthetic technique on postoperative outcomes in hip fracture repair

BACKGROUND: The impact of anesthetic choice on postoperative mortality and morbidity has not been determined with certainty. METHODS: The authors evaluated the effect of type of anesthesia on postoperative mortality and morbidity in a retrospective cohort study of consecutive hip fracture patients, aged 60 yr or older, who underwent surgical repair at 20 US hospitals between 1983 and 1993. The primary outcome was defined as death within 30 days of the operative procedure. The secondary outcomes were postoperative 7-day mortality, postoperative myocardial infarction, postoperative pneumonia, postoperative congestive heart failure, and postoperative change in mental status. Numerous comorbid conditions were controlled for individually and by several comorbidity indices using logistic regression. RESULTS: General anesthesia was used in 6,206 patients (65.8%) and regional anesthesia in 3,219 patients (3,078 spinal anesthesia and 141 epidural anesthesia). The 30-day mortality rate in the general anesthesia group was 4.4%, compared with 5.4% in the regional anesthesia group (unadjusted odds ratio = 0.80; 95% confidence interval = 0.66-0.97). However, the adjusted odds ratio for general anesthesia increased to 1.08 (0.84-1.38). The adjusted odds ratios for general anesthesia versus regional anesthesia for the 7-day mortality was 0.90 (0.59-1.39) and for postoperative morbidity outcomes were as follows: myocardial infarction: adjusted odds ratio = 1.17 (0.80-1.70); congestive heart failure: adjusted odds ratio = 1.04 (0.80-1.36); pneumonia: adjusted odds ratio = 1.21 (0.87-1.68); postoperative change in mental status: adjusted odds ratio = 1.08 (0.95-1.22). CONCLUSIONS: The authors were unable to demonstrate that regional anesthesia was associated with better outcome than was general anesthesia in this large observational study of elderly patients with hip fracture. These results suggest that the type of anesthesia used should depend on factors other than any associated risks of mortality or morbidity.     

Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.

Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.     

Hexamethylmelamine, methotrexate, 5-fluorouracil as second line chemotherapy after platinum for epithelial ovarian malignancies

Thirty-three patients were treated with HexAF after previous treatment with cyclophosphamide (C), Adriamycin (A), and cisplatin (P). The patients had either progressed on CAP, had persistent disease after CAP, or recurred after a negative second look. Treatment schedule was hexamethylmelamine (Hex) 150 mg po qd days 1-14, methotrexate (A) 40 mg/m2 IV days 1 and 8, and 5-fluorouracil (F) 600 mg/m2 IV days 1 and 8. Courses were repeated every 4 weeks. Thirty-one of 33 patients were evaluable for response. Three of 31 patients had partial responses, 7 of 31 had stable disease, and 21 of 31 progressed. Median survival of the responders (n = 3) was 23 months and the nonresponders (n = 28) was 6 months (p = 0.027). Patients with less than 1 cm disease (n = 12) had a median survival of 20 months, and those with greater than 1 cm (n = 21) had a median survival of 6 months (p = 0.004). Toxicity was mild. Even with a statistically significant survival advantage for HexAF responders, we consider a response rate of less than 10% unacceptable.