Isoflurane-induced cerebral hyperemia is partially mediated by nitric oxide and epoxyeicosatrienoic acids in mice in vivo

BACKGROUND: Despite intense investigation, the mechanism of isoflurane-induced cerebral hyperemia is unclear. The current study was designed to determine the contributions of neuronal nitric oxide synthase, prostaglandins, and epoxyeicosatrienoic acids to isoflurane-induced cerebral hyperemia. METHODS: Regional cerebral cortical blood flow was measured with laser Doppler flowmetry during stepwise increases of isoflurane from 0.0 to 1.2, 1.8, and 2.4 vol% end-tidal concentration in alpha-chloralose-urethane-anesthetized, C57BL/6 mice before and 45 min after administration of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI, 40 mg/kg, intraperitoneal), the cyclooxygenase inhibitor indomethacin (INDO, 10 mg/kg, intravenous), and the cytochrome P450 epoxygenase inhibitor N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (PPOH, 20 mg/kg, intravenous). RESULTS: Isoflurane increased regional cerebral cortical blood flow by 9 +/- 3, 46 +/- 21, and 101 +/- 26% (SD) at 1.2, 1.8, and 2.4 vol%, respectively. The increases in regional cerebral cortical blood flow were significantly (*P < 0.05) smaller after 7-NI (5 +/- 6, 29 +/- 19*, 68 +/- 15%*) or PPOH (4 +/- 8, 27 +/- 17*, 67 +/- 30%*), but not after administration of INDO (4 +/- 4, 33 +/- 18 [NS], 107 +/- 35% [NS]). The effect of combined treatment with 7-NI, PPOH, and INDO was not additive and was equal to that of either 7-NI or PPOH alone (5 +/- 5, 30 +/- 12*, 76 +/- 24%*). Chronic treatment of mice for 5 days with 7-NI (2 x 40 mg/kg, intraperitoneal) produced similar decreases in regional cerebral cortical blood flow as those seen with acute administration. Neither PPOH nor INDO conferred a significant additional block of the hyperemia in these animals. CONCLUSIONS: Nitric oxide and epoxyeicosatrienoic acids contribute to isoflurane-induced hyperemia. However, only approximately one third of the cerebral hyperemic response to isoflurane is mediated by autacoids. The remaining part of this response appears to be mediated by a direct action of isoflurane on smooth muscle by some yet-unknown mechanism.     

Results of laparoscopic repair of giant paraesophageal hernias: 200 consecutive patients

BACKGROUND: Giant paraesophageal hernias (GPEH) have traditionally required open operations. Increasingly, a laparoscopic approach is being applied to more complex esophageal surgery. Our objective was to update our growing experience with laparoscopic repair of GPEH. METHODS: We performed a retrospective review at our institution of patients undergoing laparoscopic repair of GPEH from July 1995 to July 2001. The GPEH was defined as greater than one-third of the stomach in the chest. RESULTS: Elective laparoscopic repair of a GPEH was attempted in 203 patients. Mean age was 67 years. The most common symptoms included heartburn (96 patients), dysphagia (72), epigastric pain (56), and vomiting (47 patients). Laparoscopic procedures included 69 Nissens, 112 Collis-Nissens, and 19 other procedures. There were three open conversions due to adhesions, but no intraoperative emergencies. Median length of stay was 3 days (range, 1 to 120 days). Minor or major complications occurred in 57 patients (28%). There were six postoperative esophageal leaks (3%), and 1 death. Median follow-up was 18 months. Five patients required reoperation for recurrent hiatal hernia. Excellent results were reported in 128 (84%) patients, 12 (8%) had a good result, 7 (5%) fair, and 5 (3%) poor (based on postoperative follow-up and GERD questionnaire). The mean postoperative GERD Health-related Quality of Life Score was 2.4 (scale 0 to 45; 0 = no symptoms, 45 = worst). CONCLUSIONS: Laparoscopic repair of GPEH is possible in the majority of patients with acceptable morbidity, a median length of hospital stay of 3 days and excellent intermediate-term results in an experienced center.     

Surgical treatment of hyperparathyroidism improves health-related quality of life

HYPOTHESIS: The surgical treatment of primary hyperparathyroidism results in an improved health-related quality of life. DESIGN: Prospective cohort analysis of consecutive patients with primary hyperparathyroidism analyzed preoperatively and 1 year postoperatively. SETTING: Academic multispecialty referral clinic. PATIENTS: We prospectively evaluated 74 consecutive patients who underwent parathyroid exploration for primary hyperparathyroidism during a 15-month period. INTERVENTIONS: The Medical Outcomes Study Short-Form Health Survey (SF-36) was administered before consultation with a surgeon. Patients were categorized based on reason for referral as either asymptomatic (group 1; n = 43) or symptomatic (group 2; n = 29). All patients underwent parathyroid exploration and normalization of calcium levels postoperatively. The SF-36 was then re-administered after 1 year. MAIN OUTCOME MEASURES: Statistical analysis of preoperative and postoperative SF-36 scores, and comparisons with national norms. RESULTS: The SF-36 was completed preoperatively and 1 year postoperatively by 72 (97%) of 74 patients. When the results were compared with published national norms, the preoperative population was significantly impaired in 5 of 8 domains, whereas the postoperative one had improved and was nearly indistinguishable from the norm. In 7 of 8 domains, the postoperative scores were significantly improved compared with preoperative scores. Group 1 patients showed significant preoperative impairment in 3 domains and significantly improved in 2, whereas group 2 patients showed significant impairment and improvement in 7 domains. CONCLUSION: The surgical treatment of primary hyperparathyroidism is associated with durable, statistically significant improvements in health-related quality of life.     

Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry

Our objective in this study was to evaluate the mortality of workers exposed to sulfur dioxide in the pulp and paper industry. The cohort included 57,613 workers employed for at least 1 year in the pulp and paper industry in 12 countries. We assessed exposure to SO(2) at the level of mill and department, using industrial hygiene measurement data and information from company questionnaires; 40,704 workers were classified as exposed to SO(2). We conducted a standardized mortality ratio (SMR) analysis based on age-specific and calendar period-specific national mortality rates. We also conducted a Poisson regression analysis to determine the dose-response relations between SO(2) exposure and cancer mortality risks and to explore the effect of potential confounding factors. The SMR analysis showed a moderate deficit of all causes of death [SMR = 0.89; 95% confidence interval (CI), 0.87-0.96] among exposed workers. Lung cancer mortality was marginally increased among exposed workers (SMR = 1.08; 95% CI, 0.98-1.18). After adjustment for occupational coexposures, the lung cancer risk was increased compared with unexposed workers (rate ratio = 1.49; 95% CI, 1.14-1.96). There was a suggestion of a positive relationship between weighted cumulative SO(2) exposure and lung cancer mortality (p-value of test for linear trend = 0.009 among all exposed workers; p = 0.3 among workers with high exposure). Neither duration of exposure nor time since first exposure was associated with lung cancer mortality. Mortality from non-Hodgkin lymphoma and from leukemia was increased among workers with high SO(2) exposure; a dose-response relationship with cumulative SO(2) exposure was suggested for non-Hodgkin lymphoma. For the other causes of death, there was no evidence of increased mortality associated with exposure to SO(2). Although residual confounding may have occurred, our results suggest that occupational exposure to SO(2) in the pulp and paper industry may be associated with an increased risk of lung cancer.     

Human hippocampus and viewpoint dependence in spatial memory

Virtual reality was used to sequentially present objects within a town square and to test recognition of object locations from the same viewpoint as presentation, or from a shifted viewpoint. A developmental amnesic case with focal bilateral hippocampal pathology showed a massive additional impairment when tested from the shifted viewpoint compared with a mild, list length-dependent, impairment when tested from the same viewpoint. While the same-view condition could be solved by visual pattern matching, the shifted-view condition requires a viewpoint independent representation or an equivalent mechanism for translating or rotating viewpoints in memory. The latter mechanism was indicated by control subjects' response latencies in the shifted-view condition, although the amnesic case is not impaired in tests of mental rotation of single objects. These results show that the human hippocampus supports viewpoint independence in spatial memory, and suggest that it does so by providing a mechanism for viewpoint manipulation in memory. In addition, they suggest an extremely sensitive test for human hippocampal damage, and hint at the nature of the hippocampal role in episodic recollection.     

Integration of service systems for homeless persons with serious mental illness through the ACCESS program. Access to Community Care and Effective Services and Supports

OBJECTIVE: The aim of this study was to evaluate the first of the two core questions around which the ACCESS (Access to Community Care and Effective Services and Supports) evaluation was designed: Does implementation of system-change strategies lead to better integration of service systems? METHODS: The study was part of the five-year federal ACCESS service demonstration program, which sought to enhance integration of service delivery systems for homeless persons with serious mental illness. Data were gathered from nine randomly selected experimental sites and nine comparison sites in 15 of the nation's largest cities on the degree to which each site implemented a set of systems integration strategies and the degree of systems integration that ensued among community agencies across five service sectors: mental health, substance abuse, primary care, housing, and social welfare and entitlement services. Integration was measured across all interorganizational relationships in the local service networks (overall systems integration) and across relationships involving only the primary ACCESS grantee organization (project-centered integration). RESULTS: Contrary to expectations, the nine experimental sites did not demonstrate significantly greater overall systems integration than the nine comparison sites. However, the experimental sites demonstrated better project-centered integration than the comparison sites. Moreover, more extensive implementation of strategies for system change was associated with higher levels of overall systems integration as well as project-centered integration at both the experimental sites and the comparison sites. CONCLUSIONS: The ACCESS demonstration was successful in terms of project-centered integration but not overall system integration.     

A clinical review of cognitive therapy for schizophrenia

Major advances have been made in the cognitive understanding and treatment of the symptoms of schizophrenia, including delusions, hallucinations, and emotional withdrawal. Experimental studies on the psychologic aspects of schizophrenia demonstrate the importance of information processing biases, such as cognitive biases and distortions, that are functionally related to the maintenance of symptoms. Understanding the aspects of schizophrenia in cognitive terms provides a framework for psychotherapeutic intervention with the adaptation of the cognitive strategies proven effective in the treatment of mood and anxiety disorders. The authors of this paper first outline the cognitive conceptualization and strategies employed by cognitive therapists to treat positive and negative symptoms, and conclude with a summary of the empiric status of cognitive therapy for schizophrenia. Cognitive therapy has been shown to be an important adjunct to standard treatments of schizophrenia.