Sex differences in diencephalon serotonin transporter availability in major depression.

BACKGROUND: Major depression is more prevalent in women than men. The present study evaluated if previous findings that demonstrated decreased 5-hydroxytryptamine (5-HT) transporter availability in depressed patients would be confirmed in a larger sample and also evaluated sex differences. METHODS: Depressed (n = 32) and healthy subjects (n = 32), including 16 pairs of women and men, participated in an iodine-123-2 beta-carbomethoxy-3beta-(4-iodophenyltropane) ([(123)I]beta-CIT) single photon emission computed tomography (SPECT) and a magnetic resonance imaging (MRI) scan. Participants were administered [(123)I]beta-CIT (225.7 +/- 3.7 MBq) and imaged 23.0 +/- 1.6 hours later. Statistical analyses included analysis of variance and a regression analysis of the main and interactive effects of age, sex, and depression. RESULTS: Overall, depressed patients demonstrated 12% lower diencephalon and no change in striatal or brainstem [(123)I]beta-CIT uptake. Significant age by sex, sex by depression, and age by sex by depression interactions were noted due to 22% lower diencephalon [(123)I]beta-CIT uptake in depressed women compared with less than a 1% decrease in depressed men. CONCLUSIONS: As observed previously, diencephalon 5-HT transporter availability is decreased in depressed patients. However, the decrease appears to be sex-specific and age-dependent. These findings suggest that serotonergic mechanisms mediating depressed mood differ between men and women in an age-dependent manner and may explain why young women respond better to treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants.     

Intraluminal irradiation for TIPS stenosis: preliminary results in a swine model.

PURPOSE: To evaluate the ability of 32phosphorus intraluminal irradiation to reduce pseudointimal hyperplasia in a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: TIPS were successfully placed in 11 swine with normal portal pressures. Six animals received 15.2 Gy intraluminal irradiation to the hepatic parenchyma and venous outflow tract at the time of TIPS placement with use of a NA32P-filled balloon angioplasty catheter. Five control animals underwent TIPS and balloon angioplasty with saline. All animals were followed up for 28 days, at which time percutaneous portography was performed, the animals were killed, and the tissue around the TIPS stent was processed for histologic analysis. Maximum pseudointimal hyperplasia as a percentage of estimated TIPS diameter was calculated for each animal. RESULTS: At the time of euthanasia, all five control TIPS and all but one irradiated TIPS were occluded. Histologic analysis demonstrated considerable variability in the degree of pseudointimal hyperplasia within each TIPS and between animals. No statistically significant difference was found in the maximum pseudointimal hyperplasia, measured as a percentage of stent radius, between control (80.2%+/-17.4%) and irradiated animals (69.2%+/-25.2%). CONCLUSIONS: Irradiation of TIPS with 15.2 Gy 32P delivered at the time of TIPS placement did not significantly improve TIPS patency or reduce the degree of pseudointimal hyperplasia in swine with normal portal pressures.     

凝血酶肽促进缺血创面愈合与皮瓣存活的实验研究

目的探讨凝血酶受体激活肽(TP508)对促进缺血创面愈合与皮瓣存活的作用.方法SD大鼠66只,制作部分缺血创面(16只)、完全缺血创面(16只)、正常创面(18只)及皮瓣(16只)模型,每一模型又分为TP508治疗组和等渗盐水对照组.术后第3、7、10、14天,将创面或皮瓣坏死轮廓描记至醋酸纸七,输入计算机求出创面面积或坏死面积.结果术后7 d和14 d,TP508组正常创面面积仅为对照组的73.7%和45.4%.术后7 d,TP508组部分缺血创面面积为(99.8±30.7)mm2,而对照组为(128.0±43.4)mm2.术后第10天,TP508组完全缺血创面面积为(293.0±34.0)mm2,对照组为(352.4±41.2)mm2.术后第7天,TP508组皮瓣坏死面积为对照组皮瓣坏死面积的80.4%,第14天为56.8%.结论 TP508对促进大鼠缺血创面愈合和皮瓣存活均有显著作用.     

Surgeon and hospital characteristics as predictors of major adverse outcomes following colon cancer surgery: understanding the volume-outcome relationship

HYPOTHESIS: Although numerous studies have demonstrated an association between surgical volume and improved outcome in cancer surgery, the specific structures and mechanisms of care that are associated with volume and lead to improved outcomes remain poorly defined. We hypothesize that there are modifiable surgeon and hospital characteristics that explain observed volume-outcome relationships. DESIGN: Retrospective cohort study. SETTING: Surveillance, Epidemiology, and End Results cancer registry areas. PATIENTS: Patients aged 66 years and older, diagnosed and surgically treated for stage I, II, or III colon cancer between 1992 and 1996 (n = 22 672). MAIN OUTCOME MEASURES: Thirty-day postoperative mortality and 30-day postoperative procedural interventions, including reoperation and image-guided percutaneous procedures. RESULTS: Surgeon volume, but not hospital volume, is a significant predictor of postoperative procedural intervention (adjusted odds ratio for very high-volume surgeons vs low-volume surgeons, 0.79; 95% confidence interval, 0.64-0.98). In the unadjusted analyses, high hospital volume (odds ratio, 0.67; 95% confidence interval, 0.56-0.81) and very high hospital volume (odds ratio, 0.65; 95% confidence interval, 0.54-0.79) is associated with lower postoperative mortality. Postoperative procedural intervention is not a significant mediator of the relationship between hospital volume and mortality. A single variable-the presence of sophisticated clinical services-was the most important explanatory variable underlying the relationship between hospital volume and mortality. CONCLUSIONS: Very high surgeon volume is associated with a reduction in surgical complications. However, the association between increasing hospital volume and postoperative mortality appears to derive mainly from a full spectrum of clinical services that may facilitate the prompt recognition and treatment of complications.     

Reoperation as a quality indicator in colorectal surgery: a population-based analysis

OBJECTIVE: To describe unplanned procedures following colorectal cancer surgery that might be used as intermediate outcome measures, and to determine their association with mortality and length of stay. SUMMARY BACKGROUND: Variation in the quality of surgical care, especially for common illnesses like colorectal cancer, has received increasing attention. Nonfatal complications resulting in procedural interventions are likely to play a role in poor outcomes but have not been well explored. METHODS: Cohort analysis of 26,638 stage I to III colorectal cancer patients in the 1992 to 1996 SEER-Medicare database. Independent variables: sociodemographics, tumor characteristics, comorbidity, and acuity. Primary outcome: postoperative procedural intervention. Analysis: Logistic regression identified patient characteristics predicting postoperative procedures and the adjusted risk of 30-day mortality and prolonged hospitalization among patients with postoperative procedures. RESULTS: A total of 5.8% of patients required postoperative intervention. Patient characteristics had little impact on the frequency of postoperative procedures, except for acute medical conditions, including bowel perforation (relative risk [RR] = 3.0, 95% confidence interval [CI] = 2.5-3.6), obstruction (RR = 1.6; 95% CI = 1.4-1.8), and emergent admission (RR = 1.3; 95% CI = 1.1-1.4). After a postoperative procedure, patients were more likely to experience early mortality (RR = 2.4; 95% CI = 2.1-2.9) and prolonged hospitalization (RR = 2.2; 95% CI = 2.1-2.4). The most common interventions were performed for abdominal infection (31.7%; RR mortality = 2.9; 95% CI = 2.3-3.7), wound complications (21.1%; RR mortality = 0.7; 95% CI = 0.4-1.3), and organ injury (18.7%; RR mortality = 1.6; 95% CI = 1.1-2.3). CONCLUSIONS: Postoperative complications requiring additional procedures among colorectal cancer patients correlate with established measures of surgical quality. Prospective tracking of postoperative procedures as complication markers may facilitate outcome studies and quality improvement programs.     

Synergistic Deposition of C4d by Complement-Activating and Non-activating Antibodies in Cardiac Transplants

The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection.     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Graded responses of human neutrophils induced by serum-treated zymosan

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3'- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.     

Synthesis, radiolabeling and baboon SPECT imaging of 2beta-carbomethoxy-3beta-(3'-[(123)I]iodophenyl)tropane ([(123)I]YP256) as a serotonin transporter radiotracer

To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2beta-carbomethoxy-3beta-(3'-[(123)I]iodophenyl) tropane (YP256, 6). The radiolabeling was performed by iododestannylation using sodium [(123)I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.