Structure-activity relationship of toxic-shock-syndrome toxin-1: derivation and characterization of immunologically and biologically active fragments

Toxic-shock-syndrome toxin-1 (TSST-1), a 22-kilodalton (kDa) polypeptide, was proteolyzed by papain, generating three distinct fragments, identified as 16, 12, and 10 kDa (based on molecular masses estimated from the predicted amino acid sequence). The NH2-terminal sequence analysis of the fragments indicated that the peptide bonds between Tyr-52 and Ser-53 and between Gly-87 and Val-88 were cleaved. Functional activity, evaluated through enzyme-linked immunosorbent and inhibition assays, was demonstrated only with the 16- and 12-kDa fragments. The presence of homologous and heterologous antigenic determinants on the fragments was demonstrated by immunoblotting. In in vitro stimulation of human peripheral blood mononuclear cells, the 12-kDa fragment was significantly (P = .003) more active than the 16-kDa fragment. The former composed 75% of the latter and occupied the COOH-terminal portion of the holotoxin. The functional domains were located on two-thirds of the TSST-1 molecule, toward the COOH-terminal end, and mitogenicity apparently was separable from serological activity.     

Influence of a brief aerobic training program on heart rate and subjective response to a psychologic stressor

An experiment was conducted to determine whether a brief program of aerobic exercise would reduce the heart rate and subjective responses of high- and low-fit subjects to a psychologic stressor. Thirty-four high-fit and 34 low-fit subjects were exposed to a moderate stressor (recall of digits backwards test) while their heart rates and subjective responses were monitored. Approximately half of the high- and low-fit subjects then participated in a 13-week aerobic exercise training program, whereas the other subjects did not. After the 13-week period, the subjects were again exposed to the stressor. Results indicated that a) in the pretest the low-fit subjects showed a greater heart rate response to the stressor than the high-fit subjects, b) the training program was effective for increasing subjects' levels of aerobic fitness, and c) the training program was effective for reducing the heart rate response to the stressor of low-fit subjects. These findings provide support for the relationship between fitness and the response to psychologic stressors and they suggest that aerobic training may be an effective way of helping low-fit persons deal with psychologic stressors.     

The Use of Performance Improvement Methods to Enhance Emergency Department Patient Satisfaction in the United States: A Critical Review of the Literature and Suggestions for Future Research

Objectives: The authors reviewed the evidence on performance improvement methods for increasing emergency department (ED) patient satisfaction to provide evidence-based suggestions for clinical practice.
Methods: Data sources consisted of searches through MEDLINE, CINAHL, PSYCHINFO, Cochrane Library, and Emergency Medicine Abstracts and a manual search of references. Articles were included if they reported a performance improvement intervention targeting patient satisfaction in the ED setting. Articles on studies not conducted in the United States or that failed to provide enough details to allow critical evaluation of the study were excluded. Two authors used structured evaluation criteria to independently review each retained study.
Results: Nineteen articles met all selection criteria. Three studies found varying levels of support for multicomponent interventions, predominantly focused on implementation of clinical practice guidelines for specific presenting complaints and process redesign. Sixteen studies evaluated single-component interventions, with the following having at least one supportive study: using alternating patient assignment to provider teams rather than "zone"-based assignment, enhancing provider communication and customer service skills, incorporating information delivery interventions (e.g., pamphlets, video) that target patient expectations, using preformatted charts, and establishing ED-based observation units for specific conditions such as asthma and chest pain.
Conclusions: There is modest evidence supporting a range of performance improvement interventions for improving ED patient satisfaction. Further work is needed before specific, evidence-based recommendations can be made regarding which process changes are most effective. Recommendations are made for improving the quality of performance improvement efforts in the ED setting.     

Mechanisms and treatment issues for neuropathic pain

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Human Renal Allograft Rejection Despite the Absence of Allogeneic Passenger Leukocytes

Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression.     

Inhibition of platelet aggregation by novel triphenylethylene analogs

The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carboxyl function into the alpha-ring, which should enhance binding according to proposed structural models for cyclooxygenase inhibitors, was not found to be beneficial. Increased structural rigidity, which resulted from covalent linkage of two aromatic rings in this series, did not eliminate anti-aggregatory properties.     

Nonreflux complications of hiatal hernia

Patients with massive incarcerated hiatal hernia and no appreciable esophagitis present with a distinctly different clinical picture from those with hiatal hernia and reflux peptic esophagitis. In a recent review, 17 patients were encountered with this problem. The patients were often elderly and presented with the following grave complications: upper gastrointestinal obstruction; upper gastrointestinal bleeding, both acute and chronic, from gastric ulcerations; and perforated gastric ulcerations. In these patients, the surgical approach is better accomplished through the abdominal route. These patients should be distinguished from those with a shortened esophagus resulting from chronic reflux peptic esophagitis who often require thoracotomy for surgical correction.     

Influence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events

An experiment was conducted to determine whether aerobic exercise training or relaxation training would be effective for reducing the deleterious effects of life stress on physical and psychologic health. Over 1000 college students were surveyed, and 55 of those who reported experiencing a high number of negative life events over the preceding year were assigned to an aerobic exercise training condition, a relaxation training condition, or a no-treatment control condition. Physical and psychologic health were assessed with self-report measures before, halfway through, immediately following, and 8 weeks after the 11-week training (and control) period. Heart rate data collected during a treadmill test indicated that the aerobic exercise training was effective for improving cardiovascular fitness. Psychologic measures indicated that the exercise training condition was more effective than the other two conditions for reducing depression during the first 5 weeks of training. No differences were found among the conditions on self-report measures of physical health. These findings suggest that aerobic exercise training may be useful for reducing the severity and duration of depressive reactions following stressful life change.     

Men’s pathways to risky sexual behavior: Role of co-occurring childhood sexual abuse,posttraumatic stress disorder,and depression histories

Recent reports of sexually transmitted infection-rate increases among men indicate the need for renewed study of male sexual risk behavior to aid development of updated and novel risk reduction interventions. Men who have childhood sexual abuse (CSA) histories consistently report frequent sexual risk behavior. The objective of this sturdy is to explore whether posttraumatic stress disorder (PTSD) and depression are moderators and/or mediators of the association between CSA and sexual risk in adult men. A cross-sectional survey study employing random digit dial recruitment was administered to men aged 18–49 years from Philadelphia County. Two bundred ninety eight men were recruited and screened for CSA history, administered items from the Posttraumatic Stress Diagnostic Scale (PDS) and Center for Epidemiologic Studies—Depression (CES-D), and asked to estimate their number of lifetime sexual partners (LSPs). Effects of sociodemographic characteristics, CSA, PTSD, and depression on the number of LSPs were modeled using Poisson regression. Results show that 197 (66%) men participated; 43 (22%) had CSA histories. CSA was significantly associated with PTSD/depression (P=.03). Four sociodemographic variables (age, race, sexual identity, and education), CSA (incidence rate ratio, IRR=1.47, P<.001), PTSD (IRR=1.19, P=.04), depression (IRR=1.29, P=.001), all 2-way interactions, and the 3-way CSA/PTSD/depression interaction (IRR=11.00, P<.001) were associated with the number of LSPs (R²=0.27). In conclusion, sexual partnership patterns unique to men with CSA histories and comorbid PTSD/depression appear to lead to substantially higher numbers of LSPs. Estimates of this relationship may have been biased toward the null by underreporting that can occur with phone surveys. Cross-sectional studies do not support causal inferences; however, the identification of a moderating and mediating influence of PTSD/depression on the relationship between CSA and sexual risk behavior is important and suggests the need for future studies with larger samples that examine trajectories for CSA, psychiatric illness, and sexual partnerships.     

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.