The pattern of disulfide linkages in the extracellular loop regions of connexin 32 suggests a model for the docking interface of gap junctions

This study evaluated the contribution of acute parenchymal rejection and interferon (IFN)-gamma to the development of graft arterial disease (GAD) in totally allogeneic murine cardiac transplants. BALB/c (H-2d) hearts were transplanted into wild-type C57BL/6 (B6, H-2b) or B6 IFN-gamma-deficient (GKO) recipient mice. Assessing the role of acute parenchymal rejection in the GAD process involved two different immunosuppression protocols using anti-CD4 and -CD8 monoclonal antibodies (MAbs): virtually complete long-term immunosuppression (denoted as complete immunosuppression) was achieved by administering both MAbs 6, 3, and 1 day before transplantation and weekly thereafter; in contradistinction, a single, early, transient episode of rejection (transient rejection) was attained by administering MAbs beginning 4 days after transplant and then at weekly intervals. The extent and duration of T cell depletion under these two regimens were evaluated using flow cytometric analysis of peripheral blood lymphocytes. After a single injection of MAbs, peripheral blood CD4+ and CD8+ T cell depletion was approximately 98% at 1 week and approximately 88% at 2 weeks. After three injections (analogous to days 6, 3, and 1 before transplant), peripheral blood CD4+ and CD8+ T cell depletion was >98% at 2 weeks and approximately 87% at 4 weeks. Functioning cardiac allografts were removed at 8 and 12 weeks after transplant and analyzed by hematoxylin and eosin, elastic tissue, and immunohistochemical stains, and the severity of parenchymal rejection versus GAD was scored. With complete immunosuppression (antibody before and after transplant), BALB/c allografts showed little parenchymal rejection or GAD, suggesting that persistent depletion of T cells blocked subsequent development of GAD. However, even a single transient acute rejection episode allowed the subsequent development of GAD accompanied by augmented major histocompatibility complex (MHC) class II, VCAM-1, and ICAM-1 expression at 12 weeks; these allografts showed no residual CD4+ or CD8+ T cells. In comparison, allografts undergoing transient rejection in GKO recipients did not develop GAD, despite persistent macrophage and natural killer cell (NK) infiltrates comparable to those seen in wild-type recipients. Moreover, the arterioles of hearts transplanted into GKO recipients showed no or minimal increases in MHC class II, ICAM-1, and VCAM-1 relative to baseline expression. In conclusion, a single episode of allogeneic injury mediated by T cells suffices to evoke subsequent graft arteriosclerosis, even in the absence of additional T-cell-mediated injury, and the process appears to depend on IFN-gamma.     

Transvenous cold mapping and cryoablation of the AV node in dogs: observations of chronic lesions and comparison to those obtained using radiofrequency ablation

Lymphocyte transfusion from the marrow donor (DLT) is well established as an effective therapy for relapse of CML post allogeneic BMT. Reports thus far have been mostly limited to patients who received DLT from a matched sibling donor. We compared the efficacy and toxicity of DLT in 30 patients who were treated with cells from their HLA-identical sibling (n = 18) or from their phenotypically HLA-matched unrelated marrow donor (n = 12). The overall probability of obtaining a cytogenetic remission was 69% (95%CI: 51-83%) and was not significantly different between the two groups. The disease stage at the time of DLT was the only factor associated with cytogenetic remission by multivariate analysis; patients treated in cytogenetic or molecular relapse (n = 11) were seven times more likely (RR = 7.4, 95%CI: 2.4-22.4, P = 0.0005) to respond compared to patients treated for hematologic relapse (n = 19). There was a trend towards more acute GVHD II-IV in the unrelated donor group (58 vs 39%, P = 0.09), but the probability of developing extensive chronic GVHD was not significantly different (56 vs 39%, P = 0.4). We conclude that transfusion of donor cells from HLA-matched volunteer donors does not appreciably increase the risk of GVHD compared with transfusion of cells from HLA-identical siblings in patients with CML who relapse following allogeneic BMT. Conversely, there is no evidence for an increased graft-versus-leukemia effect after DLT from volunteer donors.     

The pediatrician and the sexually active adolescent. Treatment of common menstrual disorders

Menstrual disorders in adolescents are a common medical problem. For young adolescents, the onset of menses is a time of dramatic physical and psychological change. Providing education to young women regarding the normal process of puberty helps ease some of the anxiety regarding this change. Health professionals can participate in the education of young women by defining the normal process of puberty and menstruation. Menstrual disorders, such as dysmenorrhea, irregularities in menstrual flow, and premenstrual symptoms, can be effectively diagnosed and treated in the adolescent population.     

Survey of malathion resistance and avermectin susceptibility in field populations of Drosophila melanogaster (Diptera: Drosophilidae) and D. simulans

Populations of Drosophila melanogaster (Meigen) and Drosophila simulans (Sturtevant) from various geographic locations in North America and elsewhere were sampled to assess the distribution of malathion resistance and avermectin tolerance. Comparisons are made to previous reports of a differential response to malathion selection in these species. Results indicate that for malathion, resistance is widespread in D. simulans but varies considerably in D. melanogaster. For avermectins, although the pattern of tolerance is similar in both species, there exists a significant amount of variation in these levels between geographic regions. We consider how these different geographic patterns of resistance distribution may shed insight on the relative roles of population structure and exposure history in affecting the spread of resistance. In addition, we consider further the use of D. melanogaster and D. simulans as a model for examining the effects of insecticide exposure on sympatric populations.     

Comparing i.v. and non-i.v. cocaine users. Characteristics of a sample of cocaine users seeking to participate in research

Psychiatric disorders were studied in an epidemiological and representative sample of 1964 pupils attending the first to ninth grade in various types of schools in the Canton of Zürich, Switzerland. Using a two-stage procedure, parents were asked to respond to a standardized behaviour problem checklist in the screening phase. In the second stage, structured interviews were performed with 399 parents representing both screen positive and control children. DSM-III-R diagnoses were derived from the interviews. The total prevalence figure for any disorder amounted to 22.5%. Prevalence rates were influenced by the multi-screen procedure. Among various correlates, sex, nationality, age and residence were to some extent significant. Comorbid disorders were present in 12.5% of the subjects.     

The global diversity of protozoa and other small species

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further.     

Investigations on the renin-angiotensin system in acute severe asthma

The renin-angiotensin system is activated in acute severe asthma. The precise mechanism of activation is at present unknown, but may involve, beta2-agonists, catecholamines or proteases released in airway inflammation. This study aims to identify potential factors involved in the activation of the renin-angiotensin system in acute asthma. Forty asthmatics with severe exacerbations of asthma, assessed by measurement of peak expiratory flow rate (mean (SD) 35 (18)% predicted), oxygen saturation (94 (4)%) and pulse rate (108 (16) beats x min(-1)) were recruited. Nineteen (48%) asthmatics had elevated plasma angiotensin II levels (median (interquartile range) 10.9 (4.3-23.5) pg x mL(-1) (normal range 3-12 pg x mL(-1))) and 10 (25%) had elevated plasma renin concentration (22.0 (10.0-50.0) microU x mL(-1) (normal range 9-50 microU x mL(-1))). Plasma renin and angiotensin II correlated strongly, implying renin-dependent angiotensin II formation. No correlation was found between plasma salbutamol, adrenaline, nor-adrenaline, endothelin-1, histamine, eosinophilic cationic protein, serum angio-tensin-converting enzyme (ACE) activity, total immunoglobulin E (IgE), urea and electrolytes, indicators of the severity of the attack, atopic status, blood pressure and renin or angiotensin II levels. We conclude that although a subpopulation of asthmatics appear to have raised renin and angiotensin II during attacks of acute, severe asthma, the mechanism of activation of the renin-angiotensin system remains unclear.     

Departmental audit in surgical anatomical pathology

Chronic obstructive pulmonary disease (COPD) is the result of many years of accelerated decline in lung function in susceptible cigarette smokers. Although risk factors for the susceptibility of smokers to COPD have been established, there are still large gaps in our knowledge of the biological basis for these risk factors and of how to identify individuals at risk. COPD is the fourth leading cause of death and, in contrast to other major chronic diseases in the United States, has not shown declines in mortality over the past 20 years. Mortality trends reflect patterns of initiation of cigarette smoking that occurred 30 to 50 years previously. Current mortality trends indicate that COPD mortality may be leveling off among white males, but will continue to increase among women, African-Americans, and the elderly. Recent studies indicate that early identification of individuals with airflow obstruction and smoking intervention can halt the progression of COPD, but widespread screening and intervention programs have not yet been established.