Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Chronic intestinal pseudo-obstruction: manifestations, natural history and management

Chronic intestinal pseudo-obstruction (CIPO) is a rare pathological condition characterized by a marked derangement of gut propulsive motility mimicking mechanical obstruction, in the absence of any lesion occluding the gut lumen. This disease is often associated with a disabling and potentially life-threatening complications and is still too often unrecognized even in referral centres. As a result, patients receive neither appropriate care nor recognition of their severe health condition. Medical and surgical therapies are often unsatisfactory and long-term outcome turns out to be poor in the vast majority of cases. This article focuses on the main clinical features, the management and long-term outcome of patients affected by CIPO, with particular emphasis on those aspects which remain a matter of debate.     

Identification of human T-cell epitopes on the S4 subunit of pertussis toxin.

Ten adult humans were vaccinated with the Japanese acellular pertussis vaccine JNIH-3, containing detoxified pertussis toxin (PT), formaldehyde, and filamentous hemagglutinin. The vaccination induced a specific antibody response to PT and filamentous hemagglutinin, and a Western blot (immunoblot) analysis of the antibody response to PT revealed antibodies to PT subunits S1, S2, S3, S4 and S5. The response of peripheral lymphocytes to PT was assessed in an in vitro proliferation assay. A proliferative response to detoxified PT and PT dimers S2-S4 and S3-S4 was found, and it was further demonstrated that the proliferative response to detoxified PT and dimer S2-S4 was mediated by T cells of the CD4+ phenotype. The specificity of the proliferative response to subunit S4 was analyzed with a range of synthetic peptides synthesized on the basis of the primary sequence of subunit S4. The proliferative response to the peptides revealed two major and one minor T-cell epitope located in the NH2-terminal end of subunit S4.     

Endokrine Therapie des metastasierten Mammakarzinoms

One of the characteristics of breast cancer is its hormone dependency, which provides a number of effective approaches for treatment. Endocrine therapies usually have a good tolerability and oral application is convenient. Third generation aromatase inhibitors are well established in the treatment of metastatic breast cancer, having overtaken Tamoxifen. In the adjuvant setting, the ATAC trial is beginning to demonstrate the superiority of anastrozol compared to Tamoxifen. A new set of trials, coordinated by the International Breast Intervention Study Group, will compare the anti-hormones in healthy postmenopausal women with a moderate risk of developing breast cancer and in women after surgery for ductal carcinoma in situ. This article will discuss the various options for endocrine therapy in metastatic breast disease. The indications for endocrine manipulation as well as the various drugs will be discussed.     

Operative treatment of femoral head necrosis

Summary The cases of 80 patients with necrosis of the femoral head who underwent operative treatment in the period April 1980 to April 1988 are reported. Altogether, 102 operative procedures were carried out: 48 intertrochanteric osteotomies, 50 arthroplasties, 3 subchrondral bone graftings, and in one case drilling of the necrotic focus. Joint-preserving methods in advanced-stage disease seem to be of doubtful use when judged by clinical and socio-economic criteria over a mean follow-up time of 4.5 years. Since no conservative treatment exists, an improvement in therapeutic results can only be achieved by early diagnosis using magnetic resonance imaging and operating when the disease is still at an early stage.     

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND. The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS. The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS. In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS. SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.