Methods for epidemiologic analyses of multiple exposures: A review and comparative study of maximum-likelihood,preliminary-testing,and empirical-bayes regression

Many epidemiologic investigations are designed to study the effects of multiple exposures. Most of these studies are analysed either by fitting a risk-regression model with all exposures forced in the model, or by using a preliminary-testing algorithm, such as stepwise regression, to produce a smaller model. Research indicates that hierarchical modelling methods can outperform these conventional approaches. I here review these methods and compare two hierarchical methods, empirical-Bayes regression and a variant I call ‘semi-Bayes’ regression, to full-model maximum likelihood and to model reduction by preliminary testing. I then present a simulation study of logistic-regression analysis of weak exposure effects to illustrate the type of accuracy gains one may expect from hierarchical methods. Finally, I compare the performance of the methods in a problem of predicting neonatal mortality rates. Based on the literature to date, I suggest that hierarchical methods should become part of the standard approaches to multiple-exposure studies.     

Paget-von Schroetter syndrome: case description in the light of the literature

A 27 year old patient with a thrombosis of the subclavian vein (Paget- von Schroetter's-syndrome) was treated successfully with a systemic streptokinase thrombolysis. Indications and success of the different therapeutic ways in current literature (conventional management, systemic and local thrombolysis) are compared to each other. The authors prefer treatment with systemic thrombolysis, patients with contraindications should be treated with conservative management. Nevertheless no final conclusions can be drawn, as there are no controlled studies comparing the different concepts in treatment.     

Naturlatexallergie

As a consequence of AIDS prevention strategies, the use of powdered disposable latex gloves in hospitals and private medical practices has increased conspicuously in the past 10 years, and allergic reactions to natural latex have become a frequently observed problem. The clinical picture of type I allergies (immediate hypersensitivity) to natural latex ranges from slight, local allergic symptoms (urticaria, rhinitis, and conjunctivitis) to asthmatic complaints up to severest anaphylactic reactions. In addition to health care employees, patients are being affected with an increasing tendency during a variety of surgical and other medical interventions. Due to its enormous hygienic and economic significance, natural latex has become one of the most frequently studied sources of allergies. Efforts were undertaken to identify the causes and triggering factors, to develop diagnostic tools and continue to improve upon them, and to establish preventive measures and implement them successfully.     

Ulcus cruris an der Fußaußenkante

Ohne Zusammenfassung     

Mediastinal lymphoblastic lymphoma with an immature B-cell immunophenotype.

A 19-year-old woman presented with a large mediastinal mass, histologically shown to be malignant lymphoma of lymphoblastic type (LBL). Immunophenotypic and gene rearrangement analysis unequivocally demonstrated that the neoplasm was of B-cell lineage. The neoplastic cells expressed terminal deoxynucleotidyl transferase, the pan-B cell antigens CD19, CD20, and CD22, and were negative for immunoglobulins and numerous T-cell antigens tested. Southern blot analysis showed rearrangement of one allele of the immunoglobulin heavy chain gene while the immunoglobulin kappa and T-cell receptor beta chain genes were in the germline configuration. Thus, the immunophenotypic and molecular findings in this case correspond to an early stage of B-cell differentiation, the pre-pre B-cell stage as has been named by others. In contrast with LBL of immature T-cell lineage, precursor B-cell LBLs involving the mediastinum are truly rare. Occasional cases have been reported that have arisen elsewhere and subsequently involved the mediastinum at time of relapse or tumor progression. Well-documented examples of immature B-cell LBL arising in the mediastinum are virtually unreported. The site and cell population giving rise to this neoplasm is unknown. However, origin from precursors of normal thymic medullary B cells is proposed as one possibility.     

Primary stimulation of CD4+ cells in the presence of IL-4 or IFN-gamma alters the frequencies of cytokine-producing cells at restimulation.

The induction of specific effector functions in naive T cells may be directed by accessory signals during activation. These could be elicited through binding to cell surface molecules or through factors secreted by antigen-presenting cells or other simultaneously activated cells. We have investigated the influence of CD8+ cells and of exogenously added cytokines (interleukin (IL)-2, IL-4 and interferon (IFN)-gamma) on the cytokine production in splenic CD4+ T cells. IL-2, IL-4, IL-5 and IFN-gamma production in CD4+ cells was measured at the single cell level during primary mitogen stimulation in vitro in the presence or absence of factors or CD8+ cells. On day 5 the cells were restimulated with mitogen alone and analysed to evaluate the short-term development of cytokine-producing cells in such cultures. Preactivation in the presence of either exogenous IL-4 or IFN-gamma led to an increased production of IL-4 and IFN-gamma respectively at restimulation, and the effects of both IL-4 and IFN-gamma were augmented by IL-2. After preactivation in the presence of IL-2 and IL-4, every third CD4+ cell could be induced to produce IL-4. Exogenous IL-4 or IFN-gamma further decreased each other's production. Depletion of CD8+ cells before activation resulted in a slight increase of IL-4-producing cells, indicating that simultaneous activation of CD8+ cells will influence lymphokine production in CD4+ cells. The results suggest that the pattern of lymphokines induced in naive cells may be influenced by factors secreted by preactivated CD4+ and CD8+ cells, and that naive cells are preferentially 'recruited' to produce similar cytokines.