Israel Medical Association Journal

Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc[1] was recently launched (ASTIS) and a trial involving MS[2] is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.

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Henri Bergson (1859-1941) was probably the most influential French philosopher at the turn of the twentieth century. In 1927 he was awarded the Nobel Prize for literature. Far beyond the restricted academic philosophical milieu, the impact of his thinking reached personalities as diverse as Claude Debussy, Marcel Proust, George Bernard Shaw, and the impressionists.  His essay The Laughter (Le Rire) is one of the most profound and original ever written on the sense of humor. Bergson’s opinions, with their emphasis on life, instinct and intuition, represented a deviation from the rationalist mainstream of western philosophical tradition. In some circles he was received with skepticism and irony as in Bertrand Russel’s History of Western Philosophy. Today, unbiased by theoretical "bergsonism," neurophysiologic research - as undertaken mainly by Antonio Damasio’s team at Iowa University - confirms many of his hypotheses and elucidates their mechanisms. In this new light, intuition and “recognition by the body” should not be seen as the personal fantasy of an original thinker but as fundamental cognitive tools.

Background: The emergency department is one of the hospital’s busiest facilities and is frequently described as a bottleneck. Management by constraint is a managerial methodology that helps to focus on the most critical issues by identifying such bottlenecks. Based on this theory, the benefit of adding medical staff may depend on whether or not physician availability is the bottleneck in the system.

Objective: To formulate a dynamic statistical model to forecast the need for allocating additional medical staff to improve the efficacy of work in the emergency department, taking into account patient volume.

Methods: The daily number of non-trauma admissions to the general ED[1] was assessed for the period 1 January 1992 to 1 December 1995 using the hospital computerized database. The marginal benefit to shortening patient length of stay in the ED by adding a physician during the evening shift was examined for different patient volumes. Data were analyzed with the SAS software package using a Gross Linear Model.

Results: The addition of a physician to the ED staff from noon to midnight significantly shortened patient LOS[2]: an average decrease of 6.61 minutes for 80–119 admissions (P<0.001). However, for less than 80 or more than 120 admissions, adding a physician did not have a significant effect on LOS in the ED.

Conclusions: The dynamic model formulated in this study shows that patient volume determines the effectiveness of investing manpower in the ED. Identifying bottleneck critical factors, as suggested by the theory of constraints, may be useful for planning and coordinating emergency services that operate under stressful and unpredictable conditions. Consideration of patient volume may also provide ED managers with a logical basis for staffing and resource allocation.

Severe combined immunodeficiencies represent a heterogeneous group of hereditary defects of the immune system that affect both T and B cells and whose etiology has only recently begun to be understood. A portion of these SCID patients bear a defect in either of the two recombination-activating genes, Rag-1 or Rag-2, while others have mutations in a newly identified gene, Artemis. Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells, and peculiar features also due to a defect in Rag-1 or Rag-2 genes. All these three forms are characterized by an impairment of the VDJ recombination, the process that insures the somatic diversification of immunoglobulin and T cell receptor-encoding genes. Recent findings have enabled us to better understand the pathophysiology of these three immunodeficiencies, which affect the V(D)J recombination process to a different extent and in different ways.

Background: One of the measures adopted in Israel since 1959 as part of the tuberculosis control program was screening children aged 12–13 years old. The screening comprised single-step tuberculin skin testing using the Mantoux method.

Objective: To assess the efficacy of tuberculin skin screening for TB[1] in schoolchildren in southwestern Israel as well as the compliance to treatment for latent tuberculosis infection.

Methods: We retrospectively reviewed the records of children in the Ashkelon region who underwent a tuberculin skin test during the period 1995–99.

Results: Of the 28,016 eligible children, 27,232 were tested. In 923 children, mostly from the former USSR and Ethiopia, an induration of 10 mm or more was found. Only 52 Israeli-born children tested positive. Tuberculosis was found in seven children with a positive test, five of whom were from Ethiopia. All children who tested positive were referred to the local TB clinic; only 266 children (28.8%) presented. Only 151 completed the recommended treatment of isoniazid for 6 months. Thus, although screening included most of the targeted children aged 13, only a third of them presented to a TB clinic, of whom only about half completed treatment of latent infection.

Conclusions: Our results indicate that the current policy of screening for latent TB in our region is ineffective in terms of implementation of the recommended treatment. We suggest that only high risk groups be screened, and that a concerted effort be made to implement treatment.

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