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עמוד בית
Fri, 25.07.25

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March 2001
Itzhak Pappo, MD, Michal Lotem, MD, Martine Klein, MD and Ruben Orda, MD

Background: High dose interleukin-2 therapy, adminis­tered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma.

Objectives: To present our experience using this mode of therapy in 21 patients with metastatic melanoma.

Materials and Methods: The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 lU/kg of IL-2 per dose iv. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit.

Results: Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P=0.115). Toxic side effects were significant, but they were treated successfully with no residual damage.

Conclusions: High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of auto­logous vaccines prior to high dose IL-2 may be recommended.

Eliad Karin, MD, Riad Haddad, MD and Hanoch Kashtan, MD
Asher Ben-Arieh, PhD and Yehuda L. Danon, MD

Cancer is a multi-step disease involving a series of genetic alterations that result in the loss of control of cell proliferation and differentiation. Such genetic alterations could emerge from the activation of oncogenes and the loss or malfunctioning of tumor suppressor gene activity. Our understanding of cancer has greatly increased through the use of DNA tumor viruses and their transforming proteins as a biological tool to decipher a cascade of events that lead to deregulation of cell proliferation and subsequent tumor formation. For the past ten years our laboratory has focused on the molecular biology of the human neurotropic papovavirus, JCV. This virus causes progressive multifocal Ieukoencephalopathy, a fatal neuro­degenerative disease of the central nervous system in immunocompromised patients. JCV is a common human virus that infects more than 80% of humans but does not induce any obvious clinical symptoms. The increased incidence of acquired immune deficiency syndrome and the use of immunosuppressive chemotherapy have dramatically raised the incidence of PML. The coincidental occurrence of malignant astrocytes and oligodendrocytes in PML patients, coupled with the induction of glioblastoma in JCV-intected non­human primates, provides intriguing speculation on the association between JCV and CNS malignancies. In this report we discuss clinical data and laboratory observations pointing to the direct involvement of JCV in cancer.

February 2001
Horacio Senties-Madrid, MD and Felipe Vega-Boada, MD

Paraneoplastic syndromes are disorders associated with cancer but without a direct effect of the tumor mass or its metastases on the nervous system. Small cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been termed “anti-Hu syndrome. Anti-­Hu associated PSN-PEM is an immune disorder in which both cell-mediated and humoral mechanisms are involved. Patients are consiaered affected by Anti-Hu associated PSN-PEM when they develop clinical signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by metas­tases or other disorders, and serum or cerebrospinal fluid is positive for Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM, Iimbic encephalitis, brainstem encephalopathy, opsoclonus-myoclo­nus, paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes. There are two types of treatment: the first is to treat the cancer, the second is to suppress the immune reaction with the use of corticosteroids, cyclophosphamide, azathioprine, plasma ex­change, intravenous immunoglobulin and immunoadsorption however, treatment of paraneoplastic syndromes is generally unsatisfactory.

January 2001
Ofer Nativ MD, Edmond Sabo MD, Ralph Madeb MSc, Sarel Halachmi MD, Shahar Madjar MD and Boaz Moskovitz MD

Objective: To evaluate the feasibility of using combined clinical and histomorphometric features to construct a prognostic score for the individual patient with localized renal cell carcinoma.

Patients and Methods: We studied 39 patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and 1983. Univariate and multivariate analyses were used to determine the association between various prognostic features and patient survival.

Results: The most important and independent predictors of survival were tumor angiogenesis (P=0.009), nuclear DNA ploidy (P=0.0071), mean nuclear area (P=0.013), and mean elongation factor (P=0.0346). Combination of these variables enabled prediction of outcome for the individual patient at a sensitivity and specificity of 78% and 89% respectively.

Conclusion: Our results indicate that no single parameter can accurately predict the outcome for patients with localized RCC. Combination of neovascularity, DNA content and morphometric shape descriptors enabled a more precise stratification of the patients into different risk categories.
 

Paul E. Slater, MD, MPH, Alex Leventhal, MD, MPH, MPA and Emilia Anis, MD, MPH
December 2000
Sonia Habib, MD, MPH, Shmuel Rishpon, MD, MPH and Lisa Rubin, MD, MPH
 Objective: To determine the vaccination rates among healthcare workers in the Haifa subdistrict and to assess factors associated with vaccination uptake among them.

Methods: The study was conducted in the three general hospitals in Haifa City, and in five nursing homes in the Haifa subdistrict. Self-administered questionnaires were distributed to 1,014 employees of whom 71% were females, 34% were nurses, 27% were physicians and 28% were non-professional workers.

Results: The crude response rate was 66%. Response rates were higher in females (71%) than in males (49%), in nurses (70%) than in physicians (43%), and in staff of internal and pediatric departments than in workers of surgery departments and emergency rooms. The overall vaccination rate among the respondents was 11%, which was higher among males (15%) than among females (10%). No significant relationship between vaccination rate and age, occupation and department was found. The vaccination rate among employees with chronic illness was very low (7%). Influenza vaccine was actively recommended to 29% of the employees. The main reasons for non-compliance were low awareness of the severity of the disease and of the vaccine's efficacy and safety, and unavailability of the vaccine within the workplace.

Conclusions: Educational efforts and offering the vaccine at the workplace at no cost are the most important measures for raising influenza vaccination rates.

Zvi H. Abramson, MD, MPH and Vered Cohen-Naor, MD
 Background: Influenza is a major cause of morbidity and mortality in the elderly. While immunization has been shown to reduce these complications, many of the elderly are not immunized.

Objective: To identify correlates for under-utilization of influenza immunization among the elderly.

Methods: A telephone survey was conducted among a random sample of patients aged 65 and over registered at a Jerusalem primary care community clinic. The 626 questionnaires were analyzed for associations of immunization receipt for the latest influenza season. Multivariate logistic regression was performed to identify independent correlates. Respondents were also asked what factors had influenced their decision about immunization.

Results: The most frequently reported influence on getting immunized was a physician's recommendation. Immunization was independently associated with the identity of the primary care physician (P0.0001) and with having visited the physician during the previous 3 months (P=0.0006). Immunization was more likely among persons who believed that it provides complete protection from influenza (P0.0001) and less likely among those who believed immunization can cause influenza (P0.0001). Higher immunization rates were also associated with being married (P=0.0031).

Conclusion: Through their influence on patient knowledge and the effect of their recommendation, primary care physicians play a pivotal role in determining immunization rates. Physicians should routinely discuss the effects of immunization and recommend it to the elderly.

Rita Rachmani, MD, Zohar Levi, MD, Rika Zissin, MD, Merav Lidar, MD and Mordechai Ravid, MD, FACP
Rosalie Ber, MD, DSc, Gershon B. Grunfeld, PhD and Gideon Alroy, MD
 The Rappaport Faculty of Medicine of the Technion established an Ethics in Medicine Forum in March 1993. The main objective of the forum was to increase awareness of the philosophical principles of ethics in medicine, as defined and developed in the western world during the last three decades. The multidisciplinary forum meets once a month during the academic year. Our 7 years experience is documented. Of the 45 meetings, 30 were clinically oriented and of these more than half were based on cases. Only 15 meetings were purely theoretical. Our principal a assumption was that any and every topic could be discussed, including those covered by the law We explored a how well western philosophical principles and rules fit the Israeli picture. Many of the forum discussions related to 0 the draft of the Patient’s Bill of Rights which came into effect on 12 May 1996. The role of the ‘legal’ hospital ethics committees was compared to that of the “advisory” ethics committees whose members constituted a large share of our forum. The multicultural Israeli population and the practice of medicine therein raised many lively discussions. The principle of autonomy in the ultra-orthodox and in the family setting was a highly controversial issue. The forum served as a workshop for examining traditional medical ethical principles, which we strongly feel needs to he amended in light of the 1996 Patient’s Bill of Rights. From our 7 years experience with an Ethics in Medicine Forum we recommend that medical ethical deliberations focus on genuine medical cases.

November 2000
Shmuel Fennig, MD, Dan Yuval, PhD, Miriam Greenstein, Stanley Rabin, PhD and Michael Weingarten, MA, BM, BCh

Background: The aim of family medicine is to provide patients with comprehensive care within the biopsychosocial model. High job satisfaction is necessary to attract physicians to this specialty

Objective: To compare job satisfaction levels between primary physicians with training in family medicine and physicians without specialty training.

Methods: A self-report questionnaire, the "Task Profiles of General Practitioners in Europe," was mailed to a stratified random sample of 664 primary care physicians in Israel. The response rate was 77.6%. Bivariate and logistic regression procedures were used to analyze the data.

Results: Physicians with training in family medicine were less satisfied with the rewards for their work than general practitioners with no formal specialization in family medicine. Satisfaction with the intrinsic aspects of the work was found to be equal. Women and rural physicians were more satisfied than men and urban physicians.

Conclusion: Measures should be taken by health maintenance organizations to increase the level of job satisfaction of specialist-certified family physicians to avoid a crisis in the profession.
 

October 2000
Zalmzn Kaufman MSc, Irit Cohen-Manheim MSc and Manfred S. Green MD MPH PhD

Background: Although influenza is usually a mild self-limiting disease it can cause serious complications in high risk groups. The economic costs of influenza are large due to the burden on the health system and absenteeism from work. There is evidence that the vaccine is underused in groups targeted for vaccination.

Objectives: To estimate: a) the compliance rate with the influenza vaccination in Israel during the winter seasons of 1998/1999 and 1999/2000, b) the role of health care personnel and the media in influencing compliance, and c) the reasons for lack of compliance in the elderly.      

Methods: Two national population-based random telephone surveys of 1,500 households were performed during October 1999 and January 2000 to survey influenza vaccination compliance prior to the winters of 1998/1999 and 1999/2000 respectively. Each survey was performed during four successive evenings. The response rate was 78.1% for the first survey and 79.1% for the second.

Results: Vaccination compliance was similar in both surveys. The average rate of vaccination was 6% for the population under 65 years and 50% for the population of 65 years and above. The overall vaccination rate was around 10%. The family physician was the main authority to recommend the vaccination, followed by the community nurse. Absence of recommendation and lack of faith in the efficacy of the vaccine were the main reasons for non-compliance.

Conclusion: Compliance rates with influenza vaccine in targeted groups in Israel remain relatively low. Health care personnel should be more involved in promoting the vaccine.
 

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