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עמוד בית
Fri, 22.11.24

Search results


March 2001
Talia Weinstein, MD, Ran Tur-Kaspa, MD, Avry Chagnac, MD, Asher Korzets, MD, Yacov Ori, MD, Dina Zevin, MD, Michal Herman, MD and Uzi Gafter, MD PhD

Background: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy.

Objectives: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population.

Methods: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay.

Results: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02).

Conclusions: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, lb being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Itzchak Levi, MD, Baruch Modan, MD, Tzvia Blumstein, MA, Osnat Luxenburg, MD, Tamar Yehuda-Cohen, PhD, Barak Shasha, MD, Amir Lotan, MD, Arie Bundstein, MD, Asher Barzilai, MD and Ethan Rubinstein, MD

Objectives: To compare risk behavior between subjects attending anonymous and confidential clinics for human immunodeficiency virus testing, and to assess whether anonymous testing results in a higher accrual of persons at risk for HIV.

Methods: An anonymous questionnaire that addressed sociodemographic and risk behavior aspects was administered to 140 subjects attending an anonymous clinic and 124 attending a confidential clinic in the Tel Aviv area. A logistic regression analysis was used to compare the effects of various behavioral factors on the probability of attending each clinic.

Results: Chronological age, age at first sexual intercourse and the percent of married subjects were similar in both clinics. However, there was a significant difference in the sex ratio and in educational attainment (85.0% versus 55.6% were males, P< 0.001 and 58% vs. 34% had over 12 years of education, P<0.001, in the anonymous and confidential clinics respectively).

There was a striking difference between the two clinics with regard to sexual experience characteristics: of the subjects reaching the anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6% in the confidential clinic. A logistic regression analysis, comparing the effects of various behavioral factors on the probability of attending each clinic showed that gender (male), high education, homosexuality, number of partners and sexual encounter with sex workers were the strongest predictors for selecting anonymous HIV examination.

Conclusions: Individuals at high risk for HIV, such as homosexuals and bisexuals, prefer to attend an anonymous clinic.
 

Michael Davidovitch, MD, Gabriela Holtzman, MD and Emanuel Tirosh, MD

Background: Autism is a pervasive developmental dis­order. The incidence rate and other related epidemiological characteristics of the Israeli population are not available.

Objectives: To assess the incidence rate of autism in the Haifa area and to compare family characteristics with previous reports from other countries.

Methods: We approached facilities in the Haifa area that are involved with the diagnosis and treatment of autism. The study group comprised children born between 1989 and 1993. Records of the children were scrutinized and 69% of the mothers were interviewed. Live-birth cohorts of the same years were employed for incidence computation.

Results: An incidence rate of 1/1000 was derived. Male to female ratio was 4.2:1. Pregnancy and perinatal periods were mostly uneventful. A low prevalence of developmental and emotional morbidity was reported for family members.

Conclusions: The epidemiological characteristics found in the Haifa area are similar to those reported from non-Israeli communities. This finding supports an underlying biological mechanism for this disorder. These data can be used for future trend analyses in Israel.
 

Eduardo Shahar, MD and Margalit Lorber, MD

Background: Asthma, allergic rhinitis, and atopic derma­titis are leading causes of chronic diseases in developed countries, with at least one allergic condition troubling 10 to 20% of the general population. The few studies performed in Israel determined the prevalence of allergic conditions in selected populations (schoolchildren and soldiers) no study representative of the general population has previously been done.

Objectives: To determine the prevalence of allergic conditions in the general population in Israel and the differences between ethnic and socioeconomic groups.

Method: Using a computer-assisted telephone interview, a telephone questionnaire was conducted in a representative sample of the general Israeli population.

Results: Of the population studied, 140/a claimed to have bronchial asthma, 14% allergic rhinitis, and 6% other allergic conditions. Prevalence rates were higher in the Israeli Arab population and in those with low income and low education levels. Of those with allergic conditions, 58% were treated by a primary physician, 32% were not treated at all, and only 10% were treated by a different specialist physician.

Conclusions: The prevalence of allergic conditions in this study concurs with that found by other studies in developed countries. Allergic conditions are higher in the Israeli Arab population and in those with low income and low education level.

Marina Leitman, MD, Eli Peleg, MD, Simcha Rosenblat, MD, Eddy Sucher, MD, Ruthie Wolf, Stanislav Sedanko, Ricardo Krakover, MD and Zvi Vered, MD
Boaz Amichai, MD, Marcelo H. Grunwald, MD and Lesley Brenner, BSc

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.

Rasmi Magadle, MD, Paltiel Weiner, MD, Alexander Sozkover, MD and Noa Berar-Yanay, MD
Jonathan M. Lehmann, MB, Bchir, Ali Shnaker, MD, Daniel Silverberg, MD, Kati Dayan, MD and Misha Witz, MD
February 2001
Donato Alarcon-Segovia, MD and Yehuda Shoenfeld, MD
Bo Johanneson, BSc and Marta E. Alarcon-Riquelme, MD, PhD
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.

Marcia Hiriat, MD, PhD, Roman Vidaltamayo, PhD and M.Carmen Sanchez-Soto, MSc

Trophic factors such as nerve and fibroblast growth factors are important modulators of 13 cell physiology. These two factors induce the extension of neurite-Iike processes in primary cultures of adult rat 13 cells. Moreover, both NGF and FGF enhance glucose-induced insulin secretion. Since â cells synthesize NGF and pancreatic islet cells produce FGFs, it is possible that autocrine/paracrine interactions may be major regulators of insulin secretion, and impairment of these interactions could lead to pathological states such as diabetes mellitus.

Zvi R. Cohen, MD, Revital Duvdevani, PhD, Dvora Nass, MD, Moshe Hadani, MD and Zvi Ram, MD

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.

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