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עמוד בית
Sat, 23.11.24

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March 2001
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.
 

Maurit Beeri, MD, Ziv Haramati, MD, JJT. Azaria Rein, MD and Amiram Nir, MD

Background: Parental knowledge of their child’s heart disease, while often overlooked, contributes to compliance and reduces anxiety. Prior studies have shown that 36% of parental diagnostic descriptions are incorrect.

Objectives: To assess parental knowledge and attitudes among outpatients at a hospital pediatric cardiology clinic.

Methods: Seventy-four families completed a questionnaire in which they described their child’s condition and stated their attitude towards dental hygiene and future prenatal diagnosis.

Results: Eighteen percent of the parents failed to describe their child’s malformation correctly. We found that parental understanding of the heart defect correlated with parental education. Future prenatal diagnosis was considered by 88% of families, and termination of pregnancy by 40%. Only 40% of children were aware of their heart problem. Children of parents who were ignorant about the condition tended to lack knowl­edge themselves. An additional finding was that 68% of Jewish families turn to non-medical personnel for medical advice - an interesting finding not hitherto addressed.

Conclusions: Ignorance of their child’s problem did not correlate with its severity or complexity but rather with parental background: the less educated the parent, the more likely was the problem perceived incorrectly.
 

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
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
Elizabeth Fireman, MD, Mordechai R. Kramer, MD, Nathan Kaufman, MD, Joachin Muller-Quernheim, MD and Yehuda Lerman, MD, MPH
Jonathan M. Lehmann, MB, Bchir, Ali Shnaker, MD, Daniel Silverberg, MD, Kati Dayan, MD and Misha Witz, MD
Eitan Scapa, MD, Eli Yona, MD and Lily Amram, MD
February 2001
Donato Alarcon-Segovia, MD and Yehuda Shoenfeld, MD
Max J. Schmulson, MD

Knowledge on the pathophysiology of irritable bowel syndrome has evolved, beginning with disturbances in motility to visceral hypersensitivity, and ultimately to alterations in brain-gut bi­directional communication, where neurotransmitters such as serotonin play a key role. Recently, a multicomponent disease model that integrates all these alterations was proposed. This model is divided into physiological, cognitive, emotional and behavioral components that explain the gastrointestinal as well as the constitutional symptoms. In recent years there has been an explosion of research together with new developments in pharmacological treatments for lBS that support each compo­nent of this model. This review presents recent data in favor of these alterations in IBS.

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.

Alejandro Ruiz-Arguelles, MD and Donato Alarcon-Segovia, MD, MSc

The formerly prevalent concept that intact autoantibodies could not penetrate into viable cells has been defeated by a large amount of experimental findings and clinical observations that indicate otherwise. The penetration of autoantibodies into living cells seems to participate in the pathogenesis of diverse autoimmune diseases, but it may also play a physiological role in healthy individuals. Although the fine mechanisms of the phenomenom remain to be elucidated, the potential use of penetrating autoantibodies as vectors to deliver molecules into cells, with diverse therapeutic purposes, has gained growing interest during the last few years.

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