Arie Figer, MD, Yael Patael Karasik, MD, Ruth Gershoni Baruch, MD, Angela Chetrit, MSc, Moshe Z. Papa, MD, Revital Bruchim Bar Sade, MSc, Shulamith Riezel, MD and Eitan Friedman, MD, PhD
Background: Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients.
Objective: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls.
Methods: We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212-sporadic and 56 carriers of either a BRCA1:or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent auloradiography,
Results: Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only {3/536, 0.6%).
Conclusions: The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.
Yehuda Neumark, PhD, Yechiel Friedlander, PhD and Rachel Bar-Hamburger, PhD
Background: Various studies support the concept of an inherited vulnerability to drug dependency, while emphasizing the importance of social and environmental influences and their interactions
Objectives: To compare the characteristics of heroin-dependent Jewish men in Israel with those of the general population, focusing on the nature of family history of substance abuse.
Method: This case-control study compares 64 heroin-dependent Jewish male residents of Jerusalem with a community sample of 131 randomly selected Jerusalem residents with no drug use disorder. Univariate and mulbvariate moderns were employed to appraise the independent associations between heroin dependence and exposure variables such as family history of substance misuse and exposure to legal psychoactive substances.
Results: The case group is characterized by heavy tobacco and' alcohol involvement. Nearly 70% of the cases report an alcohol and/or drug problem in at least one first-degree relative compared with 10% of controls (odds ratio 14.5, adjusted for sociodemographic and other potential confounders). Cases with a positive family history have, on average, higher alcohol consumption levels and higher heroin-use severity scores, as compared with cases with no such history.
Conclusions: Familial aggregation of drug and alcohol problems, along with smoking at a young age, is the strongest predictor of heroin dependence in this population. Better understanding of the components underlying this familial aggregation can lead to improved prevention and treatment strategies.
Abraham Benshushan, MD, Avi Tsafrir, MD, Revital Arbel, MD, Galia Rahav, MD, Ilana Ariel, MD and Nathan Rojansky, MD
Background: Although Listeria monocytogenes is widely distributed in nature, it rarely causes clinical infection in previously healthy people. This microorganism. however, may cause severe invasive disease in pregnant women and newborns.
Objectives: To investigate – in our pregnant population – the impact, severity and outcome of listeriosis on both mother and fetus.
Method: The study was carried out at a level III, university two-hospital complex, In a retrospective chart review of 65,022 parturients during a 10 year period (1990-1999), we identified and: evaluated 11 pregnant patients and their offspring with Listeria infection;
Results: Chorioamnionitis with multiple. placental abscesses were observed in all five placentae examined. Clinically 4 of 11 parturients had a cesarean section for fetal distress (36.3%), as compared to the 14% mean CS rate in our general population. Two of 11 had a fate abortion (18.1%), as compared with the 4% rate in our hospital. Four of 11 had premature labor (36%), which was about four times the rate in our population. Finally, although no intrauterine feta1 death was recorded in our series, there was one neonatal death of a term infant. (1/11, 9%), which is about 10 times higher than our corrected perinatal mortality rate.
Conclusions: If not promptly and adequately treated, listeriosis in pregnancy may present serious hazards to the fetus and newborn through direct infection-of the placenta and chorioamnionitis.
Mark J. Yaffe, MD, CM, M, MCISc, CCFP, FCFP and Jacqueline Klvana, MD, CM, CCFP
Background: Eldercare often necessitates the presence of a family caregiver at the senior's visit to a doctor’s office. Studies indicate that some caregivers are not satisfied with these encounters or with as An understanding of the dynamics of these complex interactions is required.
Objectives: To explore family physicians’ attitudes to interfacing family caregivers of the elderly, to identify factors within the family patient-caregiver encounters in the office setting that for physicians, to ascertain factors that might be problematic for physicians, to ascertain factors that might contribute to doctors’ behaviors and concerns, and to propose possible solutions for optimizing the outcomes of these visits.
Method: A questionnaire for self-administration was mailed to 200 family physicians in Montreal, Canada who are affiliated with two community secondary care and one tertiary care hospital and involved in geriatric office practice. The survey focused on family physician attitudes, concerns and observations on the interactions among themselves, elderly patients and their family caregivers during office visits.
Results: A total of 142 completed questionnaires were returned with a 71% response rate. Most family doctors felt that it was their responsibility to respond to caregiver concerns (90.6%) and that they were generally meeting their needs (94.2%). In contrast, 81% found this activity stressful and that as few as three such encounters per day were sufficient to generate stress. Causes of stress included: a) concern regarding misdiagnosis, b) different agendas or conflicting responses of patient and caregiver to doctors’ suggestions, and c) reluctance of the elderly or the caregiver to use community resources. A common physician strategy was reliance on acquired professional experience to solving problems of the elderly or of their caregivers.
Conclusions: Despite the stress involved, physicians are interested in assisting caregivers in the management of the elderly. Many doctors lack adequate knowledge about or confidence in community resources. Clinicians may require enhanced skills in conflict resolution necessary to achieve optimal outcomes.
Veronica Silva Vilela, MD, Nilson Ramirez de Jesus, MD and Roger Abramino Levy, MD, PhD
by Amir Karban, MD, Rami Eliakim, MD and Steven R. Brant, MD
The etiology of inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function.
Recent genome wide searches reported several susceptibility loci for Crohn’s disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn’s disease will have a major impact on the understanding of the genetics of this disease.
Marina Shargorodsky, MD and Reuven Zimlichman, MD
Hannah Tamary, MD, Raanan Bar-Yam, BSc, Michal Zemach, MD, Orly Dgany, PhD, Lea Shalmon, MSc and Isaac Yaniv, MD
Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.
Misha Witz, MD, Jonathan M. Lehmann, MB, BChir, Ali Shnaker, MD, Itamar Pomeranz, MD,George Leichtman, MD and Benthly Novis, MD, FRCP
Aharon Klar, MD, Ariel Halamish, MD, David Shoseyov, MD, Pascal Cassinotti, PhD, Gunter Siegl, Chaim Springer, MD, Gila Shazberg, MD and Haggit Hurvitz, MD