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.
Judith Barash, MD, Doron Dushnitzky, MD, Dalia Sthoeger, MD, Rita Bardenstein, MSc and Yigal Barak, MD,
Background: Human parvovirus B19 is responsible for a variety of clinical syndromes, such as erythema infectiosum, non-immune hydrops fetalis, transient aplastic anemia, and arthropathies. HPV is also suspected of playing a role in the pathogenesis of various chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Kawasaki disease and multiple sclerosis.
Objectives: To study the age distribution and clinical presentation of patients hospitalized for human parvovirus B19 infection.
Method: We reviewed the case records of all pediatric patients with serologic evidence of HPV infection who were admitted during a 20 month period to a major community hospital
Results: Of 128 children tested for HPV, 48 had evidence of acute infection based on the presence of immunoglobulin M antibodies; 8 patients who also had positive IgM for other viruses were excluded, thus 40 case records were studied. The mean age of the patients was 5.21 years, but 22 patients were under 4: The clinical presentations included 25 patients with fever, either recurrent or prolonged, accompanied in some by enlarged spleen, liver and lymph nodes, skin rash and arthropathy; the remaining patients were investigated for anemia, skin rash, joint complaints and hepatitis. In addition; HPV infection was documented in several well-defihed clinical conditions, such as SLE, vasculitic skin lesions, acute lymphoblastic leukemia, pure red cell aplasia, and optic neuritis.
Conclusions: In a group of 40 pediatric patients exhibiting anti-HPV IgM antibodies, a younger age and less common clinical presentations were observed, furthermore 5 patients had clinical syndromes in which the causative role of HPV infection was not clear.
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.
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.