Israel Medical Association Journal

Objectives: To define the incidence of congenital CMV infection in two different subpopulations, as a model for the entire population of Israel.

Methods: Urine specimens were randomly collected from 2,000 newborns in Shaare Zedek Medical Center, Jerusalem, and HaEmek Medical Center, Afula (1,000 specimens each). These hospitals have many characteristic differences, presumably representing the diverse population of Israel. Urine specimens were subjected to a CMV PCR[2] reaction and positive specimens were validated by urine viral culture. Maternal seroprevalence was determined in a representative sample of the mothers in each hospital. Epidemiologic characteristics of the mothers were extracted from hospital records and compared.

Results: The population in Shaare Zedek Medical Center was mostly Jewish (95.8%) and urban (87.0%), as compared to that of HaEmek Medical Center (49.2% and 61.0%, respectively, P < 0.01). Nevertheless, CMV seroprevalence was similar: 81.5% and 85%, respectively. Ten (1.0%) and 4 (0.4%) newborns, respectively, were found to have congenital CMV infection (not significant).

Conclusions: The combined incidence of congenital CMV infection in the study population was 0.7% (95% confidence interval 0.3–1.0%). If this rate is extrapolated to the entire population of Israel, then a total of 945 cases of congenital CMV can be expected among the 135,000 annual deliveries. A nationwide screening program for congenital CMV should be considered.

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[1] CMV = cytomegalovirus

[2] PCR = polymerase chain reaction

Israel has a National Screening Program for early detection of breast cancer. The need to continue and even expand this program was recently stressed in light of the high risk in the population. However, the optimal modalities for breast cancer screening are controversial, especially for women at risk. Mammography, the established screening method, is critically examined, and molecular imaging techniques, such as magnetic resonance spectroscopy and spectroscopic imaging are explored, especially for primary breast cancer detection. MRS[1] and MRSI[2] are currently limited by their reliance on the conventional framework for data analysis in biomedical imaging, i.e., the fast Fourier transform. Recent mathematical advances in signal processing via the fast Pade transform can extract diagnostically important information, which until now has been unavailable with in vivo MRS. A clinical MRS signal illustrates the rapid and stable convergence provided by FPT[3], yielding accurate information about key metabolites and their concentrations at short acquisition times. We suggest that the next step would be to apply the FPT to in vivo MRS/MRSI signals from patients with breast cancer and to compare these to findings for normal breast tissue. The potential implications of such an optimized MRS/MRSI for breast cancer screening strategies are discussed, especially for younger women at high risk.

Background: Prenatal care in Israel is established as a universal service, but the degree of compliance with care recommendations may vary with the healthcare provider or the characteristics of the population.

Objectives: To study referral to and compliance with the performance of ultrasound, alpha-fetoprotein and amniocentesis and the factors associated with them in a national sample. 

Methods: The sampling frame consisted of women who gave birth during March 2000. The sample included 1,100 Israeli Jewish and Arab women who resided in localities with over 50,000 and 20,000 inhabitants respectively. They were interviewed by phone 3 months after delivery. 

Results: In both population groups 30% reported having seven or more ultrasounds during pregnancy. The performance of fetal body scans was relatively low. Factors associated with non-performance among Jewish women were: lower education, religiousness, and attending Mother and Child Health services as compared to all other services. Seventy-seven percent of Jewish women and 84% of Arab women reported that they had been referred for alpha-protein tests. For women aged 35 and over, 55% of Jewish women were referred and 63% complied, whereas 39% of Arab women were referred but none complied.

Conclusions: Ultrasound is almost universally performed among Jewish and Arab women; however fetal body scans, alpha-fetoprotein and amniocentesis (for women over the age of 35) are not. The reasons for the lower coverage may be due to under-referral and/or lack of compliance of the women, perhaps due to sociocultural barriers. In both population groups considerable out-of-pocket money is paid for the tests.

Background: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available.

Objective: To assess the impact of these changes on breast cancer surgical treatment in our hospital.

Methods: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision.

Results: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001.

Conclusions: The mammography screening program in Jerusalem in 1997–2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

Background: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80–100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation.

Objective: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study.

Methods: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism- polymerase chain reaction analysis.

Results: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation £ 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 µg/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation.

Conclusion:We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
 

Background: The number of child adoptions from abroad is increasing, but the adverse living conditions of these children prior to the adoption raise questions on their medical and neurodevelopmental status, particularly since there are no guidelines for pre- or post-adoption medical evaluation.

Objectives: To describe the condition of a cohort of young children who were candidates for adoption in East European orphanages and foster homes, and to determine those attributes associated with a family's decision to adopt or refuse a particular child.

Methods: Eighty-two young children, median age 11 months, were evaluated by Israeli pediatricians in Eastern Europe between 3 weeks and 6 months prior to their adoption. The evaluation consisted of comprehensive medical and neurodevelopmental testing on site using a battery of standardized assessment tools, and observation of free play and social interactive behaviors recorded on videotape. Laboratory tests included complete blood count, chemistries, serology screening, and metabolic and genetic testing.

Results: The children were growth-retarded. Medical problems were classified as resolved (pneumonia and diarrhea) in 32.8%; or ongoing, such as hepatitis B and (3, failure to thrive, organomegaly, and visual and hearing disorders, in 14.8%. Neuromotor status was grossly abnormal in 13.4%. Twenty-two percent of the children were rejected for adoption by families in Israel. Factors associated with the adoption decision were performance skills on developmental testing (P = 0.0001), present medical status (P = 0.002), and weight )P = 0.016(.

Conclusions: Pre-placement comprehensive screening of children eligible for foreign adoption, which includes developmental screening, helps to identify a wide variety of strengths and impairments in a child's background before the adoption procedure is finalized. A family's decision to adopt or not was associated with the child's performance on Bayley Scales, weight, and current medical status, but not with language delays, serious past medical history or suspect family background.
 

Background: Colorectal cancer is the second leading cause of cancer mortality in Israel. Unfortunately, compliance  with annual fecal occult blood testing is very low.

Objective: To assess the effectiveness of interventions to increase FOBT[1] screening in primary care clinics in Israel.

Methods: A prospective, randomized study included all 50–75 year old enrollees of six family physicians in two primary care clinics. The register of two physicians, one from each clinic, was allocated to one of three groups. Two FOBT reminder strategies were tested: a physician reminder (753 patients), and a patient reminder that was either a phone call (312 patients) or a letter (337 patients). The control group (913 patients) of physicians continued administering their regular level of care. The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period.

Results: In the intervention groups 14.3% (201/1,402) were screened using the FOBT over the course of the study year. Using an intent-to-screen analysis, the screening rate in the physician and patient reminder groups was significantly higher than in the control group(16.5 and 11.9%,vs. 1.2% respectively, P < 0.0001). Phone reminders were significantly more efective as compared to letters (14.7 vs. 9.2%, P = 0.01).

Conclusions: Our study has shown the benefit of various FOBT reminder systems, especially those centered around the family physician. Further research should focus on this area, in conjunction with other novel approaches.

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[1] FOBT = fecal occult blood testing

Background: The Bloom syndrome gene, BLM, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase. The Fanconi anemia complementation group C gene was mapped to chromosome 9q22.3, but its product function is not sufficiently clear. Both are recessive disorders associated with an elevated predisposition to cancer due to genomic instability. A single predominant mutation of each disorder was reported in Ashkenazi Jews: 2281delATCTGAinsTAGATTC for Bloom syndrome (BLM-ASH) and IVS4+4A®T for Fanconi anemia complementation group C.

Objectives: To provide additional verification of the mutation rate of BLM and FACC[1] in unselected Ashkenazi and non-Ashkenazi populations analyzed at the Sheba Medical Center, and to trace the origin of each mutation.

Methods: We used polymerase chain reaction to identify mutations of the relevant genomic fragments, restriction analysis and gel electrophoresis. We then applied the Pronto^TM kit to verify the results in 244 samples and there was an excellent match.

Results: A heterozygote frequency of 1:111 for BLM-ASH and 1:92 for FACC was detected in more than 4,000 participants, none of whom reported a family history of the disorders. The Pronto^TM kit confirmed all heterozygotes. Neither of the mutations was detected in 950 anonymous non-Ashkenazi Jews. The distribution pattern of parental origin differed significantly between the two carrier groups, as well as between each one and the general population.

Conclusions: These findings as well as the absence of the mutations in non-Ashkenazi Jews suggest that: a) the mutations originated in the Israelite population that was exiled from Palestine by the Roman Empire in 70 AD and settled in Europe (Ashkenazi), in contrast to those who remained; and b) the difference in origin distribution of the BS[2] and FACC mutations can be explained by either a secondary migration of a subgroup with a subsequent genetic drift, or a separate geographic region of introduction for each mutation.

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[1] FACC = Fanconi anemia complementation group C