Israel Medical Association Journal

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of traumatic findings, identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001).  The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001), and in the detection of musculoskeletal injuries (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination.

Background: Studies have found ethno-cultural disparities in health care delivery in different countries. Minority populations may receive lower standards of care.

Objectives: To test a hypothesis that Jewish Ethiopian women may be receiving less preventive recommendations than other women in Israel.

Methods: A telephone survey was conducted using a structured questionnaire designed specifically for this study in Hebrew, Russian and Amharic (Semitic language of Ethiopia). The study group included 51 post-menopausal women of Ethiopian origin, aged 50–75. The control group included 226 non-Ethiopians matched by age, some of whom were immigrants from the former Soviet Union. The questionnaire dealt with osteoporosis and breast cancer screening and prevention.

Results: All the parameters measured showed that the general population received more preventive treatment than did Jewish Ethiopian women, including manual breast examination, mammography, osteoporosis prevention, bone density scans, and recommendations for a calcium-rich diet, calcium supplementation, hormone replacement therapy, biphosphonates and raloxifen. On a logistic regression model the level of knowledge of the Hebrew language, age, ethnicity and not visiting the gynecologist were significantly related to not having received any preventive medicine recommendations.
Conclusions: Differences in cultural backgrounds and language between physicians and their patients may become barriers in the performance of screening and preventive medicine. Recognizing this potential for inequity and using methods to overcome these barriers may prevent it in the future

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm³) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

Background: Infective endocarditis is a common disease with significant morbidity and mortality.

Objectives: To define clinical and echocardiographic parameters predicting morbidity and in-hospital mortality in patients with infective endocarditis hospitalized in a tertiary hospital from 1991 to 2000.

Methods: All patients with definite IE diagnosed according to the Duke criteria were included. We examined relevant clinical features that might influence outcome.

Results: The study group comprised 100 consecutive patients, 77 with native valve and 23 with prosthetic valve endocarditis. The overall in-hospital mortality rate was 8%. There was a higher mortality in the PVE[1] group compared to the NVE[2] group (13% vs. 7%, P = 0.07). The mortality rate in each group, with or without surgery, was not significantly different. Clinical predictors of mortality were older age and hospital-acquired endocarditis. The presence of vegetations and their size were significant predictors of major embolic events and mortality. Staphylococcus aureus was a predictor of mortality (25% vs. 5%, P < 0.005) and abscess formation. Multivariate logistic analysis identified vegetation size and S. aureus as independent predictors of mortality.

Conclusions: Mortality is higher in older hospitalized patients. S. aureus is associated with a poor outcome. Vegetation size is an independent predictor of embolic events and of a higher mortality.

Renal vein occlusion in adults is usually a result of vein thrombosis, which is frequently associated with the nephrotic syndrome. The anatomy of renal vascularization is of primary importance for understanding its pathophysiological responses and the clinical and diagnostic presentation of patients with this condition. The reaction of the kidney to its vein occlusion is determined by the balance between the acuteness of the disease, extent of the development of collateral circulation, involvement of one or both kidneys and the origin of the underlying disease. Renal vein occlusion is generally a complication of some other condition, but may also occur as a primary event. The main goals of therapy should be to conserve renal parenchyma in order to maintain renal function and prevent thromboembolic phenomena.