Israel Medical Association Journal

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: The prevalence of obesity among children and adolescents in the western world has increased dramatically.

Objective: To assess the efficiency of routine childhood obesity screening by primary physicians in the pediatric population in Israel and the utilization of health services by overweight children.

Methods: The electronic medical records of children aged 60–83 months registered in 39 pediatric primary care centers between January 2001 and October 2004 (n=21,799) were reviewed. Those in whom height and weight were documented during a clinic visit (index visit) were classified as overweight, at risk of overweight, and normal weight by body mass index percentiles. The number of visits to the pediatrician, laboratory tests and health care costs 12 months after the index visit were calculated.

Results: Anthropomorphic measurements were performed in 1556 of the 15,364 children (10.1%) who visited the clinic during the study period. Of these, 398 (25.6%) were overweight, 185 (11.9%) were at risk of overweight, and 973 (62.5%) were normal weight. Children in the first two groups visited the clinic slightly more often than the third group, but the differences was not statistically significant (P = 0.12), and had significantly more laboratory tests than the rest of the children visiting the clinics (P = 0.053). Health care costs were 6.6% higher for the overweight than the normal-weight children.

Conclusions: Electronic medical records are a useful tool for population-based health care assessments. Current screening for obesity in children during routine care in Israel is insufficient and additional education of community pediatricians in diagnosis and intervention is urgently needed.

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.

Background: Numerous studies have shown an association between asthma and mental disorders. While elevated rates of asthma have been noted among psychiatric patients with anxiety disorders and post-traumatic stress disorder, several studies have found elevated rates of mental disorders among asthma patients. Such studies, however, have generally relied upon questionnaires and assessment by non-specialist physicians to diagnose mental disorders and asthma.

Objectives: To examine a possible association between asthma and psychiatric diagnoses in Israeli military recruits and soldiers.

Methods: In this cross-sectional study we compared the prevalence of mental diagnoses in asthmatic recruits and soldiers to that in non-asthmatic recruits and soldiers. A total of 195,903 recruits and soldiers were examined by Israel Defense Forces recruiting offices and fitness boards. Diagnoses of asthma were based on a pulmonologist's diagnosis, including spirometry at rest and exercise testing as indicated; diagnoses of mental disorders were based on examination by a psychiatrist.

Results: The prevalence of asthma was found to be 7.8% (current) and 9.8% (lifetime). The prevalence of mental disorders was 13.4%. Current asthma was associated with an increased likelihood of any mental disorder (OR = 1.20, 95% CI = 1.15–1.26), and specifically with mood and anxiety disorders (1.31, 1.19–1.46), introvert personality disorders (1.20, 95% 1.12–1.28) and adjustment disorder (1.43, 1.26–1.62). Lifetime asthma was associated with an increased likelihood of the same disorders, but the association was not as powerful.

Conclusions: The results validate the previously documented association between asthma and mental disorders, using a sample of unprecedented size and improved methodology. A multidisciplinary approach to asthma that incorporates mental health professionals in the treatment of poorly controlled asthma and perhaps of asthma in general is recommended.
 

Background: Echocardiographic assessment of left ventricular function includes calculation of ejection fraction and regional wall motion analysis. Recently, speckle imaging was introduced for quantification of left ventricular function.

Objectives: To assess LVEF[1] by speckle imaging and compare it with Simpson’s method, and to assess the regional LV strain obtained by speckle imaging in relation to conventional echocardiographic scores.

Methods: Thirty consecutive patients, 28 with regional LV dysfunction, underwent standard echocardiographic evaluation. LV end-diastolic volume, LV end-systolic volume and EF were calculated independently by speckle imaging and Simpson’s rule. The regional peak systolic strain presented by speckle imaging as a bull's-eye map was compared with the conventional visual estimate of echo score.

Results: Average EDV[2] obtained by speckle imaging and by Simpson’s method were 85.1 vs. 92.7 ml (P = 0.38), average ESV[3] was 49.4 vs. 48.8 ml (P = 0.94), calculated EF was 43.9 vs. 50.5% (P = 0.08). The correlation rate with Simpson’s rule was high: 0.92 for EDV, 0.96 for ESV, and 0.89 for EF. The peak systolic strain in two patients without wall motion abnormality was 17.3 ± 4.7; in normal segments of patients with regional dysfunction, peak systolic strain (13.4 ± 4.9) was significantly higher than in hypokinetic segments  (10.5 ± 4.5) (P < 0.000001). The strain in hypokinetic segments was significantly higher than in akinetic segments (6.2 ± 3.6) (P < 0.000001).

Conclusions: Speckle imaging can be successfully used for the assessment of LV volumes and EF. Bull's-eye strain map, created by speckle imaging, can achieve an accurate real-time segmental wall motion analysis.

Background: Femoral artery vascular complications are the most common adverse events following cardiac catheterization. Smaller diameter introducer sheaths and catheters are likely to lower the puncture site complication rate but may hinder visualization.

Objectives: To evaluate the safety and angiographic quality of 4 French catheters.

Methods: The study was designed to simulate real-life operator-based experience. Diagnostic angiography was performed with either 4F or 6F diagnostic catheters; the size of the catheter used in each patient was predetermined by the day of the month. Patients undergoing 4F and 6F diagnostic angiography were ambulated after 4 and 6 hours, respectively. The following technical parameters were recorded by the operator: ease of introducer sheath insertion, ease of coronary intubation, ease of injection, coronary opacification, collateral flow demonstration, and overall assessment. Adverse events were recorded in all patients and included minor bleeding, major bleeding (necessitating blood transfusion), minor hematoma, major hematoma, pseudo-aneurysm formation and arteriovenous fistula.

Results: The study group included 177 patients, of whom 91 were in the 4F arm and 86 in the 6F arm. Demographic and procedural data were similar in both groups. Seventy-seven percent of 6F and 50% of 4F procedures were evaluated as excellent (P < 0.05). This difference was attributed to easier intubation of the coronary ostium and contrast material injection, increased opacification of the coronary arteries, and demonstration of collateral flow with 6F catheters. Complications occurred in 22% of patients treated with 6F catheters and 10% of those treated with 4F catheters (P = 0.11). Of the 50 patients who switched from 4F to 6F 12% had complications. In patients undergoing diagnostic angiography, the complication rate was 10% vs. 27% (most of them minor) in the 4F and 6F groups, respectively (P < 0.05).
Conclusions: Patients catheterized with 4F have fewer complications compared with 6F diagnostic catheters even when ambulated earlier. Although 4F had a reduced quality compared to 6F angiographies, they were evaluated as satisfactory or excellent in quality 85% of the time. 4F catheters have a potential for reduced hospitalization stay and are a good option for primary catheterization in patients not anticipated to undergo coronary intervention

Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

Background: Healthcare behavior occurs within the context of the family unit. Little research has investigated the influences among adult family members regarding their use of medical care services.

Objectives: To investigate the effects of maternal attendance patterns and maternal self-assessed health status on those of adult children.

Methods: This study was a retrospective cohort, analyzing both patient records for physician visits and mailed self-administered questionnaires regarding subjective health assessment. We evaluated a unique study group of multi-generational families with free and equal access to medical services at a primary care kibbutz clinic in Israel. This enabled an exclusive focus on the association between the use of healthcare by mothers and their grown children.

Results: Controlling for the subjects' age, gender and number of chronic diagnoses, a significant association exists between the family physician visit rates of a mother and those of her grown offspring (P = 0.03). Low self-health assessment is associated with higher levels of physician utilization (P = 0.003). Maternal self-health evaluation is associated with her adult children's own self-health evaluation (odds ratio 5.9, P = 0.04) and their rates of physician utilization (one additional offspring visit per year for low maternal self-health, P = 0.02).

Conclusions: A mother’s behavior patterns measured via self-rated health status and physician visit rates serve as a proxy for maternal attitudes regarding healthcare, and these attitudes are possibly imparted to her children for life. This study provides unique evidence for a maternal health behavior effect on grown children, and enables a more complete understanding of families attending the primary care clinic.
 

Background: Necrotizing enterocolitis is a common progressive gastrointestinal disease affecting more than 5% of very low birth weight infants and associated with a high mortality rate.

Objectives: To determine whether excessive weight gain in preterm infants is an early sign of NEC[1].

Methods: Seventeen preterm infants with perforated NEC were identified and matched with 17 control subjects for birth weight and gestational age. The postnatal age (days) at diagnosis of NEC was identified, and weight changes as well as clinical and laboratory data were recorded and compared for 7 days prior through 7 days post-diagnosis.

Results: A significant difference in weight gain was noticed between D-1 and D 0. The NEC and control groups gained 5.1% and 1.2%, respectively (P = 0.002). None of the sick infants lost weight on days -1 to D 0.

Conclusions: Excessive weight gain was observed in premature infants who subsequently developed NEC. Daily evaluation of weight changes should be considered part of a strategy for early identification of infants at risk for developing NEC. Future studies are needed to confirm this finding in a prospective manner and to investigate its pathogenesis.