Israel Medical Association Journal

Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.

Objectives: To examine whether their prevalence differs in two latitudinally different populations.

Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.

Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV[1] were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).

Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

Background: The frequency of performing percutaneous endoscopic gastrostomy in demented older people has increased in recent years. Several reports indicate flaws in the criteria for performing PEG[1] and in the decision-making process, raising concerns about the adequacy of the consent.

Objectives: To examine knowledge and attitudes of referring doctors and gastroenterologists, and to evaluate attitudes and feelings of family members concerning PEG insertion.

Methods: We conducted a survey of 72 doctors who referred 126 demented patients for PEG, as well as 126 family members and 34 gastroenterologists. Closed-ended questionnaires were designed for each study group, completed by the participants, and computer analyzed.

Results: Approximately 50% of family members expressed dissatisfaction with the decision-making process. Referring physicians reported that PEG insertion was often dictated by the need to transfer patients to a nursing home, with 50% admitting institutional pressure. Most of the referring physicians believed that PEG improved quality of life and longevity, whereas gastroenterologists did not expect an improved quality of life and thought that administrative demands should not intervene in the decision to insert PEG.

Conclusions: The decision-making process in the patient's families regarding PEG insertion for their demented relative is unsatisfactory, often takes place under pressure, and does not provide sufficient information about the procedure or its complications. Interpersonal communication between the patient's family and the medical team need to be improved and institutional demands should not play a major role in the medical decision to insert PEG. Gastroenterologists should take a more active role in the deliberations regarding PEG.

Background: Surgical repair of tetralogy of Fallot may leave the patient with pulmonary regurgitation causing eventual right ventricle dilatation and dysfunction. Predicting clinical deterioration may help to determine the best timing for intervention.

Objectives: To assess whether the clinical and humoral status of patients in the second decade after repair of ToF[1] is worse than that of patients in the first decade after repair.

Methods: Twenty-one patients with repaired ToF underwent clinical assessment, electrocardiogram, echocardiogram and measurement of plasma B-type natriuretic peptide and N-terminal pro-BNP[2] as well as the 6 minute walk distance test. Patients were divided into two groups: group A – less than 10 years after repair (n=10, age < 12 years old), and group B – more than 10 years after repair (n=11, age > 12 years old). The age at repair was similar in both groups.

Results: In all but one patient the distance in the 6 min walk test was less than the minimum for age. RV[3] end-diastolic volume and the 6 min walk test correlated with age. NT-proBNP[4] levels were significantly higher in the ToF group compared to 26 healthy controls (P < 0.0001) and were inversely correlated with RV ejection fraction. Comparison of the two groups showed no difference in RV end-diastolic volume indexed for body surface area, pulmonary regurgitation severity, right or left ventricular myocardial performance index, RV ejection fraction, QRS duration, or 6 min walk indexed to minimum for age.

Conclusions: In this group of patients with similar age at operation and pulmonary regurgitation severity, most clinical, echocardiographic and humoral parameters were not worse in the second decade after repair of ToF. These data suggest that very early pulmonary valve replacement may not be of benefit.

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: Babies born with extreme prematurity and low birth weight (< 1000 g) present a unique treatment challenge. In addition to the complexity of achieving survival, they may require surgical interventions for abdominal emergencies. Usually, these infants are transferred to a referral center for surgery treatment. Since 2000 our approach is bedside abdominal surgery at the referring center.

Objectives: To evaluate whether the approach of bedside abdominal surgery at the referring center is safe and perhaps even beneficial for the baby.

Methods: We retrospectively reviewed our data since 2000 and included only babies weighing < 1000 g who were ventilated, suffered from hemodynamic instability and underwent surgery for perforated bowel at the referring neonatal unit. Results were analyzed according to survival from the acute event (> 1 week), survival from the abdominal disease (> 30 days) and survival to discharge.

Results: Twelve babies met the inclusion criteria. Median weight at operation was 850 g (range 620–1000 g) and median age at birth was 25 weeks (range 23–27). Eleven infants survived the acute event (91.7%), 9 survived more than 30 days (81.8%), and 5 survived to discharge.

Conclusions: Our results show that bedside laparotomy at the referring hospital is safe and feasible. A larger randomized study is indicated to prove the validity of this approach.

Background: The Pittsburgh Sleep Quality Index is a standardized self-administered questionnaire for the assessment of subjective sleep quality. It has been translated into several languages and is widely used in clinical research studies.

Objectives: To assess the reliability and validity of the Pittsburgh Sleep Quality Index Hebrew translation in a sleep clinic sample and in comparison with the Technion Mini Sleep Questionnaire.

Methods: The PSQI[1] was translated into Hebrew based on standard guidelines. The final Hebrew version (PSQI-H) was administered to 450 patients from two sleep clinics and to 61 healthy adults from the community as a non-clinical control sample. The MSQ[2] was administered to 130 patients in one sleep clinic.

Results: For the PSQI-H[3], Cronbach's-alpha scores for sleep clinic and non-clinical samples were 0.70 and 0.52 respectively and 0.72 combined. Clinical sample scores were significantly higher than the non-clinical group, indicating lower sleep quality for the former. Significant correlations were found between the MSQ subscores and PSQI-H component scores for common underlying constructs.

Conclusions: The PSQI-H differentiated between clinical and non-clinical samples and showed adequate reliability and good validity. It may be used as a standardized tool for the assessment of subjective sleep quality in clinical research studies conducted in the Hebrew-speaking population.

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment. 

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.