Israel Medical Association Journal

The lethal poisoning of Alexander Litvinenco with the radioactive element polonium-210, and the risk that many civilians (including Israeli citizens) who were in the same location in London at the same time were exposed to radiation, was an unprecedented event in the western world. This was only the second known death due to ²¹⁰Po[1], a natural alpha radiation-emitting element. A task team was created to handle the event. The team comprised representatives from the Ministry of Health's advisory committee for radiological events (which includes the Israel Defense Force, the Israeli Atomic Energy Commission and the Ministry of Environmental Protection), the Public Health Services Central District, and a public relations expert. Forty-seven people were located and underwent an epidemiological inquiry, and urine samples for detection of ²¹⁰Po were sent abroad to a specialized laboratory. The radiotoxicological results were analyzed and evaluated by the expert team and follow-up recommendations were made. This unfamiliar and potentially stressful scenario was handled successfully by a multi-organizational multidisciplinary task team. The joint work of the task team was a real-life "exercise" simulating a radiological event in Israel. This team has recommended further evaluation of various vital missions in the event of any possible future radiological event, with special emphasis on a proactive communication approach to the media and the public.

Background: Regular physical activity is known to have a beneficial impact on multiple cardiovascular risk factors, but there is no routine provision of exercise training programs to patients after ischemic stroke.

Objectives: To assess the tolerability, safety and effect of an outpatient supervised exercise training program in patients after a non-disabling ischemic stroke.

Methods: Patients discharged home following a minor ischemic stroke (modified Rankin scale; mRS ≤ 2) were referred to a 3 month outpatient supervised exercise training program, performed twice weekly as prescribed by a physiologist and supervised by physical therapy. Exercise capacity was evaluated by the 6 minute walk test, and by the modified Bruce exercise test.

Results: Of the 52 patients who met the selection criteria, 43 underwent supervised exercise training within 2 months of stroke onset and 9 did not (control group). The baseline characteristics were comparable between the two groups. Following the exercise training program, an improvement in exercise capacity was observed manifested by improvement in the 6 minute walk test (444 ± 90 to 557 ± 99 meters in the exercise group vs. 438 ± 101 to 418 ± 126 in the control group; P = 0.002 for the score changes) and in the exercise duration achieved in the modified Bruce test and the metabolic equivalents achieved [9.6 ± 3.7 to 12.4 ± 3.2 minutes and 6.2 ± 2.8 to 8.5 ± 3.4 respectively in the exercise group (n=41) vs. 9.2 ± 3.5 to 8.0 ± 3.4 min and 5.8 ± 1.8 to 5.8 ± 2.8 in the control group (n=7); P = 0.0009 and 0.01 for score changes, respectively].

Conclusions: An outpatient supervised exercise training program after a minor ischemic stroke is feasible, well tolerated and is associated with improvement in exercise capacity. We strongly recommend that an aerobic exercise program be offered to suitable patients after an ischemic stroke.
 

Background: Non-operative management following abdominal stab wounds is possible in selected patients who are both hemodynamically stable and do not have signs of peritonitis. However, the rate of failure of non-operative management is higher in Israel than in western countries.

Objectives: To assess the patterns of injury following abdominal stabbing.

Methods: Data from the Israeli Trauma Registry were used to identify all patients with abdominal stab injury admitted to eight different trauma centers between 1997 and 2004.

Results: The number of patients admitted per year more than doubled between 1997 and 2004, from 257 to 599. The percentage of patients with severe injury (Index Severity Score ≥ 16) increased from 9.4% to 19.0%. The incidence of multiple stab injuries almost doubled, from 37% to 62%.

Conclusions: Review of the data in the Israeli Trauma Registry indicates an increase in both absolute rate and relative incidence of serious stab injuries. This indicates that patterns of injury following stab wounds are not necessarily similar, not even within the same geographical area over time.
 

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: 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: Burns are a major public health problem, with long hospitalization stay in both intensive care units and general wards. In Israel about 5% of all hospitalized injuries are burn injuries. There are no long-term epidemiological studies on burn injuries in adults in Israel.

Objectives: To identify risk factors for burn injuries and provide a starting point for the establishment of an effective prevention plan.

Methods: We analyzed the demographic, etiologic and clinical data of 5000 burn patients admitted to the five major hospitals with burn units in Israel during a 7 year period (1997–2003). Data were obtained from the records of the Israeli National Trauma Registry. The differences between various groups were evaluated using the chi-square test.

Results: Male gender was twice as frequent as female gender in burn patients (68.0% vs. 31.9%), and Jewish ethnicity was more common than non-Jewish (62.3% vs. 36.8%). Second and third-degree burns with body surface areas less than 10% constituted the largest group (around 50%). The largest age group was 0–1 years, constituting 22.2% of the cases. Inhalation injury was uncommon (1.9%). The most common etiologies were hot liquids (45.8%) and open fire (27.5%). Children less than 10 years old were burnt mainly by hot liquids while the main cause of burns for adults > 20 years old was an open flame. The majority of burns occurred at home (58%); around 15% were work related. The mean duration of hospitalization was 13.7 days (SD 17.7); 15.5% were in an intensive care unit with a mean duration of 12.1 days (SD 17.1). Surgical procedures became more common during the period of the study (from 13.4% in 1998 to 26.59% in 2002, average 19.8%). The mortality rate was 4.4%. We found a strong correlation between burn degree and total body surface area and mortality (0.25% mortality for 2nd to 3rd-degree burns with less than 10% TBSA[1], 5.4% for 2nd to 3rd-degree burns with 20–39% TBSA, and 96.6% for burns > 90% TBSA). The worst prognosis was for those over the age of 70 (mortality rate 35.3%) and the best prognosis was for the 0–1 year group (survival rate 99.6%).

Conclusions: The groups at highest risk were children 0–1 years old, males and non-Jews (the incidence rate among non-Jews was 1.5 times higher than their share in the general population). Those with the highest mortality rate were victims of burns > 90% TBSA and patients older than 70. Most burns occurred at home.

Background: Interleukin-8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK[1] was induced by IL-8[2] only when the receptor transmitting the chemokine signals was CXCR2, and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties.

Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoietic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process.

Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation.

Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation.
Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes

Background: The use of computed tomography in Israel has been growing rapidly during recent decades. The major drawback of this important technology is the exposure to ionizing radiation, especially among children, who have increased organ radiosensitivity and a long lifetime to potentially develop radiation-related cancer.

Objective: To estimate the number of excess lifetime cancer deaths related to annual CT scans performed in children in Israel.

Methods: We used CT scan utilization data from 1999 to 2003 obtained from the second largest health management organization in the country to project age and gender-specific CT scan use nationwide. Based on published organ doses for common CT examinations and radiation-related cancer mortality risk estimates from studies in survivors of the atomic bomb, we estimated the excess lifetime risks for cancer mortality attributed to use of CT in children and adolescents (up to 18 years old) in Israel.

Results: We estimated that 17,686 pediatric scans were conducted annually in Israel during 1999–2003. We project that 9.5 lifetime deaths would be associated with 1 year of pediatric CT scanning. This number represents an excess of 0.29% over the total number of patients who are eventually estimated to die from cancer in their lifetime.

Conclusions: Pediatric CT scans in Israel may result in a small but not negligible increased lifetime risk for cancer mortality. Because of the uncertainty regarding radiation effects at low doses, our estimates of CT-related cancer mortality should be considered with caution. Nevertheless, physicians, CT technologists, and health authorities should work together to minimize the radiation dose for children to as low as reasonably achievable and encourage responsible use of this essential diagnostic tool.
 

Background: Posterior glottic stenosis is a complication of prolonged intubation, manifesting as airway stenosis that may mimic bilateral vocal cord paralysis. It presents a variety of features that mandate specific surgical interventions.

Objectives: To summarize our experience with PSG[1] and its working diagnosis.

Methods: We conducted a retrospective review of a cohort of adult patients with PGS operated at the Sheba Medical Center between 1994 and 2006.

Results: Ten patients were diagnosed with PGS, 6 of whom also had stenosis at other sites of the larynx and trachea. Since 2000, all patients underwent laryngeal electromyographic studies and direct laryngoscopy prior to surgery. Surgical interventions included endoscopic laser procedures (in 2 patients), laryngofissure and scar incision (in 1), laryngofissure with buccal mucosa grafting (in 3) or with costal cartilage grafting (in 1), laryngofissure with posterior cricoid split and stenting (in 1); one patient was not suitable for surgery. Postoperative follow-up included periodical fiberoptic endoscopies. Voice analysis was evaluated by the GRBAS grading. Seven patients were successfully decannulated within one to three procedures. Voice quality was defined as good in 7 patients, serviceable in 2 and aphonic in 1.

Conclusions: Posterior glottic stenosis may be isolated or part of complex laryngotracheal pathologies. Electromyographic studies and direct laryngoscopy must be included in the diagnostic workup. Costal cartilage or buccal mucosa grafts are reliable, safe and successful with respect to graft incorporation and subglottic remodeling.