Israel Medical Association Journal

Emerging and re-emerging infections cause huge concern among public health workers and international and national bodies such as the World Health Organization (WHO) and the U.S. National Institutes of Health (NIH). Indeed, scientists around the world express the view that despite the danger, research on these emerging virulent pathogens is crucial and must continue. While most of the studies underway are targeted at improving and protecting public health, some studies bear potentially serious risks resulting from misuse. These studies are defined as dual-use research (DUR) of concern, where it is not evident that the benefits outweigh the risks. The H5N1 controversy has pushed various governments to institute new policies to govern such research. We describe the regulations that govern this emerging field of research in the United States and Israel, two countries that have taken leading stands on these issues. We suggest that the existing policies are able to mitigate many of the risks that this research encapsulates, yet more work is required – especially on the global level.

Background: Gaucher disease is the most prevalent inherited disorder among Ashkenazi Jews (carrier frequency of about 6%) and six mutations account for about 96% of their mutant alleles. Two mutations, N370S and R496H, have been reported only in mildly affected or asymptomatic patients, Due to the rarity of R496H, it was recommended that it be excluded from screening programs. 

Objectives: To verify the frequency and trace the origin of Gaucher mutations in screened individuals whose Ashkenazi ethnicity was confirmed by the birthplace of their grandparents.

Methods: We conducted a retrospective analysis of the screened results for the period 2006–2011. Mutations were identified by restriction analysis, Tag-It^TM detection system, Pronto® diagnostic kit and Nanogen technology (NanoChip® 400).

Results: The heterozygote frequency of eight mutations was estimated in a cohort of 16,910 alleles. Two mutations, N370S and R496H, were the most frequent in our population. However, while the occurrence of N370S carriers was similar to other reports (1:19.4), that of R496H carriers was considerably elevated (1:207). Examination of the screened individuals' ethnicity showed a significant difference in the distribution pattern of the country of origin between the carriers of these two mutations.

Conclusions: The origin pattern differences between the two groups of heterozygotes might reflect a separate geographic region of introduction for various mutations. As a result, secondary subgroups could be formed within the Ashkenazi population. This might clarify the dissimilarities in the occurrence of R496H mutation reported by various centers. 

Background: The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services.

Objectives: To report data on the epidemiology of poisonings and poison exposures in Israel.

Methods: We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012.

Results: A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children < 6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink).

Conclusions: Poison exposures and poisonings have increased significantly and have contributed substantial to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.

Background: Medical evaluation of a suspected meniscus injury begins with a history-taking and physical examination. Suspected meniscus injuries not responding to treatment are usually sent for imaging to confirm the diagnosis before arthroscopy. Tc-MDP bone single photon emission computed tomography (SPECT) scan has been suggested as an alternative to magnetic resonance imaging (MRI) in evaluating suspected knee meniscus tears.

Objectives: To examine the accuracy of knee SPECT as a tool to identify meniscus tears versus that of MRI as compared to the gold standard of arthroscopy.

Methods: The Israel Defense Forces database for 2005 through 2009 was searched according to the key words knee MRI, knee SPECT and knee arthroscopy. We identified 330 subjects who had undergone both a single knee SPECT and a single knee MRI prior to knee surgery. The medical files of 193 of the 330 subjects were randomly selected for review. A comparison was made between the preoperative SPECT and MRI studies and the arthroscopic finding. The sensitivity, specificity and accuracy were calculated.

Results: The subjects’ age was 21.3 ± 3.9. The agreement between SPECT and arthroscopy was 0.14 for the medial meniscus and 0.29 for the lateral meniscus. The agreement between MRI and arthroscopy was 0.59 for the medial meniscus and 0.69 for the lateral meniscus. SPECT scan was found to be 61% sensitive, 54% specific and 58% accurate in detecting common knee pathology, whereas MRI was found to be 95% sensitive, 67% specific and 85% accurate.

Conclusions: Knee SPECT has a lower sensitivity, specificity and accuracy than MRI in evaluating meniscal injuries and its use can result in increased unnecessary surgery.

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.