Israel Medical Association Journal

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: 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.

A fundamental challenge for multiple sclerosis (MS) therapy is to promote repair and remyelination beyond their limited spontaneous extent. Glatiramer acetate (GA, Copaxone®), an approved treatment for MS, has been shown to induce immunomodulation as well as neuroprotection in the inflamed central nervous system (CNS) in MS and in its model, experimental autoimmune encephalomyelitis (EAE). Using electron microscopy, immunohistochemistry, and advanced magnetic resonance imaging, we have demonstrated diminished myelin damage in GA-treated mice, in both relapsing-remitting and chronic EAE, even when treatment was applied late after the disease exacerbation, suggesting repair. Furthermore, quantitative analysis indicated significant elevation in remyelinated axons in GA-treated compared to untreated EAE mice. To further prove that GA can promote myelination, we studied its effect in the developing naïve CNS, when injected postnatally. Immunohistochemical and ultrastructural analyses revealed significant increase in the number of myelinated axons, the thickness of the myelin encircling them, and the resulting g-ratios in the spinal cords of GA-injected mice compared to their phosphate-buffered saline-injected littermates. A prominent elevation in the amount of progenitor oligodendrocytes and their proliferation, as well as in mature oligodendrocytes, implied that the effect of GA is linked to the differentiation along the oligodendroglial cascade. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates. These cumulative findings indicate that GA treatment affects myelination under inflammatory as well as non-inflammatory conditions, supporting the notion that the repair process in the CNS can be up-regulated by therapy.

Background: Previous studies led to the recommendation to schedule planned elective cesarean deliveries at or after 39 weeks of gestation, and not before 38 weeks. The question is whether this practice is appropriate in face of possible risks to the newborn should the pregnancy have to be ended by cesarean section before the scheduled date.

Objectives: To compare the outcomes of newborn infants who were delivered on their scheduled day by elective cesarean section versus those who required delivery earlier.

Methods: This single-center retrospective study was based on medical records covering a period of 18 months. We compared the neonatal outcomes of 272 infants delivered by elective cesarean section as scheduled (at 38.8 ± 0.8 weeks gestation) and 44 infants who had to be delivered earlier than planned (at 37.9 ± 1.1 weeks). 

Results: We found no morbidity directly related to delivery by cesarean section before the scheduled date. There were no significant differences in the need for resuscitation after delivery. Although more of the infants who were delivered early were admitted to intensive care and overall stayed longer in the hospital (5.8 ± 7.3 vs. 3.9 ± 0.8 days, P < 0.02), their more severe respiratory illness and subsequent longer hospitalization was the result of their younger gestational age. Transient tachypnea of the newborn was associated with younger gestational age at delivery in both groups.

Conclusions: We suggest continuing with the current recommendation to postpone elective cesarean singleton deliveries beyond 38–39 weeks of gestation whenever possible.

Background: The prevalence of thyroid dysfunction in early pregnancy in Israel is not known.

Objectives: To assess the rate of abnormal thyroid-stimulating hormone (TSH) tests in low risk pregnant women attending a community clinic in Israel.

Methods: We conducted a retrospective analysis of the charts of low risk pregnant women (n=303) who had undergone a TSH screening during the first trimester of pregnancy at Clalit Health Services Women's Health Centers in Ashkelon and Tel Aviv. The TSH normal range during first trimester was considered to be 0.1–2.5 mIU/L.

Results: The TSH levels ranged from 0.04 to 13.3 mIU/L (median 1.73 mIU/L, mean 1.88 mIU/L). The rate of abnormal TSH was 25.6%, with low TSH 2.3% and high TSH 23.4%. The prevalence of abnormal TSH was not influenced by gravidity (primigravidas versus multigravidas) or place of residence (Ashkelon or Tel Aviv).

Conclusions: In view of the high prevalence of abnormal TSH (25.6%) in pregnant women in Israel during the first trimester, a universal country-wide screening should be considered.

Background: Low back pain (LBP) is chronic disease without a curative therapy. Alternative and complementary therapies are widely used in the management of this condition.  

Objectives: To evaluate the efficacy of home application of Dead Sea mud compresses to the back of patients with chronic low back pain (LBP).

Methods: Forty-six consecutive Patients suffering from chronic LBP were recruited. All patients were followed at the Soroka University Rheumatic Diseases Unit.  The patients were randomized into two groups: group 1 was treated with mineral-rich mud compresses, and group 2 with mineral-depleted compresses. Mud compresses were applied five times a week for 3 consecutive weeks. The primary outcome was the patient’s assessment of the overall back pain severity. The score of the Ronald & Morris questionnaire served as a secondary outcome.

Results: Forty-four patients completed the therapy and the follow-up assessments: 32 were treated with real mudpacks and 12 used the mineral-depleted packs. A significant decrease in intensity of pain, as described by the patients, was observed only in the treatment group. In this group, clinical improvement was clearly seen at completion of therapy and was sustained a month later. Significant improvement in the scores of the Roland & Morris questionnaire was observed in both groups.

Conclusions: The data suggest that pain severity was reduced in patients treated with mineral-rich mud compresses compared with those treated with mineral-depleted compresses. Whether this modest effect is the result of a “true” mud effect or other causes cannot be determined in this study.