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. 

Objectives: To devise a clinical classification of children diagnosed with ASD according to etiologic workup.

Methods: Children diagnosed with ASD (n=436) from two databases were divided into groups of symptomatic, cryptogenic or idiopathic, and variables within each database and diagnostic category were compared.

Results: By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. Conclusions: Differences in gender and clinical and diagnostic features were found when etiology was used to create subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s).

Objectives: To assess the influence of ultrasound performed by intensive care physicians.

Methods: This retrospective descriptive clinical study was performed in a medical-surgical intensive care unit of a university-affiliated general hospital. Data were collected from patients undergoing ultrasound examinations performed by a critical care physician from January 2010 to June 2011.

Results: A total of 299 ultrasound exams were performed in 113 mechanically ventilated patients (70 males, mean age 65 years). Exams included trans-cranial Doppler (n=24), neck evaluation before tracheostomy (n=15), chest exam (n=83), focused cardiac echocardiography (n=60), abdominal exam (n=41), and comprehensive screening at patient admission (n=30). Ultrasound was used to guide invasive procedures for vascular catheter insertion (n=42), pleural fluid drainage (n=24), and peritoneal fluid drainage (n=7). One pneumothorax was seen during central venous line insertion but no complications were observed after pleural or abdominal drainage. The ultrasound study provided good quality visualization in 86% (258 of 299 exams) and was a diagnostic tool that induced a change in treatment in 58% (132 of 226 exams).

Conclusions: Bedside ultrasound examinations performed by critical care physicians provide an important adjunct to diagnostic and therapeutic performance, improving quality of care and patient safety. 

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

Objectives: To evaluate health utilization patterns in two primary care clinics in southern Israel: one under continuous attacks of Qassam rockets as compared with a similar clinic not under a rocket threat.

Methods: We conducted a retrospective cross-sectional study in two primary care clinics in southern Israel, with 11,630 persons listed in the two clinics during the entire study period. The primary outcome measures were total annual number of visits per person to the clinic and for specific diagnoses, and the number of drug prescriptions issued, emergency room (ER) visits, hospitalization days, cardiac catheterizations and coronary bypass surgeries.

Results: In both clinics there was an increase over time in the mean annual number of visits per person. During the years of severe attacks there was an increase in visits with a chief complaint of depression and anxiety and an increase in the number of anxiolytic prescriptions in the study clinic compared with the control. During the same period there was a decrease in the number of ER visits in the study clinic compared with the control.

Conclusions: The population under continuous life-threatening events showed more depression and anxiety problems. Under severe bombardment, the residents prefer not to leave home, unless necessary.

Objectives: To investigate current smoking trends among Israeli physicians.

Methods: All practicing physicians at a tertiary university-affiliated medical center in central Israel were invited to complete a Web-based questionnaire on smoking habits and smoking-related issues via the institutional email. Findings were compared to those in the general population and between subgroups.

Results: Of the 90 responders (53 male, 88 Jewish), 54 (60%) had never smoked, 21 (23.3%) were past smokers, and 15 (16.7%) were current smokers. The rate of current smokers was lower than in the general population. The proportion of current smokers was higher among residents than attending physicians and among physicians in surgical compared to medical specialties. Past smokers accounted for 17.9% of the residents (average age at quitting 26.2 years) and 28.1% of the attending physicians (average age at quitting 33.0 years). Non-smokers more frequently supported harsh anti-smoking legislation.

Conclusions: The rate of smoking is lower in physicians than in the general population but has not changed over the last 15 years. Anti-smoking programs should particularly target physicians in surgical specialties. 

Objectives: To evaluate the course and management of visual and pregnancy outcomes of consecutive pregnancies with IIH.

Methods: The medical records of women with IIH in consecutive pregnancies were reviewed for neuro-ophthalmological findings, management, and visual and pregnancy outcomes.

Results: The study group comprised eight women with at least two consecutive pregnancies (mean age 27.3 ± 5.3 years). The mean duration of IIH prior to the first pregnancy was 3.4 ± 3.16 years. One woman with IIH pre-pregnancy symptoms and three women with clinical features of IIH during the second trimester of pregnancy (gestational week 21.7 ± 4.04) were treated with acetazolamide (250 mg every 8 hours). Symptoms resolved, resulting in uncomplicated first deliveries for all four. The first deliveries of four other women were by cesarean section due to obstetric indications. Only one woman developed symptoms and signs of IIH during her second pregnancy and was thus treated with acetazolamide. Two women who completed three pregnancies had no IIH symptoms during their pregnancies. The course and outcome of those pregnancies were normal.

Conclusions: IIH apparently does not worsen or even become symptomatic in consecutive pregnancies. The appropriate management of IIH in pregnant women is similar to management for non-pregnant women; neither the course nor the obstetric outcome of first and consecutive pregnancies is influenced by the presence of IIH.