Israel Medical Association Journal

Background: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases.

Objectives: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype.

Methods: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. 

Results: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05).

Conclusions: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.

 

Background: Gastrointestinal malignancies comprise a broad spectrum of neoplasms and have a high overall incidence. The incidence rates in Israel vary among ethnic groups due to different risk factors.

Objectives: To investigate incidence trends of these cancers in Israel in both Jewish and Arab ethnic groups in order to better understand the risks in those groups.

Methods: This study is based on data published by the Israel National Cancer Registry and the Central Bureau of Statistics. We compared statistics between ethnicities and genders. We examined the eight most common gastrointestinal cancers, focusing on colon, rectal and gastric cancers.

Results: Between 1980 and 2012 there was a decline in the incidence of gastric cancer in the Jewish population; in contrast, a significant increase occurred in Arab women, but there was no significant change in Arab men. Colon cancer showed a relative decrease in incidence in the Jewish population, but an increase in the Arab population. A decrease in the incidence of rectal cancer in the Jewish population and an increase in the Arab population was observed. 

Conclusions: Gastric, colon and rectal cancers exhibit differences in incidence and outcome between Jewish and Arab populations in Israel. These differences were not observed in the other five types of less common gastrointestinal cancers.

 

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

Background: Despite the increased worldwide recognition of attention deficit/hyperactivity disorder (ADHD), there is a variability in the diagnostic rate of both ADHD and its co-morbidities. These diversities are probably related to the methodology and instruments used for the diagnosis of ADHD and to awareness and cultural interpretation of its existence. 

Objectives: To identify consistent differences in the clinical profile of Arab and Jewish children with ADHD in Israel who differ in their cultural, ethnic and socioeconomic background. 

Methods: We analyzed the data of 823 children and adolescents with ADHD (516 Jews and 307 Arabs) and compared the clinical characteristics between these two ethnic groups. All patients were evaluated in two neuropediatric and child development centers in northern Israel: one in Haifa and one in Hadera. Children with autism and intellectual disabilities were excluded. 

Results: The distribution of ADHD subtypes was similar in both populations. However, learning disorders and psychiatric co-morbidities (behavioral difficulties and anxiety) were reported more frequently in the Jewish population. The most commonly reported adverse effects to psychostimulants were mood changes, anorexia, headache, insomnia and rebound effect, and were more frequently reported in the Jewish population (42.0% vs.18.0%, P < 0.05).

Conclusions: We assume that these differences are related to cultural and socioeconomic factors. We suggest that the physician take cultural background into consideration when treating patients with ADHD.

 

Objectives: To evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at presentation, diabetic complications rate, and associated autoimmune diseases in a pediatric T1DM patient population in the Negev area.

Methods: Clinical and demographic details of 168 T1DM patients were evaluated, including HbA1C levels, long-term complications, related autoimmune diseases, and insulin pump usage. The data were analyzed and the Jewish and Bedouin patient groups compared.

Results: Only 13.1% of the patients had reached the HbA1C levels recommended by the current guidelines at the first and second year follow-up visits, and 9.5% and 7.1% at the third and fourth year visits, respectively. A significant difference in HbA1c levels between Jewish and Bedouin patients was found (P = 0.045 at the first year follow-up, P ≤ 0.01 thereafter). Significant difference was found between the Jewish and the Bedouin groups regarding presentation with DKA, 33% and 56% of the patients respectively (P = 0.01).

Conclusions: Existent glycemic control in daily practice is far from the guideline goals. Bedouin ethnicity was associated with less favorable diabetes control, emphasizing the need for better awareness of T1DM and its treatment options in this population. More resources should be directed to address T1DM in the general population, especially among the Bedouin.

Background: Alcohol consumption in Israel has increased over the last 20 years. Patients with alcohol use disorder (AUD) who present at a hospital enable early intervention. Objectives: To examine, for the first time, the characteristics of AUD patients in an Israeli general hospital, including whether their alcohol use is documented in their file.

Methods: A group of 178 consecutive patients referred for psychiatric consultation was compared to a second group of 105 hospitalized patients who were not referred. These two groups were studied to compare risk factors for AUD. Patients in both groups were prospectively interviewed using a CAGE questionnaire, demonstrated as an effective screening instrument for AUD. Patients' files in both groups were examined for documentation of alcohol use.

Results: There was no significant difference between the prevalence of AUD in the two groups. The groups were then merged since no significant difference in the risk factor effects between the two groups was found. The risk factors for AUD in the final statistical analysis were lower educational status, living alone, being born in the Former Soviet Union and weaker religious observance. Post-traumatic stress disorder (PTSD), cigarette smoking and substance use were found to be independent risk factors. Soldier status was associated with significant alcohol misuse and AUD (CAGE1–4). Alcohol consumption was documented in the files of AUD patients in 48% of the first group and 21% of the second.

Conclusions: Physicians often neglect to take a history of alcohol consumption. Routine use of the CAGEquestionnaire is recommended in Israeli general hospitals. Special attention should be given to PTSD patients and to soldiers.
 

Background: Little is known of the risk factor disparities in first stroke among Jewish and Arab patients undergoing rehabilitation in Israel.

Objectives: To investigate the age, gender and risk factor disparities in first stroke among Jewish (immigrant and non-immigrant) and Arab patients undergoing rehabilitation and to compare the prevalence and odds ratio of stroke risk factors in these patients.

Methods: The database of the Department of Neurological Rehabilitation C at Loewenstein Rehabilitation Center was used to investigate first ischemic and hemorrhagic stroke patients admitted for hospital rehabilitation over a 15 year period, January 1993 to December 2008. Particular attention was paid to age, gender and risk factor disparities.

Results: The 2000 patients with first stroke who were included in the study were grouped as Jewish (immigrant and non-immigrant) and Arab (237 Arabs, 370 non-immigrant Jews and 1393 immigrant Jews). A high percentage of Arab patients were found to have hypertension and diabetes mellitus, while a high percentage of Jewish immigrants had stenosis of the internal carotid artery.

Conclusions: The study demonstrated some differences in the effect of risk factors between the groups. It may be important to address such differences when developing stroke preventative strategies in this population of Jewish and Arab stroke survivors in Israel.
 

The incidence of invasive uterine cervical cancer in Israeli Jewish women is persistently lower than in many other countries, although the frequency of premalignant lesions is similar to that in other populations. Most characteristics, except certain traditional habits, are similar to those in other populations. The incidence among women born in North Africa and their Israeli born descendants is significantly higher than in those born in other continents, possibly due to genetic factors. In view of the similarities to other populations the reason for the low incidence in Israel remains obscure, and whether it may be attributed to genetic reasons or to some traditional habits remains to be confirmed
 

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features – cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate) – that have been identified for their possible association with vitamin D status.

Objectives: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons.

Methods: We obtained serum samples from 195 healthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy).

Results: The mean vitamin D level for the entire cohort was surprisingly low (22.9 ± 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/ml). Vitamin D status was better in infants than in older age groups. Differences by gender were significant only in the infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 ± 12, 24.1 ± 10, and 17.6 ± 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer.

Conclusions: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

Background: The incidence of stroke varies among ethnically and culturally diverse groups.

Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke.

Methods: Patients with documented coronary heart disease were followed for 6–8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measures of blood lipids. Among 15,052 patients, a total of 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack.

Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000) but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin, resulting from factors that remain unrecognized,or with variables unassessed in this study.

Conclusions: We identified an ethnic diversity in stroke risk among Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.
 

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.
 

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background: Dupuytren’s disease is a fibroproliferative disorder of the palmar fascia that can cause disabling digital contractures. The pathogensis of the disease is still unclear, and it afflicts predominantly white males of northern European origin. Gender-related differences of Dupuytren's disease and the distinctive characteristics of the disease in females are not yet well defined.

Objectives: To evaluate and illustrate the distinctive characteristics of Dupuytren's disease in females.

Methods: A retrospective study was performed of all female patients with Dupuytren’s disease seen and followed at our Hand Surgery Unit over a 20 year period. The study group consisted of 48 women (56 hands). The collected data included clinical and epidemiological features on admission, and outcome of surgical intervention.

Results: Of the 48 women (56 hands) with Dupuytren's disease, 23 (26 hands) underwent limited fasciectomy. The average age at presentation was 60.1 years. A few of the patients originated from Asia and Africa. Manifestations and pattern of the disease were nearly comparable to those observed in the male group, except for a slightly higher incidence of proximal interphalangeal joint contracture in female patients. Generally, females expressed less severe contractures on presentation, and a slow progression thereafter. A favorable functional postoperative outcome was observed. Seven patients had minor complications including local hematoma and painful scars. Two patients developed moderate signs of complex regional pain syndrome.

Conclusions: Further investigations are needed to assess the potential role of androgens in the pathogenesis of Dupuytren's disease, and a possible protective role of estrogenic hormones, rendering Dupuytren’s contracture a postmenopausal affliction.
 

Background: Parental fear and misconceptions about fever are widespread in western society. Ethnicity and sociodemographic factors have been suggested as contributing factors.

Objectives: To test the hypothesis that undue parental concern about fever is less in traditional than in western cultural-ethnic groups.

Methods: Bedouin (traditional society) and Jewish (western society) parents of children aged 0–5 years with fever were interviewed in a pediatric emergency unit. Interviews were conducted in the parents' most fluent language (Hebrew or Arabic). A quantitative variable (a 9 item “fever phobia” scale) was constructed.

Results: The parents of 101 Jewish and 100 Bedouin children were interviewed. More Bedouin parents were unemployed, had less formal education and had more and younger children than the Jewish parents. Parents of both groups expressed erroneous beliefs and practices about fever; quantitative but not qualitative differences in fever phobia variables were documented. Compared with their Jewish counterparts, more Bedouin parents believed that fever may cause brain damage and death, administered antipyretic medications for temperature ≤ 38ºC and at excessive doses, and consulted a physician within 24 hours even when the child had no signs of illness other than fever (all P values < 0.001). The mean fever phobia score was higher in the Bedouin than in the Jewish group (P < 0.001). By multivariate analysis, only the cultural-ethnic origin correlated with fever phobia.

Conclusions: A higher degree of fever phobia was found among parents belonging to the traditional Bedouin group as compared to western society parents.