Israel Medical Association Journal

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

Background: There are no national data on the burden and management of acute cerebrovascular disease in Israel.

Objectives: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines.

Methods: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004.

Results: During the survey period 2,174 patients were admitted with acute cerebrovascular disease (mean age 71 ± 13 years, 47% women; 89% ischemic stroke or TIA[1], 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of Medicine and a third to Neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean length of hospital stay was 12 ± 27 days for ICH[2] and 8 ± 11 days for ischemic stroke. Among patients with ICH, 28% died and 66% died or had severe disability at hospital discharge, and for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke.

Conclusions: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Background: The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions.

Objectives: To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity.

Methods: The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13–18 years) with morbid obesity (body mass index over the 95th percentile for age and/or ≥ 30 kg/m²) were treated with sibutramine 10 mg once a day for 1 year.

Results: Mean BMI[1] was 40 ± 5.6 kg/m² (range 30.1–49.5 kg/m²) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 ± 4.9 and 35.9 ± 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated.

Conclusions: Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

Background: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care.

Objective: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma during this period.

Methods: All records from pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions

Results: There were 1584 admissions, 1208 were first-time admissions and 374 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease of re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates.

Conclusions: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease the asthma's severity, morbidity, and resultant hospital admissions.
 

Non-steroidal anti-inflammatory drugs, mainly ibuprofen, are extensively used in children as analgesics and antipyretics.

Background: Since 1984, several waves of Ethiopian immigrants have settled in Israel. On arrival they were found to be highly infected with intestinal parasites and to have increased serum immunoglobulin E and eosinophilia. 

Objectives: To study serum IgE [1] levels in Ethiopian children growing up in the environment of Israel . 

Methods: We assessed four groups of children of Ethiopian origin: a) adolescents examined on their arrival to Israel (group 1, n=11); b) adolescents born in Ethiopia and living in Israel for more than 7 years (group 2, n=10); c) children of Ethiopian origin born in Israel, without a history of allergy or asthma (group 3, n=15); and d) asthmatic children of Ethiopian origin born in Israel (group 4, n=8). A thorough clinical interview and examination as well as serum IgE levels, stool parasites and absolute eosinophil count were performed. 

Results: Group 1 (11 newly arrived Ethiopian adolescents) had a mean eosinophil count of 688 cells/ml (0–1739) and a mean serum IgE of 1043 IU/ml (253–2932), P < 0.0009 as compared to group 2. Helminthic parasites were observed in 8/11 individuals; after 1 year of follow-up and anti-parasitic treatment, serum IgE levels did not change significantly. Group 2 (10 Ethiopian born adolescents living in Israel for on average 10 years, 7–15 years) had a normal leukocyte count, MEC [2] 192 cells/ml (range 54–289), serum IgE 142 IU/ml (range 14–399 IU/ml) and no parasites in stool. Group 3 (15 Ethiopian children born in Israel) had a normal leukocyte count, MEC 128 cells/ml (0–324), serum IgE 55 IU/ml (7–189 IU/ml), similar to age-matched Israeli controls. In group 4 (8 Israeli born children of Ethiopian descent diagnosed with asthma), serum IgE showed significant elevation compared to Israeli age-matched asthmatic children (P < 0.005).  

Conclusions: High levels of IgE found in Ethiopian children on arrival to Israel declined to Israeli control levels after several years of living in the new environment. Ethiopian children born in Israel had normal levels of IgE, suggesting that environment is the main factor affecting IgE levels in this population. Israeli born Ethiopian children with asthma had significantly increased serum IgE levels compared to asthmatics of Israeli origin. These findings suggest that both environmental and genetic factors determine the level of serum IgE in these children. 

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 [1] Ig = immunoglobulin

 [2] MEC = mean eosinophil count
 

Objectives: To establish the impact of breast MRI on women undergoing testing in our institution.

Methods: We analyzed 82 cases that underwent MRI between January 2001 and April 2003. Analysis appraised the clinical impact of MRI testing in cases where medical summaries were available.

Results: Studies were categorized into five indications: a) screening in high risk women (n=7), b) search for primary disease in the presence of disease (n=5), c) monitoring of chemotherapy (n=2), d) postoperative assessment of tumor bed (n=9), and e) diagnostic/characterization of primary or recurrent breast cancer (n=59). Results were defined as negative, positive or no impact on clinical management. MRI testing had a positive impact in 62 cases, affecting measurable change in 9 cases. Benefit was seen in screening, diagnosis and postoperative cases. In 15 cases, MRI stimulated investigations.

Conclusion: MRI is a valuable tool in breast imaging and affects management. Further trials are necessary to define clearly the role of MRI and to ascertain whether in cases where beneficial impact on management is noted, there is ultimate impact on outcome. 

Objectives: To investigate the effect of low calcium dialysis on post-dialysis hypertension in view of an evident link between serum calcium and blood pressure in both normal renal function and chronic renal failure patients.

Methods: We evaluated 19 chronic hemodialysis patients in whom both post-dialysis hypertension and PDHCa[1] were observed. We investigated changes in serum total calcium, ionized calcium, intact parathormone levels and arterial blood pressure in response to 4 weeks low calcium dialysis as a treatment for PDHCa.

Results: When PDHT[2] patients were treated with low calcium dialysis, post-dialysis blood pressure was significantly decreased compared to pre-dialysis values (155.3 ± 9.7/82.2 ± 7.9 mmHg pre-dialysis vs. 134.1 ± 20.8/80 ± 8.6 mmHg post-dialysis, P = 0.001). Additionally, post-dialysis blood pressure was significantly lower than post-dialysis blood pressure prior to the low calcium dialysis treatment (176.1 ± 15/86 ± 10.8 mmHg post-standard dialysis, 134.1 ± 20.8/80 ± 8.6 mmHg after low calcium dialysis, P = 0.001). A decline in post-dialysis serum calcium (2.34 ± 0.2 vs. 2.86 ± 0.12 mmol/L, P = 0.04) and ionized calcium (1.17 ± 0.12 vs. 1.3 ± 0.06 mmol/L, P = 0.03) compared to pre-dialysis levels was also achieved by this treatment, with no significant changes in iPTH[3] levels.

Conclusions: These data suggest a role for low calcium dialysis in treating acute serum calcium elevation and post-dialysis hypertension in patients receiving maintenance hemodialysis.

Objectives: To evaluate trends in the incidence of hip fractures in this population.

Methods: The study was based on two surveys done approximately 20 years apart. It included women and men 50 years and older with radiographic evidence of a new hip fracture caused by low impact trauma. Only fractures that resulted from low or moderate trauma were considered for the current study. Incidence rates were calculated based on population data obtained from the official Central Bureau of Statistics.

Results: There was an overall twofold increase in the incidence rate of hip fractures. However, this increase occurred almost exclusively in the over-75 year old age groups (2.5-fold increase, both in women and men). The mean (and median) age of patients with hip fractures increased significantly over the study period, corresponding with the increase in longevity between the two periods.

Conclusions: There was a marked secular increase in the incidence of proximal hip fractures in both genders, primarily because of an increase in the fracture rate in the very old. The increase in median age of fracture patients suggests that the observed increase in fracture rate can be attributed mainly to aging of the population rather than to deterioration in bone quality over the generations.

Objectives: To estimate self-medication with antibiotics by a population in northern Israel.

Methods: We sent by post a questionnaire on antibiotic usage to 2,615 adults, both Jewish and Arab, living in northern Israel.

Results: The overall response rate was low (17.9%), particularly among the Arab population (9.4% of respondents). Among the 467 respondents, 169 (36.2%) reported 215 antibiotic courses within the last year. Amoxicillin was the antibiotic most commonly used (32.7% of courses); 89.4% of antibiotics were obtained via a physician’s prescription; 114 respondents (24.4%) stored leftover antibiotics at home and 81 (18.7%) would consider self-medication with antibiotics without a medical consultation.

Conclusions: Our results show that over-the counter acquisition of antibiotics is rare in Israel. However, the storage of leftover antibiotics in the home constitutes an alternative potential source of self-medication that can have untoward consequences, not only for the individual patient but also for the general population since inappropriate antibiotic usage contributes to the increasing rates of antimicrobial resistance.

Objectives: To examine whether hostility, anxiety and autobiographical memory (a correlate of depression) are associated with IIH[1].

Methods: Using a case-control cross sectional design, 20 patients with IIH were compared with 9 healthy controls of similar age, weight and height, and 11 headache controls. Patients were assessed for hostility and anxiety. The Autobiographical Memory Test was used to assess episodic memories.

Results: The IIH group reported significantly more anxiety and more general episodic memories than the healthy controls, but not the headache control group. The headache control patients reported more general memories than did the healthy controls.

Conclusions: Patients with headaches, whether of general origin or related to IIH, have a poor psychosocial profile. While the study design does not permit any conclusions regarding causality, our results support the need to consider psychological factors in evaluating and treating IIH and headache patients. 

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[1] IIH = idiopathic intracranial hypertension

Objectives: To determine the effectiveness of a neuroreflexology-based screening test, specifically the Medex device (Medex Screen Ltd.), for diagnosing patients undergoing conventional internal organ assessment, in a hospital setting.

Methods: Patients admitted to an internal medicine department, who met the inclusion criteria and agreed to participate, underwent conventional medical evaluation that included past medical history and physical examination. Another examination was conducted by a second physician using the Medex device to determine internal organ pathologies. A third researcher compared the actual “conventional” diagnosis with the Medex device output using standard statistical analysis.   

Results: Overall, 150 patients participated in the study. Correlation was significant for all categories (P < 0.01) except for blood and lymphatic disease. A high sensitivity (>70%) was measured for cardiovascular, respiratory, gastrointestinal and genitourinary diseases. The highest measure of agreement, as represented by the Cohen-Kappa factor, was found for respiratory disease (0.57).

Conclusions: Although the exact mechanism is not entirely clear, measurement of electroskin impedance of dermal-visceral zones has the potential to serve as a screening tool for inner organ pathologies. Further research should be conducted to create more evidence to support or dispute the use of this technique as a reliable diagnostic tool.