Israel Medical Association Journal

Background: Left atrial volume and exercise capacity are strong predictors of cardiovascular risk. Decreased exercise capacity is expected when LAV[1] is increased due to its association with abnormal left ventricular filling pressure. However, LAV enlargement is expected in chronic mitral regurgitation as well.

Objectives: To examine the linkage between LAV and exercise capacity in chronic MR[2] and to determine whether larger LAV has indeed better exercise capacity in patients with chronic severe degenerative MR and good LV systolic function.

Methods: The study included asymptomatic patients with severe chronic degenerative MR and normal LV[3] systolic function that underwent stress echocardiography. LAV was measured at rest using the biplane Simpson’s method and indexed to body surface area. The cutoff of good exercise capacity was determined at 7 METS.

Results: The patient group comprised 52 consecutive patients (age 60 ± 14 years, 36 males). Two subgroups (19 vs. 33 patients), age- and gender-matched, were formed according to LAVi[4] cutoff of 42 ml/m². Those with higher LAVi had lower exercise capacity (P = 0.004) albeit similar MR grade, baseline blood pressure, LV function and size. Receiver-operator curve analysis revealed indexed LAV value of ≤ 42 as 51% sensitive and 88% specific for predicting exercise capacity > 7 METS (AUC[5] = 0.7, P = 0.03). In multivariate analysis, age, gender and LAVi were identified as independent predictors of exercise capacity.

Conclusions: In asymptomatic patients with severe chronic degenerative MR and normal LV systolic function, mild enlargement of the left atrium (≤ 42 ml/m²) is associated with good exercise capacity.

Background: Tuberculosis is the most common opportunistic infection among people infected with human immunodeficiency virus and its first cause of morbidity and mortality.

Objectives: To analyze the characteristics of a population in Israel with both tuberculosis disease and HIV[1] infection in order to identify factors that contribute to outcome.

Methods: The study group comprised patients hospitalized in the Pulmonary and Tuberculosis Department of Shmuel Harofeh Hospital during the period January 2000 to December 2006. They were located by a computer search in the hospital registry and the pertinent data were collected.

Results: During the study period 1059 cases of active tuberculosis disease were hospitalized; 93 of them were co-infected with HIV. Most of them came from endemic countries (61.2% from Ethiopia and 20.4% from the former Soviet Union; none of them was born in Israel). Ten percent of the cases were multiple-drug resistant and 32% showed extrapulmonary involvement. The response rate to the treatment was good, and the median hospitalization time was 70 days. The mortality rate was 3.2%.

Conclusions: Despite the high prevalence of pulmonary disease in our group, the short-term outcome was good and the Mycobacterium was highly sensitive to first-line drugs. These encouraging results can be attributed to the fact that tuberculosis patients in Israel are identified early and treated continuously and strictly, with early initiation of antiretroviral therapy, which ensures that the development of drug resistance is low.

Background: Hodgkin’s lymphoma is a distinct primary solid tumor of the immune system that shows wide variation in incidence among different geographic regions and among various races. It was previously suggested that susceptible people living in certain parts of Israel had a higher risk of HL[1] because of exposure to unidentified environmental factors in these regions. Compared with other parts of Israel, these regions were characterized by a higher proportion of Israeli-born Jews.

Objectives: To study time trends in the incidence rate of HL in Israeli-born Jews of all age groups during the years 1960–2005.

Results: A total of 4812 Jewish cases of HL were reported to the Israel Cancer Registry during the study period 1960–2005. There has been a persistent increase in the age-standardized incidence rate of HL, all subtypes pooled, in Israeli-born Jews in both men and women. The age distribution pattern in both genders was bimodal in all periods. The highest incidence was observed in the 20–24 year age group: for women (9.13 per 100,000 per year) during the period 1988–1996, and for men (6.60 per 100,000 per year) during the period 1997–2005.

Conclusions: The reported incidence level of HL in Israeli-born young adult Jews in Israel has increased in recent years to high levels compared with other western countries. Our findings suggest a cohort effect to unidentified factors affecting Israeli-born young adult Jews in Israel.

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).

Objectives: To evaluate the migratory capacity and efficacy of NTF-SC[1] in animal models of Parkinson's disease and Huntington's disease.

Methods: MSCs[2] underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA[3] administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.

Results: NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA[4]-induced lesion.

Conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.

Background: Mite allergy is an indoor allergen responsible for most respiratory allergies in the western world. Environmental control can modify disease activity in these patients.

Objectives: To examine the benefit of the Plasma Cluster^® device (Sharp, Japan) for inactivating and removing mites from the environment of patients diagnosed with either mite‑sensitive perennial allergic rhinitis or mite‑sensitive allergic asthma.

Methods: Patients with AR[1] (n=30) or AA[2] (n=10) were enrolled into a prospective open observational 8 week study. The first 2 weeks involved initial evaluation, the following 4 weeks consisted of active usage of the device, and the last 2 weeks were designated for follow‑up. Symptom scores (recorded daily by patients and during visits by physicians) were recorded and analyzed.

Results: Patients with AR experienced a significant (P < 0.05) reduction in nasal discharge, post‑nasal drip, nasal congestion, nasal itching, watery eyes, itchy eyes, headache, itchy ears, night disturbances and an improvement in general well‑being during the last 2 days of the study compared to baseline. Patients with AA reported significant (P < 0.05) reduction in dyspnea, wheezing and the need to avoid dust mites. There was a significant (P < 0.05) improvement in mean peak expiratory flow rate at study closure compared to baseline.

Conclusions: Short-term usage of the Plasma Cluster^® device resulted in considerable clinical improvement and increased peak expiratory flow rate in patients with AR or AA. The findings of this pilot study warrant longer and controlled studies to determine the value of this device in the treatment of various allergic disorders.

Background: A high incidence of abnormal pulmonary function tests has been reported in cross-sectional studies among patients with rheumatoid arthritis. Few patients have been enrolled in longitudinal studies.

Objectives: To perform PFT[1] in rheumatoid arthritic patients without pulmonary involvement and to identify variables related to changes in PFT over 5 years of follow-up.

Methods: Consecutive RA[2] patients underwent PFT according to American Thoracic Society recommendations. All surviving patients were advised to repeat the examination 5 years later.

Results: PFT was performed in 82 patients (21 men, 61 women). Their mean age was 55.7 (15.9) years and the mean RA duration was 11.1 (10) years. Five years later 15 patients (18.3%) had died. Among the 67 surviving patients, 38 (56.7%) agreed to participate in a follow-up study. The initial PFT revealed normal PFT in only 30 patients (36.6%); an obstructive ventilatory defect in 2 (2.4%), a small airway defect in 12 (17%), a restrictive ventilatory defect in 21 (25.6%), and reduced DLco in 17 (20.7%). Among the 38 patients participating in the 5 year follow-up study, 8 developed respiratory symptoms, one patient had a new obstructive ventilatory defect, one patient developed a restrictive ventilatory defect, and 5 patients had a newly developed small airway defect. The DLco had improved in 7 of the 8 patients who initially had reduced DLco, reaching normal values in 5 patients. Over the study period a new reduction in DLco was observed in 7 patients. Linear regression analyses failed to identify any patient or disease-specific characteristics that could predict a worsening in PFT. The absolute yearly decline in forced expiratory volume in 1 sec among our RA patients was 47 ml/year, a decline similar to that seen among current smokers.

Conclusions: Serial PFT among patients with RA is indicated and allows for earlier identification of various ventilatory defects. Small airways disturbance was a common finding among our RA patients.

Background: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps.

Objectives: To study the impact of computerized intervention on secondary prevention of CAD[1].

Methods: The CDSS[2] was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization.

Results: Follow-up was available for 7448 patients with CAD (median 19.8 months, range 6–36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment recommended to lower lipid level. A significant decrease in low density lipoprotein levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 ± 34.2 vs. 124.3 ± 34.6 mg/dl (P < 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P < 0.001).

Conclusions: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation.

Background: Studies from many countries have reported an increasing prevalence of autistic spectrum disorder in childhood. No comprehensive epidemiological studies of ASD[1] have been performed in Israel.

Objectives: To describe time trends in the reported number of patients with ASD in Israel and to characterize the demographic features of the reported patients.

Methods: We reviewed the charts of the National Insurance Institute of Israel from 1972 to 2004 for all children with a diagnosis of ASD receiving disability benefits.

Results: A total of 3509 children met the study criteria. Eighty percent were boys and 98% were Jewish. The incidence data showed an increase in the number of cases from zero in 1982–84 and 2 (1.2 per million capita under 18 years) in 1985 to a high of 428 cases in 2004 (190 per million).

Conclusions: This is the first comprehensive study of the incidence of ASD in Israel. According to data derived from official health records, the rate of occurrence of ASD has substantially increased in the last 20 years. Further studies are needed to determine if this is a true increase or if the findings were confounded by external factors, such as recent improvements in diagnostic measures and social stigmas.

Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.

Objectives: To examine the relation between CmsIgE[1] and the probability of resolution of milk allergy.

Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.

Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.

Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.