Israel Medical Association Journal

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: The incidence of cardiovascular disease increases with age, and visits by elderly patients to the outpatient cardiac clinic are becoming more frequent.

Objectives: To characterize cardiovascular pathologies of patients 70 years of age and over who visit the outpatient cardiac clinic.

Methods: We investigated cardiovascular pathologies, risk factors, and medications in new patients over a 2 month period.

Results: The study population comprised 290 patients: 139 (47.9%) were older than 70 years. Among the cardiovascular pathologies, aortic stenosis, angina pectoris, congestive heart failure, s/p coronary artery bypass graft, and stroke were more frequent in the elderly patients than in those under age 70. Among the risk factors for ischemic heart disease, only hypertension was more frequent in the elderly population, whereas fewer in this group were active smokers. The mean number of medications administered was 3.51 ± 1.63 among the elderly patients compared to 1.99 ± 1.71 among the younger ones (P = 0.0001). Beta-blockers were the most frequently used cardiovascular drugs both in the elderly (59.7%) and in the younger patients (43%) (P = 0.0046).

Conclusions: Patients over age 70 represent about half the visits in our outpatient clinic. Their multiple cardiovascular pathologies and therapeutic requirements raise the issue of developing the cardiology service to meet the special needs of geriatric patients.
 

Background: The forced oscillation technique is a non-invasive and effort-independent technique and is well suited for lung function measurement in young children. FOT[1] employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers.

Objectives: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy.

Methods: Forty-six children (median age 4.9 years, range 1.8–18.3) attending the Pulmonary Clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed. 

Results: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r² = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry.

Conclusions: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years of age. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

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: The TANTALUS^™ System (MetaCure Ltd.) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date.

Objectives: To re-analyze previously reported data from different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterize the significance of baseline A1c in the determination of the expected clinical outcome.

Methods: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM[1] on a stable regime of oral medication for 3 months prior to implant were identified. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline.

Results: Data after 24 weeks demonstrate a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 ± 0.1%. The average weight loss was 5.5 ± 0.7 kg.

Conclusions: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.
 

Background: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance.

Objectives: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel.

Methods: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel.

Results: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used.

Conclusions: Hematology centers should monitor infection rates and report them in a uniform methodology.
 

Background: Early-onset neonatal sepsis is a major cause of morbidity and mortality among newborn infants.

Objectives: To determine the incidence, type of pathogens and resistance to antibiotics among newborns with early-onset neonatal sepsis, and to identify the risk factors predisposing infants to resistant pathogens in order to reevaluate antibiotic regimens appropriate for resistant bacteria in these high risk neonates.

Methods: We retrospectively studied maternal and neonatal variables of 73 term and near-term infants and 30 preterm infants, born over a period of 10.5 years and exhibiting early-onset neonatal sepsis (positive blood cultures in the first 72 hours of life).

Results: Predominant pathogens in term and near-term infants were gram-positive compared with gram-negative organisms (mostly Escherichia coli) in preterm infants. Mothers of infants with antibiotic-resistant organisms were more likely to have prolonged rupture of membranes and prolonged hospitalization before delivery and to be treated with antibiotics. No trends towards more resistant strains of pathogens were recorded over the 10.5 years of the study period.

Conclusions: Early-onset neonatal sepsis in term infants differs in bacterial species from that in preterm infants, with predominantly gram-positive organisms in term and near-term infants and gram-negative organisms in preterms. Rates of bacterial resistance to the combination of ampicillin and gentamicin, though higher among infants born to mothers with prolonged hospitalization who had been treated with antibiotics, still remained very low in our department. Thus, it seems that our classic antibiotic regimen is still appropriate for both term and preterm newborns.