Israel Medical Association Journal

Objectives: To estimate usual patterns of acute illness in the community as a baseline for integration into pandemic influenza and bioterrorism preparedness plans.

Methods: Between 2000 and 2003 we conducted 13 telephone surveys to estimate the usual incidence and prevalence of symptoms of acute illness in the community.

Results: On average, 910 households were included in each of the surveys, representing about 3000 people. The compliance rates for full interviews ranged from 72.3% to 86.0%. In winter, on average, about 2% of the Israeli population (individuals) suffered each day from fever of ≥ 38ºC, and about 0.8% during the other months. The prevalence of cough was higher, 9.2% in winter and 3% during summer. Daily incidence of fever ranged from about 0.4% per day in winter to about 0.2% in the fall. The prevalence and incidence of both fever and cough were highest for infants followed by children aged 1–5 years.

Conclusions: These background morbidity estimates can be used for planning the overall treatment requirements, in addition to actual cases, resulting from pandemic influenza or a bioterrorist incident.

Objectives: To report a 14 year experience of RFA[2] of the slow pathway in patients with AVNRT treated in our laboratory.

Methods: A total of 901 consecutive patients (aged 9–92, mean 50.8 ± 18.2 years) underwent RFA of the slow pathway. All patients had sustained AVNRT induced with or without intravenous administration of isoproterenol. A standard electrophysiologic method with three diagnostic and one ablation catheter was used in 317 patients (35.2%); in the remaining 584 patients (64.8%), only two electrode catheters (one diagnostic, one ablation) were used ("two-catheter approach").

Results: Catheter ablation of the slow pathway abolished AVNRT induction in 877 patients (97.3%). In 14 patients (1.6%) the procedure was discontinued while in 10 (1.1%) the procedure failed. In 864 patients (95.9%) there were no complications. Transient or permanent AV block occurred during the procedure in 31 patients (3.4%), of whom 8 (0.9%) eventually required pacemaker insertion (n=7) or upgrade of a previously implanted VVI pacemaker (n=1) during the month following the procedure. The number of catheters used did not significantly affect the rate of results or complications of the ablation procedure. The success and complication rates remained stable over the years, although a significant trend for increased age and associated heart disease was observed during the study period.

Conclusions: The results of this single-center large study, which included patients with a wide age range, showed results similar to those of previous studies. The use of a "two-catheter approach" (one diagnostic and one ablation) was as effective and safe as a multi-catheter approach.

Objectives: To determine whether reliable data could be obtained at lower cost.

Methods: The study sample consisted of 50 patients with mild to severe stable COPD]1[. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated.

Results: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 ± 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64).

Conclusions: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Objectives: To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia.

Methods: We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings.. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1.

Results: There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (± SD) leukocyte counts in the pediatric and adult groups were 21,018/mm (± 10,420) and 12,628/mm (± 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correslation was also found between age and platelet counts. Although cuytokine levels in both groups were not significantly different, age was

Conclusions: The immune response in community-aquired bronchopneumonia is, at least partly, age-dependent.

Objectives: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT.

Methods: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex and who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus. Post-implantation levels were determined 2 weeks post-procedure in the PVB[2]. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure.

Results: At baseline, coronary sinus levels of BNP[3] but not hsCRP[4] were significanly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 ± 102.5 pg/ml, 95% confidence interval 24.2–434, P < 0.0001; hsCRP mean difference 5.2 ± 2.4 mg/dl, 95% CI[5] 0.3–10.1, P = 0.001). During a mean follow-up of 17.7 ± 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF[6]. Baseline New York Heart Association and CS[7] BNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations.

Conclusions: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict cilinical response and may guide patient management.

Objectives: To report 3 years national experience with orthotopic liver transplantation, and to evaluate patient and perioperative risk factors that could affect 1 year graft survival.

Methods: The study related to all 124 isolated adult liver transplantations performed in Israel between October 1997 and October 2000. Data were abstracted from the medical records. One-year graft survival was described using the Kaplan-Meier survival curve and three multivariate logistic regression models were performed: one with preoperative case-mix factors alone, and the other two with the addition of donor and operative factors respectively.

Results: Of the 124 liver transplantations performed, 32 failed (25.8%). The 1 year survival was lower than rates reported from both the United States and Europe, but the difference was not significant. Of the preoperative risk factors, recipient age ≥ 60 years, critical condition prior to surgery, high serum bilirubin and serum hemoglobin ≤ 10 g/dl were independently associated with graft failure, adjusting for all the other factors that entered the logistic regression equation. Extending the model to include donor and operative factors raised the C-statistic from 0.79 to 0.87. Donor age ≥ 40, cold ischemic time > 10 hours and a prolonged operation (> 10 hours) were the additional predictors for graft survival. A MELD score of over 18 was associated with a sixfold increased risk for graft failure (odds ratio = 6.5, P = 0.001).

Conclusions: Graft survival in Israel is slightly lower than that reported from the U.S. and Europe. Adding donor and operative factors to recipient characteristics significantly increased our understanding of 1 year survival of liver grafts.

Background: Poliovirus rapidly evolves by nucleic acid substitutions and genetic recombination with other polioviruses and non-polio enteroviruses. Evolving oral poliovirus (Sabin strains) can rapidly revert to neurovirulence and undergo antigenic alterations.

Objectives: To evaluate the threat of vaccine-derived poliovirus (1–15% divergence from the respective Sabin strain) for a poliomyelitis-free population in a country with a long-standing routine vaccination program.

Methods: We characterized genetic and antigenic changes in OPV[1] strains isolated from sewage in Israel and evaluated intestinal immunity by measuring fecal excretion after OPV challenge of vaccinated children.

Results: Characterization of poliovirus from sewage revealed eight type 2 and three type 3 vaccine polioviruses that had replicated and started to evolve (vaccine that replicated and diverged by 0.5 to ≤ 1.0%) and nine highly diverged type 2 vaccine-derived polioviruses (1–15% divergence from the respective Sabin strain) with 8–14% divergence between the years 1998 and 2005. Six of the eleven VRPV[2] uniquely recombined with OPV and/or NPEV[3]. The nine VDPV[4] were epidemically related, genotypically neurovirulent, and had 10–15 amino acid substitutions in antigenic sites altering their antigenicity, but shared a single recombination. Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months after partial immunization (two doses each of OPV and enhanced inactivated poliovirus) or full immunization (three doses of each) respectively, despite high humoral antibody titers.

Conclusions: Our findings, which show that OPV is excreted for a significant period by children with high humoral immunity, emphasize the long-term potential threat from VDPV in highly vaccinated populations. An adequate immunization program, combined with environmental surveillance, is necessary to prevent poliomyelitis and community transmission of poliovirus. 

Background: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over0diagnosis may be costly.

Objectives: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel.

Methods: During a 5 week pilot study, we examined resource utilization and ER [1] diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU[2] team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS[3], exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded.

Results: All patients had at least two cardiac troponin T measurements, 19 underwent EST[4], 9 echocardiography and 29 cardiac MDCT[5]. Fourteen patients were referred for early cardiac catheterization (same/next day). Specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 (56%) of patients who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 ± 8.6 hours vs. 12.9 ± 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after re-assessment. 

Conclusions: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to decision regarding admission/discharge from the ER.

The Ashkenazi-Jewish population is at increased risk for several recessively inherited disorders. While some of the disorders have severe or fatal symptom manifestations, others, such as non-neuronopathic Gaucher disease, do not usually pose a serious, life-threatening illness. Many healthcare centers in Israel offer prenatal panel screening. Controversy exists over the inclusion of Gaucher disease in the panel screening, especially since Gaucher disease screening lacks prognostic reliability. Most screening participants do not discriminate between the specific tests in the panel and are unable to discern between severe, life-threatening diseases and those that are less severe and even treatable. By including screening for Gaucher in the panel screening program, there is risk of a "panel effect," leading to termination of a pregnancy positive for Gaucher disease, without sufficient knowledge and understanding of the disease. Increasing medical and public awareness and knowledge of the disease, its prognosis and treatment options may reduce the rate of under-informed abortions associated with prenatal screening of Gaucher disease.

Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.

Background: Physicians in the community work on a tight and often pressured schedule; verbal and non-verbal techniques to terminate the patient-physician encounter are therefore necessary.

Objectives: To characterize ways of terminating the encounter.

Methods: Using a structured questionnaire we observed seven family physicians and nine consultants and recorded patient-physician encounters to assess techniques for terminating the encounter.

Results: In all, 320 encounters were recorded, 179 (55.9%) by consultants and 141 (44.1%) by family physicians. The mean duration of the encounters was 9.02 ± 5.34 minutes. The mean duration of encounters with family physicians was longer than consultants (10.39 vs. 7.93 minutes, P < 0.001). In most cases the encounter ended with the patient receiving printed documentation from the physician (no difference between family physicians and consultants). Consultants were more likely to end the encounter with a positive concluding remark such as “feel good” or “be well” (P < 0.01). There was no single occasion where termination of the encounter was initiated by the patient.

Conclusions: Giving a printed document to the patient appears to be perceived by both patients and physicians as an accepted way to end an encounter. Another good way to end the encounter is a positive greeting such as “feel good” or “be well.”