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 define the length of time required to rehabilitate and discharge these patients, and to identify predictors of a prolonged or failed discharge process.

Methods: We conducted a retrospective chart review of patients admitted to the Respiratory Rehabilitation Unit at Alyn Hospital, Jerusalem, over a 4 year period.

Results: Of the 48 patients identified, 31 (64.7%) were eventually discharged, 13 (27.1%) remained hospitalized long-term, and 4 (8.3%) died during their hospitalization. The median length of hospitalization was 10 months: 6 months for purposes of rehabilitation therapy, and 4 months thereafter to resolve the logistics of discharge. Specific family characteristics – an unemployed father (odds ratio = 4.6, P = 0.02) and an additional family member with a disability (OR[1] = 5.8, P = 0.03) – as well as ongoing mechanical ventilation at the time of discharge (OR = 5.5, P < 0.01) were found to positively correlate with a prolonged or failed discharge process.

Conclusions:  Hospitalization in a pediatric respiratory rehabilitation unit may be prolonged for both medical and non-medical reasons, with the process of discharge home being particularly difficult in certain subsets of patients. A proactive discharge policy by hospitals, improved community support services, and legislation defining the rights of home-ventilated children may facilitate more efficient discharge home of these patients.

Objectives: To evaluate the national Israeli experience with lung transplantation in patients with CF[1].

Methods: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that performed this procedure.

Results: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 ± 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1–113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 ± 8.1% to 76 ± 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS[2] was 34.2 months (range 17–64 months).

Conclusion: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

The Israel Ministry of Health’s epidemiology department reported a record number of 1564 new pertussis cases in 2004. This brings the incidence rate to 23 per 100,000 population, indicating a marked increase in the prevalence of pertussis, from 1–3/100,000 in 1998, 9 in 2001, to 14 in 2003. The rate of atypical pertussis presentations in vaccinated patients, the decline in pertussis immunity post-vaccination, and the decreased awareness of potential infections in the adult population make the diagnosis of pertussis difficult and contribute to the rising incidence. In this article we review the current literature in order to increase awareness of the occurrence of pertussis in children as well as adults, discuss the laboratory diagnostic methods being used, and report the currently recommended means of treating the disease.

Background: Debate continues in Israel as to whether to allow patients in public hospitals to choose their physician in return for an additional, out-of-pocket payment. One argument against this arrangement is that the most senior physicians will devote most of their time to private patients and not be sufficiently available to public patients with complex cases.

Objectives: To analyze the patterns of surgical seniority in Jerusalem hospitals from a number of perspectives, including the extent to which: a) opting for private care increases the likelihood of being treated by a very senior surgeon; b) public patients undergoing complex operations are being treated by very senior surgeons, c) the most senior surgeons allocate a significant portion of their time to private patients.

Methods: Demographic and clinical data were retrieved from the operating room records of three of the public hospitals in Jerusalem for all 38,840 operations performed in 2001. Of them, roughly 6000 operations (16%) were performed privately. Operations were classified as "most complex," "moderately complex" and "least complex" by averaging the independent ratings of eight medical and surgical experts. The surgeon's seniority was graded as "tenured" (tenured board-certified specialists, including department heads), "senior" (non-tenured board-certified specialists), and "residents." For each operation, we considered the seniority of the lead surgeon and of the most senior surgeon on the surgical team.

Results: The lead surgeon was of tenured rank in 99% of the most complex private cases and 74% of the most complex public cases, in 93% of the moderately complex private and 35% of the moderately complex public cases, and in 92% of the least complex private and 32% of the least complex public cases. The surgical team included a tenured physician in 97%, 66%, and 53% of the most complex, moderately complex, and least complex public operations, respectively. In both private and public cases, a board-certified (tenured or senior) specialist was a member of the surgical team for almost all of the most complex and moderately complex operations. On average, over half of the operations in which the lead surgeon was a department head were performed on public patients. Among tenured surgeons, those who spent more hours than their colleagues leading private operations also tended, on average, to spend more hours leading public operations.

Conclusions: Private patients have an advantage over public patients in terms of the seniority of the lead surgeon. However, there is also substantial involvement of very senior surgeons in the treatment of public patients, particularly in those cases that are most complex. 

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Background: Magnetic resonance imaging is a diagnostic tool of growing importance. Since its introduction, certain medical implants, e.g., pacemakers, were considered an absolute contraindication, mainly due to the presence of ferromagnetic components and the potential for electromagnetic interference. Patients with such implants were therefore prevented from entering MRI systems and not studied by this modality. These devices are now smaller and have improved electromechanical interference protection. Recently in vitro and in vivo data showed that these devices may be scanned safely in the MRI.

Objectives: To report our initial experience with three patients with pacemakers who underwent cerebral MRI studies.

Methods: The study included patients with clear clinical indications for MRI examination and who had implanted devices shown to be safe by in vitro and in vivo animal testing. In each patient the pacemaker was programmed to pacing-off. During the scan, continuous electrocardiographic telemetry, breathing rate, pulse oximetry and symptoms were monitored. Specific absorption rate was limited to 4.0 W/kg for all sequences. Device parameters were assessed before, immediately after MRI, and 1 week later.

Results: None of the patients was pacemaker dependent. During the MRI study, no device movement was felt by the patients and no episodes of inappropriate inhibition or rapid activation of pacing were observed during the scan. At device interrogation here were no significant differences in device parameters pre-, post-, and 1 week after MRI. Image quality was unremarkable in all imaging sequences used and was not influenced by the presence of the pacemaker.

Conclusion: Given appropriate precautions, MRI can be safely performed in patients with a selected permanent pacemaker. This may have significant implications for current MRI contraindications.  

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.
 

Tumor necrosis factor-associated fever syndrome is an autosomal dominant disorder caused by mutations of the TNFRSF 1A gene encoding the 55 kD TNF receptor (p55 TNF-RI).

Background: In Japan, helicopters have rarely been used for emergency medical services. The use of helicopters not only ensures rapid evacuation but may also serve to provide emergency management to patients with life-threatening injuries in the prehospital setting.

Objectives: To evaluate a Japanese helicopter-based emergency medical system including an onboard physician, particularly in terms of probability of survival.

Methods: We conducted a retrospective review of trauma victims, and calculated two estimates of PS[1] – at the scene and on arrival at the emergency department – based on patient age, Injury Severity Score, and Revised Trauma Score.

Results: We identified trauma victims who had an ISS[2] above 15 and were transported from the scene by helicopter. Excluding cardiopulmonary arrest at the scene, 151 cases were studied. Thirty-two patients had hemodynamic instability with systolic blood pressures below 90 mmHg, caused by hemorrhagic shock (29 cases) or obstructive shock (3 cases). Their PS values were 0.56 ± 0.38 in the prehospital setting and 0.65 ± 0.38 on arrival at the ED[3], representing a significant difference (P = 0.0003). Twenty-four of these patients survived, reflecting successful resuscitation during prehospital and ED management.

Conclusions: A doctor-helicopter system was shown to improve probability of survival for life-threatening trauma in the Japanese emergency medical system.