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עמוד בית
Fri, 19.07.24

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October 2006
H.S. Oster, M. Hoffman, S. Prutchi-Sagiv, O. Katz, D. Neumann and M. Mittelman
 Recombinant human erythropoietin has become an essential part of the management of anemic patients with end-stage renal disease. It is also used to treat the anemia associated with cancer and other diseases, and it improves quality of life. In recent years, studies in animals and humans have focused on the use of rHuEPO[1] for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy. On the other hand, concerns have been raised following two studies of patients with solid tumors in whom those treated with rHuEPO had diminished survival. Criticism of the design of these studies makes it clear that large, well-designed, randomized trials must be performed to determine the role of rHuEPO in the treatment of cancer, and more generally to clarify the full clinical benefits of the drug, while minimizing the harm.







[1] rHuEPO = recombinant human erythropoietin


August 2006
D. Tekes-Manova, E. Israeli, T. Shochat, M. Swartzon, S. Gordon, R. Heruti, I. Ashkenazi and D. Justo
 Background: Coronary heart disease is a major cause of morbidity and mortality worldwide. Early detection of cardiovascular risk factors and intervention may reduce consequential morbidity and mortality.

Objectives: To assess the prevalence of reversible and treatable cardiovascular risk factors among 26’477 healthy Israeli adults: 23’339 men and 3138 women aged 25-55 years.

Methods: We collected data during routine examinations performed as part of a screening program for Israel Defense Force personnel.


Results: The three most prevalent cardiovascular risk factors were a sedentary lifestyle (64%), dyslipidemia (55.1%) and smoking (26.8%). Overall, 52.9% of the men and 48.4% of the women had two or more cardiovascular risk factors. Moreover, 52.4% of young adult men and 43.3% of young adult women, age 25-34 years, had two or more reversible cardiovascular risk factors.


Conclusions: In this expectedly healthy population there was a high prevalence of reversible and treatable cardiovascular risk factors in both genders and in young age. These observations stress the need for routine health examinations and lifestyle modification programs even in the young healthy Israeli population.

July 2006
H. Liss
 Background: A publication bias exists towards positive results in studies funded by pharmaceutical companies.

Objectives: To determine whether drug studies in the pulmonary/allergy literature also demonstrate a publication bias towards more favorable results when a pharmaceutical company funds the study.

Methods: We reviewed all original articles published in seven pulmonary and allergy journals between October 2002 and September 2003. Included in the review were studies of inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators, or leukotriene receptor antagonists. Articles with funding from a pharmaceutical company and/or one or more authors employed by a pharmaceutical company were considered pharmaceutical company-sponsored studies. The remaining studies were considered not sponsored by a pharmaceutical company. Results were compared to ascertain whether positive results were obtained more frequently in the company-sponsored studies.

Results: Of the 100 articles included in this review 63 were considered pharmaceutical company-sponsored research. Results favorable for the drugs studies were significantly more common in those funded by a pharmaceutical company (98% vs. 32%).

Conclusions: In the pulmonary and allergy literature, as in other fields, there is a publication bias towards positive results in pharmaceutical company-sponsored research.

June 2006
H. Desatnik, Z. Habot-Wilner, A. Alhalel, I. Moroz, J. Glovinsky and J Moisseiev
 Background: The major cause of visual impairment in diabetic patients is macular edema. The failure of laser photocoagulation in a large subgroup of patients with clinically significant diabetic macular edema has prompted interest in other treatment methods.

Objectives: To evaluate the long-term efficacy and safety of an intravitreal injection of triamcinolone acetonide for clinically significant diabetic macular edema.

Methods: In a retrospective case series 31 diabetic patients with persistent, recurrent or diffuse clinically significant diabetic macular edema received a single 4 mg (0.1 ml) intravitreal triamcinolone acetonide injection and were followed for at least 6 months. The main outcome measures evaluated were classified as primary: visual acuity and central macular thickness, and secondary: intraocular pressure and cataract progression. Statistical analyses included Student’s t-test, chi-square test and the McNamar test.

Results: Best visual acuity results were observed 2.6 ± 2.4 months post-injection. At that time the mean foveal thickness had decreased by 37% from a baseline of 455 ± 100 to 288 ± 99 µ (P < 0.001) and the mean visual acuity improved from 6/42 to 6/23 (P < 0.001). Final mean visual acuity after an average of 10 ± 1.8 months follow-up (range 6–13 months) was identical to the baseline, although mean foveal thickness was still significantly lower than the initial thickness (368 ± 166 vs. 455 ± 100 µ, P < 0.01). Statistical analysis did not identify any pre-injection prognostic factors for improved visual acuity. The only complications that occurred were elevated intraocular pressure in 42% of patients and cataract progression in 21%. There was no endophthalmitis.

Conclusions: Intravitreal injection of triamcinolone acetonide for clinically significant diabetic macular edema is effective in reducing foveal thickness and improving visual acuity in the short term. Longer follow-up revealed that visual acuity returned to pre-injection values, even though a modest decrease in the foveal thickness persisted. Further studies are needed to evaluate the long-term efficacy in conjunction with laser photocoagulation treatment.

May 2006
L.M. Shulman, Y. Manor, D. Sofer, T. Swartz and E. Mendelson

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. 


 




[1] OPV = oral poliovirus

[2] VRPV = vaccine poliovirus that has replicated and started to evolve but is < 1 % but at least 0.5% diverged from the respective Sabin strain

[3] NPEV = non-polio enterovirus

[4] VDPV = vaccine-derived poliovirus 1–15% divergence from the respective Sabin strain


February 2006
E. Leshinsky-Silver, S. Cheng, M.A. Grow, S. Schwartz, L. Scharf, D. Lev, M. Boaz, D. Brunner and R. Zimlichman

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.
 

E. Averbukh and E. Banin

Diabetic retinopathy is one of the leading causes of blindness worldwide.

January 2006
Z. Habot-Wilner, H. Desatnik, A. Greenbaum and I. S. Barequet.

Orbital dog bites, although uncommon, occur mostly in children and are reported to be associated with severe ocular adnexal injury without globe involvement.

December 2005
K. Sade, S. Kivity, E. Fireman, Y. Schwartz, S. Kivity.

Background: The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active part in the late allergic response.

Objectives: To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who were given the drug for 4 weeks.

Methods: Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment.

Results: During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE‑induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 ± 550 pg/ml at baseline to 2225 ± 430 pg/ml at 4 weeks, P = 0.02).

Conclusions: Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

September 2005
S. Schwartz, A.I. Eidelman, A. Zeidan, D. Applebaum and D. Raveh
Background: Large family size may be a risk factor for childhood accidents. A possible association with quality of child supervision and rapidity of seeking medical care has not been fully evaluated.

Objectives: To determine whether children with multiple siblings are at increased risk for accidents, to assess whether quality of child supervision varies with family size, and to evaluate the relationship of family size with the rapidity of seeking medical care after an accident.

Methods: We prospectively studied 333 childhood accidents treated at TEREM (emergency care station) or Shaare Zedek Medical Center. Details on family composition and the accident were obtained through parental interview. Family size of the study population was compared with that of the Jerusalem population. Families with one to three children (Group 1) and four or more children (Group 2) were compared with regard to type of supervision and different "Gap times" – the time interval from when the accident occurred until medical assistance was sought ("Gap 1"), the time from that medical contact until arrival at Shaare Zedek ("Gap 2"), and the time from the accident until arrival at Shaare Zedek for those children for whom interim medical assistance either was ("Gap 3A") or was not ("Gap 3B") sought.

Results: Children from families with 1, 2, 3, 4 and ≥5 children comprised 7.2%, 18.3%, 14.4%, 18.6% and 41.4% of our sample compared to 20.4%, 21.8%, 18.4%, 14.7% and 24.7% in the general population respectively. Children from Group 2 were less often attended to by an adult (44.5% vs. 62.0%) and more often were in the presence only of other children at the time of the accident (27.0% vs. 10.5%). Gaps 1, 2 and 3A in Group 2 (6.3 hours, 16.5 hours, 27.8 hours respectively) were longer than for Group 1 (2.7, 10.7, 13.3 hours respectively).

Conclusions: The risk for accidents is increased among children from families with four or more children. The adequacy of child supervision in large families is impaired. There is a relative delay from the time of the accident until these children are brought for treatment. 

August 2005
I. Klaz, Y. Wohl, N. Nathansohn, N. Yerushalmi, S. Sharvit, I. Kochba and S. Brenner
 Background: The Israel Defense Forces implemented a pilot teledermatology service in primary clinics.

Objectives: To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units.

Methods: A multi-center, prospective, uncontrolled, cohort pilot trial was conducted for a period of 6 months. Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs. Diagnosis, therapy and management were sent back to the referring PCP[1]. Patients were asked to evaluate the level of the CSAFTD[2] service, effect of the service on accessibility to dermatologists, respect for privacy, availability of drugs, health improvement and overall satisfaction. PCPs assessed the quality of the teledermatology consultations they received, the contribution to their knowledge, and their overall satisfaction.

Results: Tele-diagnosis alone was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals also required face-to-face consultation. Satisfaction with CSAFTD was high among patients in both rural and urban clinics, with significantly higher scores in rural units. Rural patients rated the level of service, accessibility and overall satisfaction higher than did urban patients. PCPs were satisfied with the quality of the service and its contribution to their knowledge. Rural physicians rated level of service and overall satisfaction higher than the urban physicians. Tele-referrals were completed more efficiently than referral for face-to-face appointments.

Conclusions: CSAFTD provided efficient, high quality medical service to rural and urban military clinics in the IDF[3].


 



[1] PCP = primary care physician

[2] CSAFTD = computerized store and forward teledermatology

[3] IDF = Israel Defense Force



 
D. Schwartz
 Background: Many emergency departments use coagulation studies in the evaluation of patients with suspected acute coronary syndromes.

Objectives: To determine the prevalence of abnormal coagulation studies in ED[1] patients evaluated for suspected ACS[2], and to investigate whether abnormal international normalized ratio/partial thromboplastin time testing resulted in changes in patient management and whether abnormal results could be predicted by history and physical examination.

Methods: In this retrospective observational study, hospital and ED records were obtained for all patients with a diagnosis of ACS seen in the ED during a 3 month period. ED records were reviewed to identify all patients in whom the cardiac laboratory panel was performed. Other data included demographics, diagnosis and disposition, historical risk factors for abnormalities of coagulation, ED and inpatient management, INR[3]/PTT[4], platelet count and cardiac enzymes. Descriptive statistical analyses were performed.

Results: Complete data were available for 223 of the 227 patients (98.7%). Of these, 175 (78.5%) patients were admitted. The mean age was 64.2 years. Thirteen patients (5.8%) were diagnosed with acute myocardial infarction. Of the 223 patients, 29 (13%) and 23 (10%) had INR and PTT results respectively beyond the reference range. Seventy percent of patients with abnormal coagulation test results had risk factors for coagulation disorders. The abnormal results of the remaining patients included only a mild elevation and therefore no change in management was initiated.

Conclusions: Abnormal coagulation test results in patients presenting with suspected ACS are rare, they can usually be predicted by history, and they rarely affect management. Routine coagulation studies are not indicated in these patients.


 


[1] ED = emergency department

[2] ACS = acute coronary syndromes

[3] INR = international normalized ratio

[4] PTT = partial thromboplastin time


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