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עמוד בית
Sat, 22.06.24

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December 2006
E. Zimlichman, M. Szyper-Kravitz, U. Katz and Y. Shoenfeld
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.

October 2005
E. Zimlichman, A. Lahad, A. Aron-Maor, A. Kanevsky and Y. Shoenfeld.
 Background: As complementary and alternative medicine is gaining popularity among health consumers, diagnostic screening tools based on neuroreflexology are also being developed. These techniques, which are based on the rationale that measurement of electrical impedance of specific dermatomes reflects corresponding internal organ pathologies, have not yet been the subject of conventional scientific research.

Objectives: To determine the effectiveness of a neuroreflexology-based screening test, specifically the Medex device (Medex Screen Ltd.), for diagnosing patients undergoing conventional internal organ assessment, in a hospital setting.

Methods: Patients admitted to an internal medicine department, who met the inclusion criteria and agreed to participate, underwent conventional medical evaluation that included past medical history and physical examination. Another examination was conducted by a second physician using the Medex device to determine internal organ pathologies. A third researcher compared the actual “conventional” diagnosis with the Medex device output using standard statistical analysis.   

Results: Overall, 150 patients participated in the study. Correlation was significant for all categories (P < 0.01) except for blood and lymphatic disease. A high sensitivity (>70%) was measured for cardiovascular, respiratory, gastrointestinal and genitourinary diseases. The highest measure of agreement, as represented by the Cohen-Kappa factor, was found for respiratory disease (0.57).

Conclusions: Although the exact mechanism is not entirely clear, measurement of electroskin impedance of dermal-visceral zones has the potential to serve as a screening tool for inner organ pathologies. Further research should be conducted to create more evidence to support or dispute the use of this technique as a reliable diagnostic tool.

September 2005
G. Twig, E. Zimlichman, M. Szyper-Kravitz and G. Zandman-Goddard
March 2005
E. Zimlichman, D. Mandel, F.B. Mimouni, S. Vinker, I. Kochba, Y. Kreiss and A. Lahad
Background: The health system of the medical corps of the Israel Defense Force is based primarily upon primary healthcare. In recent years, health management organizations have considered the primary care physician responsible for assessing the overall health needs of the patient and, accordingly, introduced the term “gatekeeper.”

Objectives: To describe and analyze how PCPs[1] in the IDF[2] view their roles as primary care providers and to characterize how they perceive the quality of the medical care that they provide.

Methods: We conducted a survey using a questionnaire that was mailed or faxed to a representative sample of PCPs. The questionnaire included demographic background, professional background, statements on self-perception issues, and ranking of roles as a PCP in the IDF.

Results: Statements concerning commitment to the patient were ranked higher than statements concerning commitment to the military organization. Most physicians perceive the quality of the medical care service that they provide as high; they also stated that they do not receive adequate continuous medical education.

Conclusions: Our survey shows that PCPs in the IDF, like civilian family physicians, perceive their primary obligation as serving the needs of their patients but are yet to take on the full role of “gatekeepers” in the IDF’s healthcare system. We conclude that the Medical Corps should implement appropriate steps to ensure that PCPs are prepared to take on a more prominent role as “gatekeepers” and providers of high quality primary medical care.


[1] PCP = primary care physician

[2] IDF = Israel Defense Force

September 2004
E. Zimlichman, D. Mandel, F.B. Mimouni, R. Wartenfeld, M. Huerta, I. Grotto and Y. Kreiss

Background: Oral contraceptive users are at increased risk for both arterial and venous thrombosis, some of which can be fatal. Studies are consistent with the existence of a synergism between cigarette smoking and OC[1] use in the pathogenesis of myocardial infarction in young women.

Objectives: To study the relationship between OC use, cigarette smoking and other cardiovascular risk factors among young women.

Methods: A systematic sample of military personnel, upon discharge from service in the Israel Defense Forces, was asked to complete a research questionnaire. Body weight and height were measured and body mass index computed.

Results: Overall, 16,258 questionnaires were collected and analyzed during this 20 year study. There was a gradual, significant increase in OC use until the mid-1980s, from approximately 45% to 60% (P < 0.001), followed by steady rates of 58–64% since then. In contrast, the rates of smoking decreased significantly in the mid-1980s, from approximately 42% to a nadir of 22% in 1991. Since then, the rate of smoking has increased slowly but steadily, to reach a level of 35% in 1999. The OC users were more often of western (Ashkenazi) origin and came from families with more education and fewer siblings. They were more often smokers than non-OC users, and started smoking at a younger age. They had significantly lower BMI[2] than non-users. OC use was nearly identical in groups with or without multiple cardiovascular risk factors (smoking, obesity, family history).

Conclusions: Smoking and OC use are strongly associated. Other cardiovascular risk factors (smoking, obesity, family history) do not prevent OC users from smoking or smokers to use OC. We suggest that primary care physicians discourage smoking among adolescent females who wish to start using OC. A thorough medical history should be obtained to recognize all risk factors for cardiovascular disease and to provide for appropriate contraception counseling.

[1] OC = oral contraceptives

[2] BMI = body mass index

July 2004
Sharabi, R. Zimlichman, R. Mansouri, J. Chun and D.S. Goldstein

Background: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.

Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.

Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48–72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10-7 to 10-3 M), for 1–20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.

Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.

Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

October 2002
Marina Shargorodsky, MD and Reuven Zimlichman, MD
September 2002
Dov Gavish, MD, Eyal Leibovitz, MD, Itzhak Elly, MD, Marina Shargorodsky, MD and Reuven Zimlichman, MD

Background: The implementation of treatment guidelines is lacking worldwide.

Objectives: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Methods: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP[1] target level was assessed.

Results: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of <100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA1C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up.

Conclusion: Follow-up of patients in a specialized clinic enhances the achievement of LDL[2]-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.


[1] NCEP = National Cholesterol Education Program

[2] LDL = low density lipoprotein

January 2002
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