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עמוד בית
Sun, 14.07.24

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July 2007
T.Naftali, D.Novick, G.Gabay, M.Rubinstein, and B.Novis

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases with an unknown etiology. Interleukin-18 is a pro-inflammatory cytokine that is up-regulated in Crohn’s disease. IL-18[1] binding protein neutralizes IL-18. The relationship of IL-18 and IL-18BP[2] and disease activity in these diseases is not fully understood.

Objectives: To investigate the correlation of IL-18 and IL-18BP with disease activity and other disease parameters in inflammatory bowel disease.

Methods: IL-18 and IL-18BP isoform α were measured in 129 patients and 10 healthy individuals. Patients' mean age was 40.5 (range 15–70 years) and 43 were women; 58 Crohn's and 28 colitis patients were in remission and 52 and 14, respectively, were in exacerbation. Twenty-three (19 and 4 respectively) were studied in both remission and exacerbation.

Results: The mean level of free IL-18 was significantly different between healthy individuals and Crohn's patients, and between Crohn's patients during exacerbation and remission (167 ± 32 vs. 471 ± 88 and 325 ± 24 pg/ml, respectively, P < 0.05). Mean level of IL-18BP was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (2.1 ± 1.1, 7.5 ± 4 and 5.23 ± 2.8 ng/ml, respectively, P < 0.01). In the colitis patients, mean free IL-18 level and IL-18BP were significantly different between healthy individuals and patients, but not between disease remission and exacerbation (167 ± 32, 492 ± 247 and 451± 69 pg/ml for IL-18, and 2.1 ± 1.1, 7.69 ± 4 and 6.8 ± 7 ng/ml for IL-18BP, respectively, P = 0.05).

Conclusions: IL-18 and IL-18BP levels are higher in patients with inflammatory bowel disease compared to healthy individuals. In Crohn's disease, but not in ulcerative colitis, IL-18 (but not free IL-18) and IL-18BP levels are significantly higher during exacerbation compared to remission. This observation highlights the importance of IL-18 in the pathogenesis of inflammatory bowel diseases, especially in Crohn's disease.






[1] IL = interleukin



[2] IL-18BP = IL-18 binding protein


April 2007
M. Shechter, I. Marai, S. Marai, Y. Sherer, B-A. Sela, M. S. Feinberg, A. Rubinstein and Y. Shoenfeld

Background: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value.

Objectives: To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease.

Methods: We prospectively assessed brachial artery flow-mediated dilation in 110 consecutive subjects (46 CVD[1] patients and 64 healthy controls), mean age 57 ± 11 years; 68 were men. After an overnight fast and discontinuation of all medications for ≥ 12 hours, percent improvement in FMD and nitroglycerin-mediated vasodilatation were assessed using high resolution ultrasound.

Results: %FMD[2] but not %NTG[3] was significantly lower in CVD patients (9.5 ± 8.0% vs. 13.5 ± 8.0%, P = 0.012) compared to healthy controls (13.4 ± 8.0% vs. 16.7 ± 11.0%, P = 0.084; respectively). In addition, an inverse correlation between %FMD and the number of traditional CVD risk factors was found among all study participants (r = -0.23, P = 0.015) and healthy controls (r = -0.23, P = 0.036). In a mean follow-up of 15 ± 2 months, the composite CVD endpoints (all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with FMD < 6% compared to subjects with FMD > 6% (33.3% vs. 12.1%, P < 0.03, respectively).
Conclusions: Thus, brachial artery %FMD provides important prognostic information in addition to that derived from traditional risk factor assessment







[1] CVD = cardiovascular disease



[2] %FMD = percent improvement in flow-mediated dilation



[3] %NTG = percent improvement in nitroglycerin-mediated vasodilatation


January 2007
A. Kesler, P. Pianka, E. Rubinow, Y. Segev and N. Bornstein.
May 2006
R. Rubinshtein, D.A. Halon, A. Kogan, R. Jaffe, B. Karkabi, T. Gaspar, M.Y. Flugelman, R. Shapira, A. Merdler and B.S. Lewis

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.


 




[1] ER = emergency room

[2] CPU = chest pain unit

[3] ACS = acute coronary syndrome

[4] EST = exercise stress testing

[5] MDCT = multi-detector cardiac computed tomography angiography


November 2005
N. Sharon, J. Schachter, R.T. Talnir, J. First, U. Rubinstein and R. Bilik
August 2005
R. Elazary, A. Maly, A. Khalaileh, C. Rubinstein, K. Olstain-Pops, G. Almogy, A.I. Rivkind and Y. Mintz
June 2005
E. Bamberger, N. Lahat, V. Gershtein, R. Gershtein, D. Benilevi, S. Shapiro, I. Kassis, L. Rubin and I. Srugo
 Background: Whereas the diagnosis of classical pertussis has traditionally been based on clinical criteria, increasing numbers of atypical presentations suggest the need for an extensive laboratory-based approach.

Objectives: To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.

Methods: We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.

Results: PCR[1] and culture identified 41% and 7% of patients with B. pertussis, respectively (P < 0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P < 0.001) and post-vaccinated groups (P < 0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P < 0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P < 0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P < 0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.

Conclusions: PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.


 





[1] PCR = polymerase chain reaction


March 2005
Z. Habot-Wilner, J. Moisseiev, H. Bin and B. Rubinovitch
October 2004
O. Shevah, M. Rubinstein and Z. Laron

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.






[1] GH = growth hormone

[2] GH-R = growth hormone receptor


December 2003
H. Gur, A. Rubinow, D. Buskila
June 2003
H. Amital, Y.H. Applbaum, H. Bar-on and A. Rubinow
December 2002
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