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עמוד בית
Sat, 23.11.24

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May 2007
D. Starobin, M. Bargutin, I. Rosenberg, A. Yarmolovsky, T. Levi and G. Fink

Background: Asthma control and treatment compliance are widely investigated issues around the world. Studies have demonstrated relatively low asthma compliance and control in 40–90% of asthma patients in different countries. There are no available data on the Israeli adult asthmatic population

Objectives: To investigate the level of asthma control and compliance in adult asthmatic patients.

Methods: This cross-sectional study of consecutive adult asthmatic patients visiting the pulmonary clinic used a combined questionnaire that included demographics, data on asthma severity and management, and asthma control and compliance scores. Each patient was interviewed and questionnaires were filled out during a routine visit.

Results: The study group comprised 142 males (35.4%) and 259 females (64.6%). Compliance was found optimal in 8 patients (2%), fair in 146 (36%), partial in 156 (39%) and poor in 92 (23%) of the participating asthmatic patients. Asthma control was found optimal in 26 (7%), fair in 124 (31%), partial in 122 (30%) and poor in 129 (32%) patients. Sephardic and Ashkenazi Jewish origin, higher level of education, and treatment protocol including either single fixed-dose inhalers or short-acting beta-agonist bronchodilators significantly improved compliance in our cohort. Socioeconomic status and compliance were found to positively affect asthma control, whereas active smoking negatively affected asthma control in the study patients.

Conclusions: The figures of optimal asthma control and compliance to treatment in Israeli adult asthmatics are low and worse than reported in other studies abroad.
 

April 2007
N. Uriel,G. Moravsky, A. Blatt, A. Tourovski, Z. Gabara, I. Yofik, V. Danicek, A. Hendler, R. Braunstein, R. Krakover, Z. Vered and E. Kaluski

Background: Spontaneous coronary reperfusion occurs in 7–27% of patients with ST elevation myocardial infarction, and is an independent predictor of myocardial salvage, percutaneous coronary intervention success, and improved outcome.

Objectives: To determine the optimal PCI[1] time for patients admitted to the hospital due to STEMI[2] with SCR[3].

Methods: We performed a retrospective analysis of all patients admitted to the coronary care unit between July 2002 and November 2004 with a diagnosis of STEMI with SCR.

Results: The study group comprised 86 patients. There was not a single reinfarction episode during an observation period of 6579 patient hours. Cardiac catheterization was executed early (< 24 hours from pain onset) in 26 patients and late (> 24 hours) in 55. Pre-PCI angiographic TIMI flow 2–3 was seen in > 95% in both groups. PCI was performed more frequently in the “early” group (P = 0.024), while multi-vessel coronary artery disease (P = 0.094) requiring coronary bypass surgery (P = 0.056) was observed more frequently in the “late catheterization” group. Myocardial infarction and angina pectoris at 30 days occurred more frequently in the early catheterization group (P = 0.039), however no difference in any major adverse cardiac events was detected during long-term follow-up (491 ± 245 days).

Conclusions: Reinfarction after STEMI with SCR is a rare event. Early PCI in patients with STEMI and SCR, even when executed with aggressive anti-platelet therapy, seems to result in an excess of early MACE, without any long-term advantage. Prospective randomized trials should determine the optimal PCI timing for these patients.








[1] PCI = percutaneous coronary intervention

[2] STEMI = ST elevation myocardial infarction

[3] SCR = spontaneous coronary reperfusion


R. Durst, C. Lotan, H. Nassar, M. Gotsman, E. Mor, B. Varshitzki, P. Greganski, R. Jabara, D. Admon, D. Meerkin and M. Mosseri

Background: Femoral artery vascular complications are the most common adverse events following cardiac catheterization. Smaller diameter introducer sheaths and catheters are likely to lower the puncture site complication rate but may hinder visualization.

Objectives: To evaluate the safety and angiographic quality of 4 French catheters.

Methods: The study was designed to simulate real-life operator-based experience. Diagnostic angiography was performed with either 4F or 6F diagnostic catheters; the size of the catheter used in each patient was predetermined by the day of the month. Patients undergoing 4F and 6F diagnostic angiography were ambulated after 4 and 6 hours, respectively. The following technical parameters were recorded by the operator: ease of introducer sheath insertion, ease of coronary intubation, ease of injection, coronary opacification, collateral flow demonstration, and overall assessment. Adverse events were recorded in all patients and included minor bleeding, major bleeding (necessitating blood transfusion), minor hematoma, major hematoma, pseudo-aneurysm formation and arteriovenous fistula.

Results: The study group included 177 patients, of whom 91 were in the 4F arm and 86 in the 6F arm. Demographic and procedural data were similar in both groups. Seventy-seven percent of 6F and 50% of 4F procedures were evaluated as excellent (P < 0.05). This difference was attributed to easier intubation of the coronary ostium and contrast material injection, increased opacification of the coronary arteries, and demonstration of collateral flow with 6F catheters. Complications occurred in 22% of patients treated with 6F catheters and 10% of those treated with 4F catheters (P = 0.11). Of the 50 patients who switched from 4F to 6F 12% had complications. In patients undergoing diagnostic angiography, the complication rate was 10% vs. 27% (most of them minor) in the 4F and 6F groups, respectively (P < 0.05).
Conclusions: Patients catheterized with 4F have fewer complications compared with 6F diagnostic catheters even when ambulated earlier. Although 4F had a reduced quality compared to 6F angiographies, they were evaluated as satisfactory or excellent in quality 85% of the time. 4F catheters have a potential for reduced hospitalization stay and are a good option for primary catheterization in patients not anticipated to undergo coronary intervention

R. Jabara, S. Namouz, J. D. Kark and C. Lotan

Background: There is little published information on the coronary risk characteristics of Palestinian women. However, there are documented lifestyle differences as well as socioeconomic inequalities between Arab and Jewish women in Israel.

Objectives: To compare the risk factor characteristics of coronary heart disease patients in Palestinian and Israeli women.

Methods: This study included 546 women (444 Jews and 102 Arabs) aged 35-74, all residents of Jerusalem, who underwent cardiac catheterization at the Hadassah-Hebrew University Medical Center between 2000 and 2003, and were confirmed to have coronary artery disease; Data on multiple risk factors were obtained from patient interviews and files.

Results: Compared with Jewish women, Arab women had a higher prevalence of diabetes, had borne more children/were younger, had a lower socioeconomic status, consumed jess alcohol and more olive oil, suffered more passive smoking and were less physically active. On the other hand, fewer Arab women had dyslipidemia, used hormone replacement therapy and had a family history of CHD.

Conclusions: Compared to Jewish women, Palestinian Arab women in Jerusalem appear to have more diabetes and exhibit lifestyle factors that generally increase the risk for CHD. Greater attention to primary prevention in this ethnic group is needed. This study suggests the need to investigate determinants of the metabolic syndrome and the possible role of passive smoking in Arab women as well as modes of intervention via health promotion and risk factor management in this population.
 

S. Alroy, M. Preis, M. Barzilai, A. Cassel, L. Lavie, D. A. Halon, O. Amir, B. S. Lewis and M. Y. Flugelman

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.






[1] ECF = endothelial cell function



 
March 2007
A. Melman, N. Bar-Chama, A. McCullough, K. Davis and G. Christ

Background: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca++ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca++ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access

A. Brautbar, Y. Esyag, G.S Breuer, Y. Wiener-Well and G. Nesher

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.

 

 







[1] HPV = human papillomavirus


Y. Barak

The association between the Holocaust experience and suicide has rarely been studied systematically. The dearth of data in this area of old-age psychiatry does not necessarily imply that Holocaust survivors are immune from suicide. Recent work on the aging of survivors seems to suggest that as a group they are at high risk for self-harm. Published reports on suicide and the Holocaust identified by means of a MEDLINE literature search were reviewed. A similar search was performed on the Internet using the Google search engine. Thirteen studies were uncovered, 9 of which addressed the association of suicide and the Holocaust experience and 4 focused on the suicide within the concentration camps during the genocide. Eleven of the 15 studies explicitly reported on the association of suicide, suicidal ideation or death by suicide with the Holocaust experience, or reported findings suggesting such an association. The Internet search yielded three sites clearly describing increased suicide rates in the concentration camps. An increased rate of suicidal ideation and suicide attempts among the elderly who were exposed to the Holocaust experience is confirmed. There is a need for further study, intervention and resource allocation among the growing numbers of elderly persons who suffered traumatic events in earlier phases of their lives. This is especially critical for Holocaust survivors.

  
 

February 2007
December 2006
A. Nemets, I. Isakov, M. Huerta, Y. Barshai, S. Oren and G. Lugassy
 Background: Thrombosis is a major cause of morbidity and mortality in polycythemia vera. Hypercoagulability is principally due to hyperviscosity of the whole blood, an exponential function of the hematocrit. PV[1] is also associated with endothelial dysfunction that can predispose to arterial disease. Reduction of the red cell mass to a safe level by phlebotomy is the first principle of therapy in PV. This therapy may have some effect on the arterial compliance in PV patients.

Objectives: To estimate the influence of phlebotomies on large artery (C1) and small artery compliance (C2) in PV patients by using non-invasive methods.

Methods: Short-term hemodynamic effects of phlebotomy were studied by pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before and immediately after venesection (300–500 ml of blood). We repeated the evaluation after 1 month to measure the long-term effects.

Results: Seventeen PV patients were included in the study and 47 measurements of arterial compliance were performed: 37 for short-term effects and 10 for long-term effects. The mean large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5–28.6), and 12.6 ml/mmHg x 10 (range 5.2–20.1) immediately after phlebotomy (NS). The mean small artery compliance (C2) before and immediately after phlebotomy were 4.4 mg/mmHg x 10 (range 1.2–14.3) and 5.5 mg/mmHg x 10 (range 1.2–15.6) respectively (delta C2–1.1, P < 0.001). No difference in these parameters could be demonstrated in the long-term arm.

Conclusions: Phlebotomy immediately improves arterial compliance in small vessels of PV patients, but this effect is short lived.


 





[1] PV = polycythemia vera


November 2006
Y. Schwammenthal, R. Tsabari, M. Bakon, D. Orion, O. Merzeliak and D. Tanne
 Background: Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke, has been available in the United States for over a decade and was approved for use in Israel at the end of 2004.

Objectives: To assess the implementation of intravenous rt-PA[1] in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel.

Methods: Patients with acute ischemic stroke, admitted between January 2005 and June 2006, who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed.

Results: Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. Mean age of intravenously treated patients was 67 years (range 22–85 years), median baseline NIHSS score was 14 (range 10–18, 25–75%) and the median ‘onset to drug time’ was 150 minutes (range 120–178, 25–75%). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients and 38% of patients were independent at hospital discharge.

Conclusions: Use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with ‘onset to drug time’, safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.


 





[1] rt-PA = recombinant tissue plasminogen activator


October 2006
R. Segal, E. Lubart, A. Leibovitz, A. Iaina and D. Caspi
 Background: Aspirin is commonly used by elderly patients. In previous studies we found transient changes in renal function induced by low doses of aspirin.

Objectives: To investigate the mechanisms of these effects.

Methods: The study group included 106 long-term care stable geriatric inpatients. Diet and drugs were kept stable. The study lasted 5 weeks; during the first 2 weeks 100 mg aspirin was administered once a day. Clinical and laboratory follow-up were performed at baseline and weekly for the next 3 weeks. The glomerular filtration rate was estimated by creatinine clearance measured in 24 hour urine and serum creatinine, and by the Cockcroft-Gault formula (C-G) equation. Uric acid clearance (Cu acid) was determined from serum concentrations and 24 hour excretion of uric acid. Patients with serum creatinine > 1.5 mg/dl were not included.

Results: After 2 weeks on low dose aspirin, measured creatinine and uric acid clearances decreased significantly compared with the initial values in 70% and 62% of the patients, respectively, with mean decreases of 19% and 17%, respectively (P < 0.001). Blood urea nitrogen increased by 17% while serum creatinine and uric acid concentrations increased by 4% (P < 0.05 for all). The C-G[1] values decreased by 3% (P < 0.05). After withdrawal of aspirin all parameters improved. However, 67% of the patients remained with some impairment in their measured Ccr[2], compared to baseline. Patients who reacted adversely to low dose aspirin had significantly better pre-study renal function (Ccr), lower hemoglobin and lower levels of serum albumin.

Conclusions: Short-term low dose aspirin affected renal tubular creatinine and uric acid transport in the elderly, which may result in a prolonged or permanent deterioration of the renal function. It is suggested that renal functions be monitored even with the use of low dose aspirin in elderly patients.


 





[1] C-G = Cockcroft-Gault formula

[2] Ccr = creatinine clearance


E. Kaluski, Z. Gabara, N. Uriel, O. Milo, M. Leitman, J. Weisfogel, V. Danicek, Z. Vered and G. Cotter
 Background: External counter-pulsation is a safe and effective method of alleviating angina pectoris, but the mechanism of benefit is not understood.

Objectives: To evaluate the safety and efficacy of external counter-pulsation therapy in heart failure patients.

Methods: Fifteen symptomatic heart failure patients (subsequent to optimal medical and device therapy) underwent 35 hourly sessions of ECPT[1] over a 7 week period. Before and after each ECPT session we performed pro-B-type natriuretic peptide and brachial artery function studies, administered a quality of life questionnaire, and assessed exercise tolerance and functional class.

Results: Baseline left ventricular ejection fraction was 28.1 ± 5.8%. ECPT was safe and well tolerated and resulted in a reduction in pro-BNP[2] levels (from 2245 ± 2149 pcg/ml to 1558 ± 1206 pcg/ml, P = 0.022). Exercise duration (Naughton protocol) improved (from 720 ± 389 to 893 ± 436 seconds, P = 0.0001), along with functional class (2.63 ± 0.6 vs. 1.93 ± 0.7, P = 0.023) and quality of life scores (54 ± 22 vs. 67 ± 23, P = 0.001). Nitroglycerine-mediated brachial vasodilatation increased (11.5 ± 7.3% vs. 15.6 ± 5.2%, P =0.049), as did brachial flow-mediated dilation (8.35 ± 6.0% vs. 11.37 ± 4.9%, P = 0.09).

Conclusions: ECPT is safe for symptomatic heart failure patients and is associated with functional and neurohormonal improvement. Larger long-term randomized studies with a control arm are needed to confirm these initial encouraging observations.


 





[1] ECPT = external counter-pulsation therapy

[2] BNP = B-type natriuretic peptide


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