Israel Medical Association Journal

Background: Coronary heart disease and ischemic stroke are among the leading causes of morbidity and mortality in adults, and cerebrovascular disease is associated with the presence of symptomatic and asymptomatic CHD[1]. Several studies noted an association between coronary calcification and thoracic aorta calcification by several imaging techniques, but this association has not yet been examined in stable angina pectoris patients with the use of spiral computed tomography.

Objectives: To examine by spiral CT the association between the presence and severity of CC[2] and thoracic aorta calcification in patients with stable angina pectoris.

Methods: The patients were enrolled in ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) in Israel. The 432 patients (371 men and 61 women aged 40–89 years) underwent chest CT and were evaluated for CC and aortic calcification.

Results: CC was documented in 90% of the patients (n=392) and aortic calcification in 70% (n=303). A significant association (P < 0.05) was found between severity of CC and severity of aortic calcification (as measured by area, volume and slices of calcification). We also found an association between the number of coronary vessels calcified and the presence of aortic calcification: 90% of patients with triple-vessel disease (n=157) were also positive for aortic calcification (P < 0.05). Age also had an effect: 87% of patients ≥ 65 years (n=219) were positive for both coronary and aortic calcification (P = 0.005) while only 57% ≤ 65 (n=209) were positive for both (P = 0.081).

Conclusions: Our study demonstrates a strong association between the presence and severity of CC and the presence and severity of calcification of thoracic aorta in patients with stable angina pectoris as detected by spiral CT.

Background: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia.

Objectives: To assess the added diagnostic value of a new cardiac performance index (dP/dt^ejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-nduced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia.

Methods: The study group comprised 40 patients undergoing Sestamibi-SPECT[1]/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dt^ejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dt^ejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dt^ejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone.

Results: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%.
Conclusions: If ECG alone is used for specificity, the combination with dP/dt^ejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise

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

Background: The use of the bilateral internal mammary arteries has been reserved mainly for younger and low risk patients.

Aim: To assess the safety and efficacy of BIMA[1] grafting in older patients (≥ 70 years).

Methods: We reviewed the records of all consecutive patients ≥ 70 years old who underwent coronary artery bypass surgery with a BIMA graft in our institute over a 2 year period. Demographic data, operative data, perioperative morbidity and mortality were recorded. Findings were compared with a matched-size group of patients who underwent CABG[2] with a left internal mammary artery graft to left anterior descending artery.

Results: The study sample included 136 patients, of whom 68 underwent BIMA grafting and 68 LIMA[3] grafting. Baseline demographic and clinical characteristics were similar in the two groups. There was no significant difference in operative mortality between the BIMA and LIMA groups (1.5% vs. 0%, P = 0.3) or in mortality during follow-up at a mean of 16 months (4.4% vs. 2.9%, P = 0.4, respectively). There was no difference between the groups in the incidence of perioperative complications, re-admission and re-intervention rates during follow-up. Significant between-group differences were noted for mean cardiopulmonary bypass time (93.2 ± 34.7 BIMA vs. 108.8 ± 40.7 LIMA min, P = 0.02) and for red blood cell transfusion (1.9 ± 1.9 vs. 4.3 ± 2.8 packed cells/patient, P < 0.001).

Conclusions: The performance of mainly arterial revascularization with BIMA grafting in patients 70 years or older is as safe as LIMA grafting, with the added advantage of being a better conduit than saphenous vein graft, requiring fewer blood transfusions, and shorter cardiopulmonary bypass time.

Backgound: The use of intraoperative transesophageal echocardiogram in patients with infective endocarditis is usually reserved for cases of inadequate preoperative testing or suspected extension to perivalvular tissue.

Objectives: To explore the impact of routine intraoperative TEE[1] in patients with infective endocarditis.

Methods: The impact of intraoperative TEE on the operative plan, anatomic-physiologic results, and hemodynamic assessment or de-airing was analyzed in 59 patients (38 males, 21 females, mean age 57.7 ± 16.8 years, range 20–82) operated for active infective endocarditis over 56 months.

Results: Immediate pre-pump echocardiography was available in 52 operations (86.7%), and changed the operative plan in 6 of them (11.5%). Immediate post-pump study was available in 59 patients (98.3%) and accounted for second pump-run in 6 (10.2%): perivalvular leak (3 cases), and immobilized leaflet, significant mitral regurgitation following vegetectomy, and failing right ventricle requiring addition of vein graft (1 case each). Prolonged de-airing was necessary in 6 patients (10.2%). In 5 patients (8.5%) the postoperative study aided in the evaluation and treatment of difficult weaning from the cardiopulmonary bypass pump. In 21 patients (35.6%) the application of intraoperative TEE affected at least one of the four pre-specified parameters.
Conclusions: Intraoperative TEE has an important role in surgery for infective endocarditis and should be routinely implemented

Background: Previous studies found some factors such as physical exertion, anger and heavy meals to be triggers for acute coronary syndrome.

Objectives: To estimate the relative risk of an ACS[1] episode associated with positive and negative emotional experiences and anger as potential work-related triggers.

Methods: A total of 209 consecutive patients were interviewed a median of 2 days after a cardiac event that occurred at work or up to 2 hours later. The case-crossover design was used. Positive and negative emotional experiences and anger episodes in the hours immediately before the onset of ACS were compared with episodes in the comparable hours during the previous workday. For anger the episodes were compared with the usual frequency at work during the previous year. Positive and negative emotional experiences were assessed by the PANAS questionnaire (Positive and Negative Affect Scale), and anger by the Onset Anger Scale.

Results: The relative risks of an acute coronary event during the first hour after exposure to negative and positive emotional experiences were RR[2] = 14.0 (95% confidence interval 1.8–106.5) and RR = 3.50 (95% CI[3], 0.7–16.8) respectively and RR = 9.0 (95% CI, 1.1–71) for an episode of anger. Using conditional logistic regression analysis, the highest relative risk was associated with negative emotional experiences.

Conclusions: Negative emotional experiences and anger at work can trigger the onset of an ACS episode. This could have implications for recognizing a cardiac event as a work accident. The implementation of stress-reduction programs in the workplace or use of preventive medications in workers at high risk for coronary heart disease should be investigated.

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.
 

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

Background: Most Israeli males aged 16–17 undergo a thorough medical examination prior to recruitment into the army. During the last 50 years, extensive data have been gathered enabling a study of time trends in the prevalence of common diseases in this age group.

Objectives: To examine the current prevalence of common diseases, compare the results with those of previous cohorts, and assess the influence of the massive immigration during the 1990s.         

Methods: The health examination at the recruitment centers includes a medical history, complete physical examination, and review of medical documentation provided by the family physician. If needed, additional tests and referral to specialists are ordered. The prevalence of selected diseases and severity was drawn from the computerized database of the classification board. Two cohorts, 1992–94 and 2003–04, were examined and compared with three previous cohort studies in 1957–61, 1977–78 and 1982–84. Data were stratified according to origin and country of birth.

Results: The prevalence of asthma increased dramatically during the years from 10.2 per 1000 examinees in 1957–61 to 111.6 per 1000 examinees in 2003–04. The prevalence of tuberculosis declined and then increased from 0.6 per 1000 adolescents in 1982–84 to 2.4 per 1000 adolescents in 2003–04. The prevalence of type 1 diabetes mellitus increased from 0.2 cases per 1000 examinees in 1957–61 to 0.8 cases in 1977–78 and 1982–84 and 0.9 cases per 1000 examinees in 2003–04. The prevalence of severe heart defects and severe epilepsy declined in the last 20 years (1.4 and 1.7 cases per 1000 examinees in the 1982–84 cohort to 0.4 and 0.3 cases per 1000 examinees in the 2003–4 cohort respectively). The patterns of disease prevalence were different for immigrants: tuberculosis was more common while asthma and allergic rhinitis were less prevalent.

Conclusions: The prevalence of common diseases among adolescents in Israel has changed over the last 50 years. There is a different pattern for immigrants and for those born in Israel.

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.

Quantitative chimerism testing has become an indispensable tool for following the course and success of allogeneic hematopoietic stem cell transplants. In this paper, we describe the current laboratory approach to quantitative chimerism testing based on an analysis of short tandem repeats, and explain why performing this analysis longitudinally is important and feasible. Longitudinal analysis focuses on relative changes appearing in the course of sequential samples, and as such exploits the ultimate potential of this intrinsically semi-quantitative platform. Such an analysis is more informative than single static values, less likely to be confused with platform artifacts, and is individualized to the particular patient. It is particularly useful with non-myeloablative conditioning, where mixed chimerism is common. When longitudinal chimerism analysis is performed on lineage-specific subpopulations, the sensitivity, specificity and mechanistic implications of the data are augmented. Importantly, longitudinal monitoring is a routinely feasible laboratory option because multiplex STR-PCR[1] kits are available commercially, and modern software can be used to perform computation, reliability testing, and longitudinal tracking in a rapid, easy to use format. The ChimerTrack© application, a shareware program developed in our laboratory for this purpose, produces a report that automatically summarizes and illustrates the quantitative temporal course of the patient’s chimeric status. Such a longitudinal perspective enhances the value of quantitative chimerism monitoring for decisions regarding immunomodulatory post-transplant therapy. This information also provides unique insights into the biological dynamics of engraftment underlying the fluctuations in the temporal course of a patient’s chimeric status.