Israel Medical Association Journal

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

Background: During the last decade new surgical techniques for mitral valve repair were developed. We have been using those techniques in order to widen the spectrum of patients eligible for MV[1] repair.

Objectives: To assess the operative and mid-term results a wide variety of surgical techniques.

Methods: From January 2004 through December 2006, 213 patients underwent MV repair in our institution. Valve pathology was degenerative in 123 patients (58%), ischemic in 37 (17%), showed annular dilatation in 25 (12%), endocarditis in 16 (8%), was rheumatic in 13 (6%), and due to other causes in 14 (7%). Preoperative New York Heart Association score was 2.35 ± 0.85 and ejection fraction 53 ± 12%. Isolated MV repair was performed in 90 patients (42%) and 158 concomitant procedures were done in 123 patients (58%). A wide variety of surgical techniques was used in order to increase the number of repairs compared to valve replacement.

Results: There were 7 in-hospital deaths (3.3%). NYHA[2] class improved from 2.19 ± 0.85 to 1.4 ± 0.6, and freedom from reoperation was 100%. Echocardiography follow-up of patients with degenerative MV revealed that 93% of the patients (115/123) were free of mitral regurgitation greater than 2+ grade. In patients operated by a minimal invasive approach there were no conversions to sternotomy, no late deaths, none required reoperation, and 96% were free of MR[3] greater than 2+ grade. The use of multiple surgical techniques enabled the repair of more than 80% of pure MR cases.

Conclusions: MV repair provides good perioperative and mid-term results, and supports the preference for MV repair over replacement, when feasible. Multiple valve repair techniques tailored to different pathologies increases the feasibility of mitral repair.

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.

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.

Background: When encountering complaints of pain in the area of Achilles tendon with a suspected lesion, the clinician seldom reaches a precise diagnosis based only on X-ray and clinical examination. Ultrasonography is useful for evaluating the pathology and treatment.

Objectives: To assess the relative contribution of real-time intraoperative ultrasound examination and immediate postoperative ultrasound in patients with acute rupture of the Achilles tendon treated by percutaneous suture method. The combination of both procedures provides a unique advantage that could facilitate better results.

Methods: Ultrasound examination was used in 20 patients with acute rupture of the Achilles tendon who were treated surgically. Intraoperative as well as postoperative ultrasound examinations were performed in 5 patients whereas 15 patients underwent an immediate postoperative ultrasound.

Results: Ultrasound pathologies were found in all patients. Percutaneous surgical correction of ruptured Achilles tendon with accurate positioning of the foot using real-time sonography was successful in all the patients.

Conclusion: As in many other soft tissue lesions, ultrasonography is a useful tool for evaluating the pathology and for planning the surgical correction of ruptures in the Achilles tendon.

Background: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial.

Objectives: To study the association of reperfusion arrhythmia with short and long-term survival.

Methods: We used a prospective registry of consecutive STEMI[1] patients undergoing PPCI[2]. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded.

Results: Of the 688 patients in the study group, 22% were women. Mean (± SD) age of the cohort was 61 (± 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA[3] was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow-up period of 466 days was 0.46 (95% confidence interval 0.23–0.92).

Conclusions: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis.

Background: Fractures of the femur in neonates are relatively uncommon. The infants feel pain and discomfort, causing parental distress, and the hospital stay is longer. Treatment of this specific fracture is problematic because of the small size of the baby.

Objectives: To review the results of the treatment of neonatal femoral fractures.

Methods: We retrospectively reviewed all neonatal fractures of the femur during a 12 year period. Thirteen fractures of the femur in 11 babies were treated with improvised Bryant skin traction of both legs. All the patients were re-examined after a mean follow-up period of 5.2 years.

Results: All fractures healed satisfactorily clinically and radiographically, with no residual deformity, no leg length discrepancy and no functional impairment.

Conclusions: Bryant’s traction for 2–3 weeks in hospital is a safe method for the treatment of femoral fractures in neonates, and the outcome is good.
 

Background: The Muslim Circassians in Israel represent a unique ethnic community, distinct from Jews and Arabs. This endogamous group has a limited genetic variability that allows studying risk factors associated with type 2 diabetes.

Objectives: To estimate the prevalence of type 2 diabetes among Israeli Circassians and its correlation to obesity and genetic susceptibility.

Methods: Israeli Circassian women (n=450) and men (n=289) older than 35 were included in the study. They were classified as having or not having diabetes, and their risk factors, including hypertension, body mass index, family history of diabetes, and laboratory tests, were examined retrospectively.

Results: The age-adjusted prevalence of diabetes among the 739 participants was 12% (men 14.6%, women 10.7%). It was higher among those with BMI[1] > 30 than in those with lower BMI and a family history of diabetes without high BMI. But the risk of diabetes with BMI > 30 plus a family history was three times higher than when these factors were missing (odds ratio 2.96, 95% confidence interval 1.30–6.6). Multivariate analysis, however, found familial history of diabetes to be the strongest risk factor, independent of obesity (OR[2] 2.47, 95% CI[3] 1.45–4.20).

Conclusions: The results yielded by this homogeneous Circassian population, sharing the same environmental influences and having an endogamous pattern of marriage, suggest a role of genetic risk factors for diabetes. Israeli Circassians are suitable for additional genetic studies that may lead to the identification of susceptibility genes for type 2 diabetes.