Background: Early detection of malignant melanoma of the skin is the most important factor in patient survival. Naked-eye diagnostic sensitivity and specificity are low. Patients with multiple nevi are at high risk to develop melanomas and the clinical follow-up of such patients is difficult, resulting in missed melanomas on the one hand and unnecessary biopsies on the other.

Objectives: To describe the set-up of a special clinic aimed at early detection of melanoma and follow-up of high risk patients and preliminary results from 20 months of operation.

Methods: We established a pigmented lesions clinic based on a digital photography studio enabling documentation and comparison over time of full body photography and dermoscopy.

Results: In the first 20 months of work, 895 patients were seen, 206 of them for follow-up visits. A total of 29,254 photos were taken. Altogether, 236 lesions were suspicious (either clinically or dermoscopically) and the patients were advised to excise them. Seven melanomas were found in this initial examination (which did not include long-term follow-up).

Conclusions: With multimode photographic cutaneous surveillance, early detection of melanoma in high risk patients has been reported. Our clinic utilizes the same techniques and diagnostic algorithm as other leading clinics throughout the world, thus enabling us to deliver better follow-up for those patients.
 

Background: Burns are a major public health problem, with long hospitalization stay in both intensive care units and general wards. In Israel about 5% of all hospitalized injuries are burn injuries. There are no long-term epidemiological studies on burn injuries in adults in Israel.

Objectives: To identify risk factors for burn injuries and provide a starting point for the establishment of an effective prevention plan.

Methods: We analyzed the demographic, etiologic and clinical data of 5000 burn patients admitted to the five major hospitals with burn units in Israel during a 7 year period (1997–2003). Data were obtained from the records of the Israeli National Trauma Registry. The differences between various groups were evaluated using the chi-square test.

Results: Male gender was twice as frequent as female gender in burn patients (68.0% vs. 31.9%), and Jewish ethnicity was more common than non-Jewish (62.3% vs. 36.8%). Second and third-degree burns with body surface areas less than 10% constituted the largest group (around 50%). The largest age group was 0–1 years, constituting 22.2% of the cases. Inhalation injury was uncommon (1.9%). The most common etiologies were hot liquids (45.8%) and open fire (27.5%). Children less than 10 years old were burnt mainly by hot liquids while the main cause of burns for adults > 20 years old was an open flame. The majority of burns occurred at home (58%); around 15% were work related. The mean duration of hospitalization was 13.7 days (SD 17.7); 15.5% were in an intensive care unit with a mean duration of 12.1 days (SD 17.1). Surgical procedures became more common during the period of the study (from 13.4% in 1998 to 26.59% in 2002, average 19.8%). The mortality rate was 4.4%. We found a strong correlation between burn degree and total body surface area and mortality (0.25% mortality for 2nd to 3rd-degree burns with less than 10% TBSA[1], 5.4% for 2nd to 3rd-degree burns with 20–39% TBSA, and 96.6% for burns > 90% TBSA). The worst prognosis was for those over the age of 70 (mortality rate 35.3%) and the best prognosis was for the 0–1 year group (survival rate 99.6%).

Conclusions: The groups at highest risk were children 0–1 years old, males and non-Jews (the incidence rate among non-Jews was 1.5 times higher than their share in the general population). Those with the highest mortality rate were victims of burns > 90% TBSA and patients older than 70. Most burns occurred at home.

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.

Background: Surgery for spinal stenosis is a frequent procedure in elderly patients. Presentation, hospital course and outcome of disease, including pain perception, may vary among patients of different ethnic origin.

Objectives: To evaluate whether differences in various medical indicators can explain differences in pain perception between two ethnic groups

Methods: We conducted a case-control study on the experience of two spinal units treating a mixed Arab and Jewish population, and compared the data on 85 Arab and 189 Jewish patients undergoing spinal lumbar surgery.

Results: Arab patients were younger (P = 0.027), less educated (P < 0.001), had a higher body mass index (P = 0.004) and included a higher proportion of diabetics (P = 0.013). Preoperative pain intensity (P = 0.023) and functional disability (P = 0.005) were more prominent, and factors associated with pre- or postoperative pain perception differed between the two ethnic groups. Despite these differences, results on follow-up were similar with respect to pain perception and level of disability.

Conclusions: A better understanding of ethnic differences is crucial for predicting surgery outcomes.

Background: The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.

Objectives: To evaluate the clinical effect of IFNβ-1b[1] (Betaferon®) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS[2]) in MS patients during 1 year of follow-up.

Methods: This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin Card Sorting Test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin Card Sorting Test score at baseline was measured using the paired t-test.

Results: There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNβ-1b: from 20.3 ± 8.3 μv to 13.1 ± 10.6 μv (P = 0.026) for amplitude, and from 312.9 ± 15.6 msec to 302.0 ± 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement – from 20.7 ± 30.7 to 13.1 ± 10.6 (P = 0.001) and 96.7 ± 15.7 to 100.1 ± 11.1 (P = 0.0025) respectively – after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 ± 0.5 to 2.8 ± 1.1.

Conclusions: A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNβ-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.

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.

Background: Catheter ablation is assuming a larger role in the management of patients with cardiac arrhythmias. Conventional fluoroscopic catheter mapping has limited spatial resolution and involves prolonged fluoroscopy. The non-fluoroscopic electroanatomic mapping technique (CARTO) has been developed to overcome these drawbacks.

Objectives: To report the early and late outcome in patients with different arrhythmias treated with radiofrequency ablation combined with the CARTO mapping and navigation system.

Methods: The study cohort comprised 125 consecutive patients with different cardiac arrhythmia referred to our center from January 1999 to July 2005 for mapping and/or ablation procedures using the CARTO system. Forty patients (32%) had previous failed conventional ablation or mapping procedures and were referred by other centers. The arrhythmia included atrial fibrillation (n=13), atrial flutter (n=38), atrial tachycardia (n=25), ventricular tachycardia (n=24), arrhythmogenic right ventricular dysplasia (n=9), and supraventricular tachycardia (n=16).

Results: During the study period, a total of 125 patients (mean age 49 ± 19 years, 59% males) underwent electrophysiological study and electroanatomic mapping of the heart chambers. Supraventricular arrhythmias were identified in 92 patients (73 %) and ventricular arrhythmias in 33 (27%). Acute and late success rates, defined as termination of the arrhythmia without anti-arrhythmic drugs, were 87% and 76% respectively. One patient (0.8%) developed a clinically significant complication.

Conclusions: The CARTO system advances our understanding of arrhythmias, and increases the safety, efficacy and efficiency of radiofrequency ablation.

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.