Israel Medical Association Journal

Background: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated.

Objectives: To analyze demographic, clinical and laboratory data of AGEP[1] cases in Israel, based on the RegisCAR study, a multinational European study.

Methods: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system.

Results: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10–60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs.

Conclusions: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, unique findings consisting of marked female predominance, seasonality and a profile of culprit drugs were noted.

7.4.10.6.04

background: many electrophysiologists recommend implantable cardioverter defibrillators for patients with Brugada syndrome who are cardiac arrest survivors or presumed at high risk of sudden death (patients with syncope or a familial history of sudden death or those with inducible ventricular fibrillation at electrophysiologic study).

objectives: To assess the efficacy and complications of ICD therapy in patients with Brugada syndrome.

Methods: The indications, efficacy and complications of ICD therapy in all patient with Brugada syndrome who underwent ICD implantation in 12 Israeli centers between 1994 and 2007 were analyzed.

Results: there were 59 patients (53 males, 89.8%) with a mean age of 44.1 years. At diagnosis 42 patients (71.2%) were symptomatic while 17 (28.8%) were asymptomatic. The indications for ICD implantation were: a history of cardiac arrest (n=11, 18.6%), syncope (n=31, 52.5%), inducible VF in symptomatic patients (n=14, 23.7%), and a family history of sudden death (n=3, 0.5%). The overall inducibility rates of VF were 89.2% and 93.3% among the symptomatic and a symptomatic patients, respectively (P=NS). During a follow-up of 4-160 (45+-35) months, all patients (except one who died from cancer) are alive. Five patients (8.4%), all with a history of cardiac arrest, had appropriate ICD discharge. Conversely, none of the patients without prior cardiac arrest had appropriate device therapy during 39+-30 month follow-up. Complications were encountered in 19 patients (32%). Inappropriate shocks occurred in 16 (27.1%) due to lead failure/dislodgment (n=5), T wave oversensing (n=2), device failure (n=1), sinus tachycardia (n=4), and supraventricular tachycardia (n=4). One patient suffered a pneumothorax and another a brachial plexus injury during the implant procedure. One patient suffered a late (2 months) perforation of the right ventricle by the implanted lead. Eleven patients (18.6%) required a reintervention either for infection (n=1) or lead problems (n=10). Eight patients (13.5%) required psychiatric assistance due to complications related to the ICD (mostly inappropriate shocks in 7 patients).

Conclusions: In this Israeli population with Brugada syndrome treated with ICD, appropriate device therapy was limited to cardiac arrest survivors while none of the other patients including those with syncope and/or inducible VF suffered an arrhythmic event. The overall complication rate was high.
 

A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of traumatic findings, identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001).  The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001), and in the detection of musculoskeletal injuries (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination.

Background: In the western world, trauma is the leading cause of disability and mortality in the 1–39 years age group. Road accidents constitute the most frequent cause of mortality among children older than 1 year and falls from a height are the most frequent cause of injuries requiring hospitalization.

Objectives: To analyze the epidemiology and characteristics of severe pediatric trauma due to falls from a height in northern Israel. This analysis should aid in planning an effective intervention plan.

Methods: This observational study included all patients aged 0–14 who died or were admitted to an intensive care unit in northern Israel following a steep fall. Demographic and clinical data were collected retrospectively for 3 years and prospectively for 1 year.

Results: A total of 188 children were severely injured or died following such a fall, with an annual rate of 11.4 per 100,000 children. Over 85% of severe injuries due to falls occurred among non-Jewish children, with an incidence rate 6.36 times higher than among Jewish children (20.17 and 3.17 per 100,000 children, respectively). In the non-Jewish sector 93.7% of the falls occurred at or around the child’s home, mainly from staircases, balconies and roofs.

Conclusions: A very high incidence of severe trauma due to domestic falls from a height was found among non-Jewish children in northern Israel. Domestic falls represent an important epidemiological problem in the non-Jewish pediatric sector, and an effective prevention plan should include measures to modify parents’ attitudes towards safety issues and the creation of a safe domestic environment.
 

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.

Objectives: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT.

Methods: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex and who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus. Post-implantation levels were determined 2 weeks post-procedure in the PVB[2]. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure.

Results: At baseline, coronary sinus levels of BNP[3] but not hsCRP[4] were significanly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 ± 102.5 pg/ml, 95% confidence interval 24.2–434, P < 0.0001; hsCRP mean difference 5.2 ± 2.4 mg/dl, 95% CI[5] 0.3–10.1, P = 0.001). During a mean follow-up of 17.7 ± 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF[6]. Baseline New York Heart Association and CS[7] BNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations.

Conclusions: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict cilinical response and may guide patient management.

Ubiquitin-proteasome degradation is a key cellular process involved in almost every aspect of cell life. According to the current concept, proteins are stable unless they are marked by poly-ubiquitination for degradation by the 26S proteasomes. A new twist in the concept became evident while studying the degradation of the tumor suppressor p53, a protein that appeared to satisfy this principle. We have discovered that native p53 is also prone to ubiquitin-independent 20S proteasomal degradation, suggesting that certain proteins are inherently unstable. We further found that this process of degradation is mediated by 20S proteasomes and inhibited by NADH quinone oxidoreductase 1. Our recent findings together with previous observations of ubiquitin-independent degradation suggest the existence of ubiquitin-independent mechanisms for proteasomal protein degradation in the cells.

Background: The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions.

Objectives: To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity.

Methods: The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13–18 years) with morbid obesity (body mass index over the 95th percentile for age and/or ≥ 30 kg/m²) were treated with sibutramine 10 mg once a day for 1 year.

Results: Mean BMI[1] was 40 ± 5.6 kg/m² (range 30.1–49.5 kg/m²) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 ± 4.9 and 35.9 ± 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated.

Conclusions: Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

Objectives: To determine the overall prevalence of PBC[1] in southern Israel and the specific rates for different immigrant groups between January 1993 and October 2004.

Methods: Multiple case-finding methods were used to identify all cases of PBC in the study region. Age-adjusted prevalence rates were compared among the different immigrant groups.

Results: A total of 47 cases of PBC were identified with an overall prevalence of 55 cases per million. All patients were women, and all except for a Bedouin Arab were Jewish. Foreign-born patients comprised 70% of our PBC cohort even though they represent only 45.4% of the regional population. This predominance of immigrants did not change when the rates were adjusted for age (P < 0.001). The prevalence rates were 40, 177, and 58 cases per million for those born in Israel, North Africa or Asia, and Eastern Europe, respectively. The age-specific prevalence rate for women older than 40 years varied from 135 cases per million among those born in Israel to 450 among immigrants from Eastern Europe and the former USSR to 700 cases per million among immigrants from North Africa and Asia.

Conclusions: The prevalence of PBC in southern Israel is similar to that reported from some European countries. The rate is much higher among Jews than Arabs and among immigrants to Israel compared to native Israelis.