Israel Medical Association Journal

Background: Locally delivered steroids by inhalers or nebulizers have been shown in small trials to be effective in acute asthma attack, but evidence-based data are insufficient to establish their place as routine management of adult asthma attacks.

Objectives: To determine the efficacy of nebulized compared to systemic steroids in adult asthmatics admitted to the emergency department following an acute attack.

Methods: Adult asthmatics admitted to the ED[1] were assigned in random consecutive case fashion to one of three protocol groups: group 1 – nebulized steroid fluticasone (Flixotide Nebules®), group 2 – intravenous methylprednisolone, group 3 – combined treatment by both routes. Objective and subjective parameters, such as peak expiratory flow, oxygen saturation, heart rate, and dyspnea score, were registered before and 2 hours after ED treatment was initiated. Steroids were continued for 1 week following the ED visit according to the protocol arm. Data on hospital admission/discharge rate, ED readmissions in the week after enrollment and other major events related to asthma were registered.

Results: Altogether, 73 adult asthmatics were assigned to receive treatment: 24 patients in group 1, 23 in group 2 and 26 in group 3. Mean age was 44.4 ± 16.8 years (range 17–75 years). Peak expiratory flow and dyspnea score significantly improved in group 1 patients compared with patients in the other groups after 2 hours of ED treatment (P = 0.021 and 0.009, respectively). The discharge rate after ED treatment was significantly higher in groups 1 and 3 than in group 2 (P = 0.05). All 73 patients were alive a week after enrollment. Five patients (20.8%) in the Flixotide treatment arm were hospitalized and required additional systemic steroids. Multivariate analysis of factors affecting hospitalization rate demonstrated that severity of asthma (odds ratio 8.11) and group 2 (OD[2] 4.17) had a negative effect, whereas adherence to chronic anti-asthma therapy (OD 0.49) reduced the hospitalization rate.

Conclusions: Our study cohort showed the advantage of nebulized steroid fluticasone versus systemic corticosteroids in adult asthmatics managed in the ED following an acute attack. Both these and previous results suggest that nebulized steroids should be used, either alone or in combination with systemic steroids, to treat adults with an acute asthma attack.

Background: The frequency of colorectal cancer screening tests in Israel is poor, and is much lower than in the United States. This low rate has been attributed to health system failures as well as to barriers on the part of both physicians and patients.

Objectives: To further identify particular health system failures, physician and patient-based barriers, and the effectiveness of public lectures in improving the frequency of performance of CRC[1] screening tests.

Methods: Public lectures on colorectal cancer prevention were held. A gastroenterologist presented the lectures, which were followed immediately by a questionnaire and 4 months later by a telephone call.

Results: Of the 80% of attendees who had never undergone any CRC screening test, only 18% reported family physician recommendations for such tests. Eighty-four percent reported willingness to undergo fecal occult blood testing and 52% to undergo colonoscopy; 62% replied that they should undergo some CRC screening test and 90% believed that these tests save lives. Of the women, 47% expressed preference for a female gastroenterologist. Follow-up showed that 34% proceeded to undergo some CRC screening test: 60% chose colonoscopy and 40% FOBT[2].

Conclusions: Public lectures are effective at improving compliance with the CRC screening test. Physicians should recommend these tests to appropriate individuals. Same-gender gastroenterologists should be considered for individuals uneasy about someone from the opposite gender performing the test. Assessing the various health-promotion efforts can direct us in implementing finite resources to greatest effect. Local cancer institutes and societies may be supportive in disseminating screening information in this way.

Background: Cardiac computed tomography angiography is a relatively new imaging modality to detect coronary atherosclerosis.

Objectives: To explore the diagnostic value of CTA[1] in assessing coronary artery disease among asymptomatic patients.

Methods: In this retrospective single-centered analysis, 622 consecutive patients underwent CTA of coronary arteries between November 2004 and May 2006 at the Mor Institute for Cardiovascular Imaging in Bnei Brak, Israel. All patients were asymptomatic but had at least one risk factor for atherosclerotic CAD[2]. The initial 244 patients were examined with the 16-slice Brilliance CT scanner (Philips, Cleveland, OH, USA), and in the remaining 378 patients the 64-slice scanner (GE Healthcare, The Netherlands) with dedicated cardiac reconstruction software and electrocardiography triggering was used. Scanning was performed in the cranio-caudal direction. Images reconstructed in different phases of the cardiac cycle using a retrospective ECG-gated reconstruction algorithm were transferred to a dedicated workstation for review by experienced CT radiologists and cardiologists.

Results: Of 622 patients, 52 (8.4%) had severe obstructive atherosclerosis (suspected ≥ 75% stenosis) according to CTA interpretation. Invasive coronary angiography was performed in 48 patients while 4 patients had no further procedure. A non-significant CAD (e.g., diameter stenosis < 70%) was identified in 6 of 48 patients (12%) by selective coronary angiography. Forty-two patients showed severe CAD with at least one lesion of ≥ 70% stenosis. Percutaneous coronary intervention was performed in 35 patients and coronary artery bypass grafting surgery in the other 4 patients. Angioplasty procedures were successful in all 35 patients and stents were utilized in all cases without complications. No further complications occurred among the study cohort undergoing either PCI[3] or surgery. The 6 month survival rate in these patients was 100%.

Conclusions: Non-invasive coronary CTA appears to be a reliable technique, with reasonably high accuracy, to detect obstructive atherosclerosis in asymptomatic high risk patients for atherosclerotic CAD.

The question of who discovered insulin is controversial. One of the scientists working on pancreas extracts was Nicolae Paulescu, the so-called Forgotten Man. In addition to his scientific research he was also active in politics. He was the father of the virulent antisemitic fascist movement “Garda de Fer” in Romania; he raved against the “Jewish Peril,” claimed in his writings that the Jews are a genetically degenerate people trying to cheat and poison the Rumanian people by alcoholism, and more. His name came up in 2003 when Romanian diabetologists initiated a move to honor him. But voices rose in protest, claiming that persons who incite hatred, support persecution and genocide and distort science as their political tools cannot be accepted or rewarded. The protesters won.

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

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 Drug-specific CD8+ TH1 lymphocytes have been found in the peripheral blood and involved skin of patients with drug-induced bullous exanthems.

Objectives To determine whether the interferon-gamma release test can identify culprit drugs in pemphigus patients.

Methods Clinical and laboratory workup for pemphigus was performed in 14 pemphigus vulgaris patients who had been exposed to drugs, and the IFNl[1] release test was conducted on their lymphocytes from heparinized venous blood cultured with medium, phytohemagglutinin and one of 32 drugs, or medium and phytohemagglutinin alone.

Results Ten of the patients and 13 of the 32 drugs exhibited a positive response to the test. Eight of the 10 patients with positive IFNl test results had a less severe course of the disease, with fast reduction in steroid dosage.

Conclusions The findings demonstrate both the ability of the IFNl release test to identify drugs that can induce pemphigus, and its usefulness in the diagnostic workup of pemphigus patients.