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עמוד בית
Sun, 23.06.24

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July 2015
Einat Fireman-Klein MD, Avraham Man MD, Yehuda Schwartz MD and Elizabeth Fireman PhD

Background: Determining the accuracy of interferon gamma-releasing assays (IGRAs) is difficult due to the lack of a gold standard test for diagnosing latent tuberculosis (LTB). 

Objectives: To analyze the guidelines used for interpreting IGRAs in determining prophylactic treatment management for latent tuberculosis (LTB) in Israel.

Methods: We analyzed the retrospective data of 367 subjects who were referred to our laboratory during the period 2007–2011 for QuantiFERON Test-Gold In Tube (QFT-GIT) tests because of suspected LTB. Demographics and clinical data were retrieved from a questionnaire at enrollment, and 166/367 (45%) were further interviewed by phone in order to complete follow-up information on prophylactic TB treatment. 

Results: The majority of subjects (116/166, 69.9%, P < 0.0001) were spared prophylactic treatment subsequent to QFT-GIT testing. Subjects with negative QFT-GIT and positive tuberculin skin test (TST) results who were BCG-vaccinated had the lowest treatment rates (6/68, 8.8%, P < 0.0001). Most BCG-vaccinated subjects with positive TST and negative QFT-GIT test results received treatment with anti-tumor necrosis factor-alpha (TNFα) (17/19, 89.5%, P = 0.004). We found more negative QFT-GIT test results in subjects who were receiving anti-TNFα or steroid and other immunosuppressive treatment prior to testing (11/11, 100%, P = 0.029; 22/26, 84.6%, P = 0.06; 15/17, 88%, P = 0.06, respectively). 

Conclusions: Deciding on LTB prophylactic treatment in Israel is highly influenced by QFT-GIT test results. QFT-GIT findings contribute to clinical decisions, but their interpretation must also consider the patient’s medical history and clinical characteristics. 

 

April 2008
Z. Fireman and Y. Kopelman

Capsule endoscopy was launched at the beginning of this millennium and has since become a well‑established tool for evaluating the entire small bowel for manifold pathologies. CE[1] far exceeded our early expectations by providing us with a tool to establish the correct diagnosis for such elusive gastrointestinal conditions as obscure gastrointestinal bleeding, Crohn's disease, polyposis syndrome and others. Recent evidence has shown CE to be superior to other imaging modalities – such as small bowel follow‑through X-ray, colonoscopy with ileoscopy, computerized tomographic enterography, magnetic resonance enteroclysis and push enteroscopy – for diagnosing small bowel pathologies. Since the emergence of CE, more than 500,000 capsules have been swallowed worldwide, and more than 700 peer-reviewed publications have appeared in the literature. This review summarizes the essential data that emerged from these studies.






[1] CE = capsule endoscopy


February 2006
Z. Fireman, R. Zachlka, S. Abu Mouch and Y. Kopelman

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

December 2005
S. Kivity, E. Fireman, K. Sade.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

K. Sade, S. Kivity, E. Fireman, Y. Schwartz, S. Kivity.

Background: The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active part in the late allergic response.

Objectives: To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who were given the drug for 4 weeks.

Methods: Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment.

Results: During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE‑induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 ± 550 pg/ml at baseline to 2225 ± 430 pg/ml at 4 weeks, P = 0.02).

Conclusions: Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

September 2004
Z. Fireman, Y. Kopelman, L. Fish, A. Sternberg, E. Scapa and E. Mahajna

Background: During ingestible capsule endoscopy, video images are recorded throughout the device's natural propulsion through the digestive system. Shortening the transit time of the wireless video capsule through the stomach and small bowel could reduce the time needed to read and analyze the resultant images, utilize more effectively the short life of the capsule battery (7 ± 1 hours) and make it possible to image the entire small bowel.

Objective: To measure gastric and small bowel transit times, with and without preparation, using capsule endoscopy.

Methods: Capsule transit times through the stomach, small bowel and colon were evaluated by analysis of the videos generated during the capsule's passage. The study group included 62 patients with small and large bowel pathologies (e.g., iron deficiency anemia, Crohn's disease). The patients were divided into three groups: prepared with polyethylene glycol (Group A, n = 9), prepared with sodium phosphate (Group B, n = 13), and with no preparation (Group C, n = 40).

Results: The gastric emptying times were 20.4 ± 15.2 minutes in group A, 55.7 ± 45.1 in group B, and 48.3 ± 28.7 in group C (P = 0.01). The capsule produced views of the cecum in only 49 of the 62 patients. The mean small bowel transit time for these 49 patients was 238.8 ± 82.1 minutes, making the mean times for the groups (A,B,C) 148.9 ± 32.6, 289.4 ± 77.2 and 249.3 ± 73.9 minutes respectively (P = 0.0001).

Conclusion: Compared to both SP[1] and no preparation, preparation of the colon with PEG[2] significantly shortened the transit time of the capsule through the stomach and small bowel.







[1] SP = sodium phosphate

[2] PEG = polyethylene glycol


July 2003
E. Fireman

The induced sputum technique allows sampling of the airways in a non-invasive manner and thus offers a unique opportunity to identify biomarkers of potential clinical utility in respiratory medicine. Sputum cells were originally examined in stained smears and the procedure was applied in both research and clinical settings from the 1950s through the 1970s. The cells, recovered from spontaneous coughing, were used to study lung cancer and respiratory infections and, later on, to diagnose Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. The method was largely improved by the induction of sputum with aerosol of hypertonic saline and was extended to become part of the assessment of airway inflammation in bronchial asthma and chronic obstructive pulmonary disease. It was recently shown that induced sputum can be used to study interstitial lung diseases and, more specifically, sarcoidosis, non-granulomatous ILD[1], occupational lung diseases and other systemic diseases with lung involvement.

____________________________________


[1] ILD = interstitial lung diseases

September 2002
Zvi Fireman, MD, Arkady Glukhovsky, PhD, Harold Jacob, MD, FACG, Alexandra Lavy, MD, Shlomo Lewkowicz, DSc and Eitan Scapa, MD
March 2001
Elizabeth Fireman, MD, Mordechai R. Kramer, MD, Nathan Kaufman, MD, Joachin Muller-Quernheim, MD and Yehuda Lerman, MD, MPH
August 2000
Timna Naftali MD, Ben Novis MD, Itamar Pomeranz MD, George Leichtman MD, Yaakov Maor MD, Rivka Shapiro MD, Menachem Moskowitz MD, Beni Avidan MD, Yona Avni MD, Yoram Bujanover MD and Zvi Fireman MD

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients.

Objectives: To review the current experience of six hospitals in central Israel that used cyc-losporin in patients with severe ulcerative colitis.

Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests.

Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9–28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4–14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn.

Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.

January 2000
Zvi Fireman MD, Leonid Trost MD, Yael Kopelman MD, Arie Segal MD and Amos Sternberg MD

Background: Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa.

Objectives: To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease.

Methods: The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9.

Results: H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P=0.05). A significant correlation was found between CA 19-9 (γ=0.3432, n=49, P=0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer.

Conclusions: The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.
 

December 1999
Zvi Fireman MD, Victor Gurevich MD, Daniel Coscas MD, Yael Kopelman MD, Arie Segal MD and Amos Sternberg MD
 Background: Chronic occult blood loss from the gastrointestinal tract is widely accepted as a major cause of iron deficiency anemia.

Objectives: To evaluate the diagnostic yield of gastroscopy, colonoscopy and fecal occult blood testing of hospitalized IDA patients, plus follow-up.

Methods: IDA was defined as hemoglobin <12.5 g/dl (men) and 11 g/dl (women), and serum iron <50 g/dl. The study group comprised 90 patients (42% male) with a mean age of 65±15 years and mean Hb 8.1 g/dl.

Results: Gastroscopy and colonoscopy revealed a bleeding source in 28.8% and 14.4% respectively. Gastrointestinal symptoms were found in 23% of patients with diseases of the upper gastrointestinal tract and in 15.3% of the lower. The sensitivity of fecal occult blood tests in detecting lesions in the lower and upper GI tracts was 100% and 30.7% respectively. Forty-four patients (48.9%) were discharged from the hospital with IDA of unknown origin. Over the following year, 20 of the 44 patients required further hospitalization, and of these, 13 were found to have anemia. Of the remaining 24 patients who were not hospitalized again, 15 had anemia. Four patients (9%) had significant gastrointestinal lesions and two died during the follow-up.

Conclusions: Fecal occult blood is a sensitive examination for lower but not for upper GI tract lesions.

__________________________________ 

IDA= iron deficiency anemia

October 1999
Shmuel Kivity MD, Amir Onn MD, Yoel Greif MD, Elizabeth Fireman PhD, Shmuel Pomeranz MD and Marcel Topilsky MD
 Background: Nedocromil sodium confers both acute and chronic protective effects in patients with bronchial asthma, the interactions of which are unknown.

Objective: To examine to what extent and for how long nedocromil sodium prevents exercise-induced asthma when given immediately before exertion compared to chronic administration.

Patients and Methods: Eighteen asthmatic patients were given 4 mg NS at 30 min or 3.5 hours before exertion. We compared the resultant effect with that of the same protocol measured after 2 and 4 weeks of continuous treatment with the drug.

Results: Nedocromil sodium decreased exercise-induced asthma similarly at both points when given acutely. Chronic treatment of up to 4 weeks did not improve this protective effect at either interval following the inhalation.

Conclusion: Nedocromil sodium most likely reaches its maximal effect on exercise-induced asthma upon the first administration, although treatment for longer than 4 weeks might be required to prove a chronic effect of the drug.

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