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Biomedical subjects

Rami Eliakim

Publications and source records attributed to Rami Eliakim.

At least 37 records · Page 2Linked to original sources
PubMed2005

Is age of onset of Crohn's disease governed by mutations in NOD2/caspase recruitment domains 15 and Toll-like receptor 4? Evaluation of a pediatric cohort.

Crohn's disease (CD) is caused by a combination of environmental and genetic factors. It is not clear at present whether age of onset (AOO) is a random event or dictated by genotype or environmental factors. Mutations in the NOD2/caspase recruitment domains 15 (CARD15) and in the Toll-like receptor 4 (TLR4) gene have been associated with increased susceptibility for CD. We sought to determine whether single or multiple mutations in these genes are linked to earlier susceptibility for CD. A cohort of 189 patients with CD (82 pediatric onset, 107 adult onset) were genotyped for three disease-associated single-nucleotide polymorphisms (SNPs), one haplotype association (JW1-SNP5), and one background polymorphism (P268S) of the NOD2/CARD15 gene and for two SNPs of TLR4. Analysis of heterozygosity, homozygosity, alleles, and haplotypes of cohort on age or pediatric onset was performed. AOO ranged from 8 mo to 68 y. The presence of the three NOD2/CARD15 and two TLR4 mutations, the NOD2/CARD15 JW haplotype, compound heterozygosity, and homozygosity were not associated with AOO. Presence of P268S in the absence of known NOD2/CARD15 mutations was correlated with increasing age and adult onset of CD, whereas pediatric-onset disease was associated with male gender and the wild-type NOD2/CARD15 haplotype. Mutations in NOD2/CARD15 and TLR4 are not significantly associated with AOO in our population. Mutations that are not in linkage disequilibrium with the background mutation P268S of the NOD2/CARD15 gene probably play a more significant role in pediatric-onset disease.

Adolescent↗
PubMed2004

Wireless capsule video endoscopy: three years of experience.

AIM: To review and summarize the current literature regarding M2A wireless capsule endoscopy. METHODS: Peer reviewed publications regarding the use of capsule endoscopy as well as our personal experience were reviewed. RESULTS: Review of the literature clearly showed that capsule endoscopy was superior to enteroscopy, small bowel follow through and computerized tomography in patients with obscure gastrointestinal bleeding, iron deficiency anemia, or suspected Crohn's disease. It was very sensitive for the diagnosis of small bowel tumors and for surveillance of small bowel pathology in patients with Gardner syndrome or familial adenomatous polyposis syndrome. Its role in celiac disease and in patients with known Crohn's disease was currently being investigated. CONCLUSION: Capsule video endoscopy is a superior and more sensitive diagnostic tool than barium follow through, enteroscopy and entero-CT in establishing the diagnosis of many small bowel pathologies.

Contraindications↗
PubMed2004

Neurological abnormalities associated with celiac disease.

BACKGROUND: Celiac disease (CD) is a gluten-sensitive enteropathy in genetically susceptible individuals. Anecdotal reports suggest that the nervous system might be affected in the disorder, but the severity and prevalence of such an involvement have not been systematically evaluated. MATERIALS AND METHODS: Analysis of files of CD patients diagnosed between 1980 and 1999 for neurological abnormalities. Diagnosis of CD was based on the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition. RESULTS: Of 148 CD patients, 18 (12%) had 21 neurological disorders that could not be attributed to any other condition including muscle abnormality (3), epilepsy (3), psychiatric disease (4), peripheral neuropathy (3), cerebrovascular disease (1), myelopathy (1) and Down syndrome (2). Other disorders probably unrelated to CD were present in 8 patients. CONCLUSION: If this association is not coincidental, both the central and the peripheral nervous systems may be affected in CD by a spectrum of neurological disorders that are either the outcome of CD or share the same pathogenesis with the enteropathy.

Adolescent↗
PubMed2004

Second capsule endoscopy for patients with severe iron deficiency anemia.

BACKGROUND: Patients with iron deficiency anemia are subjected to multiple endoscopic and radiologic examinations of the GI tract. If negative, some of the examinations are repeated, occasionally with positive findings. The diagnostic yield of a second capsule endoscopy in such patients is unknown. The aim of the current study was to assess the diagnostic yield of a second capsule endoscopy in patients with significant iron deficiency anemia and a previous negative evaluation. METHODS: Twenty patients with iron deficiency anemia (Hb < 10 g/dL) were enrolled. All had at least one normal evaluation of the GI tract, including capsule endoscopy. A second capsule endoscopy examination was offered to all patients. RESULTS: The time between the first and the second capsule endoscopy ranged from 2 months to 1 year. Depending on the nature of an abnormality and its relevance to blood loss, the findings were classified as positive, suspicious, clinically irrelevant, or negative. In 7 patients, the second capsule endoscopy disclosed findings that were classified as either positive or suspicious findings, including arteriovenous malformations (2), flat polypoid lesion (1), edematous inflamed mucosa (1), erosions (1), and hemorrhagic gastritis (1). Lesions were located in the small intestine (5), the stomach (1), and the cecum (1). Based on the findings of the second capsule endoscopy, therapy was changed in two patients (10%). CONCLUSIONS: A second capsule endoscopy should be considered for patients with severe iron deficiency anemia and negative initial evaluation.

Adult↗
PubMed2004

The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients.

Susceptibility to inflammatory bowel disease (IBD) has a strong genetic component. The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be associated with IBD in some studies. In this case-control study we determined the association between the BsmI VDR gene polymorphism and IBD in patients with Crohn's disease (CD) and ulcerative colits (UC). Three hundred seventy-nine Jewish Israeli patients with IBD, 228 with CD (129 Ashkenazi and 99 non-Ashkenazi), and 151 patients with UC (72 Ashkenazi, 79 non-Ashkenazi) were studied. The control group included 495 healthy blood donors (352 non-Ashkenazi and 143 Ashkenazi). All subjects were genotyped for the BsmI VDR gene polymorphism. The frequency of the BB genotype was higher in Ashkenazi patients with UC compared to Ashkenazi controls (0.21 vs. 0.11, p = 0.042, odds ratio 2.27, 95% confidence interval [CI] 1.06-4.9). There were no differences in the prevalence of the BB genotype or the B allele between ethnically matched patients with CD and UC. Nor were there differences in the BB genotype or B allele frequencies between CD patients and ethnically matched controls. The BsmI VDR gene polymorphism is associated with increased susceptibility to UC in Israeli Ashkenazi patients with UC.

Case-Control Studies↗
PubMed2004

Capsule endoscopy in real life: a four-centre experience of 160 consecutive patients in Israel.

OBJECTIVE: The Given Capsule procedure is a new system designed to aid the gastroenterologist in diagnosing small-bowel disease. Capsule endoscopy has provided gastroenterologists with easy access to small-bowel mucosa for examination by direct visualisation. The aim of our prospective study was to determine the indication for capsule endoscopy and to describe the identified pathology within the gastrointestinal tract. METHODS: Patients with unexplained gastrointestinal bleeding from suspected small-bowel pathology of an undisclosed nature or with unexplained abdominal pain for more than 6 months were eligible to undergo capsule endoscopy. Patients with suspected intestinal obstruction or with a history of major abdominal surgery were excluded. RESULTS: One hundred and sixty patients (70 women, 90 men; mean age 49.0 +/- 19.8 years, range 13-91 years) ingested the capsule easily. They had undergone 6 +/- 2.9 investigative procedures before capsule endoscopy. Two (1.25%) patients who had non-natural excretions underwent surgery: one was found to have Meckel's diverticulum and the other had stricturing Crohn's disease. The mean haemoglobin in iron-deficiency anaemia patients was 9.1 +/- 2.2 g%. The diagnostic yield of capsule endoscopy was 57.7% in iron-deficiency anaemia and 52.4% in suspected Crohn's disease. CONCLUSIONS: Capsule endoscopy detected the more clinically significant intestinal lesions. It was of diagnostic value in patients with obscure bleeding, suspected Crohn's disease and malabsorption, but the diagnostic yield in patients with chronic pain or irritable bowel syndrome-type symptoms was low.

Adolescent↗
PubMed2004

NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease.

OBJECTIVES: The etiology and mechanism leading to granuloma formation in patients with Crohn's disease (CD) are presently unknown. The first susceptibility gene to be identified as a risk factor for CD is the NOD2/CARD15 gene on Chromosome 16. Mutations in NOD2 could affect the intracellular response to bacterial products and may eventually lead to granuloma formation. The association between NOD2 and granulomas has not been previously explored. We evaluated a possible association between NOD2 mutations and granuloma formation, and compared the prevalence of granulomas in both pediatric and adult cohorts. METHODS: Patients were consecutively recruited through pediatric gastroenterology and adult gastroenterology programs. Patients were eligible if CD was confirmed, and they had undergone full colonoscopy with biopsy and/or surgical resection. Patients underwent genotyping for NOD2 disease-associated mutations. RESULTS: A total of 230 patients were enrolled into the study, of whom 169 patients met all inclusion/exclusion criteria (Group 1, 77 patients [age range 1-16 years]; Group 2, 92 patients [age range 17-68 years]). Surgical resection was performed more often in adults (P < 0.005), and gastroscopy was performed more frequently in children (P < 0.001). Granulomas were found in 34% of the patients studied. The prevalence of granulomas did not differ by age, age group, or gender. A disease-associated NOD2 mutation was found in 37.8% of patients. Granulomas were found in 39% of patients with NOD2 mutations compared with 31% of those without NOD 2 mutations (difference was not significant). In addition, no difference was noted for the specific mutations. CONCLUSIONS: We did not find any correlation between NOD2 mutations and granuloma formation. The cause of granulomas in CD remains elusive.

Adolescent↗
PubMed2004

NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease.

OBJECTIVE: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations. METHODS: Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined. RESULTS: The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1% versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients. CONCLUSIONS: NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.

Adolescent↗
PubMed2004

The month of birth is linked to the risk of Crohn's disease in the Israeli population.

OBJECTIVE: The main objective is to study whether the month of birth is associated with the development of Crohn's disease (CD) in the Israeli Jewish population. BACKGROUND: It was suggested that perinatal exposure to infectious agents may have a role in the pathogenesis of CD. Due to the seasonal nature of some infections, a linkage between birth dates and a risk to develop CD would support such a hypothesis. Previous studies that addressed this question were conducted in Europe and differed in their findings. METHODS: Birth dates of 844 Jewish ulcerative colitis (UC) and CD patients from three medical centers representing the north, central, and the south of Israel were compared with the monthly rates of birth during the same period of time. The standard incidence ratio was used to define the risk to develop either disease according to the month of birth. The Score method was used for the evaluation of seasonality trends. RESULTS: Birth during the winter period in Israel was associated with increased risk to develop CD, whereas birth during the spring was associated with a reduced risk. The Score method for seasonality showed a significant peak during winter time in these patients (z = 2.02, p= 0.021). No such seasonal variation was noted for UC patients. CONCLUSIONS: A seasonal pattern was observed in the risk to develop CD but not UC. The findings may support the involvement of environmental factors in the pathogenesis of CD.

Adult↗
PubMed2003

Wireless capsule video endoscopy is a superior diagnostic tool in comparison to barium follow-through and computerized tomography in patients with suspected Crohn's disease.

BACKGROUND: The recently introduced wireless M2A capsule video endoscopy (CVE) has been demonstrated to be superior to barium follow-through and enteroscopy in diagnosing patients with occult blood loss and iron-deficiency anaemia. OBJECTIVE: To further investigate CVE in comparison to barium follow-through and entero-computerized tomography (CT) in establishing the diagnosis of patients with suspected Crohn's disease. DESIGN AND SETTING: The study was conducted in one academic hospital. Twenty patients with recurrent abdominal pain and/or weight loss or chronic diarrhoea underwent barium follow-through as their initial examination, followed by CVE (if there was no stricture) and entero-CT. The radiologist that performed the barium follow-through and entero-CT was blinded to the results of the CVE. A blinded reader who was unaware of the study objective diagnosed the results of the CVE. In most cases in which there was a discrepancy between examinations, colonoscopy and ileoscopy were performed. For each patient, the diagnosis and disease extent were recorded. RESULTS: Twenty patients (13 males, 7 females; mean age 31 years, range 20-57) were included in the study. Ninety-five per cent of the patients had abdominal pain, 75% had diarrhoea, and 65% had weight loss. The mean haemoglobin level of the group was 13.1 g% (range 10-15.5). Only 13 patients underwent entero-CT.CVE confirmed the diagnosis of Crohn's disease that was suspected by alternative methods in six of the 20 patients. CVE made the diagnosis of Crohn's disease in six patients that had normal barium follow-through or entero-CT. CVE ruled out a diagnosis of Crohn's disease suspected by other modalities in three patients. CVE extended the involvement of Crohn's disease in three of the patients, and established new diagnoses in two patients. SUMMARY: CVE established new diagnoses, confirmed existing diagnoses, enlarged the extent of the disease, and ruled out the suspicion of Crohn's disease in 70% of the patients. Barium follow-through established diagnoses, measured the extent of the disease, and ruled out the suspicion of Crohn's disease in 37% of the patients. The capsule detected all of the lesions diagnosed by barium follow-through and entero-CT. CVE detected additional lesions that were not detected by other modalities in 47% of cases and ruled out lesions that were detected by other modalities in 16% of cases (P < 0.05). CONCLUSION: CVE is a superior and more sensitive procedure than barium follow-through and entero-CT in establishing the diagnosis and estimating the extent of Crohn's disease.

Adult↗
PubMed2003

Divergent effects of nicotine administration on cytokine levels in rat small bowel mucosa, colonic mucosa, and blood.

BACKGROUND: Chronic nicotine administration has a dual effect on inflammatory bowel disease: augmentation of jejunitis and amelioration of colitis. We previously showed that chronic nicotine administration has divergent regional effects on small bowel and colonic mucosal mediators and blood flow. OBJECTIVE: To examine the effects of nicotine administration on cytokine levels in normal rat small bowel mucosa, colonic mucosa, and blood. METHODS: Male Sprague-Dawley rats weighing 200-250 g were given nicotine (12.5 micrograms/ml) that was dissolved in tap water. Rats were sacrificed on days 1, 2, 7 and 14 after nicotine initiation; blood was withdrawn, and small bowel and colon were resected, washed and weighed. Mucosal scrapings were extracted in 2 ml Krebs-Hemselest buffer for determination of interleukins-2, 6 and 10 using the Biosource International Immunoassay Kit. RESULTS: Nicotine decreased IL-10 and increased IL-6 levels in small bowel mucosa (from 3.5 +/- 0.5 to 0.4 +/- 0.1 pg/ml and from 1.9 +/- 0.4 to 13.6 +/- 0.4 pg/ml respectively; P < 0.05). Nicotine decreased IL-2 levels in the colon (from 15.8 +/- 3.0 to 7.9 +/- 1.0 pg/ml; P < 0.05), having no effect on IL-10 or IL-6 levels. Rats treated with nicotine had lower IL-6 and IL-2 blood levels compared to control rats. CONCLUSIONS: Nicotine has different regional effects on small bowel and colonic cytokine mucosal levels, which might explain some of its opposite effects on small bowel and colonic inflammation.

Administration, Oral↗
PubMed2003

[Virtual colonoscopy in real life--is it that good?].

BACKGROUND: Colon cancer is the main cause of mortality among the gastrointestinal cancers in Israel. Early detection of the average risk population is recommended from the age of 50 to 75 years. Private departments of radiology aggressively advertise virtual colonoscopy for the early detection of colon cancer, although it is not recognised as such in any country. METHODS: We collected all cases in which virtual colonoscopy was followed by endoscopic colonoscopy in the same patient from four medical centers in Israel. RESULTS: Total discrepancy between the results of the two examinations was found in 2/3 of the patients. In some cases colon cancer was missed. CONCLUSIONS: The results presented herein, raise many questions and "red lights" as to the use of virtual colonoscopy in its present form for screening purposes in Israel unless it is in the setting of clinical research.

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