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Biomedical subjects

Rami Eliakim

Publications and source records attributed to Rami Eliakim.

At least 19 recordsLinked to original sources

Ferrus calcium citrate is absorbed better than iron bisglycinate in patients with Crohn's disease, but not in healthy controls.

Our purpose was to compare the absorption of iron bisglycinate and ferrous calcium citrate in volunteers using an oral iron tolerance test. Twenty volunteers, 10 healthy controls and 10 with stable Crohn's disease, agreed to participate in the study. All were given 50 mg of elemental iron as iron bisglycinate or ferrous calcium citrate. Serum iron levels were monitored for 4 hr. After a week, each received the other regimen. Using the area under the curve as indicator, the oral iron absorption test revealed that absorption of iron post-ingestion of ferrous calcium citrate was better than after ingestion of iron bisglycinate for the group as a whole (P < 0.03). Volunteers with Crohn's disease absorbed ferrous calcium citrate better than iron bisglycinate (P=0.005). No difference was noted in the absorption of either preparation by healthy volunteers. Ferrus calcium citrate is apparently more effective than iron bisglycinate in patients with Crohn's disease.

Adult↗

Polymorphisms in the TNF-alpha promoter and variability in the granulomatous response in patients with Crohn's disease.

Granulomas may be found in 30-70% of patients with Crohn's disease (CD). The etiology of granuloma formation in CD is presently unknown. Elevated levels of TNF-alpha are found within granuloma tissue, and are required to maintain granuloma formation in animal models. TNF-alpha production has been shown to influenced by TNF-alpha promoter polymorphisms. We hypothesized that heterogeneity for granulomas in CD might be influenced by the TNF-alpha promoter genotype. Patients with confirmed CD that had undergone full colonoscopy with multiple biopsies and/or surgical resection, served as the study group. One hundred healthy individuals served as a control population for genotyping. Patients and controls underwent genotyping for four TNF-alpha polymorphisms: 238G/A, 308 G/A,857 C/T, and 863 C/A. Inclusion and exclusion criteria were met in 155 patients (1-68 y). Polymorphisms in the TNF promoter were found in 16.6% (238G/A), 14.5% (308 G/A), 36.6% (857 C/T) and 30.7% (863G/A). No significant association was found for any of the individual polymorphisms with presence or absence of granulomas. In conclusion, we did not find an association between individual polymorphisms in the TNF-alpha promoter and presence of granulomas in CD. The reason for heterogeneity in granuloma formation in patients with CD remains elusive.

Adult↗

Probiotics and the gastrointestinal tract: where are we in 2005?

Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.

Diarrhea↗

Eradication of Helicobacter pylori can be accurately confirmed 14 days after termination of triple therapy using a high-dose citric acid-based 13C urea breath test.

BACKGROUND: Confirmation of Helicobacter pylori eradication by urea breath test (UBT) is currently performed 4-6 weeks after completion of therapy because of unacceptable false-negative results in UBTs performed earlier. Use of a high-dose citric acid test meal appears to enable accurate detection of H. pylori even during short term therapy with proton pump inhibitors. AIM: To evaluate if use of a high dose citric acid (4.0 g) test meal can decrease the interval required for confirmation of eradication after triple therapy. METHODS: 233 patients positive for H. pylori were randomized to undergo UBT at 7 days or 14 days after triple therapy, and again at 6 weeks. The latter test was considered the gold standard test. RESULTS: The UBT performed 6 weeks after the end of treatment found that 79.9% were cured. The same test 7 days after therapy found false-negative detection of H. pylori in 7.3% patients compared to 3.2% patients examined after 14 days. The sensitivity, specificity, positive and negative predictive values and accuracy for evaluation on day 14 were 80, 100, 100, 96.3 and 96.7%, respectively. CONCLUSIONS: High-dose citric acid-based UBT is a valid test for the assessment of H. pylori status 14 days after triple therapy. This may obviate the delay in instituting second-line eradication therapy, or further evaluation of the symptomatic patient unresponsive to therapy despite eradication.

Adolescent↗

Paraoxonases (PONs) 1, 2, and 3 are expressed in human and mouse gastrointestinal tract and in Caco-2 cell line: selective secretion of PON1 and PON2.

The paraoxonase (PON) family contains three genes (PON1/2/3) that are believed to be involved in the protection against oxidative stress. PON1 and PON3 are circulating in serum attached to high-density lipoprotein fraction (HDL), whereas PON2 is ubiquitously expressed. The intestine is the second major organ that synthesizes lipoproteins; therefore, we examined PON mRNA expression and protein levels in gastrointestinal biopsies from humans, from C57BL6 mice, and from Caco-2 cells, a colon carcinoma-derived cell line that exhibits properties of intestinal epithelium at differentiation. PON 1/2/3 mRNA and proteins were present in human biopsies with variable expression among different gastrointestinal segments. Only PON2 and PON3 were present in mice. All PON mRNA, proteins, and enzymatic activities were present in Caco-2 cells. Oxidation of CaCo-2 cells with ferrum ascorbate had no significant effect on PON mRNA expression, but it increased paraoxonase and lactonase activity, whereas statinase activity was decreased. We showed polarized secretion of PON1 (basolateral) and PON2 (apical) into Caco-2 culture medium, raising the possibility that intestine is capable of producing and releasing PON1 and PON3 to the circulation, whereas PON2 is released at the brush-border membrane to intestinal lumen where it may perform another yet unclear function.

Animals↗

Minidose aspirin and gastrointestinal bleeding--a retrospective, case-control study in hospitalized patients.

Low or minimal doses of aspirin are widely used for prevention of cardiovascular diseases. Aspirin is known to produce severe adverse gastrointestinal effects, such as bleeding and perforation. Less is known about the risk associated with minidose aspirin. Our aim was to assess the possible association of upper gastrointestinal tract bleeding with minidose aspirin therapy. A retrospective controlled design was used. Patients hospitalized for melena or hematemesis between January 1, 2000, and December 31, 2001, were identified by ICD-9 codes, and their clinical findings were compared to these of patients without upper gastrointestinal bleeding hospitalized during the same period and matched for age and sex. Bleeding was attributed to therapy if patients used a nonsteroidal anti-inflammatory drug or aspirin therapy within 30 days before hospitalization. The study group included 318 patients (59% male), and the control group 141 (65% male). Mean ages were 67 +/- 19 and 64 +/- 19 years, respectively. Study patients had more accompanying diseases, used more medications, and required more blood transfusions than controls (37%, vs. 2% of controls; P < 0.001). Minidose aspirin was used by 28% of the study group and 18% of the controls (P = 0.03). The average dose was 40 +/- 86 and 21 +/- 55 mg/day, respectively (P = 0.012). Only 26% of the study patients received a gastric protective agent. On multivariate analysis, aspirin consumption was the only independent risk factor for upper gastrointestinal tract bleeding. There appears to be an association between minidose aspirin treatment and hospitalization for upper gastrointestinal tract bleeding. Despite the advanced age of the patients, only one-quarter were treated with gastric protective agent.

Aged↗

The relation between NOD2/CARD15 mutations and the prevalence and phenotypic heterogeneity of Crohn's disease: lessons from the Israeli Arab Crohn's disease cohort.

The prevalence of Crohn's disease depends on geographic location and racial background. Arg702Trp, Gly908Arg, and Leu1007fsinsC mutations in the NOD2/CARD15 gene are associated with Crohn's disease in Caucasians. The mutation rate among Israeli Jewish patients is 27%-41%. The prevalence of Crohn's disease is much lower in the Israeli Arab compared to the Israeli Jewish population. We studied the NOD2/CARD15 mutation rate and disease phenotype (according to the Vienna classification) among the Israeli Arabs and compared them with those in an Israeli Jewish cohort. We recruited 66 Israeli Arab patients and 122 ethnically matched controls. Five patients (8.2%) and three controls (2.3%) carried one NOD2/CARD15 mutation. The phenotypic characteristics of the Arab and Jewish patients were very similar. We conclude that NOD2/CARD15 mutations do not contribute to Crohn's susceptibility in the Israeli Arab population and suggest that NOD2/CARD15 mutations have an important effect on Crohn's prevalence within a specific population but not on the phenotype.

Adult↗

A prospective study of the diagnostic accuracy of PillCam ESO esophageal capsule endoscopy versus conventional upper endoscopy in patients with chronic gastroesophageal reflux diseases.

INTRODUCTION: Endoscopy is commonly performed to evaluate for suspected or established esophageal diseases including gastroesophageal reflux disease (GERD) and its complications. The newly developed PillCam ESO Esophageal Capsule offers an alternative approach to visualize the esophagus and to evaluate patients with suspected esophageal disease. AIM: Compare the accuracy (specificity, sensitivity, positive predictive value [PPV], and negative predictive value [NPV]) of esophageal capsule endoscopy (ECE) compared with esophagogastroduodenoscopy (EGD) in evaluating patients with GERD. METHODS: A multicenter pivotal trial was conducted at seven sites. The PillCam ESO esophageal capsule is similar to the standard capsule endoscope used for the small bowel but acquires video images from both ends of the device at 2 frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE followed by EGD. ECE videos were evaluated by an investigator blinded to EGD findings. A blinded adjudication committee reviewed all discrepant findings between ECE and EGD. RESULTS: Sixty-six of 106 patients had positive esophageal findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%; specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by all patients. There were no adverse events related to ECE. CONCLUSIONS: ECE is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease.

Endoscopy, Gastrointestinal↗

A polymorphism in the TNF-alpha promoter gene is associated with pediatric onset and colonic location of Crohn's disease.

OBJECTIVES: Studies suggest that pediatric onset of Crohn's disease (CD) may demonstrate more frequent upper intestinal and colonic location and in male gender, in comparison to adults. Variability in age of onset (AOO) and location of disease have not been adequately explained to date. NOD2/CARD15 is highly expressed in the ileum, while TNF-alpha expression is distributed throughout the gastrointestinal tract. We hypothesized that polymorphisms that affect TNF-alpha function may influence variability of disease location and AOO of CD. METHODS: We evaluated two CD cohorts based on AOO (pediatric and adult onset) and 100 ethnically matched healthy controls. Patients were evaluated for AOO, disease location, and genotyped for the presence of polymorphisms in NOD2/CARD15 and in the TNF-alpha promoter region. RESULTS: Early AOO was associated with male gender, upper intestinal involvement, and a polymorphism in the binding site for NF-kappaB (TNF-863A polymorphism). NOD2 mutations and TNF-863A polymorphism had equivalent but opposite effects on disease location, with a strong combined effect (p= 0.004 corrected for multiple testing). NOD2/CARD15 was associated with ileal involvement, while presence of TNF-863A was inversely associated with ileal disease (OR = 0.42, p= 0.008) and positively associated with isolated colitis (OR = 2.16, p= 0.008, OR = 2.12, p= 0.03 corrected) and familial disease (p= 0.004). CONCLUSIONS: Pediatric onset of CD in our population was associated with a frequent polymorphism in the binding site for NF-kappaB in TNF-alpha promoter but not to defined NOD2/CARD15 disease-associated mutations. This polymorphism is associated with colitis and familial disease. NOD2/CARD15 mutations and the TNF-863C/A polymorphism have equivalent but opposite effects on disease location. These findings may help explain differences in CD phenotype.

Adult↗

Esophageal varices: evaluation with esophagography with barium versus endoscopic gastroduodenoscopy in patients with compensated cirrhosis--blinded prospective study.

PURPOSE: To prospectively evaluate the accuracy of esophagography with barium in diagnosis of esophageal varices (EV) in patients with compensated cirrhosis, with endoscopic gastroduodenoscopy as the reference standard. MATERIALS AND METHODS: In this study, which was approved by the local Helsinki Committee and in which all patients consented to participate, 61 patients with cirrhosis (34 men, 27 women; mean age, 61 years; range, 36-76 years) received a diagnosis clinically or with liver biopsy. In 87% (n = 53) of patients, Child-Pugh classification was A; in 13% (n = 8), Child-Pugh classification was B. They were evaluated with endoscopic gastroduodenoscopy, according to Japanese general criteria. Esophagography was performed within 3 weeks of endoscopic gastroduodenoscopy, and EV were assigned grades as follows: 0, no EV were seen; 1, EV manifested as very mild irregularities of the folds; and 2, the irregularity of the folds (EV) was clearly present. They were also assigned grades for shape and size: grade F0, no EV detected; grade F1, small straight EV; grade F2, slightly enlarged tortuous EV occupying less than one-third of esophageal lumen; and grade F3, large coil-shaped EV that occupied more than one-third of esophageal lumen. The sensitivity and specificity and positive and negative predictive values of esophagography for identification of each grade of EV were calculated separately, as was the 95% confidence interval. RESULTS: All large EV (grades F2 and F3) were diagnosed at esophagography. Sensitivity declined with small EV (grade F1) to 71. The overall sensitivity of esophagography was 89% (95% confidence interval: 75.9%, 96.5%), the overall specificity was 83% (95% confidence interval: 64.5%, 94.7%), the overall positive predictive value was 89%, and the overall negative predictive value was 83% (95% confidence interval: 64.5%, 94.7%). Overall accuracy was 87%. CONCLUSION: Esophagography is highly accurate in diagnosis of EV and can be considered a viable noninvasive alternative for determination of patients who should be selected for prophylactic treatment.

Adult↗

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↗

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↗

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↗

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↗

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↗