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Arie Levine

Publications and source records attributed to Arie Levine.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Encephalopathy associated with Hashimoto thyroiditis: pediatric perspective.

In recent years, neuropsychiatric symptoms associated with Hashimoto thyroiditis have been increasingly recognized in both adult and pediatric patients. This neurologic complication has been termed "Hashimoto encephalopathy," and it can begin abruptly, in the form of seizures or agitation, with or without other neurologic complaints, or it can develop gradually, in a relapsing-remiting manner, including, among others, cognitive deterioration and psychiatric illness. The occurrence of Hashimoto encephalopathy is unrelated to the patient's thyroid function status. Although the pathogenesis of this encephalopathy is not fully understood, evidence for both autoimmune and vasculitic mechanisms exists. Owing to a low index of suspicion, this encephalopathy is very likely underdiagnosed in children. The diagnosis of Hashimoto encephalopathy is based on detecting antithyroid antibodies in these patients, although there is no correlation between antibody levels and the severity of the illness. Cerebrospinal fluid analysis, electroencephalography, and neuroimaging studies do not show consistent findings to support the diagnosis. Physicians' awareness of this complication is of great importance because most patients respond dramatically to corticosteroid therapy. Moreover, early recognition might also avoid an expensive diagnostic work-up in patients with unexplained encephalopathy (J Child Neurol 2006;21:1-5).

Acute Disease↗
PubMed2006

Fat intolerance in developmentally impaired children with severe feeding intolerance.

Children with a variety of genetic, metabolic, and neurologic disorders can suffer from severe feeding intolerance that is unresponsive to medical, surgical, and nutritional therapy. Developmentally disabled tube-fed children with severe upper gastrointestinal symptoms that persisted after fundoplication who were unresponsive to all medical, surgical, and nutritional interventions underwent a thorough gastrointestinal evaluation, including gastroscopy, pH-metry, upper gastrointestinal barium series, and gastric emptying studies. They were placed on a low-fat diet, and the symptoms before and after the diet were compared. The patients were then rechallenged with incremental increases in fat until the symptoms recurred or the patients reached their former fat concentration. Six children meeting the study criteria were evaluated. Four of these patients had a significant improvement in symptoms, oral intake and feeding tolerance with a decrease in fat intake, and relapse of symptoms when fat calories were increased. Improvement occurred in children who had been intolerant to duodenal feeding. We were subsequently able to wean two children from tube feeding. Dietary fat can provoke upper gastrointestinal symptoms in children with gastric and intestinal dysmotility. Short-term manipulation of dietary fat intake can improve tolerance to feeding.

Child, Preschool↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn's disease.

OBJECTIVES: Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype. METHODS: Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed. RESULTS: Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity. CONCLUSION: Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.

Adenine↗
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

Application of Maastricht 2-2000 guidelines for the management of Helicobacter pylori among specialists and primary care physicians in israel: are we missing the malignant potential of Helicobacter pylori?

BACKGROUND: The Maastricht 2-2000 guidelines on the current management of Helicobacter pylori infection were recently adopted by the Israeli Gastroenterological Association. GOAL: To determine the impact of these clinical guidelines on the current knowledge, attitudes, and management of H. pylori among primary care physicians, hospital internists, and gastroenterologists in Israel. STUDY: Self-administered, voluntary, anonymous questionnaires were given personally to 229 physicians, 73 primary care physicians, 71 internists, and 85 gastroenterologists. The questions evaluated 4 main issues in the management of H. pylori: (1). the optimal diagnostic test, (2). indications for eradication, (3). combination and duration of triple therapy, and (4). the need for confirmation following eradication. RESULTS: There were significant variations in the adherence of those recommendations among gastroenterologists, internists, and primary care physicians. Specifically, 94.1% of gastroenterologists and 88.9% of internists consider the urea breath test the test of choice for H. pylori diagnosis compared with 60.0% of the primary care physicians. Significant differences in the eradication indications for mucosa-associated lymphoid tissue (MALT) lymphoma, first-degree relatives of gastric cancer patients, atrophic gastritis, functional dyspepsia, and concomitant use of nonsteroidal antiinflammatory drugs were demonstrated among gastroenterologists and the other groups. CONCLUSIONS: Primary care physicians may not be aware of important indications for diagnosis and eradication of H. pylori related to the risk of gastric malignancy or concomitant use of nonsteroidal antiinflammatory drugs. Public health agencies may need to increase penetration of the Maastricht 2000 recommendations to primary care physicians.

Amoxicillin↗
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

Influence of Helicobacter pylori eradication on gastroesophageal reflux symptoms and epigastric pain in children and adolescents.

OBJECTIVE: Conflicting reports have noted a possible association linking eradication of Helicobacter pylori with aggravation of gastroesophageal reflux (GER) disease. We prospectively evaluated the effect of eradication of H pylori on GER symptoms and epigastric pain and the association among these 3 parameters in a pediatric cohort. METHODS: Patients who were referred for gastroscopy were evaluated for frequency, severity, and nocturnal presence of symptoms related to GER as well as epigastric pain. Patients who were positive for H pylori received triple antibiotic therapy. The patients were followed for at least 6 months after therapy. Patients with successful eradication had symptoms compared with their pre-eradication state and were compared with a cohort of patients without H pylori or those with persistent H pylori. RESULTS: Of 119 children and adolescents who were recruited, 95 patients completed the study, with a mean follow-up of 11.2 months. The distribution of outcomes for each GER symptom (better, worse, unchanged) was similar before and after eradication and did not depend on prior H pylori status. Among patients with GER and epigastric pain, improvement in epigastric pain was significantly correlated with the improvement in GER symptoms but not with eradication of H pylori. CONCLUSIONS: Eradication of H pylori is not associated with increased symptoms of GER in children and adolescents. Improvement in epigastric pain in children is significantly correlated with the improvement in GER symptoms but not with eradication of H pylori.

Abdominal Pain↗
PubMed2004

Pediatric Crohn's disease and growth retardation: the role of genotype, phenotype, and disease severity.

BACKGROUND: Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity. METHODS: Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed. RESULTS: NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively). CONCLUSIONS: Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.

Child↗
PubMed2003

Severity of acid gastroesophageal reflux assessed by pH metry: is it associated with respiratory disease?

About 50% of children with chronic respiratory diseases (RD) have "silent" gastroesophageal reflux (GER). Our purpose was to evaluate the possibility that RD in patients with GER reflects the presence of more severe acid reflux. We compared the severity of parameters from pH studies in children with chronic RD and "silent" GER, to children with signs of symptomatic gastrointestinal (GI) GER with and without RD. This study included 236 children (aged 1 month to 15 years) with abnormal 24-hr pH monitoring among 718 patients studied for suspected diagnosis of GER. Patients were divided into three groups. Group 1 consisted of children with chronic RD but without any GI symptoms of GER. Group 2 was comprised of children with symptomatic GI presentation of GER such as regurgitation, vomiting, heartburn, and failure to thrive, but without any signs or symptoms of RD. Group 3 included children with prevalent RD and concomitant signs of symptomatic GER. Patients with predominant GI manifestations (group 2) had a significantly higher fraction of time with pH <4 (P < 0.01), total time value of pH <4 (P < 0.05), and longest episode with pH <4 (P < 0.05). Esophageal clearance was significantly longer in group 1 patients than in the other two groups (P < 0.05). Patients with mixed disease (group 3) were similar to patients in group 2. Patients with GI symptoms had significantly worse scores for all parameters evaluated except esophageal clearance score, compared to patients without GI symptoms. Longer esophageal clearance was the only parameter associated with respiratory signs in patients with respiratory symptoms compared to those without. In conclusion, the presence of RD in pediatric patients with silent GER is related to longer esophageal clearance, but is not related to severity of reflux.

Adolescent↗
PubMed2003

Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis.

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid.

Chi-Square Distribution↗
PubMed2003

The pattern of sesame sensitivity among infants and children.

Recently, we found sesame to be a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE-mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients 'outgrew' their allergy within 1-2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut - a major cause of severe food allergic reactions.

Angioedema↗
PubMed2003

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease.

OBJECTIVES: Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. METHODS: A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. RESULTS: Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01). CONCLUSIONS: Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.

Adolescent↗
PubMed2003

Consensus and controversy in the management of pediatric Crohn disease: an international survey.

OBJECTIVES: Treatment options for patients with Crohn disease (CD) have expanded, but the use of some of these options in pediatric patients remains controversial. The authors evaluate current trends in treatment and areas of consensus or controversy. METHODS: An international survey of certified pediatric gastroenterologists was conducted using an e-mail questionnaire in an attempt to evaluate management of active Crohn disease, attitudes toward four types of therapy, and prevalence of testing for osteopenia and 6-thioguanine levels. RESULTS: One hundred sixty-seven physicians from the United States, Canada, Western Europe, and Israel were included. The majority of North American physicians (71%) prefer to use conventional steroids and azathioprine (AZA) before nutritional therapy or budesonide for patients with mild to moderately active disease, versus 21% of Western Europeans (P < 0.001). Western Europeans prefer nutritional therapy followed by budesonide or steroids for those with mild or moderate disease. Only 4% of North American gastroenterologists use nutritional therapy frequently versus 62% of their Western European colleagues (P < 0.001). Infliximab was thought to be effective for steroid-unresponsive disease by almost all physicians surveyed, although its efficacy as a maintenance therapy was rated higher by North American physicians than by their Western European and Israeli colleagues (P < 0.01). Bone mineral density is routinely evaluated by about 45% of physicians in Western Europe and North America. CONCLUSIONS: Attitudes toward current therapies vary significantly by region, with North Americans strongly favoring corticosteroids followed by immunomodulatory therapy, and Western Europeans favoring nutritional therapy or budesonide and the avoidance of conventional corticosteroids.

Adrenal Cortex Hormones↗