Publications (7)16.76 Total impact
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Article: Risk of fracture in celiac disease: gender, dietary compliance, or both?
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ABSTRACT: To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture risk. We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age- and sex-matched controls who had been diagnosed with functional gastrointestinal disorders. Data were collected through in-person interviews with an investigator. The overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis). Compared with the control group, the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR): 1.78, 95% CI: 1.23-2.56, P < 0.002] and in men (HR: 2.67, 95% CI: 1.37-5.22, P < 0.004). Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003). In the time period after diagnosis, the risk of fractures was comparable between the CD cohort and controls in both sexes (HR: 1.08, 95% CI: 0.55-2.10 for women; HR: 1.57, 95% CI: 0.57-4.26 for men). CD patients have higher prevalence of fractures in the peripheral skeleton before diagnosis. This is associated with male sex and classic clinical presentation. The fracture risk was reduced after the treatment.World Journal of Gastroenterology 07/2011; 17(25):3035-42. · 2.47 Impact Factor -
Article: Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet.
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ABSTRACT: Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD). We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a subdimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains. At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P < .001). At baseline, 30.1% of CD patients had moderate to severe GERD (score >3) compared with 5.7% of controls (P < .01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%; P < .03). A rapid improvement was evidenced at 3 months after initial treatment with a GFD (P < .0001) with reflux scores comparable to healthy controls from this time point onward. GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2011; 9(3):214-9. · 5.64 Impact Factor -
Article: Very high rate of misdiagnosis of celiac disease in clinical practice.
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ABSTRACT: We evaluated the accuracy of the diagnosis of celiac disease (CD) performed in the community clinical setting compared with that of an academic experienced center. Original biopsy slides and reports used for diagnosis in the community setting and the CD serology were revised in 70 consecutive patients attending our institution for a second opinion. An expert team determined the final diagnosis unaware of the original consideration. The poor quality of samples made histology assessment by the expert pathologist uncertain in 8.7% of slides with CD external diagnosis. We detected a divergent diagnosis between the two practice settings in 46.3% of available cases with a significant overdiagnosis of CD in the community (p < 0.0001). Congruent serology results were demonstrated in 72.2% of cases. Our study detected a high rate of histopathological and serological misdiagnosis of CD in community practice which may have profound negative impact on patients.Acta gastroenterologica Latinoamericana 12/2009; 39(4):250-3. -
Article: The simultaneous presence of IL-1B and TNFA two-positions risk haplotypes enhances the susceptibility for celiac disease.
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ABSTRACT: To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis factor alpha (TNFalpha) to the genetic risk of developing celiac disease (CD), we analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and 244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA-DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered to perform haplotype analyses. Two-position risk haplotypes were first defined by the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype-stratified association analysis showed that the simultaneous presence of TNFA risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest that the coexistence of both risk haplotypes seems to work synergistically (OR 29.59), which enhances the risk of developing CD.Cytokine 05/2008; 42(1):48-54. · 3.02 Impact Factor -
Article: Multidrug resistance gene (MDR-1) expression in the colonic mucosa of patients with refractory ulcerative colitis.
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ABSTRACT: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. These results suggest a critical role of P-gp overexpression in steroid-refractory UC.Acta gastroenterologica Latinoamericana 04/2006; 36(1):23-32. -
Article: Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution.
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ABSTRACT: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight. We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.Acta gastroenterologica Latinoamericana 04/2006; 36(1):10-22. -
Article: Permeability, zonulin production, and enteropathy in dermatitis herpetiformis.
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ABSTRACT: Dermatitis herpetiformis (DH) is characterized by variable degrees of enteropathy and increased intestinal permeability. Zonulin, a regulator of tight junctions, seems to play a key role in the altered intestinal permeability that characterizes the early phase of celiac disease. Our aim was to assess both intestinal permeability and serum zonulin levels in a group of patients with DH having variable grades of enteropathy. We studied 18 DH patients diagnosed on the basis of characteristic immunoglobulin (Ig)A granular deposits in the dermal papillae of noninvolved skin. Results were compared with those of classic celiac patients, patients with linear IgA dermatosis, and healthy controls. According to Marsh's classification, 5 patients had no evidence of enteropathy (type 0), 4 patients had type II, 2 patients had type IIIb damage, and 7 patients had a more severe lesion (type IIIc). Intestinal permeability (lactulose/mannitol ratio [lac/man]) was abnormal in all patients with DH. Patients with more severe enteropathy had significantly greater permeability ( P < .05). The serum zonulin concentration (enzyme-linked immunosorbent assay) for patients with DH was 2.1 +/- .3 ng/mg with 14 of 16 (87.5%) patients having abnormally increased values. In contrast, patients with linear IgA dermatosis had normal histology, normal intestinal permeability, and negative celiac serology. Increased intestinal permeability and zonulin up-regulation are common and concomitant findings among patients with DH, likely involved in pathogenesis. Increased permeability can be observed even in patients with no evidence of histologic damage in biopsy specimens. Patients with linear IgA dermatosis appear to be a distinct population with no evidence of gluten sensitivity.Clinical Gastroenterology and Hepatology 04/2005; 3(4):335-41. · 5.63 Impact Factor
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2005–2011
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Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo
Buenos Aires, Buenos Aires F.D., Argentina
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