Publications (130)450.49 Total impact
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Article: Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.
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ABSTRACT: Background Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled. Methods Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors. Key Results Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect. Conclusions & Inferences Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.Neurogastroenterology and Motility 09/2012; · 3.41 Impact Factor -
Article: Slow gallbladder emptying reverts to normal but small intestinal transit of a physiological meal remains slow in celiac patients during gluten-free diet.
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ABSTRACT: Background Alterations of small intestinal transit and gallbladder (GB) motility have been reported in celiac disease (CD) in studies involving, in most cases, non-physiological experimental conditions and artificial stimuli to motility. Our aims were to quantitate non-invasively small intestinal transit time and GB emptying during administration of a physiological and palatable solid meal, and to assess the effect of gluten-free diet (GFD). Methods We simultaneously measured mouth-to-cecum transit time (MCTT) using a validated H(2) breath test, and GB motility using ultrasonography. We studied CD patients before (n = 19) and during (n = 14) GFD, and healthy volunteers (n = 24) following administration of a physiological solid meal (Kcal 539). Key Results Mouth-to-cecum transit time was more prolonged in CD (mean ± SEM: 235 ± 96 min) than in controls (169 ± 65 min, P = 0.0039). The GB fasting volume and postprandial residual volume were significantly higher in CD than in controls, and GB emptying constant was slower in CD than in controls. During GFD, GB emptying reverted to normal, but MCTT remained unchanged (229 ± 69 min) and more prolonged in CD than in controls (P = 0.0139). During GFD, duodenal infiltration with lymphocytes and mast cells persisted higher than that in controls, and the number of mast cells lying in proximity of nervous endings did not change. Conclusions & Inferences Slow postprandial MCTT in response to a physiological meal does not revert to normal during GFD, an effect mirroring incomplete histopathologic recovery.Neurogastroenterology and Motility 11/2011; 24(2):100-e80. · 3.41 Impact Factor -
Article: Patient-reported outcomes and gut dysmotility in functional gastrointestinal disorders.
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ABSTRACT: Unlike chronic idiopathic intestinal pseudo-obstruction (CIIP), severe digestive syndromes that are not characterized by episodes resembling mechanical obstruction remain poorly characterized. The present study compared clinical features, small bowel motility, and quality of life (QoL) in patients with CIIP or severe functional gastrointestinal disorders (SFGID), compared to irritable bowel syndrome (IBS). We enrolled 215 consecutive patients: 70 CIIP, 110 malnourished SFGID [body mass index (BMI) 17.8±1.8kg m(-2) ] and 35 non-malnourished SFGID (BMI 22.8±3.6kgm(-2) ). Abnormal motor patterns that fulfilled diagnostic criteria for small bowel dysmotility were virtually absent in IBS patients, but were recorded in69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 SFGID patients without malnutrition (65.7%) (P<0.0001). CIIP patients presented more frequently abnormal activity fronts, lack of response to feeding, and hypomotility than malnourished and non-malnourished SFGID patients (61.4%vs 42.7% and 31.4%, P<0.05 only vs non-malnourished SFGID; 8.6%vs 0.9% and 2.9%; 21.4%vs 0.9% and 0%, P<0.05). Quality of life mean scores were all significantly lower in CIIP patients and malnourished SFGID patients than in IBS. Bodily pain, general health, and vitality scores were lower in CIIP also compared to non-malnourished SFGID. Chronic idiopathic intestinal pseudo-obstruction and SFGIDs are frequently associated with small bowel dysmotility and marked derangements of QoL which are significantly more severe than in IBS and result particularly in being severe in patients with recurrent sub occlusive episodes or inability to maintain a normal body weight.Neurogastroenterology and Motility 09/2011; 23(12):1084-91. · 3.41 Impact Factor -
Article: Use of macrogol 4000 in chronic constipation.
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ABSTRACT: Chronic constipation is a common functional disorder of the gastrointestinal tract, affecting up to 35% of the general population, and especially the elderly. However, its definition as perceived by the patient can vary, making it difficult to understand the problem and find appropriate therapeutic measures. The approach to chronic constipation, thus, needs a thorough understanding of the patient's complaint and the main pathophysiological mechanism requiring treatment. Lifestyle changes do not usually meet with complete patient satisfaction. Other treatments include different types of laxatives. Of these, osmotic laxatives appear one of the most effective and are, therefore, frequently prescribed. This review will cover the topic of osmotic laxatives, specifically focusing on polyethylene glycol (PEG/macrogol 4000) in chronic constipation and as a key agent for bowel cleansing prior to colonoscopy. PEG formulations, including macrogol 4000, are safe, effective treatments for constipation, even in children and elderly patients. Macrogol 4000 may well be more palatable than combined formulations (macrogol 3350 with electrolytes), which could help improve adherence to the long-term treatment required for chronic constipation. PEG/macrogol is also recommended as an effective option for bowel cleansing prior to colonoscopy. The improved cost-effectiveness of macrogol over other commonly prescribed laxatives, such as lactulose, should be taken into consideration.European review for medical and pharmacological sciences 08/2011; 15(8):960-6. · 1.04 Impact Factor -
Article: Dried plums vs. psyllium.
Alimentary Pharmacology & Therapeutics 05/2011; 33(10):1180-1; author reply 1181-2. · 3.77 Impact Factor -
Article: Enteric neuropathy evoked by repeated cisplatin in the rat.
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ABSTRACT: Acute administration of the antitumoral drug cisplatin can induce nausea/emesis and diarrhea. The long-term effects of cisplatin on gastrointestinal motility, particularly after repeated administration, are not well known. Because cisplatin is highly neurotoxic, myenteric neurons can be affected. Our aim was to study the prolonged effects of repeated cisplatin administration in a rat model, focusing on gastrointestinal motor function and myenteric neurons. Rats received saline or cisplatin (1 or 3 mg kg(-1), i.p.) once weekly for 5 weeks. One week after treatment, both upper gastrointestinal transit and colonic activity were evaluated, and tissue samples from ileum, colon and rectum were processed for histological analysis. Intestinal transit was measured invasively (charcoal method). Colonic activity was determined electromyographically. The gut wall structure was evaluated in sections using conventional histology and immunohistochemistry. Whole-mount preparations from the distal colon were labeled for different markers, including nitric oxide synthase (NOS) and calcitonin-gene related peptide (CGRP) to determine relative proportions of myenteric neurons vs the total neuronal population labeled with HuC/D. One week after repeated cisplatin exposure, the upper gastrointestinal transit rate and colonic activity were dose-dependently reduced. The number of NSE- or HuC/D-immunoreactive myenteric neurons per ganglion was decreased; the proportion of CGRP-immunoreactive neurons was decreased, whereas that of NOS-immunoreactive cells was increased. Chronic cisplatin may induce an enteric neuropathy characterized by changes in myenteric neurons associated with marked gastrointestinal motor dysfunction.Neurogastroenterology and Motility 02/2011; 23(4):370-8, e162-3. · 3.41 Impact Factor -
Article: New perspectives in irritable bowel syndrome: introduction to part 2.
Digestive and Liver Disease 09/2009; 41(12):843. · 3.05 Impact Factor -
Article: New perspectives in Irritable Bowel Syndrome: introduction to part 1.
Digestive and Liver Disease 09/2009; 41(11):771. · 3.05 Impact Factor -
Article: Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study.
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ABSTRACT: Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS). To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study. A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed. Mesalazine markedly reduced immune cells as compared with placebo (P = 0.0082); this effect was ascribed to a marked inhibition of mast cells (P = 0.0014). Mesalazine significantly increased general well-being (P = 0.038), but had no significant effects on abdominal pain (P = 0.084), bloating (P = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study. Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS.Alimentary Pharmacology & Therapeutics 06/2009; 30(3):245-52. · 3.77 Impact Factor -
Article: Overlapping functional syndromes: a way forward for medical therapy?
European review for medical and pharmacological sciences 09/2008; 12 Suppl 1:138. · 1.04 Impact Factor -
Article: Review article: molecular, pathological and therapeutic features of human enteric neuropathies.
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ABSTRACT: Considerable information has been gathered on the functional organization of enteric neuronal circuitries regulating gastrointestinal motility. However, little is known about the neuropathophysiological mechanisms underlying gastrointestinal motor disorders. To analyse the most important pathological findings, clinical implications and therapeutic management of idiopathic enteric neuropathies. PubMed searches were used to retrieve the literature inherent to molecular determinants, pathophysiological bases and therapeutics of gastrointestinal dysmotility, such as achalasia, gastroparesis, chronic intestinal pseudo-obstruction, Hirschsprung's disease and slow transit constipation, to unravel advances on digestive disorders resulting from enteric neuropathies. Current data on molecular and pathological features of enteric neuropathies indicate that degenerative and inflammatory abnormalities can compromise the morpho-functional integrity of the enteric nervous system. These alterations lead to a massive impairment in gut transit and result in severe abdominal symptoms with associated high morbidity, poor quality of life for patients and established mortality. Many pathophysiological aspects of these severe conditions remain obscure, and therefore treatment options are quite limited and often unsatisfactory. This review of enteric nervous system abnormalities provides a framework to better understand the pathological processes underlying gut dysmotility, to translate this knowledge into clinical management and to foster the development of targeted therapeutic strategies.Alimentary Pharmacology & Therapeutics 08/2008; 28(1):25-42. · 3.77 Impact Factor -
Article: Impaired contractility of colonic muscle cells in a patient with chronic intestinal pseudo-obstruction.
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ABSTRACT: Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either "secondary" to specific conditions or "chronic intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine.Digestive and Liver Disease 04/2008; 40(3):225-9. · 3.05 Impact Factor -
Article: Chronic intestinal pseudo-obstruction: manifestations, natural history and management.
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ABSTRACT: Chronic intestinal pseudo-obstruction (CIPO) is a rare pathological condition characterized by a marked derangement of gut propulsive motility mimicking mechanical obstruction, in the absence of any lesion occluding the gut lumen. This disease is often associated with a disabling and potentially life-threatening complications and is still too often unrecognized even in referral centres. As a result, patients receive neither appropriate care nor recognition of their severe health condition. Medical and surgical therapies are often unsatisfactory and long-term outcome turns out to be poor in the vast majority of cases. This article focuses on the main clinical features, the management and long-term outcome of patients affected by CIPO, with particular emphasis on those aspects which remain a matter of debate.Neurogastroenterology and Motility 07/2007; 19(6):440-52. · 3.41 Impact Factor -
Article: Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire?
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ABSTRACT: Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. To evaluate the validity of available GERD measurement tools. An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.Digestion 02/2007; 75 Suppl 1:3-16. · 2.05 Impact Factor -
Article: International validation of ReQuest in patients with endoscopy-negative gastro-oesophageal reflux disease.
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ABSTRACT: Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test-retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale 0.6; Psychological General Well-being -0.4). ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.Digestion 02/2007; 75 Suppl 1:48-54. · 2.05 Impact Factor -
Article: Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest.
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ABSTRACT: The changes in gastroesophageal reflux disease (GERD)-related symptoms on treatment are variously described, but currently available questionnaires have shortcomings. We therefore developed a self-assessment reflux questionnaire (ReQuest). This article describes the process of development and testing. For the first version of ReQuest the symptom spectrum of GERD and the various symptom descriptions were investigated. The 67 identified symptom descriptions were condensed empirically into 6 dimensions, to which a 7th dimension on general well-being was added. The symptom burden of the dimensions was measured by frequency and/or intensity. ReQuest was translated into different languages and then tested in focus groups. The initial validation was based on data from a clinical trial of patients with erosive GERD, treated with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the contribution of each symptom to the different dimensions. Additionally, correlation analyses between the identified factors and the dimensions were performed. On the basis of factor analyses, ReQuest was reduced to a 60-item scale. The factors generated correlated strongly with the dimensions and confirmed the empirical process mathematically. ReQuest provides a valuable, self-assessment tool for evaluating the daily treatment response in patients with erosive GERD.Digestion 02/2007; 75 Suppl 1:32-40. · 2.05 Impact Factor -
Article: Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD.
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ABSTRACT: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest). This publication describes the psychometric evaluation and validation of ReQuest. This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest. The psychometric analyses of ReQuest included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. Validation of ReQuest indicated very high internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. ReQuest is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.Digestion 01/2007; 75 Suppl 1:41-7. · 2.05 Impact Factor -
Article: Gastro-oesophageal reflux and interstitial lung disease.
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ABSTRACT: Interstitial lung disease is a heterogeneous entity, which encompasses a large number of pulmonary disorders, including idiopathic pulmonary fibrosis. Gastro-oesophageal reflux appears to be more prevalent in idiopathic pulmonary fibrosis than in controls and in patients with secondary pulmonary fibrosis, but its contribution to interstitial lung disease remains unsettled. To prospectively evaluate gastro-oesophageal reflux in patients with interstitial lung disease and to define acid reflux patterns in patients with idiopathic and secondary forms of pulmonary fibrosis. Twenty-eight patients (15M, median age 66 years, interquartile range 60-71) were studied by history taking, pulmonary function tests, high resolution computed tomography, oesophageal manometry and 24h oesophago-gastric pH monitoring. Sixteen patients (57%) had typical reflux symptoms. All patients completed 24h pH metry and 14 underwent oesophageal manometry. An abnormal oesophageal acid exposure was observed in 19 patients (68%), 13 of which complained of predominant typical reflux symptoms. A diagnosis of idiopathic pulmonary fibrosis was made in 18 patients, while the remaining 10 patients were classified as secondary pulmonary fibrosis. Secondary pulmonary fibrosis patients had more restrictive lung defect, as expressed as Tiffeneau index (p<0.05) and greater acid reflux at nighttime (p<0.05) than idiopathic pulmonary fibrosis patients. The prevalence of abnormal acid reflux in interstitial lung disease patients is high and, in particular, patients with secondary pulmonary fibrosis show higher oesophageal acid exposure than those with idiopathic form.Digestive and Liver Disease 01/2007; 38(12):879-84. · 3.05 Impact Factor -
Article: HLA and enteric antineuronal antibodies in patients with achalasia.
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ABSTRACT: The aetiopathogenesis of primary achalasia is largely unknown, although an immunogenetic predisposition is suspected. To establish whether a correlation exists among possible aetiological factors, including class II human leucocyte antigen (HLA) alleles and autoantibodies to enteric neurones, and clinical features of patients with achalasia, a total of 60 patients and 200 healthy subjects were typed by high-resolution HLA-DQ and HLA-DR alleles. Circulating antineuronal antibodies were investigated by using indirect immunofluorescence on enteric neurones of rat ileum and colon and immunoblotting assay in a subset of achalasic patients and in all controls. The DQB1*0502 and DQB1*0601 alleles were significantly increased in patients with achalasia compared with controls (P < 0.03, P < 0.001, respectively). Moreover a negative correlation with the DQB1*0201 allele was found (P = 0.016). As a whole, 14 of 60 (23.3%) achalasia patients were carriers of HLA risk alleles, and 10 of 41 (24.4%) presented antineuronal antibodies. No significant correlation among HLA risk alleles, antineuronal antibodies and clinical features was found. In achalasia, no correlation exists among HLA alleles, antineuronal antibodies and clinical features. However, given the association between achalasia and HLA-DQ1, further research is needed to clarify the role of HLA antigens and antineuronal antibodies in this disease.Neurogastroenterology and Motility 07/2006; 18(7):520-5. · 3.41 Impact Factor -
Article: Anti-ganglioside antibodies in coeliac disease with neurological disorders.
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ABSTRACT: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.Digestive and Liver Disease 04/2006; 38(3):183-7. · 3.05 Impact Factor
Top Journals
Institutions
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1987–2012
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University of Bologna
Bologna, Emilia-Romagna, Italy
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2004–2011
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Policlinico S.Orsola-Malpighi
Bologna, Emilia-Romagna, Italy
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2008
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Sapienza University of Rome
Roma, Latium, Italy
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2006
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University of Mississippi Medical Center
- Division of Digestive Diseases
Jackson, MS, USA
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2000
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Università degli studi di Pavia
- Department of Internal Medicine and Therapeutics
Pavia, Lombardy, Italy
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1996–1998
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Università degli Studi di Perugia
- Department of Clinical and Experimental Medicine
Perugia, Umbria, Italy -
Università degli Studi del Sannio
Benevento, Campania, Italy
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