Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum o...Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (- 26% of NSE positive neurones; p = 0.016) and VIP (- 54% ; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+ 16% ; p< 0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (- 7.6 (2.6) v - 14.5 (5.0); p = 0.036). Conclusions: Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.展开更多
Aims-Determine the proportion of infants whose celiac disease (CD) was confirmed in childhood and evaluate their prognosis in adulthood. Patients and methods-The diagnosis of CD was established between 1971 and 1982 i...Aims-Determine the proportion of infants whose celiac disease (CD) was confirmed in childhood and evaluate their prognosis in adulthood. Patients and methods-The diagnosis of CD was established between 1971 and 1982 in 84 infants based on intestinal biopsy data; a gluten-free diet was prescribed and the cohort followed prospectively. Results-Thirty-six infants were followed less than 5 years. A second biopsy was performed in 25. Mucosa had healed in 13 and remained atrophic in 12. Three children developed partial villous atrophy between 6 and 12 years of age in spite of the gluten-free diet. Forty-five patients underwent a gluten challenge between 5 and 10 years of age: in 41 histological lesions relapsed, in two mucosa remained normal and clinical and immunological relapse developed in two. Among those 45 patients, 18 were examined after 18 years follow-up: the exclusion diet was resumed in four, overt clinical relapse developed in four and four experienced intermittent gastrointestinal disorders. All biopsies performed during a period of normal diet showed villous atrophy (except in one patient) without correlation with clinical symptoms. Conclusion-The diagnosis of celiac disease in infants was confirmed in nearly all cases in childhood. When they reached adulthood, these patients had few symptoms but their histological lesions persisted. These data are in favor of a lifelong exclusion diet.展开更多
文摘Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (- 26% of NSE positive neurones; p = 0.016) and VIP (- 54% ; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+ 16% ; p< 0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (- 7.6 (2.6) v - 14.5 (5.0); p = 0.036). Conclusions: Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.
文摘Aims-Determine the proportion of infants whose celiac disease (CD) was confirmed in childhood and evaluate their prognosis in adulthood. Patients and methods-The diagnosis of CD was established between 1971 and 1982 in 84 infants based on intestinal biopsy data; a gluten-free diet was prescribed and the cohort followed prospectively. Results-Thirty-six infants were followed less than 5 years. A second biopsy was performed in 25. Mucosa had healed in 13 and remained atrophic in 12. Three children developed partial villous atrophy between 6 and 12 years of age in spite of the gluten-free diet. Forty-five patients underwent a gluten challenge between 5 and 10 years of age: in 41 histological lesions relapsed, in two mucosa remained normal and clinical and immunological relapse developed in two. Among those 45 patients, 18 were examined after 18 years follow-up: the exclusion diet was resumed in four, overt clinical relapse developed in four and four experienced intermittent gastrointestinal disorders. All biopsies performed during a period of normal diet showed villous atrophy (except in one patient) without correlation with clinical symptoms. Conclusion-The diagnosis of celiac disease in infants was confirmed in nearly all cases in childhood. When they reached adulthood, these patients had few symptoms but their histological lesions persisted. These data are in favor of a lifelong exclusion diet.
