Histological aspects of the terminal ileum: a windows on coeliac disease too?
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Biopsy↗
Biomedical subjects
V Villanacci
Publications and source records attributed to V Villanacci.
Transglutaminase 2 in the enterocytes is coeliac specific and gluten dependent.
BACKGROUND: Tissue transglutaminase, the coeliac autoantigen, was shown to localise in the enterocytes of coeliac patients and controls. It was speculated that surface tissue transglutaminase has a role in the pathogenesis of coeliac disease. AIMS: To study localisation of tissue transglutaminase in different stages of coeliac disease and other enteropathies with and without villous flattening. METHODS: Immunofluorescent and immunoblotting assays were used. Duodenal cryostat sections from 23 coeliac patients (10 untreated, 8 treated, 5 potential) and 18 controls (2 autoimmune enteropathy and 16 normal duodenal mucosa) were incubated with an anti-tissue transglutaminase monoclonal antibody. Slides were blindly examined. RESULTS: The immunofluorescent assay showed that monoclonal antibody localised in the subepithelial layer, in the lamina propria, and in the pericryptal connective tissue of all samples. It also bound to surface enterocytes in 8/10 untreated, 1/8 treated, and 3/5 potential coeliac patients. None of the controls showed an epithelial distribution of tissue transglutaminase. Immunoblotting experiments performed in enterocytes freshly isolated from duodenal biopsy confirmed these findings. CONCLUSION: Epithelial distribution of tissue transglutaminase is specific for coeliac disease rather than due to a non-specific mucosal inflammation. Analysis of different stages of coeliac disease suggests that the epithelial distribution of tissue transglutaminase is gluten dependent.
Adult↗
Coeliac disease in primary care: evaluation of a case-finding strategy.
BACKGROUND: Coeliac disease is still under-diagnosed as a consequence of poor physician awareness of the clinical spectrum of the disease. We evaluated the feasibility and the cost-effectiveness of a case-finding approach for early identification of cases, carried out by primary care practitioners. METHODS: We developed a case-finding strategy based on testing for anti-tissue transglutaminase IgA antibodies in subjects showing predefined signs and symptoms or belonging to at-risk groups. RESULTS: Sixty-nine primary care doctors and 60 primary care paediatricians agreed to participate. One thousand forty-one adults and 447 children were selected for anti-tissue transglutaminase testing during the year of the study (2001). Thirty-one (2.08%, 19 adults and 12 children) were ultimately diagnosed as coeliac patients. While no cases of coeliac disease had been diagnosed by the participating doctors in the previous year, 29 subjects were diagnosed as coeliacs in the year after the completion of the study (2002). The prevalence of confirmed coeliac disease in the population under study increased from 1:1,506 to 1:1,073 in adults and from 1:827 to 1:687 in children from year 2000 to 2001. When cases diagnosed in 2002 are included, the prevalence is 1:832 and 1:602, respectively. We calculated a cost of 923.25 euros for each new case diagnosed. CONCLUSIONS: Case-finding is a feasible and successful strategy for detecting undiagnosed coeliac patients and has the important added value of increasing the awareness of the disease among primary care physicians; it represents a cost-effective alternative to population screening for reducing the burden of undiagnosed coeliac disease.
Adolescent↗
Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet.
BACKGROUND: It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS: We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS: Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.
Adult↗
Is pseudomelanosis coli a marker of colonic neuropathy in severely constipated patients?
AIMS: To study relationships between the number of pseudomelanosis coli cells and that of colonic enteric neurons and interstitial cells of Cajal, which are significantly reduced compared with controls in severely constipated patients. Pseudomelanosis coli is frequent in patients using anthraquinone laxatives. It is not known whether the prolonged use of these compounds damages the enteric nervous system in constipated patients. PATIENTS AND METHODS: The relationship between the number of pseudomelanosis coli cells and that of colonic enteric neurons (as well as that of apoptotic enteric neurons) and of interstitial cells of Cajal was assessed by histological and immunohistochemical methods in 16 patients with chronic use of anthraquinone laxatives undergoing surgery for severe constipation unresponsive to medical treatment. No relationship was found between the number of pseudomelanosis coli cells and that of enteric neurons (and that of the apoptotic ones), nor of interstitial cells of Cajal, in either the submucosal or the myenteric plexus. CONCLUSION: The use of anthraquinone laxatives, leading to the appearance of pseudomelanosis coli, is probably not related to the abnormalities of the enteric nervous system found in severely constipated patients.
Adult↗
European evidence based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis.
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Biopsy↗
The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation.
BACKGROUND: Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. AIMS: We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). PATIENTS AND METHODS: Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. RESULTS: Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. CONCLUSION: Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.
Adult↗
Anti-Saccharomyces cerevisiae antibodies in long-term consumers of anthranoid-containing laxatives.
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Anthraquinones↗
Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.
BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.
Aged↗
Terminology for the diagnosis of colitis.
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Colitis↗
Immunological markers anti-saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: a helpful diagnostic tool.
AIM: Nowadays the diagnosis of inflammatory bowel disease (IBD) and the differentiation between Crohn disease (CD) and ulcerative colitis (UC) is still based on morphological changes identified at endoscopy, radiology, and histopathology. In 5-15% of cases this differentiation is not possible (diagnosed with indeterminate colitis). METHODS: We evaluated if recently developed commercial kits for the determination of anti-Saccharomyces Cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) are useful in differentiating cases of UC from CD diseases with a consequent reduced number of undefined colitis and improved clinical management. Sera from 56 consecutive patients with a clinical diagnoses of IBD were evaluated in a blinded fashion for the presence of ASCA IgA and IgG and ANCA IgG with 2 different diagnostic methods: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In our cases we observed good agreement between histopathological examination and laboratory results and the combined use of ASCA and ANCA yielded a correct diagnosis in 93% of patients with CD and in 97% of the UC patients. CONCLUSIONS: We confirm the value of the test for the diagnosis of CD and UC and the differentiation from other forms of colitis.
Adult↗
Laparoscopic relief of obstructing folded muscular cuff after transanal pull-through for aganglionosis.
Transanal endorectal resection and colonic pull-through (TERPT) is a good technique for the management of Hirschsprung's disease. This procedure is feasible in the vast majority of patients and is associated with excellent results, early postoperative recovery, and no visible scars. We report the case of a patient who developed early postoperative severe constipation after TERPT due to unusual folding of the muscular cuff rim, which tightly narrowed the pulled-through colon. This complication was diagnosed and treated by laparoscopy. To prevent it, we recommend splitting of the aganglionic muscular cuff during TERPT.
Anastomosis, Surgical↗
The phenotype of gut endocrine tumours.
Endocrine tumours of gut and pancreas tract are rare entities originating from cells of the diffuse endocrine system. The endocrine phenotype is assessed by the expression of general and specific endocrine markers. General endocrine markers associate to organelles like large dense core vesicles (e.g. chromogranin A) and small synaptic-like vesicles (e.g. synaptophysin), or to the cytosol, like neuron specific enolase and protein gene product 9.5 (PGP9.5). The specific markers correspond to the hormones produced by tumour cells. Two major categories of endocrine tumours are identified as (i) well-differentiated and (ii) poorly differentiated neoplasms. Well-differentiated tumours/carcinomas (also known as carcinoids) express all general markers of endocrine differentiation and various hormones. Poorly differentiated endocrine carcinomas lack large dense core vesicles markers (chromogranin A), while widely express synaptophysin and cytosol endocrine markers. The clinical behaviour of endocrine tumours spans from benign to low-grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The Multiple Endocrine Neoplasia type 1 syndrome (MEN1) gene is involved in the genesis of a proportion of both well- and poorly differentiated sporadic tumours. p53 gene abnormality appears as restricted to poorly differentiated endocrine carcinomas.
Biomarkers, Tumor↗
Osteitis fibrosa cystica, coeliac disease and Turner syndrome. A case report.
Today, osteitis fibrosa cystica is seldom present in primary hyperparathyroidism while it is mainly observed in uraemic osteodystrophy. We describe the case of a 54-year-old woman who was found to have huge bone cysts due to osteitis fibrosa cystica in the long bones. A parathyroid adenoma was identified and removed. Coeliac disease and Turner syndrome were diagnosed. Metabolic bone disease due to secondary hyperparathyroidism is common in coeliac disease; however, osteitis fibrosa cystica has not yet been described.
Celiac Disease↗
Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency.
BACKGROUND: Selective IgA deficiency is associated with coeliac disease, and studies have shown an increased prevalence of coeliac disease in these patients ranging from 0.71 to 30.7%, depending on the test used for screening. AIMS: To determine the sensitivity of IgG anti-gliadin-antibodies and of IgG human-tissue-transglutaminase for diagnosing coeliac disease and assessing its prevalence in subjects with IgA deficiency. SUBJECTS: We tested serum samples from 126 IgA-deficient children (66 female, median age: 10.8 years). METHODS: All samples were analysed to measure IgG anti-gliadin-antibodies and IgG anti-human-tissue-transglutaminase. Patients testing positive to either test underwent intestinal biopsy. Subjects testing positive for IgG anti-human-tissue-transglutaminase underwent genetic testing for the human leucocyte antigen heterodimer. RESULTS: Twenty-seven of 126 subjects tested positive for IgG anti-gliadin-antibodies (five of whom tested positive also for IgG anti-human-tissue-transglutaminase) and 18 (including the aforementioned five) for IgG anti-human-tissue-transglutaminase. Intestinal biopsy was performed in 37 of the 40 patients who tested positive (three subjects refused). Eleven had positive intestinal biopsies all of whom tested positive for IgG anti-human-tissue-transglutaminase, but only five of these tested positive also for IgG anti-gliadin-antibodies. All 22 patients testing positive for anti-gliadin-antibody alone had normal intestinal mucosa. All the patients who tested positive for IgG anti-human-tissue-transglutaminase and underwent genetic screening (15/18) had the coeliac-related human leucocyte antigen. Overall, coeliac disease was diagnosed in 11 of the 126 subjects with IgA deficiency (8.7%). CONCLUSIONS: The prevalence of coeliac disease in subjects with total IgA deficiency was 8.7%. Assay of IgG anti-human-tissue-transglutaminase can be recommended for screening coeliac disease in IgA-deficient subjects.
Adolescent↗
Type 1 gastric carcinoid: is the conservative approach always indicated?
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Aged↗
Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?
BACKGROUND: The counting of intraepithelial lymphocytes (IELs) in the villous tips of architecturally normal small bowel biopsy specimens was proposed as a method to measure mucosal infiltration in gluten sensitive patients. AIMS: To apply this straightforward method in duodenal biopsy specimens from patients affected by potential coeliac disease (PCD) to verify whether it can discriminate these patients from controls. METHODS: Paraffin wax embedded duodenal sections from 11 patients affected by PCD were stained with an antihuman CD3 antibody. Sections from 19 patients affected by treated coeliac disease (TCD) and 17 patients in whom coeliac disease was excluded were stained with the same antibody to serve as controls. The slides were examined blindly. IELs/20 enterocytes in five randomly chosen villous tips were counted. Patients affected by PCD were all on a gluten containing diet. They had an architecturally normal duodenal mucosa and were positive for endomysial antibody. Both TCD and non-coeliac controls were negative for endomysial antibody. RESULTS: The mean villous tip IEL scores were 4.6 (SD, 1.5; range, 1.4-7.8) in non-coeliac controls, 7.9 (SD, 4.0; range, 2.0-18.6) in TCD, and 9.2 (SD, 4.7; range, 5.8-21.8) in patients with PCD. The difference between PCD and non-coeliac controls was significant. CONCLUSIONS: This is a very simple and sufficiently reliable method to count IELs. In patients with an architecturally normal duodenal mucosa, the IEL count in villous tips helps to distinguish between patients with PCD and non-coeliac controls.
Adolescent↗