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G R Corazza

Publications and source records attributed to G R Corazza.

At least 37 records · Page 2Linked to original sources
PubMed2002

Coeliac disease.

In the last few decades, the comprehension of epidemiological, pathogenic and clinical aspects of coeliac disease has increasingly improved. Serological screening studies on the general population have shown that the true coeliac disease prevalence in Europe is higher than previously reported. It has become clear that tissue transglutaminase has a crucial role in the pathogenesis of coeliac disease pathogenesis, and there is evidence that substitution of deamidated amino acidic residues at a critical position along the gliadin sequence dramatically increases immunological activation. The toxicity of many gluten epitopes has been investigated, so far, but recent studies have indicated the region 57-75 of alpha gliadin as a possible candidate epitope in the pathogenesis of coeliac disease. However, the wide heterogeneity of gliadin and glutenin molecules complicate any attempts to identify the toxic epitope, and the fascinating idea to produce detoxified grains will represent a great challenge in the near future. From a clinical point of view, there is now evidence of a broad spectrum of gluten conditions. Extra-intestinal signs, i.e., alopecia, unexplained neurological disorders, cryptic hypertransaminasaemia, increased red cell width, frequently constitute the only clinical manifestation at the diagnosis.

Celiac Disease↗
PubMed2002

Clinical features of coeliac disease.

Aim of this review is to describe the extremely variable clinical presentation of coeliac disease. Moreover due to these varying manifestations, "coeliac literature" is characterised by a very rich terminology, which has not been unified, so far To help readers, not familiar with that terminology, we have given an explanation for the most common coeliac terms.

Celiac Disease↗
PubMed2002

Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease.

Since in coeliac disease mucosal flattening has been suggested to result from an increased enterocyte apoptosis triggered by Fas/Fas ligand system and perforin cytolytic granules, we looked for a similar mechanism in autoimmune enteropathy. Moreover, we tried to assess whether enterocyte autoantibodies, which are the hallmark of autoimmune enteropathy, may be involved in triggering enterocyte apoptosis in this condition. Immunohistochemical staining with anti-Fas, -FasL and -perforin MoAb, and TUNEL technique were applied on endoscopic duodenal biopsies of two autoimmune enteropathy patients, two untreated coeliac patients and two biopsied controls. Cytotoxicity assays were carried out by incubating peripheral blood mononuclear cells from a healthy subject (effectors) with enterocytes primed with patient or control sera (targets). In autoimmune enteropathy a large number of enterocytes were apoptotic, as in coeliac disease, whereas neither Fas/Fas ligand or perforin expressions were up-regulated. On the other hand, antibody-dependent cellular cytotoxicity assay revealed the ability of sera from patients with autoimmune enteropathy to mediate enterocyte death through apoptosis. These results point to enterocyte autoantibody-dependent cellular cytotoxicity as the prevalent mechanism of increased enterocyte apoptosis in autoimmune enteropathy but not in coeliac disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2001

Mortality in patients with coeliac disease and their relatives: a cohort study.

BACKGROUND: Although previous studies have shown increased mortality in patients with coeliac disease and their relatives, no data are available in relation to different patterns of clinical presentation. We assessed mortality in patients with coeliac disease and their first-degree relatives. METHODS: We enrolled, in a prospective cohort study, 1072 adult patients with coeliac disease consecutively diagnosed in 11 gastroenterology units between 1962 and 1994, and their 3384 first-degree relatives. We compared the number of deaths up to 1998 with expected deaths and expressed the comparison as standardised mortality ratio (SMR) and relative survival ratio. FINDINGS: 53 coeliac patients died compared with 25.9 expected deaths (SMR 2.0 [95% CI 1.5-2.7]). A significant excess of mortality was evident during the first 3 years after diagnosis of coeliac disease and in patients who presented with malabsorption symptoms (2.5 [1.8-3.4]), but not in those diagnosed because of minor symptoms (1.1 [0.5-2.2]) or because of antibody screening (1.2 [0.1-7.0]). SMR increased with increasing delay in diagnosis and for patients with poor compliance with gluten-free diet. Non-Hodgkin lymphoma was the main cause of death. No excess of deaths was recorded in relatives with coeliac disease. INTERPRETATION: Prompt and strict dietary treatment decreases mortality in coeliac patients. Prospective studies are needed to clarify the progression of mild or symptomless coeliac disease and its relation to intestinal lymphoma.

Adult↗
PubMed2001

Intestinal permeability in Crohn's disease patients and their first degree relatives.

BACKGROUND: Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's disease patients and 26 of their cohabiting first degree relatives were studied. METHODS: To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS: In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohn's disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS: These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohn's disease and their relatives.

Adult↗
PubMed2001

Small intestine bacterial overgrowth and metabolic bone disease.

Small intestine bacterial overgrowth is a malabsorption syndrome and, therefore, it may contribute to the occurrence of metabolic bone disease. However, studies that evaluate the magnitude of this problem and the potential underlying mechanisms are still needed. Fourteen patients with bacterial overgrowth and 22 comparable healthy volunteers took part in this study. All patients were affected by conditions known to predispose to bacterial overgrowth. Diagnosis was based on the following criteria: increased breath hydrogen levels in the fasting state and/or increased breath hydrogen excretion after the ingestion of 50 g of glucose solution, improvement after a 10-day course of antibiotic therapy of severity of symptoms and of H2 excretion parameters. Measurement of bone mineral density by dual-energy x-ray absorptiometry at lumbar spine and femoral level and evaluation of nutritional status were performed. Physical activity, sunlight exposure, and cigarette smoking were also evaluated. Patients showed lumbar and femoral bone mineral density values significantly lower than control group; also the prevalence of bone loss at both lumbar and femoral levels was higher in patient group than in healthy volunteers. Body mass index was significantly lower in patients than in healthy volunteers. Lumbar and femoral bone mineral density were significantly correlated and both correlated with body mass index and with duration of symptoms. No correlation between BMD values and physical activity, sunlight exposure, and cigarette smoking was evident. Our results show that small intestine bacterial overgrowth is an important cofactor in the development of metabolic bone disease. The severity of bone loss is related to poor nutritional status and duration of malabsorption symptoms.

Absorptiometry, Photon↗
PubMed2001

Apoptosis and peripheral blood lymphocyte depletion in coeliac disease.

In coeliac disease (CD) immunological abnormalities are not confined to the small bowel and it has been suggested that changes in peripheral blood lymphocytes (PBL), such as lymphopenia and increased T-cell activation, may predispose to malignant or autoimmune complications of this condition. In the light of the recent findings about the Fas-Fas ligand (FasL) system in regulating lymphocyte homeostasis, the aim of the present study was to investigate peripheral lymphocyte Fas-mediated apoptosis in CD to establish whether the homeostatic role of apoptosis in peripheral T-cell selection is maintained. Moreover, because a soluble form of Fas has been described to be functionally implicated in the Fas signalling system, suggesting a relationship between some disorders and soluble Fas function, we measured levels of soluble Fas in sera of coeliac patients and analysed the relationship between these levels and the proportions of apoptotic and Fas(+) PBL to further explore the function of the Fas-FasL pathway in this condition. Finally, we evaluated whether the increased prevalence of anticardiolipin antibodies, recently described in CD, could be related to PBL apoptosis in this condition. We demonstrated an increased apoptosis and higher levels of Fas and FasL expression in PBL isolated from untreated coeliac patients when compared to treated coeliac patients and controls. In addition, low levels of soluble Fas and a significant positive correlation between anticardiolipin antibodies and PBL apoptosis were found in untreated CD. Then, our results showed an increased susceptibility of PBL to undergo Fas-mediated apoptosis in active CD. This increased apoptosis could be responsible for both lymphopenia and immunogenic exposure of phospholipids with subsequent production of autoantibodies.

Adult↗
PubMed2001

Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families.

Coeliac disease (CD) is a malabsorptive disorder of the small intestine resulting from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the whole genetic susceptibility. Several regions of potential linkage on chromosomes 3q, 5q, 10q, 11q, 15q and 19q have already been reported in the literature. These six regions were analyzed with the Maximum Lod Score method on a dense set of markers. A new sample of 89 Italian sibpairs was available for study. There was no evidence for linkage for any of the regions tested, except for chromosome 5q. For this region, our data, as well as a sample of 93 sibpairs from our first genome screen (Greco et al. 1998), are compatible with the presence of a risk factor for CD with a moderate effect.

Celiac Disease↗
PubMed2001

Lactose malabsorption and intolerance in the elderly.

BACKGROUND: Lactase activity declines with age in rats, but it is not clear whether this model is also shared by humans. Few studies have evaluated lactose intolerance and malabsorption in the elderly and no definite conclusions can be drawn. The aim of our study was therefore to verify the impact of age on lactose intolerance and malabsorption. METHODS: Eighty-four healthy subjects took part in the study. Thirty-three were <65 years, 17 were between 65 and 74 years and 34 were >74 years. All the subjects underwent a preliminary evaluation of intestinal gas production capacity and oro-cecal transit time by H2/CH4 breath test after lactulose. After a 3-day period, an H2/CH4 breath test after lactose was performed. The occurrence of intolerance symptoms during the test and in the 24 h after the test was recorded. RESULTS: Breath H2 and CH4 excretion parameters at fasting and after lactulose did not differ between the three groups. Cumulative breath H2 excretion after lactose was higher in subjects >74 years than in subjects <65 years and in subjects aged 65-74 years, while no difference was found between the latter two groups. In subjects >74 years, the prevalence of lactose malabsorption was higher than in the other two groups, while no significant difference was observed between subjects <65 years and subjects aged 65-74 years. Within the malabsorber subjects, the prevalence of lactose intolerance was higher in subjects <65 years than in those aged 65-74 years and in those aged >74 years. No significant difference was found between the latter two groups. No difference was found between the three groups in terms of daily calcium intake and a significant negative correlation between symptom score and daily calcium intake was only found in the group of subjects aged <65 years. CONCLUSIONS: As age increases, the prevalence of lactose malabsorption shows an increase while the prevalence of intolerance symptoms among malabsorbers shows a decrease. Accordingly, daily calcium intake was similar among the adults and elderly studied.

Aged↗
PubMed2001

Endomysial and tissue transglutaminase antibodies in coeliac sera: a comparison not influenced by previous serological testing.

BACKGROUND: Since transglutaminase was shown to be the antigen of endomysial antibodies (EMA), it has become possible to screen for coeliac disease (CD) with an enzyme-linked immunosorbent assay (ELISA) for transglutaminase antibodies (TTA). However, it is possible that sera used to show that TTA are found in CD were obtained from patients diagnosed because they were positive for EMA. So, a comparison between EMA and TTA has not been possible so far. METHODS: EMA and TTA were tested in sera from 52 controls and 56 untreated CD patients, who had not undergone serological testing. Samples were tested for TTA with an ELISA kit. Based on the ROC analysis of a pilot study, results were considered as either positive, borderline, or negative. EMA were analysed by indirect immunofluorescence on monkey oesophagus. RESULTS: Forty-nine CD patients were positive for TTA, six borderline, one negative. Forty-four controls were negative, seven borderline, one positive. If we consider borderline results to be positive, sensitivity is 98.2% and specificity 84.6%. EMA were positive in 53 CD patients; the controls were all negative. Performing TTA in all cases and EMA only in the few TTA borderline cases (12.0%) would have a sensitivity of 94.6% and a specificity of 98.1%. CONCLUSIONS: This study is the first to compare TTA with EMA. Due to 100% specificity and high sensitivity, EMA seems to be the most accurate coeliac antibody. Conversely, TTA offer advantages in terms of sensitivity and simplicity. A satisfactory strategy is to use TTA first and then EMA to confirm the borderline results.

Adult↗
PubMed2001

Defining gluten refractory enteropathy.

OBJECTIVE: The diagnosis of coeliac disease (CD) is based on the responsiveness of the enteropathy to a gluten-free diet (GFD). This implies that terms such as 'non-responsive CD' and 'refractory CD' are almost paradoxical. In spite of this, these terms are commonly used in the literature, often with different and confusing meanings. METHODS: On the basis of both a review of the literature and our clinical experience, we propose the following classification. A condition characterized by a refractory enteropathy, not due to lymphoma, ulcerative jejunoileitis or collagenous sprue, but in which gluten sensitivity has been shown previously or could be shown while the patients were on an immunosuppressive therapy should be indicated as refractory CD. Those patients in whom gluten sensitivity can be excluded should be considered to be affected by non-coeliac refractory sprue. Finally, patients in whom the presence of CD cannot be either confirmed or excluded should be considered to be affected by undefined sprue. RESULTS: Twenty-four certain refractory patients are described in the literature. The data suggest a diagnosis of refractory CD in 13 patients, non-coeliac refractory sprue in three patients, and undefined sprue in eight patients. CONCLUSIONS: We define refractory CD as a form of CD that no longer responds to a GFD. Non-coeliac refractory sprue is a condition unrelated to CD. It could be either an independent condition or a common end point of different enteropathies.

Adult↗
PubMed2001

Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease.

BACKGROUND: Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial role in the generation of villous atrophy in coeliac disease (CD). However, the mechanisms by which they mediate the killing of enterocytes in this condition are still poorly characterised. AIM: We investigated Fas mediated cytotoxicity and apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls. METHODS: Fas and Fas ligand expression were assessed by flow cytometry and immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA. RESULTS: LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs manifested increased apoptosis whereas IELs showed decreased apoptosis. CONCLUSIONS: Our results support the involvement of the Fas/Fas ligand system in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to downregulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.

Adult↗
PubMed2001

Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease.

Our aim was to evaluate whether increased enterocyte apoptosis was responsible for mucosal flattening in celiac disease (CD), and, since the mechanisms responsible for tissue injury in this condition are unknown, we studied the possibility that the Fas-Fas ligand (FasL) system may be involved. Endoscopic duodenal biopsy specimens from 12 patients with untreated and 12 with treated CD and 12 control subjects were evaluated for enterocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling assay and for Fas and FasL expression by immunohistochemistry. A coculture of isolated enterocytes (targets) and purified lamina propria mononuclear cells (LPMCs) (effectors) was performed in the absence or presence of an antagonistic ZB4 anti-Fas antibody. We found a significant correlation between the degree of villous atrophy, morphometrically evaluated, and the level of enterocyte apoptosis, suggesting that mucosal flattening is a consequence of exaggerated epithelial cell death. Most celiac enterocytes express Fas, and LPMCs express FasL. The abolishment of enterocyte apoptosis observed in the presence of ZB4 antibody suggests that enterocytes are potential targets of lymphocyte infiltrate. These results directly demonstrate that FasL-mediated apoptosis is a major mechanism responsible for enterocyte death in CD.

Adult↗
PubMed2001

Lack of association with spondyloarthritis and HLA-B27 in Italian patients with Whipple's disease.

OBJECTIVE: To examine consecutive patients with Whipple's disease (WD) for the full clinical spectrum of spondyloarthritis. METHODS: Nine consecutive patients, 8 men, 1 woman, with WD were clinically evaluated and examined for clinical and radiological manifestations of spondyloarthritis by 2 rheumatologists with special interest in spondyloarthritis. The mean age of the patients at the time of study and at the time of their initial diagnosis of WD by duodenal biopsy was 62.4 years (range 42-71) and 54.4 years (range 40-62), respectively. Each patient had an anteroposterior radiographic view of the pelvis and also had HLA typing for class I and II alleles. Pelvis radiographs were read blindly for evidence of sacroiliitis. RESULTS: All but one patient had rheumatologic manifestations related to WD. The mean interval between the onset of these symptoms and the diagnosis of WD was 6.1 years (range 1-15). One had recurrent polyarthritis, 1 recurrent oligoarthritis, 3 recurrent monoarthritis, 2 recurrent synovitis with pitting edema of the dorsum of hands and/or feet, and 1 isolated De Quervain's tenosynovitis. Of the 5 patients with arthritis, 3 also had episodes of swelling with pitting edema over the dorsum of hands and/or feet together with flexor digit tenosynovitis, 2 also had olecranon bursitis, and 1 tibial tenosynovitis. No patient had clinical or radiological manifestations of spondyloarthritis. None had the HLA-B27. CONCLUSION: In Italian Caucasian patients with WD there was no association with spondyloarthritis and HLA-B27.

Adult↗