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Biomedical subjects

G R Corazza

Publications and source records attributed to G R Corazza.

At least 19 recordsLinked to original sources
PubMed1999

A non-toxic analogue of a coeliac-activating gliadin peptide: a basis for immunomodulation?

BACKGROUND: A-gliadin residues 31-49 (peptide A) binds to HLA-DQ2 and is toxic to coeliac small bowel. Analogues of this peptide, which bind to DQ2 molecules but are non-toxic, may be a potential route to inducing tolerance to gliadin in patients with coeliac disease. METHODS: Toxicity was investigated with small bowel organ culture in six patients with untreated coeliac disease, four with treated coeliac disease and six controls. Analogue peptides comprised alanine substituted variants of peptide A at L31 (peptide D), P36 (E), P38 (F), P39 (G) and P42 (H). RESULTS: Peptides D and E were toxic in biopsies from some patients. Peptides F, G and H were not toxic. CONCLUSIONS: Peptide F, which binds to DQ2 more strongly than peptide A, is not toxic in patients with coeliac disease in-vitro; this could be an initial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.

Adult↗
PubMed1999

A reassessment of splenic hypofunction in celiac disease.

OBJECTIVES: Because there is controversy regarding the prevalence, familial occurrence, and possible factors inducing splenic hypofunction in celiac disease, we have reassessed them in a large series of untreated patients and their first-degree relatives. METHODS: Pitted red cell counting was used to measure splenic function and the effect that age at diagnosis has on it, while severity of intestinal lesions and nutritional status were estimated by multiple linear regression analysis. Moreover, serum tuftsin activity was assayed by measuring its ability to stimulate phagocytosis of opsonized Staphylococcus aureus. RESULTS: We found that 32.8% of untreated celiacs and none of their relatives had pitted red cell values in the range of splenic hypofunction (>4%). Only age at diagnosis, but not the other two covariates, was significantly associated with the degree of splenic hypofunction. Tuftsin activity was depressed in celiac disease and this reduction was significantly greater in hyposplenic patients. CONCLUSIONS: In celiac disease the prevalence of splenic hypofunction is lower than formerly believed. The duration of preexposure to gluten is a crucial factor for the prevalence and severity of this complication that does not affect celiac relatives. In celiac disease splenic hypofunction is accompanied by a reduced phagocyte activity linked to the decreased release of tuftsin.

Adult↗
PubMed1999

The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases.

OBJECTIVE: The demographic, clinical, and epidemiological features of subclinical/silent celiac disease in Italy were analyzed in a multicenter study carried out with the participation of 42 centers, in the years between 1990 and 1994. METHODS: One thousand twenty-six subclinical/silent patients (644 children and 382 adults, 702 women and 324 men) were considered eligible for the study. RESULTS: The prevalence of the subclinical/silent form increased significantly during the study both in adults (p < 0.001) and in children (p < 0.005), but its prevalence was always lower (p < 0.001) in children than in adults. This increase appears more likely due to a greater diagnostic awareness and to a better use of screening than to a higher number of subclinical/silent cases. Whereas in 1990 a significantly higher proportion (p < 0.001) of subclinical/silent celiac patients was diagnosed in Northern Italy rather than in Southern-Insular Italy, both in adults (46.7% vs 17.2%) and in children (22.0% vs 9.0%), in 1994 such a difference was no longer conspicuous. Both in children and in adults, iron-deficiency anemia appeared to be the most frequent extraintestinal symptom, followed by short stature in children and cutaneous lesions of dermatitis herpetiformis in adults. In 25.9% of the cases another disease was present, with a significantly higher frequency (p < 0.05) in adults (30.1%) than in children (20.7%). Diabetes and atopy appeared to be the most frequently associated conditions both in children and in adults. CONCLUSIONS: This study has provided an analysis of the largest series of subclinical/silent celiac disease reported to date. In Italy, this form is most frequently recognized in adults, and prospective studies will clarify whether the lower frequency observed in children is a real or apparent phenomenon.

Adolescent↗
PubMed1999

Tissue transglutaminase antibodies in celiac disease.

OBJECTIVE: Tissue transglutaminase is the antigen for antiendomysial antibodies, whose power in screening for celiac disease is well known. Our aim was to assess the efficacy of an ELISA assay for tissue transglutaminase antibodies. METHODS: Tissue transglutaminase antibodies were analyzed in serum from 39 untreated celiac disease patients and 61 controls. Tissue transglutaminase was used as antigen, and test sera analyzed by ELISA. Results higher than 0.6 optical density were considered positive, lower than 0.4 negative, and between 0.4 and 0.6 borderline. RESULTS: Optical density of the serum from the patients with untreated celiac disease (median: 1.41; range: 0.33-1.47) were significantly higher than the controls (median: 0.32; range: 0.17-0.68; p < 0.0001; 95% confidence interval 0.87-1.08). Thirty-three patients with untreated celiac disease were positive, 4 borderline, and 2 negative. Fifty-five controls were negative, 4 borderline, and 2 positive. If we consider borderline results to be positive, sensitivity is 94.8% and specificity 90.1%. None of the controls gave results higher than 0.7 optical density. Apart from the 2 negative patients with untreated celiac disease, the two groups overlapped only between 0.4 and 0.7 optical density. CONCLUSIONS: Because of the high sensitivity (approximately 95%) and technical simplicity, tissue transglutaminase antibodies may prove useful for the screening of celiac disease in population at low or medium risk of celiac disease. To avoid duodenal biopsies in patients without celiac disease, the specificity of the screening procedure may be increased by confirming with antiendomysial antibodies by immunofluorescence on human umbilical cord in individuals with results between 0.4 and 0.7 optical density.

Adolescent↗
PubMed1999

Apoptosis and gastrointestinal tract.

The gastrointestinal tract is characterized by a rapid proliferation of stem cells that differentiate to become terminal mature cells and ultimately die through a genetically programmed form of cell death, termed apoptosis, which is responsible for maintaining of tissue size. Apoptosis has also been shown to play an important role in the pathophysiology of several gastrointestinal diseases. The development of many infectious and immune-mediated diseases, such as gastritis, coeliac disease, inflammatory bowel diseases, may be triggered by the prevalence of pro-apoptotic signals, whereas prolonged cell survival, due to apoptosis inhibition, may give rise to neoplastic clones. Elucidation of the biochemical pathways and of specific proteins regulating apoptosis may provide a remarkable opportunity to manipulate the life and death decisions of the gastrointestinal cells and to develop new therapeutic strategies. This review will deal with the mechanisms potentially involved in apoptosis and with the clinical relevance of this phenomenon in gastrointestinal diseases.

Apoptosis↗
PubMed1998

Proliferating cell nuclear antigen expression is increased in small bowel epithelium in the elderly.

Although previous studies suggest that in aging animals the small intestine is in a hyperproliferative state, no information is currently available on the influence of age on the proliferation pattern of human small bowel enterocytes. The immunohistochemical expression of the proliferating cell nuclear antigen (PCNA), the villous height to total mucosal thickness ratio and the enterocyte height were evaluated in a panel of duodenal biopsy specimens obtained from 18 subjects aged less and 14 subjects aged more than 65 years. There was a significant positive correlation (P < 0.001) between age in years and percent of positive PCNA enterocytes both at the level of crypts (rs = 0.50) and villi (rs = 0.77). Moreover, the percentage of PCNA+ enterocytes was significantly higher in elderly versus adult subjects, both at the level of villi (6.5 vs 0%; P < 0.001) and of crypts (40.0 vs 23.7%; P < 0.01). No correlation was found between the percentage of PCNA + enterocytes and enterocyte height or villous height to total mucosal thickness ratio. Our results show that PCNA reactivity increases with advancing age both in crypts and villi. This abnormality of the proliferation pattern may explain the coexistence of normal morphology and impaired absorptive function in the elderly.

Adult↗
PubMed1998

Phenotyping of peripheral blood lymphocytes in adult coeliac disease.

In coeliac disease immunological abnormalities are not confined to the small bowel and it has been suggested that changes in peripheral blood lymphocytes may predispose to autoimmune or malignant complications. Using dual-colour immunofluorescence with labelled monoclonal antibodies, multiparameter flow cytometry was used to analyse peripheral blood lymphocytes in 32 untreated coeliacs, 29 treated coeliacs and 20 healthy volunteers. When the absolute numbers were considered, a decrease of CD3+, CD4+, CD8+ and CD19+ lymphocytes was found in untreated coeliacs compared with treated coeliacs and healthy volunteers. The proportion of CD3+ was significantly higher in untreated coeliacs (P<0.05) than in healthy volunteers. No differences were observed in CD4+, CD8+ and CD19+ subsets between the three groups studied. The proportion of CD3+ CD25+ and CD3+ HLA-DR+ cells were higher in untreated coeliacs (P<0. 001 and P>0.005) and in treated coeliacs (P<0.005 and P<0.05) than in healthy volunteers. On the contrary, natural killer cells and cytotoxic cells were lower in untreated and treated coeliacs than in healthy volunteers. As regards B-cell subsets, the only difference was the increase in FcepsilonR+ B cells in untreated coeliacs. The absolute reduction of peripheral lymphocytes in coeliac disease probably reflects their compartimentalization in intestinal mucosa. The decrease of natural killer cells and cytotoxic cells may be in keeping with the increased prevalence of malignancy in this condition. Finally, the phenotypic changes found in untreated coeliacs indicate T-cell activation.

Adult↗
PubMed1998

Bone mass and metabolism in Whipple's disease: the role of hypogonadism.

BACKGROUND: Whipple's disease, like other malabsorption syndromes, ought to predispose to osteopenia. We therefore evaluated bone mass and mineral metabolism in a cohort of patients with this condition. METHODS: Twelve male patients with Whipple's disease and 36 male age-matched healthy subjects took part in the study. None of the patients complained of diarrhea at the time of the study. Bone mineral density at the lumbar and femoral level and serum levels of indices of bone and mineral metabolism and of gonadal function were measured. RESULTS: Bone mineral density at the total femur and femoral neck were significantly lower in patients with Whipple's disease than in healthy volunteers, whereas no significant difference was found at the lumbar level. In patients with Whipple's disease serum levels of type-I collagen teleopeptide (ICTP) and sex-hormone-binding globulin were significantly higher, whereas serum levels of testosterone and luteinizing hormone were significantly lower than in healthy volunteers. Moreover, testosterone correlated significantly (P < 0.05) with lumbar bone mineral density (r(s) = 0.64) and serum ICTP levels (r(s) = -0.63). CONCLUSIONS: In patients with previously treated Whipple's disease and without any current symptoms of malabsorption, bone loss is generally moderate and linked to the presence of hypogonadism.

Bone Density↗
PubMed1998

Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study. Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP) and "Club del Tenue" Working Groups on Coeliac Disease.

BACKGROUND: Selective immunoglobulin A (IgA) deficiency (SIgAD) is associated with coeliac disease (CD). AIM: To make a retrospective study of the association of SIgAD with CD in Italy. METHODS: Hospital medical records of 2098 patients consecutively diagnosed as having CD were reviewed. RESULTS: Of 2098 patients with CD, 54 (2.6%) had SIgAD, representing a 10-16-fold increase over that in the population in general. This increase was not influenced by age or geographical factors. Patients with SIgAD had a higher incidence of silent forms (7/54, 13%), recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those without. The association with autoimmune and malignant diseases and the outcome after eating a gluten free diet were similar in patients with or without SIgAD. In all patients with SIgAD, antibodies for IgA gliadin and endomysium were absent, but serum levels of IgG anti-gliadin antibodies were high in almost all of them (51/54). CONCLUSIONS: Serum IgA should be measured in order to be able to interpret negative results for IgA anti-gliadin antibodies and anti-endomysial antibodies in patients being screened for CD. Since some patients with CD and SIgAD may be negative for IgG anti-gliadin antibodies, an intestinal biopsy should be performed in all suspected cases.

Adolescent↗
PubMed1998

Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition.

BACKGROUND: Reticuloendothelial system function is impaired in humans receiving lipid regimens. AIMS: To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function. METHODS: Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn's disease who were not receiving intravenous nutrition, and 50 healthy controls. RESULTS: Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p<0.001) than in healthy controls (0.6%) and in patients with Crohn's disease (0.9%). No difference was found between healthy controls and patients with Crohn's disease. There was a correlation (r=0.50; p<0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p<0.01) and healthy volunteers (17.8%, p<0.001). An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition (r(s) =-0.44, p<0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12 months. CONCLUSIONS: Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection.

Adult↗
PubMed1998

Splenic function in old age.

Hyposplenism has been reported in elderly people. However, from previous studies, it was not clear whether the observed alterations in splenic function were a physiologic effect of advanced age itself or a consequence of age-related diseases. As hyposplenism is believed to predispose to infections, autoimmune phenomena and thrombosis, this question is of great clinical concern. In the present study splenic function was assessed by counting the pitted red cells in 65 healthy subjects aged 50-108 years. At variance from previous studies, our study population consisted of free-living individuals carefully selected in order to exclude any underlying disease. The percentage of pitted red cells in 37 subjects over 70 years was significantly higher than in 28 younger subjects, although only 1 subject had a pitted red cell count indicating splenic hypofunction. A positive, but weak, correlation between the percentage of pitted red cells and age was also found when considering the whole population (rs = 0.273, p = 0.029). In conclusion, although slightly reduced with advancing age, splenic function seems basically to be maintained in elderly people.

Aged↗
PubMed1998

Tissue transglutaminase antibodies for coeliac disease screening.

We have prospectively searched for IgA anti-transglutaminase antibodies by an enzyme-linked immunosorbent assay test in 20 untreated coeliacs and 21 patients with small bowel diseases other than coeliac disease consecutively referred to our Malabsorption Clinic. All the untreated coeliacs and one out of 21 disease controls turned out to be positive for the presence of these antibodies. The use of the enzyme-linked immunosorbent assay test for anti-transglutaminase antibodies could represent a new screening test for coeliac disease, in fact, this new enzyme-linked immunosorbent assay test has an absolute sensitivity and a satisfactory specificity and, in comparison to antiendomysial antibodies, is less expensive and avoids the ethical problems related to the use of monkey oesophagus.

Adult↗
PubMed1997

Autoimmune enteropathy and villous atrophy in adults.

BACKGROUND: Autoimmune enteropathy is a condition described in children and characterised by villous atrophy, which is unresponsive to any dietary restrictions, and by the presence of enterocyte autoantibodies. We report two adult patients who fulfilled all the criteria for the diagnosis of this disorder. METHODS: Over the past 5 years we have seen four adult patients (all women, median age 51.5 [range 38-64] years) with subtotal villous atrophy, which was unresponsive to a gluten-free diet. The patients were HLA-DQ2 positive. IgA antigliadin and antiendomysial antibodies were not found in any of the patients. We did an indirect immunofluorescence search for enterocyte autoantibodies on monkey jejunum and for other autoantibodies for all four patients. FINDINGS: Of the four patients, two were positive for enterocyte autoantibodies and one of these two patients was positive for antiactin, antiparietal cell, and antithyroid microsomal autoantibodies. INTERPRETATION: To the best of our knowledge the two patients affected by severe enteropathy, who had never responded to any exclusion diet, and who were positive for enterocyte autoantibodies are the first cases of autoimmune enteropathy described in adults. We propose that adult patients whose disorders are unresponsive to a gluten-free diet should be tested for enterocyte autoantibodies.

Actins↗
PubMed1997

Propeptide of type I procollagen is predictive of posttreatment bone mass gain in adult celiac disease.

BACKGROUND & AIMS: Adult celiac disease is associated with osteopenia, which is not always reversible after gluten-free diet (GFD). A prospective study was conducted to evaluate whether pretreatment indices of bone and mineral metabolism are predictive of the extent of bone mass gain after diet. METHODS: Lumbar and femoral bone mineral density (z-score) and serum levels of parathyroid hormone, 1,25-dihydroxycholecalciferol, COOH-terminal propeptide of type I procollagen (PICP), and COOH-terminal telopeptide of type I collagen (ICTP) were measured in 20 celiac patients at diagnosis and after 2 years of GFD. RESULTS: All patients showed a posttreatment improvement in bone mass and in serum levels of indices of bone and mineral metabolism. Nevertheless, only in 12 of 20 patients was this improvement at least equal to half the SD of the z-score, which equals a gain of at least 5% in bone mass. Pretreatment levels of PICP strictly correlated with the increase in lumbar (r(s) = 0.92; P < 0.001) and femoral z-scores (r(s) = 0.89; P < 0.001). Only in patients with basal PICP above the normal range did the z-score increase after GFD by at least half the SD. CONCLUSIONS: In adult celiac disease, a high rate of osteosynthetic activity before treatment is predictive of the satisfactory recovery of bone mass after GFD.

Absorptiometry, Photon↗
PubMed1997

The impact of HIV infection on lactose absorptive capacity.

Forty HIV-infected adult patients at different disease stages and 44 healthy volunteers were evaluated for lactose malabsorption using the hydrogen breath test after 20 g lactose ingestion. All subjects were previously tested for breath hydrogen (H2) excretion after 12 g lactulose ingestion. The presence of intestinal superinfections, gastrointestinal symptoms and the intensity of clinical intolerance after lactose load were accurately searched in each patient. The cumulative H2 excretion after lactulose did not significantly differ between the different groups studied. The prevalence of lactose malabsorption turned out to be significantly higher (P < 0.001) in HIV-infected patients (70%) than in controls (34%). Moreover, in patients in more advanced disease stages the degree of lactose malabsorption was significantly greater than in patients at earlier disease stages, who did not differ from healthy volunteers. Furthermore the degree of lactose intolerance was significantly greater (P < 0.001) in symptomatic patients than in those without intestinal symptoms and in healthy volunteers, while no significant difference was observed between these latter groups. The results here demonstrate the negative impact of HIV infection on lactose absorptive capacity in adult patients, particularly marked in more advanced stages of the disease, suggesting that, in addition to the presence of the virus alone, other factors may contribute to determine the enterokinetic alterations responsible for lactase deficiency.

Adolescent↗