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Biomedical subjects

G R Corazza

Publications and source records attributed to G R Corazza.

At least 55 records · Page 3Linked to original sources

Increased red cell distribution width and coeliac disease.

BACKGROUND/AIMS: Despite availability of sensitive screening tests, coeliac disease is still underdiagnosed. To determine which haematochemical abnormalities might be more predictive of this condition, we reviewed the clinical records of our series of adult patients affected by coeliac disease. METHODS: Six haematochemical parameters (haemoglobin, red cell distribution width, serum levels of iron, albumin, calcium and potassium) were evaluated in 126 consecutive adult untreated coeliac patients diagnosed since 1990. RESULTS: Elevated red cell distribution width was the most frequent haematochemical abnormality, being present in 57.9% of our patients (Chi square analysis, p<0.01 versus other laboratory changes). CONCLUSION: The increase of red cell distribution width was more common than iron-deficiency anaemia, a well-known indicator of coeliac disease. Elevated red cell distribution width can thus be considered a new predictor of coeliac disease and in the presence of this a search should be made for antiendomysial antibodies.

Adolescent↗

Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis.

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Adult↗

Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth.

BACKGROUND: Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non-absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double-blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first-choice drug. METHODS: In 21 patients affected by small intestinal bacterial overgrowth, fasting, peak and total H2 excretion after ingestion of 50 g glucose and severity of symptoms were evaluated before and after a 7-day course of rifaximin, 1200 mg/day (400 mg t.d.s.), or chlortetracycline, 1 g/day (333 mg t.d.s. ). RESULTS: Fasting, peak and total H2 excretion decreased significantly in the group of patients treated with rifaximin whereas chlortetracycline did not modify these parameters. The H2 breath test normalized in 70% of patients after rifaximin and in 27% of patients after chlortetracycline. The improvement in symptoms was significantly higher in patients treated with rifaximin. CONCLUSIONS: Rifaximin is a promising, easily-handled and safe drug for the short-term treatment of small intestinal bacterial overgrowth.

Adult↗

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms.

BACKGROUND: Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. AIM: To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. METHODS: Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. RESULTS: Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. CONCLUSIONS: In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.

Absorption↗

Cytolytic mechanisms of intraepithelial lymphocytes in coeliac disease (CoD).

The effector arm of the mucosal immune system comprises lymphocytes scattered at intraepithelial and lamina propria levels. Intraepithelial lymphocytes (IEL) are a large population of oligoclonal resting cells which exhibit phenotypic and functional characteristics of cytolytic T cells when activated. Several mechanisms have been demonstrated to account for their cytotoxicity. Among them, one is mediated by perforin and granzyme molecules, another is mediated by Fas ligand (FasL) which delivers apoptotic signals through Fas receptor on target cells. There is good evidence that a flat intestinal mucosa may be produced by activated T cells. The aim of our study was to evaluate FasL and perforin expression by IEL, and its possible correlation with the increased enterocyte apoptosis in coeliac mucosa. Endoscopic duodenal biopsy specimens from 10 untreated coeliac patients, 10 treated coeliac patients, and 10 biopsied controls were evaluated for enterocyte apoptosis by terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end label method, for perforin expression by immunohistochemistry, and for FasL expression by immunocytochemistry. In untreated CoD there was a significant increase of percentage of both FasL+ and perforin+ IEL which positively correlated with enterocyte apoptosis in comparison with controls. All these parameters were significantly lower in treated CoD, even though they did not normalize. Our study demonstrates that in untreated CoD FasL and perforin expression by IEL is increased, and significantly correlates with the level of enterocyte apoptosis.

Adolescent↗

Role of lifestyle factors in the pathogenesis of osteopenia in adult coeliac disease: a multivariate analysis.

OBJECTIVES: Coeliac disease is frequently complicated by alterations of bone mass and mineral metabolism. In this condition the degree of malabsorption is a major determinant of bone loss. However, the role of lifestyle factors such as exposure to sunlight, physical activity and cigarette smoking, which have been demonstrated to influence bone mass and mineral metabolism in other conditions, has never been investigated in coeliac disease. DESIGN: We evaluated the impact of potential co-factors on bone homeostasis in coeliac disease by means of a multivariate analysis model. METHODS: Thirty-nine adult patients with untreated coeliac disease (18 symptomatic, 21 subclinical/silent) were studied. Bone mineral density was measured by dual-energy X-ray absorptiometry at lumbar spine and femoral neck levels. Age at diagnosis, gender, duration of symptoms and severity of symptoms were recorded. Nutritional status, cigarette smoking habit, exposure to sunlight, and physical activity were evaluated. The impact of each independent variable on lumbar and femoral bone mineral density was evaluated by means of a multivariate analysis model. RESULTS: The severity of symptoms and nutritional status were significant sources of variability of both lumbar and femoral bone mineral density. Physical activity was a significant source of variability at femoral level, while gender was at lumbar level. Cigarette smoking habit and exposure to sunlight showed no significant effect on bone mineral density. CONCLUSIONS: Gender, malnutrition, global severity of the disease and physical activity are important co-factors in the pathogenesis of bone loss in coeliac disease.

Absorptiometry, Photon↗

IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency. Working Groups on Celiac Disease of SIGEP and Club del Tenue.

BACKGROUND: In selective IgA deficiency (IgAD), there is no reliable screening test for coeliac disease (CD). AIM: To evaluate the usefulness of IgG(1) antiendomysium and IgG antitissue transglutaminase tests for CD diagnosis in IgAD. METHODS: IgA and IgG antigliadin antibodies (IgA- and IgG-AGA), IgA and IgG(1) antiendomysium antibodies (IgA- and IgG(1)-EMA), and IgA and IgG antitissue transglutaminase (IgA- and IgG-anti-tTG) were assayed in: (a) 20 untreated IgAD/CD patients; (b) 34 IgAD/CD patients on a strict gluten free diet (GFD); (c) 10 IgAD/CD patients not on a strict GFD; (d) 11 untreated CD patients without IgAD; (e) 10 healthy IgAD patients; and (f) 25 healthy controls. RESULTS: In all untreated IgAD/CD patients, IgG(1)-EMA, IgG-anti-tTG, and IgG-AGA were positive whereas IgA antibodies against these antigens were negative. IgAD/CD patients on a strict GFD did not produce IgG-AGA or IgG(1)-EMA but four of 34 produced IgG anti-tTG. IgAD/CD subjects not on a strict GFD produced IgG-AGA whereas 5/10 and 4/10 were IgG(1)- EMA and IgG-anti-tTG negative, respectively. Untreated CD patients without IgAD were AGA (IgA and IgG), EMA (IgA and IgG(1)), and anti-tTG (IgA and IgG) positive. Healthy controls were AGA and EMA negative whereas two of 10 apparently healthy IgAD subjects and one of 25 healthy negative control were IgG-anti-tTG positive. CONCLUSIONS: Both IgG(1)-EMA and IgG-anti-tTG tests appear to be useful for identification of IgAD/CD patients whereas they are less satisfactory for monitoring dietary compliance in these subjects. In addition, our findings seem to suggest that IgG-EMA autoantibodies produced by coeliac patients are mainly of the IgG(1) subtype.

Case-Control Studies↗

Immune reaction against the cytoskeleton in coeliac disease.

BACKGROUND: The cytoskeleton actin network of intestinal microvilli has been found to be rapidly impaired after gluten challenge in coeliac disease (CD). The aim of this study was to investigate the presence of an immune reaction towards cytoskeleton structures such as actin filaments in CD. METHODS: Eighty three antiendomysial antibody positive CD patients (52 children and 31 adults) were studied at our outpatient clinics from 1996 to 1998 using indirect immunofluorescence, ELISA, and western blotting for antiactin (AAA) and antitissue transglutaminase (TGA) antibodies before and after a gluten free diet (GFD). Sixteen patients with smooth muscle antibody positive autoimmune hepatitis, 21 with inflammatory bowel diseases, seven with small bowel bacterial overgrowth, and 60 healthy subjects were studied as controls. RESULTS: Fifty nine of 83 CD patients (28/31 adults (90.3%); 31/52 children (59.6%)) were positive for IgA and/or IgG AAA. Seventy seven (92.7%) were positive for IgA TGA. IgA AAA were strongly correlated with more severe degrees of intestinal villous atrophy (p<0.0001; relative risk 86.17). After a GFD, AAA became undetectable within five months. CONCLUSIONS: Apart from the immune reaction against the extracellular matrix, we have described an immune reaction against the cytoskeleton in both children and adults with CD. As AAA are strongly associated with more severe degrees of villous atrophy, they may represent a useful serological marker of severe intestinal atrophy in CD.

Adolescent↗

Bone mass and metabolism in dermatitis herpetiformis.

Dermatitis herpetiformis is a gluten-sensitive skin disease with intestinal lesions and malabsorption symptoms less severe than those found in celiac disease. While several studies have shown the occurrence of osteopenia in celiac disease, bone mass and metabolism have never before been evaluated in dermatitis herpetiformis. Therefore, in 16 untreated patients, 16 sex- and age-matched untreated celiac patients, and 16 sex- and age-matched healthy volunteers, lumbar and femoral bone mineral density were measured and bone and mineral metabolism and nutritional status were evaluated. All these parameters were significantly altered in the two groups of patients and although the degree of these alterations was milder in patients with dermatitis herpetiformis than in celiac patients, the presence of subtotal villous atrophy in patients with dermatitis herpetiformis was associated with the presence of more severe alterations. Bone mineral density was significantly correlated with nutritional status, and patients showing bone loss were characterized by a body mass index lower than 20. Alterations of bone mass and mineral metabolism complicate dermatitis herpetiformis when severe intestinal lesions coexist. A low nutritional status may be predictive of the presence of bone loss.

Absorptiometry, Photon↗

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↗

Transglutaminase and coeliac disease: endomysial reactivity and small bowel expression.

This study was aimed at verifying whether tissue transglutaminase (tTG) is the sole autoantigen eliciting anti-endomysial antibodies in coeliac disease (CoD) and investigating tTG expression in normal and coeliac mucosa. Twelve anti-endomysial-positive coeliac sera and 12 anti-endomysial-negative control sera (10 microl, diluted 1:5-1:400 in PBS pH 7.3) were preincubated with 10, 20 or 50 microg guinea pig liver tTG at 4 degrees C overnight. Monkey oesophagus tissue slides were then tested with tTG-preincubated and non-preincubated sera to search for IgA anti-endomysial reactivity by indirect immunofluorescence. Moreover, six sections of monkey oesophagus were incubated with an anti-tTG mouse MoAb, six sections with an anti-cytokeratin mouse MoAb and six sections with only 3% bovine serum albumin. Finally, endoscopic duodenal biopsy sections obtained from 12 patients affected by untreated CoD, six patients affected by treated CoD and 10 biopsied controls were immunohistochemically stained with a peroxidase-conjugated anti-tTG MoAb. Our results show that (i) preincubation with tTG abolished endomysial immunofluorescence in most, but not in all, coeliac sera; (ii) the incubation of anti-tTG MoAb with sections of monkey oesophagus resulted in an immunofluorescence staining pattern similar but not identical to that of anti-endomysial-positive coeliac sera; (iii) although tTG expression was present at muscularis mucosae and pericryptal fibroblast in both normal and coeliac mucosa, it was slightly more marked and evident in the latter. Although our absorption experiment was performed with guinea pig liver tTG, we confirm that tTG is the predominant antigen of endomysial antibodies, but we speculate that, at least in some patients, it is not the only one.

Animals↗

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↗

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↗

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↗

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↗