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Biomedical subjects

C Sategna-Guidetti

Publications and source records attributed to C Sategna-Guidetti.

At least 19 recordsLinked to original sources

Hypoparathyroidism and co-existing celiac disease.

A 62-yr-old woman with idiopathic hypoparathyroidism was admitted to our hospital for severe anemia (Hb 5.6 gr/dl) and hypoalbuminemia (3.2 gr/dl). Hypoparathyroidism was diagnosed when she was 33 yr old, because of repeated hypocalcemic tetanic crises, low calcium and high phosphate levels. Since then she has been treated with oral calcium gluconate and calcitriol, with satisfactory clinical balance and normalization of calcium serum levels. After menopause, despite this therapy, the patient still had frequent hypocalcemic tetanic crises, resolving with iv administration, in high doses, of calcium gluconate. The anemia, for which the patient came to our attention, was hypochromic microcytic and in the past she had been treated with iron and transfusion therapy. The patient's recent history also revealed recurrent long lasting episodes of diarrhea, hyporexia and weight loss. The clinical presentation seemed related to a malabsorption syndrome: a celiac disease (CD) diagnosis was confirmed, based upon the finding, at duodenal biopsy, of a severe villous atrophy. A bone mineral density (BMD) evaluation showed a limited reduction of femoral values classified as osteopenia according to the World Health Organization (WHO) criteria. Thereafter, the patient was instructed to follow a gluten-free diet which rapidly led to an improvement of the nutritional parameters and to a reduction of calcium and vitamin D requirements. Difficult clinical and metabolic control in hypoparathyroidism patients may suggest the possible co-existence of both endocrine and extra-endocrine autoimmune diseases, such as CD. Moreover, bone density, normally reduced in celiac patients, seems to be preserved (maintained) by the lack of parathyroid secretion.

Bone Density↗

Binding by serum IgA antibodies from patients with coeliac disease to monkey heart tissue.

BACKGROUND: The recently reported increased prevalence of coeliac disease in heart transplant candidates and in patients with autoimmune myocarditis may suggest an autoimmune process towards antigenic components of both myocardium and small bowel. The objective of this study was to determine the possible presence of IgA antibodies directed against heart tissue in sera from patients with coeliac disease. METHODS: Sera samples from 28 biopsy-proven coeliac disease patients and 81 controls (both healthy and diseased) were assessed by indirect immunofluorescence, with fluorescein isothiocyanate labelled rabbit anti-human IgA, on commercial monkey cardiac muscle sections. RESULTS: A strong fluorescence around heart muscle fibres was found in 13 out of 15 untreated patients but none in either those treated for coeliac disease or in controls. Pretreatment with tissue transglutaminase, a prominent coeliac auto-antigen, abolished the typical fluorescent pattern almost completely. CONCLUSIONS: Our study demonstrates that in untreated coeliac disease there is a reaction of IgA antibodies sera, yielding a strong fluorescence, with monkey heart structures, and that tissue transglutaminase is the target antigen in this reaction.

Animals↗

Psychiatric predictors of noncompliance in inflammatory bowel disease: psychiatry and compliance.

Compliance with medications is very important in the management of many gastrointestinal disorders: in inflammatory bowel disease (IBD), controlled trials have shown the benefit of prophylactic medical treatment in lowering the risk of recurrences. Our aim was to appraise the association between current psychiatric disorders and medication adherence in an unselected consecutive group of outpatients with IBD. In 85 unselected consecutive outpatients with IBD, a professional structured diagnostic interview and a psychiatric assessment, by the Structured Clinical Interview for Diagnostic and Statistical Manual-III-Reviewed, were carried out. In a stepwise regression analysis, compliance, as dependent variable, correlated positively with disease duration and inversely with both disease severity and presence of psychiatric disorders. In patients with IBD, preventive liaison psychiatry interventions seem indicated.

Female↗

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.

OBJECTIVES: Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function. METHODS: A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies. RESULTS: Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later. CONCLUSIONS: The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Adult↗

The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients.

OBJECTIVES: To evaluate the impact of a 1-year gluten-free diet on bone metabolism and nutritional status in coeliac disease. METHODS: Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly-diagnosed, biopsy proven, coeliac disease patients (untreated). A complete reevaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated). RESULTS: Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone-Gla-protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten-free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre-albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment. CONCLUSIONS: Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten-free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.

Adult↗

A novel method for detecting IgA endomysial antibodies by using human umbilical vein endothelial cells.

BACKGROUND: Although tissue transglutaminase was recently identified as the main autoantigen recognized by endomysial antibodies in coeliac patients, anti-endomysium antibody detection still persists as the gold standard for coeliac disease screening and diagnosis. OBJECTIVES: (1) To evaluate human umbilical vein cells (HUVEC) as an alternative source of endomysial antigen and to assess their suitability in the diagnosis of coeliac disease. (2) To verify whether tissue transglutaminase is one target antigen eliciting the endomysial antibody fraction of coeliac serum IgA. SETTING: University teaching hospital. PATIENTS AND METHODS: Sera from 123 untreated adults with biopsy-proven coeliac disease and 84 controls (40 healthy and 44 diseased) were assessed by indirect immunofluorescence, using HUVEC on glass slides prepared by cytocentrifugation and permeabilized by using Triton X (0.5%). Indirect immunofluorescence was performed: (1) using coeliac disease serum samples on HUVEC with or without prior incubation with tissue transglutaminase; and (2) incubating both HUVEC and monkey oesophagus with goat anti-guinea pig tissue transglutaminase antibody. RESULTS: All the coeliac patients, who were also positive on monkey oesophagus, showed the typical fluorescent homogeneous cytoplasmic stain on HUVEC. All control sera were negative both on HUVEC and on monkey oesophagus. IgA antibodies did not react with non-permeabilized cells, with intact membrane. Preincubation of coeliac sera with tissue transglutaminase abolished the typical fluorescent pattern. The incubation of anti-tissue transglutaminase antibody with monkey oesophagus and HUVEC resulted in an immunofluorescence staining pattern identical to that obtained with positive coeliac sera. CONCLUSIONS: (1) As a substrate for anti-endomysial antibody, HUVEC may provide the same diagnostic accuracy as monkey oesophagus, thus bypassing economical and ethical problems. The HUVEC antigen reacting with IgA from coeliac disease sera is an intracellular rather than a cell-surface antigen, as IgA antibodies reacted only with permeabilized cells. (2) Pretreatment of untreated coeliac sera with tissue transglutaminase abolished almost completely the specific staining; incubation with anti-tissue transglutaminase antibody elicited the characteristic fluorescent pattern, thus confirming that tissue transglutaminase represents the prominent autoantigen in coeliac disease.

Adult↗

Indirect immunofluorescence for anti-jejunum antibody detection in celiac disease: comparison among different antigenic substrates.

BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunum antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscularis, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use.

Journal Article↗

Autoimmune thyroid diseases and coeliac disease.

BACKGROUND: Coeliac disease may be associated with a wide variety of diseases of known or suspected immunological aetiology. OBJECTIVE: To screen for both (a) the prevalence of coeliac disease in adults with autoimmune thyroid diseases, and (b) thyroid impairment among adults with coeliac disease, as compared to sex- and age-matched controls. DESIGN: Prospective cohort study. SETTING: University teaching hospital. PATIENTS: A total of 152 consecutive adults with autoimmune thyroid diseases, 185 consecutive coeliac disease patients (53 newly diagnosed and 132 already on a gluten-free diet) and 170 sex- and age-matched controls. METHODS: Screening for coeliac disease was done by means of IgA anti-endomysium antibodies, detected by indirect immunofluorescence on monkey oesophagus. Patients with positive sera underwent duodenal biopsy for diagnostic confirmation. Thyroid function was assessed by measuring the levels of serum thyroid-stimulating hormone, free T3, free T4, thyroperoxidase and thyroid microsome antibodies. Autoimmune thyroid diseases were classified according to the American Thyroid Association guidelines. RESULTS: Anti-endomysium antibodies were positive in five of 152 autoimmune thyroid disease patients (3.3%) and coeliac disease was histologically confirmed in all: this prevalence is 10-fold higher than expected. Only one patient presented with gastrointestinal complaints, but iron deficiency was found in three and alterations at bone mineralometry in all. The overall prevalence of autoimmune thyroid diseases was significantly higher (38/185, 20.5%) in coeliac patients than in controls (19/170, 11.2%). The prevalence of both hypo- and hyperthyroidism was not different from that of controls, while the prevalence of autoimmune thyroid disease with euthyroidism was 13% in patients and 4.7% in controls. CONCLUSIONS: The association of coeliac disease with autoimmune thyroid disease is not surprising as they share common immunopathogenetic mechanisms. It is advisable to screen autoimmune thyroid disease patients for coeliac disease as there is an increased risk for gluten intolerance. In contrast, thyroid function assessment in coeliac disease patients is probably less justified, although the need for a strict clinical follow-up of those patients with euthyroidism and autoimmune thyroid disease, who could develop overt thyroid impairment, remains an open question.

Adolescent↗

Indirect immunofluorescence for of anti-jejunum antibody detection in celiac disease: comparison among different antigenic substrates.

BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunun antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscolaris, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use.

Adult↗

Is human umbilical cord the most suitable substrate for the detection of endomysium antibodies in the screening and follow-up of coeliac disease?

BACKGROUND: Immunoglobulin A (IgA) anti-endomysium antibodies, the most reliable immunological marker for both the screening and follow-up of coeliac disease, need monkey oesophagus as antigenic substrate; this limits their use because of high costs and the exploitation of endangered species. OBJECTIVES: (1) To compare the diagnostic accuracy of anti-endomysium antibodies detected by indirect immunofluorescence on monkey oesophagus and on human umbilical cord; (2) to evaluate their reliability during follow-up in detecting non-compliant patients. PATIENTS: One hundred and four untreated adults with biopsy-proven coeliac disease and 94 controls were investigated. RESULTS: Endomysium antibodies were found in 99 patients (95%) on both substrates, with a specificity, respectively, of 100% and 99% on monkey oesophagus and umbilical cord. One year after gluten withdrawal, out of 47 patients who were investigated, only six presented with complete mucosal recovery: none of these subjects was positive on either substrates, while, among patients with persistent histological alterations, endomysium positivity persisted in only 10 on monkey oesophagus, but in 32 on umbilical cord. Histology (recovery or persistent involvement) was in agreement with endomysium (negative or positive) in 34% on monkey oesophagus, but in 81% on umbilical cord (P < 0.0001). CONCLUSION: Human umbilical cord, with its comparable diagnostic efficiency, could replace monkey tissues, with the advantages of saving both money and monkeys. Moreover, it seems the most suitable substrate in the follow-up, as it enables detection of non-compliant patients with persisting mucosal alterations.

Adolescent↗

Reliability of immunologic markers of celiac sprue in the assessment of mucosal recovery after gluten withdrawal.

We studied 47 adults (21 men, 26 women), with biopsy-proven celiac sprue and anti-endomysin antibody (EmA) positivity while untreated, to evaluate the usefulness of both serologic markers of celiac sprue [i.e., immunoglobulin A (IgA)-EmA and total Ig-anti-gliadin (AGA) antibodies] and of a detailed dietary inquiry in predicting the mucosal pattern after gluten withdrawal. A second biopsy was repeated 8-30 months after beginning a gluten-free diet, along with EmA and AGA determinations and the dietary inquiry. Both EmA and AGA were appraised by indirect immunofluorescence on monkey esophagus and rat kidney, respectively. Intestinal biopsy was graded according to Cooke's criteria. After gluten withdrawal, intestinal mucosa reverted to normal in only nine patients. Both EmA and AGA showed high positive but low negative predictive values on intestinal histologic outcome. The positive predictive value of admission of dietary lapses was 100%, whereas the negative predictive value was 39.1%. Neither serologic markers nor dietary inquiries are to be regarded as reliable predictors of intestinal outcome after a gluten-free diet. Biopsy remains the best means of ascertaining mucosal recovery.

Adolescent↗

Reinfection or recrudescence after apparently successful eradication of Helicobacter pylori infection: can the type of gastritis solve the problem?

Unexpectedly high early reinfection rates are reported in duodenal ulcer patients in whom Helicobacter pylori infection had been considered eradicated two months (T2) after appropriate therapy. Since some of these re-conversions to Helicobacter pylori positivity were probably recrudescences of a latent infection rather than reinfections, studies were performed to evaluate whether the type of antral gastritis could predict the infection outcome. In 142 eradicated patients at T2, endoscopies were repeated 6 (T6), 12 (T12) and 24 (T24) months after therapy to assess Hp status and to score antral gastritis. Re-conversion to Hp positivity occurred in 14.79% between T2/T6, in 5.40% between T6/T12 and 11.11% between T12/T24. The absence of active antral gastritis at T2 with its 87.31% negative predictive value was a fairly good marker of subsequently confirmed eradication (p = 0.017). It is suggested that, evaluation of antral gastritis soon after an eradicating course, could be a reliable parameter in assessing "true" Hp eradication.

Biopsy↗

A twelve-month follow-up after Helicobacter pylori eradication. A clinical and histological evaluation.

To evaluate a twelve-month effect of Helicobacter pylori eradication, 258 consecutive out-patients with H. pylori related active duodenal ulcer were given a ten-day eradicating treatment. After healing no maintenance antiulcer medication was given. On entering the study and then 2, 6 and 12 months after the completion of therapy patients were scored for symptoms and underwent endoscopy to assess the presence of duodenal ulcer and to score antrum and corpus gastritis. Statistical analysis was performed by means of the chi 2 test. Histological eradication, defined as the inability to detect H. pylori six months after the completion of the eradication course, was proved in 85 subjects while the 123 non-eradicated ones were considered as the control group. Ulcer relapse rate and ulcer-like symptoms were significantly less frequent among eradicated than non eradicated throughout the follow-up. As compared to non eradicated, gastritis significantly improved among eradicated in both antrum and corpus. H. pylori eradication may be recommended since, by reducing ulcer relapse rate and related symptoms, there is no need for further antiulcer maintenance therapy with a significant drop in socioeconomic costs.

Adolescent↗

Comparison of serum anti-gliadin, anti-endomysium, and anti-jejunum antibodies in adult celiac sprue.

We compared the diagnostic accuracy of a new immunological marker of celiac sprue (CS), the antijejunum antibody (JAB), with that of antigliadin (AGA) and antiendomysium (EmA) antibodies. One hundred untreated adults with biopsy-proven CS, 52 healthy controls, and 57 patients with inflammatory bowel disease, lymphoma of the small bowel, Whipple's disease, and irritable bowel syndrome were investigated. Only JAB and EmA were detected at a similar titer in all patients with untreated CS but in no controls (100% sensitivity and specificity). Sensitivity of AGA was, respectively, 55% for IgA and 78% for Ig class, with a 100 and 82% specificity. The differences in frequencies between both EmA and JAB with IgA and IgG AGA were highly significant. We conclude that JAB and EmA provide a reliable noninvasive screening test for clinically significant gluten-sensitive enteropathy. The lower cost of IgA-JAB is a major advantage, owing to the different availability of the lower third of the esophagus and jejunum from primates. The sensitivity and specificity of the two tests are almost identical, but we find interpreting EmA easier than JAB especially when the titer is low.

Adolescent↗

Do dietary antibodies still play a role in the diagnosis and follow-up of coeliac disease? A comparison among different serological tests.

OBJECTIVE: Comparison between the usefulness of immunological markers and intestinal biopsy in the diagnosis and follow-up of coeliac disease. MATERIALS AND METHODS: Serum antibodies to gliadin, several dietary proteins and endomysium were appraised in 27 patients with biopsy proven coeliac disease, both while untreated and 6-8 months after gluten withdrawal, when an intestinal biopsy was repeated. Forty-six healthy volunteers entered the study as controls. Antibodies to gliadin and dietary proteins were assessed by ELISA, antibodies to endomysium by indirect immunofluorescence using monkey oesophagus as antigen. RESULTS: Mean antibody levels to dietary proteins were significantly higher in untreated patients as compared to controls. Their titers decreased after gluten withdrawal, but a significant difference was found, except for casein, for the IgA class only. However, because of their unlinear and unpredictable behaviour, they showed a poor reliability. Antigliadin antibodies showed higher diagnostic accuracy, although they also produced false-positive and false-negative results. Anti-endomysium antibodies, albeit the more expensive, proved the more reliable, due to their 100% specificity. CONCLUSION: To date, anti-endomysium antibodies are the most reliable marker for coeliac disease: a positivity warrants an intestinal biopsy. The actual role of antibodies to gliadin, cheaper than endomysium, is during follow-up when many determinations are needed. Antibodies to dietary proteins, useful in the pre-endomysium era, only have a historical role.

Adolescent↗

Celiac disease and insulin-dependent diabetes mellitus. Screening in an adult population.

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.

Adolescent↗