Search

Background: Gliadins, a family of wheat proteins, are central to the pathogenesis of celiac disease (CD). In addition to 'immunogenic' effects, gliadin directly affects cultured cells and intestine preparations, and produces damage in vivo, via a separate 'toxic' peptide, such as A-gliadin p31-43 (P31-43)., Aims: Understanding the molecular mechanisms underlying direct non T-cell mediated effects of gliadin peptides, and assessing their potential role in promoting CD., Method: Gliadin effects were tested on a number of cell lines and on cultured mucosa samples by evaluating cytoskeleton rearrangements, endocytosis, proliferation and apoptosis. Standard biochemical methods were used to assess prolonged epidermal growth factor receptor (EGFR) activation., Results: Crude gliadin peptic-tryptic peptides (PTG], or P31-43 alone, fully reproduce the effects of epidermal growth factor (EGF] on actin cytosketon, cell cycle and cell proliferation of various cell lines. Inhibitor studies demonstrate the role of EGFR in the early response to gliadin exposure, pointing to activation of the EGFR pathway. Peptide P31-43 is not similar to any EGFR ligand, but can delay inactivation of the EGFR interfering with its endocytosis. Gliadin-induced delay of EGFR endocytosis in cultured intestinal biopsies, together with S-phase entry of epithelial intestinal cells, confirm a role for EGFR activation in CD., Conclusion: The ability of gliadin peptides to delay EGFR inactivation through interference with the endocytic pathway suggests a model where gliadin fragments amplify the effects of trace amounts of EGF, and possibly of other growth factors, by prolonging receptor activation. The results, using cultures of coeliac intestinal biopsies, highlight the role of the EGF pathway in establishing and maintaining the typical atrophic and proliferative alterations of the small intestine in CD.

Myoepithelioma is a rare benign neoplasm of the salivary glands occurring more frequently in the parotids. Myasthenia gravis (MG) is a chronic, T-cell dependent, antibody and complement-mediated autoimmune neuromuscular transmission disorder. Interleukine-6 (IL-6) is an immune protein belonging to the family of the hematopoietins, liberated in response to infection, burns, trauma, and neoplastic diseases. It seems that an overproduction of IL-6 might play an important role in the pathophysiology of MG. Moreover, it has been discussed the possible role of IL-6 as a modulating factor either in proliferation or in differentiation of pleomorphic adenoma cell line into myoepithelioma. The authors present a rare case of parotid myoepithelioma occurred in a patient affected by myasthenia gravis and suppose a possible IL-6 mediated relationship between myasthenia gravis and parotid myoepithelioma.

Background and Aims: We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability., Methods: We crosslinked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting, and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by antiendomysial, anti-human tissue transglutaminase antibodies, and bowel biopsy., Results: Concordance was significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ (16.7% probandwise, 9.1% pairwise) pairs. Concordance was not affected by sex or HLA genotype of the co-twin and being MZ was significantly associated with the occurrence of CD (Cox adjusted hazard ratio 14.3 (95% confidence interval 4.0-50.3)). In 90% of concordant pairs the discordance time was

The authors historically review bibliographic research concepts and define globalization in time. Moreover, recent free online data exchange is important in terms of medical progress, scientific updating and patient-care improving. In the author's opinion, data globalization is favoring medical knowledge flow even more. The concept of a traditional library has radically changed over time, gradually missing their pivotal role in research activity. To date, the birth of the Internet and its sudden development has given a great boost to the spread of worldwide information, quickly and cheaply. Nevertheless, besides the advantages, the Internet also hides misleading risks. In this paper, the professional Medline source is compared to common Internet sources. The authors state that Internet sources have a great importance in the spread of medical knowledge. They conclude, however, that the risk of too much available information could lead to a decrease in quality.

Background: Antiendomysium antibodies have a high sensitivity and specificity for celiac disease. A small percentage of subjects positive for these antibodies have a small intestinal mucosa hitherto considered normal., Objectives: The aim of this study was to characterize the clinical, serological, immunogenetic, and immunohistological features of these subjects., Methods: From 409 patients who were positive for celiac-related antibodies, we selected 24 (5.9%) patients who had an architecturally normal small intestinal mucosa. One hundred age-matched celiac patients with a "flat" small intestinal mucosa, and 50 age-matched nonceliac children were also studied. The number of CD3+ and gammadelta+ intraepithelial lymphocytes and of CD25+ lamina propria mononuclear cells, and the expression of crypt HLA-DR and lamina propria ICAM-1 were assessed. HLA haplotyping was also performed., Results: Eleven (45.8%) of the 24 patients had a distinct infiltrative pattern, i.e., an increase in CD3+ intraepithelial lymphocytes (> 2SD of the nonceliac group), whereas 17 (70.8%) had a higher density of intraepithelial gammadelta+ cells. In 17 (70.8%) patients, the number of lamina propria CD25+ cells was increased and/or the expression of ICAM-1 and crypt HLA-DR was enhanced. All 24 patients carried the celiac disease-associated HLA haplotypes. Two of the six patients who remained on a normal diet and underwent a second jejunal biopsy developed villous atrophy., Conclusions: Most of the patients with serum antiendomysium antibodies and normal jejunal histology showed immunohistochemical signs of immune activation in the epithelium, lamina propria, and crypts. We recommend that such patients be monitored to assess their progress and to determine whether they need a gluten-free diet.

Dietary gluten has been associated with an increased risk of type 1 diabetes. We have evaluated inflammation and the mucosal immune response to gliadin in the jejunum of patients with type 1 diabetes. Small intestinal biopsies from 17 children with type 1 diabetes without serological markers of celiac disease and from 50 age-matched control subjects were examined by immunohistochemistry. In addition, biopsies from 12 type 1 diabetic patients and 8 control subjects were cultured with gliadin or ovalbumin peptic-tryptic digest and examined for epithelial infiltration and lamina propria T-cell activation. The density of intraepithelial CD3(+) and gammadelta(+) cells and of lamina propria CD25(+) mononuclear cells was higher in jejunal biopsies from type 1 diabetic patients versus control subjects. In the patients' biopsies cultured with peptic-tryptic gliadin, there was epithelial infiltration by CD3(+) cells, a significant increase in lamina propria CD25(+) and CD80(+) cells and enhanced expression of lamina propria CD54 and crypt HLA-DR. No such phenomena were observed in control subjects, even those with celiac disease-associated HLA haplotypes. In conclusion, signs of mucosal inflammation were present in jejunal biopsies from type 1 diabetic patients, and organ culture studies indicate a deranged mucosal immune response to gliadin.

Background: Faecal calprotectin (FC) is a new marker of intestinal inflammation. Data on FC in paediatric gastroenterology clinical practice are still scarce., Aims: To assess FC values in different paediatric gastrointestinal diseases comparing them with those obtained in healthy children., Patients: Two hundred and eighty-one children (age range 13-216 months) consecutively referred for gastrointestinal symptoms. Seventy-six healthy controls (age range 13-209 months). The exclusion criteria in healthy children were the following: any known underlying chronic disease or a history of abdominal pain, diarrhoea, acute respiratory tract infection, intake of non-steroidal anti-inflammatory drugs, gastric acidity inhibitors, antibiotics, drugs influencing gut motility, and menstrual or nasal bleeding in the last 3 weeks., Methods: Stool samples stored, prepared and analyzed by an ELISA assay., Results: In healthy children the median FC value was 28.0 microg/g (15-57 interquartile range) with a 95th percentile value of 95.3 microg/g. An increase in FC concentration was observed in all diseases characterized by gastrointestinal mucosa inflammation, and the active inflammatory bowel disease patients showed the higher FC values. All children affected by functional bowel disorders or by non-inflammatory diseases showed normal values. We calculated an optimized FC cut off value of 102.9266 microg/g (revealed by the receiver operating characteristic curve) to distinguish patients with active organic/inflammatory disorders from healthy subjects and from patients with functional bowel disorders., Conclusions: Calprotectin is a sensitive, but not disease specific, marker to easily detect inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal mucosa inflammation and in the differential diagnosis of functional bowel disorders.

Background: In a previous hospital based study, we suggested that undiagnosed coeliac disease has a prevalence, among pregnant women, of 1:80, and is a cause of unfavourable outcome of pregnancy., Aims: In order to confirm or dismiss this hypothesis, which has significant public health implications, we carried out a large population based study on a stratified sample from the whole Campania region., Patients: During the period of the study, 5345 women were admitted to the OBS-GYN wards regional network: 5055 (95%) were enrolled in the study., Methods: Antihuman IgA class antitissue transglutaminase (TGASE) antibodies were tested by an ELISA method. Endomysial antibodies (EMA) were investigated on thin sections of human cord blood by an immunofluorescence test. The HLA class II DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the Eurospital Eu-DQ kit. Duodenal biopsy was not considered feasible by the ethics committee for pregnant women near delivery., Results: Fifty one of 5055 patients had confirmed positive results. We added to these 12 women with known coeliac disease, giving a prevalence rate for coeliac disease of 1:80 (exactly the value observed during the first study). Comparing the 51 TGASE positive with 4997 negative women, we did not observe an excess risk of abortion, premature delivery, small birth weight, or intrauterine growth retardation. Anaemia was more frequent in cases than controls., Conclusions: Undiagnosed coeliac disease is frequent among pregnant women (>1%) but is not associated with an unfavourable outcome of pregnancy.

Tinnitus and temporomandibular joint dysfunction (TMJD) are among the most common complaints encountered by physicians. Though the relationship between tinnitus and TMJD has attracted great interest during the past several years, theories attempting to explain this association are still few and inconsistent. Conceivably, TMJD could irritate auricolo-temporal nerve (ATN), triggering a somatosensory pathway-induced disinhibition of dorsal cochlear nucleus (DCN) activity in the auditory pathway. In genetically-predisposed TMJD patients, signals from cronically stimulated DCNs activating specific cortical neuronal networks, could yield plastic neural changes resulting in tinnitus. Based on current evidence of serotoninergic modulation of neural activity and plasticity in sensory pathways, reduced serotoninergic tone could promote plastic changes underlying tinnitus through diminished filtering of incoming signals. Therefore, the early establishment of specific treatments aimed at improving TMJD and/or boosting serotoninergic activity may be required to prevent the creation of 'tinnitus memory circuits'.

Objectives: The molecular and functional properties of small intestinal tissue transglutaminase are largely unknown despite growing interest because of its role in celiac disease (CD). In this study, we aimed to evaluate tissue transglutaminase expression and enzymatic activity in bioptic fragments obtained from the duodenum of untreated individuals with CD and from control subjects., Methods: Analysis of tissue transglutaminase mRNA expression was performed by reverse transcription-polymerase chain reaction (RT-PCR). The presence of the enzyme in bioptic fragments as well as in homogenates from CD patients and controls was revealed by immunohistochemistry and Western blot, respectively, using the antitissue transglutaminase CUB 7402 clone. To evaluate in situ transglutaminase activity, sections of bioptic fragments were incubated in the presence of 5 mmol/L CaCl(2) with 5-(biotinamido)pentylamine or, alternatively, with a biotinylated glutamine-containing hexapeptide (TVQQEL) and the biotinylated 31-43 A-gliadin-derived peptide., Results: Tissue transglutaminase mRNA levels were 1.0-fold higher (p < 0.05) in CD patients than in controls. Immunohistochemistry and in situ demonstration of enzymatic activity in celiac mucosa clearly showed an increased expression of active tissue transglutaminase in the extracellular matrix of the subepithelial region and in the enterocytes. Staining of the biotinylated 31-43 A-gliadin peptide in the same area of tissue transglutaminase suggested the presence of lysine-donor substrates in intestinal mucosa., Conclusions: Tissue transglutaminase is more expressed and active in defined areas of the small intestinal mucosa from patients with CD. The presence in the celiac mucosa of proteins able to act as amine-donor substrates suggests that tissue transglutaminase-mediated post-translational modification of proteins cross-linked with gliadin peptides may represent a pathogenic mechanism of CD.

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

Objectives: The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge., Methods: Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3(+) and gamma delta(+) lymphocytes were counted with reference to a standard reference area of muscularis mucosae (10(4) microm(2))., Results: After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3(+) and of lamina propria and epithelium gamma delta(+) lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease., Conclusions: Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.

Background: Studies on intestinal T cell clones from the mucosa of patients with coeliac disease have led to the identification of immunogenic gliadin epitopes. One is HLA-DQ8 restricted, its recognition by T cells being increased by introduction of negatively charged residues operated by tissue transglutaminase., Aim: To test HLA-DQ8 restricted epitope in both native (QYPSGQGSFQPSQQNPQA) and deamidated (QYPSGEGSFQPSQENPQA) forms in an organ culture system of treated coeliac mucosa from HLA-DQ8 positive and HLA-DQ8 negative patients., Patients and Methods: Jejunal biopsies obtained from 10 patients with coeliac disease (six HLA-DQ8 positive and four HLA-DQ8 negative) were cultured in vitro with a peptic-tryptic digest (PT) of gliadin, or with the native (peptide A) or deamidated (peptide B) peptide. Intraepithelial CD3(+) and lamina propria total CD25(+) and CD3(+)CD25(+) cells were counted, lamina propria intercellular adhesion molecule 1 (ICAM-1) expression was evaluated, as well as that of Fas molecules on epithelial cells., Results: In HLA-DQ8 positive, but not in HLA-DQ8 negative, coeliacs the density of intraepithelial CD3(+) cells, lamina propria total CD25(+), and CD3(+)CD25(+) cells, as well as expression of ICAM-1 and Fas molecules were significantly increased in biopsies cultured with PT, peptide A, or peptide B compared with biopsies cultured in medium alone., Conclusion: These data show that the DQ8 restricted gliadin peptide is immunogenic only in the intestinal mucosa of HLA-DQ8 positive coeliac patients in both native and deamidated forms.

Objective: Chronic gastrointestinal symptoms and histologic changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux disease (GERD) may be improved by the use of elemental formulas. The aim of our study was to evaluate the efficacy of a dietary trial in neurologically impaired children unresponsive to medical and surgical therapy for GERD., Methods: Nine children (three boys and six girls; median age, 44 months; range, 13-180 months) affected by cerebral palsy associated with severe mental retardation and with long-standing history of GERD were fed the elemental formula, Neocate, for a minimum of 4 weeks. Before and after the dietary trial, each child underwent endoscopy with esophageal biopsy and a cellobiose/mannitol sugar permeability test. The diagnosis of GERD was based on the microscopic changes of the esophagus., Results: Before the dietary trial, according to conventional histologic criteria, esophagitis was considered moderate in seven children and mild in two. Five of nine patients also had abnormal sugar permeability test results. During and after the dietary trial, seven of nine patients experienced resolution of their long-term symptom complaints. Furthermore, after the dietary trial, both endoscopic ( < 0.01) and histologic ( < 0.05) findings significantly improved. At 6-month follow-up, progressive reintroduction of individual dietary proteins, except for cow's milk protein, did not cause reappearance of the symptoms., Conclusions: In neurologically impaired children unresponsive to conventional antireflux treatments, a course of a highly restricted diet with an amino acid-based formula may bring an immediate and sustained, endoscopically and histologically proven improvement in long-standing gastrointestinal symptoms and esophagitis.

Background and Aims: Coeliac disease (CD) is a multifactorial disorder which has an autoimmune component characterised by the occurrence of disease specific autoreactive antibodies against the enzyme tissue transglutaminase (tTG). The aim of this study was to investigate whether binding of antibodies to the enzyme influences tTG activity., Methods: tTG activity was assayed in the presence of immunoglobulin A (IgA) and immunoglobulin G (IgG) purified from the serum of coeliac patients, CUB 7402 (an anti-tTG mouse monoclonal antibody), and human anti-tTG monoclonal antibodies derived from both intestinal lymphocytes from three patients with CD and from peripheral blood lymphocytes from healthy subjects. For our studies we used calcium treated and untreated recombinant human tTG. Furthermore, the effects of antibodies were determined by immunohistochemical detection of tTG activity in sections of human umbilical cord., Results: IgG and IgA from CD patients inhibited tTG activity in vitro in a dose dependent manner, with a different rate of inhibition among patients. The monoclonal antibody CUB 7402 and human monoclonal antibodies displayed a dose dependent inhibitory effect towards the catalytic activity of the enzyme, both in vitro and in situ. Preincubation of tTG with CaCl(2) caused loss of the inhibitory effect due to CUB 7402 but not that caused by human monoclonal antibodies., Conclusions: Purified CD IgA, IgG, as well as human anti-tTG monoclonal antibodies inhibited the enzymatic activity of human tTG both in vitro and in situ.

Background and Aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study., Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules., Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype., Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.

We previously demonstrated a specific gluten-induced response in the rectal mucosa of coeliac patients. In the present study, we have evaluated the immune response to local gliadin challenge in the nasal mucosa of coeliac patients preliminary to exploring the feasibility of immune modulation by the nasal route. The local response to gliadin was evaluated on non-invasive scrapings of nasal mucosa. Cells harvested from the nasal scrapings of 21 coeliac patients and 12 healthy controls were counted after immunohistochemical staining. Six hours after gliadin challenge, the total number of cells was increased in coeliacs but not in controls. The increase was due principally to lymphoid cells and granulocytes. CD3+ cells doubled after gliadin challenge, but not after albumin control challenge. There was a similar rise in CD25+ cells, whereas the number of ICAM-expressing cells did not increase significantly. In control subjects, both gliadin and albumin induced a moderate but not significant increase in total cell number. In conclusion, the gliadin antigen provokes a mild inflammatory response in coeliac nasal mucosa.

Background: The diagnosis of oesophagitis is mainly based on histology, but interpretation of endoscopic biopsies is often difficult. We performed immunohistochemical studies on oesophageal biopsies to see if better characterization of the inflammatory cell infiltrate would improve the accuracy of the histologic diagnosis of gastro-oesophageal reflux disease., Methods: The study groups consisted of 40 consecutive children (mean age +/- SD: 79.6 +/- 5l.9 months; 20 boys) with gastro-oesophageal reflux disease and 7 symptomatic children (mean age +/- SD: 52.6 +/- 37.0 months; 3 boys) without gastro-oesophageal reflux disease. All patients underwent upper gastrointestinal endoscopy with oesophageal biopsies. The diagnosis of gastro-oesophageal reflux disease was established by conventional endoscopic and histologic criteria. In each mucosal biopsy specimen, the number of intraepithelial CD3+, CD25+ (IL2 receptor+), ICAM+, HLA-DR+ and mucosal mast cells were determined., Results: Conventional histology was in close agreement with endoscopic findings (p<0.001) and reflected the clinical score even more than endoscopic findings. Conventional histology significantly correlated with each inflammatory immunohistochemical marker (<0.05 for each), but the markers were not predictive of symptom severity. Immunohistochemical markers were always abnormal in the gastro-oesophageal reflux disease patients, even in the mildest cases of oesophagitis., Conclusions: Although there is a good correlation between symptoms and histology, in a subset of patients, immunohistochemical studies appear useful in supporting the histological diagnosis of gastro-oesophageal reflux disease.

We analyzed the transglutaminase 1 gene locus in patients from six unrelated Italian families affected by autosomal recessive lamellar ichthyosis. In two families we identified a novel mutation (E520G) in the gene coding region, a previously reported splicing mutation (A3447G), and the mis-sense mutations S272P and V518M. The latter mutation, hitherto considered disease causing, was found to be a simple polymorphism. Linkage to transglutaminase 1 gene was excluded in two of the other four families examined. Single strand conformational polymorphism analysis of the transglutaminase 1 gene in the remaining two families did not reveal any alteration in the coding region. This finding confirms the genetic heterogeneity of the disease.

Background: Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6-12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed. The prevalence of undiagnosed coeliac disease among pregnant women is not known., Aim: To determine the prevalence of untreated coeliac disease among women attending the obstetrics-gynaecological department., Methods: Endomysial antibodies, which are specific and sensitive for coeliac disease, were evaluated in all women attending the obstetrics-gynaecology department of a large city hospital over a 90 day period., Results: Of 845 pregnant women screened, 12 were identified as having coeliac disease. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year., Conclusions: Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.

Celiac disease is sustained by an immunological process that mainly affects the jejunal mucosa (1). Nonetheless, jejunum is not the only site of the gastrointestinal tract that is involved in celiac disease. In recent years, Ensari and colleagues (2,3), by using immunohistochemical analysis and computerized image analysis for numerical quantitation, have significantly contributed to a definitive and clear demonstration of a celiac disease-associated "proctitis," and its gluten dependence. Morphometry has shown increased populations of plasma cells, lymphocytes, and mast cells in the rectal mucosa of untreated patients, with these changes being reverted, with the sole exception of mast cells, by dietary treatment (2). The immunohistochemical approach has demonstrated highly significant increases in CD3(+) and γδ(+) lymphocytes within both the lamina propria and the epithelium. Mononuclear cells, both lymphocytes (CD3(+)) and macrophages (CD68(+)) expressing interleukin-2 (IL-2) receptors (CD25(+)), have been found to be increased in the lamina propria, usually immediately below the basal lamina. Enterocytes have been noted to be positive for major histocompatibility complex class II display, a pattern usually absent in normal colon. Furthermore, increased expression of vascular cell adhesion molecule-1 (VCAM-1) molecules in the rectal mucosa of untreated, compared to either treated celiac rectum or control mucosae, has been reported (3). As a whole, these data suggest, analogously to jeunum, an ongoing T-cell-dependent, cell-mediated immune response in the rectal mucosa.

The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis.

Background: We have shown in previous studies the presence of a patchy pattern of lactase protein expression in the proximal jejunum of hypolactasic humans, adult rabbits, and rats. The present study investigated the mechanisms underlying the heterogeneous expression of lactase on the villus., Methods: Proximal jejunal tissue from 18 adult humans and 12 adult rabbits was examined using enzymocytochemical and surface-staining techniques for lactase protein and activity., Results: In the proximal jejunum of hypolactasic humans and adult rabbits, lactase activity is patchily distributed on the villus enterocytes. In humans, the patches of lactase-positive enterocytes are randomly distributed on the villus, whereas in rabbits, vertical, continuous sheets of positive enterocytes arise from the base of the villus., Conclusions: The presence of enterocytes without lactase activity is one of the mechanisms causing adult-type hypolactasia in the proximal jejunum of humans and mammals. The patchy pattern of lactase in rabbits suggests a clonal origin with heterogeneity of the cells arising from the crypts. In hypolactasic humans, the enterocyte heterogeneity occurs as a consequence of mechanisms that do not have a clonal origin.

Flutter and atrial fibrillation are extremely rare in children. Their aetiology and pathogenesis vary from one case to another. The clinical picture may be influenced by a number of factors (age, duration of the arrhythmia, ventricular frequency), while the natural history is often related to the presence or otherwise of associated cardiopathies. There is no standard treatment. Digitalis with or without other antiarrhythmic drugs is often employed as the drug of choice, though its place may be taken by ayodarone or verapamil.