Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

Neurological complications of celiac disease and autoimmune mechanisms: preliminary data of a prospective study in adult patients.

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti-ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Fibrogenesis serum markers in patients with chronic hepatitis C treated with alpha-IFN.

The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with alpha-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over 2 years, were tested for markers of liver neofibrogenesis. Serum N-terminal procollagen III peptide (PIIINP) displayed a significant and persistent decrease (P < 0.05) in sustained responders but not in non-responders; significantly lowered (P < 0.05) mean levels of C-terminal procollagen I peptide (PICP) were transiently observed in both patient groups, apparently as a result of IFN administration. Serum laminin (Lam) levels remained unchanged. One year after the cessation of treatment, liver biopsy re-testing showed an improvement in necro-inflammatory scores only in sustained responders, with the histological fibrosis scores remaining unaltered in both groups. IFN treatment seemed to exert an influence on serum levels of markers of hepatic connective tissue turnover even in patients that did not respond to therapy, while no effect was observed on preexistent liver fibrosis.

Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet.

UNLABELLED: Coeliac disease is an autoimmune enteropathy characterized by an enhanced permeability of the intestinal epithelial barrier. In epithelial cells paracellular permeability is regulated by intercellular tight junction. The cytoplasmic protein ZO-1 interacts directly with F-actin and plays a pivotal role in the structural and functional organization of tight junction. AIM: The aim of this study was to investigate the expression and localization of ZO-1 in the intestinal mucosa of coeliac patients. PATIENTS AND METHODS: Twenty patients with active coeliac disease, seven of whom underwent a repeat biopsy following a gluten-free diet and 27 control subjects, were studied. In all subjects, three biopsies were obtained from distal duodenum during upper gastrointestinal endoscopy. ZO-1 protein localization and levels were detected by immunofluorescence followed by confocal microscopy analysis and immunoblotting. ZO-1 mRNA expression was assessed by RT-PCR. F-actin distribution was also investigated. RESULTS: In patients with active coeliac disease, both ZO-1 protein levels and mRNA were clearly reduced. Cytoskeletal organization was disrupted with F-actin staining concentrated at the subcortical and basal surface regions. Abnormalities in ZO-1 expression and actin organization were reversed after a gluten-free diet. CONCLUSIONS: In active coeliac disease, ZO-1 protein expression is downregulated at the transcriptional level in association with F-actin redistribution. These changes are completely reversed after a gluten-free diet and could contribute to the increased intestinal paracellular permeability observed in this disorder.

Food allergy to wheat products: the effect of bread baking and in vitro digestion on wheat allergenic proteins. A study with bread dough, crumb, and crust.

The effect of baking and digestion on the allergenicity of wheat flour proteins has been studied. Pooled sera of patients suffering from food allergy to wheat products were tested for IgE binding to the proteins of the wheat dough and of the bread crumb and crust, before and after being in vitro digested. During in vitro digestion, the IgE binding protein components of the unheated dough tended to disappear, whereas a permanence of IgE recognition was evident for both the bread crumb and crust. This indicates that the baking process increases the resistance of the potential allergens of the wheat flour to proteolytic digestion, allowing them to reach the gastrointestinal tract, where they can elicit the immunological response. Therefore, the effects of baking must be carefully considered in studying food allergies to wheat products.

[Immunologic changes in chronic pancreatitis]. / Alterazioni immunologiche nella pancreatite cronica.

In 35 patients with chronic pancreatitis, C3, C4, s-immunoglobulins, circulating immunocomplexes and T-lymphocytes were assessed in order to verify whether an immunological role may be postulated in the pathogenesis and/or in the maintenance of the disease. A significant increase of serum IgM together with normal values of C3 and C4 and without circulating immunocomplexes was found. A significant decrease in the total number of lymphocytes as well as in the number and percentage of T-lymphocytes was also documented. These results suggest a possible involvement of immunological (humoral and cellular) processes in maintaining the chronic pancreatic damage.

[Specific IgE in the gastric and duodenal mucosa. An epiphenomenon or pathogenetic mechanism of some forms of "peptic" ulcer?]. / IgE specifiche nella mucosa gastrica e duodenale. Epifenomeno o meccanismo patogenetico di alcune forme di ulcera "peptica"?

Allergic mechanisms have been shown to induce gastric and intestinal damage in animal models. It has been demonstrated that people allergic to food may complain of gastrointestinal disorders. Furthermore food allergens can induce gastric mucosal damage in sensitized people. Little is known as regards allergic mechanisms underlying "peptic" ulcers although there are reports suggesting that some forms of gastric and duodenal ulcer may be caused by allergy. AIM. Of the study was to evidence if IgE specific to food and inhalants are localized in gastric and duodenal mucosa and if the in vitro incubation of gastric and duodenal biopsies with specific allergens, stimulate mast-cell mediators. MATERIALS AND METHODS. Twenty-one patients affected by gastric/duodenal ulcers (14 with high total IgE serum levels) and 16 controls were studied. All patients were submitted to upper digestive endoscopy and biopsies were taken from gastric fundus, body and antrum and duodenal bulb. Specific IgE to food and inhalant allergens were tested after homogenization of biopsies, using commercial kits. In 3 selected patients, 3 biopsies from gastric fundus and 3 from duodenal bulb were taken. After incubation of mucosal of mucosal biopsies with allergens (wheat, lactoalbumin, Parietaria J. pollen), the release of histamine and tryptase was measured. The release of Pepsinogen A was measured in the same conditions, as control. RESULTS. Specific IgE to food and inhalants allergens have been found in 164/586 tests (27.9%) of "peptic" ulcer patients and in 17/430 tests (4%) of controls. The duodenal bulb resulted the site in which most frequently IgE have been found. The release of histamine and tryptase has been stimulated only in 1/6 tests by incubation of biopsies with specific allergens in patients with specific IgE. PG-A release has been always stimulated by incubation of gastric biopsies, but not duodenal biopsies, with all tested allergens. DISCUSSION AND CONCLUSION. Specific IgE may be localized in gastric and duodenal mucosa of patients with "peptic" ulcer and/or food allergy. This event is linked to high total IgE serum levels and in a lesser extent, intestinal parasitosis, it is not strictly correlated with specific IgE in the serum and it regards both food and inhalant allergens. No relevant effects were observed after incubation of specific allergens with gastric or duodenal mucosa biopsies containing specific IgE. The possibility that higher allergens concentration stimulate mediator release from mast cells should be investigated. A defect of the gastric or duodenal epithelial barrier which permit a passage way for proteins with subsequent IgE production in the submucosa, appears to be the cause of localization of specific IgE in stomach and duodenum.

[Recurrent aphthous stomatitis: which role for viruses, food, and dental materials?]. / Stomatite aftosa ricorrente: quale ruolo per i virus, gli alimenti ed i materiali odontoiatrici?

Recurrent aphthous stomatitis is a frequently occurring disorder which may be a clinical feature of systemic disease. For many other patients, it is a tedious problem often having no known cause. The aim of this study was to verify if immune responses to common foods and/or viruses are involved in the etiopathogenesis of recurrent aphthous stomatitis. Sixteen patients with this disorder were studied by measurement of immunoglobulin classes (IgG, IgA, IgM), blood lymphocyte subpopulations, blood circulating immune complexes, and complement fractions (C3 and C4). Intradermal skin tests for common food and inhalant allergens were performed in all cases. In 5 patients with positive skin tests, serum specific IgE were tested for the same allergens by radioallergosorbent test. Skin patch tests for dental material were performed in all cases. Oral mucosal biopsies and/or cytology samples were taken in 10 cases for histopathological evaluation and in situ hybridization for Papillomavirus, Cytomegalovirus, Herpes simplex virus I and II, Epstein Barr virus. In 13 patients, lymphocyte subpopulations were altered, with a reduced CD4/CD8 ratio. No other alterations of serum immunological parameters were observed. Skin patch tests for dental material were negative in all cases, while skin tests for food allergens were positive in 5 cases (not confirmed by radioallergosorbent test or food challenge tests). Virus antigen and DNA were not found in mucosal specimens, although one patient was positive for Epstein Barr virus DNA by in situ hybridization. An alteration of the CD4/CD8 ratio was demonstrated in most of the patients with recurrent aphthous stomatitis, although immune responses to food and/or dental material and/or common viruses did not seem to be involved in the etiopathogenesis of this disorder.

Laparoscopic treatment of post-hysterectomy colovaginal fistula in diverticular disease. Case report.

Colonic diverticular disease is a benign condition typical of the Western world, but it is not rare for even the 1st episode of diverticulitis to carry potentially fatal complications. The evolution of a peridiverticular process generally poses problems for medical treatment and exposes patients to repeated episodes of diverticulitis, making surgical treatment necessary in approximately 30% of symptomatic patients. One of the most worrying complications of diverticulosis is internal fistula. The most common types of fistula are colovesical and colovaginal, against which the uterus can act as an important protective factor. The symptoms and the clinical and instrumental management of patients with diverticular fistulas are much the same as for patients with episodes of acute diverticulitis. Staging of the disease (according to Hinchey) should be done promptly so that the necessary action can be taken prior to surgery, implementing total parenteral nutrition (TPN), nasogastric aspiration and broad-spectrum antibiotic treatment. The best surgical approach to adopt in patients with diverticulitis complicated by fistula is still not entirely clear, though the 3-step strategy is currently tending to be abandoned due to its high morbidity and mortality rates. There is a widespread conviction, however, that the 2-step strategy (Hartmann, or resection with protective stomy) and the 1-step alternative should be reserved, respectively, for patients in Hinchey stages 3, 4 and 1, 2 with a situation of attenuated local inflammation. The 1-step approach seems to be safe and effective. This report describes a case of colovaginal fistula in a patient with colonic diverticulosis who had recently undergone hysterectomy, but who, unlike such cases in the past, was treated in a single step using a laparoscopic technique.

Gastric cell c-AMP stimulating autoantibodies in duodenal ulcer disease.

Gastric cell c-AMP stimulating antibodies (GCS-Ab) were studied in 30 patients with duodenal ulcer (DU) disease. Semipurified immunoglobulin (Ig) preparations from 13/30 patients stimulated c-AMP production in parietal cell enriched gastric cell suspensions obtained from male guinea pig stomachs. Maximum stimulation (varying between 260 and 547%) was reached after four hours incubation with 2 and 4 mg/ml Ig concentrations. The 13 patients with gastric cell stimulating antibodies (GCS-Ab), all male patients, developed the disease at a younger age (nine of 13 under the age of 30), had a longer duration of symptoms (mean 18.4 years), and had a higher incidence of DU in their families (61%). Eight of 13 (61%) in the GCS-Ab+ group did not respond to anti-H2-R drugs, whereas in the negative patients only three of 17 (18%) were classified as 'non-responders'. Remarkably few conventional autoantibodies were detected in our series. Gastric cell stimulating antibodies are a new addition to the growing list of receptor antibodies in human diseases and the described in vitro test should provide an easier tool for screening large populations.

Fistular complication of gastric ectopia in the proximal oesophagus and pyriform sinus.

Gastric ectopias in the upper oesophagus and hypopharynx are relatively rare and often misinterpreted. They may become symptomatic due to the onset of a fistula involving adjacent structures in the neck. This case report describes a 20-year-old patient with swallowing difficulties and laterocervical pain, with a diagnosis of fistula of the pyriform sinus due to secernent gastric mucosal ectopia. The significance of this case lies in the fact that accurate aetiopathogenic study and careful differential diagnostic procedures enabled the proper identification of this rare upper oesophageal pathology, which is often misdiagnosed due to the technical difficulties involved in conventional endoscopy of the digestive tract.

Discrepancies between reported food intolerance and sensitization test findings in irritable bowel syndrome patients.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of "intestinal" food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food. METHODS: The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the chi2 test. RESULTS: Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 [58.7%] vs 20 of 48 [41.7%]); this difference was not statistically significant, although it suggests a trend (p < 0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%). CONCLUSIONS: More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.

Organ-specific autoimmunity and genetic predisposition in interferon-treated HCV-related chronic hepatitis patients.

AIMS: Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition. METHODS: A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL). RESULTS: Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes. CONCLUSIONS: These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.

High IgE serum levels and "peptic" ulcers: clinical and functional approach.

The prevalence of high total IgE serum levels was evaluated in 232 consecutive patients suffering from peptic ulcer. Twenty-one percent of the patients presented total IgE serum levels above 200 KU/L compared with the 5% found in a healthy control population (p < 0.004). Similar prevalence was found in gastric and/or duodenal ulcers. No significant differences in the duration of the disease, smoking habits, familiarity for peptic ulcer, symptomatology and frequency of complications were observed between patients with high and with normal total IgE serum levels. Gastric function studies (gastric acid secretion, serum pepsinogen and gastrin levels) did not show any significant differences between the two groups. The incidence of Helicobacter pylori infection was 65% in patients with normal IgE levels and 75% in those with high IgE levels (p: n.s.). The response to treatment with full dose of H2-receptor antagonists was comparable in both groups (91.25% and 90.7% of ulcer healing after 6-8 weeks of treatment). A relapse of the ulcer after 6 months of maintenance therapy (half dose of H2-receptor antagonists) was observed in 39.5% of the patients with ulcer and high total IgE serum as against the 11.9% observed in patients with normal IgE (p < 0.001). These data lend further support to the hypothesis of an underlying immuno-allergic reaction in some forms of gastric or duodenal ulcer.

[IgE levels in cord blood in an area of the Veneto region]. / Determinzione delle IgE nel sangue dal cordone ombelicale in un'area della regione Veneto.

BACKGROUND: Cord blood IgE levels have been studied as a possible marker of allergy in infants but few studies are available in our Region. The aim of this paper was to test IgE levels in cord blood of 60 consecutive newborns in a restricted area of Veneto, to correlate cord blood IgE levels with family history of allergy and to verify the risk of contamination from mother's blood. METHODS: Cord blood was obtained from 60 consecutive newborns. Immunoglobulin levels (IgG, IgA, IgM, and IgE) were measured in cord blood of newborns and in serum of all mothers. Family history for allergy was previously investigated from the mothers. RESULTS: IgE were detectable in cord blood of 5 newborns but only 2 of them had positive family history for allergy which was pointed out in 11/60. In one of these cases the contamination of sample from mother's blood was postulated. IgG levels in newborn cord blood were higher than in mothers' blood and it was not related with IgE levels or other investigated factors. CONCLUSIONS: Only 6.6% of newborns in a restricted area of Veneto region have detectable IgE in cord blood whereas 18.3% of them have positive family history for allergy. Measurable levels of IgE in cord blood are not related with positive family history of allergy and are rarely influenced by mothers' blood contamination.

Eosinophilic gastroenteritis: report of two atypical cases.

Eosinophilic Gastroenteritis (EG) is a poorly understood disorder defined by eosinophilic infiltration of the bowel wall, eosinophilia and gastrointestinal symptoms. The disease's aetiology, course and treatment are not well known. We report two atypical cases of EG: one involving the mucosal layer and another involving the serosal and muscularis layer. The first shows how EG may present with a long history of episodes of intestinal obstruction and malabsorption and how the disease could take a severe course and may be unresponsive to treatment. The second case shows EG presenting as acute abdomen and which subsequently became asymptomatic without therapy, regardless of the fact that peripheral eosinophilia remained present. This case raises the problem of how to treat an asymptomatic patient, what parameters should be considered in order to assess the progress of the disease and the indications for treatment.

IgE binding to soluble and insoluble wheat flour proteins in atopic and non-atopic patients suffering from gastrointestinal symptoms after wheat ingestion.

BACKGROUND: The involvement of IgE-mediated hypersensitivity reactions in the genesis of gastrointestinal symptoms after ingestion of foods containing wheat has been rarely reported. OBJECTIVE: To detect IgE specifically binding to wheat proteins in the sera of atopic and non-atopic patients suffering from gastrointestinal symptoms after ingestion of wheat and to evaluate the reliability of skin prick test and CAP in the diagnosis of food allergy to wheat. METHODS: The sera of patients (10 atopic and 10 non-atopic) previously diagnosed as suffering from irritable bowel syndrome and complaining of symptoms after wheat ingestion were analysed by immunoblotting for IgE binding to water/salt-soluble and insoluble wheat flour proteins. RESULTS: All the atopic patients and only one of the non-atopic patients were positive to wheat CAP. For the patients tested, skin prick test was positive for all the atopic patients and for only one of the non-atopic patients. However, immunoblotting experiments showed the presence of specific IgE to wheat proteins in all the patients. Ten out of 11 of the wheat CAP-positive patients had IgE binding to a soluble 16-kDa band, but the same band was recognized, in a slighter way, by only two out of nine of the wheat CAP-negative patients. Moreover, although almost all of the patients were negative in CAP testing with gluten, 19 out of 20 recognized protein bands belonging to the prolamin fraction. CONCLUSIONS: For the atopic patients the positivity to skin prick test and CAP to wheat was in accordance with the immunoblotting results and a food allergy to wheat could be diagnosed. In these patients a major allergen was a 16-kDa band corresponding to members of the cereal alpha-amylase/trypsin inhibitors protein family, the major allergens involved in baker's asthma. In the non-atopic patients the positive immunoblotting results contrasted with the responses of the allergologic tests, indicating that the allergenic wheat protein preparations currently used are of limited value in detecting specific IgE to wheat and that the fraction of irritable bowel syndrome (IBS) patients with food allergy may be larger than believed.