Ettore Cardi

Abnormal intestinal permeability in children with autism

We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls. Compared to the controls, these nine patients showed a similar mean mannitol recovery, but a significantly higher mean lactulose recovery (1.64%± 1.43 vs 0.38%±0.14; P < 0.001). We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.

Genome Search in Celiac Disease

Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.

Prevalence of coeliac disease in idiopathic dilated cardiomyopathy.

We examined 52 patients with idiopathic cardiomyopathy (IDCM) for coeliac disease. Three of them had coeliac disease, suggesting that prevalence of coeliac disease in IDCM patients is increased.

Helicobacter pylori seropositivity in children with atopic dermatitis as sole manifestation of food allergy

A positive association between Helicobacter pylori antibodies and food allergy presenting with gastrointestinal symptoms has recently been reported. A subset of a H. pylori strain possesses an antigen, CagA, as a virulence factor. Anti‐H. pylori and anti‐CagA IgG titre have been determined in children with atopic dermatitis (AD) as the sole clinical manifestation of food allergy. In this study, thirty patients with AD as the sole clinical manifestation of food allergy were examined (group A). For comparative purposes, 30 patients affected by food allergy with gastrointestinal symptoms (group B) and 30 affected by atopic asthma (group C) were studied. Anti‐H. pylori and anti‐CagA immunoglobulin G (IgG) were determined in all individuals by means of the enzyme‐linked immunosorbent assay. The anti‐H. pylori IgG titre was significantly higher in group A and group B vs. group C (p < 0.05); no significant difference was detected between group A and group B (p > 0.05). No significant difference in anti‐CagA titre was found between the groups. These data demonstrate a positive association between H. pylori antibodies and AD as the sole manifestation of food allergy. Further investigations are needed to evaluate the cause–effect relationship between H. pylori seropositivity and AD.

Increased levels of prostaglandins and nitric oxide in esophageal mucosa of children with reflux esophagitis

BACKGROUND Prostaglandin E2 (PGE2) is said to be both protective and detrimental for esophageal mucosal integrity. Nitric oxide (NO) controls several esophageal neuromuscular functions, including relaxation of the lower esophageal sphincter. The purpose of this study was to verify PGE2 and NO levels in esophageal mucosa of children with reflux esophagitis. METHODS The patients were 10 children, age range 7 to 12 years, affected by reflux esophagitis. The control subjects were 10 children, age range 6 to 11 years, with recurrent abdominal pain. Tissue fragments obtained by esophageal biopsies were placed in a culture medium and processed to obtain a cell suspension. Cells were incubated for 24 hours at 37 degrees C. Thereafter, supernatants were collected and divided into aliquots to determine the amounts of PGE2 and NO metabolites. RESULTS Esophageal cells obtained from reflux esophagitis patients synthesize and release a significantly higher (p < 0.01) amount of PGE2 and NO (PGE2 1.9 +/- 0.56 ng/10(6) cells per 24 hours; NO 124.94 +/- 18.36 microM/10(6) cells per 24 hours) than did the control group (PGE2 0.66 +/- 0.14 ng/10(6) cells per 24 hours; NO 68.03 +/- 12.3 microM/10(6) cells per 24 hours). CONCLUSIONS These results suggest that in esophageal mucosa, PGE2 and NO, in low concentrations, are protective, whereas, at high doses, they can be harmful. Higher amounts of PGE2 and NO in the esophageal mucosa of reflux esophagitis patients suggest that similar noxious stimuli trigger the inducible forms of the respective enzyme.

Increased release of interleukin-6 by oesophageal mucosa in children with reflux oesophagitis.

OBJECTIVE To evaluate the release of interleukin-6 (IL-6) by oesophageal mucosa and to establish the serum levels of IL-6 and C-reactive protein (CRP), and plasma fibrinogen in children with reflux oesophagitis. DESIGN In a prospective study, IL-6 release by tissue fragments obtained from oesophageal biopsies was determined and serum IL-6 and CRP as well as plasma fibrinogen were analysed. METHODS The study population comprised ten children with reflux oesophagitis, diagnosed on the basis of 24 h oesophageal pH monitoring and endoscopy with biopsies. Ten children with recurrent abdominal pain were studied for comparative purposes. Biopsy tissue fragments were processed to obtain a cell suspension and the release of IL-6 was determined in culture medium. Serum IL-6 levels were measured by ELISA, serum CRP by turbidimetry, and plasma fibrinogen by spectrophotometry. RESULTS Oesophageal cells obtained from reflux oesophagitis patients synthesize and release in vitro a significantly higher amount of IL-6 than controls (71.26+/-19.5 versus 31.67+/-8.02 pg/10(6) cells; P<0.01). Serum IL-6, serum CRP and plasma fibrinogen levels were not statistically different between patients with reflux oesophagitis and controls. CONCLUSIONS These results suggest a short-term action of IL-6 since its effects could be exerted only in the microenvironment of the oesophageal mucosa.

Cyclic Vomiting Syndrome

Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of nausea and vomiting with complete resolution of symptoms between attacks. Nitric oxide plays a critical role in regulating several components of gastrointestinal mucosal defense and injury. Interleukin-6 has a wide variety of actions in the gastrointestinal apparatus. The purpose of this study was to evaluate the synthesis and release of nitric oxide and interleukin-6 by the esophageal and gastric mucosa in 10 children with cyclic vomiting syndrome, during symptom-free periods, and in 10 controls. The nitric oxide and interleukin-6 release by esophageal mucosa cells obtained from cyclic vomiting patients was quite similar to that in controls, but the release of nitric oxide from gastric mucosa cells of patients was significantly higher than that of controls. Conversely, no interleukin-6 was detectable in gastric mucosa cell supernatants in any of the patients. Further studies are needed to evaluate the relationship between factors triggering cyclic vomiting syndrome and the release of nitric oxide and interleukin-6 by gastric mucosa.

Increased Taurine Content in Esophageal Mucosa of Children Affected by Gastroesophageal Reflux

We studied the possible involvement of mucosal amino acid metabolism in the pathogenesis of gastroesophageal reflux disease in children. Eighteen children with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without) and 10 children with normal 24-h esophageal pH monitoring as a comparative group underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa amino acids were assayed by liquid chromatography. In children affected by gastroesophageal reflux disease we found an increase of mucosal taurine (P < 0.01) and a decrease of serine (P < 0.01). No differences were noted between patients with and without esophagitis. Significant positive correlations (P < 0.001; r = 0.626) were found between mucosal taurine content and reflux index. Plasma amino acid concentrations did not show any significant differences among groups. Our results indicate that biochemical alterations precede the histological findings of inflammation, likely reflecting the adaptive response of the esophageal mucosa to the gastric contents exposure.