Gm markers in celiac disease.

The association of Ig allotypes with celiac disease was analyzed in a sample of 95 Italian patients typed for HLA polymorphisms. No significant association was found for any Gm, A2m, or Km specificity when the overall sample was considered. However, significant different sex ratios were shown by patients' fnb positive and fnb negative genotypes, with a relative risk of 10.7 for this haplotype in males, suggesting that sex and Gm influence the penetrance of the HLA-linked genes. The significance of this finding is strengthened by the recent report that H-2 and Ig allotypes intervene in the genetic control of murine immune response to A-gliadin (M.F. Kagnoff, Nature 296:158, 1982).

An alternative approach to the assessment of gamma delta T-cell clonality in celiac disease intestinal lesions through cDNA heteroduplex analysis of T-cell receptor VJ junctions.

We have investigated the clonality of the gamma delta T lymphocytes infiltrating the intestinal mucosa of CD patients and control subjects by means of a simple and powerful method based on the heteroduplex analysis of the TCR VJ junctions. Each V-specific TCR chain, amplified either from fresh biopsy material or intestinal T-cell-line cDNA, is denatured and renatured to allow the random reshuffling of the various strands carrying different junctional sequences, coamplified in the same reaction. The mismatched chains (heteroduplexes) are separated from the matched ones (homoduplexes) through polyacrylamide gel electrophoresis, and whenever one or more T-cell clones are emerging over the polyclonal background, discrete bands are visible by ethidium-bromide staining. Through this method, we have estimated the diversity of the V delta 1-3 chains and a newly described V gene (V delta 8) whose homologue in mice is abundantly expressed in gamma delta iLs. We demonstrate that the well-documented expansion of V gamma 1+ gamma delta lymphocytes in the jejunum of CD patients is polyclonal. Overall, the heteroduplex analysis on fresh intestinal and peripheral blood lymphocytes from both healthy and affected subjects shows a polyclonal pattern of all the V delta+ subsets. In contrast, most intestinal T-cell lines produce oligoclonal patterns, suggesting a dramatic in vitro selection effect. The cell expansion in culture is generally not required for the TCR heteroduplex analysis, which can therefore be applied to rapidly monitor the T-cell response in a variety of physiologic and autoimmune reactions, substituting the standard approach of TCR cloning and multiple VJ sequencing.

Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori.

Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information.

Prostaglandin E2 in gastric mucosa of children with Helicobacter pylori gastritis: relation to thickness of mucus gel layer.

AIMS: To evaluate the changes in mucus gel layer thickness and prostaglandin E2 (PGE2) content caused by Helicobacter pylori infection in the antral mucosa of children: to assess whether decreased mucus gel thickness is related to PGE2 production. METHODS: Antral biopsy specimens were taken at endoscopy from 153 children. H pylori gastritis was evident in 45 and normal mucosa in 59. The other 49 children were studied one month after antibiotic treatment that eradicated the infection in 37 of them had been stopped. One antral specimen was immersed in ice-cold saline, put under an inverse microscope with an eyepiece graticule. Mucus gel thickness was measured and then the processed for histological examination; another specimen was weighed and processed for in vitro prostanoid generation. RESULTS: Mucus gel layer thickness was significantly decreased in children with H pylori gastritis (90 (SD) 29) microns v 120 (58) microns in controls, p < 0.01) but returned to control values after H pylori had been eradicated. PGE2 generation was significantly increased in children with H pylori gastritis (1022 (811) ng/g v 641 (473) ng/g in controls, p < 0.01). One month after treatment PGE2 generation significantly decreased in children without infection (880 (534), p < 0.01), but was still high where infection persisted. A significant inverse correlation was found between PGE2 generation and mucus gel layer thickness (p < 0.05). CONCLUSIONS: These data suggest that H pylori damages the mucus gel layer, and that the gastric mucosa increases generation of PGE2 in response to back diffusion of acid and pepsin.

Estimating the incidence of coeliac disease with capture-recapture methods within four geographic areas in Italy.

STUDY OBJECTIVE: To estimate the incidence rate of newly diagnosed cases of coeliac disease in Italy. DESIGN: This was a descriptive study of coeliac disease incidence in the period 1990-91. SETTING: During 1990-91 newly diagnosed cases of coeliac disease were signalled by several sources including diagnostic records of departments of paediatrics, general medicine and gastroenterology, national health service records for the supply of gluten free diets and the archives of the Italian Coeliac Society. PATIENTS: Altogether 1475 cases were flagged throughout Italy, 478 of whom were selected, corresponding to 270 individual patients from a target population resident in four areas: Provices of Turin and Cuneo (Piedmont Region, northern Italy); Province of Brescia (Lombardia Region, northern Italy); Umbria Region (central Italy) and Sardinia Region (insular Italy). Only for these areas were patients flagged from several sources and the reference population was identifiable. MAIN RESULTS: The overall crude incidence rates for all ages per 100,000 residents per year were 2.4, 2.7, 1.5, and 1.7 in the four areas, respectively. The childhood cumulative incidence rates (aged < or = 15 years) per 100,000 live births were 143, 141, 72, and 80 respectively. The mean ages at diagnosis were similar for both childhood and adult cases throughout the areas--these were around 4 and 34 years respectively. For each area, the incidence rate was constantly higher in the main city than elsewhere. Using the capture-recapture method, an estimated completeness of case archives of 0.84 was obtained, whereas this figure was only 0.47 for hospital sources. CONCLUSIONS: This population based study on the incidence of coeliac disease shows that several information sources should be used to avoid underestimation. The incidence rate of coeliac disease in Italy was among the highest in Europe, and was widely variable showing highest figures in Piedmont and Lombardia and the lowest in Umbria and Sardinia. This trend was not due to different age at diagnosis, which suggests variable diagnostic awareness of the disease rather than different environmental patterns affecting the clinical presentation.

[Antigen detection in stools as a first choice for laboratory diagnosis of Helicobacter pylori disease]. / La ricerca dell'antigene nelle feci può essere proposto come test di prima diagnosi della malattia da Helicobacter pylori.

BACKGROUND: Several techniques have been suggested for Helicobacter pylori infection diagnosis, invasive (histology) and not invasive (Urea Breath Test C13, or serological assays). An enzyme immunoassay able to detect Helicobacter pylori antigen directly in stool specimens was recently developed. A study was carried out in order to evaluate the sensibility and the specificity of this test comparing it with the Urea Breath Test C13 and histology. The patients studied are all in pediatric age, and great are the advantages of a non-invasive method to detect infection. METHODS: In this study 60 patients were enrolled. In 34 of them Helicobacter pylori infection was diagnosed by Urea Breath Test C13, all confirmed by histology. In all the 60 patients studied the fecal antigen was researched by an immunoenzymatic method (Premier Platinum HpSA, Meridian Diag.). RESULTS: The detection of Helicobacter pylori in stool shows a sensibility of 100% and a specificity of 97%. CONCLUSIONS: Sensibility and specificity, considering also the low cost of the examination, the short time to perform it and the very easy technique, allows us to propose the test as the first choice in the diagnosis of Helicobacter pylori disease.

[Adherence to a diet and the social aspects of patients with celiac disease]. / Aderenza alla dieta ed aspetti sociali dei pazienti con malattia celiaca.

We studied the social behaviour and dietary habits of 335 coeliacs older than 6 yrs diagnosed in our paediatric gastroenterology unit by a mailed questionnaire, 156 patients (45.2%) answered all questions; their median age was 14.7 yrs (range 6-29). We found that the disease does not compromise educational achievement and working capacity of patients. A majority of our coeliacs are students (from primary school to university) and rather successful ones since 55% of them passed their previous year examinations. Some are already employed and work as clerks, artisans, masons or skilled workers. 89.6% of our patients reported to be on a strict gluten-free diet, 9% introduce small amounts of gluten and 1.4% are on a normal diet by their own decision. Coeliac patients originating from Northern Italy have more of their gluten-free foods home made and use more gliadin free cereals (rice, maize), whereas coeliacs originating from the Southern regions consume more ready made gluten-free foods. We have assessed the amount of gluten-free products consumed monthly by our patients and their food preferences. Females eat less than males and prefer bread and flour based dishes, whereas males east more pasta and biscuits.

[Advantages and limits of rigid rectosigmoidoscope and flexible colonoscope in childhood]. / Vantaggi e limiti del rettosigmoidoscopio rigido e del coloscopio flessibile nell'esplorazione del rettocolon in età pediatrica.

During the past ten years 220 pediatric proctosigmoidoscopies with the rigid instrument in 182 infants and children, and 71 colonoscopies in 62, were performed. Advantages and limits of these two instruments are discussed. The indications and results of the different procedures are presented. Positive diagnoses were obtained in 81% with both techniques while the histological examination was positive in 85% of specimens obtained by colonoscopy and only in 51% of the proctosigmoidoscopical ones. Colonoscopy has increasingly became a complementary method for colonic pathology in children, in comparison with adult medicine, however, pediatric indications have been handled mostly with the shorter instrument for two main reasons: 1) Pediatric colonic pathology affects predominantely the lower tract; 2) Neoplastic lesions, in which total colonoscopy with biopies at different levels is mandatory, are extremely rare in children.

[Therapy of pancreatic insufficiency]. / Terapia dell'insufficienza pancreatica.

The replacing therapy in the treatment of pancreatic insufficiency is considered the first and most important step. At present, the choice is between highly concentrate or enteric-coated enzymatic compounds. Their administration before or during each meal has to be the one able to reduce fecal fat and nitrogen, allowing a satisfactory growth. A long term therapy even at low dosage with antacids or cimetidine must be considered with caution and evaluated in each case. In CF children the nutritional care has now been emphasized for the possible relationship between malnutrition and lung disease; the caloric intake must be higher than normal. The limitation of fat intake is not so important any more when the enzymes replacement is adequate. The vitamins requirement is usually satisfied doubling the normal daily requirement. An increase of vitamins and/or minerals must be considered when clinical or laboratory signs of deficiency are found.

[Campylobacter pylori and gastroduodenal pathology in children]. / Campylobacter pylori e patologia gastroduodenale nel bambino.

Since Warren and Marshall rediscovered in 1983 the presence of a spiral microorganism on the gastric mucosa, and named it Campylobacter Pylori (CP), its significance and characteristics have been largely studied. CP has fulfilled Koch's postulates, which need to proven before a microorganism can be said to cause a disease. The natural source of infection is unknown, but in human volunteer studies, ingestion of a suspension of CP was followed by the development of severe dyspepsia associated with colonization of gastric antrum and histologically proven gastritis B. CP is found overying the gastric epithelium, in the gastric crypts and in the mucus gel layer that protects it from gastric acid. There it causes infiltration of the mucosa by polymorphonuclear leucocytes and mononuclear cells, and mucin depletion. It is found in 60-70% of children with chronic active antral gastritis and can cause various lesions of upper intestinal tract, like esophagitis, duodenitis and gastric or duodenal ulcers. Several tests have been proposed to detect serum antibody against CP, but they are not yet commercially available. Breath test with C 13 or C 14-urea are promising, but up to now the diagnosis can be made only by upper G.I. endoscopy and antral biopsy. A pseudopolypoid antral gastritis seems to be the peculiar lesion caused by CP, but in children it is present only in 40% of cases. CP is easily seen in antral biopsies by Giemsa or Hematoxylin-Eosin staining, or can be cultured in Skirrow's agar under microaerophilic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Self care in celiac disease]. / Autogestione della malattia celiaca.

The need for patients with coeliac disease to be introduced to a self-management program is well established. This program frequently raises some problems for young patients in relation to social condition and personal habits, and to the life and culture of their community. Data from a questionnaire given to 62 young patients show a strong interest in self-management and in periodic meetings. Some problems usually arise only on early adolescence (12/15 years).

[Clinico-histological behavior of celiac patients after gluten load following the definitive diagnosis]. / Comportamento clinico-istologico nei celiaci dopo carico di glutine eseguito a distanza dalla diagnosi definitiva.

In the last 18 years we have followed 330 children with Coeliac Disease (CD), diagnosed according to the ESPGAN criteria (with 3 jejunal biopsies: during the acute phase, after a gluten-free diet and after a gluten challenge). One to fifteen years after the diagnosis, 61 of them asked to be exposed to a second gluten challenge to see if their intolerance was persistent. Ten percent of them had already started the challenge by themselves, the others were on Gluten Free Diet (GFD). To all 61 serial clinical controls, one-hour-blood-xylose absorption test every three months and a jejunal biopsy was suggested. The jejunal biopsy was performed when symptoms recurred, or when xylose-test showed an impaired absorption, or after 2 years. If the first jejunal biopsy showed a villous atrophy the GFD was restarted, while if a normal mucosa was found the gluten challenge was continued and the jejunal biopsy repeated every year. 52 children (85%) showed a villous atrophy after 1.5 to 72 months. 6 (10%) did not show a clinical or histological relapse, 2 refused the jejunal biopsy because symptomless, and 1 had to restart the GFD because she developed a dermatitis herpetiformis. One-hour-blood-xylose test was performed in 29 children and 20 (69%) showed a low absorbtion, the majority of them in the first year of challenge, and the remaining refused it. 36 of the relapsed children presented with mild clinical symptoms while 16 were symptomless.(ABSTRACT TRUNCATED AT 250 WORDS)

[Up-date on the etiopathogenesis of celiac disease]. / Aggiornamento sull'eziopatogenesi della malattia celiaca.

Wheat, oat, rye and barley flours are toxic for celiac patients. Prevalence and incidence of Celiac Disease (CD), quite variable from country to country, are very high in Austria (1 out of 476 born alive) and low in France (1 out of 41.667 born alive). This difference is probably due to its multifactorial genesis. In a multicentric Italian study, histocompatibility antigens of HLA complex II were typed in 460 CD children. DR3 was present in 63% of the cases (Relative Risk = RR: 6.8), DR7 in 67% (RR: 3.8) and DR3/DR7 in 22.5% (RR: 10.5), while in 7.7 of patients both antigens were absent. Therefore in a certain percentage of CD patients these risk antigens are absent, while in the normal population they can be present. The probability of CD increases when HLA DR3 and DR7 are present (but their absence cannot exclude the disease. The main etiological factor is gluten and its fractions (B, B1, B2, fraction 9 etc.). It seems that breast feeding can prevent or delay the onset of CD, while the age at gluten introduction does not modify the risk. Pathogenetic mechanisms are still under discussion: 3 theories are under investigation. 1) Enzymatic theory: a proteolytic enzyme for gluten digestion could be lacking. This theory is not yet proven, while Bruce et al. found in the jejunal mucosa of CD patients an elevation of a transglutaminase, which binds the gluten to enterocytes. Its level does not seem to vary with the diet. 2) Lectinic theory: the gluten bind the enterocyte membrane by a lectinic mechanism and damage it.(ABSTRACT TRUNCATED AT 250 WORDS)

[Jejunal biopsy]. / La biopsia digiunale.

Considering many years' experience in various centres, the authors evidence indications, contraindications, and possible technical inconveniences relative to jejunum biopsy. They analyze various aspects concerning the rightest methods of performance particularly concerning the patient's sedation and immobilization, the local anaesthesia of the back pharynx, techniques facilitating the placement of the capsule the sampling of the mucosa (mucous membrane) and the recovery of the capsule. Then the authors examine the criteria of evaluation of the biopsy sample through both stereomicroscopical and traditional microscopical examinations. They analyze the main parameters in the histological evaluation of biopsy and the basic conditions to observe in order to evaluate histological aspects correctly. Finally they propose a score of histological evaluation, for quick, easy routine use; its results can be reproduced in accordance with traditional histological reading which allows examiners from different centres to confirm their judgements about the atrophy of the mucosa and enables more significant comparisons in case of biopsy repeated on the same subject.

[Behavior of pepsin in childhood and its correlation with gastric acid secretion]. / Comportamento della pepsina nell'infanzia e sue correlazioni con la secrezione acida gastrica.

Little attention has been given to the gastric secretion of pepsin in children. The purpose of this paper is to define the behaviour of peptic concentration (UI/ml) and Basal (BPO) and Stimulated (SPO) Peptic Outputs in children with normal and altered gastric acid secretion. 54 children, aged 15 months to 12 years, were studied: 20 of them were normal, 20 had gastric hypersecretion and 14 were hyposecretors. In the normal subjects the BPO is inversely correlated with age, while the SPO increases with the body weight, but this increment diminishes after the age of 6 years. From these data one can assume that the gastric principal cells reach their functional maturity around the age of 6 years. In the hypersecretors peptic and acid secretions are not correlated in basal conditions, while after pentagrastrin stimulation peptic secretion is greater than in normal subjects but not as the acid one. The SPO is correlated with body weight and height. The different behaviour of hydrochloric acid and pepsin is probably due to the use of pentagrastrin, which is a specific stimulant of oxyntic but not of principal cells. In the hyposecretors both BPO and SPO are lower than in normal children and no correlation was found with age, body weight and acid secretion.

[Irritable bowel syndrome in children]. / La sindrome dell'intestino irritabile nell'infanzia.

The irritable bowel syndrome (IBS) is the most common chronic functional gastroenterological disorder both in adults and in children. In this study we evaluate the different aspects of this syndrome, comparing our observations on 332 children with other studies. Epidemiological data (frequency, sex, age) are examined so as the family histories of gastroenterological disorders. We take in account several pathogenic hypotheses, especially with reference to the alterations of gastrointestinal motility, which could be caused by several factors (psychological, prostaglandins, bile acids, etc.). The clinical picture is very variable, variations depending on the age of children and on the time of onset of IBS. The colic of neonate, caused by retention of air, is the main symptom in the first months of life, followed by chronic diarrhoea, also defined as toddler's diarrhoea, sometime alternating with constipation. In later childhood, recurrent abdominal pain represents a common complaint, in association with diarrhoea or constipation. The principal steps for a proper diagnosis so as the main differential diagnosis are defined. We explain the most important features of management (reassuring parents, free diet), excluding prescription of drugs, that produce only a transitory and symptomatic relief, so as elimination diets, that cause only a failure to thrive without any improvement of symptoms.

Prognostic value of serum pepsinogen I in children with peptic ulcer.

Serum pepsinogen I (PG I) levels were determined by radioimmunoassay in 23 children with peptic ulcer disease (PUD) before and after treatment with ranitidine and in 44 children who were being investigated for recurrent abdominal pain. Upper gastrointestinal endoscopy was performed in all. No lesions were detected in controls, while 18 patients showed a duodenal ulcer, 4 had an antral ulcer, and 1 had both. An 8-week course of ranitidine healed PUD in 93.5% of them, while long-term (1-5 years) endoscopic follow-up showed a 41.9% ulcer relapse rate after stopping treatment. Gastric acid secretion after pentagastrin stimulation [maximal acid output (MAO)] was tested in all controls and in 22 PUD patients: While controls had normal MAO values for their age, 65% of patients had a secretion above the normal range. No significant correlation was detected between serum PG I and MAO either in controls or in patients. Mean serum PG I concentrations were not significantly higher in the whole patient group than in controls, but PUD patients who relapsed after discontinuing ranitidine treatment had shown on admission significantly higher PG I levels when compared both with those who did not relapse and with controls. All patients who relapsed, but only 42.8% of those who did not, had a serum PG I concentration above the normal upper limit for a pediatric population (56.7 ng/ml). None of the PUD patients who had serum PG I levels under this limit relapsed. Our results suggest that pretreatment serum PG I levels in children with PUD may predict fairly accurately which will not relapse after attaining ulcer healing by a short-term ranitidine course.

Campylobacter pylori gastritis: long term results of treatment with amoxycillin.

To evaluate the efficacy of amoxycillin in eradicating Campylobacter pylori, endoscopic biopsy specimens were taken from the antral mucosa of 40 children with gastritis before, immediately after, and (in 30 patients) three months after treatment. Immediately after treatment 34 patients (85%) no longer had the organism in the mucosa, and the gastritis had healed in 23 (58%). Three months later the infection had recurred in 22 of 30 patients (73%), and the gastritis had relapsed in all of them. Significantly more children in whom C pylori recurred had family histories of peptic ulcer disease. The results suggest that amoxycillin alone is ineffective in the long term treatment of C pylori gastritis.