Nicoletta Ansaldi

AMOXYCILLIN PLUS TINIDAZOLE FOR CAMPYLOBACTER PYLORI GASTRITIS IN CHILDREN: ASSESSMENT BY SERUM IgG ANTIBODY, PEPSINOGEN I, AND GASTRIN LEVELS

32 children (mean age 12 years, range 6-18) with non-specific abdominal pain and Campylobacter pylori positive gastritis received a six week course of daily oral amoxycillin (50 mg/kg) and tinidazole (20 mg/kg). Before treatment and one month after stopping treatment, endoscopic biopsy samples were taken from the antral mucosa and serum C pylori IgG antibody, pepsinogen I, and gastrin levels were measured in fasting blood samples. One month after treatment 30 children (94%) were cleared of C pylori and gastritis had resolved in 27 (84%) and was improved in the remaining 5. Serum IgG, pepsinogen I, and gastrin levels were significantly decreased after treatment. Of 12 children assessed at six months, 9 remained free of C pylori. Increases or decreases in IgG level indicated clearance or recurrence, respectively, of C pylori.

Helicobacter pylori in children with peptic ulcer and their families

Little is known about the source and spread ofHelicobacter pylori, but transmission from infected family contacts has been suggested. We have therefore investigated 15 children with peptic ulcer and their first-degree relatives forH. pylori. Serum anti-H. pylori IgG, pepsinogen I, and gastrin levels were measured. Endoscopy was carried out on the children and relatives, and biopsies were taken from the gastric antrum for histology, microbiology, and urease testing. Six of 11 children with duodenal ulcer (55%) and two of four children with gastric ulcer (50%) were positive forH. pylori. Fourteen of 16 parents (87%) and eight of 13 siblings (61%) ofH. pylori-positive children with peptic ulcer were also infected compared with eight of 14 parents (57%) and none of four siblings ofH. pylori-negative children with peptic ulcer (P< 0.10, >0.05, and NS, respectively). The children withH. pylori-negative peptic ulcer and negative siblings combined were younger than positive children with peptic ulcer and positive siblings (P<0.001). The reliability of serum anti-H. pylori IgG level as a screening test for infection was confirmed. These findings call into question a pathogenetic role forH. pylori in some childhood peptic ulceration, but do suggest that person-to-person spread of infection occurs.

Serologic IgG recognition of Helicobacter pylori cytotoxin-associated protein, peptic ulcer and gastroduodenal pathology in childhood

Objective To assess seropositivity to Heiicobacter pylori cytotoxin-associated proteins in a group of children with H. pylori gastritis and to correlate seropositivity to their disease characteristics, in a prospective study. Patients and methods Sera were collected from 68 children with H. pylori gastritis and IgG recognition of H. pylori cytotoxin-associated proteins was assessed by western blotting. Endoscopic and histologic findings, severity of antral inflammation, mucus gel layer thickness, symptom severity, serum pepsinogen I and gastrin levels of seropositive and seronegative children were compared. Results Forty-four children (64.7%) had serum IgC antibodies that recognized the 130 kDa cytotoxin-associated protein. In seropositive children, the antrum was more frequently nodular at endoscopy (P < 0.01) and duodenal ulcer was more common (P < 0.05). Gastritis was more frequently active (P < 0.01), inflammatory infiltrate was heavier (P < 0.02) and serum pepsinogen I levels were higher (P < 0.001). All children with duodenal ulcer, but only one out of five with gastric ulcer, were seropositive. Conclusions Infection with H. pylori strains which do or do not express the cytotoxin-associated protein may partly account for the difference in disease severity seen in H. pylori gastritis.

Endoscopic and histologic findings in the upper gastrointestinal tract of children with coeliac disease

Frequency of mucosal damage to the esophagus, stomach, and duodenum was investigated in 176 children with coeliac disease (CD) during 230 upper GI en-doscopies performed to obtain duodenal biopsy specimens and was compared with findings in 230 age-matched children who underwent endoscopy for upper GI complaints without CD (non-CD patients). To evaluate a possible association with gluten ingestion, we then compared frequency of mucosal damage in patients on a gluten-containing diet and those on a gluten-free Diet (GFD). In children with CD, frequency of esophageal damage seen at endoscopy and of peptic esophagitis shown by histology were significantly lower than in non-CD patients (p < 0.01) due to the very low frequency of mucosal damage in CD children on GFD; however, frequency of columnar metaplasia was significantly higher (p < 0.05). At endoscopy, CD children had a significantly lower frequency of gastric abnormalities, but histology showed a higher prevalence of superficial chronic gastritis (SCG; p < 0.01). SCG was associated with gluten ingestion, since its frequency in CD children on GFD was similar to the frequency in non-CD patients. At endoscopy, frequency of duodenal mucosal damage was similar in CD and non-CD patients. In addition to villous atrophy, histology showed a significantly higher frequency of duodenitis in CD children on a gluten-containing diet (p < 0.001 vs. non-CD patients; p < 0.05 vs. CD children on GFD). Our findings show that the mucosa of the whole upper GI tract can be damaged in CD patients and that the prevalence of some changes is higher with a gluten-containing diet.

Increased tight junction width in two children with Ménétrier's disease.

Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in children with Ménétriers disease. However, the changes in gastrointestinal mucosa that can cause PLE have not been described yet in children. We studied by electron microscopy the mucosa of the gastric fundus, which is the site where macroscopic changes are most prominent, in two children with Ménétriers disease. We found that tight junction width was increased to 10.5 +/- 0.94 nm (mean +/- 1 SD) in one child and to 9.7 +/- 0.7 in the other. Tight junction width returned to normal when PLE and edema subsided. These ultrastructural changes were similar to those described in adults with the disease, although the clinical course of Ménétriers disease is very different in adults and in children. Both patients showed evidence of cytomegalovirus (CMV) infection, as indicated by increasing IgG antibodies against the virus or recovery of the virus in the urine. Although Helicobacter pylori was found in the antral mucosa of one patient, the clinical course of the disease was not related to this microorganism. We conclude that increased tight junction width plays a role in PLE seen in Ménétriers disease in children and that CMV, rather than Helicobacter pylori, is associated with the disease.

An alternative approach to the assessment of γδ 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.

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.

Helicobacter pylori Gastritis in Children: Wide Spectrum of Symptoms

Helicobacter pylori (HP) gastritis in adult patients can present with a wide variety of symptoms, but it is not yet clear whether gastritis is related to particular symptoms and which symptoms are most frequently associated.

Childhood Peptic Ulcer Can Be Cured by Eradicating Helicobacter pylori

Since fiberoptic endoscopes of small caliber have been available in the last 2 decades, peptic ulcers are diagnosed more frequently in children. Little is known on the long-term prognosis for pediatric peptic ulcer disease. A high incidence of morbidity persisting into adulthood has been reported, with a 47% endoscopically proven relapse rate [1] and a 70% recurrence of symptoms [2]. In adult patients the history of peptic ulcer is now changing after several reports showed the possibility of decreasing relapse rate by Helicobacter pylori eradication [3–6]

Upper G.I. Damages seen at Endoscopy in Children with Coeliac Disease

Endoscopic duodenal biopsies to diagnose Coeliac Disease (CD) can be easily obtained with forceps. AIM: to study mucosal damages seen during gastroscopy performed to obtain duodenal biopsies, and their relation to a gluten containing diet in childhood CD.