Pietro Strisciuglio

Detection of Helicobacter pylori in stool specimens by non›invasive antigen enzyme immunoassay in children: multicentre Italian study

Helicobacter pylori infection is mainly acquired in childhood and may predispose to peptic ulcer or gastric cancer later in life.1 Non-invasive diagnostic tools are particularly useful in children as screening tests and for epidemiological studies, but their accuracy has to be tested against that of invasive tests in symptomatic patients before they are used in any particular population. Of the non-invasive tests now available, serological testing is not accurate in young patients and the 13C urea breath test is expensive. In 1998 an enzyme linked immunoassay (ELISA) (Premier-Platinum-HpSA, Meridian Diagnostics, Cincinnati, OH, USA) was approved by the Food and Drug Administration for both diagnosis in adult symptomatic patients, and monitoring the response to treatment. It is now commercially available, but its correlation with gastric infection has not been assessed in children. We evaluated its diagnostic accuracy against invasive tests in children undergoing endoscopy for clinical evaluation, and we determined the cut off values for the paediatric population. View this table: Test performance calculated according to different reading techniques (at 450 …

A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency

The insulin-like growth factors (IGFs; somatomedins) comprise a family of peptides that play important roles in mammalian growth and development. The principal members of this family are IGF1 and IGF2. IGF1 (somatomedin C), a 70 residue basic polypeptide, mediates many of the growth promoting actions of growth hormone (GH) and has metabolic and mitogenic effects.1 The major source of circulating IGF1 is the liver, but it is also produced in a wide variety of tissues and has endocrine and paracrine modes of action. The mature IGF1 peptide has A, B, C, and D domains with homology to insulin, and is highly conserved.2 It is produced as an inactive precursor, pre-pro-IGF1, with an additional carboxyterminal E region that plays an important role in the maturation of normal IGF1 peptide. This regulatory region is obtained by alternative splicing of the last two exons. IGF1 resides on the long arm of chromosome 12 (12q 22–24.1),3 and several molecular studies have demonstrated that the structure of this gene is very complex. The gene contains six exons, which extend over more than 85 kb on chromosomal DNA. For human IGF1, two potential primary translation products exist: IGF1A and IGF1B, with sizes of 153 and 195 amino acids respectively. The two precursors are synthesised from distinct messenger RNAs produced by alternative splicing of the primary transcript. IGF1A mRNA contains exons 1, 2, 3, 4, and 6 of the human IGF1 gene while IGF1B is encoded by exons 1, 2, 3, 4, and 5. It has been speculated that IGF1B plays the major role during intrauterine growth, while the same function during postnatal growth is taken over by IGF1A.4 Recent studies have focused attention on the genetic causes of growth alterations. Mutations involving the molecular structure of GH5 or the function of …

Prevalence and Natural History of Gastroesophageal Reflux: Pediatric Prospective Survey

OBJECTIVE. The prevalence and natural history of gastroesophageal reflux in infants have been poorly documented. The aim of this study was to evaluate the prevalence and natural history of infant regurgitation in Italian children during the first 2 years of life. METHODS. A detailed questionnaire, according to the Rome II criteria, was completed by 59 primary care pediatricians to assess infant regurgitation in consecutive patients seen in their office over a 3-month period. A total of 2642 patients aged 0 to 12 months were prospectively enrolled during this 3-month period. Follow-up was performed at 6, 12, 18, and 24 months of age. RESULTS. A total of 313 children (12%; 147 girls) received the diagnosis of infant regurgitation. Vomiting was present in 34 of 313 patients. Their score for the Infant Gastroesophageal Reflux Questionnaire was 8.51 ± 4.75 (mean ± SD). Follow-up visits were conducted to the end in 210 of 313 subjects. Regurgitation had disappeared in 56 of 210 infants by the first 6 months of age, in 128 by the first 12 months, in 23 at 18 months, and in 3 patients by the first 24 months. At follow-up, 1 of 210 patients had developed a gastroesophageal reflux disease with esophagitis, proven endoscopically and histologically; another patient received a diagnosis of cow milk protein intolerance. The Infant Gastroesophageal Reflux Questionnaire score reached 0 after 8.2 ± 3.9 months in breastfed infants (89 of 210) and after 9.6 ± 4.1 months in artificially fed infants. CONCLUSIONS. We found that 12% of Italian infants satisfied the Rome II criteria for infant regurgitation. Eighty-eight percent of 210 infants who had completed a 24-month follow-up period had improved at the age of 12 months. Only 1 patient later turned out to have gastroesophageal reflux disease. Use of breast milk was associated with a shorter time necessary to reach an Infant Gastroesophageal Reflux Questionnaire score of 0.

Expression of proinflammatory and Th1 but not Th2 cytokines is enhanced in gastric mucosa of Helicobacter pylori infected children

BACKGROUND Helicobacter pylori-induced gastric inflammation is thought to be largely regulated by cytokines. PATIENTS AND METHODS The expression of interferon-gamma, interleukin-12, interleukin-4, interleukin-10, interleukin-8, and interleukin-17 mRNA was examined on gastric mucosal samples from 24 children by semiquantitative reverse transcription polymerase chain reaction and southern blotting. Biopsy-based tests, serology, and urea 13C breath test were used to assess Helicobacter pylori status. Gastric biopsies were also evaluated for bacterial density, chronic inflammation, and acute inflammatory activity. RESULTS Interferon-gamma, interleukin-12, interleukin-8 and interleukin-17 expression was higher in Helicobacter pylori-infected (n=13) than uninfected (n=11) children. Conversely, interleukin-4 and interleukin-10 expression did not differ between Helicobacter pylori-infected and uninfected children. In Helicobacter pylori-infected children, interferon-gamma, interleukin-12, interleukin-8 and interleukin-17 expression correlated with bacterial density, and Interferon-gamma and interleukin-12 expression with chronic inflammation score. CONCLUSIONS The findings of this study indicate that, in children, Helicobacter pylori-induced inflammatory response would favour production of proinflammatory cytokines and development of cell-mediated immunity, namely Th1 response.

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport caused by mutations in the SLC7A7 gene. We report the genomic structure of the gene and the results of the mutational analysis in Italian, Tunisian, and Japanese patients. The SLC7A7 gene consists of 10 exons; sequences of all of the exon-intron boundaries are reported here. All of the mutant alleles were characterized and eight novel mutations were detected, including two missense mutations, 242A-->C (M1L) and 1399C-->A (S386R); a nonsense mutation 967G-->A (W242X); two splice mutations IVS3 +1G-->A and IVS6 +1G-->T; a single-base insertion, 786insT; and two 4-bp deletions, 455delCTCT and 1425delTTCT. In addition, a previously reported mutation, 1625insATCA, was found in one patient. It is noteworthy that 242A-->C causes the change of Met1 to Leu, a rare mutational event previously found in a few inherited conditions. We failed to establish a genotype/phenotype correlation. In fact, both intrafamilial and interfamilial phenotypic variability were observed in homozygotes for the same mutation. The DNA-based tests are now easily accessible for molecular diagnosis, genetic counseling, and prenatal diagnosis of LPI.

Early detection of podiatric anomalies in children with Down syndrome

AIMS To verify the importance of podiatric evaluation in patients with Down syndrome for the early diagnosis and treatment of minor orthopaedic problems. METHODS Case-control study of 50 children affected by Down syndrome (aged 4-10 y) without major orthopaedic malformations compared to 100 healthy children. A complete podiatric examination was performed on all patients and controls. RESULTS Children with Down syndrome showed several orthopaedic anomalies including bony deformity of the forefoot (90%), flat foot (60%), isolated calcaneal valgus (24%), knee valgus (22%) and pronated flat foot (16%). These abnormalities were responsible for postural alterations as confirmed by baropodometric examination. CONCLUSION The data demonstrated a greater incidence of minor orthopaedic alterations and suggest the necessity of regular podiatric examinations in the follow-up of this syndrome.

Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients

BACKGROUND/AIMS To describe in detail the specific clinical and biological characteristics of three patients with MPV17 gene mutations, a rare hepatocerebral mitochondrial DNA depletion syndrome (MDS) and the positive effects of a novel dietetic treatment based on avoidance of fasting. METHODS We describe the case histories of three members of the same family with MPV17 mutations. RESULTS Two patients had a very severe and progressive liver disease: 1 died in the first year of life and the other underwent liver transplantation. The third patient, now 13 years of age, had a milder form of liver disease and developed progressive ataxia. Psychomotor involvement at onset of disease was mild or absent. No patient had severe hyperlactataemia. In vivo functional studies on two patients showed no hyperlactataemia even after intravenous and oral glucose loading, regular fasting hypoglycemia 3-4h after meals and no response to glucagon. Liver function tests improved when patients received continuous iv glucose infusion or were regularly fed every 3h. CONCLUSIONS These clinical and biochemical features allow us to differentiate patients with MPV17 mutations from other liver MDS and suggest that regular glucose intake at short intervals may be beneficial in slowing the progression of the disease.

Early signs of vascular disease in homocystinuria: A noninvasive study by ultrasound methods in eight families with cystathionine-β-synthase deficiency☆

Fourteen patients (six males, eight females; mean age, 20 years) with homocystinuria due to homozygous cystathionine-beta-synthase (CBS) deficiency, underwent a vascular examination. Fourteen heterozygotes (seven males, seven females; mean age, 46 years), including 12 parents and one daughter of homozygotes (obligate heterozygotes), and one sister of a homozygote (with low enzyme activity as evaluated in vitro), were also examined. Homozygotes and heterozygotes were compared with two separate control groups of different age (mean age, 20 and 43 years, respectively). Ankle/arm systolic pressure index (by continuous-wave Doppler) was, on average, lower in homozygotes (P less than .01) and heterozygotes (P less than .05) as compared with the controls. An ankle/arm index less than 0.97 and suggesting flow-reducing arterial lesions was found in six (21%) lower limbs of homozygotes versus zero in controls (P less than .05). Echo Doppler (Duplex Scanner) abnormalities, indicating early, non-flow-reducing lesions of iliac arteries were more frequent in homozygotes (seven wall abnormalities or stenoses less than 15%) than in young controls (P less than .05). The corresponding figures for heterozygotes were seven wall abnormalities or stenoses (1% to 15% and one stenosis 16% to 50%) (P less than .01 v middle-aged controls). Early lesions (three wall abnormalities or stenoses less than 15%, three stenoses 16% to 50%) were detected in six (23%) internal carotids of heterozygotes versus three (3%) of corresponding controls (P less than .05). Technical limitations precluded the accurate detection of early lesions in the internal carotid arteries of young homozygotes and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Helicobacter pylori infection in children with celiac disease : Prevalence and clinicopathologic features

BACKGROUND Celiac disease is frequently associated with chronic gastritis. Helicobacter pylori is the main etiologic agent of chronic gastritis. The aim of this study was to assess the prevalence of H. pylori, the related symptoms, and the endoscopic and histologic gastric features in children with celiac disease. METHODS Eight-one (24 boys, 57 girls; age range: 1.4-17.7 years, median 6.8) children with celiac disease were studied. All children had a blood sample taken. In a subgroup of 30 children who underwent endoscopy, three gastric biopsy specimens were taken for histology (hematoxylin and eosin, Giemsa, immunohistochemistry) and urease quick test. Symptom complaints were recorded. Age- and sex-matched (one case, one control) children without celiac disease were used for comparison. Serum H. pylori IgG were measured by means of a locally validated commercial enzyme-linked immunoassay. RESULTS Overall, 15 of 81 (18.5%) children with celiac disease and 14 of 81 (17.3%) control children were positive for H. pylori. The percentage of H. pylori positivity was similar in children with untreated and treated celiac disease. Recurrent abdominal pain was the only symptom that helped to distinguish between H. pylori-positive and H. pylori-negative children. However, symptoms disappeared in patients with celiac disease after gluten withdrawal, irrespective of H. pylori status. All endoscopic (erythema, nodularity) and histologic (superficial-, interstitial-, lymphocytic-gastritis, activity, lymphoid follicles) findings did not differ between celiac and nonceliac H. pylori-positive children. CONCLUSIONS Prevalence and clinical expressivity of H. pylori infection is not increased in children with celiac disease. The clinicopathologic pattern of the infection is not specifically influenced in this condition.

Dual vs. Triple Therapy for Childhood Helicobacter pylori Gastritis: a Double-Blind Randomized Multicentre Trial

Background.  Data on the efficacy of eradication treatment for Helicobacter pylori gastritis in children are scarce.