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G de Ritis

Publications and source records attributed to G de Ritis.

18 recordsLinked to original sources
PubMed2000

Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator gene and characteristically leads to prominent lung and pancreatic malfunctions. Although an inflammatory reaction is normally observed in the CF airways, no studies have been performed to establish whether a chronic inflammatory response is also present in the CF intestine. We have investigated whether immunologic alterations and signs of inflammation are observed in CF small intestine. Fourteen CF, 20 negative, and four disease controls underwent duodenal endoscopy for diagnostic purposes. Two CF patients were rebiopsied, one after 3 mo of an elemental diet and the other after 2 wk of pancreatic enzyme withdrawal. In three CF and 10 controls, in vitro small intestine organ cultures were also performed. Expression of ICAM-1, IL-2 receptor, IL-2, IFN-gamma, CD80, and transferrin receptor was studied by immunohistochemistry before and after in vitro organ culture. In CF small intestine, an increased number of lamina propria mononuclear cells express ICAM-1 [mean 114 (SD 82.8), p < 0.001 versus controls], CD25 [20.2 (18.7), p < 0.01], IL-2 [23.6 (13.7), p < 0.05], and IFN-gamma [19 (15.9), p < 0.05], whereas villus enterocytes highly express transferrin receptor. Reduced expression of immunologic markers was observed after 24 h of in vitro culture in all three CF patients as well as in the patient kept on elemental diet for 3 mo. These results indicate that chronic inflammation is observed in CF duodenum and suggest that the perturbation of local mucosal immune response may contribute to the overall clinical picture in CF patients.

Adolescent↗
PubMed1998

Cystic fibrosis: when should high-resolution computed tomography of the chest Be obtained?

OBJECTIVE: To provide indications for high-resolution computed tomography (HRCT) of the chest in patients with cystic fibrosis (CF). DESIGN: We compared the HRCT and conventional chest radiography (CCR) scores and assessed their correlation with clinical scores and pulmonary function tests. SETTING: Department of Pediatrics, Federico II University, Naples, Italy. SUBJECTS: A total of 30 patients with CF 6.75 to 24 years of age. RESULTS: CCR scores correlated highly with HRCT (r = -0.8) and clinical (r = 0.5) scores, whereas total HRCT scores were not related to clinical scores. Of all the specific HRCT findings, only bronchiectasis appeared related significantly to the clinical score (r = 0.6). Most pulmonary function tests were related to CCR and total HRCT scores, but not to HRCT scoring of specific changes. Forced vital capacity and CCR scores appeared the best predictors of the HRCT score (multiple R = 0.58 and 0.79, respectively). In patients with mild lung disease, HRCT detected bronchiectasis and air trapping in 57% and 71% of the cases, respectively. In patients with more abnormal chest radiographs, bronchiectasis and air trapping were demonstrated on HRCT in all cases. CONCLUSIONS: These findings suggest that HRCT of the chest is most useful in the identification of early lung abnormalities in patients with CF with mild respiratory symptoms, whereas for established disease, CCR is still the first-line imaging technique. The advantage of detecting early changes on CT imaging awaits additional confirmation, at least until early therapeutic interventions affecting significantly the final outcome of the disease are demonstrated. In patients with advanced disease, HRCT may be useful in the evaluation of specific lung changes when more aggressive treatment such as chest surgical interventions is indicated. Given the cost of the procedure and the high radiation dosage compared with CCR, a careful assessment of the cost:benefit ratios of HRCT is strongly recommended in CF.

Adolescent↗
PubMed1997

DNA fragmentation is a feature of cystic fibrosis epithelial cells: a disease with inappropriate apoptosis?

Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR gene, which result in disrupted chloride secretions with inspissated mucous secretions by exocrine glands. Nick-end labelling was used to assess DNA fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two control lung tissues. In CF small intestine median 46% (range: 30-82) villus enterocytes show DNA fragmentation (vs. 3% (range: 1-7) in controls P < 0.001) and median 37.5% (range: 23-79) crypt enterocytes show Ki67 antigen (P < 0.001). In CF airways 57% (range: 54-70) of epithelial cells show DNA fragmentation. Inappropriate high DNA fragmentation is a feature of various CF epithelia. This could have great impact in understanding the mechanisms leading to disease.

Adolescent↗
PubMed1997

Severe liver impairment in a cystic fibrosis-affected child homozygous for the G542X mutation.

The clinical and laboratory findings of a cystic fibrosis (CF) patient homozygous for the G542X mutation are described. This is the first case, among the 7 G542X homozygous CF subjects described so far who shows severe liver involvement, associated pancreatic insufficiency, and moderate pulmonary expression of the disease, as demonstrated by laboratory and imaging data. This case adds to the conclusion that genotype/phenotype correlation in cystic fibrosis is more complex than formerly suspected.

Child↗
PubMed1996

Clinical features of cystic fibrosis patients with rare genotypes.

We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear rare genotypes: (1) a patient homozygous for the 2183 AA-->G mutation who was affected by a very early pulmonary form of cystic fibrosis, and five patients who were compound heterozygotes either for the 2183 AA-->G mutation or for the I148T mutation, in both instances with the delta F508 mutation; and (2) a patient homozygous for the early nonsense R553X mutation who showed only a moderately severe form of cystic fibrosis. Our results confirm that environmental or genetic factors unrelated to the CF disease contribute significantly to the development of the phenotype.

Adolescent↗
PubMed1996

Molecular epidemiology of cystic fibrosis mutations and haplotypes in southern Italy evaluated with an improved semiautomated robotic procedure.

We screened for 22 cystic fibrosis (CF) mutations in DNA from a first cohort of 69 CF patients from southern Italy using a semiautomated allele specific oligonucleotide (ASO) dot blot procedure based on two multiplex PCR amplifications. Seven mutations (delta F508, N1303K, G542X, 1717-1 G-->A, W1282X, 1148T, and R553X) identified 77.6% of CF chromosomes. Detection reached 79.8% with the 2183 AA-->G mutation analysed with the restriction generating PCR method. Thus, we included the 2183 AA-->G mutation in the ASO protocol and set up the conditions to amplify the gene regions that include the eight mutations in a single multiplex PCR reaction. With this method we tested the DNA of the first cohort of 69 CF patients, a second cohort of 63 CF patients, and 300 carrier relatives; we also performed 12 prenatal diagnoses. The results from the 132 CF patients showed differences in the distribution of CF mutations between the south and north of Italy. The XV2c, KM19, and intron 8 VNDR haplotypes suggested the presence, in CF chromosomes bearing undetected mutations, of a limited number of unknown mutations typical of southern Italy. Finally, for six of the eight mutations, we compared the ASO procedure with the methods based on restriction enzymes; the results obtained with the two procedures were identical for all the 57 chromosomes compared.

Carrier State↗
PubMed1993

Growth dynamics in cystic fibrosis.

The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71-82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity.

Adolescent↗
PubMed1992

Lung involvement, the delta F508 mutation and DNA haplotype analysis in cystic fibrosis.

Molecular studies of cystic fibrosis (CF) have allowed the genetic analysis of patients by means of DNA markers and the direct analysis of the CF gene. Some limited observations are available on the correlation between phenotype and genotype. Here, we report a study on the correlation of DNA haplotypes identified by KM-19 and XV-2c, the presence of the delta F508 mutation and lung involvement in 82 unrelated CF patients. Pulmonary involvement was defined by Chrispin's chest X-ray score, pulmonary function, sputum microbiology, serum immunoglobulin (SIg) levels and Shwachman's clinical score. Patients homozygous for haplotype B showed worse X-ray and clinical scores, more frequent sputum colonization by Pseudomonas aeruginosa and Staphylococcus aureus, lower spirometric values and raised concentrations of SIg G, A and M, compared with patients with other haplotypes. When lung involvement parameters were examined in patients homozygous, heterozygous or null for the delta F508 mutation, no difference was found among the three groups. Our data indicate a significant occurrence of severe pulmonary involvement in patients homozygous for the B haplotype; this is not influenced by the delta F508 mutation. We suggest that simple DNA haplotypes may provide data of both diagnostic and prognostic value, without the need for extensive and expensive molecular analyses.

Adolescent↗
PubMed1991

Mechanisms of gastro-oesophageal reflux in cystic fibrosis.

Abnormal degrees of gastro-oesophageal reflux (GOR) were detected by 24 hour intraoesophageal pH measurement in 12 of 14 children (mean age 7.9 years; range 5 months-16 years) affected by cystic fibrosis and complaining of symptoms suggesting GOR. These patients underwent combined recording of distal oesophageal motility and intraluminal pH in order to investigate mechanisms of GOR. Inappropriate lower oesophageal sphincter relaxation was the most common mechanism of reflux in all patients. Other mechanisms (appropriate relaxation or lowered pressure of the lower oesophageal sphincter, increased intragastric pressure) were detected less frequently. Frequency of inappropriate lower oesophageal sphincter relaxations was significantly higher in patients with cystic fibrosis than in other study groups (symptomatic GOR, GOR disease complicated by respiratory complaints). Inappropriate lower oesophageal sphincter relaxations occurred with the same frequency in patients with cystic fibrosis and in a group of children with GOR disease complicated by oesophagitis. Abnormalities of distal oesophageal contractions such as decreased amplitude or uncoordinated waves were also recorded in cystic fibrosis patients. Seven patients with cystic fibrosis completed a therapeutic trial for eight weeks consisting of postural treatment and oral cisapride, a new prokinetic drug. The oesophageal acid exposure improved in only three patients. We conclude that pathologic GOR is commonly associated with cystic fibrosis. The predominant reflux mechanism in these patients is a transient inappropriate lower oesophageal sphincter relaxation rather than a low steady state basal lower oesophageal sphincter pressure.

Adolescent↗
PubMed1988

In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease.

Specific peptides of known amino acid sequence were prepared from alpha-gliadin (A-gliadin) by cleavage of the protein with cyanogen bromide and chymotrypsin and purification of the resulting peptides. The three peptides derived from the cyanogen bromide cleavage spanned the complete sequence of A-gliadin (266 residues). Four peptides derived from chymotryptic digestion covered the N-terminal sequence through residue 68. These peptides were tested for toxicity in celiac disease by organ culture of biopsied small intestinal tissues taken from patients with active celiac disease. Enterocyte height was used as a measure of peptide effect on cultured tissues. Five of seven peptides tested significantly inhibited increase of enterocyte height in the cultures and were considered toxic on this basis. The largest common sequences among the toxic peptides were -pro-ser-gln-gln- and -gln-gln-gln-pro-; these sequences were absent from the nontoxic peptides. The relationship of these sequences to the damaging effect of gliadins on the small intestinal mucosa in celiac disease remains to be investigated.

Biopsy↗
PubMed1986

In vitro activation of adenylate cyclase of atrophic celiac intestinal mucosa by wheat gliadin-derived peptides.

In order to demonstrate that gliadin peptides may interact with cell membranes of celiac small intestinal mucosa, the capacity of these peptides to activate the cell membrane enzyme adenylate cyclase was tested. The addition of peptides from bread wheat purified A-gliadin and whole gliadin (proteins that are toxic for celiac patients) enhanced the adenylate cyclase activity of crude cell membrane preparations obtained from atrophic small intestinal mucosa of celiac patients. No activation of adenylate cyclase of this tissue was observed with peptides from proteins nontoxic for celiac patients (bread wheat albumin and maize prolamin). Gliadin peptides did not activate adenylate cyclase of morphologically normal small intestinal mucosa from normal subjects or from celiac patients in remission. These results, therefore, suggest that peptides from bread wheat gliadin may interact with cell membrane of atrophic small intestinal mucosa of celiac patients.

Adenylyl Cyclases↗
PubMed1984

Chronic diarrhea and failure to thrive in an infant with Campylobacter jejuni.

We report the case of an infant with chronic diarrhea and failure to thrive. Campylobacter jejuni was isolated from stools and treatment with erythromycin resulted in eradication of infection and prompt resolution of symptoms. A 22-month-old girl was referred to our University Hospital because of weight loss and chronic diarrhea, which did not respond to repeated dietetic trials that excluded milk, gluten, and other foodstuffs. Microscopic examination of the jejunal biopsy specimen revealed a mild degree of partial mucosal atrophy with inflammatory infiltrates in the lamina propria without any hallmarks of celiac disease. Repeated stool cultures on Butzler medium were positive for C. jejuni. This finding was associated with a high titer of specific serum antibodies. Erythromycin therapy without any other form of therapy led to prompt improvement, and the patient reached her "own" 50th centile as weight/height ratio. The aim of this report is to alert pediatric gastroenterologists of the possibility that Campylobacter may be associated with chronic diarrhea and failure to thrive.

Campylobacter Infections↗
PubMed1983

Does breast feeding protect against the development of clinical symptoms of celiac disease in children?

A retrospective approach has been adopted to investigate the frequency and duration of breast feeding and the time of gluten introduction in the diet in 216 celiac children and their healthy siblings of three different centers--Naples, Milan, and Turin. In this matched case-control study, the selected controls were healthy siblings of the cases. Children formula-fed from birth, or breast-fed for less than 30 days, were found to have a relative risk of developing symptoms of celiac disease four times higher than children breast-fed for more than 30 days (p less than 0.0001). To investigate more deeply the effect of the duration of breast feeding as a possible protecting factor, the linear trend for different periods of breast feeding was tested and found to be highly significant (G1: 18.3 with 1 df). Therefore, increased duration of breast feeding is associated with decreased risk of developing celiac symptoms. On the contrary, there was no apparent relationship between early introduction of gluten into the diet and frequency of celiac disease. Our findings are consistent with the hypothesis that a wider diffusion of breast feeding is a factor underlying the recently reported decrease of the incidence of celiac disease in children.

Age Factors↗
PubMed1983

Sigmoidoscopy, colonoscopy, and radiology in the evaluation of children with rectal bleeding.

The authors evaluated the diagnostic role of sigmoidoscopy, colonoscopy, and double contrast radiology in 103 children with rectal bleeding, with or without other gastrointestinal symptoms. The children's mean age was 44 months, with a range from 1 month to 12 years. In 74.5% of the subjects investigated, visual inspection of the anus and sigmoidoscopy with rectal biopsy disclosed a positive diagnosis. Of the remaining patients, a conclusive diagnosis was reached by either colonoscopy or double contrast radiology in all but six patients. These six, with mild painless hematochezia, remained without a diagnosis. The diagnostic procedure in pediatric patients with rectal bleeding should include an initial visual inspection of the anus, and sigmoidoscopy; air contrast enema and colonoscopy should be performed only in children whose sigmoidoscopy is negative, in diagnostic assessment of inflammatory bowel disease, and in cases of recurrent bleeding after removal of rectal polyps. Colonoscopy is important also in the follow-up examination of children with inflammatory bowel disease and allows the removal of polyps located in the proximal colon.

Barium Sulfate↗