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Biomedical subjects

L Greco

Publications and source records attributed to L Greco.

At least 55 records · Page 3Linked to original sources

Susceptibility to coeliac disease in Tunisian children and GM immunoglobulin allotypes.

Coeliac disease is a malabsorption disorder of the small intestine resulting from ingestion of gluten. The immunogenetic component is clearly demonstrated by the association of the disease with human leukocyte antigens (HLA). Among other candidate genes are the GM allotypes, which are the markers of the constant parts of heavy chains of the subclasses IgG1, IgG2 and IgG3. GM immunoglobulin allotypes have been analysed in 131 unrelated Tunisian children with coeliac disease. All patients and their parents were tested for G1M(1, 2, 3, 17), G2M(23) and G3M(5, 6, 10, 11, 13, 14, 15, 16, 21, 24, 28) by the classical haemagglutination method. Genotypes and haplotypes were deduced from phenotypes in patients and their parents. Transmission disequilibrium tests were performed in 79 informative families. The GM*3;..;5* haplotype was transmitted more often (23) than not (8) by heterozygous parents (chi 2 = 7.26; P = 0.007). This difference remained significant after correction for multiple testing. This study provides evidence for association and linkage between GM and coeliac disease. It suggests that GM or genes close to GM play a role in the development of the disease.

Celiac Disease↗

Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease.

Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten-composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D' = D/Dmax) between the polymorphic sites were calculated. Significant D' values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkage disequilibrium (D' approximately equal to 1) with them. The power of the test was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed.

Alleles↗

Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease.

BACKGROUND & AIMS: The relationship between celiac disease and many autoimmune disorders has been explained by the sharing of a common genetic factor. In a multicenter national study, we examined the relationship between the prevalence of autoimmune disorders in celiac disease and the duration of exposure to gluten. METHODS: Over a 6-month period, 909 patients with celiac disease (group A; mean age, 16.1 +/- 3.8 years; grouped according to age at diagnosis into three subgroups [group A1, <2 years; group A2, 2-10 years; and group A3, >10 years]), 1268 healthy controls (group B; mean age, 20.8 +/- 4.5 years), and 163 patients with Crohn's disease (group C; mean age, 28.8 +/- 10 years) were evaluated for the presence of autoimmune disorders. RESULTS: Prevalence of autoimmune disorders in group A was significantly higher than in group B (14% vs. 2.8%; P < 0.000001) but not higher than in group C (12.9%). Prevalence of autoimmune disorders in celiac disease increased with increasing age at diagnosis: 5.1% in group A1, 17% in group A2, and 23.6% in group A3 (P = 0.000001). In group A3, the prevalence of autoimmune disorders was significantly higher than in group C. In a logistic regression model, age at diagnosis was the only significant predictor variable of the odds of developing an autoimmune disorder (r = 0.3; P < 0.000001). CONCLUSIONS: Our data show for the first time that the prevalence of autoimmune disorders in celiac disease is related to the duration of exposure to gluten.

Adolescent↗

Ciliary motility at light microscopy: a screening technique for ciliary defects.

To verify whether or not ciliary motility can be reliably assessed by light microscopy alone, we examined the nasal brushings of 53 patients with suspected ciliary dyskinesia and 10 healthy controls. The results of light microscopy were compared with cilia ultrastructure assessed with electron microscopy. Ciliary motility was significantly related with cilia ultrastructure. However, eight cases of lung disease due to bronchiectasis of unknown origin had immotile cilia on light microscopy, but normal ciliary ultrastructure on electron microscopy. Instances of normal and abnormal ultrastructure were detected in one case with motile cilia. There was an 83% agreement between electron microscopy and light microscopy. Sensitivity and specificity of light microscopy were 92% and 80%, respectively. In conclusion, light microscopy evaluation of ciliary motility does not appear to be a reliable screening test for ciliary dyskinesia because it does not quantify ciliary beat activity, which is a criterion for deranged ciliary motion. A complete evaluation of ciliary ultrastructure together with in vivo, if applicable, or in vitro function test (namely, the analysis of ciliary beat frequencies and/or waveform) is required for a definite diagnosis of ciliary dyskinesia.

Adolescent↗

Increased concentrations of eosinophilic cationic protein in whole-gut lavage fluid from children with inflammatory bowel disease.

BACKGROUND: Eosinophils may be involved in the pathogenesis of inflammation in inflammatory bowel disease. The purpose of this study was to verify whether concentrations of eosinophilic cationic protein in gut lavage fluid from children with inflammatory bowel disease correlate with clinical and laboratory indexes of disease activity. METHODS: Twenty-three children with Crohn's disease, 14 with ulcerative colitis, and 22 age-matched control subjects entered the study. Radioimmunoassay and sandwich enzyme-linked immunosorbent assay techniques were used to measure eosinophilic cationic protein, total immunoglobulin G and interleukin-1beta, respectively. RESULTS: Gut lavage eosinophilic cationic protein levels were significantly (p < 0.005) higher in patients with Crohn's disease and ulcerative colitis than in control subjects. Intestinal eosinophilic cationic protein levels decreased in three of four children with Crohn's disease who were fed an elemental diet. There was a significant (p < 0.001) correlation between eosinophilic cationic protein concentrations and immunoglobulin G and interleukin-1beta levels in gut lavage fluid. CONCLUSIONS: Elevated intestinal eosinophilic cationic protein levels in inflammatory bowel disease suggest that eosinophils are involved in the gastrointestinal inflammation in this disease. Intestinal eosinophilic cationic protein concentration is another marker with which to discriminate between active and inactive inflammatory bowel disease.

Adolescent↗

Microsurgery and varicocele: state of the art.

Many surgical procedures have been proposed in the treatment of varicocele; however, the rate of recurrence and of postoperative complications, together with important correlation of this disease with male sterility, has played an important role in determining the success of microsurgery. In the present brief review, the indications for microsurgery and microsurgical dissection and/or anastomosis are described in comparison to traditional surgery.

Anastomosis, Surgical↗

Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-gamma and interleukin-4.

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

Adolescent↗

Early childhood feeding practices in southern Italy: is the Mediterranean diet becoming obsolete? Study of 450 children aged 6-32 months in Campania, Italy. Cultural Paediatric Association.

With increasing affluence, the traditional food choices of Mediterranean populations are changing. The changes appear to begin in early infancy, with increased consumption of processed foods. To determine current consumption patterns of the diets of 450 toddlers, 6-32 months old, enrolled from 17 paediatric practices in the Campania region of Italy, quantitative data were collected for 7 d, using calibrated feeding bottles, cups and dishes. Automated food analysis was employed and quality control was performed on a sub-sample. The average daily intake was 373 kJ/kg. Forty-three percent of energy was provided by carbohydrates, while fats supplied 39%, 45% of fats were saturated and 46.7% were monosaturated (primarily olive oil). Proteins provided 18% of daily energy; most (81.4%) were of animal origin. Fibre was virtually absent from the study children's diet. Total daily cholesterol reached an average value of 191 mg/d, corresponding to 201 mg/4.2 mJ. The intake per kg of cholesterol increased with age in the first year, while proteins and fats decreased. Dairy products were the main source of energy, fats and cholesterol. Vegetables and legumes were a minor source of energy at all ages: the consumption of fruit decreased with age. Although the overall pattern of feeding of this cohort remains favourable compared with other children groups in developed countries, consumption of whole milk and full fat dairy products may be reduced to equilibrate the diet.

Age Factors↗

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.

Celiac Disease↗

Lack of correlation between genotype and phenotype in celiac disease.

BACKGROUND: Celiac disease has a wide range of clinical features. The goal of this study was to evaluate whether specific HLA genotypes are associated with particular clinical appearances. METHODS: One hundred forty-five patients with confirmed celiac disease were oligotyped for DR and DQ HLA genes. Clinical notes, physical examination, and a questionnaire provided their personal data. Patients were grouped into nine genotypic categories, according to the presence of the specific DQ heterodimer DQA1*0501-DQB1*0201 (hence termed alpha0beta0), in single or double dose, and the presence of the DRB4 antigen. RESULTS: Age at first symptoms and age at beginning of gluten-free diet were not significantly different in the nine groups. The initial symptoms of the disease had a similar distribution in all groups. In twenty-seven patients, disease was diagnosed by family screening: they shared a similar HLA genotype with those who had relevant symptoms. The actual growth status-evaluated by standardized height, percentage of median weight for age, and percentage of median weight for height--was not different in the nine groups. Presence of unusual health complaints was not associated with a specific genotype. CONCLUSIONS: There is no evidence that clinical features of celiac disease are associated with different HLA genotypes. Genes outside the HLA may play a relevant role.

Body Height↗

Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings.

BACKGROUND: CD3 and gamma delta cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings. Aim- To establish an in vitro system for assessing immunological changes induced by gluten in the rectum. PATIENTS AND METHODS: Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated. RESULTS: In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group. CONCLUSIONS: Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.

Adolescent↗

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↗

Aneurysms of the supra-aortic trunks in Takayasu's disease. Report of two cases.

Takayasu's arteritis is a chronic inflammatory disease of unknown etiology, which affects the aorta and its branches. The resulting lesions can be of steno-occlusive or aneurysmatic type; the latter form is relatively rare. The authors report 2 cases which came under their observation for treatment. The first was a young man of 22 years with aneurysm of the common right carotid artery and of the subclavian left intrathoracic artery. The carotid aneurysm was operated first; arterial reconstruction was ensured by means of a dacron bypass as the saphenous vein was not usable. Three months later, exeresis of the subclavian aneurysm was performed with a left thoracotomy in the IV space. The postoperative course was uneventful and no untoward event has been observed during follow-up (15 months). The second case was a young girl of 16 years with poststenotic aneurysmatic dilatation of the anonyma artery, tight stenosis of the left renal artery and occlusion of the right renal artery. The patient underwent median sternotomy and removal of the aneurysmatic wall together with the stenosis, and a dacron patch was applied. During preoperative angiography, the stenosis of the left renal artery had been treated with PTA; one month after the first operation, a right aorto-renal bypass was fashioned with the saphenous vein. Postoperative stay was free from complications on both occasions and complete normalization of the pressure values was obtained, which persists after 12 months.

Adolescent↗

Synergistic effect of two HLA heterodimers in the susceptibility to celiac disease in Tunisia.

The DR and DQ HLA genotypes of 94 Tunisian children affected with celiac disease are analyzed so that we can gain a better understanding of the HLA component of this disease. All of them carry at least one of two specific heterodimers: a DQ heterodimer, encoded by DQA1*0501, DQB1*0201 and/or a DR heterodimer, encoded by the nonpolymorphic gene DRA and the DRB4 gene. Quantifying the relative penetrances of all susceptible genotypes gives evidence for a synergistic effect of these two heterodimers and for a dose effect of the alleles encoding the beta chains of these two heterodimers. The DR3DR7 individuals have the greatest risk. They present the two kinds of heterodimers and carry two DQB1*0201 alleles. Celiac disease is the first HLA-associated disease for which the at-risk genotypes are so well delineated.

Adolescent↗