G Lombardi

Publications (13)59.76 Total impact

• Article: HLA-DRB1 alleles may influence disease phenotype in patients with inflammatory bowel disease: a critical reappraisal with review of the literature.

  V Annese, A Piepoli, A Latiano, G Lombardi, G Napolitano, N Caruso, E Cocchiara, L Accadia, F Perri, A Andriulli
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  ABSTRACT: The HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohn's disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies. Blood samples were obtained from 102 Crohn's disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status. As a whole, after applying Bonferroni's correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn's disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohn's disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohn's disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic. Some clinical features of Crohn's disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohn's disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.
  Diseases of the Colon & Rectum 02/2005; 48(1):57-64; discussion 64-5. · 3.13 Impact Factor
• Article: Anti-Saccharomyces cerevisiae mannan antibodies in inflammatory bowel disease: comparison of different assays and correlation with clinical features.

  V Annese, A Piepoli, F Perri, G Lombardi, A Latiano, G Napolitano, G Corritore, P Vandewalle, D Poulain, J F Colombel, A Andriulli
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  ABSTRACT: Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as a new serological marker associated with Crohn's disease. However, their clinical value is still unclear; furthermore, a standardization of anti-S. cerevisiae mannan measurements is lacking. In this study, we aimed to assess the correlation between anti-S. cerevisiae mannan detection and specific clinical features in Crohn's disease and ulcerative colitis. Moreover, we tested the concordance of four different anti-S. cerevisiae mannan assays. Serum samples from 196 patients with Crohn's disease, 197 patients with ulcerative colitis and 100 unrelated healthy controls were tested for anti-S. cerevisiae mannan with a standard enzyme-linked immunosorbent assay method (Lille) by one of the authors (VP). Subsequently, 60 randomly selected serum samples (27 Crohn's disease, 28 ulcerative colitis and five healthy controls) were tested for anti-S. cerevisiae mannan with three different commercial kits. With the Lille assay, anti-S. cerevisiae mannan were detected in 100 of 196 patients with Crohn's disease (51%; P < 0.0001 vs. controls), 32 of 197 patients with ulcerative colitis (16%; P < 0.02 vs. controls), and six of 100 controls (6%). No correlation between presence of anti-S. cerevisiae mannan and specific clinical features was found in both ulcerative colitis and Crohn's disease patients. The percentages of anti-S. cerevisiae mannan detected with four different assays ranged from 28 (Bouty) up to 43% (Inova), but these differences did not reach statistical significance. The concordance rate of anti-S. cerevisiae mannan detection in the four assays was very low (11 concordant results of 60 samples, 18.3%) (k = 0.15). No improvement of the concordance rate was obtained by modifying the suggested cut-off values (k = 0.20). In this study, we confirm that anti-S. cerevisiae mannan are significantly more frequent in Crohn's disease patients compared with ulcerative colitis patients (P < 0.0001) and controls. However, no correlation with clinical features was found in both ulcerative colitis and Crohn's disease. The low prevalence of anti-S. cerevisiae mannan, at least in our population, and the low concordance rate between different assays, makes the clinical role of this marker questionable.
  Alimentary Pharmacology & Therapeutics 11/2004; 20(10):1143-52. · 3.77 Impact Factor
• Article: Clinical features in familial cases of Crohn's disease and ulcerative colitis in Italy: a GISC study. Italian Study Group for the Disease of Colon and Rectum.

  V Annese, A Andreoli, M Astegiano, M Campieri, R Caprilli, S Cucchiara, R D'Incà, S Giaccari, G Iaquinto, G Lombardi, G Napolitano, A Pera, G Riegler, D Valpiani, A Andriulli
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  ABSTRACT: Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families. In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year (< 1 yr or > or = 1 yr). Statistical analysis was performed with chi2, Fisher's, Mann-Whitney U, and binomial probability tests, when appropriate. A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p < 0.4) in CD families and extensive colitis (p < 0.05) in UC families was demonstrated. A generation difference of 15-20 yr in mean ages at onset of symptoms and at diagnosis was recorded. No features of more aggressive disease in subsequent generations and no differences in gender of transmitting parents and relatives were found. Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15-20 yr earlier than in previous generations without features of increased severity.
  The American Journal of Gastroenterology 10/2001; 96(10):2939-45. · 7.28 Impact Factor
• Article: Clinical features in familial cases of Crohn's disease and ulcerative colitis in Italy: a GISC study

  V Annese, A Andreoli, M Astegiano, M Campieri, R Caprilli, S Cucchiara, R D'Inc|[agrave, S Giaccari, G Iaquinto, G Lombardi, G Napolitano, A Pera, G Riegler, D Valpiani, A Andriulli
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  ABSTRACT: OBJECTIVE: Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families.
  The American Journal of Gastroenterology 09/2001; 96(10):2939-2945. · 7.28 Impact Factor
• Article: Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study.

  V Annese, A Andreoli, A Andriulli, R Dinca, P Gionchetti, A Latiano, G Lombardi, A Piepoli, D Poulain, B Sendid, J F Colombel
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  ABSTRACT: Recent studies in familial Crohn's disease (CD) have suggested that anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.
  The American Journal of Gastroenterology 08/2001; 96(8):2407-12. · 7.28 Impact Factor
• Article: Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical role and review of the literature.

  G Lombardi, V Annese, A Piepoli, P Bovio, A Latiano, G Napolitano, F Perri, P Conoscitore, A Andriulli
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  ABSTRACT: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohn's disease, with particular attention to the possible correlation with clinical features. Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohn's disease, and 252 unrelated healthy subjects. Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9 percent), and 2 of 252 healthy subjects (<1 percent; P < 0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43 vs. 27 percent; P < 0.002), and patients with Crohn's disease with colitis (27 vs. 2.5 percent; P < 0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18 vs. 34 percent; P < 0.0025). In this study we confirm the relative specificity of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohn's disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.
  Diseases of the Colon & Rectum 08/2000; 43(7):999-1007. · 3.13 Impact Factor
• Article: Inflammatory bowel diseeses are associated with the DNA repair gene MLH

  V. Annese, A. Piepoli, P. Bovio, G. Lombardi, P. Forabosco, M. Devoto, A. Latiano, G. Napolitano, N. Caruso, A. Andriulli
  Digestive and Liver Disease - DIG LIVER DIS. 01/2000; 32.
• Article: Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus--a GISC study.

  V Annese, A Latiano, P Bovio, P Forabosco, A Piepoli, G Lombardi, A Andreoli, M Astegiano, P Gionchetti, G Riegler, G C Sturniolo, M Clementi, E Rappaport, P Fortina, M Devoto, P Gasparini, A Andriulli
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  ABSTRACT: Epidemiological studies suggest that inherited factors influence susceptibility to inflammatory bowel disease (IBD), and some candidate loci have been described. In order to verify whether the same loci are responsible for predisposition to IBD in our population, we carried out a linkage study in a series of 58 Italian families with Crohn's disease (CD) and ulcerative colitis (UC). HLA-DQ alleles, motilin gene, and 34 microsatellites flanking the previously described loci on chromosomes 3, 6, 7, 12 and 16 were analysed by non-parametric linkage analysis in 16 and 23 families with CD and UC, respectively, and in 19 families where CD and UC coexisted. Non parametric analysis using GENEHUNTER yielded maximum NPL scores for marker D16S408 in all IBD families combined (2.71, P = 0.003), for marker D16S419 in CD (1.97, P = 0.026) and for marker D16S514 in UC families (2.44, P = 0.007). These markers map in the previously described IBD1 region. No significant linkage was found for markers of chromosomes 3, 6, 7 and 12. The present study performed in a Southern European population provides additional support for the conclusion with the IBD1 locus has a clear role in the genetic susceptibility to IBD.
  European Journal of HumanGenetics 08/1999; 7(5):567-73. · 4.40 Impact Factor
• Article: Fatal ulcerative panenteritis following colectomy in a patient with ulcerative colitis.

  V Annese, N Caruso, M Bisceglia, G Lombardi, R Clemente, G Modola, B Tardio, M R Villani, A Andriulli
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  ABSTRACT: A 37-year-old man, previously submitted to colectomy for ulcerative pancolitis unresponsive to medical therapy, presented with nausea, vomiting, epigastric pain, and bloody diarrhea. An upper gastrointestinal endoscopy revealed mucosal friability, petechiae, and erosions throughout the duodenum, whereas prestomal ileum showed large ulcers and pseudopolyps. Histologically, a dense inflammation chiefly composed of lymphocytes and plasma cells with few neutrophils was detected. No bacteria, protozoa, and fungi could be detected. Despite intensive care, intra-1194 venous antibiotics and steroids, the patient died of diffuse intravascular coagulation and multiorgan failure. At post-mortem examination severe ulcerative lesions were observed scattered throughout the duodenum up to the distal ileum. The dramatic clinical presentation with fatal outcome, the widespread ulcers throughout the intestine, and the histological picture are peculiar features in our patient which can not be ascribed to any type of the ulcerative jejunoenteritis so far reported. Patients with pancolitis and diffuse ileal involvement do not necessarily have Crohn's disease but rather may have ulcerative colitis.
  Digestive Diseases and Sciences 07/1999; 44(6):1189-95. · 2.12 Impact Factor
• Article: HLA antigens and pANCA define ulcerative colitis as a genetically heterogeneous disorder.

  F Perri, V Annese, A Piepoli, G Napolitano, G Lombardi, G Ciavarella, G Di Giorgio, A Andriulli
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  ABSTRACT: Several genetic and subclinical markers have been associated with ulcerative colitis. To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence. Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones. We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.
  Italian journal of gastroenterology and hepatology 03/1998; 30(1):56-61.
• Article: Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin-dependent) diabetes mellitus.

  V Annese, G Lombardi, V Frusciante, U Germani, A Andriulli, G Bassotti
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  ABSTRACT: Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs. The purpose of the present study was to compare the effects of erythromycin (250 mg 60 min before meals) and cisapride (10 mg 30 min before meals) on gastric emptying of healthy subjects and insulin-dependent diabetics. Six type 1 diabetic patients with a previous scintigraphic demonstration of gastroparesis and five healthy subjects were recruited for the study. Gastric emptying was scintigraphically studied by labelling the solid component of a standard test meal. Three scintigraphic studies, spaced at least 3 days apart, were carried out on each subject, basally and after erythromycin or cisapride. Cisapride significantly accelerated gastric emptying in both the healthy subjects and the diabetic patients without any significant effect on the lag-time, whereas erythromycin in addition to a significant improvement of the overall gastric emptying also showed a pronounced effect on the lag-time in both groups (controls 25 +/- 5 vs. 37 +/- 8 min, P < or = 0.04; diabetics 65 +/- 11 vs. 112 +/- 16 min, P < 0.03). Erythromycin may represent an effective therapeutic alternative to more established forms of treatment in patients with diabetic gastroparesis, especially when other drugs have failed.
  Alimentary Pharmacology & Therapeutics 07/1997; 11(3):599-603. · 3.77 Impact Factor
• Article: Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia.

  V Annese, M Basciani, F Perri, G Lombardi, V Frusciante, P Simone, A Andriulli, G Vantrappen
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  ABSTRACT: Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported. Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed. One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia. Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer.
  Gastroenterology 12/1996; 111(6):1418-24. · 11.68 Impact Factor
• Article: Perendoscopic injection of botulinum toxin is effective in achalasia after failure of myotomy or pneumatic dilation.

  V Annese, M Basciani, G Lombardi, N Caruso, F Perri, P Simone, A Andriulli
  Gastrointestinal Endoscopy 11/1996; 44(4):461-5. · 4.88 Impact Factor
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  Available from: europeanreview.org

  Article: NOD2/CARD15 in healthy relatives of IBD patients.

  V Annese, A Latiano, O Palmieri, G Lombardi, A Andriulli
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  ABSTRACT: Crohn's disease (CD) and Ulcerative Colitis (UC) are related chronic inflammatory disorders of the intestine (IBD) caused by a combination of genetic and environmental factors. Three polymorphisms within the NOD2/CARD15 gene are highly associated with CD, increasing the risk from 2 up to 44-fold, depending on the presence of one or two risk alleles. Aim of this study was to investigate the presence of two risk alleles on healthy relatives of IBD patients and prospectively follow them for possible development of IBD. Healthy relatives of familial IBD patients were recruited in our Institution and across Italy in a multicenter study of the IG-IBD. One hundred and twenty one IBD families were identified and blood samples were obtained from 415 first-degree healthy relatives. Single nucleotide polymorphisms (SNPs) R702W, G908R, and L1007finsC of the CARD15 gene were investigated by multiplex pyrosequencing technique. Data obtained in 205 healthy controls (HC) were compared by chi-square or Fisher's test. Ninety eight (28.7%) healthy relatives had one risk allele (HC 14.6%; p = 0.002, OR 2, C.I. 1-4), while 8 had two risk alleles (vs 0.5% of healthy controls; p = 0.01). All subjects were asymptomatic at the time of blood sample and record collections (between 1996 and 1999) and were further investigated with abdominal ultrasonography, blood chemistry and haemoccult test, after 5-8 years of follow-up. All were still asymptomatic with negative findings. Our study once again supports the importance of gene-gene and gene-environment interactions for the final development of the disease.
  European review for medical and pharmacological sciences 10(1):33-6. · 1.04 Impact Factor