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1.
Dig Liver Dis ; 42(9): 624-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20308024

ABSTRACT

BACKGROUND: Inappropriateness of upper endoscopy (EGD) indication causes decreased diagnostic yield. Our aim of was to identify predictors of appropriateness rate for EGD among endoscopic centres. METHODS: A post-hoc analysis of two multicentre cross-sectional studies, including 6270 and 8252 patients consecutively referred to EGD in 44 (group A) and 55 (group B) endoscopic Italian centres in 2003 and 2007, respectively, was performed. A multiple forward stepwise regression was applied to group A, and independently validated in group B. A <70% threshold was adopted to define inadequate appropriateness rate clustered by centre. RESULTS: discrete variability of clustered appropriateness rates among the 44 group A centres was observed (median: 77%; range: 41-97%), and a <70% appropriateness rate was detected in 11 (25%). Independent predictors of centre appropriateness rate were: percentage of patients referred by general practitioners (GP), rate of urgent examinations, prevalence of relevant diseases, and academic status. For group B, sensitivity, specificity and area under receiver operating characteristic curve of the model in detecting centres with a <70% appropriateness rate were 54%, 93% and 0.72, respectively. CONCLUSIONS: A simple predictive rule, based on rate of patients referred by GPs, rate of urgent examinations, prevalence of relevant diseases and academic status, identified a small subset of centres characterised by a high rate of inappropriateness. These centres may be presumed to obtain the largest benefit from targeted educational programs.


Subject(s)
Endoscopy, Digestive System/statistics & numerical data , Patient Selection , Referral and Consultation , Upper Gastrointestinal Tract/diagnostic imaging , Adult , Age Distribution , Humans , Italy , Middle Aged , Practice Guidelines as Topic , ROC Curve , Retrospective Studies , Ultrasonography
2.
Dig Liver Dis ; 38(5): 347-51, 2006 May.
Article in English | MEDLINE | ID: mdl-16055395

ABSTRACT

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.


Subject(s)
Hepatic Encephalopathy/complications , Hepatic Encephalopathy/diagnostic imaging , Hyperammonemia/diagnostic imaging , Hyperammonemia/etiology , Aged , Angiography , Hepatic Artery/diagnostic imaging , Humans , Liver Cirrhosis , Male , Mesenteric Artery, Superior/diagnostic imaging , Portal Vein/diagnostic imaging , Ultrasonography, Doppler, Color
3.
Gut ; 53(9): 1356-62, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15306600

ABSTRACT

BACKGROUND: Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions. AIMS: To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis. PATIENTS AND METHODS: Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up. RESULTS: Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm. CONCLUSIONS: In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Cirrhosis/complications , Liver Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle/methods , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/etiology , Diagnosis, Differential , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/etiology , Male , Middle Aged , Population Surveillance/methods , Prospective Studies , Ultrasonography
4.
Br J Cancer ; 90(4): 882-7, 2004 Feb 23.
Article in English | MEDLINE | ID: mdl-14970868

ABSTRACT

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with constitutional mutations in a class of genes involved in DNA mismatch repair. We identified 32 kindreds, with germline mutations in one of three genes hMSH2, hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk individuals in each family underwent genetic testing: moreover, we assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and the main findings of the recommended follow-up. Families were identified through a population-based registry, or referred from other centres. Members of the families were invited for an education session with two members of the staff. When a kindred was consistent with HNPCC, neoplastic tissues were examined for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region. Of the 164 subjects assessed by genetic testing, 89 were gene carriers (66 affected - that is, with HNPCC-related cancer diagnosis - and 23 unaffected) and 75 tested negative. Among the 23 unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo genetic testing. The main reasons for this were: (a) difficulty to reach family members at risk, (b) lack of collaboration, (c) lack of interest in preventive medicine or 'fatalistic' attitude towards cancer occurrence. The number of colorectal lesions detected at endoscopy in gene carriers was significantly (P<0.01) higher than in controls (noncarriers). We conclude that a large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance. This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/genetics , Genetic Predisposition to Disease , Genetic Testing , Germ-Line Mutation , Patient Compliance , Proto-Oncogene Proteins , Adaptor Proteins, Signal Transducing , Adult , Base Pair Mismatch , Carrier Proteins , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , DNA Mutational Analysis , DNA Repair , DNA-Binding Proteins/genetics , Female , Humans , Immunohistochemistry , Male , Microsatellite Repeats , Middle Aged , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Neoplasm Proteins/genetics , Nuclear Proteins , Pedigree , Proteins/genetics , Risk Factors
6.
Ann Oncol ; 12(6): 813-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11484957

ABSTRACT

BACKGROUND: About 15%-20% of colorectal cancers (CRCs) are familial. While a fraction of these arise in the context of hereditary syndromes, the causes underlying the majority of familial CRCs are not yet understood. PATIENTS AND METHODS: Family history of cancer, clinical characteristics, and microsatellite instability (MSI) in a series of 100 consecutive CRC patients were evaluated. RESULTS: Eighteen patients had a positive family history of CRC in a first-degree relative. Of these, two had a clinical diagnosis of familial adenomatous polyposis (FAP), and three were diagnosed with hereditary non-polyposis colorectal cancer (HNPCC) following results of MSI analysis. A diagnosis of HNPCC was also established in a fourth patient with early onset CRC, who had a second-degree relative with CRC, and whose tumor was positive for MSI. The remaining 13 familial CRCs did not show MSI in tumor DNA. The mean age at tumor diagnosis in patients with familial microsatellite-stable (MSS) CRC was higher than in HNPCC and FAP patients and similar to that recorded in sporadic cases. The incidence of second primary malignancies was significantly higher in familial MSS CRC probands (n = 4) compared to patients who did not have a diagnosis of FAP or HNPCC and did not have first-degree relatives affected with CRC (n = 6, in a total of 81 probands with these characteristics). CONCLUSIONS: These results define the existence of a subset of familial CRCs characterized by relatively late age at onset, high incidence of second primary tumors, and absence of MSI in tumor DNA.


Subject(s)
Colorectal Neoplasms/genetics , Microsatellite Repeats/genetics , Adenomatous Polyposis Coli/diagnosis , Adenomatous Polyposis Coli/epidemiology , Adenomatous Polyposis Coli/genetics , Adult , Age of Onset , Base Pair Mismatch/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/secondary , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA, Neoplasm/genetics , Female , Genes, APC/physiology , Humans , Male , Middle Aged , Pedigree
7.
Ann Ital Chir ; 72(1): 5-11, 2001.
Article in Italian | MEDLINE | ID: mdl-11464496

ABSTRACT

Among the suspected bacterial causes of cancer, H. pylori is the agent more consistently linked to malignancy. After its discovery in 1983 and the later confirmation as the leading cause of chronic gastritis, several studies were performed to prove an association between H. pylori infection and gastric carcinoma. The epidemiological data have been so strong that in 1994 the International Association for Research on Cancer stated that "there was sufficient evidence" to classify H. pylori as a group I carcinogen in humans. However, the exact mechanisms underlying the link between H. pylori infection and gastric carcinoma remain still to be elucidated. The natural history of H. pylori infection shows that, although roughly half of the world's human population bears the organism, only a minority of individuals develop clinically important outcomes (e.g. peptic ulcer, lymphoproliferative diseases, atrophic gastritis and gastric carcinoma): host's genetic make-up, duration of infection, diet and differences between H. pylori strains have been proposed as factors potentially able to influence the outcomes in different individuals. The damaging agents by which H. pylori could promote gastric carcinogenesis are produced either by the organism or as a consequence of the host inflammatory response to the infection. Gastric mucosal chronic damage may, therefore, lead to changes in the pattern of epithelial cell kinetic (increase in cell proliferation and induction of apoptosis) in gastric glands which may induce DNA injury with irreversible genetic lesions. Finally, a direct association between H. pylori infection and the induction of gastric carcinoma has been recently demonstrated in an animal model, giving further credence to the role of this organism in gastric carcinogenesis.


Subject(s)
Helicobacter Infections/complications , Helicobacter pylori , Stomach Neoplasms/microbiology , Helicobacter Infections/epidemiology , Humans , Stomach Neoplasms/epidemiology
9.
Eur J Gastroenterol Hepatol ; 13(2): 185-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11246619

ABSTRACT

OBJECTIVES: To evaluate the prevalence of and the risk factors for Helicobacter pylori in a population of medical and non-medical workers at a teaching hospital in Rome, Italy. DESIGN: A cross-sectional study. METHODS: From January to October 1998, 655 subjects (65% of the total population) underwent a 13C-urea breath test to assess H. pylori infection. Subjects completed a questionnaire concerning sociodemographic characteristics, work departments and history of some gastrointestinal symptoms. Differences in means and proportions were evaluated and independent predictors of H. pylori infection status were assessed by multiple logistic regression analysis. RESULTS: Forty percent of the subjects were found to be H. pylori infected. The mean age of positive subjects was significantly higher than that of negative ones (38 +/- 14 versus 34 +/- 12 years; P < 0.01). No significant difference was found between males and females concerning the infection status (40.2% males versus 39.9% females). Lower years of father's education [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.9-5.1] and age older than 35 years (OR, 2.0; 95% CI, 1.3-3.1) were the only independent predictors of the likelihood of H. pylori positivity. Prevalence of gastrointestinal symptoms was similar in infected and uninfected subjects. Physicians were significantly less infected than nurses and auxiliary personnel (26% versus 47% versus 55%, respectively); however, a loss of association was observed after adjustment by multiple logistic regression (OR, 1.8; 95% CI, 0.9-3.7). In all groups, some specific departments appear to be associated with a higher infection status. CONCLUSIONS: Among healthcare workers, H. pylori infection was associated with specific sociodemographic characteristics, such as age and level of father's education. The prevalence of H. pylori infection was not associated with different professional categories. However, some specific departments seem to increase infection risk.


Subject(s)
Health Personnel , Helicobacter Infections/epidemiology , Helicobacter pylori , Adult , Breath Tests , Cross-Sectional Studies , Female , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/microbiology , Helicobacter Infections/diagnosis , Hospitals, Teaching , Humans , Italy/epidemiology , Logistic Models , Male , Middle Aged , Prevalence , Risk Factors
10.
Aliment Pharmacol Ther ; 15(2): 163-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11148433

ABSTRACT

BACKGROUND: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations. AIM: To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden. METHODS: Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability. RESULTS: Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1-0.9; relative risk=0.3, 95% CI: 0.1-0.9; relative risk=0.5, 95% CI: 0.2-0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04). CONCLUSIONS: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Helicobacter Infections/drug therapy , Lactobacillus , Probiotics/therapeutic use , 2-Pyridinylmethylsulfinylbenzimidazoles , Administration, Oral , Adult , Anti-Ulcer Agents/adverse effects , Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Clarithromycin/adverse effects , Clarithromycin/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Helicobacter pylori/drug effects , Humans , Male , Omeprazole/analogs & derivatives , Prospective Studies , Rabeprazole , Tinidazole/adverse effects , Tinidazole/therapeutic use , Treatment Outcome
11.
Gut ; 48(2): 238-46, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11156647

ABSTRACT

BACKGROUND: Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". AIMS: To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS: Pancolonoscopy was performed in 15 patients with resected adenomas (> or =1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS: No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS: The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.


Subject(s)
Adenoma/pathology , Apoptosis/physiology , Cell Division/physiology , Colorectal Neoplasms/pathology , Adenoma/physiopathology , Adult , Aged , Analysis of Variance , Biopsy , Bromodeoxyuridine , Case-Control Studies , Colorectal Neoplasms/physiopathology , Female , Humans , In Situ Nick-End Labeling , Intestinal Mucosa/pathology , Male , Middle Aged , Statistics, Nonparametric
12.
Fam Cancer ; 1(2): 93-9, 2001.
Article in English | MEDLINE | ID: mdl-14574004

ABSTRACT

Mutations of the mismatch repair (MMR) genes MLH1 and MSH2 are associated with hereditary nonpolyposis colorectal cancer (HNPCC), a highly penetrant autosomal dominant condition characterized by hypermutability of short tandemly repeated sequences in tumor DNA. Mutations of another MMR gene, MSH6, seem to be less common than MLH1 and MSH2 defects, and have been mostly observed in atypical HNPCC families, characterized by a weaker tumor family history, higher age at disease onset, and low degrees of microsatellite instability (MSI), predominantly involving mononucleotide runs. We have investigated the MSH6 gene sequence in the peripheral blood of 4 HNPCC and 20 atypical HNPCC probands. Two frameshift mutations within exon 4 were detected in 2 patients. One mutation was found in a proband from a typical HNPCC family, who had developed a colorectal cancer (CRC), a gastric cancer and a rectal adenoma. The CRC and the adenoma showed mild MSI limited to mononucleotide tracts, while the gastric carcinoma was microsatellite stable. The other mutation was detected in an atypical HNPCC proband, whose CRC showed widespread MSI involving both mono- and dinucleotide repeats. The phenotypic variability associated with MSH6 constitutional mutations represents a complicating factor for the optimization of strategies aimed at identifying candidates to MSH6 genetic testing.


Subject(s)
Base Pair Mismatch , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , DNA Repair , DNA-Binding Proteins/genetics , Frameshift Mutation , Genetic Testing , Adult , Base Sequence , DNA Mutational Analysis , DNA, Neoplasm/analysis , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Phenotype , Polymerase Chain Reaction , Rectal Neoplasms/genetics , Stomach Neoplasms/genetics , Tandem Repeat Sequences
13.
Aliment Pharmacol Ther ; 14(1): 79-83, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10632649

ABSTRACT

BACKGROUND: Helicobacter pylori eradication therapies do not achieve 100% success rates. Antibiotic resistant strains are among the major causes of failure. Current recommendations concerning the management of treatment failures are not fully clear. AIM: To evaluate the efficacy of a multi-step therapeutic strategy in a large group of infected patients. METHODS: A total of 2606 H. pylori-positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week. Patients with continuing infection were then given a second 1-week course of amoxycillin, clarithromycin and ranitidine bismuth citrate. Patients still infected after the second course underwent upper gastrointestinal endoscopy with H. pylori culture, and then received a 1-week quadruple proton pump inhibitor-bismuth based scheme established on H. pylori antibiotic sensitivity. RESULTS: After the first step, eradication was achieved in 2063 out of 2413 patients [86% per protocol analysis (PP); 79% intention-to-treat analysis (ITT)]. First-step failures (350 out of 2413; 14.5% PP) showed second-step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT). The specific quadruple therapy for second-step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success. This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT). CONCLUSIONS: This multi-step strategy succeeded in a high percentage of H. pylori infected patients. Given the lack of precise guidelines on treatment failures, assessing H. pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.


Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Penicillins/therapeutic use , Tinidazole/therapeutic use , Algorithms , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/therapeutic use , Bismuth/administration & dosage , Bismuth/therapeutic use , Clarithromycin/administration & dosage , Drug Resistance, Microbial , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/therapeutic use , Female , Humans , Male , Middle Aged , Penicillins/administration & dosage , Ranitidine/administration & dosage , Ranitidine/analogs & derivatives , Ranitidine/therapeutic use , Treatment Failure
14.
Eur J Hum Genet ; 7(7): 778-82, 1999.
Article in English | MEDLINE | ID: mdl-10573010

ABSTRACT

To determine the role played by MLH1 and MSH2 missense variants in cancer susceptibility, we have investigated the following genetic and biological characteristics associated with six MLH1 and four MSH2 missense changes identified in Italian hereditary nonpolyposis colorectal cancer (HNPCC) families: co-segregation with disease phenotype and/or bonafide pathogenetic mutations; presence of the variant in healthy control subjects; evolutionary conservation of the involved aminoacid and type of aminoacid change; and presence/absence of microsatellite instability (MSI) in tumour DNA. Overall, nine variants did not fulfil > or = 2 pathogenicity criteria. MSI was investigated in tumour samples from carriers of nine different missense mutations. Only 3/9 variants were associated with MSI in tumour DNA. In addition, four variants were not present in affected pedigree members, and five variants were observed in the control population. Based upon these results, we conclude that most MLH1 and MSH2 missense changes are unlikely to act as major causative factors in colorectal cancer susceptibility and development.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA-Binding Proteins , Genetic Predisposition to Disease/genetics , Mutation, Missense , Neoplasm Proteins/genetics , Proto-Oncogene Proteins/genetics , Adaptor Proteins, Signal Transducing , Adolescent , Adult , Carrier Proteins , DNA, Neoplasm/analysis , Humans , Microsatellite Repeats/genetics , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Nuclear Proteins , Polymorphism, Single-Stranded Conformational
15.
Eur J Gastroenterol Hepatol ; 11(10): 1129-34, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10524642

ABSTRACT

OBJECTIVE: To evaluate the predictive value of demographic and clinical features and of the results of an office-based test for Helicobacter pylori antibodies, in the presence of organic dyspepsia. DESIGN: Over a 1-week period, 2206 consecutive patients first referred for endoscopy in 246 Italian centres were included. METHODS: Demographic and clinical features, endoscopy findings, and histological diagnosis of H. pylori infection were recorded for all patients. IgG antibodies to H. pylori were determined in 2128 cases by a rapid, immunochromatographic method (Flex Sure HP, S.K.D., San Jose, CA). RESULTS: Endoscopic abnormalities were found in 939 patients (42.6%). Histologically assessed H. pylori infection was predictive for duodenal ulcer (odds ratio (OR), 6.79; 95% confidence interval (CI), 4.4-10.5). Being male (OR, 1.97; 95% CI, 1.7-2.3), older than 40 years (OR, 1.81; 95% CI, 1.5-2.2), a smoker (OR, 1.88; 95% CI, 1.6-2.3), and presenting nocturnal awakening (OR, 1.62; 95% CI, 1.3-2.0) were independently associated with secondary dyspepsia. Epigastric (OR, 1.50; 95% CI, 1.2-1.9) and retrosternal pain (OR, 1.39; 95% CI, 1.1 -1.8) severe enough to affect the usual activities were predictive of organic diseases. The results of the Flex Sure HP test correlated poorly with histological findings. CONCLUSIONS: Male gender, older age, cigarette smoking, a family history of peptic ulcer, symptoms severe enough to induce awakening, epigastric/retrosternal pain severe enough to influence the usual activities are all independently (although weakly) associated with organic dyspepsia. H. pylori infection is strongly associated with duodenal ulcer, but the rapid test we used was not sensitive enough to achieve clinical utility.


Subject(s)
Digestive System Diseases/diagnosis , Dyspepsia/diagnosis , Endoscopy, Gastrointestinal , Adult , Age Factors , Aged , Antibodies, Bacterial/blood , Cross-Sectional Studies , Digestive System Diseases/microbiology , Dyspepsia/microbiology , Evaluation Studies as Topic , Female , Helicobacter Infections/blood , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Humans , Male , Middle Aged , Predictive Value of Tests , Reagent Kits, Diagnostic , Risk Factors , Sensitivity and Specificity , Sex Factors
16.
Gut ; 45 Suppl 1: I9-I12, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10457029

ABSTRACT

In the past year, several studies have been carried out on the association between Helicobacter pylori infection and a miscellany of extradigestive diseases, such as cardiovascular, immunological, and various other pathologies. In particular, a higher prevalence of H pylori infection in patients affected by ischaemic heart disease has been described and there is growing evidence for an association between H pylori and some autoimmune diseases. Moreover, recent studies have shown that various helicobacter species have been detected in human bile; if confirmed, this finding could revise the diagnostic and therapeutic approach to diseases of the biliary tract.


Subject(s)
Helicobacter Infections/complications , Helicobacter pylori , Vascular Diseases/microbiology , Autoimmune Diseases/microbiology , Humans , Skin Diseases, Infectious/microbiology
17.
Gut ; 43 Suppl 1: S27-32, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9764036

ABSTRACT

The role of Helicobacter pylori in gastric carcinogenesis is supported almost exclusively by epidemiological data and prospective histopathological studies. From biological and molecular points of view, there is no evidence that H pylori or its cytotoxic products have any mutagenic effects. Nevertheless, this infection is associated with profound changes in the pattern of epithelial cell turnover in gastric glands, though the importance of these changes in gastric carcinogenesis is still controversial. H pylori infection increases cell proliferation and alters the distribution of cycling cells within these glands, but these changes can be reversed by successful eradication of the infection. Apoptosis seems to be increased in gastric epithelial cells during H pylori infection, as shown by in vitro studies. There is some, though no conclusive, evidence that this finding also occurs in H pylori positive subjects. It seems that cagA status influences the effect of H pylori on epithelial apoptosis in infected patients. An association of in vitro H pylori induced apoptosis with changes in the expression of pro- and anti-apoptotic genes is reported in the literature, but further study is necessary to clarify the effect of H pylori infection on the molecular events of the apoptotic pathway.


Subject(s)
Apoptosis , Gastric Mucosa/pathology , Helicobacter Infections/pathology , Helicobacter pylori , Stomach Neoplasms/pathology , Cell Division , Epithelial Cells/pathology , Humans , Stomach Neoplasms/microbiology
18.
Hepatogastroenterology ; 45(21): 727-32, 1998.
Article in English | MEDLINE | ID: mdl-9684123

ABSTRACT

BACKGROUND/AIMS: The purpose of this study was to determine the effects of a high-fiber diet and fluid supplementation in patients with functional chronic constipation. METHODOLOGY: One hundred and seventeen patients with chronic functional constipation (aged 18-50 years) were randomly divided into two treatment groups. For two months both groups consumed a standard diet providing approximately 25 g fiber per day. Group 1 (58 patients) was allowed ad libitum fluid intake, while Group 2 was instructed to drink 2 liters of mineral water per day. Compliance was monitored throughout the study and results were assessed in terms of bowel-movement frequency and laxative use. RESULTS: Fiber intake was similar in the two groups, while total daily fluid intake in Group 2 (mean 2.1 liters) was significantly greater than that of Group 1 (1.1 liters)(p < 0.001). In both groups, there were statistically significant increases in stool frequency and decreases in laxative use during the two-month trial, but both changes were greater in Group 2 (stool frequency: p < 0.001 vs. Group 1; laxative use: p < 0.001 vs Group 1). CONCLUSIONS: A daily fiber intake of 25 g can increase stool frequency in patients with chronic functional constipation, and this effect can be significantly enhanced by increasing fluid intake to 1.5-2.0 liters/day.


Subject(s)
Cathartics/therapeutic use , Constipation/therapy , Dietary Fiber/therapeutic use , Drinking , Adolescent , Adult , Humans , Middle Aged
19.
Int J Oncol ; 13(3): 565-9, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9683794

ABSTRACT

Hereditary non-polyposis colorectal cancer (HNPCC) is a genetically heterogeneous disease for which PMS2 gene, a member of the human PMS gene family, is believed to have a marginal role. To better define the contribution of PMS2 to hereditary colorectal cancer, we investigated this gene in 22 unrelated Italian patients that, despite a positive family history and/or early onset and development of tumors with microsatellite instability (MSI), did not carry constitutional mutations of MLH1 and MSH2 genes. No mutations with clear-cut pathogenetic significance were detected in the coding regions of PMS2 gene, but only 8 polymorphisms (7 common and 1 rare, 3 silent and 5 missense) and 3 unique molecular variants (2 missense substitutions and one 3-nucleotide deletion) were seen. Lack of PMS2 truncating mutations in our study does not disagree with its supposed marginal involvement in hereditary colorectal cancer, but at the same time points out the need to investigate the phenotypic molecular and clinical characteristics more specifically associated with PMS2 mutations.


Subject(s)
Adenosine Triphosphatases , Carrier Proteins , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Repair Enzymes , Germ-Line Mutation , Proteins/genetics , Adaptor Proteins, Signal Transducing , Adult , Aged , DNA, Neoplasm/genetics , DNA-Binding Proteins/genetics , Female , Fungal Proteins/genetics , Humans , Male , Middle Aged , Mismatch Repair Endonuclease PMS2 , MutL Protein Homolog 1 , MutL Proteins , MutS Homolog 2 Protein , Neoplasm Proteins/genetics , Nuclear Proteins , Proto-Oncogene Proteins/genetics
20.
Ital J Gastroenterol Hepatol ; 30(2): 153-9, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9675649

ABSTRACT

BACKGROUND: Several studies have shown that Helicobacter pylori infection is associated with enhanced gastric epithelial-cell proliferation, which is thought to be involved in its apparent carcinogenicity. This hyperproliferation is believed to be related to the inflammatory effects of the bacterium. The role of Helicobacter pylori in gastric epithelial apoptosis, however, is less clear. AIM: We attempted to identify the effect of Helicobacter pylori infection on apoptosis in the gastric epithelium and its possible relation to epithelial-cell proliferation and mucosal inflammation. PATIENTS AND METHODS: We studied cell proliferation (via bromodeoxyuridine labelling), apoptosis (using in situ TdT-mediated dUTP-biotin nick end labelling of DNA strand breaks) and mononuclear and polymorphonuclear cell infiltrates (computer-assisted image analysis) in gastric antral biopsies obtained from 37 gastritis patients (20 Helicobacter pylori-positive, 17 Helicobacter pylori-negative). RESULTS: Helicobacter pylori-positives displayed significantly enhanced proliferation within the gastric epithelium that was positively correlated with both acute and chronic inflammatory-cell densities. Apoptotic indexes were similar in both groups and showed no correlation with any of the parameters under consideration. CONCLUSIONS: Enhanced epithelial cell proliferation and an altered distribution of cycling cells within the gastric glands are a common feature of chronic superficial gastritis caused by Helicobacter pylori. In vivo immunohistochemically detected apoptosis of gastric epithelial cells does not seem to be affected by Helicobacter pylori infection. Further study is needed to clarify the effect of this infection on programmed cell death within gastric glands.


Subject(s)
Apoptosis , Epithelial Cells/pathology , Gastric Mucosa/pathology , Gastritis/pathology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Adult , Aged , Biopsy, Needle , Cell Division , Chronic Disease , Epithelial Cells/microbiology , Female , Gastric Mucosa/microbiology , Gastritis/microbiology , Gastroscopy , Helicobacter Infections/diagnosis , Humans , Immunohistochemistry , Male , Middle Aged , Reference Values , Statistics, Nonparametric
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