Gastric apoptosis and Helicobacter pylori infection: an intricate matter.
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Publications and source records attributed to F Parente.
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BACKGROUND: Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. METHODS: Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. RESULTS: Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(-1)h(-1)). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. CONCLUSIONS: Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.
This study examined the relation of statement type (neutral, questioning, provocative, or bizarre) and length of statement (short vs. long) to reciprocal conversation in Internet chat rooms. The results indicated that provocative statements had a significant impact on reciprocal communication in two out of three different types of Internet chat rooms. These findings support the hypothesis that the amount of reciprocal communication in a chat room is directly related to the type of statements made by the participants. The results also suggest that the type of statement that elicits the greatest reciprocal communication may vary with the type of chat room.
1) The (13)C-urea breath test is one of the most important non-invasive methods for detecting Helicobacter pylori infection in both pre- and post-treatment phases. 2) In order to render the test less expensive and more rapid, a series of modifications have recently been proposed concerning the dose of (13)C-urea and its formulation, as well as the type of measuring equipment used for detecting (13)CO(2) in breath samples. 3) The use of small doses (40--50 mg) of isotope in gelatin capsules or mixed with citric acid in rapid-releasing tablets seems to be promising as it shortens sampling time to 10--20 min. 4) Infrared spectroscopy and laser-assisted ratio analysis equipment are two new valid and less expensive alternatives to conventional isotope mass spectrometry for (13)C analysis in breath. The (13)C-urea breath test is one of the most accurate non-invasive tests for diagnosing Helicobacter pylori infection. This method has become increasingly popular in the last decade since it employs an innocuous, non-radioactive isotope that can be safely used in both children and adults. The test has been recently simplified by reducing the dose of (13)C-urea used, by adopting shorter sampling times and by using new and cheaper measuring methods for (13)C analysis in the breath samples. These include nondispersive isotope-selective infrared spectroscopy (NDIRS) and laser-assisted ratio analysis (LARA), which greatly differ from each other in their technical characteristics and cost. Both NDIRS and LARA are valid alternatives to conventional isotope ratio mass spectrometry (IRMS), although LARA appears to be more suitable for large laboratories or gastroenterological centres, which need to process many breath samples per day, whereas NDIRS seems to be more suitable for small laboratories or doctors' offices.
OBJECTIVES: Seven-day proton pump inhibitor (PPI)-based triple therapies are the first-line anti-Helicobacter pylori regimens; to date, however, there is still no agreement concerning all the predictors of H. pylori cure under these regimens. The aim of this prospective study was to evaluate whether patients with certain pretreatment characteristics may benefit from an extension from 1 to 2 wk of treatment with lansoprazole, amoxycillin, and clarithromycin. METHODS: A total of 142 patients with H. pylori infection ascertained by means of gastric histopathology and 13C urea breath test (UBT) participated in this study. In all patients H. pylori density was determined at histology both on antral and corpus biopsies, and H. pylori culture with antibiotic susceptibility testing; IgG anti-H. pylori titers were also determined before therapy. Patients were randomized to receive 1-wk versus 2-wk of treatment with lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.). The association between eradication and potential predictors was analyzed by means of unconditional logistic regression models and stratified according to the duration of treatment. A stepwise regression analysis was performed to identify variables discriminated between subjects, using eradication status as the dependent variable. RESULTS: The overall eradication rates for 1- and 2-wk treatments were 74.6% and 85.9% (intention-to-treat analysis) and 81.5% and 89.1% (per-protocol analysis), respectively (p = NS). Multivariate discriminant analysis selected as the variables independently related to eradication cigarette smoking (OR = 3.98), delta of 13C-UBT higher than 35 (OR = 9.21) and IgG anti-H. pylori titer > or = 93 (OR = 0.24) for the whole series of subjects. Stratified analysis according to the duration of therapy selected H. pylori density as the only predictor of eradication in the group treated for 1 wk (OR = 8.11). In contrast, no significant predictors were found in the group treated for 2 wk. CONCLUSIONS: Patients with a high intragastric bacterial load, as detected by histology (grade 3) or 13C-UBT (delta > 35) may benefit from an extension to 2 wk of triple therapy with lansoprazole, amoxycillin, and clarithromycin.
Deficits in social functioning are a defining characteristic of schizophrenia. Several instruments have been developed to measure social functioning in this population, but there has been little study of the correlation among different instruments. We used the Social Functioning Scale (SFS), the Multnomah Community Ability Scale (MCAS), and the Quality of Life Interview (QOLI) to evaluate 72 stable outpatients with schizophrenia. Results of canonical analyses indicate a significant but limited relationship between each set of measures. The largest overlap was between the QOLI and the SFS (R2c = .597) with less shared variance found between the SFS and the MCAS (R2c = .520) and between the MCAS and the QOLI (R2c = .335). Although the instruments share some common content. the instruments measure different aspects of social functioning. A consensus is needed about how to define and measure social functioning in this population.
BACKGROUND: H. pylori CagA seropositivity has been recently associated with ischaemic heart disease. OBJECTIVE: To evaluate whether H. pylori virulence has any effect on certain circulating coagulation factors and on markers of systemic inflammation in healthy individuals. DESIGN: Prospective cohort study. SETTING: Haematology and gastroenterology unit at a university teaching hospital. SUBJECTS: A total of 494 consecutive asymptomatic blood donors attending a blood bank. MEASUREMENTS: Blood analysis for haemostatic factors, lipids concentrations, inflammatory parameters as well as determination of anti H. pylori IgG and CagA reactivity by ELISA assayes. RESULTS: The overall prevalence of H. pylori infection was 53%; 56% of H. pylori positive sera expressed CagA reactivity. CagA seropositive subjects did not differ significantly from CagA negative or H. pylori negative subjects in values for lipids, haemostatic factors, or inflammatory parameters. CONCLUSIONS: CagA seropositivity is not associated with increased systemic inflammation or with raised concentrations of haemostatic factors - predictors of ischaemic heart disease - in healthy individuals.
OBJECTIVES: To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants. METHODS: We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis. RESULTS: Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features. CONCLUSIONS: Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.
The mouse Cig30 gene codes for a 30-kDa membrane glycoprotein, which appears to have a role in the recruitment of brown adipose tissue. To elucidate the structure of the Cig30 gene, we have isolated a lambda phage genomic DNA clone containing the entire mouse gene and found that Cig30 consists of four exons that are spread over 4 kilobase pairs of genomic sequence. Using a fluorescence in situ hybridization assay and interspecific backcross panel mapping, we have localized the Cig30 locus to the distal region of mouse chromosome 19, between the Tlx1 and Ins1 loci. Sequencing of the corresponding lambda clone to completion revealed that the insert contained yet another gene in the opposite orientation. It turned out to be the newly identified homeobox gene Pitx3. Interestingly, the genes are very tightly linked, so that the 3' ends of their transcripts are complementary. Thus, our results provide evidence for bidirectional transcription of a several hundred base pair-long DNA region as a result of the extremely tight linkage between Cig30 and Pitx3.
Neurocognitive deficits have been associated with the social functioning impairments of patients with schizophrenia. More information is needed about how cognitive status and other variables predict social functioning over defined periods of time. In this study, 72 relatively stable outpatients with schizophrenia were compared between baseline and a 2-year follow-up on measures of social functioning. Patients were also assessed with a battery of neurocognitive tests and the Positive and Negative Syndrome Scale. Results were compared by univariate and multivariate analyses. A total of four out of seven subscales of the Social Functioning Scale (SFS) and the total SFS score did not show a significant change over the 2-year period. On the three SFS subscales that did show a significant change, residual change scores were correlated with better neurocognitive performance at baseline, younger age, and shorter illness duration. For the Multnomah Community Ability Scale, 48.9% of the total score at follow-up was predicted by initial negative symptoms and scores on the Aphasia Screening Test. These results document the independent contribution of demographic variables, negative symptoms, and neurocognitive deficits to the social functioning impairments of individuals with schizophrenia.
Comparative genomic hybridization (CGH) was used to detect chromosomal gains and losses in a series of 90 frozen soft tissue primary tumors (STTs), all untreated. The material consisted of 69 malignant sarcomas, including 20 malignant fibrous histiocytomas (MFH), 23 liposarcomas (LPS), 6 leiomyosarcomas (LMS), 4 synovial sarcomas, 4 primitive neuroectodermal tumors (PNETs), and various others subtypes, in addition to 21 benign tumors. Within the benign tumors, only 2 of the 3 schwannomas showed genetic changes. In malignant sarcomas, genetic changes were detected in 64 of the 69 samples analyzed (92%), with a mean of 4.5 per sample (range 0-10). Gains and losses on chromosome 13 were observed in 32% of the sarcomas with genomic imbalance. Recurring low-level copy number increases were found at new sites on chromosomes 7 (6 MFH samples, 30%) and 8 (10 LPS samples, 43%), the minimal common regions being 7p15-pter and 8q24. No new recurring high-level amplifications were found. Surprisingly, losses of DNA sequences were more frequent than gains; particularly, losses were the main feature in LMS, with highly recurrent common minimal losses at 11q14-qter and 13q21-q22 (4 samples, 66%, and 5 samples, 83%, respectively). Losses of chromosome 2 sequences (minimal common regions at 2p24-pter and 2q32-qter) were observed in 50% of the MFH analyzed. New recurrent losses of whole or part of chromosome 14 were found in 57% of the pleomorphic LPS (PLPS) analyzed. This study uncovers new clues for the diagnosis of malignant STTs and shows the importance of deletions as events in the early steps involved in the tumorigenesis of STTs.
AIM: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C-urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago-gastro-duodenoscopy. MATERIALS AND METHODS: One-hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C-urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori-positive if two or more tests were positive. RESULTS: Eighty-one patients (70.4%) were found to be H. pylori positive. 13C-urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re-evaluation by an expert pathologist showed a high sensitivity (98. 8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%. CONCLUSION: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre-treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.
AIMS: To investigate the diagnostic approach to and management of Helicobacter pylori infection at primary care level in Italy 2 years after the Maastricht consensus report. METHODS: A total of 100 randomly selected general practitioners (GPs) answered a 12-item multiple-choice questionnaire, personally delivered and collected by non-medical staff. RESULTS: In 25% of cases, GPs preferred a prompt referral of dyspeptic patients to the specialist. The favourite diagnostic test for H. pylori infection was gastroscopy with biopsies (55%), followed by standard and office-based serology (24% and 18%, respectively), and 13C urea breath test (5%). H. pylori-eradication was prescribed in patients with peptic ulcer, reflux oesophagitis and functional dyspepsia by 64%, 43% and 66% of GPs, respectively. Only 7% of GPs adopted a test-and-treat approach. Proton pump inhibitor-based triple therapies were used by almost all physicians. In peptic ulcer disease, most of GPs re-tested patients in order to confirm H. pylori eradication (50% by gastroscopy with biopsies and 30% by serology only 2 months after therapy). CONCLUSIONS: Uncertainty seems to persist among Italian GPs concerning the indications for H. pylori treatment, the use of diagnostic tests, and patient follow-up. In contrast, no doubts exist regarding the first choice eradication regimens. This survey suggests that further efforts should be made to spread scientific knowledge and guidelines on H. pylori diagnosis and management in primary care in Italy.
BACKGROUND: The purpose of the study was to establish the clinical significance of bowel-wall thickening, measured by ultrasound, in ulcerative colitis (UC) and to evaluate the usefulness of ultrasonography (US) to define the extension, the severity, and the response to medical treatment of this pathologic condition. METHODS: Thirty consecutive patients with active UC were studied on two different occasions 2 months apart and after treatment with steroids. On both occasions the clinical, endoscopic, and biochemical activity of the disease and the ultrasonographic examination of the intestinal walls were evaluated. The maximum bowel wall thickness (BWT) was considered an index of ultrasonographic activity, and the presence of thickened bowel walls and the US appearance of loss of haustra coli were considered in the evaluation of the extension of disease. The extension of colitis was evaluated by means of a double-contrast barium enema in every patient at the beginning of the study. RESULTS: US correctly defined the extension of UC in 74% of the patients as defined by double-contrast barium enema. The degree of BWT was significantly correlated to the clinical, biochemical, and endoscopic activity of UC before and after the treatment. Moreover, BWT decreased significantly (7.3 +/- 1.9 mm versus 5.1 +/- 1.2 mm; P < 0.001) in patients who experienced clinical improvement after treatment, and it did not change (7.0 +/- 1.5 mm versus 7.0 +/- 1.4 mm; P=NS) in patients showing no significant clinical improvement. The degree of pretreatment BWT did not differ between UC patient responders and non-responders. CONCLUSIONS: US evaluation of BWT may be useful in evaluating the extension of UC. The degree of BWT, as evaluated by US, correlates with the clinical, biochemical, and endoscopic activity of UC, both before and after treatment. This suggests that US may be useful to evaluate the response of UC patients to medical therapy.
BACKGROUND/AIMS: Proper management of enterocutaneous fistulas complicating Crohn's disease largely depends on the anatomical characteristics of the sinus tracks as well as the coexistence of complications such as abscesses and distal bowel stenosis. The aim of this prospective study was to evaluate the accuracy of a new technique (hydrogen peroxide enhanced ultrasound (US)-fistulography) compared with conventional x ray fistulogram and/or surgical findings in the detection of Crohn's disease associated enterocutaneous fistulas. METHODS: Patients with known Crohn's disease and a suspicion of enterocutaneous fistulas were prospectively studied with this novel technique, conventional x ray fistulogram, and barium radiography as well as with computed tomography whenever an abdominal abscess was suspected at US. In those undergoing surgery, intraoperative findings were also compared. RESULTS: Seventeen of 502 (3.4%) consecutive patients with Crohn's disease seen over a ten month period had associated enterocutaneous fistulas and were enrolled. Hydrogen peroxide enhanced US-fistulography visualised the extent and configuration of fistula in all cases: 13 patients had a fistula arising from the ileum and two from the sigmoid colon, whereas in two there was no evidence of communication with intestinal loops; in contrast, conventional x ray fistulography missed a correct definition of the fistulous branches or communication with intestinal loops in 50% (4/8) and 36% (4/11) of patients respectively; barium radiography showed fistulas in two cases only. The presence of abscesses along or close to the sinus track, as well as the coexistence of intestinal stenosis, was correctly detected at US in all patients. CONCLUSIONS: Hydrogen peroxide enhanced US-fistulography could be considered the diagnostic procedure of choice in Crohn's disease associated enterocutaneous fistulas, as it is at least as accurate, simple, and safe as conventional x ray fistulogram, does not miss coexisting abdominal complications, and also provides information on the diseased bowel segments. In addition, it can be easily repeated over time in order to monitor the course of fistulas undergoing conservative treatment.
OBJECTIVE: Many outpatients with schizophrenia receive support or supervision in their place of residence, but the predictors of residential independence are not clearly understood. The purpose of this study was to identify factors that predict the degree of residential independence among outpatients with schizophrenia. METHODS: Seventy-two outpatients with schizophrenia were assigned to three groups based on their degree of residential independence. The three groups were compared on three measures of social functioning, on the Positive and Negative Syndrome Scale, and on a battery of neuropsychological tests. RESULTS: Patients' degree of residential independence was related to their frequency of family contact, hygiene skills, relative absence of negative symptoms, and participation in social activities. In a discriminant function analysis, the residential status of 78 percent of the patients was correctly classified. CONCLUSIONS: Aspects of social functioning are significantly associated with patients' independent living status. Future research is needed to determine how family contact, social activities, and hygiene skills may increase patients' degree of residential independence.
The gene responsible for multiple endocrine neoplasia type 1 (MEN1), a heritable predisposition to endocrine tumours in man, has recently been identified. Here we have characterized the murine homologue with regard to cDNA sequence, genomic structure, expression pattern and chromosomal localisation. The murine Men1 gene spans approximately 6.7 kb of genomic DNA and is comprised of 10 exons with similar genomic structure to the human locus. It was mapped to the pericentromeric region of mouse chromosome 19, which is conserved with the human 11q13 band where MEN1 is located. The predicted protein is 611 amino acids in length and overall is 97% homologous to the human orthologue. The 45 reported MEN1 mutations which alter or delete a single amino acid in human all occur at conserved residues, thereby supporting their functional significance. Two transcripts of approximately 3.2 and 2.8 kb were detected in both embryonal and adult murine tissues, resulting from alternative splicing of intron 1. By RNA in situ hybridization and Northern analysis the spatiotemporal expression pattern of Men1 was determined during mouse development. Men1 gene activity was detected already at gestational day 7. At embryonic day 14 expression was generally high throughout the embryo, while at day 17 the thymus, skeletal muscle, and CNS showed the strongest signal. In selected tissues from postnatal mouse Men1 was detected in all tissues analysed and was expressed at high levels in cerebral cortex, hippocampus, testis, and thymus. In brain the menin protein was detected mainly in nerve cell nuclei, whereas in testis it appeared perinuclear in spermatogonia. These results show that Men1 expression is not confined to organs affected in MEN1, suggesting that Men1 has a significant function in many different cell types including the CNS and testis.
In the process of identification of the multiple endocrine neoplasia type 1 gene, which was recently published, we isolated a novel gene in the 11q13 region. This gene (named ZFPL1, for zinc-finger protein-like 1) is expressed strongly in the exocrine pancreas as a 1.4-kb polyadenylated RNA encoding a putative protein of 310 amino acids. A mouse EST contig predicts an equally sized murine protein with 91% amino acid sequence identity to the human protein. No significant homology with known proteins could be found through database screening. However, zinc-finger-like domains and leucine-zipper-like motifs in the predicted ZFPL1 protein were identified, suggesting the presence of DNA-binding and dimerization domains possibly involved in transcription regulation. This notion is supported by the presence of a putative bipartite nuclear localization signal. This paper presents the full-length cDNA sequence for this gene, its genomic structure and chromosomal orientation, and expression studies by Northern blot hybridization and RNA in situ hybridization.