Biomedical subjects

E Solcia

Publications and source records attributed to E Solcia.

At least 55 records · Page 3Linked to original sources

PubMed1996

Significance of ammonia in the genesis of gastric epithelial lesions induced by Helicobacter pylori: an in vitro study with different bacterial strains and urea concentrations.

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain. The effect of VacA and ammonia was evaluated with and without addition of 10 mM urea, a physiological concentration for the human stomach, and with and without addition of 0.5 mg/ml acetohydroxamic and (AHA), an urease inhibitor. Our data show that: (1) both urease-positive H. pylori strains caused cell vacuolation in the absence of urea, the VacA-positive strain being approximatively twice as potent as the VacA-negative strain; (2) addition of urea to the culture medium caused an approximatively 3-fold increase in the vacuolating activity of both urease-positive strains; (3) a VacA-negative/urease-negative strain did not exert any vacuolating effect, either in the presence or in the absence of urea; (4) the ratio between cell vacuolation induced by VacA-positive and VacA-negative strains was enhanced by the presence of AHA: ratio was about 2 in the absence of AHA and about 6 in the presence of AHA, either with or without urea added. The increment of vacuolation is likely due to an interaction between AHA and VacA. In conclusion, a VacA-negative/urease-positive strain becomes highly cytotoxic when physiological levels of urea are present in the incubation medium. This finding suggests that all urease-positive H. pylori strains, both with and without VacA expression, should be considered as potentially cytotoxic for the human gastric mucosa, although VacA enhances the severity of cell damage.

Ammonia↗

PubMed1996

Effects of permanent eradication or transient clearance of Helicobacter pylori on histology of gastric mucosa using omeprazole with or without antibiotics.

Changes in Helicobacter pylori-associated gastritis of the antrum and corpus were investigated in a large number of patients treated with omeprazole, with or without the addition of amoxycillin. To investigate the role of H. pylori-associated gastritis in ulcerogenesis and its interplay with omeprazole, biopsies were taken and evaluated according to the Sydney system. Successful eradication of H. pylori (assessed histologically 4 weeks after the end of therapy) led to prompt and persistent suppression of gastritis activity, slow, partial regression of mononuclear inflammation and an ulcer recurrence rate of only 14% during the 6 months' follow-up. In patients treated with omeprazole and placebo, or where eradication treatment with omeprazole and amoxycillin had failed, transient clearance of H. pylori from the antral (but not oxyntic) mucosa was seen. In both of these groups of patients transient regression in the antrum, and worsening in the corpus, of gastritis activity and mononuclear inflammation were evident, coupled with ulcer recurrence rates of 72 and 46%, respectively. It was concluded that H. pylori colonization and gastritis activity play a crucial role in ulcerogenesis, that acid inhibition treatment improves antral H. pylori gastritis and worsens the oxyntic mucosal gastritis, and that this can be prevented by eradication of the H. pylori infection.

Amoxicillin↗

PubMed1996

Omeprazole coupled with two antibiotics for Helicobacter pylori eradication and prevention of ulcer recurrence.

BACKGROUND: Numerous therapeutic trials aimed at eradicating Helicobacter pylori (HP) from the gastric mucosa and preventing ulcer recurrence have been carried out; however, an optimal treatment has not yet been established with carefully controlled randomized studies. OBJECTIVE: The aim of our study was to evaluate the efficacy of an association of omeprazole (OM) coupled with two antibiotics in the eradication of HP and prevention of duodenal ulcer (DU) recurrence. METHODS: One hundred and eighty three patients with active DU were randomized under double-blind conditions to receive either OM 20 mg for 4 wk plus amoxycillin 3 g daily and metronidazole 1 g daily during the 2nd and 3rd wk (91 patients, group A) or OM 20 mg for 4 wk plus matching placebo (92 patients, group B). Endoscopy was performed before and at the end of the 4-wk treatment as well as 2, 6, and 12 months later. Biopsies were taken from the duodenum, antrum, and gastric body at each endoscopic examination for HP histological detection and for evaluation of inflammatory changes according to the Sydney system. RESULTS: After 4 wk, 84/86 patients (98%) of group A and 80/86 (93%) of group B were healed of their ulcers. The percentage of eradication was 90% in group A and 1% in group B. During a 12-month follow-up, DU relapsed in 4/63 (6%, including two of three reinfected cases) HP-eradicated group A patients, 4/8 (50%) HP-noneradicated group A patients, and 52/65 (80%) persistently HP-positive group B patients. Rapid, complete, and persistent suppression of gastroduodenitis activity and gastric surface epithelium lesions was observed in most HP-eradicated group A patients, whereas a transient decrease of bacterial colonization and inflammatory scores in the antrum and a transient worsening of corpus gastritis were found in group B patients. CONCLUSIONS: The combined therapy with amoxycillin, metronidazole, and omeprazole is highly effective in both HP eradication and prevention of duodenal ulcer recurrence.

Adult↗

PubMed1996

[Carcinoid tumors of the stomach in atrophic autoimmune gastritis: classification, differential diagnosis and prognosis].

With the aim of evaluating the prognosis of neuroendocrine tumours of the stomach we studied 255 patients with these tumours to gain informations about the different biological behaviour of these tumours. We examined subtypes on the basis of the type of gastritis according to RINDI et al. 1993. A classification was made on the basis of tumour size, depth of invasion, angio invasion, functioning or non functioning, metastatic or non metastatic according to CAPELLA et al. 1994 to estimate benign and low or high grade malignant behaviour. 191 carcinoid tumours in autoimmune gastritis were in 86.4% classified as benign tumours (88% not more than 1 cm in diameter, 1 case with lymph node metastasis, no carcinoid tumour related death). 12 carcinoids associated with ZES-MEN I showed a benign or low grade malignant behaviour (60% more than 1 cm in diameter, 2 cases with lymph node metastasis, 1 with distant metastasis, 1 carcinoid related death). 36 sporadic carcinoid tumours were in 42% low grade malignant (36% 1-2 cm size, 25% more than 2 cm in diameter, 3 cases with lymph node metastasis, 2 with distant, 6 with lymph node and distant, 7 carcinoid related death). 13 neuroendocrine carcinoma were high grade malignant (1.5-7 cm size, 6 cases with lymph node metastasis, 2 with distant, 4 with lymph node and distant, 8 carcinoma related death). Therefore we conclude that in the classifications compared carcinoid tumours in A-gastritis are-in contrast to the other types of neuroendocrine tumours of the stomach-benign tumours with a good prognosis. The type of gastritis is for the prognosis of gastric neuroendocrine tumours besides tumour size and metastasis the most important parameter.

Adolescent↗

PubMed1995

Revised classification of neuroendocrine tumours of the lung, pancreas and gut.

In this article new classifications of the neuroendocrine tumours of the lung, pancreas and gut are proposed. These classifications use a common frame work and attempt to consider the morphological, functional as well as biological features of the tumours.

Gastrointestinal Neoplasms↗

PubMed1995

Effects of hypochlorhydria and hypergastrinemia on structure and function of gastrointestinal cells. A review and analysis.

Since hypochlorhydria can induce hypergastrinemia, and gastrin has a trophic effect on some gastrointestinal cells, states that cause elevated plasma gastrin levels are of interest in terms of effects on cell growth and function. This article reviews the relationship between gastric mucosal cells during periods of acid stimulation and inhibition and analyses the effects of hypochlorhydria and hypergastrinemia on gastric and colonic cells and tumors. Hypochlorhydria releases the inhibitory effect of antral gastrin cells, inducing them to release gastrin in the presence of peptides or amino acids in the gastric lumen or in response to antral distension. Gastrin stimulates the oxyntic mucosa, which may lead to hyperplasia of enterochromaffin-like cells, resulting in enterochromaffin-like carcinoid tumors in aged rats and, rarely, in patients with chronic atrophic gastritis or gastrinomas. In addition to hypergastrinemia, other factors appear to be required for the progression of enterochromaffin-like hyperplasia to carcinoids; genetic factors may be involved. Gastrin elevations due to antisecretory drug therapy are indirectly proportional to the degree of acid inhibition and are reversible upon cessation of therapy. The gastrin levels during omeprazole therapy are similar to those caused by gastric vagotomy. Available evidence does not support a relationship between hypergastrinemia and the occurrence or growth of gastric carcinoma or colonic tumors.

Achlorhydria↗

PubMed1995

Endocrine tumors of the small and large intestine.

Among endocrine tumors arising in the intestinal tract, midgut argentaffin EC cell carcinoids, duodenal gastrin cell tumors and rectal trabecular L cell carcinoids, in order of decreasing frequency, are those better represented. Together they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas and poorly differentiated neuroendocrine carcinomas, are also well defined tumor entities. The carcinoid syndrome with intermittent flushing, hypotension and diarrhea, and the Zollinger-Ellison syndrome with severe peptic ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome arises in about 10% of intestinal carcinoids, usually in their advanced metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of gastrin cell tumors, including small intramural growths. Tumor prognosis depends on mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases) and associated clinical syndrome or background disease.

Humans↗

PubMed1995

[A measure of productivity in cardiology based on medical acts].

BACKGROUND: The decreased availability of economic resources, opposed to the increased demand for medical assistance, requires the use of methods to assess hospital efficiency. Purpose of our study was to evaluate and quantify the "products" of a cardiology department, as well as the changes in time of their production, by means of a catalogue of medical acts, set up for the French health system (CdAM). METHODS: The study includes the 224 admissions occurring in October 1987 and the 209 admissions of October 1992. Medical acts were recorded for all admissions, by number of acts as well as by weight of acts; this weight (expressed as complexity/cost index or ICR) takes into account the use of resources in terms of medical staff and nursing staff, together with technical resources, for each act. In 1987 and 1992, 1736 and 1603 acts were performed respectively, corresponding to a total weight of 24308 and 32194 ICR. RESULTS: The increased ICR appears to be related to an increase of invasive procedures, particularly of interventional electrophysiology and haemodynamics. By considering case mix, we observed an increment of ICR for the diagnosis of angina (from 194.3 to 227.4 ICR per patient), of arrhythmias (from 178.0 to 273.1) and of cardiomyopathy (from 95.6 to 179.7). CONCLUSIONS: In conclusion, CdAM allows to evaluate the cardiologic activity also in the Italian situation; the ICR of each act permits to estimate the human and technical burden, with subsequent easy internal and external comparisons.

Cardiology Service, Hospital↗

PubMed1995

Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis.

Endocrine cells of the gastric oxyntic mucosa, and especially the enterochromaffin-like (ECL) cells, are the progenitors of gastrin-promoted proliferative lesions whose tumorigenic potential largely depends on the background condition in which they arise. Hypertrophic gastropathy due to the familial multiple endocrine neoplasia (MEN-1)-associated or sporadic Zollinger-Ellison syndrome (ZES), diffuse chronic atrophic gastritis restricted to the corpus-fundus (type A CAG), with or without associated pernicious anemia, and Helicobacter pylori-related multifocal chronic atrophic gastritis are the usual background for such growths. The endocrine cell lesions have been classified as pseudohyperplasia (cell clustering unassociated with cell proliferation), hyperplasia (diffuse, linear, micronodular, adenomatoid), dysplasia (enlarged, adenomatous or fused micronodules, microinfiltration, nodular growth), and neoplasia (intramucosal or invasive carcinoids). The entire spectrum of endocrine cell proliferation, from hyperplasia to dysplasia and neoplasia, has been observed in MEN-ZES and diffuse type A CAG. Both hyperplastic and pseudohyperplastic changes occur with some frequency in the H. pylori-related chronic gastritis associated with ulcer disease or dyspepsia. However, because no progression to dysplastic or neoplastic lesions has thus far been documented in these latter conditions, their role in gastric endocrine cell tumorigenesis appears negligible.

Animals↗

PubMed1994

K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions.

We studied K-ras and p53 gene mutations in a panel of 57 primary pancreatic cancers including ductal and nonductal tumors. DNAs were obtained from formalin-fixed, paraffin-embedded material. Target sequences were amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis and sequencing. Both K-ras and p53 genes were frequently mutated in ductal cancers (25 of 35, 71.4%; 18 of 35, 51.4%, respectively). K-ras mutations were confined to the second position of codon 12 where base transitions and transversions were equally observed. p53 changes were mainly missense mutations. Transitions and transversions were found equally with a prevalence of G:C-->A:T changes among transitions. No gene alterations were present in the 6 exocrine nonductal tumors and (with one exception) in the 12 endocrine tumors analyzed. Our results indicate that mutated K-ras and p53 genes can cooperate in the establishment of ductal pancreatic cancers, whereas other genetic events have to be present in nonductal tumors. Moreover, K-ras alterations may represent an early event in ductal tumorigenesis, as suggested both by the high gene mutation frequency and by the presence of mutations in low-grade tumors. On the contrary, p53 gene changes seem to represent an event required for the malignancy progression of ductal tumors from lower to higher grades.

Carcinoma, Ductal, Breast↗

PubMed1994

Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients.

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.

Adult↗

PubMed1994

K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma.

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.

Adenocarcinoma↗

PubMed1994

Acid suppression and gastric mucosal cell biology.

This review examines recent concepts of gastric mucosal cell biology in relation to acid inhibition. Powerful acid-inhibitory drugs have been associated with the production of enterochromaffin-like (ECL) cell proliferation and the induction of ECL-cell carcinoids in rats. The ECL-cell lineage and its renewal is discussed, and the factors that regulate ECL-cell proliferation are reviewed. Current methods in use for assessing genotoxicity in gastric mucosa are scrutinized; the much discussed claim that antisecretory drugs induce unscheduled DNA synthesis is examined, and the methodology that is the basis for these claims is found defective and wanting. The nature of ECL-cell proliferation in rats receiving lifelong treatment with H2-receptor antagonists or acid pump inhibitors is explored, and their relationship to ECL-cell proliferation and ECL-cell carcinoids discussed. It is concluded that aged rats are very prone to developing endocrine proliferations, and this may be related to the multiple endocrine neoplasia syndrome found in humans. There is no evidence at present that long-term antisecretory therapy causes significant ECL-cell proliferation in humans.

Animals↗

PubMed1994

Helicobacter pylori infection in children with antral gastrin cell hyperfunction.

Antral gastrin cell hyperfunction (AGCH) is a rare syndrome characterized by persistent hypergastrinemia and important peptic symptoms in the absence of a gastrin-producing tumor. The pathogenesis of AGCH is still unknown and debated. Helicobacter pylori (Hp) infection has been reported as a possible cause of sustained hypergastrinemia. To assess the relevance of Hp infection in pediatric AGCH patients, Hp status, G cell function, acid secretion, and antral G and D cell populations were investigated in six children presenting with gastrointestinal bleeding of unknown origin, sideropenic anemia, and variable abdominal symptoms. All patients had moderate high basal gastrinemia with abnormally increased peak values after meals and elevated values of basal acid output (BAO), maximal acid output (MAO), and pentagastrin-stimulated acid output (PAO). Circulating pepsinogen I was also significantly increased. Three children had Hp infection, as assessed by enzyme-linked immunosorbent assay, urease test, and histology. Endoscopy showed duodenal erosions in three children, with ulcer in two Hp-positive cases. At histology, moderate gastritis was observed only in the three Hp-positive cases. In all patients, quantitative assessment of antral gastrin and somatostatin cells gave significantly elevated G cell counts; D cells were at the lower reference limit and the G/D cell ratio was significantly elevated. These data indicated a diagnosis of AGCH, possibly due to the elevated G/D cell ratio, and suggest HP infection as an overlapping factor complicating the clinical picture in some cases.

Adolescent↗

PubMed1994

Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.

Adolescent↗

PubMed1994

Revised classification of neuroendocrine tumors of the lung, pancreas and gut.

The general use of the term carcinoid for the classification of neuroendocrine tumors has become increasingly difficult during recent years. First, its definition and prognosis varies from site to site. Second, its traditional definition does not cover the whole morphological and biological spectrum of neuroendocrine tumors known today. We therefore propose new classifications of the neuroendocrine tumors of the lung, pancreas, stomach, duodenum, jejunum-ileum, appendix and colorectum. These classifications use a common framework and attempt to consider the morphological, functional and biological features of these tumors.

Appendix↗

PubMed1994

Distinct profiles of gastritis in dyspepsia subgroups. Their different clinical responses to gastritis healing after Helicobacter pylori eradication.

BACKGROUND: A contribution of Helicobacter pylori gastritis to the pathogenesis of non-ulcer dyspepsia (NUD) remains uncertain. METHODS: Administration of an appropriate clinical questionnaire followed by endoscopy allowed us to select, among 139 outpatients with dyspepsia, 87 non-ulcer dyspepsia patients with more severe and group-distinctive symptoms, 35 of whom were classified as having ulcer-like (ULD). 38 as dysmotility-like (DLD), and 14 as reflux-like dyspepsia (RLD). Biopsy specimens were evaluated for H. pylori gastritis in accordance with the Sydney system. The 70 H. pylori-positive cases were treated with omeprazole, 20 mg twice daily, and amoxycillin, 1 g three times daily for 2 weeks. RESULTS: Higher rates of H. pylori colonization were found histologically in the gastric mucosa of ULD (91%) and RLD (86%) than in that of DLD (68%) or asymptomatic (42%) patients. ULD differed from RLD patients in their higher score of antritis activity. Three and 6 months after H. pylori eradication ULD (but not DLD) showed significant regression of dypspetic symptoms scores. CONCLUSIONS: It seems likely that H. pylori gastritis, with special reference to active antritis, is among causative factors of ULD. Its role in the pathogenesis of RLD and DLD needs further investigation.

Adult↗

PubMed1994

Epithelial cytotoxicity, immune responses, and inflammatory components of Helicobacter pylori gastritis.

To clarify the mechanisms of the gastric mucosal immune--inflammatory response to Helicobacter pylori infection, surgical and biopsy specimens from asymptomatic uninfected, gastritis-free individuals and from H. pylori-positive ulcer patients with chronic gastritis were investigated using light and electron microscopy. Activation of the antigen-transporting endocytic--endosomal system, enhanced expression of the antigen-processing enzyme cathepsin E and de novo expression of antigen-presenting human leukocyte antigen (HLA)-DR molecules have been detected in H. pylori-colonized gastric epithelium. These findings may be crucial in the production of a mucosal immune-inflammatory response to H. pylori infection. Cytoplasmic swelling and vacuolation, micropapillary change, mucin loss, erosion of the juxtaluminal cytoplasm and cell desquamation were the main effects of bacterial cytotoxicity on gastric surface-foveolar epithelium. Activated macrophages and granulocytes (partly linked to the mucosal IgG immune response) concentrate in the foveolar-neck region of the mucosa, where they may enhance damage and impair regeneration of the epithelium. Both direct bacterial cytotoxicity and inflammatory cell aggression against gastric epithelium may predispose the patient to peptic ulcer disease.

Eosinophils↗