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Biomedical subjects

G M Paganelli

Publications and source records attributed to G M Paganelli.

At least 37 records · Page 2Linked to original sources

Cell-kinetic alterations induced by aspirin in human gastric mucosa and their prevention by a cytoprotective agent.

The effect on gastric epithelial cell proliferation of a short-term, low-dose treatment with aspirin was evaluated in 9 healthy volunteers. Nine days before and during aspirin administration, the subjects assumed sulglycotide, a sulfated glycopeptide with cytoprotective properties. Endoscopic biopsies were collected in each subject from the gastric body and antrum before and after treatment. The specimens were incubated in a culture medium containing bromodeoxyuridine (BrdU). The proliferative activity was evaluated by immunohistochemical detection of BrdU uptake. A decrease in BrdU-labelled cells together with a shortening of the length of gastric columns were observed after treatment with aspirin and placebo in biopsies of both body and antrum (p less than 0.05). On the contrary, no modifications were observed after treatment with aspirin and sulglycotide. We conclude that a decrease in the proliferative activity of the epithelial cells could be one of the mechanisms by which aspirin affects the defensive properties of gastric mucosa. The treatment with a cytoprotective drug seems to be effective in preventing this alteration.

Adult↗

Effect of sulglycotide treatment on cell kinetics alterations induced by aspirin in humans.

The effect on gastric epithelial cell proliferation of small doses of aspirin was evaluated in 9 healthy volunteers, with or without administration of sulglycotide, a sulfated glycopeptide with cytoprotective properties. Cell kinetics study was performed by incubation of gastric biopsies with bromodeoxyuridine (BrdU) and immunohistochemistry. A decrease of BrdU-labeling index and a shortening of the height of gastric columns were observed after treatment with aspirin and placebo. No variations were observed after treatment with aspirin and sulglycotide. A decrease of the epithelial cell renewal could be one of the damaging effects of aspirin on the gastric mucosa. The treatment with sulglycotide seems to be effective to prevent this alteration.

Adult↗

Rectal cell proliferation and colorectal cancer risk level in patients with nonfamilial adenomatous polyps of the large bowel.

The authors evaluated cell kinetics of apparently normal rectal mucosa in the following subjects: 25 with single small adenoma (smaller than 10 mm) of the large bowel, 12 with multiple small adenomas, 28 with a single large adenoma (larger than 10 mm), 22 bearing multiple adenomas among which at least one was larger than 10 mm, 32 with cancer of the large intestine, and 32 controls without colorectal diseases. The study was performed by means of incubation of biopsy specimens with tritiated thymidine and autoradiography. The labeling index was similar in all of the groups. However, patients with one or more large adenomas showed a shift of the proliferative compartment toward the top of the crypts similar to that observed in patients with cancer. This abnormal proliferative pattern was not noticed in patients with one or more small adenomas and was not related to the number of adenomas of each subject. The presence of defects of cell growth in the normal rectal mucosa of patients with large adenomas may indicate that subjects with this abnormality are at high risk of adenoma growth and progression to cancer.

Adult↗

Correlation between bromodeoxyuridine labelling and ornithine decarboxylase levels in normal rectal mucosa of patients with colorectal adenoma.

We studied rectal cell proliferation by means of bromodeoxyuridine labelling and ornithine decarboxylase activity assay in 16 patients with colorectal adenoma. In each patient, three rectal biopsy specimens taken from normal-appearing mucosa were incubated with bromodeoxyuridine (BrdU), fixed in ethanol and stained with avidin-biotin peroxidase complex using a monoclonal antibody against BrdU. In addition, two biopsies were homogenized and incubated with [1-14C]-ornithine for ornithine decarboxylase (ODC) assay. A direct, significant correlation was found between BrdU-labelling index and ODC levels in the mucosa (r = 0.6511, P less than 0.01). We conclude that BrdU labelling and ODC activity assay give comparable results in the analysis of cell proliferation rate of rectal mucosa. These methods are useful to investigate rectal cell proliferation pattern of patients with increased risk of colorectal cancer.

Adenoma↗

Cell proliferation kinetics as a marker of gastric cancer risk.

Although cell proliferation studies on gastric mucosa are relatively few compared to the results obtained in the large bowel, they brought important contributions to our knowledge of the mechanisms involved in the development and progression of neoplasia. In normal gastric mucosa, the proliferative zone is limited to the neck region of the glands. In diseases at risk for gastric cancer, such as chronic atrophic gastritis, two main features have been observed: an increased cell proliferation rate and expansion or upward displacement of the proliferative compartment. However, while a high cell turnover rate can be due to many stimuli such as inflammation or the effect of hormones (i. e. gastrin), the expansion of the proliferative compartment is more evident with the development and progression of neoplasia. It could be due to an error in the control of cell proliferation and maturation. This kinetic pattern is probably a marker of gastric cancer risk. Application of these observations in clinical investigations are the search for proliferative abnormalities and other phenotypical markers in order to define an individual profile of cancer risk, and to evaluate the effects of xenobiotics or dietary intervention in controlled trials.

Biomarkers, Tumor↗

Rectal cell proliferation and colon cancer risk in ulcerative colitis.

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.

Adenoma↗

Effect of sex and age on rectal cell renewal in humans.

We evaluated the influence of age and sex on rectal cell proliferation of 69 hospital controls and 66 patients with colorectal adenomas, by means of incubation of rectal biopsies with tritiated thymidine and autoradiography. In particular, we evaluated the labeling frequency in the upper 40% of rectal crypts (0 h), actually considered as a reliable kinetic marker of colon cancer risk. A direct correlation between 0h and age was found in control subjects (P less than 0.02) but not in adenomas patients (P = NS). Moreover, control subjects over 65 years of age showed a shift of the proliferative compartment similar to that observed in the adenomas group. After adjusting for the age, we did not observe any significant effect of the sex of patients or controls on their cell kinetics parameters. Our results are in agreement with those previously reported on smaller series and with epidemiological studies which indicate a high risk for developing colorectal neoplasia in the elderly subjects.

Adenoma↗

Ano-rectal lesions in patients taking suppositories containing non-steroidal anti-inflammatory drugs (NSAID).

We report on 3 cases in which ano-rectal lesions were associated with chronic administration of suppositories containing non-steroidal anti-inflammatory drugs (NSAID). Lesions were characterized by erosions or ulcer in the rectum and by stenosis of the anal verge. Erosions or ulcers were observed in patients taking the drugs for a relatively short time. The lesions remitted after suspension of the treatment. The cases observed indicate that suppositories containing NSAID could induce ano-rectal lesions similar to those observed after the use of suppositories containing ergotamine.

Adult↗

Effects of sucralfate and sulglycotide treatment on active gastritis and Helicobacter pylori colonization of the gastric mucosa in non-ulcer dyspepsia patients.

We conducted a double-blind randomized treatment study on patients affects by non-ulcer dyspepsia in whom multiple biopsy specimens showed active gastritis. Patients were given either 3 g/day of sucralfate (n = 39) or 600 mg/day of sulglycotide (n = 50) for 6 wk, a glycopeptide isolated from pig duodenum constituents. Endoscopy was carried out at baseline and at the end of treatment. We took biopsies from the gastric body (twice) and antrum (six times) at each endoscopy in order to determine grade and extent of gastritis and Helicobacter pylori colonization. Both treatments induced a marked regression of active gastritis (sucralfate group: p less than 0.05 and p less than 0.0001, respectively, in body and in antrum; sulglycotide group: p less than 0.01 and p less than 0.001, respectively). Conversely, Helicobacter pylori colonization remained unchanged at the end of the treatments. At baseline, a close relationship was found between grade of active inflammation in each biopsy and Helicobacter pylori density. After therapy, the association was lost in each treatment group. These results suggest that there can be a remission of active gastritis in patients with non-ulcer dyspepsia even without changes in Helicobacter pylori colonization. This result can be achieved by enhancing the protective properties of the gastric mucosa.

Adult↗

Early gastric cancer in Italy. Clinical and pathological observations on 80 cases.

Of 542 gastric cancer patients operated in the period between 1976 and 1982, we found early gastric cancer (EGC) in 80 cases (15.3%). Patients with EGC did not show specific symptoms if compared with patients affected by gastric or duodenal peptic ulcer, gallstones, functional disorders of the upper gastrointestinal tract, or advanced gastric cancer (AGC). Single-contrast radiology showed a low sensitivity, especially in the depressed lesions. In contrast, endoscopy alone diagnosed 64 EGCs (80.0%) as malignant lesions. The five-year overall survival rate of the EGC patients was 85.9% and that of AGC patients was 43.8%. From a pathological point of view, our results confirm the usefulness of the studies on EGC for the comprehension of gastric carcinogenesis. The clinical relevance of EGC is linked to the good prognosis; however, the absence of clear symptoms and lack of alternative diagnostic methods to the endoscopy cast some doubts on the feasibility of mass detection programs.

Adenoma↗

Endoscopic assessment of acute inflammation of the ileal reservoir after restorative ileo-anal anastomosis.

Forty-seven patients, undergoing ileo-anal anastomosis for ulcerative colitis (42) or familial polyposis (5), were endoscopically examined after protective ileostomy or after restorative ileo-anal anastomosis. The neorectum and the ileum above were examined in all cases and multiple biopsies were taken. No symptoms of pouch inflammation were found in 41 subjects; 80.5% of these had non-macroscopic lesions and 19.5% had focal lesions such as congestion, petechiae, mucous hypersecretion (5), or single ulcers (3). None of these developed pouchitis. Pouchitis was observed in the other six subjects, who all underwent surgery for ulcerative colitis and developed 14 clinical episodes of pouchitis during the follow-up. In these cases the entire neorectum mucosa was always affected by the lesions which, in 50%, also extended to the ileum above. The most common endoscopic features (71.4%) were congestion, potechiae, oozing areas, mucous hypersecretion, and multiple superficial ulcers. In half the remaining cases (14.3%) the neorectum showed the features, described above, while the upper ileum was affected by deep round or irregular ulcers within normal mucosa; Crohn's disease was excluded in these cases. In the remaining 14.3%, pouchitis showed a pseudomembranous feature. In our experience, the endoscopic pattern of pouchitis is polymorphic. Although an ulcerative colitis-like feature prevails, pseudomembranous and Crohn's ileitis-like features may also be present.

Adenomatous Polyposis Coli↗

Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.

The morphologic and cytoproliferative patterns of the duodenal mucosa of two adult patients, one of whom had a short bowel, were evaluated after more than 2 months of postoperative total parenteral nutrition and 2 and 12 months after the resumption of oral alimentation. Morphometric analysis was performed on routinely processed duodenal biopsies. Cell proliferation was evaluated by means of in vitro bromodeoxyuridine uptake. The results were compared with those obtained in five healthy controls. After parenteral nutrition, patients showed significantly lower villus height and crypt depth than those of controls and a normal bromodeoxyuridine labeling index. After 2 months of refeeding, villus and crypt returned to normal, and the labeling index was increased. After 12 months of oral refeeding, labeling index, villus height, and crypt depth were similar to those of controls. The patient with the short bowel showed a number of cells per unit length of villus and crypt significantly greater than those of the controls and of the patient who underwent shorter intestinal resection. In human duodenal mucosa, (1) hypoplasia develops after long-term total parenteral nutrition; (2) mucosal recovery occurs through an increased cell proliferation after oral refeeding; and (3) extensive small bowel resection determines the development of relative hyperplasia.

Adult↗

Tumor markers and lung cancer: guidelines in a cost-limited medical organization.

The aim of our study was to evaluate the cost of the tumor marker assays most widely used in pneumological practice and the effectiveness of the percentage of DRG-based reimbursements absorbed by these assays. For this purpose we assessed the cost of lung tumor marker assays in Emilia Romagna compared to the DRG-based reimbursement of inpatients affected by lung diseases in whom the use of tumor markers is indicated. As an example, we evaluated the cost/effectiveness of the CEA assay in the differential diagnosis of 68 pleural effusions from 46 patients (20 benign diseases, 26 malignant). Because the CEA assay was not a substitute for cytology when this was not diagnostic, 41.3% of the resources were not efficiently spent. If the marker assay had been performed only in cases with negative cytology, we could have spared 14 of 46 tests. Moreover, since the expense lies predominantly in the cost of reagents (81.23%), we suggest as a routine procedure to collect and store samples for tumor marker assay in all cases; the test should be performed in a selected population of patients with negative cytology and "suspect" clinical outcome.

Antigens, Neoplasm↗