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Biomedical subjects

G Biasco

Publications and source records attributed to G Biasco.

At least 55 records · Page 3Linked to original sources

Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial.

OBJECTIVES: This study was performed to evaluate the effects of L-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. BACKGROUND: Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. METHODS: The L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or L-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or L-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. RESULTS: A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with L-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and end-systolic volumes from admission to 3-, 6- and 12-month evaluation was significantly reduced in the L-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the L-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. CONCLUSIONS: L-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event.

Adult↗

Helicobacter pylori in patients with gastric and nongastric cancer.

OBJECTIVES: To compare the seroprevalence of Helicobacter pylori in gastric and nongastric carcinoma patients and to investigate the relationship between H. pylori, gastric cancer site, and histological type. METHODS: In a 24-month period, 307 gastric cancer patients (male/female: 185/122; age range 19-94 yr, mean 69 yr) were investigated by serology (IgG to H. pylori), histology, and urease test for H. pylori. One hundred and seventy-seven gastric cancers were in the antrum, 98 were in the corpus, and 32 were in the fundus; 227 were intestinal and 80 were diffuse type. In the same study period, we assessed the H. pylori seroprevalence in 162 patients with nongastric carcinoma (lung n = 41, breast n = 42, genitourinary n = 41, GI tract n = 22, others n = 16) (male/female: 84/78; age range 31-81 yr, mean 56 yr). RESULTS: The overall seroprevalence of H. pylori in gastric cancer and in nongastric cancer was 82 and 56%, respectively (p < 0.001). In asymptomatic blood donors (age range 55-65 yr) and in dyspeptic patients older than 60 yr, a seroprevalence of 55 and 58% was found, respectively, which is significantly lower (p > 0.001) than the gastric cancer patients but similar to the nongastric cancer population. No difference was found in the H. pylori status according to the gastric cancer site (83, 82, and 81% in the antrum, corpus, and fundus, respectively). Two hundred and twenty-seven gastric cancers [185 (81%) H. pylori-positive] were found to be of an intestinal type and 80 [66 (82%) H. pylori-positive] of a diffuse type (not significant). No age-related difference (below and above 60 yr) in H. pylori prevalence was observed within each cancer population, and, in both age groups, the seroprevalence of infection was higher in gastric cancer patients (86 and 81%) than in nongastric cancer patients (56 and 56%) (below and above 60 yr, respectively). CONCLUSION: H. pylori seroprevalence is significantly higher in gastric cancer compared with nongastric cancer patients. No differences were observed in H. pylori seroprevalence according to gastric cancer site or histological type. The higher H. pylori seroprevalence in gastric cancer patients is not age related.

Age Factors↗

Short- and long-term omeprazole for the treatment and prevention of duodenal ulcer, and effect on Helicobacter pylori.

OBJECTIVE: This study analyzes the effect of short- and long-term omeprazole (OM) on duodenal ulcer healing, recurrence, and H. pylori status. METHODS: Patients affected by active duodenal ulcer were randomly allocated to treatment with OM 20 mg or 40 mg once daily for 4 wk. Subsequently, patients with healed duodenal ulcer were randomly assigned to one of the following three groups: OM 20 mg once daily for 12 months, OM 20 mg alternate days for 12 months, and no treatment. Endoscopy was performed at entry, at 4 wk, and after 4, 8, and 12 months. Two biopsy specimens from antrum, body, and fundus were taken for histology and search for H. pylori. One hundred and eighty patients with active duodenal ulcer were admitted. Ninety-one were treated with OM 20 mg once daily and 89 with OM 40 mg for 4 wk. RESULTS: The results at 4 wk show 92.8% patients healed with OM 20 mg and 95.1% at 40 mg (NS). In the second part of the study, 96 of the patients who healed at 4 wk (45 with OM 20 mg, and 51 with OM 40 mg) entered the long-term study. Thirty-six patients received OM 20 mg daily for 12 months, 35 OM 20 mg on alternate days for 12 months, and 25 patients no treatment. The results show a healing rate of 100%, 100%, and 95% with OM 20 mg daily, of 97%, 95%, and 93% with OM 20 mg on alternate days, and of 81%, 50%, and 40% (p < 0.01) with no treatment at 4, 8, and 12 months, respectively. H. pylori that was found in 97% of patients at entry, at 4 wk was found in 92.8% of patients treated with OM 20 mg and in 97.5% of patients treated with OM 40 mg (NS). In one-third of the patients, H. pylori disappeared from the antrum but was found in the fundus. A 30% reduction in the presence of H. pylori was seen in the group treated with 20 mg daily for 12 months. CONCLUSIONS: We conclude that both continuous and alternate-day long-term OM treatment at 20 mg are similarly efficacious in the prevention of duodenal ulcer recurrence. Healing active duodenal ulcers with 20 or 40 mg does not influence subsequent treatment. Long-term OM at 20 mg daily for 12 months suppresses H. pylori temporarily in one-third of the patients. In these patients however, H. pylori reactivates after the end of treatment.

Adult↗

Prevalence of peptic ulcer in Helicobacter pylori positive blood donors.

This study aimed to determine the importance of raised antibodies to Helicobacter pylori in an asymptomatic population. A total of 128 asymptomatic blood donors who were seropositive for H pylori and consented to endoscopy were investigated. These subjects were from a population of 1010 blood donors screened for antibodies to H pylori. A questionnaire was completed to determine if any subjects had complained of symptoms, and they subsequently had endoscopy. Altogether 121 of 128 were positive for H pylori by histology and urease test and/or culture and all 121 had chronic active gastritis on histology. Twenty five of these subjects had peptic ulcer (20 duodenal, five gastric), a further 21 had erosive duodenitis, and two were found to have gastric cancer. H pylori associated peptic ulcer disease and duodenitis occur more frequently than previously recognised and this suggests that H pylori infection, even if asymptomatic, is of far greater clinical relevance than originally thought.

Adolescent↗

Methodological problems in the use of rectal cell proliferation as a biomarker of colorectal cancer risk.

Clinical and experimental studies have shown that the carcinogenic process of colorectal mucosa is linked to the development of proliferative abnormalities which precede the occurrence of morphological abnormalities such as epithelial dysplasia. In humans, proliferative defects have been demonstrated in the normal rectal mucosa of population groups at risk for colon cancer. Several techniques are available to study cell kinetics in the gastrointestinal mucosa. Each explores different aspects of cell proliferation. We have attempted to evaluate the correlation between various techniques in the normal rectal mucosa of high-risk patients. We found a good correlation between bromodeoxyuridine (BrdU) labeling index and the mucosal activity of the enzyme ornithine decarboxylase, and between tritiated thymidine and the percentage of cells in the S phase of the proliferative cycle as determined by flow cytometry. However, these correlations concern only labeling indices, which can be influenced by physiological events, such as active inflammation or increased cell loss. It may not be the most reliable proliferative marker of cancer risk. Moreover, methods using cells isolated from homogenized tissue do not allow us to evaluate the pool of cells which are examined nor the distribution of proliferating cells within the tissue. For example, an inflamed mucosal specimen is highly infiltrated with inflammatory cells which can interfere with the measurement of epithelial cell proliferation. Nevertheless, the labeling index may be normal even in patients at high risk. For these reasons, we think that the most reliable methods are those using tissue culture, such as tritiated thymidine or BrdU uptake and proliferating cell nuclear antigen (PCNA) immunostaining.

Adenoma↗

[Acute inflammation of ileal reservoir after restorative ileoanal anastomosis].

Ileo-anal anastomosis (IAA) is a suitable surgical treatment for selected patients with ulcerative colitis or familial adenomatous polyposis. Acute inflammation of the ileal reservoir (pouchitis) is the most frequent late complication and is characterized by endoscopic and histological changes of acute inflammation similar to ulcerative colitis with abdominal and sometimes systemic symptoms. Between May 1984 and April 1993, 160 patients (103 male and 57 female) aged between 7 and 64 years (mean age 32.6) underwent IAA; twenty of these for familial adenomatous polyposis, 138 for ulcerative colitis and 2 for indeterminate colitis. After a mean follow-up of 41.8 months (range 1-108), 138 patients (86.3%) were symptoms free and twenty-two (16 male and 6 female-13.7%) who underwent IAA for ulcerative colitis, had pouchitis. Clinical, biochemical, endoscopic and histologic findings suggest pouchitis as a chronic recurrent disease similar to inflammatory bowel disease. In conclusion, the etiopathology of this new entity is unknown. Bacterial overgrowth is one of the most popular hypothesis, but the onset of the acute inflammation observed by us only in patients with previous ulcerative colitis and in some cases during the period of protective ileostomy suggests a multifactorial pathogenesis.

Acute Disease↗

Flow cytometry and in vitro tritiated thymidine labeling in normal rectal mucosa of patients at high risk of colorectal cancer.

OBJECTIVES: To compare two different methods to evaluate rectal epithelial cell proliferation as a biomarker of risk of developing colon cancer. METHODS: Samples of normal rectal mucosa from 26 patients at increased risk for colorectal cancer (22 patients with adenoma, three with adenocarcinoma of the large bowel, and one with longstanding ulcerative colitis) were examined by means of in vitro labeling with tritiated thymidine and flow cytometry. RESULTS: We found a significant correlation between thymidine-labeling index and the percentage of cells in S-phase, measured by flow cytometry both in formalin-fixed, paraffin-embedded specimens and in frozen specimens (respectively, r = 0.7647, p < 0.001, and r = 0.4503, p < 0.01). However, using flow cytometry, the percentage of cells in S-phase was significantly higher than the thymidine-labeling index in both fixed-embedded and frozen specimens (p < 0.01). Proliferative parameters were not higher in patients with colon carcinoma, and were not related to the degree of dysplasia, the number of adenomas, or familial occurrence of colorectal cancer. Two specimens taken from normal rectal mucosa of two patients with adenomas showed aneuploidy. No aneuploidy was found in normal rectal specimens of patients with adenocarcinoma. CONCLUSIONS: These results show that the calculation of cells in S-phase with in vitro tritiated thymidine labeling or by flow cytometry produces different results. However, the significant correlation between corresponding parameters obtained with these techniques support the use of either method as "intermediate biomarkers" of colorectal cancer risk and prognosis.

Adenocarcinoma↗

Abnormal rectal cell proliferation and p52/p35 protein expression in patients with ulcerative colitis.

We evaluated the presence of cell proliferation and antigenic abnormalities in rectal biopsies from 37 patients affected by ulcerative colitis and 15 controls. The study was carried out by thymidine labeling and immunochemistry, using antibodies against specific cytoskeletal-associated proteins (p52, p35, alpha-actinin). Among ulcerative colitis patients, 24 had an immunofluorescence pattern similar to that of controls, while 13 showed an abnormal distribution of one or more proteins (p52 alone or p52 and either p35 or alpha-actinin) within the rectal crypts. Patients showed a shift of the proliferative compartment towards the top of the rectal crypts compared with controls. This finding was more evident in patients with p52 or p35 abnormalities. Proliferative and antigenic defects were not related either to age or the duration of colitis. These phenotypic changes might be a biomarker of increased risk of colon cancer in ulcerative colitis.

Adult↗

One-day therapy for treatment of Helicobacter pylori infection.

The present study evaluated the effect of a one-day high-dose combined therapy on Helicobacter pylori infection. Thirty-two consecutive patients (suffering from either peptic ulcer or nonulcer dyspepsia) with Helicobacter pylori infection received omeprazole (40 mg) + bismuth subcitrate (240 mg x 4) + amoxicillin suspension (2000 mg x 4) + metronidazole (500 mg x 4), for only one day. Endoscopy, histology, culture, and susceptibility studies were done at entry and 30 and 90 days after the treatment day. Successful eradication was obtained in 23/32 (72%) patients and gastritis had resolved in 95% of these. Side effects were induced by the treatment in 6/32 (19%) patients, but these were all self-limiting, short-lasting, and did not require any specific treatment. Development of bacterial resistance to metronidazole occurred in 6/9 (67%) non-eradicated patients. These data suggest that one-day treatment with high doses of amoxicillin, metronidazole, bismuth, and omeprazole represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection.

Adult↗

Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients.

AIMS: To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS: Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS: The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS: Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.

Adolescent↗

Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas.

Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity.

Adenoma↗

Cell proliferation biomarkers in the gastrointestinal tract.

Measurements of epithelial cell proliferation in the mucosa of the gastrointestinal tract pointed out the existence of cell kinetic abnormalities which can be involved in the first steps of carcinogenesis. In particular, an increase in the cell proliferation rate and an abnormal distribution of proliferating cells were found both in animals exposed to carcinogens and in human subjects at high risk of gastrointestinal cancer. In some diseases which predispose to cancer (i.e., chronic atropic gastritis, hereditary gastrointestinal cancer, sporadic colorectal neoplasia, chronic ulcerative colitis) we observed an expansion of the proliferative compartment even when the mucosa was not affected by morphological abnormalities. This proliferative feature seems to be associated with the presence of defects in cell differentiation. The abnormality is well detected by the histological examination of the proliferative pattern using microautoradiography after incorporation of tritiated thymidine, or using immunohistochemistry after bromodeoxyuridine uptake. The literature, and our own results, indicate that the search for abnormalities of epithelial cell proliferation can be useful in studying the earliest mechanisms leading to gastrointestinal cancer, in detecting subjects at high cancer risk, and for pilot chemoprevention studies using these abnormalities as intermediate biomarkers of gastrointestinal cancer risk.

Animals↗

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↗