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Biomedical subjects

G Mazzacca

Publications and source records attributed to G Mazzacca.

At least 73 records · Page 4Linked to original sources

Peptic ulcer in the elderly--a double-blind, short-term study comparing nizatidine 300 mg with ranitidine 300 mg. GISU (Interdisciplinary Ulcer Study Group).

UNLABELLED: This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. STATISTICS: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/170 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidine-treated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidine-treated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. IN CONCLUSION: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.

Aged↗

Serum and tissue transglutaminase correlates with the severity of inflammation in induced colitis in the rat.

Simple rat models of acute and chronic colonic inflammation were used to study the behaviour in serum and mucosa of transglutaminase (TG), an enzyme recently found to be reduced in serum of patients with inflammatory bowel disease (IBD) and related to the activity index of the disease. In the first model the intraluminal administration of 400 mM lactic acid in the colon caused an acute inflammation resembling that of florid ulcerative colitis in humans. In the second, intraluminal administration of the hapten 2,4,6-trinitrobenzenesulphonic acid (TNB) (10 or 30 mg) in 0.25 ml of ethanol as a 'barrier breaker' produced a chronic inflammatory disease. The results showed a reduced TG activity in colon of rats in both acute and chronic induced colitis (447 +/- 75 versus 1344 +/- 59 mU/g protein (p less than 0.001) and 484 +/- 59 versus 1204 +/- 75 mU/g protein (p less than 0.001)). This decreased activity was related to the severity of mucosal damage, which was dose-dependent. Moreover, in severe colitis the immunohistochemistry showed a TG location in repairing tissue. Serum TG activity was decreased after TNB administration (1.36 +/- 0.05 versus 3.44 +/- 0.20 mU/ml (p less than 0.001)) but not after lactic acid treatment (3.97 +/- 0.11 versus 3.78 +/- 0.16 mU/ml). In summary, the reduction of TG activity in both tissue and serum when the damage is stabilized reflects the altered morphofunctional integrity of the colon and suggests that serum assay of this enzyme could be a simple marker of intestinal mucosal status in IBD.

Acute Disease↗

Transglutaminase changes in intestinal mucosa after experimental small bowel resection in the rat.

The low serum transglutaminase found in various intestinal disorders (celiac disease and IBD) suggested to us to study the serum and mucosal transglutaminase behaviour in an experimental model of small intestine resection in rats to reduce cellular mass and induce enterocyte hyperproliferation in the proximal part left in continuity. Transglutaminase activity in the intestinal mucosa was significantly higher in resected rats than in control and sham operated animals from days 4 (121 +/- 10 v basal 94 +/- 3 mU/g protein, p < 0.01) to 10 (165 +/- 37 mU/g protein, p < 0.05) after surgery; no significant difference was observed at days 12 and 15 (110 +/- 15 and 105 +/- 23 respectively). Both serum alkaline phosphatase activity (partly produced in enterocytes) and serum transglutaminase were significantly lower in resected rats at each time-point beginning at day 6 (208 +/- 34 v 557 +/- 125 UI and 1.55 +/- 0.11 v 3.78 +/- 0.70 mU/ml, p < 0.001 respectively). These data suggest an involvement of transglutaminase in enterocyte proliferation and confirm the association between reduced intestinal mass and low levels of the enzyme in serum.

Alkaline Phosphatase↗

[Esaprazole vs sulglicotide in the treatment of dyspeptic patients with chronic superficial gastritis of the antrum].

Fifty dyspeptic patients with histologically proven chronic superficial antral gastritis were treated for 6 weeks, in a randomized single-blind study, with esaprazole (450 mg bid) or sulglicotide (200 mg tid). Both drugs significantly improved the symptomatic score after 3 and 6 weeks (p less than 0.01), and the percentual rate of improvement was similar in the two groups studied. Similarly, both treatments significantly reduced the inflammation of gastric mucosa. Drugs were ineffective in clearing Helicobacter pylori from the antral mucosa (as assessed by the urease test, performed at entry and after 6 weeks). No side effects occurred after esaprazole or sulglicotide administration. The results of the present study suggest that esaprazole, a new gastroprotective drug, may have a role in the therapy of dyspeptic patients with chronic superficial gastritis.

Adolescent↗

Plasma postheparin diamine oxidase in patients with small intestinal lymphoma.

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy.

Adolescent↗

Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease.

Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. This test may be useful for identifying Crohn's disease patients who are likely to relapse. Furthermore, the data indicate that mucosal damage is common in active small bowel Crohn's disease and improves at least in part after treatment.

Adult↗

Therapeutic strategy for the irritable bowel syndrome.

The major aims of medical therapy in irritable bowel syndrome (IBS) are: a) to ameliorate symptoms (pain, bowel movement abnormalities, bloating) and b) to improve psychological problems of the patients. The first step of IBS therapy is the diet. In fact some forms of IBS can be ascribed to food intolerance. When abdominal pain, meteorism and constipation are the main symptoms, treatment with high-fiber diet, antispastic and antimuscarinic drugs is indicated. Sometimes amitriptyline, an antidepressant which also shows anticholinergic and analgesic properties, can be helpful. When diarrhoea is prevalent, the most effective drug is represented by loperamide. If diarrhoea is related to meal ingestion, antispastic or antimuscarinic drugs can be successfully used. In the case of diarrhoea related to documented cholorrhoea, cholestyramine can be of benefit. Furthermore, there are some resistant cases, secondary to striking psychological problems that require sedatives and antidepressant drugs and sometimes, psycho and/or hypnotherapy.

Amitriptyline↗

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Administration, Oral↗

Comparative study of mifentidine and ranitidine in the short-term treatment of duodenal ulcer.

The efficacy and safety of mifentidine 20 mg at night, a new, potent, long-acting H2-receptor antagonist, has been compared with ranitidine 300 mg at night in 60 patients with acute duodenal ulcer, in a randomized double-blind study. Antacid tablets were allowed as additional treatment for pain relief. The treatment lasted for 4 weeks. After 4 weeks of treatment the healing rate was similar; amongst the patients who completed the treatment, healing was 68% for mifentidine, 63% for ranitidine, and on intention-to-treat analysis, healing in both groups was 63%. Pain relief and antacid consumption were similar in both groups. Clinically significant adverse effects were not detected and any changes in laboratory values were minimal, clinically insignificant and reversible. Mifentidine appears to be an effective and safe once-a-day treatment for acute duodenal ulcer disease.

Adult↗

Serum transglutaminase in inflammatory bowel diseases.

We evaluated the serum transglutaminase activity in patients with inflammatory bowel diseases (IBD) to correlate its level with clinical status. There were 49 patients with Crohn's disease (CD), 50 with ulcerative colitis (UC), 35 with diseases other than IBD as control group and 42 healthy subjects matched for sex and age. Enzyme activity was significantly lower in both IBD groups than in controls and in normal subjects (p less than 0.001); we found a significant negative correlation between serum transglutaminase (TG) activity and clinical severity of the disease in both IBD patient groups (r = -0.54 in CD, and r = -0.69 in UC). Moreover, in UC and CD patients, a serum TG value lower than 0.80 mU/ml retrospectively proved to predict the need for major surgery and/or total parenteral nutrition. These results suggest that serum TG may prove useful in the management of inflammatory intestinal diseases in predicting clinical outcome.

Colitis, Ulcerative↗

Regulation of diamine oxidase expression by ornithine decarboxylase in isolated rat small bowel enterocytes.

Ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, are highly expressed by small bowel enterocytes. Modulation of ODC expression is mediated through cellular concentration of polyamines that inhibits the enzyme synthesis and also induces the synthesis of an inhibitory protein, the antizyme, which in turn binds to ODC and inhibits its activity. DAO is an important regulator of intracellular concentration of polyamines because it catalyzes the degradation of putrescine into gamma-aminobutyraldehyde. Change in intracellular polyamine concentration has been suggested to represent a regulatory factor for DAO expression. In order to investigate a possible regulation of DAO expression by ODC, we studied the effect of difluoromethylornithine (DFMO), a selective, irreversible inhibitor of ODC, on DAO activity in isolated rat small bowel enterocytes. Our data demonstrate that in isolated small bowel enterocytes ODC inhibition by 10 mM DFMO reduced DAO activity by 53%, suggesting that, in our experimental conditions, ODC plays a regulatory role on DAO expression.

Amine Oxidase (Copper-Containing)↗

Inhibition of gastric acid secretion: advantages and risks in short and long-term treatment.

The administration of the currently available H2-blockers (at a dosage that induces only partial inhibition of the intragastric acidity) is effective in nearly all peptic ulcer patients in the short and long- term treatment. The benefits of more profound gastric acid inhibition (as achieved with omeprazole) in the short-term treatment of acid peptic diseases has been demonstrated in clinical studies. However, gastric acid has an important physiological role and the potential consequences of profound inhibition of gastric acid include intragastric bacterial colonization and hypergastrinaemia. Bacterial overgrowth of the stomach renders the gut more susceptible to enteric infection and another possible sequela of intragastric bacteria is the formation of N-nitroso compounds with carcinogenic potency. Hypergastrinaemia has a trofic effect on the gastric mucosa and gastric endocrine cells and, in animal, ECL cell hyperplasia and carcinoid formation has been observed as a result of high serum gastrin levels. So far, these potential risks have precluded the long-term administration of omeprazole.

Anti-Ulcer Agents↗

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial.

Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.

Administration, Rectal↗

The influence of severe bulb deformity on duodenal ulcer relapse.

In order to evaluate the prognostic role of duodenal bulb deformation in the recurrence of peptic ulcer, duodenal bulb morphology and the complete healing of duodenal ulcer were endoscopically evaluated in sixty patients, who were subsequently allocated at random to either maintenance therapy with ranitidine or no treatment. Endoscopic checkups were done at regular intervals, up to the first ulcer recurrence. As expected, long-term ranitidine treatment significantly reduced the relapse rate (12 month cumulative relapse rate was 32% versus 86% in the untreated). A set of prognostic factors which might interfere with this result (sex, age, alcohol consumption, history of ulcerous relatives, duration of the disease, previous H2-blocking treatment, previous complications, smoking and morphology of the duodenal bulb) were evaluated by multivariate analysis using the Cox regression model. Only duodenal bulb morphology appeared to have any independent prognostic value. In the untreated group ulcer recurrence seemed to occur earlier (median relapse time = 2 months) in the patients with severe non-stenosing bulb deformity, and later in those with normal or mildly deformed bulb (median relapse time = 8 months); ranitidine treatment delayed relapse in deformed bulb patients (median relapse time = 14 months) and almost eliminated it in those with normal duodenal bulb morphology. No association was found between the presence of duodenal bulb deformity and the above-mentioned covariates. Our study confirms the primary importance of anti-H2 treatment and suggests that anatomical characteristics of the duodenal bulb also influence the occurrence of ulcer relapse.

Adult↗