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Biomedical subjects

M Campieri

Publications and source records attributed to M Campieri.

At least 73 records · Page 4Linked to original sources

Lack of effect of antineutrophil cytoplasmic antibodies associated with ulcerative colitis on superoxide anion production from neutrophils.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

Antibodies, Antineutrophil Cytoplasmic↗

Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group.

BACKGROUND: The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism. AIMS: To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon. PATIENTS AND METHODS: One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less. RESULTS: After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023). CONCLUSIONS: Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.

Acute Disease↗

Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.

BACKGROUND: Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects. METHODS: We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes. RESULTS: Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7). CONCLUSIONS: In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

Adult↗

Systemic availability of 5-aminosalicylic acid: comparison of delayed release and an azo-bond preparation.

AIM: To determine the systemic uptake of 5-aminosalicylic acid (5-ASA) and acetyl-5-ASA (Ac-5-ASA) at steady state during treatment with either an azo-bond preparation, olsalazine, or a delayed-release mesalazine. METHODS: In an open cross-over trial with randomized sequence, 15 patients with ulcerative colitis in remission were given 7-day courses of olsalazine (Dipentum 1.0 g daily) and of mesalazine (Asacol 1.6 g daily). Plasma and urine were collected on days 6 and 7 of each course and concentrations of 5-ASA and Ac-5-ASA were determined by high-performance liquid chromatography (HPLC). RESULTS: Mean steady-state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher after treatment with mesalazine than with olsalazine (P < 0.0001). Total urinary excretion of 5-ASA and Ac-5-ASA as a percentage of the given dose was significantly higher on mesalazine than on olsalazine (P < 0.01). Only two patients experienced, during the first 3 days of treatment with olsalazine, transient watery diarrhoea which resolved spontaneously. No unexpected or major changes in haematology or biochemistry were detected during the study. CONCLUSION: As 5-ASA acts locally, the lower systemic load provided by olsalazine may increase efficacy and reduce the potential risk of nephrotoxicity during long-term maintenance treatment of ulcerative colitis.

Adult↗

Management of severe ulcerative colitis with the help of high resolution ultrasonography.

OBJECTIVES: The prognosis of attacks of ulcerative colitis is clearly linked to the extent and activity of the disease. The aim of this study was to investigate the value of high resolution ultrasonography in assessing both the extent and activity of severe ulcerative colitis and its response to medical treatment. METHODS: Fifty-seven consecutive patients affected by a severe (32 patients) or moderately severe (25 patients) attack of ulcerative colitis underwent ultrasonographic examination. The ultrasonographic extent of the disease was evaluated in 32 patients by comparing ultrasonography and scintigraphy. RESULTS: Compared with scintigraphy, sensitivity, specificity, and overall accuracy of ultrasonographic extent were 89%, 100%, and 91%, respectively. These results were also confirmed in a subgroup of patients submitted to surgery, comparing ultrasonographic and scintigraphic data versus specimens. Using the ultrasonographic score of activity, it was possible to discriminate severe and moderately severe attacks with a specificity, sensitivity, and diagnostic accuracy of 96%, 90.3%, and 92.9% respectively. A close correlation was also found between ultrasonographic and scintigraphic activity (r = 0.78; p < 0.001). After 10 days of intensive treatment, the ultrasonographic activity significantly decreased in severe and moderate groups (p < 0.001) and in both subgroups of nonoperated patients (p < 0.001) but not in operated patients (p = NS). CONCLUSIONS: High resolution ultrasonography can be useful in assessing both extent and activity of severe ulcerative colitis, in monitoring the patient's condition, and in objectively evaluating the response to medical therapy.

Adult↗

Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 x 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.

Adult↗

Mucosal concentrations of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in pelvic ileal pouches.

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1 beta was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-alpha was undetectable in all specimens examined. The concentrations of IL-1 beta, IL-6, and IL-8 were significantly greater (P < 0.001) in biopsy specimens from pouchitis compared to those from pouches without pouchitis or normal ileal mucosa and in patients with pouchitis tissue levels of IL-1 beta significantly correlated with IL-6 (P < 0.05) and IL-8 (P < 0.01). Furthermore IL-1 and IL-8 levels were significantly higher in tissue specimens from nonpouchitis pouches than in those from normal ileal mucosa (P < 0.02). These results suggest that an enhanced cellular immunity operates in vivo at the mucosal level in pouchitis as in the case of ulcerative colitis.

Adult↗

Respiratory burst of circulating polymorphonuclear leukocytes and plasma elastase levels in patients with inflammatory bowel disease in remission.

The activation of circulating polymorphonuclear leukocytes was determined in terms of superoxide radical generation and granulocyte elastase release in untreated patients with ulcerative colitis (N = 10) and Crohn's disease (N = 9) in remission and in control subjects (N = 10). Superoxide radical generation was determined by monitoring spectrophotometrically the reduction of ferricytochrome, after stimulation of cells with phorbol myristate acetate. Plasma elastase concentration was measured by a solid-phase enzyme immunoassay technique as the complex with alpha-1-proteinase inhibitor. Superoxide formation by polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease was significantly lower compared with controls [median (range) nmol/min/mg protein: Crohn's disease 7.8 (7.1-9.6); ulcerative colitis 8.25 (7.4-10.3); controls 14.7 (13.6-15.8)] (P < 0.001), while no difference was found between the two groups of patients. In contrast plasma elastase levels in patients with ulcerative colitis and Crohn's disease were similar to that of controls. This defective respiratory burst of polymorphonuclear leukocytes in patients with inflammatory bowel disease in remission, in absence of an altered degranulation, could represent an important factor for the pathogenesis of these diseases.

Colitis, Ulcerative↗

Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long-chain fatty acid composition in patients with Crohn's disease.

Patients with Crohn's disease may become zinc-deficient and, in such patients, an altered metabolism of radiolabelled long-chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long-chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long-standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls. Plasma zinc levels in Crohn's were 72 +/- 8 micrograms/dL before zinc treatment and increased to 114 +/- 10 micrograms/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n-3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre-treatment differences in red-cell long-chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease.

Adult↗

Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration.

BACKGROUND: Steroids are highly effective in active Crohn's disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. METHODS: Seventy patients with active Crohn's disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks. RESULTS: Steroid therapy induced remission within 3 weeks in 91% of the whole group of patients; at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%, CI = -14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = -9 to 41, P = NS). CONCLUSIONS: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse.

Adult↗

Bioavailability of single and multiple doses of a new oral formulation of 5-ASA in patients with inflammatory bowel disease and healthy volunteers.

AIMS: An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA: mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. METHODS: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. RESULTS: In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. CONCLUSIONS: The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity.

Administration, Oral↗

Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients.

OBJECTIVES: To determine the concentrations of interleukin-1 beta, interleukin-6, and interleukin-8 in tissue homogenates of mucosal biopsy specimens from Helicobacter pylori-positive and -negative patients. METHODS: In 43 consecutive patients who underwent upper gastrointestinal endoscopy, seven antral biopsies were taken; three specimens were used for cytokine determination and the remaining four biopsies were processed for H. pylori detection. Peripheral venous blood was collected and IgG to H. pylori was assayed by an ELISA technique. RESULTS: Twenty-nine of 43 patients (67%) were histologically positive for H. pylori; all had chronic gastritis. The mucosal levels of interleukin-6 and interleukin-8 were significantly higher in H. pylori-positive patients than in the negative patients (p < 0.001). A significantly higher percentage of interleukin-8 was found in patients colonized by H. pylori with active superficial chronic gastritis (85.7%), compared to quiescent superficial gastritis (12.5%) (p < 0.01), and the median and range were, respectively, 400 (0-1000) and 0 (0-200) pg/mg protein (p < 0.001). In patients with active superficial gastritis, a significant correlation between interleukin-6 and -8 was found (p 0.01). No difference was found regarding the mucosal levels of interleukin-1 beta according to the presence of H. pylori. CONCLUSIONS: These results suggest a possible pathogenetic role for interleukin-6 and interleukin-8 in H. pylori-associated gastritis.

Adult↗

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis. A multicenter comparative trial with 5-ASA enema.

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P < 0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI -7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗

Spread and distribution of 5-ASA colonic foam and 5-ASA enema in patients with ulcerative colitis.

Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc]sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. The foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis.

Administration, Topical↗