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Biomedical subjects

P Gionchetti

Publications and source records attributed to P Gionchetti.

At least 73 records · Page 4Linked to original sources
PubMed1997

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↗
PubMed1997

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Adult↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1994

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↗
PubMed1993

Comparison of scintigraphy with indium-111 leukocyte scan and ultrasonography in assessment of X-ray-demonstrated lesions of Crohn's disease.

The aim of this study was to compare the results obtained with an indium-111 scan with those obtained with less expensive and harmless ultrasonography to evaluate the location and inflammatory activity of Crohn's disease. Thirty-one patients previously studied with x-ray underwent abdominal 111In scans and ultrasonography (US). Sensitivity and specificity of US in detecting lesions seen with 111In scan were 77% and 92.8%, respectively. Sensitivity and specificity of 111In scan in detecting x-ray-defined lesions were 69.2% and 92.7%; the figures for US were 73% and 93.3%, respectively. Considering the evaluation of disease activity, ultrasonographic bowel wall thickness was significantly related to scintigraphic intensity of emission (r = 0.75 P < 0.01). Our experience suggests that US provided information about the location and inflammatory activity of lesions similar to that obtained from 111In scan.

Abdomen↗
PubMed1992

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↗