PubMed Health⌕ Search

Biomedical subjects

P Gionchetti

Publications and source records attributed to P Gionchetti.

At least 37 records · Page 2Linked to original sources
PubMed2002

Review article: monitoring activity in ulcerative colitis.

The monitoring of patients with ulcerative colitis is easier than in patients with Crohn's disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X-ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response.

Colitis, Ulcerative↗
PubMed2002

Review article: treatment of mild to moderate ulcerative colitis and pouchitis.

The meta-analyses of published trials have shown topical therapy with 5-aminosalicylic acid (5-ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5-ASA therapy. An alternative to 5-ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5-ASA or new steroids should be treated with oral steroids. Azathioprine or 6-mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried-out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.

Administration, Oral↗
PubMed2002

Review article: the management of refractory Crohn's disease.

Refractoriness to conventional therapy is a common and intriguing problem in Crohn's disease patients. At the present time there is no agreement on its definition and several mechanisms are involved in its determination. Immunosuppressors, such as azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX) are effective drugs for controlling the inflammatory process and avoid chronic glucocorticosteroid treatment and its related side-effects. Recently, the introduction of tumour necrosis factor antibodies (infliximab) has dramatically changed the natural history of Crohn's disease and its therapeutic approach. Several studies have determined the efficacy, mechanisms and safety of infliximab. However, this molecular approach has also left several questions unanswered about the mechanisms of refractoriness, possible concomitant treatments and long-term safety and efficacy.

Antibodies, Monoclonal↗
PubMed2002

Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis.

BACKGROUND: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment. AIM: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life. METHODS: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0-18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of <or= 2, endoscopic score of <or= 1 and total score of <or= 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32-224). RESULTS: Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8-17) and 3 (range, 1-10), respectively (P < 0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175 (range, 76-215) with this therapy (P < 0.0001). The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 35 years; P=0.007), had a longer history of pouchitis (95.5 vs. 26 months; P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0-2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs. 12; P=0.13) than those who went into remission. Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8-16) to 9.5 (range, 7-10) (P=0.0078), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127 (range, 76-187) (P=0.039). The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P < 0.0001), and was significantly related to the patients' overall assessment of satisfaction (P < 0.0001). No serious side-effects were noted. CONCLUSIONS: Four-week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality of life. The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with disease activity.

Adult↗
PubMed2002

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study.

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. RESULTS: One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. CONCLUSIONS: Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.

Administration, Oral↗
PubMed2002

Effect of probiotic strains on interleukin 8 production by HT29/19A cells.

OBJECTIVES: Promising results from clinical studies on the effect of probiotics as maintenance therapy in inflammatory bowel disease and in the prevention of onset of pouchitis ask for studies to unravel the still poorly understood mechanism of action of probiotics. METHODS: To evaluate whether the probiotic bacteria that were used in the clinical studies (VSL#3, Escherichia coli Nissle 1917, and Lactobacillus GG) are able to induce chemokine production in epithelial cells, HT29/19A monolayers were incubated with cell debris and cell extract fractions of single strains of the probiotic bacteria in doses ranging from 10(3) to 10(9) colony-forming units/ml for 32 h. Supernatants were measured for interleukin 8 by ELISA. RESULTS: Lactobacilli and bifidobacteria strains from VSL#3 and Lactobacillus GG did not induce interleukin 8, whereas both cell debris and cell extracts from E. coli Nissle 1917 induced interleukin 8 production in a dose-dependent way. Cell extracts from streptococcal strains induced interleukin 8 when applied at high concentrations. CONCLUSIONS: Probiotic Gram-positive bacteria did not induce interleukin 8, whereas the nonpathogenic, Gram-negative E. coli Nissle 1917 strain induced interleukin 8 in a dose-dependent way in this culture model. These results suggest that probiotic Gram-positive bacteria and E. coli Nissle 1917 may exert their beneficial effects on the host by a different mechanism of action.

Bacterial Physiological Phenomena↗
PubMed2001

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study.

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

Administration, Oral↗
PubMed2001

Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis.

Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of the signalling pathway of other cytokines/growth factor receptors. In ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both Crohn's Disease and normal controls. Pouchitis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and aetiology of pouchitis is still unclear. Recent studies have shown an increased production of proinflammatory cytokines including IFN-gamma. To investigate the expression and activation of STAT1 in pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of pouchitis was made by clinical, endoscopic and histological criteria. Biopsies were obtained during routine endoscopy and snap frozen in liquid nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence. Patients who develop pouchitis show highly increased levels of STAT1 alpha as well as STAT1 beta expression and activation in comparison with both normal pouch and normal ileal mucosa. Improvement of pouchitis during antibiotic therapy relates to a normalization of STAT1 expression and activation. We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of pouchitis. Similarities in the pattern of activation of STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases.

Adult↗
PubMed2001

Probiotics and antibiotics in inflammatory bowel disease.

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease. Manipulation of the luminal content using antibiotics and/or probiotics may represent a potentially effective therapeutic option. Results of antibiotic treatment in inflammatory bowel disease are controversial, but this approach is frequently and successfully adopted in clinical practice. Recent data support the potential therapeutic role of probiotics in inflammatory bowel disease. In particular, a highly concentrated probiotic preparation was shown to be superior to placebo both on the prevention of pouchitis onset and of chronic pouchitis relapse. Its role in the maintenance treatment of ulcerative colitis and Crohn disease needs to be further assessed by large, double-blind, controlled trials. Future research needs to be focused on obtaining more precise information on the enteric microflora and the mechanisms of action of probiotics.

Journal Article↗
PubMed2001

Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study.

OBJECTIVES: Recent studies in familial Crohn's disease (CD) have suggested that anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. METHODS: Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. RESULTS: ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). CONCLUSIONS: In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.

Adolescent↗
PubMed2001

Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment.

OBJECTIVE: The efficacy of probiotic organisms in the treatment of pouchitis has been reported. In the present study, we evaluated the tissue levels of pro- and anti-inflammatory cytokines, nitric oxide synthase, and matrix metalloproteinases in control and inflamed pouches before and after antibiotic and probiotic treatment of patients with acute pouchitis. METHODS: Pouch biopsy samples were obtained from seven patients with pouchitis before and after antibiotic and probiotic treatment. Tissue samples from five patients with normal pouches were used as controls. Cytokines were determined by ELISA, matrix metalloproteinase activity was evaluated by zymograms, and nitric oxide synthase activity was determined by measuring arginine to citrulline conversion. RESULTS: Tissue levels of tumor necrosis factor a increased (p < 0.01) in pouchitis relative to uninflamed pouches and reduced after antibiotic and probiotic treatment. Also, interferon y and interleukin 1alpha (IL-1alpha) augmented in pouchitis, but their increase did not reach statistical significance. The latter, however, were lower (p < 0.05) after treatment with the antibiotics and probiotics. Tissue levels of IL-4 and IL-10 were unchanged in inflamed pouches and unaffected by antibiotic treatment. However, IL-10 increased (p < 0.05) after probiotic treatment. Moreover, inflamed pouches had higher levels of inducible nitric oxide synthase and gelatinase activities, which decreased after treatment. CONCLUSIONS: The ability of antibiotic and probiotic treatments to increase tissue levels of IL-10, at a higher level than those observed in control pouches, and to decrease, to levels present in control pouches, proinflammatory cytokine, inducible nitric oxide synthase, and matrix metalloproteinase activity may suggest a mechanism of action to explain the efficacy of this therapeutic regime in pouchitis.

Acute Disease↗
PubMed2001

CBP-1011. InKine Pharmaceutical Co.

CBP-1011 (medroxyprogesterone acetate) is an immunosuppressant corticosteroid under development by InKine Pharmaceuticals (formerly CorBec Pharmaceuticals) for the potential treatment of a number of inflammatory conditions. Phase III trials are underway in the US for the treatment of idiopathic thrombocytopenic purpura [234943]. By December 2000, it had completed phase II trials for the treatment of inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) [393219]. In March 2001, the FDA designated CBP-1011 an Orphan Drug for the treatment of thrombocytopenic pupura [400935]. In June 2000, InKine reported that a US patent (subsequently identified as US-06068983, entitled 'Methods of stimulating phagocytosis' and assigned to University of Pennsylvania) had been issued to Alan D Schreiber MD, Chairman of InKine's Scientific Advisory Board. The patent describes methods of increasing Fc receptors on white blood cells or macrophages, as well as inducing Fc receptors in cells that do not normally possess them, such as lung and liver cells [370990]. In April 2001, the University of Pennsylvania (inventor again Alan D Schreiber) claimed the use of medroxyprogesterone acetate for treating IBD, CD, UC, food allergies, hemorrhoids and psoriasis in WO-00122959, entitled 'Method of treating inflammatory conditions with progesterone or progesterone analogs'.

Journal Article↗
PubMed2000

Probiotics in infective diarrhoea and inflammatory bowel diseases.

Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.

Bifidobacterium↗
PubMed2000

Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Most patients have relapsing disease, and no maintenance treatment study has been performed. We evaluated the efficacy of a probiotic preparation (VSL#3) containing 5 x 10(11) per gram of viable lyophilized bacteria of 4 strains of lactobacilli, 3 strains of bifidobacteria, and 1 strain of Streptococcus salivarius subsp. thermophilus compared with placebo in maintenance of remission of chronic pouchitis. METHODS: Forty patients in clinical and endoscopic remission were randomized to receive either VSL#3, 6 g/day, or an identical placebo for 9 months. Patients were assessed clinically every month and endoscopically and histologically every 2 months or in the case of a relapse. Fecal samples were collected for stool culture before and after antibiotic treatment and each month during maintenance treatment. RESULTS: Three patients (15%) in the VSL#3 group had relapses within the 9-month follow-up period, compared with 20 (100%) in the placebo group (P < 0.001). Fecal concentration of lactobacilli, bifidobacteria, and S. thermophilus increased significantly from baseline levels only in the VSL#3-treated group (P < 0.01). CONCLUSIONS: These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic pouchitis.

Administration, Oral↗
PubMed1999

Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis.

Chemokines are thought to be important for the recruitment of granulocytes and mononuclear cells and thus for the maintenance of inflammation in ulcerative colitis (UC). We have studied the expression of interferon-gamma inducible protein-10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant protein (MCP)-1, MCP-3, and macrophage inflammatory protein (MIP)-1alpha in UC patients and control individuals to assess the role of these chemokines in disease progression. Colonic biopsies were taken endoscopically from patients and controls, frozen immediately and subsequently stained for IP-10, IL-8, MCP-1, MCP-3, and MIP-1alpha in serial sections. Cells infiltrating the lamina propria but not epithelial cells express the analyzed chemokines. They were differentiated and counted, and chemokine-expressing cells were quantified by image analysis. The percentage of cells expressing IP-10, IL-8, MCP-1, and MCP-3 was significantly enhanced in all UC samples as compared to controls. Expression in the controls was borderline, except for IP-10. No expression of MIP-1alpha was found in controls and UC. IP-10 was also markedly expressed in the mucosa of control biopsies and therefore could have a role in activated T lymphocytes' recruitment into the healthy mucosa.

Adult↗