Biomedical subjects

R Caprilli

Publications and source records attributed to R Caprilli.

At least 19 recordsLinked to original sources

PubMed2003

Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis. METHODS: This open study included seven patients (four females, three males) with chronic refractory pouchitis complicated by fistulae. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. The sites of the fistulae were as follows: pouch-bladder in one, vaginal in three, perianal in two, and both vaginal and perianal in one. Extra-intestinal manifestations (erythema nodosum, arthralgia) were present in four patients. Crohn's disease was carefully excluded in all patients after re-evaluation of the history, re-examination of the original proctocolectomy specimen and examination of the proximal small bowel. All patients had been treated with antibiotics and three with steroids. Patients received infliximab, 5 mg/kg, at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial or no response. Fistulae closure was classified as complete (cessation of fistulae drainage and total closure of all fistulae), partial (a reduction in the number, size, drainage or discomfort associated with fistulae) or no closure. The pouchitis disease activity index and quality of life were also used as outcome measures. RESULTS: Clinically, all patients improved. At the 10-week follow-up, six of the seven patients had a complete clinical response, and five had complete fistulae closure. At the 10-week follow-up, the median pouchitis disease activity index decreased from 12 (baseline) (range, 10-15) to 5 (range, 3-8); the median quality of life decreased from 37 points (range, 33-40) to 14 (range, 9-18). Erythema nodosum and arthralgia showed complete remission soon after the first infusion of infliximab. CONCLUSIONS: These preliminary results indicate that infliximab may be recommended for the treatment of refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis.

Adult↗

PubMed2003

Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial.

BACKGROUND: The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. AIM: To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. METHODS: The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate. RESULTS: Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence. CONCLUSIONS: A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow-up.

Administration, Oral↗

PubMed2003

Abdominal tuberculosis with pancreatic involvement: a case report.

A case of abdominal tuberculosis with pancreatic involvement is described. A 27-year-old Italian male, with no known cause of immunodeficiency and with no evidence of pulmonary tuberculosis, was admitted to our division because of acute pancreatitis. Abdominal imaging revealed a large 'tumour-like' mass in the pancreas head compressing the distal choledochous, and multiple adenopathy. Histological examination of multiple specimens removed during explorative laparotomy revealed granulomas with giant cells, caseous necrosis, and positive Ziehl-Neelsen staining. Tissue culture was positive for Mycobacterium tuberculosis. Once specific medical treatment was started, the pancreatic damage completely resolved.

Adult↗

PubMed2003

Effect of predominant methanogenic flora on the outcome of lactose breath test in irritable bowel syndrome patients.

BACKGROUND: The relationship between hydrogen and methane production is a possible confounding factor in the interpretation of H(2) breath tests (HBT), but is usually disregarded for the interpretation of HBT and, in most instances, only H(2) excretion is measured. The present study was designed to evaluate the effect of predominant fasting methane CH(4) or H(2) production on the outcome of lactose HBT, in a large, homogeneous series of adult patients with irritable bowel syndrome (IBS). PATIENTS AND METHODS: A lactose HBT was performed in 237 IBS patients with predominant fasting methane production (CH(4)>H(2)), recording the outcome of the test, amount of gas excreted and occurrence of clinical symptoms. Data were compared to those of 237 age- and sex-matched IBS patients with low fasting CH(4) excretion. RESULTS: The test was positive in 124 predominant CH(4) producers (52.3%) (PMP), as compared to 201 (84.8%) low methane producers (LMP) (P<0.0001). Peak hydrogen concentration and area under the curve of H(2) were significantly (P<0.001) lower, and the occurrence of symptoms during the test less frequent, in PMP vs LMP patients. During the test, CH(4) excretion doubled in 57/113 (50.4%) patients with negative HBT, and in 49/124 (39.5%) with positive HBT. CONCLUSIONS: Patients with predominant fasting methane production excrete less H(2) than LMP, after an oral load of lactose. The lower prevalence of severe lactose intolerance in PMP, as well as lower incidence of symptoms during the test, is, indeed, related to lower and slower H(2) excretion. The assumption that H(2) excretion is an effective means of quantifying the amount of malabsorbed carbohydrates is questionable in PMP. Methane-producing patients likely have a higher 'false negative' rate as compared to LMP after an oral load of lactose. Nonetheless, as symptoms are related to the amount of gas produced in the colon, HBT identifies patients with 'lactose intolerance', irrespective of the presence of lactose malabsorption, and helps in predicting the effect of lactose-restricted diet.

Adolescent↗

PubMed2003

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.

Adult↗

PubMed2002

Review article: biological agents in the treatment of Crohn's disease.

The main aim of the management of Crohn's disease is to reduce inflammation. Current approaches with corticosteroids, immunosuppressive agents, mesalazine and antibiotics have limited therapeutic benefit for many patients. Considerable progress has been made with regard to our knowledge of the basic mechanisms of the disease, which is associated with immunological imbalance characterized by an excess of pro-inflammatory cytokines. Recent advances in bio-technology have led to the development of many new therapeutic agents, so-called biological agents, which selectively target single key processes involved in the pathogenesis of the disease. A growing number of biological agents are under investigation in both randomized controlled trials and uncontrolled studies. The aim of this review is to provide the clinician with an insight into the randomized controlled trials published in the literature on the use of biological agents in the treatment of Crohn's disease.

Antibodies, Monoclonal↗

PubMed2001

Survival and causes of death in Italian patients with ulcerative colitis. A GISC nationwide study.

BACKGROUND: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease. AIM: To evaluate overall and cause-specific mortality rate in a large group of Italian patients with ulcerative colitis. METHODS: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated. RESULTS: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0). CONCLUSIONS: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system.

Adult↗

PubMed2001

Clinical features in familial cases of Crohn's disease and ulcerative colitis in Italy: a GISC study. Italian Study Group for the Disease of Colon and Rectum.

OBJECTIVE: Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families. METHODS: In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year (< 1 yr or > or = 1 yr). Statistical analysis was performed with chi2, Fisher's, Mann-Whitney U, and binomial probability tests, when appropriate. RESULTS: A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p < 0.4) in CD families and extensive colitis (p < 0.05) in UC families was demonstrated. A generation difference of 15-20 yr in mean ages at onset of symptoms and at diagnosis was recorded. No features of more aggressive disease in subsequent generations and no differences in gender of transmitting parents and relatives were found. CONCLUSIONS: Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15-20 yr earlier than in previous generations without features of increased severity.

Adolescent↗

PubMed2000

Topical butyrate for acute radiation proctitis: randomised, crossover trial.

BACKGROUND: No available therapy has, as yet, proven effective to treat acute radiation proctitis (ARP) following radiation therapy for malignant pelvic disease. We assessed whether sodium butyrate enemas, at a dose of 80 mmol/L (80 mL/24 h), might offer effective treatment for this condition. METHODS: 20 patients presenting with ARP after completing a cycle of 35-52 Gy external-beam radiation therapy for pelvic malignant disease, were treated for 3 weeks with topical sodium butyrate and saline enemas according to a randomised, double-blind, crossover protocol. Clinical, endoscopic, and histological findings were assessed at enrollment, at week 3, and then at the end of the study. Data were analysed by two-tailed t test for paired data (continuous variables) and a logistic-regression model with variable multiple response for ordered categorical data. FINDINGS: Topical butyrate, but not saline, led to remission of symptoms (clinical score from 8.2 [SE 1.6] to 1.5 [0.7] vs 7.9 [1.8] to 8.1 [3.4]). When the treatment regimen was switched, eight out of nine of the previously placebo-treated patients went into remission, whereas three patients relapsed when switched to saline. The advantage of butyrate over placebo, expressed as CI, odds ratio, and p value was significant for almost all the clinical, endoscopic and histological factors taken into consideration. INTERPRETATION: Topical sodium butyrate, unlike other therapeutic regimens used so far, proved effective in the treatment of ARP.

Administration, Topical↗

PubMed2000

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availability/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 +/- 2.02 to 2.58 +/- 2.19 (P < 0.05) in the combined treatment group and from 6.07 +/-1.60 to 3.46 +/- 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (delta9.58 +/- 4.19 vs 5.92 +/- 3.48) and the UCDAI score (delta4.67 +/- 2.19 vs 2.54 +/- 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

Administration, Oral↗

PubMed2000

Multiple organ dysfunction in ulcerative colitis.

OBJECTIVE: The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. METHODS: The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976-1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. RESULTS: Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called "impending megacolon" in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. CONCLUSIONS: These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.

Adolescent↗

PubMed2000

Anastomotic configuration and mucosal 5-aminosalicyclic acid (5-ASA) concentrations in patients with Crohn's disease: a GISC study. Gruppo Italiano per lo Studio del Colon e del Retto.

OBJECTIVE: Recurrence of Crohn's disease quite inevitably occurs after resection of distal small bowel and proximal colon, involving the neoterminal ileum close to the anastomosis. Oral 5-aminosalicylic acid (5-ASA) administered soon after surgery delays recurrence and reduces its severity. We recently observed that in operated patients submitted to prophylactic treatment with oral 5-ASA the rate of recurrence was significantly higher in those with end-to-end anastomosis than in those with other types of anastomosis (end-to-side, side-to-side). The hypothesis investigated in the present study was that patients with end-to-side or side-to-side anastomosis would benefit from a higher mucosal concentration of 5-ASA with respect to patients with end-to-end anastomosis. Therefore, the mucosal 5-ASA concentration was measured in the perianastomotic area of both groups. METHODS: The study was carried out in 19 patients submitted to radical surgery for Crohn's ileitis or ileocolitis, under oral prophylactic treatment with 5-ASA (Asacol). All patients were on regular endoscopic follow-up and were free of recurrence. Two biopsies were collected 3 cm from the anastomosis, in the neoterminal ileum, and two biopsies were collected at the colonic site 3 cm below the anastomosis. 5-ASA concentrations (ng/mg) were measured in tissue homogenates by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: The mucosal concentration of 5-ASA in the neoterminal ileum was significantly lower in patients with end-to-end anastomosis than in those with other types of anastomosis (median values: 29.4 ng/mg vs 92.9 ng/mg respectively; p < 0.001). Six of 10 patients (60%) with end-to-end anastomosis, but none of the nine patients with other types of anastomosis, showed 5-ASA mucosal concentrations <40 ng/mg at the neoterminal ileum. On the contrary, no patients with end-to-end anastomosis showed mucosal concentrations of 5-ASA >90 ng/mg, compared with the 57% of patients in the group with other types of anastomosis. No differences were observed for colonic biopsies. CONCLUSIONS: The different mucosal concentrations in these two groups may be explained by the difference in segmental transit time induced by the different anastomotic configurations. A slower preanastomotic transit time, demonstrated in patients with end-to-side or side-to-side anastomosis, could offer a prolonged contact time between the intestinal content and the mucosa, resulting in an increase in drug absorption.

Adult↗

PubMed2000

Mucosal 5-aminosalicylic acid concentration inversely correlates with severity of colonic inflammation in patients with ulcerative colitis.

BACKGROUND AND AIM: The treatment of ulcerative colitis (UC) with 5-aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all patients. We tested the hypothesis that the effectiveness of the drug is related to its mucosal concentration. PATIENTS: Twenty one UC patients receiving oral 5-ASA (2.4-3.2 g/day) were enrolled in the study. Four were also receiving topical treatment (2 g/day). METHODS: Six endoscopic biopsies were taken from the rectum for measurement of 5-ASA concentrations (ng/mg) by HPLC; soluble interleukin 2 receptor (sIL-2R) concentrations (U/ml) were measured by ELISA and histology. Endoscopic and histological appearance was graded on a four point scale (0-3). The Wilcoxon's rank test and Pearson's correlation coefficient were used for statistical analysis. RESULTS: Mucosal concentrations of 5-ASA were significantly higher (p=0.03) in patients with endoscopic scores of 0-1 compared with those with scores of 2-3 (16.1 (range 10.2-45) v 5. 5 (3.5-17.4), respectively) and in patients with lower histological inflammation compared with those with more severe scores (17.4 (10. 5-45) v 8.9 (3.5-17.2), respectively) (p<0.01). In contrast, mucosal sIL2-R concentrations were significantly lower in patients with slight endoscopic and histological lesions than in those with more severe disease. A significative inverse correlation (r=-0.85) was found between 5-ASA and sIL-2R mucosal concentrations (p=0.00008). CONCLUSIONS: In patients with UC, in the same area of the intestinal tract, we found that the higher the 5-ASA mucosal concentrations, the lower the IL-2R levels and endoscopic and histological scores. We hypothesise that maintenance of high mucosal 5-ASA concentrations in all colonic segments could contribute to improve clinical outcome in UC patients.

Adult↗

PubMed1999

Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis.

BACKGROUND: Iron deficiency anemia is the most common form of anemia worldwide. Recent studies have suggested an association between Helicobacter pylori infection and iron deficiency. OBJECTIVE: To investigate the effects of eradicating H. pylori with combination antibiotic therapy on iron deficiency anemia in patients with H. pylori-associated gastritis. DESIGN: Case series. SETTING: University hospital. PATIENTS: 30 patients with a long history of iron deficiency anemia in whom H. pylori-associated gastritis was the only pathologic gastrointestinal finding detected. INTERVENTION: Eradication therapy with two antibiotics and discontinuation of iron replacement therapy. MEASUREMENTS: Complete blood count, ferritin levels, and gastroscopy with biopsy to evaluate H. pylori status. RESULTS: At 6 months, 75% of patients had recovered from anemia (P<0.001), ferritin values increased from 5.7+/-0.7 microg/L to 24.5+/-5.2 microg/L (95% CI, 8.85 to 29.97). After 12 months, 91.7% of patients had recovered from anemia. CONCLUSIONS: Cure of H. pylori infection is associated with reversal of iron dependence and recovery from iron deficiency anemia.

Adult↗

PubMed1999

Dextran sulfate sodium (DSS) colitis in rats: clinical, structural, and ultrastructural aspects.

Aim of this study was to assess the structural, ultrastructural, immunohistochemical, and clinical aspects in Sprague-Dawley rats with dextrane sulfate sodium (DSS)-induced colitis. Colitis was induced in Sprague-Dawley rats by seven days of DSS oral administration followed by seven days of tap water only (for one, two and three cycles). Controls were fed with water only. Segments of proximal, mid-, and distal colon of each animal were adequately prepared for light and scanning electron microscope observations. The severity of the lesions was scored histologically. For immunohistochemical study, a cocktail of S-100, NSE, and antineurofilament antibodies was used. Symptoms such as weight, feces consistency, diarrhea, hematochezia were recorded daily. From a clinical point of view symptoms appeared significantly later after the first cycle than after the second and third cycles and lasted significantly longer in the second and third cycles. Treated rats showed a slower weight gain rate by 20% compared to controls, and the whole colon length appeared to be significantly shorter after colitis induction compared to controls. Structural observations by light microscopy showed prominent involvement of the distal colon. Immunohistochemical study of both submucosal and myoenteric nerve plexuses was similar to controls. Scanning electron microscope observations of the colonic mucosal surface in colitis rats showed a complete subversion of its architecture, characterized by dilatations of gland crypt openings, dropout of goblet cells, and inhomogeneous distribution or lack of microvilli. These were most evident after the third cycle. In conclusion, experimental DSS colitis in SD rats appeared to be highly reproducible and shared most features with human UC, not only from a structural and clinical but also from an ultrastructural point of view.

Animals↗

PubMed1999

Prevention of post-operative recurrence of Crohn's disease requires adequate mucosal concentration of mesalazine. Gruppo Italiano per lo Studio del Colon e del Retto.

BACKGROUND: Surgical resection of Crohn's disease is followed by early recurrence in a high percentage of patients. Mesalazine has been shown to be effective in the prevention of post-operative recurrence, but some 50% of patients under treatment recur at 3 years of follow-up. AIM: To establish whether the mucosal concentration of mesalazine might affect the development of post-operative recurrence. METHODS: Colon-ileoscopy was performed in 25 consecutive patients resected for Crohn's disease. The mean time from surgery was 14 months. After the operation, all patients were taking oral mesalazine (Asacol, 2.4 g/day). Ten patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing of the lumen) in the neoterminal ileum, five of whom also showed juxta-anastomotic colonic involvement. Fifteen patients were free of recurrence. At endoscopy, four biopsies were taken from the perianastomotic area (two specimens at the ileal site and two specimens at the colonic site of the anastomosis). The specimens were weighed and immediately frozen at -80 degrees C. Mesalazine concentration (ng/mg) was measured in tissue homogenates by high- performance liquid chromatography with electrochemical detection. Fisher's exact test was used for the statistical analysis. RESULTS: The mean value of mucosal mesalazine concentration, expressed as ng/mg of tissue, was significantly lower in patients with recurrence than in those without recurrence both in the ileum (mean +/- s.d.: 21.6+/-28.3 vs. 70.9+/-47.4; P = 0.007) and in the colon (25.8+/-26.4 vs. 60.3+/-32.5; P = 0.010). CONCLUSIONS: The mucosal concentration of mesalazine in the juxta-anastomatic area is significantly lower in patients with recurrence than in those free of recurrence. These data could suggest an association between mucosal mesalazine concentrations and the clinical effectiveness of the drug.

Adult↗

PubMed1999

Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment.

AIM: To measure mucosal concentrations of mesalazine in ulcerative colitis patients treated with oral mesalazine alone, compared to patients treated with both topical and oral mesalazine. METHODS: Twenty-two patients with mild to moderate ulcerative colitis were randomized to receive 2.4 g/day of oral mesalazine (11 patients) or 2.4 g/day oral plus 4 g/day of topical mesalazine (11 patients). After 2 weeks of treatment, endoscopic biopsies specimens were taken from the rectum and in descending colon just distal of the splenic flexure and stored to -80 degrees C for later assay (HPLC). Wilcoxon's rank sum test for unpaired data was used for the statistical analysis. RESULTS: Mucosal levels of mesalazine in the rectum were significantly higher in patients who received oral plus topical treatment than in those who had oral treatment alone (52.1 ng/mg, range: 13.6-122.1 vs. 0.2 ng/mg, range: 0.2-9.7, respectively; P < 0.0001). Similarly, in the descending colon, the mucosal concentrations of mesalazine were significantly higher in patients who had oral plus topical treatment than in those receiving oral treatment alone (46.6 ng/mg, range: 6-112.6 vs. 15.9 ng/mg, range: 2.3-42.4, respectively; P=0.01). CONCLUSIONS: Topical treatment of mesalazine significantly increases mucosal concentrations of mesalazine up to the splenic flexure, supporting the rationale to treat left-sided ulcerative colitis with topical formulations of mesalazine.

Administration, Oral↗

PubMed1999

Circulating soluble factor-inhibiting natural killer (NK) activity of fresh peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients.

This study was performed in order to assess the cytotoxic activity, both natural (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it with their clinical features. Cytotoxicity assays were performed using sensitive target cells for NK and ADCC activities. In some experiments, highly purified NK cells, obtained both by Percoll density gradient and by co-culturing non-adherent PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we evaluated NK cell parameters such as number, surface expression of adhesion molecules (CD11a/CD18, CD49d and CD54) and response to different stimuli. We observed a decreased NK cytotoxicity of PBMC from IBD patients, both in ulcerative colitis (UC) and Crohn's disease (CD), independently of the clinical activity of disease. In contrast, the ADCC lytic activity was within normal range. The lower NK cytotoxic activity observed in our IBD patients cannot be related to a decreased number of NK cells, surface expression of adhesion molecules, defective response to IL-2 and maturative defect. Decreased NK activity was induced in PBMC of controls when serum of patients was added and this was unrelated to monocyte-derived modulating factor(s). Our data show a decreased natural killing by fresh PBMC from IBD patients. This lower activity seems to be unrelated to a primary NK cell defect, since purified NK cells exhibited normal levels of killing. It might be hypothesized that serum factors, possibly derived from lymphocytes, with inhibitory properties on NK activity, might be functionally active in the blood of IBD patients, thus modulating NK activity.

Adolescent↗