Maurizio Ferretti

Comparison of oral with rectal mesalazine in the treatment of ulcerative proctitis

PURPOSE: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis. PATIENTS AND METHODS: A four-week, randomized, single-blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (≤15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n=29) compared with 400 mg of mesalazine suppositories administered three times per day (n=29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physicians assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports. RESULTS: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P<0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P<0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups. CONCLUSIONS: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.

A randomized, double-blind comparison of placebo, etodolac, and naproxen on gastrointestinal injury and prostaglandin production☆☆☆★★★

BACKGROUND NSAIDs frequently cause gastrointestinal injury and increase the risk of ulcer complications. We compared an NSAID suggested to cause less gastric injury (etodolac) with a standard NSAID (naproxen) and a placebo in a 4-week double-blind trial assessing the effects on gastroduodenal injury, symptoms, and prostaglandin production in healthy volunteers. METHODS Fifty-two healthy volunteers not taking NSAIDs, alcohol, antibiotics, bismuth, or anti-ulcer drugs: placebo, etodolac 400 mg, or naproxen 500 mg b.i.d. for 4 weeks. Endoscopies with biopsies were repeated at weeks 1 and 4. The number and dimensions of ulcers and erosions were recorded to quantitate injury. RESULTS At week 1 the mean number and area of gastric ulcers per subject were greater with naproxen than placebo or etodolac (area: naproxen, 7.4 mm2; placebo, 0.6 mm2, p = 0.02 vs naproxen; etodolac, 2.1 mm2, p = 0.06 vs naproxen). Ulcer scores at week 4 were low and comparable in the three groups. The mean number and area of gastric erosions per subject were greatest with naproxen at both weeks 1 and 4 (week 4 area: naproxen, 58.3 mm2; placebo, 29.0 mm2; etodolac, 13.9 mm2, p < 0.02, naproxen vs placebo and vs etodolac). Placebo injury was presumably due to biopsies at prior endoscopy. Gastric mucosal prostaglandin E2 production did not change significantly from baseline after 1 or 4 weeks of treatment with placebo or etodolac, but did decrease significantly with naproxen (week 0, 1689; week 1, 479; week 4, 577 pg/mg protein). Gastrointestinal symptoms were present in only 1 (5%) of 20 visits in which endoscopy showed no erosions or ulcers vs 21 (26%) of 82 visits in which a mucosal defect was identified (p = 0.666). CONCLUSION Gastric injury with 4 weeks of etodolac is comparable to that seen with placebo and significantly less than that occurring with naproxen, presumably due to the fact that etodolac does not suppress gastric mucosal prostaglandin production, whereas naproxen leads to a significant reduction.

Mucosal concentrations of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α in pelvic ileal pouches

Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) 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-1β 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-α was undetectable in all specimens examined. The concentrations of IL-1β, 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-1β 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 operatesin vivo at the mucosal level in pouchitis as in the case of ulcerative colitis.

Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis

Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed.

Long-term efficacy of bismuth carbomer enemas in patients with treatment-resistant chronic pouchitis

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long‐term complication after ileal pouch‐anal anastomosis for ulcerative colitis. Broad‐spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment‐resistant disease.

The role of the pulmonologist in rapid on-site cytologic evaluation of transbronchial needle aspiration: a prospective study.

BACKGROUND Rapid on-site cytologic evaluation (ROSE) of cytologic specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions. ROSE is not a widespread technique, however, because of a lack of time and resources. Our aim was to verify whether, in comparison with a board-certified cytopathologist, a pulmonologist could evaluate the adequacy of transbronchial needle aspiration (TBNA) specimens on-site to diagnose hilar/mediastinal adenopathies/masses after receiving training in cytopathology. Our secondary aim was to assess and compare the accuracy of ROSE as performed by both physicians. METHODS A pulmonologist and a cytopathologist, the latter deemed the gold standard, performed ROSE and classified specimens into five diagnostic categories. Agreement between clinicians was assessed through κ statistics. The accuracy of ROSE was established according to definitive cytologic assessment. RESULTS A total of 362 TBNAs were performed on 84 patients affected by hilar/mediastinal lymphadenopathies. There was an 81% overall substantial agreement between observers (κ, 0.73; 95% CI, 0.61-0.86; P , 0.001), which became excellent in cases of malignant disease (κ, 0.81; 95% CI, 0.70-0.90; P , 0.001). The accuracy of ROSE performed by the pulmonologist (80%; 95% CI, 77-90) was not statistically different from that provided by the cytopathologist (92%; 95% CI, 85-94). CONCLUSIONS Our study provides the first evidence, to our knowledge, that a trained pulmonologist can assess the adequacy of cytologic smears on-site. Training pulmonologists to have a basic knowledge of cytopathology could obviate most difficulties related to the involvement of cytopathologists in routine diagnostic activities and may reduce the costs of the procedure.

Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis

Background: Rectal treatment with mesalazine enemas is the first‐line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5‐ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema.

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.

Intracolonic Release of Nitric Oxide During Trinitrobenzene Sulfonic Acid Rat Colitis

Nitric oxide is thought to play an importantrole in modulating the inflammatory process. Recently anincrease in the inducible form of nitric oxide synthase(iNOS) has been found in the rat trinitrobenzene sulfonic acid model of experimental colitis,and inhibition of nitric oxide synthase activityresulted in an amelioration of tissue injury. The aim ofour study was to evaluate in vivo intracolonic release of nitric oxide in this model of colitis.Experimental colitis was induced in male Sprague-Dawleyrats by a single intracolonic administration oftrinitrobenzene sulfonic acid. Nitrite levels weredetermined in rectal dialysates by HPLC. The tissuemyeloperoxidase and iNOS and the luminal leukotrieneB4 were also measured. Nitrite levels weresignificantly increased in rectal dialysates duringcolitis and correlated significantly with tissue myeloperoxidase andiNOS activity. The correlation between nitrite dialysatelevels and wall iNOS activity confirms that nitrite indialysates is produced by inflammatory cells and not by colonic bacterial flora.Determination of nitrite levels in rectal dialysatesseems a valuable method to monitor colonic inflammationin rat trinitrobenzene sulfonic acid colitis.

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.