Review and clinical perspectives for the use of infliximab in ulcerative colitis.

Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn's disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn's disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members' clinical experiences.

Rectal tissue, plasma and urine concentrations of mesalazine after single and multiple administrations of 500 mg suppositories to healthy volunteers and ulcerative proctitis patients.

OBJECTIVE: Patients with ulcerative proctitis may have rectal mucosal properties different from healthy volunteers. This project compared the pharmacokinetics of rectally administered mesalazine in these two populations. METHODS: In two separate studies, nine patients with ulcerative proctitis and 16 healthy volunteers received a single 500 mg mesalazine suppository and then 500 mg every 8 h for 5 days. Blood samples were collected for 12 h in healthy volunteers and 30 h in patients, and urine for 24 h in healthy volunteers and 30 h in patients. Rectal biopsies were performed 8 h after the last dose. RESULTS: After a single dose to patients, mean mesalazine half-life (s.d.) was 5.0 (3.6) h. At steady-state, means (s.d.) were 89.1 (78.9) ng/mL for C(min), 361.1 (240.8) ng/mL for C(max), and 7.1 (7.3) h for half-life. Mean (range) rectal mesalazine concentrations were 167 (1.4-541.6) ng/mg tissue. After a single dose in healthy volunteers, mean (s.d.) half-life was 4.0 (4.7) h. At steady-state, means (s.d.) were 22.4 (61.6) ng/mL for C(min), 359.4 (166.3) ng/mL for C(max), and 0.9 (0.5) h for half-life. CONCLUSION: Mesalazine is released in the rectum of patients, with a bioavailability of about 40%. Tissue distribution is also appreciable. Both parameters appear higher than in healthy volunteers.

[Endoscopic YAG laser and palliative therapy of cancer of the esophagus]. / Le laser YAG endoscopique et la thérapie palliative du cancer de l'oesophage.

In our institution, the YAG laser has been used to treat 110 patients with inoperable esophageal carcinoma. Therapy was palliative as patients presented metastases (41.8%), advanced systemic disease (22.7%), extensive local disease (18.2%) or recurrent carcinoma (10%). The study group included 92 men (mean age 68.4 years) and 18 women (mean age 67.0 years); 47.3% of the patients had received no previous treatment while 52.7% had been treated previously with either radiotherapy, chemotherapy, surgery, stents or dilatation. The majority of lesions were adenocarcinomas (57.3%) with squamous cell carcinomas in 37.3%; 66.3% of cancers were located in the distal third of the esophagus. The patients received a mean of 2.4 laser treatments with 4883 joules per treatment on average. The rate of major complications was 2.7% and the rate of mortality 1.8%. The median survival for the group was 4.5 months. No significant difference was found in the length of survival according to the histology of the tumour (p = 0.35), the presence of metastases (p = 0.24) and the association of other treatment modalities with the laser (p = 0.06). Functional results were considered good to excellent in 82.1% of cases. In conclusion, the YAG laser does not influence overall survival of inoperable patients, but this therapy is effective and safe and is presently the treatment of choice for these patients.

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis.

Association mapping and candidate gene studies within inflammatory bowel diseases (IBD) linkage regions, as well as genome-wide association studies in Crohn's disease (CD) have led to the discovery of multiple risk genes, but these explain only a fraction of the genetic susceptibility observed in IBD. We have thus been pursuing a region on chromosome 3p21-22 showing linkage to CD and ulcerative colitis (UC) using a gene-centric association mapping approach. We identified 12 functional candidate genes by searching for literature cocitations with relevant keywords and for gene expression patterns consistent with immune/intestinal function. We then performed an association study composed of a screening phase, where tagging single nucleotide polymorphisms (SNPs) were evaluated in 1,020 IBD patients, and an independent replication phase in 745 IBD patients. These analyses identified and replicated significant association with IBD for four SNPs within a 1.2 Mb linkage disequilibrium region. We then identified a non-synonymous coding variant (rs3197999, R689C) in the macrophage-stimulating 1 (MST1) gene (P-value 3.62 x 10(-6)) that accounts for the association signal, and shows association with both CD and UC. MST1 encodes macrophage-stimulating protein (MSP), a protein regulating the innate immune responses to bacterial ligands. R689C is predicted to interfere with MSP binding to its receptor, suggesting a role for this gene in the pathogenesis of IBD.

Endoscopic Nd:YAG laser therapy of malignant esophageal obstruction on an outpatient basis.

Between May 1985 and December 1988, 41 patients were treated palliatively with endoscopic neodymium:yttrium-aluminum-garnet laser therapy for obstruction of the esophagus by malignant disease. All were considered incurable, because they presented with distant metastases, severe systemic disease, extensive local disease or recurrent disease. Thirty-nine percent were managed as outpatients; the remainder required admission to hospital. Sixty-three percent of the outpatients had adenocarcinoma, and 31% had squamous cell carcinoma; over 90% of the tumours were less than 8 cm long, and 63% were in the distal one-third of the esophagus or the cardia. Forty-four percent of the inpatients had adenocarcinoma, and 44% had squamous cell carcinoma; in this group, over 90% of the tumours were less than 8 cm long, and 56% were in the distal one-third of the esophagus or the cardia. The mean number of sessions and laser energy administered were 2.6 and 4949 J for outpatients and 2.7 and 4974 J for inpatients. Palliation of dysphagia was good to excellent in all outpatients but was not as good for the inpatient group, in which one major complication occurred. The mean length of survival for outpatients and inpatients was 6.3 months (range from 1 to 16 months) and 3.9 months (range from 1 to 18 months) respectively.