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Biomedical subjects

S J Bickston

Publications and source records attributed to S J Bickston.

At least 19 recordsLinked to original sources
PubMed2001

Infliximab.

Infliximab (Remicade, Centocor, Inc.) is an intravenously administered monoclonal antibody to TNF proven effective in the treatment of moderate to severe Crohn's disease (CD). Its introduction in October 1998 was heralded by some as the most important addition to therapy for this condition in 50 years. Since then, additional indications have been added as efficacy has been proven in fistulising CD and in rheumatoid arthritis. Even though the costs associated with a single dose are several thousand US dollars, more than 150,000 patients have received infusions since its approval.

Antibodies, Monoclonal↗
PubMed1999

IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells.

IL-18, a novel immunoregulatory cytokine with potent IFN-gamma-inducing activities, may play an important role in Th1-mediated chronic inflammatory disorders. The aim of the present study was to characterize the expression and localization of IL-18 in colonic specimens and isolated mucosal cell populations from patients with Crohn's disease (CD), a prototypic Th1-mediated disorder. Using a semiquantitative RT-PCR protocol, IL-18 mRNA transcripts were found to be increased in freshly isolated intestinal epithelial cells (IEC) and lamina propria mononuclear cells (LPMC) from CD compared with ulcerative colitis (UC) and noninflamed control (cont) patients, and were more abundant in IEC compared with LPMC. Immunohistochemical analysis of surgically resected colonic tissues localized IL-18 to both LPMC (specifically, macrophages and dendritic cells) as well as IEC. Staining was more intense in CD compared with UC and cont, and in involved (inv) vs noninvolved (n inv) areas. Western blot analysis revealed that an 18. 3-kDa band, consistent with both recombinant and mature human IL-18 protein, was found predominantly in CD vs UC intestinal mucosal biopsies; a second band of 24 kDa, consistent with the inactive IL-18 precursor, was detected in n inv areas from both CD and UC biopsies and was the sole form found in noninflamed cont. To our knowledge, this report is the first describing increased expression of IL-18 in a human Th1-mediated chronic inflammatory disease. In addition, our studies further support the concept that IEC and dendritic cells may possess important immunoregulatory functions in both normal, as well as pathological, mucosal immunity.

Adjuvants, Immunologic↗
PubMed1999

The relationship between infliximab treatment and lymphoma in Crohn's disease.

The relationship between chronic inflammatory conditions and malignancy is complex. We describe the clinical course of 2 patients with Crohn's disease (CD) in whom lymphoma was diagnosed after treatment with infliximab. The first patient was a 61-year-old man with a 30-year history of fistulizing CD in whom B-cell non-Hodgkin's lymphoma was diagnosed 9 months after treatment with infliximab. The second is a 29-year-old man with CD in whom nodular sclerosing Hodgkin's lymphoma was diagnosed 3 weeks after infusion with infliximab. The lymphoma presented with pleural effusions, mediastinal and cervical adenopathy, and no gastrointestinal lesion. We describe the implications of these cases for the use of immunomodulatory therapy in CD and the questionable association between CD and lymphoma.

Adult↗
PubMed1996

Characteristics of the propagating pressure wave in the esophagus.

Understanding the relationships of intraluminal manometric events to bolus transit through the esophagus has been limited by conventional manometric analysis methods. We reconstructed pressure events in the axial direction in order (1) to describe the peristaltic pressure wave as it propagates through the esophagus in the direction of the bolus and (2) to determine what sampling interval along the esophageal length is required for accurate representation. Esophageal manometric studies using the stepwise withdrawal method were performed in 10 asymptomatic volunteers. Propagating wave forms were created at 0.2-sec intervals and analyzed in static and dynamic fashion from averaged waves at each 1-3 cm of esophageal length. A distinctive and similar appearance to the propagating wave form, comprised of three sequential but overlapping contraction segments in the esophageal body, was present in nine subjects. The propagating wave decelerated as it approached the second region (smooth-muscle esophagus) and extended over as much as 15.1+/-0.7 cm of esophageal length. No significant differences in wave front propagation, length, or velocity could be determined if the sampling interval increased from 1 to 3 cm of esophageal length, but peak amplitudes were reduced by as much as 14.2%. We conclude that the esophageal pressure wave, when viewed in the direction of bolus transit, is broad and typically comprised of three sequential contraction components. Sampling at >1-cm intervals along the esophageal length significantly alters the wave appearance and may be unsatisfactory in the distal esophagus. Axial transformations of manometric data potentially will provide better information concerning the neuromuscular control of peristalsis and events responsible for bolus movement.

Adult↗