Crohn Disease: Marshall JK

Panaccione R, Fedorak RN, Aumais G, Bernstein CN, Bitton A, Croitoru K, Enns R, Feagan B, Fishman M, Greenberg G, Griffiths A, Marshall JK, Rasul I, Sadowski D, Seidman E, Steinhart H, Sutherland L, Walli E, Wild G, Williams CN, Zachos M, Anonymous00234. · University of Calgary, Calgary, Canada. · Can J Gastroenterol. · Pubmed #15372114 links to  free full text

This publication has no abstract.

Marshall JK. · Department of Medicine, McMaster University, Hamilton, Ontario, Canada. · Curr Opin Investig Drugs. · Pubmed #11566006 No free full text.

Abstract: Millennium (formerly LeukoSite) and Genentech are developing LDP-02, a humanized monoclonal antibody to the alpha4beta7 integrin receptor on leukocytes, for potential use in the treatment of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis [274580]. LeukoSite intended to develop iv and sc formulations of LDP-02 for acute IBD [315156]. In December 1997, Genentech entered into a collaboration with LeukoSite to develop and commercialize LDP-02 for the treatment of IBD [275395], [279420]. A phase II SBIR grant was awarded to LeukoSite in September 1996. The US $750,000 grant was used to develop LDP-02 and to conduct preclinical tests on the antibody for the treatment of IBD [218689]. In February 1999, Lehman Brothers predicted the drug had a 10% probability of reaching market. Assuming a successful launch, Lehman Brothers analysts estimated peak sales would occur in 2011 with sales at that time of US $250 million [319225].

Marshall JK. · McMaster University, Hamilton, Ontario, Canada. · ACP J Club. · Pubmed #18588260 No free full text.

This publication has no abstract.

Marshall JK, Cawdron R, Zealley I, Riddell RH, Somers S, Irvine EJ. · Department of Medicine (Division of Gastroenterology), McMaster University, Hamilton, Ontario, Canada. · Am J Gastroenterol. · Pubmed #15233672 No free full text.

Abstract: BACKGROUND AND AIMS: Both endoscopy and barium radiography are used routinely to diagnose terminal ileal (TI) Crohn's disease (CD). A prospective study was undertaken to compare ileoscopy with biopsy to small bowel meal with pneumocolon (SBMP) in patients with suspected TI CD. METHODS: A cohort of outpatients investigated for diarrhea with features of TI disease underwent SBMP followed by colonoscopy with ileal intubation and biopsy within 21 days. All results were reported in a standardized, sequential format to assign SBMP TI diagnoses by the duty radiologist and by dual reading with consensus, ileoscopy by the attending endoscopist, and ileoscopy with biopsy by a blinded panel of endoscopists and pathologists. Reference standard TI diagnoses were determined by a consensus panel with full access to medical records. RESULTS: Among 120 subjects, the reference standard TI diagnosis was normal in 47 (39.1%), lymphoid nodular hyperplasia (LNH) in 24 (20.0%), CD in 48 (40.0%), and NSAID enteropathy in 1 (0.9%). Colonoscopy provided TI images and/or biopsies in 97 cases (80.8%), while SBMP provided TI images in 119 (99.1%). When ileoscopy with biopsy succeeded, its accuracy was similar to SBMP with dual reading (89.7%vs 89.9%, p = NS) but superior to SBMP if interpreted only by the duty radiologist (80.0%, p < 0.05). Biopsy improved the accuracy of ileoscopy, while dual reading improved that of SBMP. Both ileoscopy with biopsy and SBMP with dual reading are highly accurate for diagnosing TI CD. Choice of initial test should reflect local expertise and availability, and the likelihood of associated disease in the proximal small bowel or colon.

Irvine EJ, Marshall JK. · Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. · Gastroenterology. · Pubmed #11113095 No free full text.

Abstract: Increased intestinal permeability to several specific molecular probes has been observed in patients with Crohn's disease and their first-degree relatives. A positive family history is also a potent risk factor for inflammatory bowel disease. Although it has been argued that increased permeability in relatives may confer an increased future risk of developing Crohn's disease, long-term follow-up of such family members has been lacking. We describe a 24-year-old woman with a positive family history of Crohn's disease who had an elevated gut permeability to (51)Cr-EDTA at age 13, as part of a cross-sectional cohort study in patients and their first-degree relatives. She was asymptomatic at the time, and extensive investigation found no evidence of microscopic or macroscopic Crohn's disease. Repeat investigation because of symptom onset at age 21 revealed ileocolonic Crohn's disease, which required treatment with systemic corticosteroids to induce a clinical remission. In this case, a permeability defect was clearly identified to precede the onset of Crohn's disease in a subject at increased risk. This observation provides support for the hypothesis that increased gut permeability to macromolecules is an early step in the pathogenesis of this disorder.