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Biomedical subjects

W J Sandborn

Publications and source records attributed to W J Sandborn.

At least 55 records · Page 3Linked to original sources
PubMed2001

Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study.

We report the experience of 11 patients (of 60 planned patients) enrolled in a double-blind, placebo-controlled clinical trial of infliximab in patients with severe, active steroid-refractory ulcerative colitis. The study was terminated prematurely because of slow enrollment. Patients having active disease for at least 2 weeks and receiving at least 5 days of intravenous corticosteroids were eligible to receive a single intravenous infusion of infliximab at 5, 10, or 20 mg/kg body weight. The primary endpoint used in this study was treatment failure at 2 weeks after infusion. Treatment failure was defined as 1) unachieved clinical response as defined by a modified Truelove and Witts severity score, 2) increase in corticosteroid dosage, 3) addition of immunosuppressants, 4) colectomy, or 5) death. Safety evaluations included physical examination, clinical chemistry and hematology laboratory tests, and occurrence of adverse experiences. Four of 8 patients (50%) who received infliximab were considered treatment successes at 2 weeks, compared with none of 3 patients who received placebo. Improvement in erythrocyte sedimentation rates and serum concentrations of C-reactive protein and interleukin-6 correlated with the clinical response observed in patients receiving infliximab. Infusion with infliximab produced no significant adverse events. Infliximab was well tolerated and may provide clinical benefit for some patients with steroid-refractory ulcerative colitis.

Adrenal Cortex Hormones↗
PubMed2001

Crohn's disease of the esophagus: clinical features and outcomes.

OBJECTIVES: Crohn's disease of the esophagus is rare. We sought to determine the clinical features and outcome of patients with esophageal Crohn's disease seen at our institution. METHODS: Patients with esophageal Crohn's disease evaluated at Mayo Clinic Rochester between 1976 and 1998 were identified. RESULTS: Twenty patients (0.2%) with esophageal involvement were identified. Median age at diagnosis was 31 years (range, 7-77 years). Eleven patients (55%) were female. Extraesophageal Crohn's disease preceded or was found at the same time as the diagnosis of esophageal Crohn's in all cases. Sixteen patients (80%) had symptoms referable to the esophagus. Endoscopic findings included ulcers in 17 (85%), erythema or erosions in 8 (40%), and strictures in 4 patients (20%). One patient had a fistula. The most common histological findings were active chronic inflammation (75%) and ulcer (30%). No granulomata were identified. Approximately one-half of our patients improved with first-line therapy. Eleven patients (55%) received immune modifier therapy. Six showed significant improvement on azathioprine, 6-mercaptopurine, or cyclosporine. Esophageal dilatation was required in six patients, and three patients required surgery. CONCLUSION: Esophageal Crohn's disease may be underdiagnosed. Patients with Crohn's disease complaining of esophageal symptoms should undergo upper endoscopy with biopsies, and the diagnosis of esophageal Crohn's disease should be entertained if aphthous or deep ulcers or strictures are present. Immune modifier therapy should be considered for steroid-dependent and steroid-resistant cases.

Adolescent↗
PubMed2001

Evaluation of serologic disease markers in a population-based cohort of patients with ulcerative colitis and Crohn's disease.

BACKGROUND: The sensitivity of assays for antineutrophil cytoplasmic antibody (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), and antipancreatic antibody (PAB) in different laboratories is unknown. Likewise, the sensitivity and diagnostic usefulness of these assays in patients with inflammatory bowel disease (IBD) in the community is unknown. METHODS: An incidence cohort of 290 patients with IBD were offered participation in the study. Blood was obtained from 162 patients (56%) (83 with ulcerative colitis, 79 with Crohn's disease) who agreed to participate. ANCA was determined in five laboratories. ASCA in two laboratories, and PAB in one laboratory. RESULTS: In ulcerative colitis, the sensitivity of ANCA determined in five laboratories varied widely, ranging from 0-63%. In Crohn's disease, the sensitivity of ASCA determined in two laboratories did not vary significantly, ranging from 39-44%; and the sensitivity of PAB determined in one laboratory was 15%. The optimal diagnostic usefulness was obtained from one laboratory where the positive predictive values of a positive ANCA assay combined with a negative ASCA assay for ulcerative colitis, and a negative ANCA combined with a positive ASCA for Crohn's disease, were 75% and 86%, respectively. CONCLUSIONS: In patients with IBD, the sensitivity of ANCA varied widely in different laboratories, whereas the prevalence of ASCA was similar. The positive predictive values of the ANCA assay combined with the ASCA assay for ulcerative colitis and Crohn's disease are high enough to be clinically useful.

Adolescent↗
PubMed2001

Epidemiology of inflammatory bowel disease in Asia.

Studies of Asians in Asia show relatively low incidence rates for ulcerative colitis and Crohn's disease compared with North America and Europe. The prevalence of ulcerative colitis in migrant South Asians in Europe is similar to Europeans, whereas the prevalence of Crohn's disease for migrant South Asians in Europe is decreased compared with Europeans. The prevalence for both ulcerative colitis and Crohn's disease in Japan and Korea is relatively low. There are no obvious differences in age or sex distribution or rates of familial aggregation, and there are no significant differences in the clinical characteristics and natural history of ulcerative colitis and Crohn's disease in Asians compared with other racial groups with inflammatory bowel disease.

Age Distribution↗
PubMed2001

Infliximab for Crohn's disease in clinical practice at the Mayo Clinic: the first 100 patients.

OBJECTIVE: The aim of this study was to report the clinical outcome and adverse events in the first 100 patients with refractory inflammatory and/or fistulizing Crohn's disease treated with infliximab at the Mayo Clinic. METHODS: Patient data was abstracted from medical records. Clinical response was classified as complete response, partial response, and nonresponse. RESULTS: Indications for infliximab therapy were: inflammatory disease (61 patients), fistulizing disease (26 patients), or both (13 patients). Patients received one to seven infusions of infliximab (5 mg/kg) for a total of 242 infusions. In all, 50 patients had complete response, 22 had partial response, and 28 had nonresponse. Median time to response was 7 days (range 1-21 days). Median duration of response was 10.3 weeks (range 3-25 wk). A total of 95 patients received concomitant treatment with immune modifiers. Steroid withdrawal was possible in 29/40 patients (73%). Median time of follow-up was 34 wk (range 14-48 wk). Clinically significant adverse events after infliximab included: abscess formation in two patients (perianal, peristomal), pneumonia in two patients, varicella zoster in three patients, candida esophagitis in one patient, and infusion-related reactions in 19 patients. A total of 23 patients were continued on infliximab as maintenance treatment. CONCLUSIONS: This study provides additional evidence that infliximab is safe and beneficial in clinical practice for refractory Crohn's disease.

Adolescent↗
PubMed2001

Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis.

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP). METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale. RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group. CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.

Adult↗
PubMed2001

Cigarette smoking and celiac sprue: a case-control study.

OBJECTIVE: Environmental factors other than gliadin exposure and certain HLA haplotypes may play a role in the pathogenesis of celiac disease. Previous studies have suggested a strong inverse relationship between cigarette smoking and celiac disease. We sought to determine the relationship between celiac disease and cigarette smoking in our patient population. METHODS: All newly diagnosed adults with biopsy-proven celiac disease evaluated at Mayo Clinic Rochester between January 1, 1993, and June 30, 1998, were identified. Three clinic patients who were matched to each case on geographical area of residence, age, gender, and calendar year of visit served as controls. Smoking information was obtained from a standard medical questionnaire that was completed by all clinic patients at the time of registration. The adjusted odds ratio for celiac disease in current and former smokers relative to nonsmokers was estimated with a matched three-to-one conditional logistic regression model. RESULTS: A total of 82 adults with biopsy-proven celiac disease were identified. At the time of diagnosis, the proportion of current smokers was 10% in cases and 10% in controls, yielding an adjusted odds ratio of 1.5 (95% CI = 0.5-4.3). In all, 34% of cases were former smokers versus 28% of controls, yielding an odds ratio of 1.6 (95% CI = 0.8-3.2). CONCLUSION: This case-control study was unable to detect an association between cigarette smoking and celiac disease.

Adult↗
PubMed2001

A prospective cohort study of practice guidelines in inflammatory bowel disease.

OBJECTIVES: Practice guidelines should improve care, but they are not routinely followed, in part because of lack of proven benefit. We evaluated the effect of introducing guidelines for inflammatory bowel disease (IBD) on practice variation and the IBD Quality of Life (IBDQ) score. METHODS: This was a prospective, controlled, cohort study. A total of 65 patients were matched according to month of visit, diagnosis, and disease activity with control subjects seen 1 yr earlier. Physicians were educated throughout the study regarding the guidelines. Variation was measured by the Mayo Practice Guideline Score (MPGS), a 15-point assessment of documentation of diagnosis, nutrition, social support, education, functional status, and treatment. The IBDQ was measured at baseline and at 1 yr in the intervention group and after 1 yr in the control group. RESULTS: The MPGS was significantly higher in the intervention group compared to the controls (p = 0.002), with median values of 12 versus 11. The IBDQ median score increased significantly in the intervention group (p < 0.001), baseline median of 133 versus 15-month median of 184. However, the final IBDQ was not significantly higher in the intervention group than in the controls (p = 0.33). CONCLUSIONS: Practice guidelines for IBD reduce practice variation. The quality of life improved significantly compared to baseline with practice guidelines, but not compared to controls, perhaps because of the small sample size and homogenous practice setting. The MPGS is a tool that can be used in day-to-day management of IBD patients.

Adult↗
PubMed2001

Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide.

AIM: We evaluated the effect of coadministration of sulphasalazine, mesalamine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine. METHODS: Thirty four patients with Crohn's disease receiving azathioprine or 6-mercaptopurine were enrolled in an eight week non-randomised parallel group drug interaction study and treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts < 3.0 x 10(9)/l and < or = 3.5 x 10(9)/l. Whole blood 6-thioguanine nucleotide concentrations were determined. RESULTS: Three patients could not be evaluated for the primary outcome measure. In the remaining 31 patients, the frequency of total leucocyte counts < 3.0 and < or = 3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group. There were significant increases in mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points in the mesalamine and sulphasalazine groups but not in the balsalazide group. CONCLUSIONS: In patients with Crohn's disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thioguanine nucleotide concentrations and a high frequency of leucopenia.

Adult↗
PubMed2001

Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease.

BACKGROUND: Measurement of 6-thioguanine nucleotide concentrations may be useful for optimising treatment with azathioprine and 6-mercaptopurine. METHODS: We conducted a study of 170 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between 6-thioguanine nucleotide concentrations and both disease activity, as measured by the inflammatory bowel disease questionnaire (active disease < 170, remission > or = 170) and leucopenia. Blood was submitted for whole blood 6-thioguanine nucleotide concentration and leucocyte count. RESULTS: Mean (SD) inflammatory bowel disease questionnaire score was 176 (32). There was no correlation between inflammatory bowel disease questionnaire scores and 6-thioguanine nucleotide concentrations (r(s) = -0.09, p = 0.24). Median 6-thioguanine nucleotide concentrations in 56 patients with active disease and 114 patients in remission were similar (139 v 131 pmol/8 x 10(8) red blood cells; p = 0.26). There was no correlation between 6-thioguanine nucleotide concentrations and leucocyte counts. CONCLUSIONS: In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, 6-thioguanine nucleotide concentrations did not correlate with disease activity, as measured by the inflammatory bowel disease questionnaire, or leucocyte count. These findings are discrepant with most previous studies, possibly due to selection of responding patients who tolerated the medications. A prospective, randomised, dose optimisation trial using 6-thioguanine nucleotide concentrations is warranted.

Adolescent↗
PubMed2000

Clinical outcome and pharmacokinetics after addition of low-dose cyclosporine to methotrexate: a case study of five patients with treatment-resistant inflammatory bowel disease.

INTRODUCTION: This study reports the clinical outcome, toxicity, and methotrexate pharmacokinetics after the addition of low-dose cyclosporine to methotrexate in patients with ulcerative colitis or Crohn's disease. METHODS: Three patients with steroid-refractory ulcerative colitis and two patients with steroid refractory Crohn's disease who failed monotherapy with subcutaneous methotrexate 25 mg/week for 16 weeks were treated with the combination of methotrexate and low-dose oral cyclosporine (3 mg/kg/day) for an additional 16 weeks. Clinical response was measured with the Inflammatory Bowel Disease Questionnaire (IBDQ) score. Concentrations of erythrocyte methotrexate, plasma methotrexate, and plasma 7-hydroxymethotrexate were also determined. RESULTS: Both patients with Crohn's disease withdrew from the study for toxicity (headaches, seizure). The three patients with ulcerative colitis experienced clinical improvement with a mean increase in the IBDQ score from 164 to 190 points, p = 0.01. The mean serum creatinine in the three patients who completed the study increased from 0.9 mg/dL at baseline to 1.2 mg/dL at week 16. p = 0.04. One patient developed hypertension. There was no significant change from baseline in the concentrations of erythrocyte methotrexate, plasma methotrexate, and plasma 7-hydroxymethotrexate. CONCLUSIONS: Combination therapy with methotrexate and low-dose oral cyclosporine did not alter methotrexate pharmacokinetics and resulted in high rates of cyclosporine-associated toxicity.

Colitis, Ulcerative↗
PubMed2000

Clinical pharmacology of inflammatory bowel disease therapies.

Knowledge about the clinical pharmacology of medical therapy of inflammatory bowel disease has incrementally advanced. Small studies with mesalamine have suggested that intestinal mucosal concentrations of mesalamine may predict clinical response to mesalamine therapy. Increased expression of glucocorticoid receptor beta and increased expression of the multidrug resistance drug pump P-glycoprotein 170 have been proposed as markers of drug resistance to glucocorticoids. A baseline determination of thiopurine methyltransferase phenotype or genotype may predict early leukopenia in patients treated with azathioprine or 6- mercaptopurine. Serial measurement of erythrocyte 6-thioguanine nucleotides may be useful in tailoring the dose of these medications. A loading dose of intravenous azathioprine does not accelerate the time to response in patients with steroid-treated Crohn's disease; however, standard azathioprine may work more quickly than previously reported. Methotrexate, 15 to 25 mg/wk, is effective for the treatment of Crohn's disease (active or in remission), and there is no significant difference in the erythrocyte concentrations of methotrexate polyglutamate in patients with inflammatory bowel disease receiving 15 mg, compared with 25 mg, subcutaneously on a weekly basis.

Adrenal Cortex Hormones↗
PubMed2000

Therapy for Crohn disease.

Medical therapy for Crohn disease has advanced incrementally: Small, non-definitive controlled trials of mesalamine continue to be reported, but the results are not sufficient to change the conclusion of a large meta-analysis that shows only marginal benefit of mesalamine in Crohn disease. Low-dose, controlled ileal-release budesonide is not effective for preventing postoperative recurrence of Crohn disease. A loading dose of intravenous azathioprine does not accelerate the time to response in patients with steroid-treated Crohn disease; however, standard azathioprine may work more quickly than previously reported. Mycophenolate mofetil may be therapeutically equivalent to azathioprine for active Crohn disease. There is a trend toward benefit of oral methotrexate (15 mg/wk) for active Crohn disease, and there is no significant difference in the blood concentrations of methotrexate in patients with inflammatory bowel disease who receive methotrexate (15 or 25 mg weekly) administered subcutaneously. Results in a pilot study suggest that tacrolimus may close perianal fistulas in patients with Crohn disease. The anti-tumor necrosis factor antibody infliximab is effective in closing perianal and enterocutaneous fistulas and in maintaining remission in patients with Crohn disease. Infliximab also leads to endoscopic and histologic remission. There is a trend toward benefit of subcutaneous recombinant interleukin-11 for active Crohn disease. Two pilot studies have shown that thalidomide may be of benefit in patients with refractory Crohn disease.

Journal Article↗
PubMed2000

A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998.

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.

Adult↗
PubMed2000

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10.

BACKGROUND: Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil recruitment and is down-regulated by IL-10. AIM: To look for an imbalance between IL-8 and IL-10 in patients with pouchitis. PATIENTS/METHODS: 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of > or =7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction. RESULTS: IL-8, IL-10, and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01). CONCLUSION: Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for pouchitis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Early measles virus infection is associated with the development of inflammatory bowel disease.

OBJECTIVE: The measles virus has been implicated as a possible etiological agent in the development of inflammatory bowel disease (IBD). Measles infection at an early age is associated with subacute sclerosing panencephalitis, a degenerative neurological condition caused by persistent measles infection of the central nervous system. We sought to determine whether infection with measles virus at an early age was also associated with an increased risk of developing IBD. METHODS: Patients with measles infection diagnosed before the age of 5 yr were identified through the diagnostic indices of the Mayo Clinic and the Rochester Epidemiology Project. A questionnaire was used to ascertain a subsequent history of IBD, which was confirmed by records from the subjects' physicians. The risks of developing Crohn's disease and ulcerative colitis were calculated relative to expected rates for these conditions in the Olmsted County, Minnesota population. RESULTS: Of 1164 eligible cases, 662 (57%) completed the questionnaire. There were six confirmed cases of Crohn's disease and six of ulcerative colitis. The expected number of cases was 1.9 for Crohn's disease (standardized incidence ratio [SIR] 3.1, 95% confidence interval [CI] 1.1-6.8) and 2.0 for ulcerative colitis (SIR 3.0, CI 1.1-6.5). There was a trend towards a higher risk of developing IBD with an earlier age of infection. CONCLUSIONS: Early measles infection is associated with an increased risk of developing Crohn's disease and ulcerative colitis. The risk may be higher with earlier infection.

Aging↗