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Biomedical subjects

W J Sandborn

Publications and source records attributed to W J Sandborn.

143 records · Page 8Linked to original sources
PubMed1995

Collagenous and lymphocytic colitis: subject review and therapeutic alternatives.

OBJECTIVE: To review the published studies on collagenous and lymphocytic (microscopic) colitis with specific emphasis on clinical features, investigational studies, characteristic histology, possible pathogenesis, disease course, and empirical treatment. DESIGN: Comprehensive synopsis of the stated objective, prepared for the physician treating patients with collagenous or lymphocytic colitis. MATERIALS AND METHODS: The medical literature on collagenous and lymphocytic colitis. RESULTS: Collagenous and lymphocytic colitis are chronic diarrheal illnesses of indeterminate etiology that typically present in the late sixth or early seventh decade of life. These disorders may be distinct entities, although some data support the idea that they are only different manifestations of the same disease. The pathogenesis is unknown but may be on an inflammatory, possibly autoimmune, basis. Physical examination and investigational studies are normal or nonspecific, with fecal leukocytosis the only abnormality found in the majority of patients tested. Association with various gastrointestinal, autoimmune, and rheumatologic conditions has been observed in some patients. Clinical and occasional histologic response has been observed after treatment with anti-inflammatory agents such as 5-aminosalicylate and corticosteroids, and should be used when there is no response to symptomatic therapy. CONCLUSIONS: Collagenous and lymphocytic colitis are uncommon but important causes of chronic diarrhea which are important to diagnose and treat.

Algorithms↗
PubMed1995

Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal pouch-anal anastomosis.

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies, present in 60% of patients with ulcerative colitis, may be a marker for a genetically distinct subset of patients who develop chronic pouchitis after undergoing ileal pouch-anal anastomosis. The frequency of these antibodies in chronic pouchitis was determined. METHODS: Four groups were studied: patients who underwent ileal pouch-anal anastomosis for colitis with and without chronic pouchitis, familial polyposis without pouchitis and ileostomy for colitis. Antineutrophil cytoplasmic antibody levels and titers were detected by ELISA, and positive results were confirmed by perinuclear staining with indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies in chronic pouchitis (100%) was significantly greater than in colitis (50%) or familial polyposis (0%) without pouchitis and colitis with an ileostomy (70%); p = 0.00, 0.00, and 0.01, respectively. CONCLUSIONS: The finding that perinuclear antineutrophil cytoplasmic antibodies occur more frequently in patients with chronic pouchitis raises the possibility that this antibody may mark a genetically distinct subset of ulcerative colitis patients. Further studies are needed to determine whether the presence of this antibody before ileal pouch-anal anastomosis is predictive for later development of chronic pouchitis.

Adenomatous Polyposis Coli↗
PubMed1995

Pouchitis disease course after orthotopic liver transplantation in patients with primary sclerosing cholangitis and an ileal pouch-anal anastomosis.

OBJECTIVE: Primary sclerosing cholangitis is associated with the development of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. This study determined the effect of liver transplantation for primary sclerosing cholangitis on the disease course of pouchitis. METHODS: Seven patients with an ileal pouch-anal anastomosis for ulcerative colitis underwent liver transplantation for primary sclerosing cholangitis. The medical record was reviewed to determine the pouchitis activity and pattern (no pouchitis, single acute, recurrent acute, chronic) before and after transplantation. RESULTS: Five of seven patients had pouchitis before transplant [recurrent acute (n = 3), chronic (n = 2)], and four of those five continued to have pouchitis after transplant (all chronic). Pretransplant sera were positive for antineutrophil cytoplasmic antibody in 6/6 patients, compared to 5/6 patients posttransplant. One patient with pouchitis pretransplant became negative for antineutrophil cytoplasmic antibody posttransplant but continued to have pouchitis. CONCLUSION: Pouchitis occurs frequently in patients with primary sclerosing cholangitis and an ileal pouch-anal anastomosis for ulcerative colitis. Liver transplantation does not alter the disease course of pouchitis for most of these patients.

Adult↗
PubMed1994

A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis.

BACKGROUND/AIMS: Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration. The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed. METHODS: Steroid and mesalamine enemas were withdrawn before the study. Forty patients were assigned to 1 of 4 strata: no concomitant therapy, oral steroids, oral salicylates, or oral steroids and salicylates. After stratification, patients were randomized to nightly treatment with 350 mg cyclosporine (n = 20) or placebo (n = 20) enemas. Clinical response was determined at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Trough blood cyclosporine levels were measured by high-performance liquid chromatography. RESULTS: At 4 weeks, 8 of 20 patients (40%) who received cyclosporine showed clinical improvement compared with 9 of 20 patients (45%) who received placebo. One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine, and another patient receiving cyclosporine was unable to tolerate the enema vehicle. No other toxicity was noted during the trial. Blood cyclosporine levels were detectable in only two patients. CONCLUSIONS: Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis.

Administration, Oral↗
PubMed1994

Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index.

OBJECTIVE: To develop a "Pouchitis Disease Activity Index" (PDAI) and to compare it with other diagnostic scoring systems for pouchitis. DESIGN: We compared patients who had an optimal outcome with those who had a poor result attributable to recurrent pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis at the Mayo Clinic. MATERIAL AND METHODS: We evaluated the applicability of a PDAI that quantitated clinical findings and the endoscopic and histologic features of acute inflammation in four groups of patients: (1) 10 who underwent IPAA for ulcerative colitis and had symptoms compatible with a clinical diagnosis of pouchitis, (2) 5 who underwent IPAA for ulcerative colitis and did not have pouchitis, (3) 5 who underwent IPAA for familial adenomatous polyposis and had no symptoms of pouchitis, and (4) 5 who had a Brooke ileostomy for ulcerative colitis (control group). RESULTS: The PDAI was significantly greater in patients with the clinical features of pouchitis than it was for patients in the other three groups. All 10 patients with pouchitis fulfilled the PDAI criteria for a diagnosis of pouchitis; in contrast, only 1 of these 10 patients met the diagnostic criteria for pouchitis by application of previously established scoring systems. No asymptomatic patient qualified for a diagnosis of pouchitis by the PDAI criteria. CONCLUSION: The PDAI provides simple, objective, and quantitative criteria for pouch inflammation after IPAA and is more sensitive than prior scoring systems.

Adenomatous Polyposis Coli↗
PubMed1994

Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does not result in sustained improvement in kidney function and causes cellular and ductopenic rejection.

Twelve consecutive liver transplant recipients with stable allograft function and cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an attempt to halt and possibly reverse renal damage. Only patients who met the following criteria were included: (a) triple immunosuppression with cyclosporine, azathioprine and prednisone; (b) stable graft function for at least 1 yr without rejection; and (c) serum creatinine greater than 2.1 mg/dl or renal clearance less than 35 ml/min. Cyclosporine was reduced by 50 mg every 3 wk until discontinuation, prednisone was temporarily increased from 10 to 20 mg/day and azathioprine was maintained at 2 mg/kg/day. Sustained improvement in kidney function in the 12 patients was minimal, with the mean serum creatine level decreasing from 2.5 +/- 0.5 mg/dl (mean +/- S.D.) at study entry to 2.4 +/- 1.2 mg/dl after a mean follow-up of 18 +/- 6 mo. In six patients, histologically confirmed cellular rejection developed after a mean of 5 +/- 6 mo from the time that cyclosporine withdrawal was begun. Two of six patients with rejection responded to bolus steroid therapy and are in stable condition at this writing with low-dose cyclosporine (2.8 and 3.2 mg/kg/day). Two patients initially responded to bolus steroids but later exhibited ductopenic rejection; one responded to treatment with FK 506 and the other died of sepsis. The two remaining patients were steroid unresponsive. One responded to treatment with OKT3 and is now stable on low-dose cyclosporine (2.3 mg/kg/day), but in the other ductopenic rejection developed and the patient died of sepsis during rescue therapy with FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1993

High-volume postobstructive choleresis after transhepatic external biliary drainage resolves with conversion to internal drainage.

We report high-volume postobstructive choleresis in two patients who underwent transhepatic external drainage for malignant biliary obstruction. Excessive loss of bicarbonate-rich biliary fluid (up to 6.5 L/day) caused orthostatic hypotension, prerenal insufficiency, hyponatremia, and a decrease in serum bicarbonate. Therapy with isotonic fluids containing sodium, chloride, lactate, bicarbonate, and potassium was based on measurement of biliary fluid volume and electrolyte concentrations. Biliary fluid loss was terminated by conversion to internal biliary drainage. The reason for this rare complication of external drainage of biliary obstruction is unknown, but such patients must be closely monitored for volume loss. When high-volume choleresis occurs, biliary fluid and electrolyte losses should be precisely measured and replaced, and external biliary drainage converted to internal drainage.

Adenocarcinoma↗
PubMed1993

Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin.

Thirty five adult patients with precirrhotic primary sclerosing cholangitis were randomly allocated to treatment for at least one year with low dose (4.1 mg/kg/day) cyclosporin or placebo in a double blind trial. Thirty patients had coexisting ulcerative colitis, including three who had previously undergone colectomy and one who discontinued treatment after three months. Of the remaining 26 patients, 16 received cyclosporin and 10 received placebo. Endoscopy was performed at entry to confirm the diagnosis of inflammatory bowel disease. The ulcerative colitis disease activity was prospectively classified annually as remission/mild, moderate, or severe using the Truelove and Witt's criteria. Before treatment there were no differences between the cyclosporin and placebo groups in the number of patients with remission/mild colitis, 14/16 (88%) v 9/10 (90%), and moderate colitis, 2/16 (12%) v 1/10 (10%). During treatment, a remission/mild disease course was present in 15/16 (94%) v 6/10 (60%), p = 0.05 and a moderate disease course in 1/16 (6%) v 4/10 (40%), p = 0.05. It is concluded that patients treated with cyclosporin for primary sclerosing cholangitis who have coexisting ulcerative colitis have a more benign course of colitis resulting both from improvement of moderately active colitis and from fewer flares of remission/mildly active colitis. These findings suggest that cyclosporin may be of benefit to the colon in patients with ulcerative colitis who are being treated with cyclosporin for primary sclerosing cholangitis.

Adult↗
PubMed1993

Cyclosporine enemas for treatment-resistant, mildly to moderately active, left-sided ulcerative colitis.

Ten patients with treatment-resistant left-sided ulcerative colitis were treated in an open protocol with 350 mg cyclosporine enemas nightly for 4 wk. A 12-point clinical disease activity index (DAI) score was calculated at baseline and after 4 wk. Whole blood and colonic tissue cyclosporine concentrations were determined by HPLC at the end of the study. Five of 10 patients responded to treatment, defined as a decrease in the clinical DAI score > or = 3 points. Responders retained the enemas longer than nonresponders (7.5 +/- 1.3 vs. 3.3 +/- 2.2 h, p = 0.01), and there was a positive correlation between decrease in the clinical DAI score and enema retention time (r = 0.64, p = 0.05). The mean colonic tissue cyclosporine concentration was not significantly higher in responders than in nonresponders (2884 +/- 1635 vs. 2359 +/- 576 ng/g, p = 0.52), and the correlation between decrease in the clinical DAI score index and colonic tissue cyclosporine was weak (r = 0.39, p = 0.26). Cyclosporine was undetectable in whole blood samples from all patients, and there were no apparent side effects with treatment. In conclusion, 50% of patients with treatment-resistant left-sided ulcerative colitis significantly improved during therapy with cyclosporine enemas for 4 wk. Patients with longer enema retention times were more likely to respond. A controlled trial is underway to investigate these findings further.

Administration, Topical↗
PubMed1992

Hepatic allograft cyclosporine concentration is independent of the route of cyclosporine administration and correlates with the occurrence of early cellular rejection.

This study compares the hepatic-tissue cyclosporine concentrations in liver biopsy specimens from patients with and without cellular rejection after orthotopic liver transplantation. Nine patients without cellular rejection were studied, including five patients receiving intravenous cyclosporine who had biopsies on posttransplant day 7 and four patients receiving oral cyclosporine who had biopsies on day 21. In these patients no significant differences were seen in blood cyclosporine concentrations (mean +/- S.D.) (310 +/- 162 vs. 273 +/- 310 ng/ml) and hepatic-tissue cyclosporine concentrations (3,451 +/- 1,262 vs. 3,545 +/- 456 ng/gm). These nine patients without cellular rejection were then compared with eight patients with cellular rejection who were receiving intravenous cyclosporine, including seven patients who had biopsies on post-transplant day 7 and one patient who had a biopsy on day 14. In patients with and without cellular rejection blood cyclosporine concentrations were 330 +/- 64 vs. 294 +/- 146 ng/ml, and hepatic-tissue cyclosporine concentrations were 1,879 +/- 998 vs. 3,493 +/- 936 ng/gm, p less than 0.01. We conclude that hepatic-tissue cyclosporine concentrations are independent of the route of cyclosporine administration and that low hepatic-tissue cyclosporine concentrations correlate with early cellular rejection after orthotopic liver transplantation.

Administration, Oral↗
PubMed1992

Cyclosporine treatment of inflammatory bowel disease.

Numerous uncontrolled studies and one controlled trial of cyclosporine therapy suggest that this selective inhibitor of cell-mediated immunity may be of benefit in patients with chronically active Crohn's disease. In addition, uncontrolled studies indicate that cyclosporine may be useful in the following settings: fistulous Crohn's disease; corticosteroid sparing in Crohn's disease; severe ulcerative colitis; and refractory proctosigmoiditis. The major advantages of cyclosporine therapy are apparent efficacy in patients with refractory disease and a rapid onset of response. Nevertheless, the incidence of relapse is high after cyclosporine therapy is discontinued, and this outcome is not prevented by low-dose maintenance therapy. Furthermore, the frequency of occurrence of cyclosporine-related side effects during treatment of patients with inflammatory bowel disease is high; paresthesias and hypertrichosis are the two most common adverse effects reported in the literature. Although the potential for permanent renal damage is of concern, serious, irreversible toxicity seldom occurs. Ongoing clinical trials will provide additional information about the efficacy and safety of cyclosporine for the aforementioned indications.

Cholangitis, Sclerosing↗
PubMed1992

Measurement of colonic tissue cyclosporine concentration in children with severe ulcerative colitis.

Recent studies suggest that cyclosporine may be an alternative to colectomy in children with severe ulcerative colitis who fail traditional therapy with bowel rest and high-dose corticosteroids. We report the clinical course of two such children. Patient 1 received oral cyclosporine at 15 mg/kg/day for 1 week followed by 8 mg/kg/day for 6 weeks. Clinical remission occurred within 5 days and has been sustained for 24 weeks after azathioprine was substituted for cyclosporine. Patient 2 received oral cyclosporine at 7-8 mg/kg/day for 7 days after which colectomy was performed due to lack of clinical improvement. Blood cyclosporine levels for patient 1 ranged from 95 to 406 ng/ml and for patient 2 from 36 to 65 ng/ml. Sigmoid colonic tissue cyclosporine concentrations for patients 1 and 2 were 10,058 and 3,205 ng/g, respectively. The patient who responded had significantly higher blood and colonic tissue cyclosporine concentrations than the patient who did not respond. Further studies with larger numbers of patients are needed to determine if there is a correlation between blood and colonic tissue cyclosporine concentrations and clinical response.

Administration, Oral↗
PubMed1991

The pharmacokinetics and colonic tissue concentrations of cyclosporine after i.v., oral, and enema administration.

This study compares pharmacokinetic parameters and colonic tissue concentrations of cyclosporine administered by olive-oil or water-retention enemas with conventional intravenous (i.v.) and oral dosing. Five medical students were enrolled in a prospective crossover study. All subjects received a single dose of cyclosporine on four separate occasions, once orally, once as an olive-oil enema, once as a water enema, and once i.v. Cyclosporine concentration was measured in blood and in colonic tissue obtained by flexible sigmoidoscopy. Bioavailability was 18 +/- 7% (mean +/- SD) for the oral dose and was unmeasurable for the oil and water enemas. The concentration of cyclosporine in colon tissue was 32,443 +/- 17,251 ng/g (mean +/- SD) for the i.v. dose, 2797 +/- 1812 ng/g for the oral dose, 21,727 +/- 14,090 ng/g for the oil enema, and 25,318 +/- 30,408 ng/g for the water enema. The authors conclude that the bioavailability of cyclosporine, and thus the systemic absorption after administration by a retention enema, is negligible. The colonic tissue concentration of cyclosporine after i.v. or rectal administration via an enema is tenfold higher than that for oral dosing. These findings suggest that cyclosporine-retention enemas produce high distal colonic tissue concentrations with negligible systemic absorption after a single dose in healthy subjects and should be evaluated as treatment for patients with left-sided colitis. Because cyclosporine administered by the i.v. route provided sharply higher colonic tissue concentrations than those seen with oral therapy, pulse i.v. cyclosporine should be tried for patients with severe ileitis and colitis.

Administration, Oral↗
PubMed1990

Pharmacokinetics and pharmacodynamics of oral and intravenous cimetidine in seriously ill patients.

This study was done to determine if the pharmacokinetics and gastric pH response of intravenous cimetidine are superior to oral dosing in seriously ill patients. A paired study of intravenous followed by oral liquid cimetidine was given to eight men and two women who were inpatients in a VA Hospital. Treatment was prescribed for either upper gastrointestinal (GI) bleeding or prophylaxis against GI bleeding. All patients received cimetidine 300 mg every 6 hours intravenously on day 1 and orally on day 2. After the fourth dose each day, venous blood samples and gastric pH measurements were taken serially for 6 hours. Peak serum cimetidine concentration was 2.0 +/- 0.5 mg/L for the intravenous dose and 1.5 +/- 0.3 mg/L for the oral dose (P = .001). Area under the curve (AUC) of cimetidine concentration was 3.81 +/- 1.1 mg/hr/L for the intravenous dose and 4.19 +/- 1.22 mg/hr/L for the oral dose (P greater than .30). Bioavailability (AUCpo/AUCiv) was 1.13 +/- 0.25, demonstrating complete oral absorption. The time during a 6-hour dosing interval that the gastric pH remained above 3.0 was 3.3 +/- 2.1 hours for the intravenous dose and 2.5 +/- 2.3 hours for the oral dose, P = .171). The time that the serum cimetidine concentration remained above 0.5 mg/L was 2.0 +/- 0.9 hours for the intravenous dose and 2.7 +/- 1.0 hours for the oral dose (P = .055). We concluded that bioavailability, time that gastric pH is maintained greater 3.0, and time that the serum cimetidine concentration is greater than 0.5 mg/L for intravenous cimetidine are not significantly different from oral cimetidine in seriously ill patients.

Administration, Oral↗
PubMedDate not supplied

Strategies targeting tumor necrosis factor in Crohn's disease.

Tumor necrosis factor plays an important role in mediating the inflammation of Crohn's disease. Strategies aimed at reducing tumor necrosis factor in patients with Crohn's disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human recombinant tumor necrosis factor receptor fusion protein etanercept, and the small molecule thalidomide. Infliximab is effective for treating active Crohn's disease, maintaining remission, and closing fistulas. Side effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, formation of autoantibodies, and rarely drug induced lupus. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions, and formation of autoantibodies. Pilot studies have suggested that etanercept and thalidomide may also be beneficial. Anti-tumor necrosis factor therapies are effective for the treatment for Crohn's disease.

Antibodies, Monoclonal↗
PubMedDate not supplied

Cyclosporine in ulcerative colitis: state of the art.

Forty percent of patients with severe ulcerative colitis will fail to respond to intravenous corticosteroids. Cyclosporine and other calcineurin inhibitors offer an alternative to colectomy for these patients. Intravenous cyclosporine will induce remission within 14 days in 50-80% of patients who fail intravenous corticosteroids. The long-term response rates for responding patients are 40-60%. Subsequent maintenance therapy with azathioprine or 6-mercaptopurine is recommended at the present time, although the uncontrolled studies underlying this observation have yielded variable results. Toxicity occurs frequently in patients treated with high dose cyclosporine, and there is a small risk of opportunistic infection and death. Pilot studies have suggested that the microemulsion cyclosporine formulation Neoral and tacrolimus may also be of benefit in this patient population. Additional studies to determine the dose response of intravenous cyclosporine, to determine the role of azathioprine for maintenance, and to determine the efficacy of Neoral and tacrolimus are needed.

Calcineurin Inhibitors↗