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Biomedical subjects

D H Present

Publications and source records attributed to D H Present.

At least 37 records · Page 2Linked to original sources
PubMed1997

A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.

BACKGROUND: Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. METHODS: We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. RESULTS: At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p<0.001 for the comparison of the cA2 group as a whole with placebo). Thirty-three percent of the patients given cA2 went into remission (defined as a score below 150 on the Crohn's Disease Activity Index), as compared with 4 percent of the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compared with 12 percent of the patients in the placebo group (3 of 25) (P=0.008). The rates of adverse effects were similar in the groups. CONCLUSIONS: A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.

Adult↗
PubMed1997

The modern medical management of acute, severe ulcerative colitis.

The management of patients with acute, severe ulcerative colitis requires careful in-hospital assessment of the patient and the coordinated treatment of a team of experienced gastroenterologists and surgeons. Complete understanding of the potential complications and their management, especially toxic megacolon, is essential. We review the current medical arsenal and advocate a standardized approach to management that includes continuous, high dose intravenous hydrocortisone, more aggressive use of topical steroids as well as feeding the patients and continuing (but not initiating) oral 5-aminosalicylic acid (5-ASA) agents. For those patients whose disease proves refractory to intravenous steroids, intravenous cyclosporin (with an acute response rate of 82%) is an essential component in the medical management of these patients. Antibiotics should be used only when specifically indicated. Total parenteral nutrition has not been shown to be helpful in the acute setting. Air contrast barium enema and colonoscopy have been used to predict response but may be dangerous diagnostic modalities in these acutely ill patients and are no better than good clinical judgement. We review and advocate long-term management of acute response using 6-mercaptopurine or azathioprine. The surgical experience and the postoperative complications of the ileal pouch anal anastomosis, which include acute pouchitis in 50-60%, chronic pouchitis in 5-10% and recent reports of dysplasia among patients with chronic pouchitis, must be considered before colectomy is advised. Over 80% of patients with acute severe colitis can be spared colectomy using our current arsenal of medical therapies.

Adrenal Cortex Hormones↗
PubMed1996

The long-term outcome of ulcerative colitis treated with 6-mercaptopurine.

OBJECTIVES: To determine the long term outcome of ulcerative colitis in patients treated with 6-MP. METHODS: The charts of 105 chronic refractory ulcerative colitis patients treated with 6-MP from 1973-1992 were reviewed. The focus was placed on clinical response, subsequent breakthrough while maintaining 6-MP, and relapse rates when 6-MP was discontinued. RESULTS: Complete clinical remission was achieved in 68 patients (65%), partial remission was achieved in 25 patients (24%), and 12 patients (11%) failed to achieve remission. Of complete responders who continued 6-MP, 35% had a breakthrough, although complete remission was restored in 88% with the majority not requiring systemic steroids. Of complete responders who discontinued 6-MP, 87% subsequently relapsed. There were few major toxicities associated with 6-MP use. CONCLUSION: 6-MP is a reasonably safe and effective treatment for refractory ulcerative colitis. Patients who discontinue 6-MP after successful treatment have high relapse rates, therefore, 6-MP must be maintained long term to sustain remission.

Adult↗
PubMed1994

Cyclosporine in severe ulcerative colitis refractory to steroid therapy.

BACKGROUND: There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. METHODS: We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine. RESULTS: Nine of 11 patients (82 percent) treated with cyclosporine had a response within a mean of seven days, as compared with 0 of 9 patients who received placebo (P < 0.001). The mean clinical-activity score fell from 13 to 6 in the cyclosporine group, as compared with a decrease from 14 to 13 in the placebo group. All five patients in the placebo group who later received cyclosporine therapy had a response. CONCLUSIONS: Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis.

Adolescent↗
PubMed1994

Efficacy of cyclosporine in treatment of fistula of Crohn's disease.

Sixteen Crohn's disease patients with active fistula who had failed standard medical therapy were treated with intravenous cyclosporine. Ten patients had perirectal disease, four had enterocutaneous fistula, and two had rectovaginal fistula. Patients were initially treated with intravenous cyclosporine, 4 mg/kg/day, and then switched to oral cyclosporine, 6-8 mg/kg/day. Improvement was graded using the Present-Korelitz criteria, and success was defined as moderate to total closure of the fistula. Fourteen of 16 patients (88%) responded in the acute phase to parenteral cyclosporine. Closure of fistula occurred in seven (44%) with moderate improvement in the remaining seven (44%). Subsequently, five patients (36%) relapsed to some degree on oral cyclosporine (three severe and two mild relapses). Nine (64%) patients maintained their improvement in the chronic phase. Chronic steroids could be discontinued in 6/8 (75%) of patients. Mild side effects were common [paresthesias (75%) and hirsutism (19%)]. A single patient had severe paresthesias requiring discontinuation of therapy. Mild hypertension was noted in four (25%) and one patient (6%) had to be withdrawn because of nephrotoxicity, which reversed after stopping cyclosporine. We conclude that intravenous cyclosporine is effective therapy for perianal, rectovaginal, and enterocutaneous fistula in Crohn's disease. Its future role awaits controlled trials as well as determination of the risk-benefit ratio.

Adult↗
PubMed1993

Toxic megacolon.

Toxic megacolon, its incidence, differential diagnosis, and presenting signs and symptoms are reviewed in this article. The typical histologic and radiographic features are described with a review of the potential triggering factors. An outline of requirements for adequate monitoring of the patient with toxic megacolon is provided. The general management and specific medical management are discussed in detail, and the medical outcome with both medical and surgical intervention is reviewed.

Colon↗
PubMed1991

Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease.

A private practice was surveyed for prevalence of inflammatory bowel disease (IBD) in husband-wife partners and in their children. Among approximately 2500 patients with IBD in our files, 19 couples were identified. They were subdivided into group A (n = 5) in which both partners had symptoms of IBD before marriage; group B (n = 7) in which only one spouse had IBD before marriage and the other partner experienced symptoms afterwards; and group C (n = 7) in which neither spouse had symptoms before marriage but IBD subsequently developed in both. In group B, the disease developed in the second spouse 2-16 years after marriage (mean, 6.4 years). In group C, IBD developed in the first spouse 0.3-41 years after marriage and in the second spouse 1-14 years after the first spouse (mean, 6.8 years). Thirty-five children have been born to 16 of the couples. Two children died before age 20. Of the surviving 33 children, IBD has already developed in 12 (36%). Among the other 21 unaffected children, 1 had uveitis at age 9 and 10 are still under the age of 21, perhaps too young to have yet developed IBD. The frequency of IBD in children was slightly higher if both parents had already developed IBD at the time of conception (67%) compared with when only 1 parent (50%) or neither parent (50%) had developed IBD when conception occurred. Although these data do not distinguish genetic from environmental factors, they show a higher risk of IBD in children when both parents have this illness.

Adult↗
PubMed1991

Maintenance oral sulfasalazine prolongs remission in ulcerative proctitis and proctosigmoiditis.

We have retrospectively compared the effectiveness of five different regimens for inducing and maintaining clinical remission in 206 patients with idiopathic proctitis (n = 115) and proctosigmoiditis (n = 91). The five therapeutic regimens were: corticosteroid enemas, 5-aminosalicylic acid (5-ASA) enemas, oral 5-ASA (sulfasalazine or mesalamine), corticosteroid enemas plus oral 5-ASA, or 5-ASA enemas plus oral 5-ASA. Clinical remission was achieved within 28 days of therapy in 47%, and eventually in 94% of these patients. No significant differences in efficacy were found among the five regimens. Most patients ultimately experienced a recurrence of symptoms, but the duration of remission was significantly longer with maintenance oral sulfasalazine or mesalamine (17.2 months) than with no therapy (11.8 months), P less than 0.01. We conclude that several regimens are equally effective in inducing remission of proctitis and proctosigmoiditis, although prolonged therapy may be needed to accomplish this goal. Maintenance oral 5-ASA significantly prolongs symptomatic remission in proctitis and proctosigmoiditis.

Adolescent↗
PubMed1990

Preliminary report: cyclosporin in treatment of severe active ulcerative colitis.

Intravenous cyclosporin (4 mg/kg daily) was given to fifteen patients with severe active ulcerative colitis, fourteen of whom had failed to respond to at least 10 days' treatment with intravenous steroids. In the acute phase of the open trial, eleven patients (73%) improved and avoided colectomy; the mean response time was 5.8 days. Patients who responded were maintained on oral cyclosporin (6-8 mg/kg daily) for a 6-month chronic phase. Six of the eleven patients have been weaned from steroids and remain in clinical and endoscopic remission 5-18 months after discontinuation of cyclosporin; three are well at 5 months and their steroid dose is being tapered; one patient relapsed after 5 months on oral cyclosporin and underwent colectomy; and one patient failed to show continued improvement with oral cyclosporin but is in clinical remission after changing to mercaptopurine treatment. Slight self-limiting adverse side-effects of cyclosporin were seen, but none necessitated withdrawal from the study. Cyclosporin seems to be an effective treatment for patients with severe active ulcerative colitis who have not responded to steroids.

Acute Disease↗
PubMed1990

ACTH-induced adrenal hemorrhage: a complication of therapy masquerading as an acute abdomen.

Four patients developed adrenal hemorrhage during treatment with intravenous adrenocorticotropic hormone (ACTH) for severe inflammatory bowel disease (IBD). This complication presented suddenly with upper abdominal and flank pain mimicking an acute surgical abdomen. In each patient the symptoms of the underlying bowel disease had subsided under the ACTH therapy. In our first patient the diagnosis was not made until laparotomy, but in the subsequent three patients the diagnosis was suspected by the strikingly similar clinical presentation. In each of these three latter patients the diagnosis was confirmed by sonography or computed tomography (CT) scan, and surgery was avoided. All four of our patients are doing well at 1-58 months of follow-up. Signs of adrenal insufficiency occurred only in the one of our four patients, and in those six of 11 previously reported patients, who had bilateral adrenal hemorrhage. ACTH-induced adrenal hemorrhage requires stopping ACTH and maintaining corticosteroid support. The diagnosis of adrenal hemorrhage should be considered in the patient treated with ACTH who develops unexplained acute abdominal or flank pain. Failure to recognize this complication of ACTH therapy can lead to unnecessary surgery or the dangerous continuation of the offending agent.

Abdomen, Acute↗
PubMed1989

6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity.

We assess toxicity related to 6-mercaptopurine in the treatment of inflammatory bowel disease by reporting our experience with 396 patients (120 patients with ulcerative colitis, 276 with Crohn disease) observed over 18 years. Follow-up data for a mean period of 60.3 months were obtained for 90% of the patients. Toxicity directly induced by 6-mercaptopurine included pancreatitis in 13 patients (3.3%), bone marrow depression in 8 (2%), allergic reactions in 8 (2%), and drug hepatitis in 1 (0.3%). These complications were reversible in all cases with no mortality. Most cases of marrow depression occurred earlier in our experience, when the initial drug doses used were higher. Infectious complications were seen in 29 patients (7.4%), of which 7 (1.8%) were severe, including one instance of herpes zoster encephalitis. All infections were reversible with no deaths. Twelve neoplasms (3.1%) were observed, but only 1 (0.3%), a diffuse histiocytic lymphoma of the brain, had a probable association with the use of 6-mercaptopurine. Our data, showing a low incidence of toxicity in 396 patients, coupled with the previously demonstrated efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease, indicate that the drug is a reasonable alternative in the management of patients with intractable inflammatory bowel disease.

Adolescent↗