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H D Janowitz

Publications and source records attributed to H D Janowitz.

At least 19 recordsLinked to original sources

How effective is current medical therapy for severe ulcerative and Crohn's colitis? An analytic review of selected trials.

To determine the efficacy of current medical therapies in the treatment of severe ulcerative and Crohn's colitis, we conducted a MEDLINE computer-assisted literature search using the terms "severe ulcerative colitis," "severe Crohn's colitis," "drugs," and "therapy." Studies were compared and then selected based, in decreasing order of importance, on the use of standard criteria to assess disease severity, uniform entrance criteria with prospective drug protocols using defined end points; prospective placebo-controlled trials; and retrospective studies. We then conducted an analytic review of those studies selected. For severe ulcerative colitis, we identified seven studies comprising 319 treatment episodes in 306 patients. Clinical remission was achieved on average in 62% of subjects (range, 43-80%); 38% (25-57%) came to prompt colectomy. Remission was maintained in 38-71% of patients achieving success in the acute phase. For severe Crohn's colitis, we identified five studies comprising 68 patients. Clinical remission was achieved on average in 65% of patients (range, 55-94%). Remission was maintained in 54-69% of those achieving success in the acute phase. Current medical therapies have improved the outlook for severe ulcerative colitis; however, physicians cannot predict response to therapy based upon individual's clinical features or previous presentations. Current medical therapy for severe Crohn's colitis appears to spare many patients early colectomy, but the current dearth of clinical trials postpones any further advances in the medical management of these patients.

Clinical Trials as Topic

Cyclosporine as an alternative to surgery in children with inflammatory bowel disease.

Five children with ulcerative colitis for whom surgery was recommended were treated with cyclosporine. The five had received corticosteroids for 1-24 months. The group included two patients with acute-onset ulcerative colitis and three with acute exacerbations of intractable corticosteroid-dependent chronic ulcerative colitis. The average age at initiation of cyclosporine therapy was 13.8 years (range, 11.5-16); all five patients were boys. Cyclosporine was initiated in the hospital by continuous i.v. infusion. Trough levels of 400-600 ng/dl (measured by radioimmunoassay) were achieved, at which point oral cyclosporine was given and oral dosage was adjusted to similar levels. Significant hypertension requiring medical attention was seen in one patient. Of the two recently diagnosed acute cases, one failed to respond and required subtotal colectomy after 2 weeks of treatment, and the other, despite an initial response, had a subtotal colectomy 10 months later. Of the three corticosteroid-dependent children, none was able to be weaned from corticosteroids and all underwent subtotal colectomy. Our experience emphasizes that the appropriate role of cyclosporine as therapy for children with ulcerative colitis is yet to be determined. Cyclosporine was not effective as an alternative to surgery in our patients.

Acute Disease

Adenocarcinoma in strictures of ulcerative colitis without antecedent dysplasia by colonoscopy.

We report three patients with chronic ulcerative colitis and colonic strictures that were found to harbor advanced adenocarcinomas despite previous endoscopic examinations that had failed to demonstrate dysplasia or carcinoma. This experience calls into question the reliability of endoscopic monitoring of the subset of ulcerative colitis patients with strictures. Review of the literature supports the thesis that the management of these patients requires a high index of suspicion of malignancy, and should include timely consideration of surgery. It is suggested that evaluation of the effectiveness of endoscopic surveillance programs for patients with ulcerative colitis should consider the subset of patients with strictures as a separate cohort.

Adenocarcinoma

Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis.

We have conducted a meta-analysis of 16 placebo-controlled trials of single drug therapy in ulcerative colitis (UC) for both induction (11 trials) and maintenance of remission (five trials). A total of 468 and 343 patients, respectively, was studied. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference. Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, single drug therapy for the induction of remission conferred a therapeutic advantage of 37-48% over placebo. In trials for maintenance of remission, the therapeutic advantage at 6 months was 21%, whereas at 12 months the therapeutic advantage rose to 46% because of a decline in placebo responders with time. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding therapeutic advantages, can help determine the relative value of newer agents in the therapy of UC.

Aminosalicylic Acids

Refractory pouchitis: does it reflect underlying Crohn's disease?

Typical 'pouchitis' is a well recognised complication of ileal pouches in ulcerative colitis. Infrequently, a refractory pouchitis (RP) presents with certain clinical, endoscopic, and pathological features resembling Crohn's disease and is often ascribed to misdiagnosis of the initial colitis. To test that hypothesis and to identify risk factors for RP, this study reviewed cases of presumed ulcerative colitis with ileal pouches constructed at The Mount Sinai Hospital between 1973 and 1986. Twenty four cases with RP (16 Kock pouches and eight pelvic pouches) and 21 controls were compared for eight clinical variables. The original colectomy slides from 15 RP and 18 control cases were reviewed blindly, classified into five histological categories (corresponding to definite ulcerative colitis, definite Crohn's disease, and three indeterminate groups), and scored for 23 histological features. There were no significant clinical differences between RP and control cases except for more frequent extraintestinal manifestations (38% v 5%) and male preponderance (79% v 43%) in RP. There were also no significant differences between the distributions of RP cases and controls among the five histological categories or in the 23 histological features studied. Refractory pouchitis therefore does not seem to reflect underlying Crohn's disease, but may be linked to immunological mechanisms that are manifested clinically as extraintestinal complications.

Adult

Lymphoma in inflammatory bowel disease.

Nine patients with lymphoma occurring in association with inflammatory bowel disease were admitted to The Mount Sinai Hospital between 1960 and 1983. Five (two men and three women) occurred among 1156 patients (0.43%) with ulcerative colitis (UC) and four (men), among 1480 patients (0.27%) with Crohn's disease (CD), a strong male preponderance in the latter group. In all four of the patients with CD and in four of the five patients with UC, the lymphomas were extraintestinal. The mean age of onset of UC in these patients was late (46 years, 19 years older than in our overall series), with lymphomas occurring a mean of only 12 years later. By contrast, patients with CD had bowel disease much younger (mean age, 26 years), and their lymphomas appeared after a longer disease duration (mean, 24 years). The risk factors for the one patient with colonic lymphoma were similar to those with colitis-associated colorectal carcinoma: extensive and long-standing colitis and relatively young age when malignant disease developed. Four of the patients with lymphoma had associated colonic carcinoma; in three of them, the carcinoma appeared within the first decade of colitis, an unusual occurrence. A second malignant lesion also occurred in three patients with UC.

Adult

How effective are current drugs for Crohn's disease? A meta-analysis.

We have conducted a meta-analysis of 12 placebo controlled trials to determine the efficacy of single drug therapy in Crohn's disease for both induction (seven trials) and maintenance (five trials) of remission. A total of 767 and 796 patients were studied, respectively. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference (RD). Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, we found that single drug therapy conferred an 11-29% therapeutic advantage (RD = 0.13-0.33) over placebo for the induction of remission. In trials for maintenance, no therapeutic advantage was found for single drug therapy over placebo. All forms of maintenance therapy followed nearly identical linear rates of relapse over time, showing an approximately 90% maintenance of remission rate at 3 months, which decreased to 25% at 36 months. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding risk differences and therapeutic advantages can help determine the relative value of newer agents in the therapy of Crohn's disease.

Crohn Disease

Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.

Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Malignant melanoma in inflammatory bowel disease.

Malignant melanoma occurred in 11 patients with inflammatory bowel disease (IBD). Six cases occurred in patients with ileocolitis, two in regional enteritis, one in granulomatous colitis, and two in patients with ulcerative colitis. The mean age at development of IBD was 24 yr, and at development of melanoma was 40 yr: the mean duration from onset of IBD to development of melanoma was thus 16 yr. All patients for whom complete information was available, except two, had received steroids and azulfidine for approximately a decade, as well as blood transfusions, usually multiple, and on repeated occasions. Six of the 11 patients had undergone one to seven prior operations (mean 3.5). All patients had wide radical excision of the melanoma, with or without concomitant or subsequent nodal dissection. Two patients (ages 25 and 36 yr) died rapidly from widely disseminated malignant melanoma. These cases may be coincidental, or else there may be an association between IBD and melanoma, related to immunosuppression either from the disease itself, from the medical and surgical therapy, and/or from x-ray exposure.

Adolescent

The irritable bowel syndrome. A continuing dilemma.

This article deals with the dilemmas in the definition, diagnostic work-up, and treatment of patients with the irritable bowel syndrome. The data presented are a blend of scientific insight to date and more than four decades of clinical experience with this disorder.

Colonic Diseases, Functional

Treatment of ulcerative colitis with fish oil n--3-omega-fatty acid: an open trial.

We evaluated the efficacy of fish oil n--3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. An open trial of 10 patients with mild to moderate ulcerative colitis who had either failed (n = 9) or refused (n = 1) conventional therapy was performed. Patients received 15 MAX-EPA capsules containing a total of 2.7 g of eicosapentanoic acid in three divided doses daily for 8 weeks. The activity of ulcerative colitis and response to therapy was based upon daily stool diaries, sigmoidoscopy, and symptomatic response. All patients tolerated the fish oil and showed no alteration in routine blood studies. Seven patients had moderate to marked improvement; steroid dose could be reduced in four of the five patients on prednisone. Three patients had little or no improvement. No patient worsened. These results of our open study appear to justify a double-blind trial of this dietary supplement in ambulatory patients with ulcerative colitis.

Administration, Oral

The "natural history" of ulcerative colitis: an analysis of the placebo response.

We have attempted to elucidate the "natural history" of ulcerative colitis by studying the placebo groups of 11 controlled trials of 185 patients with active disease. Most (182) of the patients were mild to moderately ill, but 3 had severe colitis. They were studied by endoscopic, pathologic, and/or clinical criteria and followed for 15-42 days. Up to 52% improved clinically and 59% sigmoidoscopically. Relapses commonly occurred within 2 months of these "spontaneous" improvements. In another six trials of 174 patients in remission receiving only placebo therapy (134 followed for 6 months and 40 for 12 months), up to 51% remained in remission. Favorable predictive factors for continued remission included a normal rectal mucosa on sigmoidoscopy, limited extent of colitis, and remission recently achieved by active therapy or maintained by therapy for at least 1 year before study entry. Thus, patients can get and stay better with no "specific" therapy. We have clarified advantageous predictive factors.

Adult

Granulomatous gastritis: a case report and review of the literature.

A 69-yr-old white female presented to her physician with a 3-yr history of epigastric pain. Gastric biopsies revealed noncaseating granulomas in the mucosa and submucosa. No definite etiological factor could be detected. A diagnosis of idiopathic granulomatous gastritis was made. In the past, this condition has prompted surgery. Steroids have also been advocated. Our patient was managed successfully with symptomatic treatment, without the use of steroids or surgical intervention. She remains well 4 yr later.

Aged