S. D. Hearing

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis

Background : Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin‐2 renders lymphocytes steroid resistant.

Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes

BACKGROUND Up to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown. AIM To investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes. METHODS Eighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured. RESULTS In vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups. CONCLUSIONS Results suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.

Basiliximab for the treatment of steroid‐resistant ulcerative colitis: further experience in moderate and severe disease

Preliminary data have suggested that interleukin‐2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid‐resistant ulcerative colitis.

Audit of cyclosporin use in inflammatory bowel disease: limited benefits, numerous side-effects.

Background The failure of standard treatments for inflammatory bowel disease (IBD) has led to the use of immuno-modulatory therapy. Most reports of the use of cyclosporin are from single specialist centres. Aim To survey the use of cyclosporin in IBD in Bristols three teaching hospitals. Patients and methods Over a 4-year period, all patients receiving cyclosporin for IBD were identified and the following data recorded: diagnosis, duration of disease, initial treatment, date initiated, dose of cyclosporin, side-effects, initial clinical response, and current patient status. Results Thirty-three patients were identified, of whom 26 had ulcerative colitis (UC), six had Crohns disease and one had indeterminant colitis. The most frequent indication was as ‘rescue’ therapy in acute severe UC. The overall initial response rate was 63%, but this was only maintained in 30% long-term patients, with over half of them reporting side-effects. Four patients had life threatening side-effects. Conclusion Although the initial response rates are encouraging, the long-term results are poor and at the expense of a high incidence of side-effects. We feel that the use of cyclosporin in IBD should be reconsidered until more information from randomized controlled studies becomes available.Eur J Gastroenterol Hepatol12:657-660

Glucocorticoid resistance - what is known?

It has become apparent in recent years that the glucocorticoid receptor is not a simple on/off switch, but instead orchestrates subtle and complex interactions between large numbers of proteins. This more sophisticated understanding awaits a unifying concept that will explain mechanisms of glucocorticoid resistance and allow new approaches to enhancing sensitivity.

Is your patient taking the medicine? A simple assay to measure compliance with 5-aminosalicylic acid-containing compounds

Background : Poor compliance with 5‐aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5‐aminosalicylic acid; however, the chemical similarity between 5‐aminosalicylic acid and salicylate might provide a solution.

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone‐secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

IN VITRO MEASUREMENT OF LYMPHOCYTE STEROID SENSITIVITY: LACK OF AGREEMENT BETWEEN WHOLE BLOOD CULTURE AND SEPARATED LYMPHOCYTE CULTURE

The use of a whole blood culture to measure steroid sensitivity has previously been compared to the use of a separated lymphocyte assay. Good correlation between the two methods was reported. However the number of subjects studied appears to have been small and no patients with steroid resistance were studied. We have studied a large number of subjects and compared steroid sensitivity measured by a whole blood culture with an established separated lymphocyte assay. Proliferation was stimulated with phytohaemagglutinin and inhibited by dexamethasone. A wide range of steroid sensitivity was found between individuals. In steroid sensitive subjects, good agreement was seen between the two assays. However in individuals identified as steroid resistant by the separated lymphocyte assay, steroid resistance was not seen using the whole blood assay. This is important because in vitro lymphocyte steroid resistance, as measured by the separated lymphocyte assay has been shown to predict a poor in vivo response to steroid therapy. Using the whole blood culture this steroid resistance would not be demonstrated. Hence the use of a whole blood assay can not be recommended.

Audit of cyclosporin use in inflammatory bowel disease: Limited benefits, numerous side-effects

Background The failure of standard treatments for inflammatory bowel disease (IBD) has led to the use of immuno‐modulatory therapy. Most reports of the use of cyclosporin are from single specialist centres. Aim To survey the use of cyclosporin in IBD in Bristols three teaching hospitals. Patients and methods Over a 4‐year period, all patients receiving cyclosporin for IBD were identified and the following data recorded: diagnosis, duration of disease, initial treatment, date initiated, dose of cyclosporin, side‐effects, initial clinical response, and current patient status. Results Thirty‐three patients were identified, of whom 26 had ulcerative colitis (UC), six had Crohns disease and one had indeterminant colitis. The most frequent indication was as ‘rescue’ therapy in acute severe UC. The overall initial response rate was 63%, but this was only maintained in 30% long‐term patients, with over half of them reporting side‐effects. Four patients had life threatening side‐effects. Conclusion Although the initial response rates are encouraging, the long‐term results are poor and at the expense of a high incidence of side‐effects. We feel that the use of cyclosporin in IBD should be reconsidered until more information from randomized controlled studies becomes available. Eur J Gastroenterol Hepatol 12:657‐660