The cognitive effects of recombinant interleukin-2 (rIL-2) therapy: a controlled clinical trial using computerised assessments.

It has been suggested that patients undergoing treatment with recombinant interleukin-2 (rIL-2) may develop cognitive impairment. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) and chemotherapy alone. Assessments were carried out daily whilst patients were in hospital and regularly between cycles of treatment using state-of-the-art computerised cognitive assessment, as well as traditional psychometric tests. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. Computerised cognitive assessments revealed that immunochemotherapy produced significant impairment in various tasks, especially reaction time, picture recognition and vigilance. These effects were not due to sleep deprivation or pyrexia. For most patients, cognitive functioning was restored to the baseline level within 10 days following the cessation of rIL-2. In conclusion, during infusions of rIL-2, some patients experience severe confusion and amnesia which resembles some of the major cognitive impairments associated with dementias such as Alzheimer's disease. Computerised cognitive assessment using the Cognitive Drug Research system provides a feasible, sensitive and reliable method of evaluating cognitive changes in patients with cancer. It could usefully be included in quality of life assessments in clinical trials where treatment-related cognitive changes need to be evaluated.

Deactivation of tannin in high tannin milo by treatment with urea.

Experiments were conducted to determine the effectiveness of urea in deactivating tannin in high tannin milo. High tannin milo (Pioneer B 815, 3.4 +/- .3% tannin) was reconstituted with aqueous urea solutions to give combinations of 26, 30, and 34% moisture with 2, 3, and 4% urea (percentage of urea per dry weight of milo). All treatments were maintained at 25 degrees C and were effective in deactivating tannin with no differences among moisture or urea content. The average rate of tannin deactivation was 68 +/- 2% d-1. Temperature affected rate of tannin deactivation in milo reconstituted to 30% moisture and 3% urea when stored at 25 or 60 degrees C. Rate of tannin deactivation was 44 +/- 5 and 89 +/- 18% d-1 at 25 and 60 degrees C, respectively. Tannin in high tannin milo can be deactivated rapidly and completely by reconstitution with aqueous urea. These studies demonstrate that tannin is deactivated completely under conditions where urea is an effective preservative of high moisture milo.

The psychological and psychiatric effects of rIL-2 therapy: a controlled clinical trial.

It has been suggested that recombinant interleukin-2 (rIL-2) may cause pyschological and psychiatric problems, although the effects of rIL-2 on its own have not been well documented. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) versus chemotherapy alone. Patients were assessed regularly by means of various psychometric tests including the Hospital Anxiety and Depression Scale, the Mood Rating Scale, the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Trail-Making Test and the Benton Revised Visual Retention Test. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. Compared with patients who were given chemotherapy alone, patients receiving immunochemotherapy reported reduced energy, impaired confidence, higher depressed mood and more confusion. Immunochemotherapy was rated as more distressing than chemotherapy alone and patients reported a greater incidence of appetite impairment, weight loss, poor concentration and fever. Cognitive assessments indicated that brain dysfunction can be caused by rIL-2. Compared with the control group, patients receiving immunochemotherapy showed significant impairment on Trail Making Test B and the Digit Symbol Substitution Test. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. These effects were not due to sleep deprivation or pyrexia. Treatment with rIL-2 should not be discarded on psychosocial grounds, although in each case the psychological morbidity and adverse effects on quality of life need to be balanced carefully against potential therapeutic benefits.