Interleukin 2 therapy in cancer: identification of responders.

C-reactive protein (CRP) levels in serum were measured in fifteen patients with metastatic colorectal carcinoma, prior to and during treatment with a continuous intravenous infusion of rIL.2. Patients were subsequently classified as responders or non-responders to this therapy. Baseline serum CRP levels, prior to treatment, were significantly lower in the responders (range < 2-8 mg l-1) when compared with the non-responders (range 7.5-116 mg l-1), P = 0.004. Furthermore, the responding patients demonstrated significantly and grossly elevated CRP stimulation indices (SI) compared with non-responders at different time intervals during the rIL2 infusion. At the cessation of rIL2 therapy, the CRP stimulation index was 31.3 +/- 9.3 in the responders, and only 1.6 +/- 0.3 in the non-responders (means +/- s.e.m, P = 0.014). These findings suggest that it is possible to predict those cancer patients who are most likely to respond to and benefit from rIL2 therapy, either prior to the commencement of or during the first course of rIL2.

Glomerulotubular function in patients undergoing moderate surgical stress.

Glomerular function and renal tubular function assessed by measurements of creatinine clearance rates (CCR), lithium clearance rates (CLi, and N-acetyl-beta-D-glucosaminidase (NAG) enzymuria were measured immediately prior to and within 24 h of operation (average operative time 150 min) in 16 patients undergoing a moderate surgical stress. Although serum creatinine concentrations and CCR were similar pre- and postsurgery at 105 +/- 21 and 108 +/- 21 mumol/L and 108 +/- 67 and 110 +/- 59 mL/min/100 kg body weight (mean +/- SD), respectively, both CLi and NAG were significantly increased following the surgical insult. CLi was increased from 19.7 +/- 6.1 to 31.7 +/- 16.7 mL/min/100 kg (p less than 0.01) and NAG from 71 +/- 58 to 164 +/- 10 U/mmol urinary creatinine (p less than 0.001). In addition, the absolute distal tubular reabsorption of sodium and water increased from 18.3 +/- 5.9 and 15.8 +/- 9.7 to 30.6 +/- 16.4 and 27.6 +/- 12.2 mL/min/100 kg body weight (both p less than 0.05), respectively. These results indicate early postoperative renal tubular dysfunction following a moderate surgical stress, undetected by conventional screening.

Metabolic and thyroidal responses to mild cold are abnormal in obese diabetic women.

Mild cold exposure (22 degrees C, with reference to 28 degrees C, thermoneutral) was studied by overnight whole-body indirect calorimetry in euthyroid women. Basal, sleeping, energy expenditure (EE) was significantly increased (+3.8%, P less than 0.05) in six normal weight women but reduced (-3.5%, P less than 0.05) in five obese type II diabetic women. Mixed responses were found in five women with simple obesity. Biochemical measurements were made on fasting blood samples taken at 0900 h after 12 h exposure to the two temperatures. Serum T4, free T3 and TSH were within the normal reference range in all subjects. Serum T4 did not show any differences between the groups, nor any effect from temperature. There was a significant increase in free T3 (P less than 0.05) at 22 degrees C in the control subjects, but no differences in the obese diabetic women. Serum thyroglobulin fell significantly in the diabetic group. Both TSH and free T3 responses to mild cold were significantly different between the groups, but both correlated positively (P less than 0.05) with the changes in sleeping energy expenditure at 22 degrees C with reference to 28 degrees C. Changes in TSH and free T3 were themselves significantly correlated within individuals (P less than 0.01). The normal physiological non-shivering thermogenesis of adult humans on exposure to a cool environment may thus be mediated by a pituitary-thyroid mechanism. The abnormal response of obese diabetic women was associated with impaired TSH and thyroid hormone responses, and may be a factor contributing to weight gain.