Interleukin-2, its soluble receptor,and soluble T8 antigen in acute ischemic stroke

The treatment of neoplasia with interleukin-2 (IL-2) can be complicated by neurological deficits resembling transient Ischemic attack and stroke. We investigated whether interleukin-2 contributes to the natural course of cerebrovascular ischemia and particularly to the pathogenesis of infection-associated stroke. Plasma levels of interleukin-2 were below the level of detectability in almost all measurements. Patients with and without previous infection (n = 11, 805 ±445 U/ml vs n = 19, 824 ± 501 U/ml) did not have significantly higher levels of soluble interleukin-2 receptors than control subjects with (n = 14, 667 ± 229 U/ml) or without vascular risk factors (n = 17, 567 ± 176 U/ml). Receptor levels increased in patients during the first week after stroke (n = 15, 1157 ± 1013, p < 0.02). Levels of soluble T8 antigen (sT8) were higher in patients (n – 26, 320 ± 112 U/ml) than in healthy control subjects (n = 15, 246 ± 92 U/ml; p < 0.05) and sT8 levels increased during the first week after stroke (p < 0.05). These results reflect an immunological response to the cerebral infarct; they do not indicate a general role of the IL-2 system in the pathogenesis of ischemic stroke with or without previous infection.     

Short term effect of diltiazem on portal hypertension in patients with non-cirrhotic portal fibrosis

Fourteen patients of non-cirrhotic portal fibrosis (NCPF) with portal hypertension were put on oral diltiazem hydrochloride (90 mg/day) or placebo on a prospective, randomised, single blind basis for 15 days. Predrug hemodynamic and biochemical status were similar in both groups. Diltiazem produced significant reduction (p less than 0.001) in mean intrasplenic pressure: from 41.88 (SD +/- 6.18) to 21.5 (+/- 7.91) cm of normal saline as against 45.56 (+/- 9.45) to 43.33 (+/- 8.27) in the placebo group. Mean arterial pressure (MAP), heart rate and cardiac output (CO) did not change in either group. Thus, the calcium channel blocker diltiazem reduces portal pressure in patients with NCPF, independent of reduction in MAP and CO; this is advantageous in situations where compromised cardiac hemodynamics may prove deleterious.     

Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer

Summary Phosphonacetyl-l-aspartate (PALA), an inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m² on day 1, followed 24 h later by 2,600 mg/m² 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.Supported in part by grant CA 06927 from the National Cancer Institute