Interleukin-4 variant (BAY 36-1677) selectively induces apoptosis in acute lymphoblastic leukemia cells.

Interleukin 4 (IL-4) suppresses the growth of acute lymphoblastic leukemia (ALL) cells, but its clinical usefulness is limited by proinflammatory activity due mainly to the interaction of cytokine with endothelial cells and fibroblasts. Stroma-supported cultures of leukemic lymphoblasts were used to test the antileukemic activity of an IL-4 variant, BAY 36-1677, in which the mutations Arg 121 to Glu and Thr 13 to Asp ensure high affinity for IL-4Ralpha/IL-2Rgamma receptors expressed by lymphoid cells, without activation of the IL-4Ralpha/IL-13Ralpha receptors mainly expressed by other cells. BAY 36-1677 (25 ng/mL) was cytotoxic in 14 of 16 cases of B-lineage ALL; the median reduction in cell recovery after 7 days of culture was 85% (range, 17%-95%) compared to results of parallel cultures not exposed to the cytokine. Twelve of the 14 sensitive cases had t(9;22) or 11q23 abnormalities; 3 were obtained at relapse. BAY 36-1677 induced apoptosis in leukemic lymphoblasts but did not substantially affect the growth of normal CD34+ cells, thus conferring a growth advantage to normal hematopoietic cells over leukemic lymphoblasts in vitro. BAY 36-1677 had antileukemic activity equal or superior to that produced by native IL-4, but it lacked any effects on the growth of endothelial cells and fibroblasts. The molecular manipulation of IL-4 to abrogate its proinflammatory activity has generated a novel and therapeutically promising cytokine for the treatment of high-risk ALL.

Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms.

Previous studies have suggested that sensory cues associated with cigarette smoking can suppress certain smoking withdrawal symptoms, including craving for cigarettes. In this study we investigated the subjective effects of a cigarette substitute delivering a vapor of black pepper essential oil. Forty-eight cigarette smokers participated in a 3-h session conducted after overnight deprivation from smoking. Subjects were randomly assigned to one of three conditions: one group of smokers puffed on a device that delivered a vapor from essential oil of black pepper; a second group puffed on the device with a mint/menthol cartridge, and a third group used a device containing an empty cartridge. Subjects puffed and inhaled ad libitum from the device throughout the session during which no smoking was allowed. Reported craving for cigarettes was significantly reduced in the pepper condition relative to each of the two control conditions. In addition, negative affect and somatic symptoms of anxiety were alleviated in the pepper condition relative to the unflavored placebo. The intensity of sensations in the chest was also significantly higher for the pepper condition. These results support the view that respiratory tract sensations are important in alleviating smoking withdrawal symptoms. Cigarette substitutes delivering pepper constituents may prove useful in smoking cessation treatment.

Adverse prognostic features in 251 children treated for acute myeloid leukemia.

Potential predictors of event-free survival (EFS) were assessed in 251 consecutively diagnosed children treated for acute myeloid leukemia (AML) on three successive clinical trials. The lack of significant differences in 4-year EFS for these studies (20% +/- 4%, 29% +/- 4%, and 20% +/- 7%) permitted combined analysis of presenting features. Splenomegaly (P = .002), coagulation abnormalities (P = .001), leukocyte count > or = 10 x 10(9)/L (P = .002), and age > 14 years (P = .01) were statistically significant predictors of a poorer EFS by univariate analysis and retained significance in multivariate analysis. Age < 2 years and monocytic leukemias (often cited as adverse factors in AML) showed no prognostic influence in this study. The estimated relative risk of failure for a child with a single adverse feature at diagnosis was at least 1.4 times greater than that for a patient with no adverse features. For children with two or more adverse features, the relative risk increased by more than threefold. These clinical variables, alone or in combination, may identify important subgroups of patients with AML at high risk for failure and for whom improved or alternative therapies are especially important.

Psychophysiological interactions between caffeine and nicotine.

The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose.