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  • 1
    ISSN: 1432-0843
    Keywords: Key words APL ; ATRA ; ATRA resistance ; Am80 ; As2O3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  All-trans retinoic acid (ATRA) is a potent differentiation drug for acute promyelocytic leukemia (APL) and is now incorporated into first-line therapy. However, ATRA resistance has become a major clinical problem. This limitation has prompted the development of alternative agents with desirable pharmacologic properties. We describe (1) our recent clinical trial using the new synthetic retinoid Am80 to overcome acquired resistance to ATRA and (2) basic in vitro effects of arsenic trioxide, a possible alternative to ATRA, on APL cells. A total of 19 APL patients who had relapsed after ATRA-induced complete remissions (CRs) received 6 mg/m2 Am80 p.o. daily until CR; 11 (58%) patients achieved a CR between days 20 and 58 (median day 37). The in vitro sensitivity to Am80, based on PML immunostaining, correlated well with the clinical effect in all patients tested. All three patients whose blasts were sensitive to Am80 in vitro despite a poor response to ATRA achieved CRs. Thus, Am80 might be an effective compound for the treatment of refractory APL and is a promising alternative retinoid. Since arsenic compounds have reportedly induced CRs in APL patients in China, we studied the in vitro effect of arsenic and other metal ions on myeloid leukemia cell lines. The effects of arsenic were limited mainly to APL cells, and the arsenic concentration was critical for the APL cell line NB4: 1 μM As3+ induced time-dependent apoptosis, whereas 0. 1 μM As3+ allowed partial NB4 cell differentiation. Arsenic trioxide was equally effective when used on ATRA-resistant NB4 cells. Among the clinical leukemia samples tested, the in vitro cytotoxic effects of As3+ were observed selectively in APL cells, regardless of their ATRA sensitivity. These data suggest that APL cells are sensitive to As3+ and that As3+ acts on APL cells via a different pathway to ATRA.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1438-8359
    Keywords: Airway resistance ; Measurement ; General anesthesia ; airflow ; Lung volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K1 + K2X. K1, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K2 value of the endotracheal tube used in this study (Portex® I.D. 8 mm, length 26 cm) was quite high (5.0 cmH2O·1−2·sec2), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K1 measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow. (Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K1 values. J Anesth 2: 139–145, 1988)
    Type of Medium: Electronic Resource
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