CLINICAL ASSESSMENTS OF MATURATION

早产导致重大死亡率和发病率 主要是由于肺、肾和血管系统的不成熟所致。这 提案请求支持三项临床方案审查 早产儿器官系统成熟的策略 产前给有早产风险的母亲用药 送货。接受测试的产前药物将是皮质类固醇 (倍他米松，12毫克，肌肉注射，24小时，最多2剂)， 皮质类固醇与促甲状腺激素释放激素(TRH)(400微克) 20分钟输注8小时，共4次)或不加任何药剂。这个 神经内分泌、肾脏和血管成熟激素各自的作用 这些治疗方法中的一种将被检查。在神经内分泌的研究中 影响，胎儿儿茶酚胺分泌反应，β-肾上腺素能 受体密度和受体介导的腺苷环化酶活性将 比较一下。肾脏成熟度研究将检查对 肾小球滤过率、尿钠和尿水排出量。这个 血管活性物质的研究将评估循环中的水平 血管内皮细胞衍生因子，以及内皮素受体数量和 在脐带血中的作用。脐带血管的收缩行为 也将接受评估。后续的临床试验将会展开。 根据动物实验的结果，婴儿将 对器官成熟的影响进行类似的评估。这些研究 在定义对各种不同的 与这些毒剂相关的器官系统在它们广泛传播之前 临床应用。如果可以证明对成熟的影响，母体 先兆早产的产前治疗可以提供一种安全的， 相对容易实施治疗以最大限度地减少显著 器官不成熟的问题。

Significant mortality and morbidity result from premature birth, due largely to immaturity of the lung, kidney and vascular systems. this proposal requests support for three clinical protocols examining strategies for maturing organ systems in preterm newborns by means of prenatally administered drugs given to the mother at risk for preterm delivery. The prenatal drugs to be tested will be corticosteroids (betamethasone, 12 mg I.M. q 24 hr for a maximum of 2 doses), corticosteroids with thyrotropin releasing hormone (TRH), (400 ug as a 20 minute infusion of 8 hr for a total of 4 doses) or no agent. The neuroendocrine, renal and vascular maturational hormone effects of each of these treatments will be examined. In the study of neuroendocrine effects, fetal catecholamine secretory responses, beta adrenergic receptor density and receptor mediated adenyl cyclase activity will be compared. The renal maturational study will examine effects on glomerular filtration rate and urinary sodium and water excretion. The study of vasoactive substances will evaluate circulating levels of endothelial derived factors, as well as endothelin receptor numbers and function in umbilical cord blood. Contractile behavior of cord vessels also will be evaluated. Subsequent clinical trials will be developed based on the results from the animal experiments, and the infants will be evaluated similarly for organ maturational effects. These studies will be important in defining any potential benefit or harm to various organ systems associated with these agents before they achieve widespread clinical use. If an effect on maturation can be demonstrated, maternal prenatal therapies in threatened preterm deliveries could provide a safe, relatively easy to administer therapy to minimize the significant problems of organ immaturity.