Brooks B R
ALS Clinical Research Center, Neurology Department University of Wisconsin Medical School.
Ann N Y Acad Sci. 1989;553:431-61.
The critical points that must be addressed in evaluating ergotropic drugs are exemplified by the current morass of positive and negative results that have been obtained in clinical investigations of TRH or its analogues. Appropriate subject selection is crucial. These patients may have bulbar symptoms, and those features of ALS should be specifically assayed for treatment effects relative to placebo. Gender-specific effects of TRH need to be accounted for in study design. In addition, electrophysiological techniques such as single fiber density may help determine the responsiveness of patients to TRH or its analogues. The clinical significance of an increase in fiber density following TRH or other drugs should be determined, as it will provide insight into the state of motor neurons in the spinal cord of patients with ALS and possibly could be important in determining those who may respond to TRH if such a response is possible. Clinical studies have quite clearly shown conflicting results. Basic studies, however, have shown that response to TRH is state dependent, that is, whether the patient is male or female. Clinical studies have shown that response to TRH is state dependent, that is, it depends on whether the patient has bulbar or nonbulbar signs and is male or female. Future studies must take into consideration this state dependence as a specific feature of the pharmacological action of TRH and its analogues.
评估促肾上腺素能药物时必须解决的关键点，可通过促甲状腺激素释放激素（TRH）或其类似物临床研究中目前大量出现的正反两方面结果得以例证。合适的受试者选择至关重要。这些患者可能有延髓症状，而且对于肌萎缩侧索硬化症（ALS）的那些特征，应专门检测相对于安慰剂的治疗效果。TRH的性别特异性效应在研究设计中需要加以考虑。此外，诸如单纤维密度等电生理技术可能有助于确定患者对TRH或其类似物的反应性。TRH或其他药物后纤维密度增加的临床意义应该予以确定，因为这将有助于深入了解ALS患者脊髓中运动神经元的状态，而且如果有可能出现反应的话，在确定哪些患者可能对TRH有反应方面可能很重要。临床研究已经非常清楚地显示出相互矛盾的结果。然而，基础研究表明，对TRH的反应取决于状态，也就是说，取决于患者是男性还是女性。临床研究表明，对TRH的反应取决于状态，也就是说，这取决于患者是否有延髓或非延髓体征以及是男性还是女性。未来的研究必须将这种状态依赖性作为TRH及其类似物药理作用的一个特定特征加以考虑。
