BIOLOGICAL BASIS OF TREATMENT FAILURE

项目0006的目标将是详细检查生物 “治疗失败”的依据。第一系列实验将 检查治疗失败的可能微生物成分，包括 假设：1)病原物种对 使用辅助抗生素；2)抗菌剂不能到达 牙周部位足以抑制病原体，3) 病原体是一种不同的、高毒力的克隆类型；4) 病原菌定植在机械设备无法到达的位置 和/或抗菌治疗。第二组实验将检验 治疗失败的主要组成部分，并包括以下假设： 1)宿主的“反应系统”(中性粒细胞、抗体、补体)不能杀死 受试者的牙龈下物种；2)宿主安装了不适当的 免疫反应表现为生产过多或生产不足 抗体，或产生无效抗体；3)宿主对 具有“过度活跃的”(破坏性的)炎症的龈下物种 回应。 项目0005中被确定为治疗失败(测试)的受试者将 输入项目0006(最小n=30)。与之相匹配的“治疗成功” 将为每个测试对象确定对象(对照)，这些对象属于 相同的种族、性别、年龄和医疗状况组。临床，人口统计学， 试验和免疫试验的微生物学和免疫学特征 对照对象将从项目0005中收集的数据中获得。 所有试验和对照对象将在基线访问时进行评估 Project 0006用于以下附加参数：1)在线状态 对四环素耐药的物种，2)克隆型牙龈假单胞菌和 直肠弯曲杆菌，3)肠道微生物和酵母菌水平，以及存在 不寻常的物种(通过聚合酶链式反应)，4)提供系统管理的能力 四环素对牙周部位的作用，5)宿主防御系统对 杀死受试者的牙龈下病原体，6)抗体反应 7)局部炎性介质的水平。如果 这些数据表明有一种“合适的疗法”，那就是 已经成立了。当“适当的治疗”不明显时，1/2 将开展密集的抗菌治疗。如果在此期间 在治疗过程中，由于牙周原因，必须拔牙， 微生物穿透牙根的牙本质小管 寻找并确认身份。完成后3个月、6个月和12个月 治疗，所有受试者都将通过临床和实验室进行监测 评估。

The goal of Project 0006 will be to examine in detail the biological basis of "treatment failure". The first series of experiments will examine a possible microbial component of treatment failure and include the hypotheses that: 1) the etiologic species are resistant to the adjunctive antibiotic employed; 2) the antimicrobial agent does not reach periodontal sites in levels sufficient to suppress the pathogens, 3) the pathogens are of a distinct, highly virulent clonal type; 4) the etiologic organisms colonize sites which are inaccessible to mechanical and/or antimicrobial treatment. A second set of experiments will examine the host component of treatment failure and include the hypotheses that: 1) the host's "response system" (PMNs, antibody, complement) cannot kill the subject's subgingival species; 2) the host mounts an inadequate immunological response manifested by an over or under production of antibody, or production of ineffective antibody; 3) the host responds to subgingival species with an "overly exuberant" (damaging) inflammatory response. Subjects in Project 0005 identified as treatment failures (test) will enter Project 0006 (minimum n=30). A matched, "treatment success" subject (control) will be identified for each test subject, who is of the same race, sex, age, and medical status group. Clinical, demographic, microbiological and immunological characteristics of both test and control subjects will be available from data collected in Project 0005. All test and control subjects will be evaluated at the baseline visit of Project 0006 for the following additional parameters: 1) the presence of species resistant to tetracycline, 2) clonal type of P. gingivalis and C. rectus, 3) level of enteric organisms and yeasts, and the presence of unusual species (by PCR), 4) ability to deliver systemically-administered tetracycline to periodontal sites, 5) ability of host defense system to kill the subject's subgingival pathogens, 6) antibody response to subgingival species and 7) levels of local inflammatory mediators. If these data suggest an "appropriate therapy", that therapy will be instituted. When an "appropriate therapy" is not apparent, 1 of 2 intensive antimicrobial therapies will be instituted. If during the course of treatment, a tooth must be extracted for periodontal reasons, microorganisms in penetrating the dentinal tubules of the root will be sought and identified. Three, 6 and 12 months after completion of therapy, all subjects will be monitored using clinical and laboratory assessments.