BIOLOGICAL BASIS OF TREATMENT FAILURE

项目0006的目标将是详细检查生物 “治疗失败”的原因。 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）病原种对 使用的抗生素; 2）抗菌剂未达到 牙周部位的水平足以抑制病原体，3） 病原体是一个独特的，高毒力的克隆型; 4） 病原微生物定植在机械无法到达的部位 和/或抗菌处理。 第二组实验将检验 治疗失败的宿主成分，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 受试者的龈下物种; 2）宿主安装不充分的 免疫反应表现为过度或不足的生产 抗体，或产生无效抗体; 3）宿主对 龈下物种与“过于旺盛”（破坏性）炎症 反应 项目0005中确定为治疗失败（试验）的受试者将 进入项目0006（至少n=30）。 一个匹配的，“治疗成功” 受试者（对照）将被识别为每个测试受试者， 同一种族、性别、年龄和医疗状况群体。 临床，人口统计， 供试品和 对照受试者将从项目0005中收集的数据中获得。 所有试验和对照受试者将在基线访视时进行评价， 项目0006的以下附加参数：1）存在 2）克隆型牙龈卟啉单胞菌和 C.腹直肌，3）肠道微生物和酵母菌的水平，以及 不常见种属（通过PCR），4）全身给药的能力 四环素对牙周部位的作用，5）宿主防御系统的能力， 杀死受试者的龈下病原体，6）抗体应答 龈下物种和7）局部炎症介质水平。 如果 这些数据表明了一种“适当的治疗”， 制定的。 当“适当的治疗”不明显时，1/2 将开始强化抗菌治疗。 如果在 在治疗过程中，由于牙周原因必须拔牙， 微生物在穿透牙根的牙本质小管中的作用将是 寻找和识别。 完成后3、6和12个月 所有受试者均将接受临床和实验室监测， 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.