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Dermatology Consultation Clinic and Clinical Research

皮肤科咨询临床及临床研究

基本信息

批准号：
7733155
负责人：
maria l turner
金额：
$ 82.62万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7733155
关键词：
Academy Acute Adolescent Adverse reactions American Antifungal Agents Atopic Dermatitis Bacteria Biological Response Modifier Therapy Calcium Caring Chronic Chronic Granulomatous Disease Clinic Clinical Clinical Research Clinical Research Protocols Collaborations Condition Congresses Consult Consultations Country Cutaneous Dependence Deposition Depsipeptides Dermatologist Dermatology Diamond Disease Disease regression Dose Doxycycline Dyskeratosis Congenita Early treatment Enrollment Exposure to Extramural Activities Fanconi&apos s Anemia Female Fever Gene Expression Gene Expression Profile Genes Genetic Genital system Gynecologist Hand Histone Deacetylase Inhibitor Human Human Microbiome Human Volunteers Human body Imatinib Immunologic Deficiency Syndromes Individual Inherited Institutes Interest Group Intervention Job&apos s Syndrome Leiomyoma Lesion Libraries Link Malignant neoplasm of kidney Manuscripts Measures Microbe Molecular Biology Molecular Profiling Monitor Mutation Mycoses Myopathy National Institute of Allergy and Infectious Disease Natural History Operative Surgical Procedures Organ Pancytopenia Panniculitis Pathogenesis Patient Care Patients Pennsylvania Pharmaceutical Preparations Pharmacogenetics Phase Phototoxicity Pilot Projects Play Preparation Prevention Principal Investigator Process Protocols documentation Publications Publishing Rare Diseases Reaction Recruitment Activity Referral and Consultation Renal Cell Carcinoma Renal carcinoma Reporting Research Personnel Resources Rest Role Safety Sampling Services Simulate Skin Sunburn Supervision Syndrome Systemic Therapy Systemic disease T-Cell Lymphoma Testing Therapeutic Agents Time Tissues Toxic effect Ultraviolet Rays United States National Institutes of Health Upper arm Vagina Voriconazole Woman calcification chronic graft versus host disease clinical phenotype drug metabolism experience graft vs host disease innovation instrument marenostrin microbial microbiome multidisciplinary novel novel therapeutics response skin disorder tool

项目摘要

The Dermatology Branch consultation service evaluates and helps manage patients with cutaneous manifestations of their systemic diseases. We also evaluate and manage the cutaneous adverse reactions experienced by patients on experimental drugs or interventions that are associated with protocols within intramural NIH. Thus, we play an important role in the recognition of adverse reactions to new therapeutic agents and/or interventions differentiating these from manifestations of the diseases for which they are being treated. These consultations help other investigators determine whether these adverse reactions are mild enough to allow continuation of the therapy being tested, or whether the reaction is potentially dangerous enough so that further treatment should be withheld temporarily or permanently. We aid other groups in the delineation of the cutaneous manifestations of the various hereditary and/or syndromic conditions that are being intensively studied at the NIH. This is important in establishing the clinical phenotype of the syndromes under study. We are also at times, called upon to manage acute exacerbations of skin diseases in patients that are not protocol-related. Most patients cared for by the consultation service have rare diseases and/or are participating in innovative Phase 1 or 2 trials. Thus, skin problems encountered in the clinic tend to be unusual and are often complicated. The clustering in time and the novelty of patients that are seen provide a rich and unique resource for both educational and clinical research endeavors. Dr. Cowen and I share coverage of the Consult Service equally. I directly supervise Dr. Kong in the phototoxicity , topical depsipeptide, and cutaneous microbiome protocols. Collaborative clinical research is extremely active by virtue of the busy consultation service. Although most of the collaborative projects currently involve me, such that I am an Associate Investigator on non-Dermatology Branch protocols, Dr. Cowen has become increasingly involved now that he shares in the coverage of the Consultation Service. Collaborative projects include continuing studies of cutaneous findings such as fibrofolliculomas and leiomyomas in patients with familial renal cell carcinoma. We are also characterizing cutaneous lesions that may be associated with several rare inherited bone marrow failure syndromes, including patients with Diamond-Blackfan, Fanconi's anemia, and dyskeratosis congenita. We continue to study cutaneous manifestations and complications of therapy that are encountered in patients with primary immunodeficiencies such as chronic granulomatous disease, hyper-IgE syndrome (Job's syndrome), and immunodeficiency related to mutations in the NEMO gene. The newly discovered mutations in pyrin genes in patients with several periodic fever syndromes, and the availability of biologic therapies that have efficacy in the resulting autoinflammatory diseases have introduced a new group of patients to the clinic. We are now systematically characterizing cutaneous manifestations in these patients and assessing responses to treatment. We are also evaluating the relationship between panniculitis and calcium deposition in patients with juvenile dermatomyosistis and assessing the benefit of intensive systemic therapy in the prevention of smoldering muscle disease and eventual calcification. Dr. Cowen and I are actively involved in the continuing operation of the multidisciplinary chronic graft versus host disease (GVHD) consortium not only within NCI but nationally. We have devised and propagated the use of an instrument meant to characterize and measure skin involvement in GVHD. This assessment tool can be used to measure extent and progression/regression of cutaneous disease and response to therapy. Dr. Cowen is the Study Chair for the cutaneous portion of the protocol on the Natural History of chronic GVHD. He is an Associate Investigator on a protocol investigating the utility of extra corporeal photophoresis as treatment for chronic GVHD and is the Principal Investigator on a new protocol investigating the usefulness of Imatinib in the treatment of sclerotic skin disease associated with chronic GVHD. Only lately has it been recognized that chronic GVHD results in significant involvement in the female genital tract. My expertise in vulvovaginal diseases has enabled me to study the manifestations and treatment of vulvovginal GVHD. Dr. Hwang's and my participation in a multidisciplinary cutaneous T-cell lymphoma (CTCL) interest group has led to similar conclusions regarding the lack of assessment tools. We are in the process of assessing the usefulness of the current tool that we have been using for several years. In particular, we will try to determine which portions of the current assessment tool can simplified so that they can be utilized by non-dermatologists as well as dermatologists and that will be embraced and implemented by extramural investigators participating in multi-center trials. Dermatology Branch-initiated projects are spearheaded by Branch principal investigators. Dr. Hwang is evaluating CTCL patients via a protocol entitled Pathogenesis and course of cutaneous T-cell lymphoma (04-C-0081). Dr. Jonathan Vogel and I collaborated on on the assessment of wavelength-dependence of erythemogenic solar simulator-derived UV radiation on gene expression profiles in skin of normal human volunteers (04-C-0120B). The manuscript is in preparation. As a sequel to the study aimed at the determination of the gene expression profile following exposure to a solar simulator, Dr. Kong and I have finished phototesting and tissue acquisition for the doxycycline portion of the protocol whose aim is to determine the gene expression profile of skin exposed to a solar simulator after ingesting a drug (doxycycline) that increases sensitivity to sunburn. We need to complete the arm of this study exploring the pharmacogenetics, that is, the relationship of drug metabolism to genetic background and how this, specifically impacts on the occurrence of a phototoxic drug reaction to an important systemic antifungal agent, voriconazole. If we find such a correlation, it might become applicable to other agents causing a similar reaction. Our newest protocol is a pilot toxicity study aimed at determination of toxicity of a novel topical therapy for early CTCL. CTCL is a relatively rare disease but it has a long cutaneous phase for which effective topical therapy is not available. Also new this year is my participation in the Human Microbiome Project (HMP) which aims to establish a library of the bacteria present on various parts of the human body, in normal individuals. This initiative is part of the NIH Roadmap and the skin will be one of the 5 organs that will be studied. There are many clinical indications that resident microbes play a major role in the initiation or perpetuation of certain diseases. Establishment of this library will allow comparisons to be made between the microbial flora in those diseases versus that in normals and the impact of these differences on disease pathogenesis and course. In collaboration with Dr. Julie Segre of NHGRI, we are enrolling patients with atopic dermatitis where there are strong clinical indications that this disease is exac [summary truncated at 7800 characters]

皮肤科咨询服务评估并帮助管理患有全身性疾病皮肤表现的患者。我们还评估和管理患者在使用与 NIH 内协议相关的实验药物或干预措施时经历的皮肤不良反应。因此，我们在识别新治疗药物和/或干预措施的不良反应并将其与所治疗疾病的表现区分开来方面发挥着重要作用。这些咨询可以帮助其他研究人员确定这些不良反应是否足够轻微，可以继续正在测试的治疗，或者反应是否有足够的潜在危险，以至于应暂时或永久停止进一步治疗。我们帮助其他团体描述 NIH 正在深入研究的各种遗传性和/或综合征病症的皮肤表现。这对于确定所研究综合征的临床表型非常重要。有时，我们还需要处理与方案无关的患者皮肤病的急性加重。大多数接受咨询服务的患者患有罕见疾病和/或正在参加创新的 1 期或 2 期试验。因此，临床上遇到的皮肤问题往往不寻常且往往很复杂。时间上的聚集和所见患者的新颖性为教育和临床研究工作提供了丰富而独特的资源。考恩博士和我平等地共享咨询服务。我直接监督 Kong 博士的光毒性、外用缩酚肽和皮肤微生物组方案。凭借繁忙的咨询服务，临床协作研究异常活跃。尽管目前大多数合作项目都涉及我，例如我是非皮肤科分支协议的副研究员，但考恩博士现在越来越多地参与其中，因为他分享了咨询服务的覆盖范围。合作项目包括继续研究家族性肾细胞癌患者的皮肤表现，例如纤维毛囊瘤和平滑肌瘤。我们还描述了可能与几种罕见的遗传性骨髓衰竭综合征相关的皮肤病变，包括戴蒙德-布莱克范（Diamond-Blackfan）、范科尼贫血和先天性角化不良患者。我们继续研究原发性免疫缺陷患者的皮肤表现和治疗并发症，例如慢性肉芽肿病、高 IgE 综合征（乔布氏综合征）以及与 NEMO 基因突变相关的免疫缺陷。新发现的几种周期性发热综合征患者的pyrin基因突变，以及对由此产生的自身炎症性疾病有效的生物疗法的出现，将一组新的患者引入了临床。我们现在正在系统地描述这些患者的皮肤表现并评估对治疗的反应。我们还在评估青少年皮肌炎患者脂膜炎和钙沉积之间的关系，并评估强化全身治疗在预防闷烧性肌肉疾病和最终钙化方面的益处。 Cowen 博士和我不仅在 NCI 内部而且在全国范围内积极参与多学科慢性移植物抗宿主病 (GVHD) 联盟的持续运作。我们设计并推广了一种仪器，旨在表征和测量 GVHD 中的皮肤受累情况。该评估工具可用于测量皮肤疾病的程度和进展/消退以及对治疗的反应。 Cowen 博士是慢性 GVHD 自然史方案皮肤部分的研究主席。他是一项研究体外光泳治疗慢性 GVHD 效用的方案的副研究员，也是一项研究伊马替尼在治疗与慢性 GVHD 相关的硬化性皮肤病中的有效性的新方案的首席研究员。直到最近人们才认识到慢性 GVHD 会严重累及女性生殖道。我在外阴阴道疾病方面的专业知识使我能够研究外阴阴道 GVHD 的表现和治疗。 Hwang 博士和我参加的多学科皮肤 T 细胞淋巴瘤 (CTCL) 兴趣小组就缺乏评估工具得出了类似的结论。我们正在评估我们已经使用多年的当前工具的实用性。特别是，我们将尝试确定当前评估工具的哪些部分可以简化，以便非皮肤科医生和皮肤科医生都可以使用它们，并将被参与多中心试验的外部研究人员接受和实施。皮肤病学分会发起的项目由分会主要研究人员带头。 Hwang 博士正在通过名为皮肤 T 细胞淋巴瘤发病机制和病程 (04-C-0081) 的方案评估 CTCL 患者。 Jonathan Vogel 博士和我合作评估了致红太阳模拟器衍生的紫外线辐射对正常人类志愿者皮肤基因表达谱的波长依赖性 (04-C-0120B)。手稿正在准备中。作为旨在确定暴露于太阳模拟器后基因表达谱的研究的后续部分，Kong 博士和我完成了方案中强力霉素部分的照片测试和组织采集，其目的是确定在摄入增加晒伤敏感性的药物（强力霉素）后暴露于太阳模拟器的皮肤的基因表达谱。我们需要完成这项研究的一部分，探索药物遗传学，即药物代谢与遗传背景的关系，以及它如何具体影响重要的全身抗真菌药物伏立康唑的光毒性药物反应的发生。如果我们发现这种相关性，它可能适用于引起类似反应的其他药物。我们最新的方案是一项试点毒性研究，旨在确定早期 CTCL 新型局部疗法的毒性。 CTCL 是一种相对罕见的疾病，但其皮肤期较长，尚无有效的局部治疗。今年的另一个新变化是我参与了人类微生物组项目（HMP），该项目旨在建立一个存在于正常个体人体各个部位的细菌库。该计划是 NIH 路线图的一部分，皮肤将成为将要研究的 5 个器官之一。许多临床迹象表明，常驻微生物在某些疾病的发生或持续中发挥着重要作用。该库的建立将允许对这些疾病中的微生物菌群与正常人中的微生物菌群进行比较，以及这些差异对疾病发病机制和病程的影响。我们与 NHGRI 的 Julie Segre 博士合作，招募特应性皮炎患者，这些患者有强烈的临床迹象表明这种疾病是确切的[摘要截断为 7800 个字符]