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Results for “Human Challenge Trials as Topic”

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At least 37 records · Page 2Linked to original sources
PubMed2000

Chronic neuropathic pain: mechanisms and treatment.

There have been considerable advances in our understanding of the pathophysiology of neuropathic pain. There is still a lack of consensus about the optimal therapeutic strategy of such conditions, however. Drugs are generally selected on the basis of their established efficacy in randomized controlled studies in etiologically based groups of patients. These studies have been important in confirming the efficacy of antidepressants, antiepileptics, local anesthetics and derivatives, capsaicin, opioids, and N-methyl-D-aspartate antagonists in neuropathic pain, specifically painful diabetic neuropathy and postherpetic neuralgia. More specific therapeutic strategies based on precise quantified assessment of the various components of neuropathic pain are now increasingly used and may provide insight regarding the effects of treatments of particular symptoms (e.g., allodynia, hyperalgesia). In some cases, such assessment may also help to analyze the mechanisms involved in pain, thus allowing selection of treatment on a more rational basis. A mechanism-based approach seems promising for clinical research studies, although its application in current management remains challenging.

Chronic Disease↗
PubMed1999

Quality-of-life end points in oncology drug trials.

Health-related quality of life (HRQL) is a multidimensional construct that represents the patient's perspective on valued aspects of health and functioning. Over the last several years, the pharmaceutical industry, as well as health care providers and the patient advocacy community, have shown increasing interest in HRQL as an outcome measure. Pharmaceutical companies and other sponsors of cancer clinical trials are seeking novel approaches with which to establish the benefits of treatment and to differentiate their products from other marketed products. Health care providers hope to provide cancer patients with therapies that positively affect their quality of life. To date, however, most oncology drug approvals have been based on traditional end points, such as survival and tumor response rate. This article will focus on some of the lessons learned from recent reviews of HRQL data and will describe some of the many challenges that lie ahead.

Clinical Trials as Topic↗
PubMed2004

Targeting the molecular target of rapamycin (mTOR).

PURPOSE OF REVIEW: The molecular target of rapamycin, which is a member of the phosphoinositide 3-kinase related kinase family and a central modulator of cell growth, is a unique and prime strategic target for anticancer therapeutic development. RECENT FINDINGS: The molecular target of rapamycin plays a critical role in transducing proliferative signals mediated through the phosphatidylinositol 3 kinase and protein kinase B signaling pathways, principally by activating downstream protein kinases that are required for both ribosomal biosynthesis and translation of mRNAs of proteins that are essential for G1 to S phase traverse. By targeting the molecular target of rapamycin with high potency and specificity, the immunosuppressant and antiproliferative agent rapamycin inhibits signals required for cell cycle progression, cell growth, and proliferation. Both rapamycin and several rapamycin analogs with more favorable pharmaceutical properties have demonstrated impressive growth inhibitory effects against a broad range of human cancers in both preclinical and early clinical evaluations. SUMMARY: This review discusses recent findings regarding the principal mechanisms of action of the rapamycins, the potential utility of these agents as anticancer therapeutics, clinical results to date, and developmental challenges that lie ahead.

Antibiotics, Antineoplastic↗
PubMed1989

In vivo and in vitro effects of antihistamines on mast cell mediator release: a potentially important property in the treatment of allergic disease.

A nasal antigen challenge model of allergic individuals was used to evaluate whether antihistamines could inhibit human mast cell and basophil mediator release in vivo. In placebo-controlled trials, topically applied azatadine base, a tricyclic antihistamine with in vitro antirelease action, effectively reduced symptoms and mediator levels in nasal lavage fluids after antigen challenge, suggesting mast cell inhibition. Both terfenadine and cetirizine, systemically administered antihistamines, were clinically effective in reducing sneezing and changes in vascular permeability. Only terfenadine significantly reduced histamine in antigen-induced nasal secretions. However, cetirizine did reduce the level of leukotriene C4 in these fluids. These results indicate that some antihistamines may be capable of suppressing mediator release from nasal mast cells. The significance of this property in those compounds' overall clinical effect is unclear because of their other concomitant activities.

Administration, Intranasal↗