Biomedical subjects

David Harden

Publications and source records attributed to David Harden.

5 recordsLinked to original sources

PubMed2004

A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells.

Potassium channels have been identified as targets for a large number of therapeutic indications. The ability to use a high-throughput functional assay for the detection and characterization of small-molecule modulators of potassium channels is very desirable. However, present techniques capable of screening very large chemical libraries are limited in terms of data quality, temporal resolution, ease of use, and requirements for specialized instrumentation. To address these issues, the authors have developed a fluorescence-based thallium flux assay. This assay is capable of detecting modulators of both voltage and ligand-gated potassium channels expressed in mammalian cells. The thallium flux assay can use instruments standard to most high-throughput screening laboratories, and using such equipment has been successfully employed to screen large chemical libraries consisting of hundreds of thousands of compounds.

Biological Assay↗

PubMed2003

Fluorine substitution can block CYP3A4 metabolism-dependent inhibition: identification of (S)-N-[1-(4-fluoro-3- morpholin-4-ylphenyl)ethyl]-3- (4-fluorophenyl)acrylamide as an orally bioavailable KCNQ2 opener devoid of CYP3A4 metabolism-dependent inhibition.

The formation of a reactive intermediate was found to be responsible for CYP3A4 metabolism-dependent inhibition (MDI) observed with (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (1). Structure-3A4 MDI relationship studies culminated in the discovery of a difluoro analogue, (S)-N-[1-(4-fluoro-3-morpholin-4-ylphenyl)ethyl]-3-(4-fluoro-phenyl)acrylamide (2), as an orally bioavailable KCNQ2 opener free of CYP3A4 MDI.

Administration, Oral↗

PubMed2003

Lichen planus associated with hepatitis C virus: no viral transcripts are found in the lichen planus, and effective therapy for hepatitis C virus does not clear lichen planus.

BACKGROUND: Although hepatitis C virus (HCV) was not discovered until 1989, it was recognized for many years that a viral agent was responsible for many cases of posttransfusion or parenterally transmitted hepatitis. Acute HCV is often relatively mild; however, 70% to 80% of patients with HCV go on to develop chronic liver disease during a prolonged period of up to 40 years, and up to 50% of them may remain relatively asymptomatic during that time. A number of associated cutaneous findings have been reported in up to 15% of these patients including lichen planus-like eruptions (LP). OBJECTIVE: We sought to determine whether viral transcripts were present within the skin of patients with HCV and LP, and if systemic virologic response to interferon alfa and ribavirin correlated with response of the LP. Materials and methods A total of 4 men and 1 woman all presented with cutaneous eruptions of LP, and 1 had oral LP lesions. Cutaneous biopsies were performed on all patients. All patients were found to have chronic HCV. In addition to pathologic examination, immunohistochemical stains for lymphoid markers and reverse-transcriptase polymerase chain reaction for HCV was performed on the biopsy specimens. All patients were treated with interferon alfa and ribavirin. RESULTS: In LP there were scattered eosinophils seen in biopsy specimens of 4 of the 5 patients. The lymphoid infiltrate contained predominantly CD3(+) T cells and scattered KP-1(+) mononuclear cells, without CD20(+) B cells. Approximately one fourth of the T cells failed to mark with CD4. Although all patients were seropositive for HCV RNA at the time of biopsy, we were unable to detect HCV RNA by reverse-transcription polymerase chain reaction in any of the patients. The patients' LP showed an inconsistent response to therapy. CONCLUSION: The virus was not found in the LP lesion using reverse-transcription polymerase chain reaction for HCV. Thus, LP appears to be related to the pattern of immune dysregulation induced by HCV, probably in a host with an underlying susceptibility for autoimmune disease. The combination of interferon alfa and ribavirin may be effective in clearing the virus, but viral response did not correlate with clearing of LP.

Adult↗

PubMed2003

Teledermatology: an intraobserver diagnostic correlation study, part I.

Many studies have been published recently on the effectiveness of teledermatology as a diagnostic tool; however, much of the data comes from live 2-way video teleconferencing consultations and very little comes from more readily available "store and forward" consultations. Moreover, most published studies compare the diagnoses of 2 different dermatologists (interobserver comparison). Given the lack of data on baseline interdermatologist diagnostic variability, the interpretation of currently available diagnostic correlation data is somewhat difficult. The objective of this study is to measure the degree of diagnostic concordance between a dermatologist seeing a patient via a teledermatology consult system and the same dermatologist seeing the same patient face-to-face in a dermatology clinic at a tertiary medical center. A random sample of 404 patients was selected from patients who had routine appointments at our dermatology clinic.

Adolescent↗

PubMed2003

Teledermatology: an intraobserver diagnostic correlation study, Part II.

This is part II of an intraobserver diagnostic correlation study comparing teledermatology with traditional face-to-face evaluation. Part I discussed the methodology and diagnostic correlation results between teledermatology and in-person consultation (Cutis. 2003;71:399-403). This second part reports the diagnostic certainty level between the 2 groups, which are shown to be significantly different (teledermatology, 7/10; in-person, 9/10). This difference held true in every category of skin condition evaluated (P < or = .0065). Unlike other studies, we found that teledermatologists recommended biopsies 10% more frequently than clinic-based evaluators. We discuss the reasons for the lower diagnostic certainty level of teledermatologists, as well as the limitations of this study. Despite the limitations, we conclude that teledermatology appears to be an effective method of delivering dermatologic care in the appropriate setting.

Biopsy↗