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Biomedical subjects

M Bigby

Publications and source records attributed to M Bigby.

At least 19 recordsLinked to original sources

A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma.

OBJECTIVE: To systematically review the use of reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase messenger RNA as a molecular serum marker for metastatic melanoma. DATA SOURCES: Computerized searches (1966-1999) of the PubMed and MDConsult databases and a manual search of retrieved article references. STUDY SELECTION: Cohort studies containing test subjects and negative controls were reviewed. DATA EXTRACTION: Three investigators independently screened abstracts for relevant studies and 2 investigators independently reviewed all eligible studies. DATA SYNTHESIS: Of 127 identified studies, 50 were reviewed in detail and 23 met all inclusion criteria. From these 23 studies, the PCR methods, the total number of patients, the number of control subjects, and the number of RT-PCR-positive patients per stage were analyzed. Results of RT-PCR for tyrosinase messenger RNA were positive in 18% (95% confidence interval [CI], 3%-22%) patients for stage I disease, 28% (95% CI, 23%-34%) for stage II disease, 19% (95% CI, 16%-21%) for stage I/II localized disease, 30% (95% CI, 26%-34%) for stage III disease, and 45% (95% CI, 41%-50%) for stage IV disease. Specificities were 100% in all but 1 study. Results of RT-PCR were positive in only 0.4% of healthy controls and patients with nonmelanoma cancer. CONCLUSIONS: The lack of data on the outcome of stage I, II, and III patients who were RT-PCR positive and the low prevalence of RT-PCR positivity in patients with known stage IV disease limit the applicability of this test at this time. Ongoing and future studies on a quantitative RT-PCR, amplification of multiple melanoma-associated antigens, and use of the test as a prognostic indicator might improve the utility of this molecular serologic tool.

Biomarkers, Tumor↗

Rates of cutaneous reactions to drugs.

OBJECTIVE: To determine the validity, magnitude, precision, and applicability of data on the rates at which drugs cause adverse cutaneous reactions. DESIGN: Systematic review of the medical literature. DATA SOURCE: The MEDLINE database was searched (1966-August 2000) for studies that contain information on the rates of cutaneous reactions to drugs. The bibliographies of retrieved articles and review articles were also examined to find relevant studies. MAIN OUTCOME MEASURES: Studies that included primary data on cutaneous reaction rates to drugs were evaluated for their validity, magnitude, precision, and applicability, using guidelines derived from existing guidelines for the evaluation of articles about harm and prognosis. RESULTS: Nine studies met the study criteria. Five of the studies were based on prospectively collected data on medical inpatients, 2 were retrospective studies based on chart or computerized medical record review, and 2 were based on spontaneous reports and consumption data. The morbilliform drug exanthem and urticaria were the most common cutaneous reactions to drugs. Reaction rates varied from 0% to 8% and were highest for antibiotics (in the range of 1% to 8% for several classes of antibiotics). CONCLUSIONS: Despite differences in the methods of the studies reviewed and their time of execution, there is remarkable agreement in the results. Reaction rates (and 95% confidence intervals) are available for many commonly used drugs.

Anti-Bacterial Agents↗

Paradigm lost.

Explore the source record for details and available documents.

Dermatology↗

Preliminary functional analysis of human epidermal T cells.

The function of human epidermal T cells (ETC) is unknown. In the present study, dermal T cells (DTC), ETC and keratinocytes were cultured from normal human skin. DTC and ETC lines were expanded in medium containing interleukin 2. The autologous keratinocytes were transfected with a human papillomavirus 16 E6 and E7 plasmid to produce an immortal keratinocyte line "HEK001". Lymphocyte migration and adhesion to HEK001 was assessed in calcein fluorimetric assays. ETC migrated towards HEK001 three to four times more than DTC. ETC adhered to HEK001 two to four times more than DTC. The proportion of ETC expressing the cutaneous lymphocyte-associated antigen was greater than that of DTC (26% and 1%, respectively). The keratinocyte line HEK001 expressed ICAM-1 following stimulation with TNF-alpha or IFN-gamma and following coculture with autologous cutaneous T cells. A blocking anti-ICAM-1 antibody reduced DTC and ETC adhesion to HEK001 by 30% and 50%, respectively. Therefore, cutaneous T cells may upregulate keratinocyte ICAM-1 expression which mediates adhesion to autologous keratinocytes. These results are consistent with the hypothesis that the ETC and DTC populations are distinct. Both directed migration (epidermotropism) and selective retention may be involved in the development and maintenance of the ETC population in normal human skin.

Antigens, CD↗

Evidence-based medicine in dermatology.

EBM is the use of the best current evidence in making decisions about the care of individual patients. Practicing EBM requires five steps: (1) formulating well-built clinical questions, (2) finding the best evidence to answer the questions, (3) critically appraising the evidence, (4) applying the evidence to specific patients, and (5) saving the critically appraised evidence. The Cochrane Library is the best source for finding the best evidence about treatment. The second best method for finding evidence about treatment and the best source for finding most other types of best evidence in dermatology is by searching the MEDLINE database using the PubMed Clinical search engine of the National Library of Medicine (http://++www.ncbi.nlm.nih.gov/PubMed/clin ica l.html). MEDLINE searches have inherent software and operator limitations that make their reliability quite variable. The quality (strength) of evidence is based on a hierarchy of evidence: results of systematic reviews of well-designed clinical studies, results of one or more well-designed clinical studies, results of large case series, and expert opinion. Once the best evidence has been found, the EBM approach involves critically appraising the quality of the evidence, determining its magnitude and precision, and applying it to the specific patient. Guidelines to appraise critically and apply evidence are available. The clinical question, best evidence, and its critical appraisal should be saved in a format that can be easily retrieved for future use.

Dermatology↗

Autocytotoxic T-cell clones in lichen planus.

We examined the in vitro cytotoxic activity of cutaneous T-cell lines and clones from lichen planus (LP) patients against autologous epidermal keratinocytes. T cells were cultured from LP lesions and adjacent clinically normal skin and cloned by limiting dilution. Keratinocytes were cultured from LP lesions and adjacent clinically normal skin and immortalized by transfection with the E6 and E7 genes from human papillomavirus 16 (HPV16). The lesional T-cell line from one LP patient contained 27% gammadelta+ T cells and was significantly more cytotoxic against autologous lesional keratinocytes than the T-cell line from clinically normal skin. Clones isolated from the lesional T-cell line were significantly more cytotoxic against autologous lesional keratinocytes than clones isolated from the non-lesional T-cell line. Most cytotoxic clones from LP lesions were CD8+ and most non-cytotoxic clones from LP lesions were CD4+. One cytotoxic clone was CD4- and CD8- and expressed the gammadelta T-cell receptor. Two CD8+ LP lesional T-cell clones showed dose-dependent killing of HPV16 E6/E7-immortalized autologous lesional and normal keratinocytes, but no cytotoxic activity against Epstein-Barr virus-transformed autologous B-cell blasts. The cytotoxic activity of CD8+ lesional T-cell clones against autologous lesional keratinocytes was partially blocked with anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These data support the hypothesis that CD8+ lesional T cells recognize an antigen associated with MHC class I on lesional keratinocytes and that CD8+ cytotoxic T cells lyse keratinocytes in LP lesions.

Antibodies, Monoclonal↗