Withholding information from study participants in clinical trials: ethical considerations.
Explore the source record for details and available documents.
Access to Information↗
Biomedical subjects
Michael Dosik
Publications and source records attributed to Michael Dosik.
Analysis of single nucleotide polymorphisms in the promoter region of interleukin-10 by denaturing high-performance liquid chromatography.
Interleukin-10 (IL10), an anti-inflammatory cytokine, has been implicated in a variety of immune- and inflammatory-related diseases. We investigated the following SNPs: -1082, -819, -592 in the promoter region of IL10 in a normal (control) population and selected diseases: breast cancer (BrCa), systemic lupus erythematosus (SLE), and B-cell chronic lymphocytic leukemia (B-CLL) by denaturing high-performance liquid chromatography (DHPLC) and found distinct genotype and haplotype patterns. DHPLC was performed using the Transgenomic WAVE instrument, a mutational discovery tool that allows for high throughout analysis of SNPs. The principle of DHPLC is based on separation of homo- and heteroduplex formation of individual polymerase chain reaction products at specific melting temperatures and set gradients. The melting temperature selected for each SNP was based on size and sequence of the polymerase chain reaction product (for -1082, 57 degrees C; for -819, 58 degrees C; and for -592, 59.2 degrees C). Before fragment mutational analysis, all samples were denatured at 95 degrees C and slowly reannealed to allow for reassociation of different strands. Heteroduplex samples were easily distinguished from homoduplex samples. In order to identify wild type from homozygous mutant, two homoduplex polymerase chain reaction samples had to be mixed together, denatured at 95 degrees C and reannealed. The homozygous mutant, when combined with wild type, displayed a double peak on chromatogram. Once distinct chromatograms were established for each of the SNPs and the nucleotide changes confirmed by sequencing, genotype and haplotype frequencies were tabulated for the groups studied.
Base Sequence↗
Raloxifene rebound regression.
The first case of clinical remission of metastatic breast after the withdrawal of raloxifene is reported. A postmenopausal woman was treated for stage II breast cancer with a modified radical mastectomy and adjuvant cyclophosphamide, doxorubicin, and 5-flurouracil followed by tamoxifen for 5 years. One year following the cessation of tamoxifen, osteopenia was noted and raloxifene was begun. Two years following the start of raloxifene, supraclavicular adenopathy and lung metastases developed, which regressed after discontinuation of raloxifene. Although raloxifene is not frequently given to women with previous breast cancer, increasing use in osteopenic women may lead to cancer developing in these raloxifene-treated women; this despite the major reduction in the incidence of breast cancer in raloxifene-treated versus placebo-treated women. A clinically significant response to the withdrawal of a hormone, used either for the treatment of breast cancer or for some other reason, is not a rare event, and the therapeutic usefulness of observation only for a rebound regression is a frequently overlooked strategy in the treatment of breast cancer.
Antineoplastic Agents↗