Biomedical subjects

Derek Gordon

Publications and source records attributed to Derek Gordon.

39 records · Page 3Linked to original sources

PubMed2002

Multiple cutaneous and uterine leiomyomas: refinement of the genetic locus for multiple cutaneous and uterine leiomyomas on chromosome 1q42.3-43.

Cutaneous leiomyomas, rare benign tumors originating from the arrector pili muscle of the hair follicle, can be associated with the common uterine fibroids in a syndrome called multiple cutaneous and uterine leiomyomas. Multiple cutaneous and uterine leiomyomas are inherited as an autosomal dominant trait, providing an excellent opportunity for the study of the common non-Mendelian manifestation of isolated uterine fibroids. This study reports the clinical and molecular characterization of an extended family with multiple cutaneous and uterine leiomyomas. Linkage analysis has shown that the disease in this family is linked to the recently reported genetic locus for multiple cutaneous and uterine leiomyomas, with a maximum two-point LOD score of 4.453 for markers D1S2670, D1S2785, D1S547, and D1S1609. The identification of key recombination events has allowed us to refine substantially the location of the genetic locus for multiple cutaneous and uterine leiomyomas, from 14 cM to an interval of 4.55 or 7.19 cM, depending on the final phenotype of a young family member in which one of the key recombination events has occurred. In addition, we provide a description of the interesting pattern and progression of the skin phenotype in this four-generation kindred. The refinement of the genetic locus for multiple cutaneous and uterine leiomyomas and the availability of an extended multigeneration pedigree will facilitate the identification of the mutated gene responsible for multiple cutaneous and uterine leiomyomas, which, in turn, may provide key information for the understanding of the molecular basis of the common uterine fibroids.

Adolescent↗

PubMed2002

Power and sample size calculations for case-control genetic association tests when errors are present: application to single nucleotide polymorphisms.

The purpose of this work is to quantify the effects that errors in genotyping have on power and the sample size necessary to maintain constant asymptotic Type I and Type II error rates (SSN) for case-control genetic association studies between a disease phenotype and a di-allelic marker locus, for example a single nucleotide polymorphism (SNP) locus. We consider the effects of three published models of genotyping errors on the chi-square test for independence in the 2 x 3 table. After specifying genotype frequencies for the marker locus conditional on disease status and error model in both a genetic model-based and a genetic model-free framework, we compute the asymptotic power to detect association through specification of the test's non-centrality parameter. This parameter determines the functional dependence of SSN on the genotyping error rates. Additionally, we study the dependence of SSN on linkage disequilibrium (LD), marker allele frequencies, and genotyping error rates for a dominant disease model. Increased genotyping error rate requires a larger SSN. Every 1% increase in sum of genotyping error rates requires that both case and control SSN be increased by 2-8%, with the extent of increase dependent upon the error model. For the dominant disease model, SSN is a nonlinear function of LD and genotyping error rate, with greater SSN for lower LD and higher genotyping error rate. The combination of lower LD and higher genotyping error rates requires a larger SSN than the sum of the SSN for the lower LD and for the higher genotyping error rate.

Case-Control Studies↗

PubMed2002

The effect of metformin on hirsutism in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterised by insulin resistance and often associated with hirsutism. Insulin sensitising agents, such as metformin, improve both the biochemical and reproductive parameters; however, no study has been designed to specifically assess the effect of metformin on hair growth. DESIGN AND PATIENTS: Sixteen women with PCOS and hirsutism were enrolled into a 14 month (two 6 month phases with a 2 month washout) double-blind placebo-controlled cross over study. MEASUREMENTS: Hirsutism was assessed using the Ferriman and Gallwey (F-G) score, patient self-assessment and growth velocity. Weight, height and waist-hip ratio were recorded. Gonadotrophins, androgens, plasma glucose and lipids were also measured. RESULTS: Ten women completed the full 14 month study. There was a significant improvement in hirsutism at the end of the metformin phase compared with placebo: F-G score 15.8+/-1.4 vs 17.5+/-1.2 (P=0.025) and patient self-assessment 2.4+/-0.1 vs 3.3+/-0.3 (P=0.014). Growth velocity, in millimetres per day at the end of each phase also improved (0.67+/-0.17 vs 0.77+/-0.11; P=0.03). There was a non-significant improvement in both sex hormone binding globulin (SHBG) and free androgen index (FAI), although there was a significant difference between baseline and metformin treatment for SHBG (P=0.023) and FAI (P=0.036). Metformin treatment also reduced weight significantly (91.5+/-7.6 vs 94.0+/-9.8 kg; P=0.009) and led to a significant improvement in cycle frequency (0.53+/-0.12 vs 0.35+/-0.08 cycles per month; P=0.008). CONCLUSION: We have demonstrated that metformin treatment in a group of women with PCOS results in a clinically and statistically significant improvement in hair growth compared with placebo.

Body Constitution↗