The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients

This study investigated the influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E ₂) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E₂ was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3%±9.5%, 70.0%±5.1% and 57.3%±5.3%, respectively (mean±SEM). Corresponding values for plasma E₂ suppression were 30.7%±6.5%, 43.4%±4.5% and 42.9%±6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E₂ levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E₂ suppression was observed. The suppression of E₂ by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.     

Mechanical Analysis of Atherosclerotic Plaques Based on Optical Coherence Tomography

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.