Biomedical subjects
Publications and source records attributed to R G Edwards.
The origin of deletions associated with non-obstructive severe oligozoospermia in men are discussed. Deletions could arise during various stages of meiosis, at later stages in spermatids, or post-fertilization. Certain embryonic stages may be highly sensitive. The possibilities of an inherited propensity to these and other deletions, and of mosaicism in embryos are assessed.
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OBJECTIVES: This paper evaluates the cultural equivalence of Cantonese, Vietnamese, and Laotian translations of the Affect Balance Scale. METHODS: The scale was completed by 399 Vietnamese, 193 Laotian, 756 Cantonese, and 319 English speakers who were participants in the Clarke Institute-University of Toronto Refugee Resettlement Project (n = 1667). RESULTS: Confirmatory factor analyses indicated a good fit between the hypothesized two-factor model (separate factors for positive and negative affect) across the original English-language version and each of the Asian-language translations. Factorial invariance (numbers and patterns of factor loadings) was evident across all versions of the scale. No evidence of item bias was detected by mixed Language x Item analyses of variance. Acceptable reliability was observed; coefficient alphas ranged from .62 to .72 for positive affect and from .62 to .70 for negative affect items. CONCLUSIONS: These findings substantiate the cultural equivalence of the three translations of the scale for population health research. Important future research directions made possible by the availability of culturally equivalent instruments are discussed.
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This review lecture is primarily concerned with the study of assisted human conception and especially in-vitro fertilization (IVF). It also places in perspective the role of endocrinology in history of IVF. A knowledge of the hypothalamic-pituitary control of ovulation, and of ovarian follicle dynamics is assumed. A detailed consideration of these topics, together with extensive references, are available in a recent textbook (Edwards and Brody, 1995). Many of the early pioneers studying animal reproduction combined reproductive physiology and endocrinology, especially Marshall, who analysed oestrous and menstrual cycles in many mammalian species. The clarification of the roles of pituitary gland and hypothalamus in the menstrual cycle and ovulation, and their regulation by steroidal feedbacks from the gonads gave an immense stimulus to studies on human reproduction (Smith and Engle, 1927; Lewis and Gregory, 1933; Harris, 1970). Three periods of research into assisted human conception are covered in this lecture including the initial work on the introduction of the endocrinology and embryology of human IVF, the rapid advances in technique as it expanded worldwide, and finally some of the recent remarkable advances in the field.
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Experimental evidence in a number of different in vivo and in vitro systems indicates clearly that the vertebrate oocyte is capable of repairing endogenous and exogenous DNA damaged as a result of meiotic recombination, the action of UV and X-irradiation or the effects of mutagenic chemicals. It would appear that both before and after the dictyate stage of meiosis the oocyte has less repair capacity and/or is more sensitive to DNA damaging agents. Epigenetic factors associated with the expression of genetic faults arising in oocytes have been largely ignored in the past. It is probable that attention to such factors, will in the future, lead to a better appreciation of the capacity of oocytes to repair genetic damage. Non-disjunctional events are particularly prone to occur in dictyate oocytes. Oxygen deprivation, perturbations of microtubular structure by temperature and other factors appear to have disastrous cytogenetic consequences at this otherwise resistant resting stage.
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Serum cystatin C has been suggested as a new marker of GFR. For the introduction of this marker into clinical use a rapid and automated method is required. We have developed and validated an assay for serum cystatin C using latex particle-enhanced immunoturbidimetry. Intra- and inter-assay precision were < 3% and < 5% across the assay range. Analytical recovery was 93 +/- 3.8% and no lack of parallelism was demonstrated. Regression analysis of a method comparison with an enzyme-enhanced radial-immunodiffusion method, gave PETIA = 0.074 + 0.93 x SRID, r = 0.98, N = 100. Inter-assay precision profiles showed cystatin C was measured with two-fold better precision than creatinine on the same analyzer. Cystatin C measurement was neither interfered with by icterus nor by hemolysis. 1/cystatin C versus 1/creatinine concentrations gave r = 0.67, N = 469. Comparison of Cr EDTA GFR with 1/cystatin C and 1/creatinine gave r = 0.81 and 0.50, respectively, N = 206. Calculating diagnostic sensitivity for abnormal GFR showed cystatin C to be significantly (P < 0.05) more sensitive than creatinine (71.4 vs. 52.4%). Cystatin C measurement using PETIA technology can be automated on the same instruments used routinely for the measurement of creatinine and offers better analytical performance and probably improved clinical sensitivity as a screening test for early renal damage.
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A greatly increased amount of knowledge on the preimplantation embryo and the molecular biology of the uterus have led to the development of new concepts on the adhesion of the embryo to the uterus and on the implantation process. This brief review covers cleavage and blastocyst formation, and the preparations of the embryo for implantation. The molecular factors involved in human implantation are then described, including the role of the steroid hormones, cytokines, adhesion molecules and substrates. The changes occurring in the embryo and uterus during implantation are described. Brief descriptions of extravillous trophoblast and the role of immune-type responses in the uterus are given. Finally, the molecular aspects of human implantation are considered.
An improvement in clinical pregnancy rate follows a natural or induced period of amenorrhoea. The cause is unknown, but it could be related to the period of uterine 'rest' which may restore full function to the steroid-sensitive systems, such as the pinopodes, after a prolonged period of constant menstrual cycling. This may result in the restoration of uterine capacity for embryo implantation to levels typical of younger women. Some other avenues of research on the unusual aspects of human implantation are worth further study. An impaired uterine blood flow could lower the chances of implantation. Immunological factors may emerge as major elements in the human implantation process, because the neutralization of antiphospholipid antibodies may enhance the activity of early trophoblast.
Coelocentesis offers a new opportunity for gaining access to the coelomic cavity of human embryos from 28 days post-fertilization (42 days menstrual age). With this technique, cells can be extracted from the cavity for the genetic typing of embryos in early pregnancy. Coelocentesis may also offer a unique opportunity of inducing tolerance to foreign grafts and chimaerism in these human embryos by replacing donor cells into the coelomic cavity. This cavity appears to be closely associated with the fetal haemopoietic system. The optimal age to inject stem cells designed to produce chimaerism may be at 5-6 weeks embryonic age, and these grafted cells may induce tolerance later in gestation. Two successive coelocenteses would be needed, the first to extract fetal cells to type the fetus, and a second within a few days to inject the donor cells into the coelomic cavity. Alternatively, non-invasive methods of diagnosis such as lower uterine pole extramembranous sampling of fetal trophoblast, or the extraction of fetal cells from maternal blood, could be combined with coelocentesis. If tolerance and chimaerism can be established, repeated tissue grafts could be carried out during fetal life and after birth, so that disorders caused by single or multiple gene defects in the haemopoietic system and other organs may be corrected.
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