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Biomedical subjects

C A Finn

Publications and source records attributed to C A Finn.

At least 19 recordsLinked to original sources

Aerogeophysical measurements of collapse-prone hydrothermally altered zones at Mount Rainier volcano.

Hydrothermally altered rocks can weaken volcanoes, increasing the potential for catastrophic sector collapses that can lead to destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and severity of subsurface alteration is largely unknown on any active volcano. At Mount Rainier volcano (Washington, USA), collapses of hydrothermally altered edifice flanks have generated numerous extensive debris flows and future collapses could threaten areas that are now densely populated. Preliminary geological mapping and remote-sensing data indicated that exposed alteration is contained in a dyke-controlled belt trending east-west that passes through the volcano's summit. But here we present helicopter-borne electromagnetic and magnetic data, combined with detailed geological mapping, to show that appreciable thicknesses of mostly buried hydrothermally altered rock lie mainly in the upper west flank of Mount Rainier. We identify this as the likely source for future large debris flows. But as negligible amounts of highly altered rock lie in the volcano's core, this might impede collapse retrogression and so limit the volumes and inundation areas of future debris flows. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock.

Journal Article↗

Reproductive ageing and the menopause.

This brief review describes early work initiated by Anne McLaren and John Biggers, in which they repeated on mice a very early experiment carried out by John Hunter on pigs, to test the effect of unilateral ovariectomy on subsequent breeding performance. This and subsequent experiments led to the conclusion that reproductive ageing in the female mouse was largely due to ageing changes in the uterus. As a result of these changes fewer implanted blastocysts are carried to term in the older females, with the result that the size of litters produced gradually drops and ceases altogether well before the expected time of death, thus leading to a period of reproductive inactivity at the end of life. Other organs undergo ageing changes but it appears to be those in the uterus which limit reproductive performance in the female. The somatic organs concerned in bringing the male gametes into the environment are still able to function effectively almost until the time of death so that males have a very short period of reproductive inactivity at the end of their lives. Due to the prenatal onset of meiosis in the germ cells, female mammals and some, but not all, other vertebrates are born with a finite crop of oocytes in the ovary, which cannot be increased after birth. Nevertheless, with the exception of women, female mammals appear to be able to produce ova well into old age, and have them fertilized. When examined after death the ovaries still contain oocytes so this is not a limiting factor in reproduction in old females. In women the situation is completely different. They also have an extended period of reproductive quiescence in middle and old age, the menopause, but, unlike other female mammals, this is not due to failure of the uterus but is caused by the ovary becoming depleted of oocytes in middle age. The reason women run out of oocytes before the end of life, whereas the other mammals which have been studied do not, is associated with the greatly extended lifespan of humans compared to other mammals of equivalent size. There is a linear relationship between longevity and body weight in mammals, small mammals have much shorter lives than large ones. This is probably associated with the increased production of free radical oxygen necessary to maintain body temperature in smaller animals. Heat is lost through the body surface which becomes relatively less as the animal increases in weight, so the smaller animal has to metabolise and thus produces more free radical oxygen to maintain body temperature. For reasons unknown this seems not to apply to humans. The menopause has thus evolved as a consequence of two adaptations: the prenatal onset of meiosis, common to all mammals and many other vertebrates and the greatly increased longevity of all humans, both male and female. In view of this dual origin it is unlikely to have evolved in response to an adaptive need to have grandmothers to help rear the young, as has been suggested!

Aging↗

Menstruation: a nonadaptive consequence of uterine evolution.

Although adaptive explanations for menstruation go back at least twenty-five hundred years, in the last decade two new hypotheses have been advanced. The first suggests that menstruation evolved to cleanse the uterus of pathogens introduced by sperm, and the second argues that the function of endometrial regression (with the associated menstruation in humans) is to save energy by getting rid of tissue, rather than maintaining it in the absence of an available blastocyst. Both these suggestions may be questioned on the grounds that they do not take into account the physiology of the reproductive processes involved. Menstruation is not an independent physiological process and is unlikely to have been selected for independently of the evolutionary events that led to it. Furthermore, most primitive menstruating animals would have menstruated infrequently, and many may have reproduced or died without ever menstruating. In order to provide a context for understanding how menstruation may have come about, the evolution of the female vertebrate reproductive tract is briefly reviewed. In later stages, the coevolution of the embryo and uterus resulted in an intimate association between the trophoblast and the uterine blood vessels. As the embryo became more invasive, the uterus responded with increased cellular growth and differentiation of the endometrium to accommodate it. This reached its peak in mammals (such as rodents and humans), where the embryo passes through the epithelium into the endometrial stroma, which responds with differentiation of cells and blood vessels. Progesterone, secreted after ovulation, plays a crucial role in preparation for pregnancy. In addition to its well-known effects on the uterus, progesterone may be important in suppressing the inflammatory reaction that would be expected in response to the presence of a foreign body, such as an embryo. It is also suggested that vascular and cellular differentiation of the endometrial stroma has evolved by adaptation of the inflammatory (granulation tissue) reaction. When progesterone levels fall at the end of the cycle, there is tissue breakdown and bleeding. The uterus then reforms for the next ovulatory cycle. It is shown that the female reproductive tract has multiple functions that must occur in sequence. The coevolution of the embryo and maternal tract thus led to the close contact of two genetically different tissues, and problems such as the inflammatory reaction had to be overcome. Menstruation is a necessary consequence of these evolutionary changes, and needed no adaptive value in order to evolve.

Adaptation, Physiological↗

Minimal progesterone support required for the maintenance of pregnancy in mice.

A study of the degree of progesterone support required for the maintenance of various stages of pregnancy was undertaken in mice. Mated females were ovariectomized at various stages of pregnancy and progesterone and oestradiol support provided by s.c. Silastic implants with known release characteristics. In the earliest stages of pregnancy (days 1-5), very low concentrations of progesterone (<25% of normal physiological values) were sufficient to maintain pre-implantation stages and allow implantation. In the immediate post-implantation period (days 5-9), the development of implantation sites and decidualization required considerably higher progesterone support. In mid-pregnancy (days 11-14), progesterone alone could not maintain pregnancy unless present in very high amounts; however, the presence of oestradiol during this period lowered the progesterone requirements to well within the physiological range. This effect of oestradiol started on day 11 but required the level of oestradiol support to be kept within strictly defined limits, with high concentrations inducing abortion. Progesterone alone was able to maintain pregnancy from day 15. These results indicate that the minimal progesterone support required for pregnancy in mice varies considerably at different stages of pregnancy and is at least partly modulated by oestradiol.

Animals↗

Why do women menstruate? Historical and evolutionary review.

Theories regarding the significance of menstruation from the time of Aristotle to the present are reviewed, followed by a brief description of the evolutionary changes in the uterus. A specific duct for the transport of ova first appears in jawed fishes. Its important role in the evolution of internal fertilisation and the protection and nourishment of the embryo is followed through the vertebrate orders, amphibia, reptiles and mammals. The problems associated with the presence of a gamete or zygote of different genetic make up inside the maternal tract is stressed, and the mechanisms to overcome or modify the maternal inflammation reaction discussed. In egg laying reptiles and birds, the secretion of coverings around the embryo presumably shields the foreignness of the tissue, while in viviparous animals, the secretion of progesterone plays a major role in controlling the inflammatory reaction. In some mammals, for example the mouse, the invasiveness of the trophoblast is such that the blastocyst penetrates inside the wall of the endometrium. The stroma responds under the influence of progesterone, to undergo an implantation/decidual reaction which bears considerable resemblance to an inflammatory/granulation tissue reaction. A similar reaction occurs in women during the luteal phase in anticipation of a very invasive blastocyst. When there is no fertilisation the progesterone drops and the differentiated stromal tissue is shed with bleeding; menstruation.

Animals↗

Relaxin and decidualization in mice: a reappraisal.

The nature of the physiological stimulus inducing decidualization in the endometrium is unknown. In this study we attempted to verify a recent report that relaxin can induce decidualization in intact mice primed with a high dose of estradiol valerate (5 micrograms) and a low dose (10 micrograms) of medroxyprogesterone acetate. In our study, neither s.c. nor intrauterine relaxin, nor intraluminal arachis oil, (an established deciduogenic stimulus) were able to induce decidualization. In addition, while oil was able to induce decidualization (increased uterine weight, and positive Pontamine Sky Blue and stromal alkaline phosphatase reactions) in ovariectomized mice treated with a regimen of estradiol and medroxyprogesterone acetate designed to produce optimum uterine sensitivity, no decidualization occurred in response to either s.c. or intraluminal relaxin. This study fails to provide any support for a role for relaxin as a deciduogenic stimulus.

Alkaline Phosphatase↗

The minimum requirements for oestradiol to induce uterine sensitivity for implantation and decidualization in mice.

Steroid-containing s.c. silastic capsules with known physiological release characteristics were used to study the control of implantation and the induction of uterine sensitivity in ovariectomized mice. In mated, ovariectomized animals maintained on progesterone, the implantation sites were detected after approximately 12 h of oestradiol exposure, and alkaline phosphatase activity at the implantation sites developed within 21 h. Implantation could be induced in > 60% of animals by 4 h exposure to an oestradiol implant, in which time approximately 1.6 ng oestradiol would have been delivered. Continuous delivery of a low dose of oestradiol near the threshold for implantation induced a full complement of implantation sites in the responding animals. The sensitivity of implantation to low amounts of oestradiol suggests that this response is at least as sensitive as either the induction of vaginal cornification or the stimulation of uterine weight. The minimum time for the induction of uterine sensitivity when oestradiol and progesterone treatment were started simultaneously was approximately 36 h. The use of slow-release oestradiol-containing capsules provides a good model to investigate the roles of oestradiol in initiating and defining the 'implantation window'.

Animals↗

Control of uterine stromal mitosis in relation to uterine sensitivity and decidualization in mice.

The relationship between mitosis, ovarian hormones, decidual stimuli and decidualization was investigated using progestagen-treated ovariectomized mice. Oestradiol, or the intraluminal instillation of oil or saline, all stimulated stromal mitosis. When oil or saline was instilled following oestradiol, the response depended on the dose of oestradiol, the interval between the oestradiol and the instillation, and the time when the mice were killed. After 20 ng oestradiol, the instillation of oil 7 h later induced large mitotic and decidual responses that were evident within 17 h of instillation and increased with time. Smaller mitotic and decidual responses were obtained when the interval between oestradiol and oil was 24 h; there was no response when the interval was 42 h. When a higher dose (100 ng) of oestradiol was given, oil injected 7 h later initially stimulated mitosis (at 17 h), but this effect was reduced at 24 h and no decidualization occurred. After instilling oil 24 or 42 h after 100 ng oestradiol, the mitotic response was limited, and there was no decidual response. Regardless of the dose of oestradiol, saline induced only a transient mitotic response and no decidualization occurred. It is concluded that there are three stimuli that can cause stromal mitosis in the progestagen-treated mouse uterus: oestrogen, an intraluminal stimulus (blastocyst, oil or saline) and factors associated with decidualization. Oestradiol not only induces mitosis, but also produces a period of heightened sensitivity to the mitotic effects of intraluminal stimuli. In addition, low doses of oestradiol induce a period of sensitivity to decidual stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Timing of the window of uterine sensitivity to decidual stimuli in mice.

The refractory period that follows the period of sensitivity to a decidual stimulus in ovariectomized hormone treated mice was investigated. Medroxyprogesterone acetate provided constant progestin concentrations and silastic implants containing oestradiol maintained constant nidatory oestrogen concentrations. The nidatory stimulus was provided by crushing the uterus with a haemostat or by the intrauterine instillation of arachis oil. The decidual response was assessed by measuring changes in uterine weight or by examining the stroma for the presence of alkaline phosphatase. Sensitivity to the oil was first observed approximately 14 h after the insertion of the oestradiol implant but this sensitivity had waned by 32 h and was absent at 40 h. Crushing the uterus initiated a decidual response in mice treated with progestin alone but if the oestradiol implant was inserted then the uterus was responsive to crushing 24 h after insertion but not at 45 h. The traumatic decidual cell reaction (crushing), although not requiring nidatory oestradiol for its successful initiation, was nevertheless subject to the refractoriness that followed oestradiol sensitivity.

Alkaline Phosphatase↗

Burst fracture of the fifth lumbar vertebra.

Burst fracture of the fifth lumbar vertebra is a rare injury. We report the cases of seven patients who were treated conservatively by immobilization for six to eight weeks in a body-jacket cast that included one lower extremity to the knee. The patients were allowed to walk ten to fourteen days after the injury. A thoracolumbosacral orthosis was worn for an additional three months. No patient had an injury to the sacral root. Two patients had mild lower lumbar motor-root deficits that resolved within one year. All patients had an occasional backache, and two had intermittent radicular-type pain in the distribution of the fifth lumbar or first sacral-nerve root. The degree of compromise of the spinal canal could not be directly related to the degree of neurological deficit; that is, a large compromise of the spinal canal did not necessarily result in a major loss of neurological function. There was no early or late loss of lordosis between the cephalad end-plate of the fourth lumbar vertebra and the cephalad aspect of the sacrum, and there were no signs of progressive collapse of the vertebral body in any patient. In our series, the burst fractures of the fifth lumbar vertebra were stable injuries that caused minimum neurological deficits, and treatment by immobilization in a body-jacket cast was effective.

Adult↗

Infiltration of neutrophil polymorphonuclear leucocytes into the endometrial stroma at the time of implantation of ova and the initiation of the oil decidual cell reaction in mice.

Polymorphonuclear leucocytes (polymorphs) were found in the endometrial stroma adjacent to implanting blastocysts approximately 100 h after mating. Areas of uterus not containing a blastocyst had very few polymorphs. Ovariectomized mice were treated with hormones to render them sensitive to a decidual stimulus, the intraluminal injection of arachis oil. Areas of uterus responding to the oil (as indicated by the Pontamine Sky Blue reaction) showed an influx of leucocytes into the endometrial stroma between 16 and 36 h after the application of the decidual stimulus. The polymorphs were largely neutrophils. The injection of oil into non-sensitized uteri did not result in polymorph infiltration nor did the injection of physiological saline (which is not deciduogenic) into sensitized uteri. It is concluded that during the early stages of decidualization there is attraction of polymorphs from the blood into the stroma.

Animals↗

Failure of platelet-activating factor (PAF-acether) to induce decidualization in mice and failure of antagonists of PAF to inhibit implantation.

The possible role of platelet-activating factor (PAF) in the uterine responses associated with implantation was investigated. Attempts to trigger a decidual cell response in the uteri of hormonally sensitized, ovariectomized mice by instilling PAF-acether (1-1000 ng) intraluminally were unsuccessful. The effect of PAF antagonists on implantation was investigated in females ovariectomized on Day 3 of pregnancy and treated with progesterone. Implantation was induced in these females by injection of 10 ng oestradiol-17 beta on Day 8. Hourly intraperitoneal injections of three PAF antagonists (WEB 2086, CV 3988 and BN 52021 at doses of 1.2-1.4 mg/kg) given over a 24-h period starting 1 h before the injection of oestradiol-17 beta had no significant effect on the occurrence of implantation sites. Intraluminal injection of WEB 2086 (15 micrograms) or BN 52021 (5 micrograms) either 3 h before or 6 h after the nidatory oestradiol also had no significant inhibitory effect on implantation. SRI 63-441 given once daily over the first 4 days of pregnancy at a dose of 40 micrograms/30 g body weight had no inhibitory effect on the establishment of pregnancy. These results are not consistent with a critical role for PAF in implantation in mice.

Animals↗

A study of the early morphological changes initiated in the uterine luminal epithelium by substances (oil and carrageenan) which induce the decidual cell reaction in mice.

Oil, carrageenan or saline were injected into the uteri of ovariectomized mice treated with hormones on schedules which would sensitize, partly sensitize or not sensitize the uterus to an intraluminal decidual stimulus. The uterine epithelium was examined histologically at various times over the succeeding 5 h. Saline did not produce any morphological change whereas almost immediately after the injection of oil or carrageenan epithelial cell death was apparent in the uterus, regardless of hormone treatment. Within 45 min the dead cells had been removed and the epithelium was re-established. Oil droplets were still present in the uterus after 5 h and these were able to stimulate a decidual reaction in partly sensitized animals when oestrogen was administered 18-44 h after the oil instillation, well after the re-establishment of the epithelium. It is suggested that the early transient cell death in the uterine epithelium is not responsible for triggering the decidual reaction but that it is the contact of the oil droplet with an intact epithelium which triggers the response when the hormonal conditions so allow.

Animals↗