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Biomedical subjects

M A Warren

Publications and source records attributed to M A Warren.

At least 55 records · Page 3Linked to original sources

Endometrial responses in artificial cycles: a prospective study comparing four different oestrogen dosages.

OBJECTIVE: To examine the endometrial response to four different regimens of oestrogen. DESIGN: A prospective, randomized cross-over study. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Twenty one women with premature ovarian failure divided into three equal groups. INTERVENTIONS: Four different regimens of hormone replacement therapy: variable, fixed 1 mg, fixed 2 mg and fixed 4 mg oestrogen dosages. Each woman received the variable dosage regimen in one cycle and crossed over to receive one of the three fixed dose regimens (1 mg, Group 1; 2 mg, Group 2; 4 mg Group 3) in another cycle. MAIN OUTCOME MEASURE: Ultrasonographic measurement of endometrial thickness and outpatient endometrial biopsy on day 19 of the artificial cycle; analysis of endometrial specimens by three separate methods: traditional histological criteria, morphometry and immunohistochemistry. RESULTS: The endometrial response was similar in those treated with the variable and the fixed 2 mg or 4 mg dosage regimens. The response was suboptimal in those treated with the fixed 1 mg dosage regimen. CONCLUSIONS: Normal endometrial development requires adequate priming of the endometrium by oestrogen, which may be administered in a sequential, variable dosage fashion, or simply by a fixed daily dosage regimen. However, the minimum daily dose required is likely to be 2 mg of oestradiol valerate. No adverse effect on the endometrium was observed at a daily dose of 4 mg oestradiol valerate, which produced plasma levels of oestradiol above the reference ranges of the natural cycle.

Adult↗

Embryo manipulation and experimentation.

I have argued that early human embryos are not human beings, and do not have normal rights. Like human sperm and ova, they are both alive and biologically human. However, they lack the physiological development necessary to sustain a capacity for sentience. If Ford is right, then they are not yet individual human organisms. But the more important point is that their lack of a capacity for sentience makes them inappropriate candidates for the ascription of moral rights. Thus, research on human embryos produced in vitro is not a wrong against them--at least so long as experimentally manipulated embryos are not returned to the womb, or artificially gestated to a stage at which they might become sentient. Some of the more difficult issues about embryo experimentation involve the rights of women as experimental subject and donors. The consent of both male and female gamete donors should normally be required for the production or experimental use of IVF embryos. (Possible exceptions might include cases in which one or both progenitors have died, and the survivor or other responsible family member wished to donate the (frozen) IVF embryos for research or other uses.) However, it is women's rights that are most apt to be endangered, for example, if the large scale therapeutic or commercial use of human embryos leads to a demand for large numbers of ova. Thus, it is vital that researchers and policy-makers heed feminist concerns about embryo research and the new biomedical technologies it may yield. Given adequate information and appropriate procedural protections, women are capable of making autonomous decisions about donating ova or embryos for biomedical research. But regulatory safeguards are needed to ensure against their being coerced, deceived, or manipulated into becoming ovum or embryo donors. As Daniel Callahan has detailed, biomedical technology has reached the point where we can no longer afford to provide everyone with all of the innovative therapies that might prove beneficial (Callahan, 1989, p 523). Thus, questions about the just and cost-effective distribution of medical resources will become increasingly difficult and important. Among these questions will be whether it is wise or just to invest large sums in the development of innovative methods of assisting human reproduction. We must also consider the interests of future persons who may suffer because of the methods used to bring them into existence.(ABSTRACT TRUNCATED AT 400 WORDS)

Beginning of Human Life↗

Wound healing and infection in pretibial lacerations.

Eighty-eight patients with pretibial lacerations were entered into a study to analyze bacteriological and wound-healing profiles. Fifty-four patients were followed to complete wound healing. A complete photographic record of wounds from time of presentation to healing was available for analysis in 49 of these patients. Staphylococcus aureus was the most common pathogen, but the correlation between clinical wound infection and growth of pathogenic bacteria was poor. Flucloxacillin alone was found to be significantly more effective in controlling wound infection than in combination with metronidazole. Computerized image analysis of the photographic records was performed. There was no significant difference in the healing times of the various classic surgical wound types, and image analysis confirmed that the rates of wound healing were generally similar in all the types of pretibial wounds.

Adolescent↗

Adaptations of the rat small intestine to a single and a double period of undernutrition.

Male rats were undernourished from birth to 3 weeks of age and then allowed a period of unrestricted access to food. These animals were subjected to a second period of undernutrition from 9 to 12 weeks. A group of rats undernourished from 9 to 12 weeks only, and a group well-fed throughout life were used for comparison. Six rats from each group were anaesthetised by intraperitoneal injection with sodium pentobarbitone and killed by perfusion with glutaraldehyde at 12 weeks of age and the small intestine removed and its length recorded. Resin-embedded sections 1 micron thick were cut in the transverse plane from proximal and distal regions of each intestine. Point and intersection counting was performed to estimate villous surface area, volume and shape as well as crypt and muscle volume. The body weight of the undernourished rats was significantly (P less than 0.01) reduced compared to controls, with doubly undernourished rats weighing significantly (P less than 0.05) less than singly deprived animals. Rats undernourished once showed larger deficits in villous surface area and volume in distal regions than in proximal ones. However, in rats undernourished during the weaning period and again in later life the proximal part also became affected, while the distal region was not affected further. Therefore, it appears that the distal region of the rat small intestine is more vulnerable to a single period of food restriction during adult life than is the proximal part.

Adaptation, Physiological↗

Evidence of non-maternally mediated acceleration of eye-opening in 'enriched' artificially reared rat pups.

Rat pups were artificially reared, without their mothers, from postnatal day 5. They were exposed thereafter to impoverished or enriched environmental conditions. The enrichment included gentling, social interaction and homing experience. Enriched rats showed accelerated eye-opening compared with their impoverished littermates (P less than 0.02). This is the first demonstration of stimulation-induced acceleration of development which cannot have been maternally mediated.

Animals↗

In vitro comparison of bleaching agents on the crowns and roots of discolored teeth.

Sixty teeth were stained in vitro to compare the decolorizing effect of three bleaching agents on the crowns and on the roots of teeth containing an intracoronal isolating base. With an intracoronal isolating base placed either at the cementoenamel junction (CEJ) or 2-mm below the CEJ, bleaching agents of Superoxol, sodium perborate, and a combination of the two were placed in the pulp chamber of teeth and the accesses sealed with IRM. Customized shade guides were used to evaluate the color changes of the crowns and roots. After three treatments, the combination technique was found to be more effective in decolorizing the crowns and roots of teeth than Superoxol or sodium perborate alone (p less than 0.05). No difference was found between the Superoxol group and the sodium perborate group. There was no difference in color shades of crowns in which the IRM base was placed either at the CEJ or 2-mm below the CEJ. The roots of all groups showed some degree of decoloration. Based on the bleaching effects on discolored roots, the effectiveness of this seal is questionable.

Borates↗

A morphometric study of the human endometrial stroma during the peri-implantation period.

In this study we have examined the human endometrial stromal cell population in well-timed biopsies during the peri-implantation period, using traditional stereological techniques. This paper reports data obtained from 16 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge (four each at LH + 2, LH + 4, LH + 6 and LH + 8). The average stromal cell nuclear diameter increased in size throughout the period of study (P less than 0.01), with a significant decrease (P less than 0.05) in the nuclear profile axial ratio. This suggests that the nuclei were increasing in size and becoming more rounded. There was a dramatic increase (P less than 0.01) in the packing density between LH + 2 and LH + 6; this is likely to be due, at least in part, to the glands filling up with secretory products and so compressing the intervening stroma. A substantial decrease (P less than 0.01) was seen in the packing density between LH + 6 and LH + 8. This corresponds to the time when stromal oedema is thought to be maximal.

Adult↗

A morphometric study of the human endometrial stroma during the peri-implantation period.

In this study we have examined the human endometrial stromal cell population in well-timed biopsies during the peri-implantation period, using traditional stereological techniques. This paper reports data obtained from 16 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge (four each at LH + 2, LH + 4, LH + 6 and LH + 8). The average stromal cell nuclear diameter increased in size throughout the period of study (P less than 0.01), with a significant decrease (P less than 0.05) in the nuclear profile axial ratio. This suggests that the nuclei were increasing in size and becoming more rounded. There was a dramatic increase (P less than 0.01) in the rounded. There was a dramatic increase (P less than 0.01) in the packing density between LH + 2 and LH + 6; this is likely to be due, at least in part, to the glands filling up with secretory products and so compressing the intervening stroma. A substantial decrease (P less than 0.01) was seen in the packing density between LH + 6 and LH + 8. This corresponds to the time when stromal oedema is thought to be maximal.

Adult↗

Synapse-to-neuron ratios in rat cerebellar cortex following lengthy periods of undernutrition.

Black and white hooded Lister rats were undernourished for various times up to 150 days of age; some of them were nutritionally rehabilitated from 75 days. Undernourished rats weighed significantly less than well-fed controls at all ages studied. After embedding in resin, sections of cerebellar cortex were cut and examined at the light and electron microscopical levels using traditional morphometric methods. Undernourished rats showed significant deficits in synapse-to-neuron ratio, compared with controls, at 21 days of age. This deficit disappeared by 75 days despite continued undernutrition. Indeed, there was no alteration in this ratio even when undernutrition was extended up to 150 days even though the ratio for the controls decreased after that period. Rats undernourished from birth to 75 days and subsequently rehabilitated to 150 days had significantly more synapses per neuron than controls. The functional sequelae of these morphological changes remain unknown.

Age Factors↗

An examination of the variation in timed endometrial biopsies.

Endometrial biopsies were obtained from fertile women, aged 20-40 years, with regular cycles of 25-35 days. Chronological dating of the material was carried out by determination of the luteinizing hormone (LH) peak by daily LH assay. Tissue was taken from three or four sites along the biopsy and processed for electron microscopy. Half micron thick sections were analysed by light microscopy and a morphometric examination of the glandular epithelium carried out. Nuclear size was assessed using an unbiased measuring technique and the volume density of the nucleus in the cell was also measured. A series of 12 women was examined, four at each of days LH + 2, 4 and 5. An attempt was made to control a variety of factors which contribute to the variability in the histological dating of the endometrial biopsy. In doing so it was possible to analyse the relative contributions of each sampling level to the overall variance. In contrast to earlier studies there is a relatively small intersubject variation with a correspondingly large within-biopsy variation. These results may indicate that the cellular events in the glandular epithelium, between ovulation and the middle of the luteal phase, are precisely regulated.

Adult↗

The effects of a lengthy period of undernutrition from birth and subsequent nutritional rehabilitation on the granule-to-Purkinje cell ratio in the rat cerebellum.

Male rats were undernourished for various lengths of time between birth and 150 days of age, with some rats being nutritionally rehabilitated between 75 and 150 days of age. Eight control and eight experimental rats were anaesthetised and perfused with 2.5% glutaraldehyde at each of 21, 75 and 150 days of age. Stereological procedures were used to estimate granule-to-Purkinje cell ratios in lobes IV, V and VI, using 0.5 micron thick toluidine blue-stained sections. Undernourished rats had significantly lower body and cerebellar weights than controls at all ages examined. These deficits persisted even after a period of nutritional rehabilitation. The granule-to-Purkinje cells ratio did not differ between control and experimental groups at 21 or 75 days of age. However, at 150 days both undernourished and rehabilitated groups of animals had significant deficits in this ratio compared with age-matched controls. These results suggest that undernutrition can have profound effects on brain development in later life even if the effects are not apparent during the period of undernutrition.

Animals↗

Effects of a lengthy period of undernutrition from birth and subsequent nutritional rehabilitation on the synapse: granule cell neuron ratio in the rat dentate gyrus.

Recent evidence showing alterations in spatial memory due to a period of undernutrition during early life has implicated the hippocampus as one of the brain centres that may be particularly adversely affected. However, there are very few quantitative morphological studies that have examined the neuronal and synaptic populations of the hippocampi from undernourished animals. We decided to carry out such experiments, paying particular attention to the granule cell of the dentate gyrus. Male rats were undernourished from the 18th day of gestation until 21, 75, or 150 days of age. Some of these previously undernourished rats were nutritionally rehabilitated between 150 and 250 days of age. Groups of well-fed control and experimental rats were killed by intracardiac perfusion with 2.5% sodium-cacodylate-buffered glutaraldehyde. The right hippocampus from each rat was dissected out and processed for electron microscopy. Stereological procedures at the light and electron microscopical levels were used to estimate the numerical densities of granular cell neurons and molecular layer synapses in the dorsal lip of the dentate gyrus. These estimates were used to calculate synapse: neuron ratios. There were 5,056 +/- 347 (mean +/- SE) and 5,002 +/- 190 synapses per neuron in 21-day-old control and undernourished rats, respectively. By 75 days these values had increased to 9,215 +/- 588 and 6,683 +/- 237. The difference was statistically significant. By 150 days of age the value for control animals had fallen once again to 6,518 +/- 209 whereas undernourished rats had increased slightly to 7,689 +/- 288 (P less than .01); 250-day-old rats, previously undernourished from birth to 150 days of age, showed a substantial increase in the synapse: neuron ratio during the period of nutritional rehabilitation. Thus these nutritionally rehabilitated rats had 9,407 +/- 365 synapses per neuron whereas age-matched controls had only 6,323 +/- 239 (P less than .01). These results indicate that the rat dentate gyrus is vulnerable to undernutrition even during the postweaning period and that a lengthy period of undernutrition can alter the developmental growth curve for synapse: neuron ratios.

Animals↗

The effects of a lengthy period of undernutrition on the skeletal growth of rats.

Male rats undernourished from about birth until 100 days of age were nutritionally rehabilitated until 200 days. Six control and six experimental rats were anaesthetised and X-rayed at each of 50, 100 and 200 days. Measurements of various skeletal dimensions, and estimates of skeletal maturity, were made from these radiographs. Undernutrition caused significant deficits in all the skeletal dimensions measured, compared to control rats matched for age. These deficits persisted even following nutritional rehabilitation. Ratios between various skeletal dimensions and body length revealed that the body shape of the undernourished rats was also permanently altered. Estimates of skeletal maturity showed that 50 and 100 days old undernourished rats were significantly retarded compared to controls. However, 200 days old, previously undernourished, rats did not show such a difference, even though their body size was smaller than that of controls.

Aging↗

The effects of a lengthy period of undernutrition on food intake and on body and organ growth during rehabilitation.

Studies were carried out on male black and white hooded Lister rats to examine the influence of a lengthy period of undernutrition on subsequent somatic growth and food consumption. Animals were undernourished from about birth until 100 days of age followed, in some cases, by nutritional rehabilitation to 200 days. At weaning, body weight was reduced by 45 g and all organ weights were significantly less in undernourished rats compared with controls. In percentage terms the liver, kidney, adrenal, testis and spleen showed the largest deficits (-45 to -60%) whereas the eyeball (-30%) and brain regions (-14 to -19%) were relatively spared. The deficits in most of the organ weights in rats undernourished until 100 days of age were, in percentage terms, similar to those seen in the 25 days old animals. The testis, spleen and adrenal gland showed smaller deficits at 100 days of age than those observed earlier. Nutritional rehabilitation caused complete catch-up growth in eyeball weight and some catch-up in the weight of other organs studied. During the period of nutritional rehabilitation, previously undernourished rats ate significantly more food per kilogram body weight than controls and were more efficient at converting this food into body mass than age-matched controls.

Aging↗

A quantitative assessment of the development of synapses and neurons in the visual cortex of control and undernourished rats.

Male rats undernourished from the 18th day of gestation until 100 days of age were nutritionally rehabilitated until 200 days of age. Six control and six experimental rats at each of 12, 25, 50, 100, and 200 days of age were killed by perfusion with buffered 2.5% glutaraldehyde. Pieces of visual cortex from each rat were postfixed in osmium tetroxide and embedded in resin. Stereological procedures at the light and electron microscope levels were used to estimate the synapse-to-neuron ratios in cortical layers II to IV. There were no statistically significant differences in the synapse-to-neuron ratio between control and undernourished rats at 12, 25, and 50 days of age. However 100-day-old undernourished rats had a significant deficit in this ratio compared to age-matched controls. Despite this, 200-day-old nutritionally rehabilitated rats were found to have, on average, 23% more synapses per neuron than controls. In both the control and the undernourished groups the synapse-to-neuron ratio increased to a peak by 50 days of age. This was followed by a significant fall in the ratio by 100 days of age. Although there was no further change in the control rats, the experimental group showed a substantial increase in the ratio by 200 days of age. This latter increase appeared to be related to the period of nutritional rehabilitation.

Animals↗