A program to foster residents' appreciation of the nurse's role.
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Biomedical subjects
Publications and source records attributed to E A Wilson.
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Immunoelectron microscopy was used to investigate the ultrastructural features and synaptic relationships of serotonin-like immunoreactive amacrine cells in the larval tiger salamander retina. Serotonin-positive somas exhibited an evenly distributed peroxidase reaction product throughout their cytoplasm. Their nuclei were unstained and possessed indented nuclear membranes. Serotonin-immunoreactive processes were generally stained throughout with the exception of their mitochondria, whose morphology was often disrupted by the staining reaction. They were further characterized by an occasional dense-cored vesicle/s in addition to a generally homogeneous population of small, round, clear synaptic vesicles. Serotonin-immunoreactive amacrine cell processes formed conventional synapses that were characterized by symmetrical synaptic membrane densities. A total of 222 synaptic arrangements were observed that involved the immunostained processes of serotonin-amacrine cells. As presynaptic elements, they primarily contacted amacrine cells processes (37.8%). They also provided substantial synaptic input to processes that lacked synaptic vesicles (16.2%) and whose origin was unidentified. Serotonin-processes provided a far fewer number of synaptic contacts onto the processes of bipolar cells (1.4%) and the somas of cells in the amacrine cell layer (0.5%). As postsynaptic elements, they received synaptic inputs from amacrine cells (27.9%) and bipolar cells (16.2%). With the exception of their synapses onto bipolar cells and the somas of cells in the amacrine cell layer, each of the synaptic relationships of serotonin-amacrine cells was observed in each of sublayers 1-5 of the inner plexiform layer.
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Metalloproteinase inhibitors regulate collagenase activity in the extracellular matrix. To assess the role of metalloproteinase inhibitors in the ovulatory process, inhibitor activity was examined in human follicular fluid collected 2-4 h before ovulation. The relationship between inhibitor activity and steroid content was determined, and the inhibitors were partially purified and characterized. Inhibitory activity in follicular fluid (n = 25) correlated with both follicular estradiol (P less than 0.001) and progesterone (P less than 0.02) concentrations per follicle. Chromatographic separation of the follicular fluid on Sepharose 6B isolated two peaks of inhibitory activity. The inhibitor from the small mol wt (Mr) peak shared many of the properties of tissue inhibitors of metalloproteinase. It was stable in response to heat (60 C) and methylamine (200 mM), and was destroyed by reduction and alkylation, a procedure reported to destroy previously characterized inhibitors. Partial purification by affinity and ion exchange chromatography demonstrated the inhibitor to be a glycoprotein with an approximate Mr of 28-29K. The large Mr inhibitor had an approximate size of 700K and exhibited many of the characteristics of alpha 2-macroglobulin, a serum-derived metalloproteinase inhibitor. It was sensitive to heat, methylamine, and reduction and alkylation. Thus, follicular fluid contains metalloproteinase inhibitor activity that is steroid related and may be hormonally regulated. Ovarian metalloproteinase inhibitors may act to regulate connective tissue remodeling during follicular rupture.
Studies with rat ovarian cells indicate that proteolytic enzymes, such as plasminogen activator (PA), play a role in the tissue remodeling that occurs before ovulation. In the rat, gonadotropins appear to increase granulosa cell tissue-type plasminogen activator (t-PA) content by increasing the cellular concentration of t-PA mRNA as well as by modulating the activity of a specific PA inhibitor (PAI). We obtained granulosa cells from preovulatory follicles of women undergoing either in vitro fertilization or gamete intra-fallopian tube transfer in order to evaluate the roles of PA and PAI in human ovulation. Samples of granulosa cell total RNA were hybridized with probes for t-PA, urokinase-type PA, PAI type 1 (PAI-1), or inhibin A-chain (as a control). Northern analyses revealed that the RNA of granulosa cells from preovulatory follicles contained little or no detectable PA mRNA. In contrast, two species of PAI mRNA were detected in relative abundance. The signal intensity produced by the PAI-1 probe varied by about 8-fold among patient samples, suggesting that PAI-1 may be useful as a marker of follicular maturation and differentiation. These results demonstrate that human granulosa cells collected immediately before ovulation contain PA inhibitor mRNA, yet have little or no PA mRNA.
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The gluten content and nutritional adequacy of the diet of a group of adult coeliac patients supposedly following a gluten-free diet for at least one year were assessed. Results were considered in relation to the nutritional state of these patients, determined by anthropometric measurement, and the histological appearance of jejunal biopsies taken at the time of nutritional assessment. Imperfect gluten avoidance, mild malnutrition and mild histological abnormalities on jejunal biopsy were frequent findings. A careful dietary and nutritional assessment when considered in light of histological findings at jejunal biopsy helps to identify the causes of persisting symptoms or malnutrition in treated coeliac patients. A normal jejunal biopsy in a malnourished patient whose dietary compliance is good should prompt a search for an alternative diagnosis.
Two hundred and twenty-three newly-diagnosed symptomatic diabetic patients with onset age 40-69 years enrolled in a prospective study of intensive dietary management of diabetes were observed for a period of six years and the data obtained is analysed. The variables studied were weight and fasting levels of plasma glucose and insulin, and of serum total cholesterol and triglyceride. These tests were monitored throughout the study and in addition the oral glucose tolerance test was analysed at entry to the study, after six months intensive dietary management and again after 72 months. Blood pressure, electrocardiogram and the presence of posterior tibial artery pulsation were recorded at entry to the study and at 36 months and 72 months. Approximately 80 per cent of the patients were managed solely by dietary restriction for the entire six years, but 25 patients received oral hypoglycaemic drugs and 26 required insulin treatment. Weight, and fasting glucose and triglyceride values fell in the first few months of intensive dietary management. Analysis of possible risk factors in survivors and patients dead at six years showed no significant differences, apart from a higher mean age at diagnosis in those who died. During the six years of intensive dietary management the mortality from all causes in these diabetic patients was no greater than that for the general population of Northern Ireland.
The severity of the symptoms of endometriosis has not always correlated well with the anatomic severity of the disease. This lack of correlation may be due to variations in the metabolic activity of the endometriotic implants present at different stages of the disease. Because prostaglandin F (PGF) has been implicated as a hormonal mediator of the clinical symptoms of endometriosis, PGF synthesis and content was measured in implants from 14 patients with mild, moderate, severe, or extensive disease. To assess whether PGF production was related to the status of implants, the authors classified implants, based on gross and histologic criteria, as petechial or reddish; intermediate or brown; or powder-burn or black. PGF production of implants from patients with mild or moderate disease was greater than that of implants from patients with severe or extensive disease (P less than 0.05), and PGF content was similar for all stages of endometriosis. Petechial implants produced twice the amount of PGF than intermediate implants (P less than 0.05), which in turn produced more PGF than powder-burn implants (P less than 0.05). Powder-burn implants did not have the in vitro capacity to produce PGF, and the amount of PGF contained in implants of all classes was similar. Therefore, endometriotic implant PGF production and possibly other biochemical activities are dependent on the physical status of the implant. The classification of implants by morphologic appearance may afford additional assistance in determining the prognosis of the disease and in the examination of the subtle effects of the disease on symptoms.
Non-directional Doppler ultrasound was used to determine patency in prosthetic microvascular grafts in 30 rats over 24 weeks. Examinations were carried out every two weeks and exploration and arteriography were used at intervals during the study to confirm the Doppler findings. Two rats died and were excluded from the study. Twenty-six grafts were patent at the time of examination and these were correctly assessed by the Doppler technique. However, only one of two occluded grafts was correctly identified. Our results suggest that while this technique is sensitive, its specificity is low, and graft exploration may still be required to confirm patency. Doppler ultrasound may prove a useful non-invasive tool for long-term follow-up of experimental microvascular grafts if the false positive rate can be reduced by improved technique and further experience.
The efficacy of 1-mm internal-diameter polytetrafluoroethylene as a microvascular prosthesis is unclear. In this study, 8-mm-long segments of this material were implanted into the femoral arteries of 30 rats. Animals were examined every 2 weeks up to 6 months by Doppler ultrasound. Cumulative patency by the life-table method was 86.7 percent at 6 months. There were 26 patent grafts, 2 occlusions, and 2 deaths. Intimal hyperplasia adjacent to the anastomoses was seen in the native arteries. The pseudointima lining the grafts was cellular near the anastomoses but usually acellular in midgraft regions. It is concluded that if early failure does not occur, then good long-term patency is possible with 1-mm polytetrafluoroethylene in this setting and that patency is not dependent on development of a cellular pseudointima. Longer graft segments should be evaluated in future studies.
As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.
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Many of the substances known to control the secretion of pituitary gonadotropins also modulate the secretion of human chorionic gonadotropin (hCG) by the placenta. In order to study the effect of estrogens and progestins on hCG secretion, term placental explants were cultured in culture media for 144 hours. During the culture period, hCG secretion increased after 48 hours, and a fortyfold increase was observed after 144 hours (p less than 0.001). Compared to concentrations of hCG in control cultures, secretion of hCG was markedly suppressed in the presence of progesterone 2.25 X 10(-5)M (p less than 0.001), a concentration similar to that found in term placental tissue (1.7 +/- 0.2 micrograms/gm of tissue). Suppression of hCG by progesterone occurred in a dose-response manner (r = -0.9100, p less than 0.01). Estradiol, an important steroid modulator of pituitary gonadotropins, did not significantly suppress the secretion of hCG, except in pharmacologic concentrations (10(-4)M), and physiologic concentrations of estradiol had no effect on the suppression of hCG by progesterone. These results suggest that the mechanism by which progesterone suppresses the secretion of hCG differs from the manner in which steroids modulate the secretion of pituitary gonadotropins.
Prior to 60 days' gestation, the maternal serum concentration of human chorionic gonadotropin (hCG) can predict the estimated date of confinement, but later in pregnancy, hCG concentrations vary widely. The current study was performed to compare the accuracy of hCG measurements with other determinants of gestational age. Fifteen patients in whom gestational age was documented were monitored prospectively throughout pregnancy. One to two determinations of hCG (beta subunit) were obtained during the first 60 days. Then, ultrasonographic measurements of crown-rump length were obtained between 8 and 16 weeks' gestation and two measurements of biparietal diameter were performed between 18 and 32 weeks. These results were compared to actual dates of gestation. The mean (+/- SD) difference between gestational age predicted by single measurements of hCG and actual gestational age was 3.2 +/- 2.5 days (r = 0.94, p less than 0.0001), which compared favorably with estimates by crown-rump measurements (6.7 +/- 6.5 days) and measurements of biparietal diameter (6.3 +/- 5.3 days). These results demonstrate that hCG measurements during the first 60 days accurately predict gestational age and complement ultrasonic determinations of gestational age used later in pregnancy.
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