Cervical human papilloma virus infection and colposcopy.
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Biomedical subjects
Publications and source records attributed to G C Liggins.
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We have developed and successfully used the first microprocessor-controlled monitors for collection of data on depth, heart rate, and body temperature of one fetal and five adult male freely swimming Weddell seals. Adult seals almost invariably experienced a prompt bradycardia at the start of each dive, and the mean heart rate during diving was significantly lower for dives greater than 20 min (P greater than 0.999). The heart rate was also significantly greater during the ascent portion of dives when compared with the descent portion (P greater than 0.95). The fetal seal experienced a slow onset of bradycardia when its mother dived; during diving the fetal heart rate decreased by an average of 1.1 beats/min for each minute of the dive. The fetal heart rate generally took approximately 10 min to recover to predive levels after its mother resurfaced to breathe. The body temperature of one adult male Weddell seal showed a decrease of greater than 1.5 degrees C from resting levels before dives of greater than 15 min were initiated and a drop of over 2 degrees C before dives of greater than 30 min duration.
The ontogenesis of elastin and collagen accumulation and growth of the lung were studied in Wistar rats from day 18 of gestation until day 30 postnatally. Dexamethasone phosphate 0.1 mg or normal saline solution every 8 h for three doses was injected into pregnant rats on day 17. The effects of treatment, age, and sex on lung wet weight, lung dry weight, body weight, DNA, protein and desmosine (estimated by radioimmunoassay), and hydroxyproline were determined in the offspring. Dexamethasone inhibited lung growth and, to a lesser extent, body weight gain. While lung wet weight, lung dry weight, and body weight remained significantly reduced until postnatal day 15, the lung weight/body weight ratio was depressed only until postnatal day 5. The lung dry weight/lung wet weight ratio was decreased on day 20 of gestation and at birth. DNA concentration remained slightly but significantly reduced throughout the study period. Desmosine but not hydroxyproline concentration was lower after dexamethasone treatment during the period of rapid postnatal desmosine accumulation (day 10 p less than 0.05, day 15 p less than 0.01, day 20 p = 0.06).
The ontogenesis of elastin (desmosine), collagen (hydroxyproline), and DNA concentrations and their rates of increase were studied in fetal sheep lungs from day 60 until term. Elastin increased 13-, 17-, 63- and 11- fold in nondissected parenchyma, dissected (free of tubular structures of greater than 0.1 mm diameter) parenchyma, pleura, and trachea, respectively. Collagen increased 2.1-, 1.8-, 5- and 3-fold, respectively, in the four tissues. A sharp rise in elastin occurred after day 100. The rate of increase in elastin was greater in dissected than in nondissected parenchyma while the reverse was true for collagen. The steepest rise of elastin concentration occurred in the pleura after day 125. DNA concentration peaked on day 125 and was lowest at term. These findings are consistent with 1) the onset of a steep rise in elastin accumulation during the canalicular period, 2) the development of a rigid, mainly collagenous structure of the central airways and blood vessels and a distensible peripheral "gas-exchange tissue," rich in elastin, 3) an important role of elastin in the function of the visceral pleura, and 4) a peak of mitotic activity during the early alveolar period.
The relationship between elastin and collagen concentration and indices of lung maturation was studied in the lungs of fetal sheep. Fetal sheep of 124 days gestation were infused for 84 h with cortisol, triiodothyronine, prolactin, or epidermal growth factor alone or in combination. Pressure-volume curves with air were performed on the lungs and saturated phosphatidylcholine was measured in lung washes. Desmosine and hydroxyproline were determined in lung tissue in seven hormone-treated fetuses that displayed distensible and stable lungs similar to term lungs [volume of air at 40 cm H2O (V40) greater than 1.5 ml/g wet weight and at 5 cm H2O (V5) greater than 0.8 ml/g] and in seven fetuses whose lungs remained nondistensible and unstable (V40 less than 0.6 ml/g and V5 less than 0.4 ml/g). Alveolar saturated phosphatidylcholine was five times higher (p less than 0.001) in distensible than in nondistensible lungs, but attained less than 20% of term values. Desmonsine and hydroxyproline concentrations in parenchyma, pleura, and trachea of nondistensible, unstable lungs were similar to intact controls of 125 days gestation and those in distensible, stable lungs were similar to controls of 137 days gestation. Desmosine (p less than 0.0001) and hydroxyproline (p less than 0.001) concentrations in parenchyma of distensible, stable lungs were higher than those of nondistensible, unstable lungs. We speculate that increased distensibility of the fetal lung in response to treatment with hormones is attributable in part to changes in the composition of connective tissue.
The paper reviews the effects on lung maturation of glucocorticoids in animals and humans and presents relevant recent findings from the author's laboratory. It is now well established that antenatal glucocorticoid treatment reduces the incidence and severity of the respiratory distress syndrome (RDS) in prematurely born infants. The recommended doses of glucocorticoids produce fetal glucocorticoid activity levels similar to those of newborns with RDS or prolonged rupture of the membranes. Extensive follow-up studies have shown that adverse effects on child development are unlikely to occur. It is also evident that a significant number of fetuses do not respond to the treatment, which is of particular consequence in fetuses of less than 28 weeks gestation. These fetuses are less likely to respond to glucocorticoid therapy that fetuses between 28 and 32 weeks gestation and are at a higher risk of developing complications due to their immaturity. In fetal sheep, there is a similar decrease in the efficacy of glucocorticoids on lung maturation with decreasing gestational age. Simultaneous infusion of cortisol, triiodothyronine and prolactin but not of any of these hormones administered singly or in combination of two produced mature lungs in fetal sheep of 125 days gestation. Similar results were obtained with thyrotropin releasing hormone (TRH) and cortisol. It remains to be seen whether the combined administration of glucocorticoids and TRH accelerates lung maturation in human fetuses.
Platelet number, mean platelet volume (MPV) and platelet distribution width (PDW) were measured in 55 women admitted consecutively during four months from January-April 1984 with pregnancy-induced hypertension. The criteria for diagnosis were a sustained diastolic blood pressure greater than 90 mmHg during the first 24 h after admission, normal blood pressure recordings in the first trimester and a plasma urate value exceeding 0.34 mmol/l. The values were grouped according to gestation length and compared with those in a control group of 96 women of similar gestation lengths who were normotensive. Both MPV and PDW were significantly greater in the hypertensive group whereas platelet numbers did not differ. It is concluded that measurement of MPV and PDW is a useful diagnostic criterion of pregnancy-induced hypertension.
Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity.
Utilizing a microprocessor-controlled peristaltic withdrawal pump, arterial blood samples were obtained from Weddell seals (Leptonychotes weddelli) while diving voluntarily under the sea ice at McMurdo Sound, Antarctica. Plasma concentrations of glucose, lactate, free fatty acids, urea, and amino acids were determined in seals at various times during rest, diving, and recovery. In addition, radiolabeled palmitate, glucose, lactate, p-aminohippurate, inulin, galactose, and cholate were injected into the descending aorta of seals in the resting state or during voluntary diving at sea. Sequential plasma samples were collected, and the kinetics of wash-in and clearance of each component were determined. Under resting conditions, the change in specific activity of palmitate, glucose, and lactate after bolus injection followed smooth multiexponential decay kinetics as in terrestrial animals. Similar decay curves for the clearance of organ-specific compounds were also obtained in seals at rest. If, during voluntary diving, Weddell seals were analogous to exercising animals, the wash-in and clearance kinetics of all metabolites and organ-specific compounds would be qualitatively similar to those observed at rest. In contrast, wash-in and clearance appeared to be qualitatively and quantitatively modified in a way consistent with utilization of the classical Scholander diving response in both short and long dives.
Arterial blood gas tensions, pH, and hemoglobin concentrations were measured in four free-diving Weddell seals Leptonychotes weddelli. A microprocessor-controlled sampling system enabled us to obtain 24 single and 31 serial aortic blood samples. The arterial O2 tension (PaO2) at rest [78 +/- 13 (SD) Torr] increased with diving compression to a maximum measured value of 232 Torr and then rapidly decreased to 25-35 Torr. The lowest diving PaO2 we measured was 18 Torr just before the seal surfaced from a 27-min dive. A consistent increase of arterial hemoglobin concentrations from 15.1 +/- 1.10 to 22.4 +/- 1.41 g/100 ml (dives less than 17 min) and to 25.4 +/- 0.79 g/100 ml (dives greater than 17 min) occurred during each dive. We suggest that an extension of the sympathetic outflow of the diving reflex possibly caused profound contraction of the Weddell seal's very large spleen (0.89% of body wt at autopsy), although we have no direct evidence. This contraction may have injected large quantities of red blood cells (2/3 of the total) into the seal's central circulation during diving and allowed arterial O2 content to remain constant for the first 15-18 min of long dives. The increase of arterial CO2 tensions during the dive and the compression increase of arterial N2 tensions were also moderated by injecting red blood cells sequestered at ambient pressure. After each dive circulating red blood cells are oxygenated and rapidly sequestered, possibly in the spleen during the first 15 min of recovery.
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A subset of women with a high rate of fetal wastage is identifiable among those with serologic but not necessarily clinical evidence of connective tissue disease. The presence of lupus anticoagulant in the plasma of a pregnant woman serves as a marker for a high rate of fetal wastage and risk of thrombosis. Lupus anticoagulant is best identified by the activated partial thromboplastin time or kaolin clotting time and can be specifically confirmed by the platelet neutralization procedure. Review of the obstetric literature indicates a total of 49 women with 160 unsuccessful pregnancies and 13 live births. Prednisone in immunosuppressive doses (40 to 60 mg/day) combined with low-dose aspirin (75 mg/day) has been demonstrated to be effective in suppressing activity of lupus anticoagulant in pregnant women and successful pregnancies have been obtained with this treatment. Lupus anticoagulant should be excluded in women with suspected collagen disease, with repeated early abortions and all unexpected late fetal losses.
Two inhibitors of PGF synthesis in human endometrial cells were found in amniotic fluid from term non-labouring patients. Both inhibitors at 10(-9)M reduced the amount of arachidonic acid released from the cells but had no effect on PGF synthesis stimulated by arachidonic acid. The molecular weights were 150-165,000 and 70-80,000 daltons as estimated from gel filtration in two systems. Both compounds precipitated with ammonium sulfate, appeared thermostable and lost activity with trypsin digestion. Both inhibited phospholipase activity and had identical retention times with HPLC. We conclude that the compounds are novel endogenous proteins which inhibit endometrial cell phospholipase.
Arterial blood nitrogen tensions of free-diving Weddell seals (Leptonychotes weddelli) were measured by attaching a microprocessor-controlled blood pump and drawing samples at depth to determine how these marine mammals dive to great depths and ascend rapidly without developing decompression sickness. Forty-seven samples of arterial blood were obtained from four Weddell seals during free dives lasting up to 23 minutes to depths of 230 meters beneath the sea ice of McMurdo Sound, Antarctica. Peak arterial blood nitrogen tensions of between 2000 and 2500 millimeters of mercury were recorded at depths of 40 to 80 meters during descent, indicating that the seal's lung collapses by 25 to 50 meters. Then arterial blood nitrogen tensions slowly decreased to about 1500 millimeters of mercury at the surface. In a single dive, alveolar collapse and redistribution of blood nitrogen allow the seal to avoid nitrogen narcosis and decompression sickness.
Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104-112 days and fetuses bilaterally adrenalectomized at 98-101 days. At 120-127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29.7 +/- 4.2 (S.E.M.) nmol/l and 14.3 +/- 2.8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18.0 +/- 1.9 nmol/l and 9.1 +/- 2.0 nmol/l were significantly (P less than 0.05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80.8 +/- 13.0 nmol/l) was higher (P less than 0.05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12.3 +/- 2.9 vs 31.6 +/- 8.5 nmol/l) and adrenalectomized (n = 4; 14.2 +/- 2.6 vs 190.6 +/- 53.0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16.0 +/- 1.9 vs 31.6 +/- 8.5 nmol/l) while infusion of ACTH (1-24) (5 micrograms/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis.
Pulmonary maturation in 8 ovine fetuses bilaterally adrenalectomized at 98-101 days and infused at term with either ACTH1-24 or cortisol was compared with that in 4 untreated sham-operated controls. Four of the adrenalectomized fetuses were infused intravascularly with ACTH1-24 5 micrograms/h for 84 h before delivery and the other four were infused with cortisol 1 mg/h for 72 h. The high plasma concentrations of immunoreactive ACTH in the adrenalectomized fetuses (2762 +/- 1339 ng/l, mean +/- SD) were not significantly elevated by infusion of ACTH1-24 but were markedly depressed by infusion of cortisol. Distensibility (V40) of the lungs was less than that of controls in both the ACTH1-24-infused and cortisol-infused fetuses (1.86 +/- 0.31 ml/g vs 0.62 +/- 0.13 ml/g and 1.27 +/- 0.34 ml/g respectively) but it was significantly greater in the cortisol-infused fetuses compared to those infused with ACTH1-24. The volume of air retained at 5 cm H2O pressure (V5) during deflation was markedly reduced in adrenalectomized fetuses (controls 1.14 +/- 0.52 ml/g vs 0.25 +/- 0.25 ml/g and 0.12 +/- 0.6 ml/g). The wet weight of the lungs and the concentrations of saturated phosphatylcholine in lung tissue and lavage fluid were lower in the adrenalectomized fetuses than in controls but the differences were not significant. It is concluded that infusion of ACTH1-24 at term in adrenalectomized fetuses is probably without effect whereas cortisol enhances distensibility.
Previous studies suggest that plasma estradiol-17 beta and progesterone concentration values differ between patients who deliver before term and those who deliver at term. To determine if these values would aid in preterm delivery risk prediction, we measured plasma estradiol-17 beta and progesterone concentrations serially in 90 patients at high risk for preterm delivery. Measurements from 17 patients who developed documented preterm labor and/or were delivered before term were compared to the tenth and ninetieth percentiles of 42 patients who were delivered at term. The sensitivity of these measurements to predict preterm delivery was very low. Also, the mean plasma estradiol-17 beta and progesterone concentrations in patients with preterm labor who had term deliveries and in patients with preterm labor that progressed to preterm delivery were not different from each other or from patients delivering at term. No change in plasma estradiol-17 beta or progesterone concentration was noted preceding labor. We conclude that serial measurements of plasma estradiol-17 beta and progesterone concentrations do not improve preterm delivery risk prediction.
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