Fluid balance, thermoregulation and sprint and passing skill performance in female soccer players.

Ten females performed 90 min of the Loughborough Intermittent Shuttle Test (LIST) on two occasions separated by 7 days. Water [3 mL/kg body mass (BM)] was provided every 15 min during exercise (FL); no fluid was given in the other trial (NF). Participants performed the Loughborough Soccer Passing Test (LSPT) before and every 15 min during the LIST. Core temperature (T(c) ) was measured throughout using ingestible temperature sensors. Heart rate (HR), blood lactate ([La(-) ]) and ratings of perceived exertion (RPE) were collected at regular intervals during exercise. Participants experienced greater BM loss in NF (2.2 ± 0.4%) than FL (1.0 ± 0.4%; P<0.001). Sprint performance deteriorated by 2.7% during exercise (P<0.001) but there was no difference between trials (P=0.294). No significant differences in LSPT performance were detected between trials (P=0.31). T(c) was higher during exercise in NF and was 38.6 ± 0.3 °C (NF) and 38.3 ± 0.3 °C (FL; P<0.01) after 90 min. HR (P<0.001), [La(-) ] (P<0.01) and RPE (P=0.009) were higher during exercise in NF. Ingesting water during a 90-min match simulation reduces the mild dehydration seen in female soccer players when no fluid is consumed. However, there was no effect of fluid ingestion on soccer passing skill or sprint performance.

Thermoregulatory demands of elite professional America's Cup yacht racing.

America's Cup yacht racing predominantly occurs during the summer months under hot and humid conditions, with athletes exposed to the environment for prolonged periods, and yet the thermoregulatory responses to competitive sailing are largely unappreciated. This study aimed to assess the thermoregulatory responses to elite professional big-boat yacht racing, according to crew position and upwind and downwind sailing. Intestinal (T(core)) and skin temperature, fluid balance and regional sweat compositions were measured in two America's Cup crews (n=32) during 100 min of racing. The environmental conditions were as follows: 32 degrees C, 52% RH and 5 m/s wind speed. Subjective race intensity was moderate. Bowmen recorded the greatest elevation in the heart rate (184 +/- 10 beats/min) and T(core) (39.2 degrees C, P<0.01). Both heart rate and T(core) were higher during downwind sailing (P<0.001). Regional skin temperatures were significantly different according to site (P=0.05), with tibia being the lowest (33.3 +/- 1.2 degrees C). The mean sweat loss during racing was 1.34 +/- 0.58 L/h (range: 0.44-2.40 L/h), with bowmen experiencing the greatest loss of sweat (3.7 +/- 0.9% of body mass). The mean fluid intake was highly correlated to sweat loss (r=0.74, P<0.001), with 72 +/- 41% of sweat losses replaced. The mean sodium concentration of sweat was 27.2 +/- 9.2 mmol/L (range: 12.0-43.5 mmol/L) and the total NaCl loss during sailing was 3.8 +/- 2.4 g (range 0.7-10.0 g). America's Cup sailing is a demanding sport that presents considerable challenges to thermoregulation, fluid and electrolyte balance. Certain crew roles (bowmen) present an increased risk of developing exertional heat illness, and for the majority of crew downwind sailing results in greater thermal strain than upwind sailing - which may have implications for clothing selection and boat design.

The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy.

Vascular refractoriness to the systemic pressor effects of angiotension II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable animal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P less than 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects of AII, requiring 0.016 microgram of AII/min per kg to elicit a 20 mm HG rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P less than 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses of AII less than 0.016 microgram/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.

Conversion of plasma progesterone to deoxycorticosterone in men, nonpregnant and pregnant women, and adrenalectomized subjects.

During the third trimester of human pregnancy the concentrations of deoxycorticosterone (DOC) in maternal plasma are 4-50 times those in nonpregnant women and men. It has been suggested that the increased amount of DOC in maternal plasma originates in the fetal compartment. We considered an alternate explanation for the high levels of DOC in plasma or near-term pregnant women, viz., that DOC may be derived in part from 21-hydroxylation of maternal plama progesterone. To test this hyposthesis we measured the fractional conversion of plasma progesterone to DOC from the relationship between the 3H:14C ratio of the infused tracers, [3H]progesterone and [14C]-DOC, and the 3H:14C ratio or urinary 3 alpha,21-dihydroxy-5 beta-pregnan-20-one (tetrahydro-DOC). The fractional conversion of plasma progesterone to DOC ([rho](BU)P-DOC), measured in this manner, was 0.007 +/- 0.001 (mean +/- SEM, n = 26) in the subjects of this study. The values for [rho](BU)P-DOC varied widely among subjects (0.002-0.022) but the range of values for [rho](BU)P-DOC was similar among women pregnant with an anencephalic or dead fetus, nonpregnant and adrenalectomized women, and men. The transfer constant of conversion of progesterone to DOC in plasma, [rho](BB)P-DOC, remained constant in a nonpregnant woman during the infusion of nonradiolabeled progesterone at rates of 0-14 mg/h. Based on the results of these studied, we conclude that DOC is formed by extra-adrenal 21-hydroxylation of plasma progesterone and that the rate of formation of DOC by this pathway is proportional to the concentration of progesterone in plasma.

A study of angiotensin II pressor response throughout primigravid pregnancy.

The present study was designed to ascertain sequentially the pressor response to angiotensin II in young primigravid patients throughout pregnancy in order a) to define when in pregnancy resistance to the pressor effects of angiotensin II develops; b) to define the physiologic sequence of events leading to this resistance; and c) to ascertain whether sensitivity to infused angiotensin II could be detected before the onset of clinical signs of pregnancy-induced hypertension. With this prospective approach, two separate groups of patients were defined. The first group of patients remained normal throughout pregnancy. The second group consisted of those patients who, while clinically normotensive during the initial phase of the study, ultimately developed hypertension of pregnancy.192 patients were studied; of these, 120 patients remained normotensive and 72 developed pregnancy-induced hypertension. In both groups, vascular resistance to infused angiotensin II (more than 8 ng/kg/min required to elicit a pressor response of 20 mm Hg in diastolic pressure) was demonstrated as early as the 10th wk of pregnancy. In the group that remained normotensive, maximum mean vascular resistance occurred at 18-30 wk of pregnancy, (mean pressor dose required being 13.5 to 14.9 ng/kg/min). In those subjects who developed pregnancy-induced hypertension, the mean maximum dose required was 12.9 ng/kg/min, which was observed at the 18th wk of pregnancy. By the 22nd wk there was a clear separation of the two groups, with the mean dose requirement of the subjects destined to develop hypertension being progressively less than that of those who remained normal. The difference between the two groups became significant (P < 0.01) by 23-26 wk of pregnancy. Among patients requiring more than 8 ng/kg/min on one or more tests done between wk 28-32, 91% remained normotensive. Conversely, during the same time period among patients requiring less than 8 ng/kg/min, on at least one occasion, 90% developed pregnancy-induced hypertension.

Effect of prostaglandin synthetase inhibitors on pressor response to angiotensin II in human pregnancy.

Pregnant women destined to develop pregnancy-induced hypertension (PIH) lose refractoriness to the pressor effects of infused angiotensin II (A-II) several weeks before the onset of hypertension. This loss of refractoriness to A-II is unrelated to plasma renin activity or circulating levels of A-II. In animal studies it has been shown that the prostaglandins are important mediators of vascular reactivity. Specifically, the uterine blood flow appears to vary directly with prostaglandin E concentrations in uterine venous effluent. The present study was designed to evaluate the effects of prostaglandin synthetase inhibitors on the pressor effects of A-II in human pregnancy. The "effective A-II pressor dose" (nanograms of A-II X kg-1 X min-1 necessary to cause a 20 mm Hg rise in diastolic pressure) was determined in 14 pregnant women before and after treatment with either 25 mg indomethacin or 600 mg aspirin given twice, 6 h apart. The effective pressor dose required before treatment [22.7 +/- 3.4 ng X kg-1 X min-1 (mean +/- SE)] was significantly greater than that after treatment [8.7 +/- 1.2 ng X kg-1 X min-1 (P less than 0.001)]. The refractoriness to A-II observed in normal human pregnancy may be mediated in part by the action of prostaglandins or related substances produced in the arteriole.

Initiation of human parturition. VI. Identification and quantification of progesterone metabolites produced by the components of human fetal membranes.

The fetal membranes play a central role in the initiation of human parturition, a role that may be subserved in part by quantitative changes in progesterone metabolism. In order to identify and to quantify the metabolites of progesterone produced by the components of the human fetal membranes, amnion and chorion laeve tissues and homogenates were incubated with [3H]progesterone in the presence of added NADPH. The radioactive metabolites, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3,20-dione and 3beta-hydroxy-5alpha-pregnan-20-one, were isolated and identified by derivative formation, a combination of chromatographic techniques, and by crystallization to constant specific activity after addition of authentic standards. A simplified technique of metabolite quantification was developed that involves one thin layer chromatographic procedure and liquid scintillation assay of radioactivity. The accuracy of this method was established by comparison with data obtained using classical techniques. This study demonstrates the presence of human fetal membranes 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase, and 3beta-hydroxy-steroid oxidoreductase, and a qualitative difference between amnion and chorion laeve.

Prenatal care evaluation and cohort analyses.

The value of prenatal care has been obscured by multiple factors, including the limitations of birth certificate data, large socioeconomic disparities between women who seek prenatal care and those who do not, and the "preterm delivery bias", ie, the reduced pregnancy duration and opportunity for prenatal care among women who give birth prematurely. Perinatal mortality and morbidity (neonatal intensive care unit admission; ventilator therapy) were carefully assessed in an indigent population (28,838 deliveries at Parkland Memorial Hospital). To avoid the preterm delivery bias, a cohort of all women whose pregnancy reached a specific week of gestation was identified and their prenatal care status (zero vs one or more visits) by that week was related to pregnancy outcome. Separate cohorts were defined at 26, 30, 34, 38, and 42 weeks. Prenatal care was associated with improved pregnancy outcomes in only the 34-, 38-, and 42-week cohorts (P less than .01). Findings suggest substantial benefit from prenatal care after 30 weeks' gestation but not from early prenatal care. Unfortunately, it may not be possible to assess prenatal care accurately in observational studies even if cohort analyses are used. Clinical trials are needed to assess the effects of strategies for increasing or improving prenatal care, especially in early pregnancy.

Partial characterization of guanylate cyclase activity of the human placenta.

An optimal assay system for the measurement of GC activity in subcellular fractions of human placenta homogenates was developed. MN2+ was more effective than Mg2+ as a cofactor and, in addition, it markedly potentiated the Mg2+-dependent GC activity. The apparent optimal temperature for GC activity was 45 degrees C and the pH optimum was in the range of 7.5 to 8.3. The apparent Km of Mn2+-dependent GC for GTP was 0.1 and that of MG2+-dependent GC for GTP was 0.4 mm. More than 95 per cent of GC activity was associated with the 100 000 X g supernatant fraction. ATP at a concentration of 0.5 mm inhibited GC activity by 50 per cent. The Mn2+-dependent GC activity was inhibited by p-hydroxymercuriphenyl sulphonate at concentrations between 10 and 50 micrometers; this inhibition was reversed, in part, by dithiothreitol at concentrations of 150 to 500 micrometers to approximately one-fifth the activity of control values. In addition, we found that dithiothreitol was an inhibitor of GC activity. Studies on the responsiveness of placental GC to nucleophilic compounds indicated that phenylhydrazine was the most potent stimulus, while hydroxylamine, hydrazine, sodium azide, sodium nitrite and sodium nitroprusside were less potent. Placental GC was unaffected by alpha- and beta-adrenergic agonists or by cholinergic agonist, as well as by steroids produced by the placenta.

Adenylate cyclase from term human placenta and its regulation.

The activation of placental AC by either Mg2+ or Mn2+, in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn2+ enhanced maximally the NaF-stimulated Mg2+-dependent AC activity. The apparent Km of Mg2+-dependent AC for ATP was 0.4 mM, with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg2+-dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 microM. In the presence of GMP-P(NH)P (10 microM) the kinetics of the AC dependence on Mg2+ ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (greater than 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by beta-adrenergic agonists. Placental AC activity was inhibited by p-hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg2+-dependent AC was inhibited by 0.5 mM phenylhydrazine (95 per cent). Mg2+-dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 microM. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17 beta, 2-hydroxyoestreone, 2-hydroxyoestradiol-17 beta, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg2+-dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.

Complications following prostaglandin F2alpha-induced midtrimester abortion.

Prostaglandin F2alpha (PGF2alpha) was injected intraamniotically in 122 patients between 14 and 20 weeks' gestation in the dosage schedule recommended by the drug manufacturer to induce abortion. Significantly more multiparous (47.5%) than primagravida patients (21.5%) aborted within 16 hours, but the mean duration between PGF2alpha injection and abortion was not significantly different. Complications occurred in 52 (42.6%) patients and included: fall in hematocrit of more than 5 percentage points, failure to abort within 48 hours after injection, infection requiring antibiotic therapy, cervical laceration or fistula, and uterine rupture. The atypical dilatation and effacement of the cervix occurring with PGF2alpha-induced contractions may possibly lead to cervical incompetence with later pregnancies. Although the efficacy of PGF2alpha as an abortifacient is confirmed, the large complication rate with the procedure cannot be ignored.

Further observations on the nature of pressor responsivity to angiotensin II in human pregnancy.

The pressor dose of infused angiotensin II was determined before and after rapid volume expansion with 800 to 1075 ml of high-hematocrit blood. There was no remarkable change in sensitivity to infused angiotensin demonstrated except in two instances in which transient volume overload developed. The data support the hypothesis that increased angiotensin sensitivity observed in patients with pregnancy-induced hypertension is the consequence of increased vascular responsivity.

Uteroplacental blood flow and estrogen production following dehydroisoandrosterone infusion.

The effects of systemic infusions of dehydroisoandrosterone on uterine blood flow and the plasma concentration of estrogen in ovine pregnancy were studied in 7 pregnant ewes 52 to 128 days of gestation. Uterine blood flow increased 17.8% after a systemic infusion of dehydroisoandrosterone of 4.67 mg +/- 0.3. Maximum blood flows occurred 111 min +/- 5.8 after injection of dehydroisoandrosterone. The increase in flow (milliliter/minute) was greatest after 100 days of gestation. Plasma estrone concentrations increased from 67.9 pg/ml to 201 pg/ml, while estradiol rose from 42.6 pg/ml to 115 pg/ml (P less than 0.001). Estriol was not detected.

Workforce projections for subspecialists in obstetrics and gynecology.

OBJECTIVE: To project the future supply of practicing subspecialists in obstetrics and gynecology based on the most recent numbers of physicians entering fellowships. METHODS: A discrete actuarial model was developed, and supply projections were examined using 1999 subspecialty fellowship numbers from the American Board of Obstetrics and Gynecology. RESULTS: The numbers of obstetrician-gynecologists entering subspecialty fellowships in maternal-fetal medicine (MFM) and reproductive endocrinology-infertility (REI) declined sharply between 1994 and 1999. There was a slow increase in gynecologic oncology (GO) fellows. Projections show that the numbers of practicing MFM and GO subspecialists will double by 2020, but they will be serving a 20% larger female population in the United States. Numbers of practicing REI subspecialists will increase slowly. CONCLUSION: The number of fellows in GO continues to enlarge progressively though slightly, whereas those in MFM and REI have fallen sharply in recent years. Among four possible factors affecting growth or decline, the ones that seem most important are existing career opportunities for both generalist and subspecialist obstetrician-gynecologists and the length of subspecialty education.

Concurrent use of prostaglandin F2alpha and laminaria tents for induction of midtrimester abortion.

One hundred sixteen women between 14 and 20 weeks of gestation were aborted with a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) and intracervical laminaria. Complications among these women were compared to those among 122 patients who aborted after PGF2alpha administration only. Shorter intervals between initiation and completion of abortion were observed in nulliparous women treated with the combined regimen than in nulliparous women treated with PGF2alpha only. In parous patients, the use of laminaria did not shorten the interval from initiation to completion of abortion. A decrease of the hematocrit in excess of 5 points and periabortal infection requiring antibiotic therapy occurred with similar frequency in both treatment groups. However, with the combined regimen no cervical tears were observed in nulliparous patients, and fewer women failed to abort within 48 hours.

Initiation of human parturition. IX. Progesterone metabolism by placentas of early and late human gestation.

In in vitro studies it was found that, in the presence of added NADPH, the human placenta metabolizes progesterone to 20alpha-hydroxy-4-pregnen-3-one at increasing rates as pregnancy advances. A fivefold increase in 20alpha-hydroxysteroid oxidoreductase activity is observed in term placentas compared with the enzymic activity of placentas of 12 to 20 weeks' gestation (368 +/- 53 pmoles/mg protein/hr vs 71 +/- 8 pmoles/mg protein/hr). The 5alpha-reductase and 3beta-hydroxysteroid oxidoreductase activities were similar in placentas obtained from early and late human pregnancies.

Initiation of human parturition. VIII. Metabolism of progesterone by fetal membranes of early and late human gestation.

A decreased rate of progesterone metabolism is detected in human fetal membranes several weeks preceding normal parturition at term. A 10- to 20-fold decrease in 20alpha-hydroxysteroid oxidoreductase activity and a 2- to 6-fold decrease in 5alpha-reductase activity are observed in human amnion and chorion laeve after 33 weeks' gestation.

PIP: The metabolism of progesterone by human fetal membranes was investigated in placental-fetal specimens obtained immediately following vaginal delivery, at Caesarean section prior to spontaneous labor, or at the time of elective abortion-sterilization. Several weeks before normal parturition, the rate of progesterone metabolism is decreased. Amnion and chorion laeve of more than 33 weeks' gestation showed a 10- to 20-fold decrease in 20alpha-hydroxysteroid oxidoreductase activity and a 2- to 6-fold decrease in 5alpha-reductase activity compared with specimens from early pregnancy.

Metabolic clearance rate of dehydroisoandrosterone sulfate. VII. Effect of lateral versus supine recumbency.

The physiologic events which may occur with the gravid women in the supine position suggest that uteroplacental blood flow may be impaired as a consequence of decreased venous return to the heart and the resulting decrease in cardiac output. Since the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) previously has been shown to reflect alterations in uteroplacental perfusion, the MCRDS was measured in a variety of different obstetric conditions during lateral and supine recumbency. No significant difference in the MCRDS was induced by this specific positional change, suggesting that uteroplacental perfusion was not altered. Experimental data are discussed which support this observation, and a possible mechanism for maintenance of uteroplacental blood flow under these circumstances is presented.

Alcohol abuse during pregnancy: changes in frequency in a large urban hospital.

The reported frequency of alcohol abuse during pregnancy was studied in a large urban public hospital in Dallas, Texas. During 1977-1980, 5602 pregnant women were surveyed and 0.7% (95% confidence interval 0.6-0.8%) reported abusing alcohol during pregnancy. In 1987, 1.4% (95% confidence interval 1.3-1.5%) of 1032 pregnant women, who were surveyed before delivery, reported alcohol abuse according to the same definition used 10 years earlier. The increase in the frequency of reported alcohol abuse during pregnancy between 1977-1980 and 1987 is statistically significant (P less than .05).

Metabolic clearance rate of dehydroisoandrosterone sulfate. V. Studies of essential hypertension complicating pregnancy.

The metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) was determined prospectively in gravidas with and without chronic essential hypertension. In normotensive patients, the MCRDS increased in linear fashion throughout pregnancy. In patients with chronic essential hypertension the MCRDS also increased progressively, but at higher values than in normotensive subjects. In normotensive gravidas who ultimately developed pregnancy-induced hypertension, the MCRDS increased progressively at a higher level than in gravidas who remained normotensive until approximately 4 weeks prior to the onset of clinical symptoms, at which time the MCRDS slowly decreased. Similarly, in gravidas with chronic hypertension who developed superimposed pregnancy-induced hypertension, the MCRDS increased progressively at higher levels than all groups studied until approximately 4 weeks prior to onset of hypertension, when a progressive decline in the MCRDS began.