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Biomedical subjects

R H Hayashi

Publications and source records attributed to R H Hayashi.

At least 19 recordsLinked to original sources

Cocaine blocks extraneuronal uptake of norepinephrine by the pregnant human uterus.

Premature labor is one of the most common complications associated with cocaine abuse during pregnancy. Still, the effect of cocaine on the pregnant uterus is largely unknown. Although inhibition of neuronal uptake is the most important effect of cocaine in most tissues, after mid-pregnancy, the uterus has few functioning adrenergic nerve endings. To determine whether cocaine has any effect on uptake during pregnancy, we evaluated the ability of the term pregnant human uterus to take up [3H]-norepinephrine (9 x 10(-8) mol/L) and the ability of cocaine (10(-6)-10(-8) mol/L) to block this uptake. Because d-propranolol has been shown to block the direct effects of cocaine on the pregnant rabbit uterus, we also evaluated the ability of d-propranolol (2 x 10(-6) mol/L) to block the effect of cocaine on catecholamine uptake. The ability of the Uptake 2 inhibitor hydrocortisone (2 x 10(-5) mol/L) to block catecholamine uptake was also studied. We found that [3H]-norepinephrine was taken up by both the pregnant myometrium and endometrium, and that cocaine blocked this uptake by up to 55% at concentrations as low as 10(-7) mol/L. D-propranolol had no effect on the ability of cocaine to block catecholamine uptake. Hydrocortisone blocked uptake by the endometrium by 15% but did not block uptake by the myometrium. We conclude that the pregnant human uterus at term retains the ability to take up catecholamines and that cocaine blocks this extraneuronal uptake. This may explain, in part, the association of cocaine use with premature labor.

Cocaine

Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length.

Risk assessment for preterm delivery remains difficult, particularly among women with no prior history of preterm birth. We hypothesized that accurate assessment of cervical length by endovaginal ultrasonography could predict preterm delivery risk. A total of 178 patients with singleton gestations and without cervical incompetence were studied with transabdominal ultrasonography and endovaginal ultrasonographic cervical length measurement and manual vaginal examination of cervical length. A total of 113 patients who were evaluated by 30 weeks' gestation (excluding four induced preterm deliveries) were analyzed. Preterm delivery risk was compared between women with cervical lengths equal to or greater than the median and those with cervical lengths less than the median. An endovaginal ultrasonographic cervical measurement less than 39 mm was associated with a significantly increased risk of preterm delivery (25.0% versus 6.7%) and detected 76% of preterm births. Manual examination of cervical effacement detected 71% of preterm births, but transabdominal ultrasonographic measurement of cervical length was not preditive. Endovaginal ultrasonographic cervical measurement predicted increased preterm delivery risk regardless of parity or obstetric history. Endovaginal ultrasonography is a promising method for the prediction of risk of preterm birth. Because it has the potential to be an objective measure of cervical length, endovaginal ultrasonography may be superior to manual digital examination for preterm delivery risk assessment.

Cervix Uteri

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood.

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.

Blood Grouping and Crossmatching

Maternal blood pressure and fetal ultrasonography in normal baboon pregnancies.

Pregnancy in baboons is characterized by lower systolic, diastolic, and mean blood pressures than in the nonpregnant state. As pregnancy progresses, diastolic and mean pressures tend to increase whereas systolic pressure remains low. Sonographic measurements of fetal growth follow a sigmoid pattern, but their increase in relation to length of gestation approximates a straight line between 6 and 21 weeks of gestation (23 to 84% of term).

Animals

Effect of uncomplicated pregnancy on body water content and distribution in baboons.

Body water content and distribution were estimated before, during, or after 32 pregnancies in baboons. Water content of the various compartments (in liters) correlated with body weight in both nonpregnant and pregnant baboons, and with length of gestation in pregnant baboons. In proportion to body weight (in ml/kg), most water compartments did not change significantly with length of gestation. Mean plasma volume and blood volume were higher during pregnancy than before or after.

Animals

A functional and structural study of the innervation of the human uterus.

We characterized the innervation of human myometrial tissues by electrical field stimulation and electron microscopy. Nerve-specific parameters (pulse duration 0.6 msec) were used for electrical field stimulation to selectively activate intrinsic nerves. In specimens from nonpregnant, nonparous women (n = 6), tetrodotoxin (10(-6) mol/L) significantly reduced the response to electrical field stimulation by 70%. Contractions to electrical field stimulation were also inhibited to 60% by atropine (10(-5) mol/L) as well as by guanethidine (10(-5) mol/L) and phentolamine (10(-5) mol/L). Propranolol (10(-5) mol/L) had no detectable effect. We obtained similar results from about 50% of the specimens from nonpregnant, parous women (n = 15). The contractile responses of specimens from the term pregnant uterus (n = 13) to electrical field stimulation were not influenced by tetrodotoxin. Ultrastructurally we found nerve profiles in close proximity to muscle cells. About 30% of nerve varicosities in tissues from nonpregnant, nonparous patients could be classified as adrenergic (small, dense-cored vesicles), 53% as cholinergic (small, agranular vesicles), and about 17% as indeterminant (sometimes large, dense-cored vesicles). However, nerve varicosities were rarely observed in term pregnant specimens. These results indicate the presence of tetrodotoxin-sensitive, excitatory innervation of human myometrium consisting of alpha-adrenergic and cholinergic components. Furthermore, denervation may be nearly complete at term and recovery of innervation occurs at a considerable length of time after delivery.

Adult

Mechanical responses of the rat uterus, cervix, and bladder to stimulation of hypogastric and pelvic nerves in vivo.

Mechanical activities of the uterus, cervix, and bladder were recorded in vivo in anesthetized rats during electrical stimulation of either the hypogastric or pelvic nerve. Ovariectomized controls and hormone-treated groups were used as well as pregnant and postpartum rats. Stimulation of either hypogastric or pelvic nerve produced voltage- and frequency-dependent contractions of the three organs with no evidence of apparent inhibition. All evoked responses were completely abolished by tetrodotoxin, suggesting that these nerves are common pathways of innervation to the three organs. Atropine abolished uterine and cervical responses to both hypogastric and pelvic nerve stimulation, whereas bladder responses were only partly reduced. Hexamethonium almost totally blocked the evoked responses of the uterus and cervix. Phentolamine partly blocked uterine and cervical responses, and propranolol or physostigmine enhanced uterine and cervical responses to both hypogastric and pelvic nerve stimulation. These results suggest that motor innervation to the rat uterus and cervix is predominantly postganglionic cholinergic, with some alpha- and beta-adrenergic components, and that the bladder is innervated by mainly cholinergic and also noncholinergic nerves. Estrogen and estrogen-plus-progesterone pretreatment significantly increased the responses of uterus and cervix but not bladder. Uterine and cervical responses to either hypogastric or pelvic nerve stimulation were markedly reduced late in pregnancy and reappeared within 7 days after delivery.

Animals

In vitro studies on the control of human myometrial gap junctions.

In this study human myometrial tissues were examined for the presence of gap junctions by quantitative electron microscopy before and after incubation in tissue culture media with and without indomethacin. The area of gap junctions was very low in tissues from pregnant women at term but not labor, before incubation. After 24 and 48 h incubation without any treatment, segments of some of the same tissues developed many gap junctions and other tissues contained few junctions. Prostaglandin E (PGE), prostaglandin F (PGF) and prostaglandin F metabolite (PGF metabolite) levels in the media at various times were measured by radioimmunoassay. The prostaglandins increased progressively during the incubation period. Treatment of tissues with indomethacin decreased prostaglandin levels in the media and increased the numbers of gap junctions in those control tissues that developed few junctions over the same incubation interval. We conclude that the capacity of human myometrial tissues to develop gap junctions in vitro may depend upon a maturational stage in preparation for labor. Furthermore, our results suggest that products of the cyclo-oxygenase or lipoxygenase pathways may control the presence of gap junctions in the human myometrium and that changes in synthesis in these patterns may occur as part of the maturational process.

Female

The presence or absence of fetal breathing movements as a predictor of outcome in preterm labor.

The presence or absence of fetal breathing movements may be helpful in differentiating between true and false preterm labor. We attempted to demonstrate the clinical utility of this simple ultrasonic observation in predicting short-term delivery outcome during suspected preterm labor. A total of 50 pregnancies between 26 and 34 weeks' gestation with presumed preterm labor were observed in a prospective manner. During 20 minutes of observation with real-time ultrasound at the time of admission, fetal breathing movements were observed in 33 patients and considered absent in the remaining 17 patients. In those pregnancies with absent fetal breathing movements, true labor with subsequent delivery occurred in 16 patients. Of the 33 pregnancies with fetal breathing movements present, 29 continued for greater than 48 hours. It appears that the absence of fetal breathing movement is a reliable indicator of imminent preterm delivery, irrespective of fetal membrane status (p less than 0.0001). The observed mean sensitivity and specificity of this phenomenon in predicting short-term delivery outcome are 96.6% +/- 3.3% (mean +/- SD) and 80.0% +/- 8.9%, respectively. A multivariant statistical model based on the frequency of contractions, white blood cell counts, initial cervical examination results, and premature rupture of membranes could successfully predict delivery outcome in 40% to 75% of cases. The addition of fetal breathing movement analysis to the model allowed for the correct prediction of outcome in 90% of the cases.

Delivery, Obstetric

Amniotic fluid in baboon pregnancies with normal versus growth-retarded fetuses.

Amniotic fluid samples from 12 pregnant baboons at 173 to 176 days of gestation were studied. Five fetuses were growth retarded and seven were normally developed. Mean amniotic fluid volumes and composition (osmolality, protein concentration, delta optical density at 450 nm, and amniotic fluid/maternal plasma creatinine ratio) were similar in the two groups. Growth-retarded fetuses had amniotic fluids with a lower mean (+/- SE) pH than their normally developed peers (7.50 +/- 0.083 versus 7.85 +/- 0.084, p = 0.023). Intrauterine growth-retarded fetuses appeared to ingest amniotic fluid at a slower mean rate than normally developed fetuses (609 +/- 50.9 versus 769 +/- 48.6 ml/day, p = 0.05), but the difference disappeared when the estimates were corrected for fetal weight. Whether these data may be extrapolated to human pregnancies is speculative but appears likely in view of the similarities between amniotic fluid volume and composition in normal baboon and human pregnancies.

Amniotic Fluid

Nonstress and contraction stress testing of baboon fetuses.

This study of six pregnant baboons at 133 to 175 days of gestation indicates that all of 26 nonstress tests (two to seven per animal) and all of eight contraction stress tests (one or two per animal) were successfully performed despite the need for sedation of the dam with ketamine.

Animals