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Biomedical subjects

R I Clyman

Publications and source records attributed to R I Clyman.

At least 91 records · Page 5Linked to original sources
PubMed1982

Ontogeny and regulation of corticosteroid binding globulin capacity in plasma of fetal and newborn lambs.

The developmental pattern for plasma corticosteroid binding globulin (CBG) and unbound corticoids was studied in fetal and newborn sheep. CBG capacity in the fetus increased progressively from a value of 1.6 micrograms cortisol bound/dl plasma at 75 days gestation to 7.1 micrograms/dl at 141 days (n = 249), with a greater rate of increase after 120 days. By contrast total plasma proteins increased by about 50% during the third trimester. There was an accelerated increase in the concentration of both CBG and total proteins with labor, apparently reflecting hemoconcentration. The rate of increase in total plasma corticoids was similar to that for CBG capacity; however, corticoids began their major rise later in gestation (approximately 130 days). The concentration of unbound corticoids was 0.09 micrograms/dl at 115 days and did not increase until after 135 days, reaching a maximal level of 1.87 micrograms/dl on the day before spontaneous term delivery. After birth, CBG capacity decreased from a prepartum value of 11.4 micrograms/dl to 0.6 micrograms/dl at 14 days of age, whereas total plasma proteins were constant. Total and free corticoid levels also decreased postnatally, but at a slower rate than for CBG. The expected rise in fetal CBG capacity during the third trimester did not occur in hydranencephalic, stalk-sectioned, and hypophysectomized fetuses with loss of pituitary function. Under the conditions used, there was no precocious increase in CBG concentrations with infusion of hydrocortisone, PRL, or 17 beta-estradiol to intact fetuses, and infusion of ACTH to a hypophysectomized fetus did not affect the level of CBG. Thus, there is a marked increase in CBG capacity prenatally and a rapid decrease after birth. These changes in CBG may be responsible, at least in part, for the similar changes in total corticoid concentrations. We conclude that pituitary hormone(s) regulate CBG in the sheep fetus and speculate that this effect involves the placenta.

Adrenal Cortex Hormones↗
PubMed1981

Effect of gestational age on pulmonary metabolism of prostaglandin E1 & E2.

The fetus and prematurely delivered newborn lamb have high concentrations of circulating PGE2 that may play a hormonal role, particularly in maintaining the patency of the ductus arteriosus. We studied the ability of the isolated, perfused lung from immature (100 +/- 2 days gestation, +/- SEM n = 8) and near term (142 +/- 1 days, n = 10; term is 150 days) lamb fetuses to metabolize PGE2 as a function of PGE2 concentration in the perfusate. After an intra-arterial infusion of 3H-PGE2 and 14C-inulin (to act as a marker of extracellular space), the bulk of the 14C-inulin was rapidly cleared through the isolated lung and the majority of the 3H activity appeared after the 14C activity had fallen to negligible values. The 3H activity that was retained longer in the lung was primarily associated with the 15-keto prostaglandin E2 and 15-keto-13,14 dihydro prostaglandin E2 metabolites. Lungs from immature fetal lambs metabolized 25% less PGE2 than did lungs from animals near term. This is consistent with our prior observation that premature lambs have decreased plasma clearance rates (in vivo) and elevated circulating concentrations of PGE2 when compared with term newborn lambs.

Alprostadil↗
PubMed1981

Risk factor analysis of intraventricular hemorrhage in low-birth-weight infants.

Sixty of 63 newborn infants weighing less than 1,250 gm, admitted consecutively to the Intensive Care Nursery during a 15-month period, were prospectively investigated for the incidence of intraventricular hemorrhage by early computerized tomography or by autopsy. Nineteen of the 60 infants had evidence of IVH. The incidence of IVH was correlated with the presence of possible neonatal, obstetrical, asphyxial, or therapeutic risk factors. There was a significant difference in only one of the risk factors: birth outside the perinatal center. Fifteen of 27 outborn infants (56%) developed IVH, whereas only four of 33 inborn infants (12%) developed IVH (P less than 0.001). There were no statistically significant differences in maternal obstetrical risk factors, infant risk factors, or indices of birth asphyxia in the inborn compared with the outborn infants. However, perinatal therapeutic risk factors differed between the two groups. Outborn infants were less likely to have received betamethasone (P less than 0.001), were less likely to have their arterial blood gases monitored and stabilized during the first 20 minutes after birth (P less than 0.001), and were given more bicarbonate (P less than 0.001) and more boluses of fluid intravenously (P less than 0.02). The risk of IVH in very low birth-weight infants may be significantly decreased by therapeutic factors at birth. Maternal transport to a perinatal center and intensive neonatal resuscitation may contribute to decreasing the incidence of intraventricular hemorrhage.

Cerebral Hemorrhage↗
PubMed1981

Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs.

We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.

Animals↗
PubMed1980

Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs.

We used pregnant sheep and their fetuses as well as newborn lambs (with and without severe respiratory distress due to prematurity) to study the differences in plasma clearance rate, production rate, and circulating concentrations of immunoreactive PGE2. Fetal PGE2 concentrations were significantly higher than simultaneous maternal concentrations. After delivery by cesarean section, all newborn animals were paralyzed and mechanically ventilated. The PGE2 concentrations fell in those lambs that required only minimal ventilatory support (FIO2 < 0.25) and were similar to maternal concentrations by two to three hours. Newborn lambs that developed severe respiratory distress (FIO2 < 0.55) continued to have concentrations that were even greater than fetal concentrations. The elevated PGE2 concentrations in severely distressed lambs were due not only to a decreased plasma clearance rate but also to an increased production rate of PGE2. Since PGE2 appears to maintain the patency of the ductus arteriosus in the fetus and preterm neonate, we examined the patency of the ductus arteriosus in 3-hour-old newborn lambs by radioactive microsphere injections. The ductus was more widely patent in lambs with higher concentrations of PGE2. The increased circulating concentrations of PGE2 in newborn lambs with severe respiratory distress may contribute to the pathogenesis of patent ductus arteriosus by exerting an additional vasodilatory effect on the vessel.

Animals↗
PubMed1980

Age-dependent sensitivity of the lamb ductus arteriosus to indomethacin and prostaglandins.

Endogenous prostaglandins inhibit the ability of the ductus arteriosus to contract in response to oxygen. We studied the effects of endogenous prostaglandins and indomethacin (an inhibitor of endogenous prostaglandin production) on isometric contraction of isolated rings of lamb ductus arteriosus from animals of different gestational ages (98 to 103 days and 136 to 147 days; term is 150 days). Rings from animals at about 100 days' gestation have a significantly larger indomethacin-induced contraction than rings from animals near term. The lamb ductus arteriosus forms two prostaglandins that relax the vessel: postaglandin E2 and prostacyclin. PGI2 was three orders of magnitude less potent than PGE2. Rings from the younger animals were significantly more sensitive to the relaxing action of PGE2 and PGI2 than were rings from animals near term. This increased sensitivity of immature animals to endogenous prostaglandins is consistent with the more potent effect of indomethacin on rings from immature animals. These observations are also consistent with the findings that preterm infants have an increased incidence of patent ductus arteriosus and that indomethacin can constrict the ductus arteriosus in preterm infants.

Animals↗
PubMed1980

Issues concerning parents after the death of their newborn.

Thirty-five families were interviewed by members of the intensive care nursery staff 2-4 months after the death of their newborn. Of the families interviewed, 74% wanted to review the events leading to their child's death and ask questions about information they already knew. Most families who were interested in the autopsy findings used the results to find out "how normal everything else was." Topics frequently discussed by parents involved feelings of guilt and problems that arose after the infant's death (isolation by friends, somatic complaints, marital and sexual problems, memories of prior losses, problems with siblings and disposal of baby's things). One-third of the families were felt to need continuing emotional support due to their inability to assume previously accepted responsibilities. For many families, the physician may be the only individual who can tolerate listening to their distress.

Adaptation, Psychological↗
PubMed1980

Circulating prostaglandin E2 concentrations and incidence of patent ductus arteriosus in preterm infants with respiratory distress syndrome.

In several species prostaglandin E2 (PGE2) appears to be the most important prostanoid to regulate patency of the ductus arteriosus. We measured the arterial plasma concentration of PGE2 in 29 premature infants (17 with respiratory distress syndrome alone and 12 with respiratory distress syndrome and patent ductus arteriosus) to determine if there was an association between circulating PGE2 and patent ductus arteriosus. The PGE2 concentrations during the first two days after birth were higher than PGE2 concentrations after the third postnatal day (17.1 +/- 3.1 pg/ml, mean +/- SEM, n = 23, vs 6.12 +/- 0.63 pg/ml, n = 19, P < .005). By the third postnatal day, arterial concentrations were similar to adult venous values. There was no significant difference between the plasma PGE2 concentrations in the 12 infants with patent ductus arteriosus and the concentrations in the 17 infants who had no signs of patent ductus arteriosus. These findings do not support the hypothesis that an increased concentration of circulating PGE2 is the primary cause for the persistent patency of the ductus arteriosus in preterm infants with respiratory distress syndrome.

Ductus Arteriosus, Patent↗
PubMed1979

Developmental response to indomethacin: a comparison of isometric tension with PGE2 formation in the lamb ductus arteriosus.

We studied the effects of oxygen and indomethacin on the isometric contractile response and the production of PGE2 in isolated rings of lamb ductus arteriosus from animals of different gestational ages (100 to 144 days; term is 150 days). Rings of ductus arteriosus from animals less than 110 days released significantly less PGE2 than did rings from animals greater than 120 days. The indomethacin-induced increase in muscle tension in relation to the decrease in endogenous PGE2 production in preparations from animals less than 110 days gestation was greater than in animals older than 120 days. These findings do not support the hypothesis that immature animals have a larger indomethacin-induced contraction due to an increased production of PGE2 earlier in gestation. They are, however, consistent with a decreased sensitivity to PGE2 in the more mature animals; they also support the hypothesis that the decreased effectiveness of indomethacin on the ductus arteriosus from later gestation animals reflects primarily a decrease in the sensitivity of the vessel to PGE2 during development.

Animals↗