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Biomedical subjects

R I Clyman

Publications and source records attributed to R I Clyman.

At least 109 records · Page 6Linked to original sources

Do parents utilize physician follow-up after death of their newborn?

Numerous authors have advocated appropriate physician-patient counseling following a perinatal death. We examined, in a prospective manner, how many families utilized physician follow-up when such follow-up was offered. Seventy-six percent of the 108 families who experienced a neonatal death chose to have physician follow-up in the weeks after the death. A family's utilization of subsequent physician contact was not related to the distance they lived from the medical center, the duration of survival of the infant, or the racial background of the mother. Parents utilized follow-up visits whether or not an autopsy was performed or an interpreter was needed. Certain features distinguished the parents who did not utilize the physician follow-up service: parents were less likely to utilize the service if they were not married, the mother was a teenager, the head of the household was unemployed, or there was no phone at home.

Adolescent↗

PGE2 is a more potent vasodilator of the lamb ductus arteriosus than is either PGI2 or 6 keto PGF1alpha.

It has been shown in vitro that the lamb ductus arteriosus forms prostaglandins PGE2, PGF2alpha, 6 keto PGF1alpha (and its unstable precursor PGI2). In this study the relative potencies of these endogenous prostaglandins were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2 and indomethacin. All the prostaglandins (except PGF2alpha) relaxed the vessel. This is consistent with the hypothesis that endogenous prostaglandins inhibit the tendency of the vessel to contract in response to oxygen. Only PGE2, however, relaxed the vessel at concentrations below 10(-8)M. PGI2 and 6 keto PGF1alpha had approximately 0.001 and 0.0001 times the activity of PGE2. Although PGE2 has been observed to be a minor product of prostaglandin production in the lamb ductus arteriosus, the tissue's marked sensitivity to PGE2 might make it the most significant prostaglandin in regulating the patency of the vessel.

Animals↗

Responsiveness of the lamb ductus arteriosus to prostaglandins and their metabolites.

The relative potencies of the prostaglandins A1, A2, E1, E2, F2alpha and their 15-keto-, 15-keto-13,14-dihydro-, and 13,14-dihydro-metabolites were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2. All the prostaglandins (except PGF2alpha and its 15-keto-metabolites) relaxed the tissue. However, only PGE1, E2, and their 13,14-dihydro-metabolites, were effective at concentrations below 10(-8) M. Therefore, events that alter metabolism of circulating PGs in the perinatal period may have significant effects on the relative patency or closure of the ductus arteriosus.

Animals↗

Formation of prostacyclin (PGI2) by the ductus arteriosus of fetal lambs at different stages of gestation.

Prostaglandins appear to play a role in maintaining patency of the ductus arteriosus during gestation. Prostacyclin (PGI2) is the major product of prostaglandin biosynthesis in the lamb ductus arteriosus. This factor is both a vasodilator and a potent inhibitor of human platelet aggregation. We used inhibition of platelet aggregation as a sensitive bioassay to measure PGI2 generation in rings of ductus arteriosus from fetal lambs. Mechanical manipulation accelerated the rate of PGI2 released from the tissue 10 to 50 times. Tranylcypromine, an antagonist of prostacyclin synthetase, suppressed production of PGI2 by rings of ductus arteriosus. Rings from immature animals (98-103 days gestation, term is 150 days) released significantly more PGI2 (190 +/- 28 ng/g wet weight/ 20 min, n = 9) than did those from near term animals (136-146 days; 106 +/- 23 ng/g wet weight/20 min, n = 10). The capacity of the ductus arteriosus to generate more PGI2 earlier in gestation is consistent with the observation that vessels from animals less than 110 days gestation have a significantly larger indomethacin induced contraction than do vessels near term.

Animals↗

The developmental response of the ductus arteriosus to oxygen.

We studied the isometric contractile effects of increased PO2 on isolated rings of lamb ductus arteriosus (from three different gestational age groups). When rings were stretched to initial lengths that result in a maximal contractile response for rings in that age group, the oxygen-induced contraction was 5.91 +/- 0.72 g/mm2 (+/-SEM, n = 18) in animals older than 135 days, 5.55 +/- 1.23 g/mm2 (n = 18) in animals between 111 and 130 days, and 3.85 +/- 0.75 g/mm2 (n = 19) in animals between 87 and 110 days. Only in the most immature vessels could a decrease in the tissue's response to oxygen be observed.

Animals↗

Ductus arteriosus responses to prostaglandin E1 at high and low oxygen concentrations.

It previously has been suggested that prostaglandin E1 (PGE1) relaxes the ductus arteriosus in a low but not in an elevated oxygen environment. However, in the experiments reported here PGE1 relaxed rings on fetal lamb ductus arteriosus in vitro at both low (14 to 20 torr) and high (680 to 720 torr) oxygen tensions. The threshold concentration for PGE1 was 10(-10) M in either PO2 and the ED50's of PGE1 relaxation in high and low oxygen were 8.5 +/- 3.4 x 10(-10) M and 5.5 +/- 0.7 x 10(-10) M respectively. The magnitude of the relaxation was greater for the oxygen contracted ductus arteriosus than for that exposed to low oxygen. It is suggested that earlier reports of the lack of response of the ductus arteriosus to PGE1 in a high oxygen environment following relaxation in a low oxygen environment may be related to loss of response of the ductus arteriosus to repeated doses of PGE1 rather than to differences in PO2. Prostaglandin E1 therefore may play a significant role in the regulation of ductus arteriosus tone in the elevated oxygen environment of the newborn as well as the low oxygen environment of the fetus.

Animals↗

Calcium uptake by subcellular fractions of human umbilical artery.

Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2.

Adenosine Triphosphate↗

The role of calcium in regulation of cyclic nucleotide content in human umbilical artery.

In term gestational human umbilical artery segments incubated in room air at 37 degrees, histamine, acetylcholine, bradykinin, K+, and serotonin (agonists that cause contraction) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering the content of adenosine 3':5'-monosphophate (cAMP); prostaglandin E1 (PGE1), which relaxes the artery, causes cAMP accumulation without affecting the cGMP content (Clyman, R. I., Sandler, J.A., Manganiello, V.C., and Vaughan, M. (1975) J. Clin. Invest., in press). It has been postulated that Ca-2+ is important in the regulation of cyclic nucleotides in other tissues. In the umbilical artery the control of cAMP content by PGE1 was independent of Ca-2+. After incubation in Ca-2+-free medium, the c GMP contentof the artery segments was decreased by 50% and was unaffected by histamine, acetylcholine, bradykinin, and K+. Readdition of Ca-2+ (2.7 mM) or Sr-2+ (3.6 mM) to the medium partially restored the basal cGMP content and the agonist effects on the cGMP content. However, Sr-2+ was not as effective as Ca-2+ in this regard. Ionophores A23187 and X537A (agents that facilitate Ca-2+ movement through membranes) mimicked the effects of these Ca-2+-dependent agonists on cGMP content. Incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (0.1 mM) increased both the basal content of cGMP and the histamine-induced accumulation 3-fold. This effect was dependent on the presence of Ca-2+ also. Accumulation of cGMP induced by serotonin, on the other hand, was not diminished in Ca-2+-depleted arteries and, in fact, seemed to be inhibited by 2.7 mM Ca-2+. These observations are consistent with the existence in the umbilical artery of two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca-2+.

Anti-Bacterial Agents↗

Oxygen and cyclic nucleotides in human umbilical artery.

In the human umbilical artery O2 has a direct contractile effect and is also required for induction of contraction by several other agents. Agonist that cause contraction (bradykinin, histamine, and serotonin) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering adenosine 3':5'-monophosphate (cAMP). They appear to act through two different mechanisms: one Ca++-dependent, the other Ca++-inhibited. O2 increased the cGMP content of the artery in a Ca++-dependent manner without affecting the cAMP content. Inhibitors of oxidative phosphorylation (oligomycin and 2,4-dinitrophenol) did not diminish this effect of O2. O2 was required for demonstration of the Ca++-dependent accumulation of cGMP in response to bradykinin, histamine, and ionophore A23187. The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine on basal cGMP content and on the bradykinin-induced accumulation was also dependent on the presence of O2. Methylene blue and sodium ascorbate caused cGMP accumulation in O2-deprived arteries. Their effects were not diminished in Ca++-depleted arteries and, in fact, seemed to be inhibited when 2.7 mM Ca++ was present in the medium. The effects of these agents and of serotonin on cGMP, which were inhibited by Ca++, were also inhibited by O2. These non Ca++-, non O2-dependent agents (methylene blue, ascorbate, and serotonin) did not, however, permit demonstration of the effects of the Ca++- and O2-dependent agonists on O2-deprived arteries. It appears that there are in the umbilical artery (and probably in other tissues also) at least two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca++- and O2-linked processes.

Anaerobiosis↗

The effect of serotonin (5-hydroxytryptamine) and derivatives on guanosine 3',5'-monophosphate in human monocytes.

The effects of several putative mediators of inflammatory responses on the cyclic nucleotide content of mononuclear leukocytes from human peripheral blood were investigated. Incubation of mononuclear cells with 100 muM serotonin (a maximally effective concentration) for 5 min caused a five- to eightfold increase in their content of guanosine 3',5'-monophosphate (cAMP)...

Bradykinin↗

Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.

Human umbilical arteries are unique vessels in that they close quickly and completely at birth. It has been suggested that cyclic uanosine 3',5'-monophosphate (cAMP) in relaxation. This hypothesis has been evaluated in term gestational human umbilical artery segments incubated at 37 degrees C and in room air. (a) The basal cGMP content (1 pmol/mg protein) of artery segments incubated in room air was almost twice that of cAMP. (b) Bradykinin, histamine, serotonin, acetylcholine, and K+ ion, which cause umbilical artery constriction, can increase the cGMP content of the artery segments within 30 s of exposure without altering the cAMP content. (c) Prostaglandin E1, but not isoproterenol, caused accumulation of cAMP which is consistent with reports that umbilical arteries lack functional beta-receptors and that only prostaglandin E1 can bring about relaxation of umbilical arteries. (d) 1 muM atropine blocked the effect of 100 muM acetylcholine on cGMP content without altering the responses to histamine, bradykinin, serotonin, or K+ ion. (e) Pyrilamine (an H1 antagonist), but not metiamide (an H2 antagonist), blocked the effect of histamine on cGMP from which it is inferred that histamine causes accumulation of cGMP in umbilical artery via its interaction with H1 receptors. The results are consistent with the view that metabolism of the two cyclic nucleotides is independently controlled in the human umbilical artery and that cGMP is involved in contraction of the artery at birth.

Acetylcholine↗