Maternal and neonatal hemostatic correlation.
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Antithrombins↗
Biomedical subjects
D B Cotton
Publications and source records attributed to D B Cotton.
Peripheral magnesium sulfate enters the brain and increases the threshold for hippocampal seizures in rats.
OBJECTIVES: Our objectives were to determine whether magnesium sulfate crosses the blood-brain barrier and whether it has central anticonvulsant action. STUDY DESIGN: In experiment 1 34 female Long-Evans rats were divided into six groups: control (n = 7); single magnesium sulfate injection and evaluation after 20 minutes in 3 conditions: normal rats (n = 7), sham-operated animals (n = 5), and after electrical stimulation by hippocampal electrode (n = 5); single injection and evaluation after 2 hours (n = 5); and prolonged (2 hours) serum magnesium elevation (n = 5). Serum, cerebrospinal fluid, and specific brain areas were analyzed for magnesium concentrations. In experiment 2 threshold for electrical seizure was measured in eight rats before and after intraperitoneal injections of magnesium sulfate versus saline solution. RESULTS: In experiment 1 there was a significant correlation between blood and cerebrospinal fluid magnesium concentrations (r = 0.80, p < 0.0001). Magnesium concentrations were increased in the cortex and hippocampus, with the largest changes occurring after two hours of sustained serum magnesium concentrations (p < 0.01). Induction of hippocampal seizure activity resulted in further elevations in cerebrospinal fluid magnesium concentrations but did not change brain concentrations. In experiment 2 magnesium sulfate increased the electrical threshold required to induce seizures by 34% (p = 0.01). CONCLUSIONS: Magnesium sulfate enters the cerebrospinal fluid and brain and has a central anticonvulsant effect.
Animals↗
Alarm substance induces convulsions in imipramine-treated rats.
Male rats were injected with imipramine (0-30 mg/kg) and subsequently tested in the forced-swim test in either fresh water or water soiled by other rats, which presumably contains an alarm substance. Imipramine did not affect the behavior of rats in fresh water. More than half the animals given the combination of imipramine (30 mg/kg) and stress from alarm substance had clonic convulsions. Adrenalectomy did not affect this relationship. This is the first study demonstrating the potential of an alarm substance for inducing convulsions.
Adrenal Glands↗
Anticonvulsant effects of magnesium sulfate on hippocampal seizures: therapeutic implications in preeclampsia-eclampsia.
OBJECTIVE: The objective of this study was to determine whether magnesium sulfate has central anticonvulsant effects. STUDY DESIGN: In three experiments we investigated the anticonvulsant properties of magnesium sulfate on the hippocampus because of its high density of N-methyl-D-aspartate receptors and link to clinical epilepsy. Seizure activity was elicited in the hippocampus of rats or in in vitro hippocampal brain slices. The effects of magnesium on seizure activity were determined. RESULTS: (1) Intraperitoneal magnesium sulfate (270 or 360 mg/kg) failed to block hippocampal seizures but reduced electroencephalographic amplitude and seizure duration. (2) Injection of magnesium sulfate directly into a seizure focus blocked seizures and elevated seizure thresholds. (3) Low magnesium levels produced epileptiform activity in an in vitro hippocampal brain slice preparation; the epileptiform activity was reversed by increasing the magnesium concentration. CONCLUSIONS: Magnesium sulfate has central anticonvulsant activity on hippocampal seizures, implicating the N-methyl-D-aspartate receptor in eclamptic seizures and in the therapeutic efficacy of magnesium sulfate.
Animals↗
The natural interleukin-1 receptor antagonist in term and preterm parturition.
OBJECTIVE: Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The interleukin-1 receptor antagonist is a new member of the interleukin-1 gene family that inhibits the biologic effects of interleukin-1 by blocking its receptors. Reduction of interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN: Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with interleukin-1 receptor antagonist and interleukin-1 alpha or interleukin-1 beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. RESULTS: (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of interleukin-1 alpha and interleukin-1 beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) interleukin-1 receptor antagonist reduced interleukin-1 beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS: (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) the release of interleukin-1 alpha and interleukin-1 beta into the amniotic fluid in women with preterm labor is not associated with an increase in interleukin-1 receptor antagonist levels in amniotic fluid; (3) interleukin-1 receptor antagonist reduces interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor.
Adult↗
Circulating lymphocyte subsets in second- and third-trimester fetuses: comparison with newborns and adults.
OBJECTIVES: Our objective was to compare the relative sizes of circulating lymphocyte subsets in fetuses, newborns, and adults. STUDY DESIGN: Two-color flow cytometric analysis of lymphocyte cell surface markers was performed on blood from 64 fetuses, 22 newborns, and 67 normal adults. RESULTS: All three groups had similar percentages of CD3+ total T cells, CD4+ helper T cells, CD8+ cytotoxic/suppressor T cells, and CD20+ B cells. Compared with adults, fetuses and newborns had markedly reduced percentages of CD57+ natural killer T cells and consistently increased percentages of CD5+CD20+ B cells. Most fetal and cord T and B lymphocytes expressed the activation marker CD38. CONCLUSIONS: Similarities and age-dependent differences exist among fetal, newborn, and adult circulating lymphocyte subsets. Lymphocyte marker analysis may prove useful in the detection of fetal infection and other complications of gestation.
Adult↗
The effect of tocolytic agents (indomethacin and terbutaline) on fetal breathing and body movements: a prospective, randomized, double-blind, placebo-controlled clinical trial.
OBJECTIVE: The null hypothesis of this study is that maternal administration of indomethacin or terbutaline will not affect fetal breathing and body movements. STUDY DESIGN: Thirty patients with a low-risk pregnancy, gestational age 26 to 32 weeks, and no signs of preterm labor were randomly assigned to receive either terbutaline (5 mg), indomethacin (50 mg), or a placebo. Ultrasonographic evaluation of fetal breathing and body movements was performed for 1 hour before and 1 hour after treatment. The total amount of time of fetal breathing and body movements in each group was subject to statistical analysis that included analysis of variance and covariance and a multiple comparison procedure. RESULTS: Indomethacin increased fetal breathing from 20.8 +/- 13.1 minutes to 42.2 +/- 14.8 minutes (p < 0.01), whereas terbutaline increased fetal breathing movements from 19.8 +/- 9.0 minutes to 35.2 +/- 12.4 minutes (p < 0.01). No significant treatment effect was detected on fetal body movements. CONCLUSION: Between 26 and 32 weeks' gestation, a single dosage of indomethacin or terbutaline increases fetal breathing movements by 103% and 78%, respectively.
Double-Blind Method↗
Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.
OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy. STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation > or = 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Gram stain was performed on all samples. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33). The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp. All patients with microbial invasion of the amniotic cavity had complications. Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss. On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture. Of 16 patients with a negative amniotic culture, nine were delivered at > 34 weeks. CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester.
Abortion, Spontaneous↗
Maternal respiration and blood gases during aerobic exercise performed at moderate altitude.
We studied whether maternal acid-base status during aerobic exercise performed at moderate altitude is affected by pregnancy. Seven primiparus women were tested at 37 wk gestation and 12 wk postpartum. Subjects were studied at rest, and during two cycle (50 W, 75 W) and two treadmill (67 m.min-1; 2.5% grade, 67 m.min-1; 12% grade) protocols. Exercise bouts lasted 6 min with a 10-min rest between sessions. Minute (VE) and alveolar (VA) ventilation, tidal volume (VT), and ventilatory equivalent for carbon dioxide (VE/VCO2) were significantly (P less than 0.01) greater when exercise was performed during pregnancy. Physiological dead space (VD) was not affected by pregnancy status and did not differ between rest and exercise. Decreases (P less than 0.01) in arterial pH during exercise averaged 0.04 units in both pregnancy and postpartum. Despite similar change in maternal pH, carbon dioxide tension (PaCO2) remained unchanged during exercise at 37 wk gestation but decreased at 12 wk postpartum. Decreases in arterial bicarbonate [HCO3-] associated with exercise were smaller during pregnancy. Our findings indicate that pregnancy did not compromise maternal acid-base status during aerobic exercise.
Acid-Base Equilibrium↗
Evolution of hydranencephaly following intracerebral hemorrhage.
A circumscribed hyperechoic mass in the mid-portion of the left cerebral hemisphere was the presenting ultrasonographic finding in a 30-week fetus. With repeat ultrasound studies, this echo-dense mass became more sonolucent. In addition, there was an increased fluid accumulation and loss of identifiable cerebral cortex over the left parietal and occipital lobes. The patient underwent induction of labor because of progressive intracranial fluid accumulation with subsequent macrocephaly. The infant died on the fourth day of life. At necropsy, an organizing hematoma with admixtures of fresh and moderately degraded old blood was found in the left hemisphere. There was extensive resorption of the underlying cortex, leaving only a fluid-filled cavity with a meningeal covering. We believe the progressive changes that occurred after fetal intracerebral hemorrhage ultimately resulted in hydranencephaly.
Adult↗
Coagulation profile in severe preeclampsia.
One hundred women with severe preeclampsia or chronic hypertension with superimposed preeclampsia were seen during a 2-year period. We sought to determine whether a normal platelet count assures that no other clinically significant clotting abnormalities are present, and what level of thrombocytopenia predicts a risk of abnormalities in other coagulation indices. Fifty women had platelet counts below 150,000/microL, of whom 13 had a fibrinogen level below 300 mg/dL and two had a prolonged prothrombin time (PT) or partial thromboplastin time (PTT). The admission platelet count was an excellent predictor of subsequent thrombocytopenia (r = 0.829, P less than .001). No subject had an abnormal fibrinogen level or prolonged PT or PTT in the absence of thrombocytopenia. When monitoring intrapartum coagulation indices in preeclampsia, one can safely follow only the platelet count at admission and subsequently, reserving PT and PTT and fibrinogen levels for those cases complicated by counts less than 100,000/microL.
Adult↗
Baroreflex function in normal pregnancy.
The sinoaortic baroreflex is one of the primary mechanisms that regulates blood pressure. Decreased baroreflex sensitivity has been reported in preeclampsia. We sought to determine whether pregnancy altered baroreflex sensitivity. From a radial artery catheter, heart rate and mean arterial pressure were recorded continuously onto a polygraph. The ratio of change in heart rate produced per unit of change in mean arterial pressure was calculated as an index of baroreflex sensitivity. Mean arterial pressure responses to incremental infusions of phenylephrine (0.4 to 2.0 micrograms/kg/min) were measured in the same patients at term (n = 9, 38.0 +/- 0.3 weeks) and again 6 to 8 weeks postpartum (n = 7). The results indicated (1) higher baroreflex sensitivity in pregnancy than in the postpartum period (0.9 vs 0.5 beats/min/mm Hg) (p less than 0.007); (2) attenuated vascular responsiveness to alpha-adrenergic stimulation in pregnancy (p less than 0.05); (3) a relationship between vascular responsiveness and baroreflex sensitivity. We conclude that pregnancy is associated with an increase in baroreflex sensitivity and that the attenuated response to phenylephrine is, at least in part, a result of increased baroreflex sensitivity.
Adolescent↗
The hemodynamic effects of intubation during nitroglycerin infusion in severe preeclampsia.
The effectiveness of intravenous nitroglycerin infusion in lowering maternal blood pressure and in blunting the hemodynamic responses to endotracheal intubation was evaluated in six primigravid women with severe preeclampsia. Monitoring consisted of continuous electrocardiogram monitoring, arterial cannulation, and flow-directed pulmonary arterial catheterization in each patient. All patients underwent oxytocin induction of labor and crystalloid and/or colloid expansion to produce a pulmonary capillary wedge pressure of 10 to 15 mm Hg and a colloid osmotic pressure of greater than 17 mm Hg. Intravenous nitroglycerin was administered before induction of general anesthesia. The hemodynamic effects associated with endotracheal intubation revealed a change in the heart rate from 104 +/- 10 to 133 +/- 17 beats/min, an increase in mean arterial pressure from 134 +/- 12 to 164 +/- 32 mm Hg, and an increase in systemic vascular resistance from 1262 +/- 342 to 1351 +/- 259 dynes-sec-cm-5 that was accompanied by a small change in the cardiac index from 4.5 +/- 1.2 to 4.5 +/- 0.9 L.min-1.m-2.
Acute Disease↗
Position change and central hemodynamic profile during normal third-trimester pregnancy and post partum.
Central hemodynamic response to position change was assessed in 10 normotensive primiparous patients between 36 and 38 weeks' gestation. Studies were repeated between 11 and 13 weeks post partum. Compared with the left lateral position, we observed a mean 9% fall in cardiac output in the supine position and an 18% fall when patients were standing. When standing, these patients had a 30% increase in pulse and a 21% fall in left ventricular stroke work index. The orthostatic response after pregnancy was much more labile than that during the third trimester. These findings have important descriptive implications for the understanding of the human response to orthostasis during pregnancy, as well as clinical implications for patients at risk of uteroplacental insufficiency and for working women during pregnancy.
Adult↗
Should continuous hydralazine infusions be utilized in severe pregnancy-induced hypertension?
Intravenous hydralazine therapy in severe preeclampsia-eclampsia may be administered by either continuous intravenous infusion or intermittent bolus therapy. We studied the hemodynamic effects of continuous intravenous hydralazine infusion in seven patients with severe pregnancy-induced hypertension. The starting infusion dose was 5 mg/hr and was increased every 15 to 20 minutes by 1 to 2 mg/hr to obtain a 20% reduction in mean arterial blood pressure. The initial mean systolic and diastolic blood pressures were 208.3 +/- 24.8 and 124.3 +/- 11.6 mmHg, respectively. The comparable mean levels following hydralazine therapy was 144 +/- 13.6 and 87 +/- 11.6 mmHg. This decline was obtained at a mean hydralazine dose of 16.04 +/- 3.65 mg/hr. Despite an increase in cardiac output, the rapid uncontrolled decline in blood pressure resulted in five of the seven patients developing fetal distress requiring cesarean delivery. If hydralazine therapy is to be used in severe preeclampsia-eclampsia, we advocate avoidance of continuous intravenous therapy.
Apgar Score↗
Urinary sediment changes in severe preeclampsia.
We analyzed the urinary sediment of 30 patients with severe preeclampsia every 4 hours during early labor, delivery, and the postpartum period. Fifteen normal control patients were also followed in a similar fashion. No casts were noticed in the urine samples of the control group. However, the urinary sediment of preeclamptic patients revealed the same uniform pattern regardless of the state of coagulation, or the presence or absence of oliguria or eclamptic seizures. Numerous granular and hyaline casts, red-cell, and tubular cell casts were identified during microscopic evaluation. These data reflect both glomerular and tubular damage in preeclampsia. We conclude that urinary sediment analysis in severe preeclampsia uniformly reflects renal parenchymal damage and does not correlate with or predict the clinical course of the disease.
Adult↗
Management of severe preeclampsia and eclampsia.
Pregnancy-induced hypertension is a disorder of unknown etiology unique to pregnant women. Classic clinical manifestations include hypertension, proteinuria, and edema. Early recognition and proper management of this disease may serve to avoid serious maternal complications. Ultimate maternal treatment depends on delivery of the fetus and placenta. Advanced stages of this disease result in multi-organ system dysfunction that may be life-threatening to the mother and her fetus. Such maternal complications of PIH include severe hypertension, oliguria or anuria, HELLP syndrome, eclamptic seizures, liver rupture, pulmonary edema, cerebral edema, and abruptio placentae. A multidisciplinary approach of the critical care team often will effect a reduction in maternal morbidity and mortality.
Abruptio Placentae↗
Severe edema-proteinuria-hypertension gestosis.
Severe edema-proteinuria-hypertension (EPH) gestosis (pre-eclampsia) appears in at least two forms (A and B). The A type is mostly complicated by fits, while the B type is characterized by multiple organ failure. The perinatal mortality rate is especially high in the B group. All gravid women with severe EPH gestosis benefit from blood volume expansion therapy.
Adult↗