Guy M. Harbert

Thrombocytopenia in preeclampsia associated abnormalities and management principles

Severe thrombocytopenia, abnormal liver function, and renal dysfunction may occur as manifestations of preeclampsia. Failure to recognize that this cluster of abnormalities represents a form of preeclampsia may result in erroneous initial diagnoses. Management of 13 such patients has shown a direct correlation between the degree of thrombocytopenia and the measures of liver dysfunction. Platelet counts and liver functions improved prior to delivery in five patients treated with corticosteroids. Management should be directed toward investigation and correction of deranged physiology and appropriate monitoring of maternal-feto-placental status. Early delivery is indicated in patients with progressive thrombocytopenia and in those with evidence of fetal maturity or distress. Provided that the disease process remains stable, consideration should be given in cases of fetal immaturity, to the use of betamethasone therapy. The occurrence of severe thrombocytopenia in 20% of neonates should be a consideration in selecting the mode of delivery.

Thrombotic thrombocytopenic purpura associated with pregnancy.

Thrombotic thrombocytopenic purpura (TTP), a disorder of unknown etiology, appears to be a syndrome often associated with infectious, vascular, or autoimmune diseases. When it occurs in pregnancy, TTP can mimic other gestational complications. Two patients with TTP associated with pregnancy form the basis of this report. On patient is the second person known to have survived longer than 2 years after concurrent TTP and pregnancy. This patient had underlying glomerulonephritis and was treated with corticosteroids and heparin. The other patient, in whom an underlying disease process was not identified, was treated unsuccessfully with most of the recommended therapeutic modalities. Patients with concurrent TTP and pregnancy have the same prognosis as nonpregnant patient with TTP. Both groups have a prolonged survival rate of only 10 per cent. Primary treatment should consist of corticosteroids and inhibitors of platelet aggregation. If a rapid response does not occur, splenectomy is indicated. Care must be taken to recognize the pregnancy complicated by TTP, a circumstance which appears to occur more frequently than past reports have indicated.

Biorhythms of the primate uterus (Macaca mulatta) during labor and delivery

The association between the documented spontaneous biorhythms of uterine activity, uterine artery blood flow, and aortaic blood pressure and the processes of labor and delivery was explored in 17 nonmedcated rhesus monkeys for 18 pregnancies. The characteristic circadian variations of higher hourly average values of uterine activity during periods of light than during periods of darkness were incorporated in a statistically distinct, predictable, and repetitive manner into the events of parturition. Variations in uterine artery blood flow reflected changes in intra-amniotic pressure. In those animals in which delivery occurred at night, a shift in maximal values of uterine activity from periods of light to periods of darkness occurred 48 to 60 hours prior to delivery. Progressive linear increases in hourly average values of frequency of contraction and aortic blood pressure consistently began 24 to 36 hours prior to delivery. These changes suggest that specific, directly related prodromal events occur within the maternal organism hours before parturition in the nonhuman primate.

Effect of toxemia therapy on uterine dynamics

Abstract Effect on uterine dynamics of magnesium sulfate, hydralazine hydrochloride, and cryptenamine acetates was evaluated by in vitro and in vivo techniques. Magnesium sulfate depressed myometrial activity in vitro. Hydralazine hydrochloride decreased the rate and increased the amplitude of contraction of human myometrial strips. In concentrations of 6 to 8 mEq. per liter of maternal serum, magnesium reduced the uterine activity of 7 pre-eclamptic patients in active spontaneous labor. The effect of each agent on myometrial and hemodynamic variables was measured in 3 pregnant rhesus monkeys during both normotensive and induced hypertensive states. Serum magnesium concentrations of 6 to 8 mEq. per liter resulted in a reduction of arterial blood pressure, a greater decrease in extrinsic myometrial resistance, and an increase in uterine artery blood flow. Intravenous administration of hydralazine hydrochloride in quantities sufficient to produce a statistically significant decrease in arterial blood pressure did not significantly alter uterine artery blood flow or average intra-amniotic pressure. Responses to cryptenamine acetates were inconclusive.

Magnesium sulfate and ritodrine hydrochloride: Systemic and uterine hemodynamic effects

Effects of magnesium sulfate and ritodrine hydrochloride on cardiovascular physiologic characteristics were studied in 70 human subjects treated for preterm labor. Systemic and uterine hemodynamic effects were investigated in five pregnant rhesus monkeys. Systolic blood pressure was minimally affected by either agent. Diastolic pressure, while not affected by magnesium sulfate, decreased 26.3% during ritodrine therapy. Maternal and fetal heart rates were minimally affected by magnesium sulfate. Ritodrine increased maternal and fetal heart rates significantly. In the monkeys, magnesium sulfate increased uterine and placental blood flows (by the microsphere technique) but failed to alter cardiac output. Ritodrine produced an increase in cardiac output but decreased perfusion pressure. Placental blood flow decreased by an average of 27.6%. Ritodrine would therefore seem contraindicated with a compromised fetal environment. Magnesium sulfate, by not altering perfusion pressure, may have a beneficial effect on uterine hemodynamics. These specific and distinct differences in cardiovascular and hemodynamic effects should be considered when either magnesium sulfate or ritodrine is selected as a tocolytic agent.

The role of ultrasonography and amniocentesis in the evaluation of pregnancies at risk for neural tube defects

To assess the relative efficacy of amniocentesis versus targeted (detailed) ultrasonography, 225 patients referred because of an elevated maternal serum alpha-fetoprotein level (79.6%) or a family history of neural tube defect (20.4%) were evaluated. Ultrasonographic examination alone detected all 26 fetal abnormalities (11 cases of anencephaly, 10 cases of open spina bifida, and five other anomalies). Twenty-eight patients declined amniocentesis; all had normal pregnancy outcomes. Of the 167 patients with apparently normal fetal anatomy by sonography, seven had elevated alpha-fetoprotein levels but no acetylcholinesterase in the amniotic fluid. Six of these pregnancies resulted in normal infants; one infant had congenital nephrosis. The remaining 160 patients had normal sonograms with normal amniotic fluid alpha-fetoprotein levels and no fetal malformations at delivery. Although these results suggest that targeted ultrasonography by experienced personnel is a reasonable alternative to amniocentesis in evaluations for neural tube defects, the availability, cost-effectiveness, and diagnostic accuracy of this approach must be well documented in large prospective studies.

Biorhythms of the pregnant uterus (Macaca mulatta)

Abstract Twelve rhesus monkeys confined to restraining chairs and maintained in a controlled environment were used to explore the existence and effect of biorhythms in the dynamics of the uterus during the last half of pregnancy. Spontaneous uterine activity, aortic blood pressure, and uterine artery blood flow were monitored continuously for periods of five to 25 days. During a 24 hour period, the variation in hourly average values of all measured functions occurred in repetitive and predictable patterns conforming to highly significant Fourier curves that were entrained by the light-dark cycle. Highest amniotic fluid and blood pressure values were recorded during the periods of light. Amplitudes of the sine curves calculated from intra-amniotic pressure data ranged from 1.8 to 59.4 per cent of the 24 hour mean, and in eight animals, they were positively correlated with blood pressure changes. In general, highest hourly average uterine artery blood flow rates occurred during the periods of darkness when intra-amniotic fluid pressures were minimal. The differences between minimal and maximal average flow rates ranged from 17.0 to 63.6 per cent of mean daily flow and were inversely correlated to amniotic fluid pressure changes. Disparities observed in the chronology and amplitude of the 24 hour periodic functions recorded for intra-amniotic pressure, blood pressure, and uterine blood flow indicate these biorhythms are modulated by factors in addition to those engendered by physiological pressure-flow relationships. The existence of these circadian rhythms should be considered when studying the kinetics and kinematics of the pregnant primate uterus.

Fetal evaluation by percutaneous blood sampling

Percutaneous umbilical blood sampling (cordocentesis) provides direct access to the fetal circulation in the second and third trimesters of pregnancy. Seventeen patients underwent this procedure between December 1985 and December 1986 for evaluation of a variety of clinical situations, including nonlethal fetal abnormalities detected by ultrasound, equivocal results of amniocentesis, nonimmune fetal hydrops, and isoimmune disorders. Our experience confirms the efficacy of the procedure and suggests that it may become an important tool for fetal assessment and therapy.

Effect of adrenergic blockade on dynamics of the pregnant primate uterus (Macaca mulatta)

Unanesthetized rhesus monkeys, conditioned to restraining chairs and monitored continuously by chronically implanted sensors, were used to explore the relationships between catecholamines and uterine dynamics during late gestation. Continuous intra-aortic infusion of phentolamine produced a dose-response decrease in uterine activity and blood flow. With alpha-adrenergic blockade the circadian (Fourier) variations of uterine activity were abolished and those of uterine blood flow were reversed. Placental blood flow (by the microsphere technique) was 86.1% of control values. Beta-adrenergic blockade (propranolol) accentuated the circadian variations of uterine dynamics. Vascular resistance to both the myometrium and the placentas was increased. The data indicate that the maternal placental vasculature is the primary site of uterine vascular resistance and is susceptible to adrenergic response. The data also suggest that the extrinsic resistance produced by the myometrium is of major importance in the distribution of uterine blood flow.

Pharmacologic control of uterine contractility. In vitro human and in vivo monkey studies.

The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor.