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Biomedical subjects

T J Benedetti

Publications and source records attributed to T J Benedetti.

At least 37 records · Page 2Linked to original sources

The maternal hemodynamic effect of indomethacin in normal pregnancy.

The vasodilation of pregnancy is thought by many to be due to increased endothelial production of prostacyclin, a vasodilatory prostanoid. Indomethacin, a potent inhibitor of prostaglandin synthesis, is known to increase the maternal blood pressure response to angiotensin II infusion. We sought to measure directly the hemodynamic effects of a short course of indomethacin. Twenty-three healthy pregnant women with uncomplicated pregnancies between 26-32 weeks' gestation completed the study. Using Doppler technology, we determined cardiac output, stroke volume, and total peripheral resistance before and after three 25-mg doses of indomethacin. Although blood pressure did not change, peripheral resistance rose and stroke volume fell following indomethacin administration. Our findings support the hypothesis that indomethacin interferes with tonic prostaglandin-induced vasodilation in pregnancy. However, the increase in vascular resistance was very slight, suggesting that other vasodilators are also at work in pregnancy. We recommend that indomethacin be used judiciously in hypertensive pregnant patients until more information concerning possible adverse hemodynamic effects becomes available.

Blood Pressure↗

Antiepileptics and the development of congenital anomalies.

We are conducting a prospective cohort study of epilepsy and pregnancy to determine the nature and extent of adverse pregnancy outcomes in infants of mothers with epilepsy (IME). Women with epilepsy were enrolled no later than the first trimester and were matched with controls; their infants were examined at 8 weeks by pediatricians blinded to maternal status. A number of variables were compared between case and control infants: birth weight, length, gestational age, head circumference, Apgar scores, feeding difficulties, neonatal irritability, and presence of major malformations and minor anomalies. The number of minor anomalies per infant was greater for IME than for controls (mean, 5.05 and 3.65, p less than 0.0001 per infant, respectively). Prominent occiput was the only anomaly seen significantly more often in IME than in controls (p less than 0.05).

Abnormalities, Drug-Induced↗

Cesarean section before the onset of labor and subsequent motor function in infants with meningomyelocele diagnosed antenatally.

Background. Meningomyelocele can now be detected before birth. Few data are available on its natural history, however, and optimal management at the time of delivery is controversial, although it has been suggested that labor and vaginal delivery may cause pressure on exposed nerve roots, resulting in additional loss of neural function. Methods. To assess the effect of labor and the type of delivery on the level of motor function in fetuses with uncomplicated meningomyelocele, we identified 200 cases of this disorder, accounting for 95 percent of the cases that occurred in the state of Washington during our 10-year study period. We compared the outcomes of 47 infants delivered by cesarean section before labor began, 35 delivered by cesarean section after a period of labor, and 78 who were delivered vaginally (another 40 were ineligible for the study). In cases of meningomyelocele detected prenatally, cesarean section was performed before the onset of labor if isolated meningomyelocele without severe hydrocephalus was present. The infants delivered in this manner were compared with those who were delivered either vaginally or by cesarean section after labor began. Results. At two years of age, the infants who had been exposed to labor were 2.2 times more likely to have severe paralysis than those delivered by cesarean section without labor (95 percent confidence interval, 1.7 to 2.8). Infants delivered by cesarean section before the beginning of labor had a mean (+/- SD) level of paralysis 3.3 +/- 3.0 segments below the anatomical level of the spinal lesion at two years of age, as compared with 1.1 +/- 2.3 for infants delivered vaginally and 0.9 +/- 4.1 for infants delivered by cesarean section after the beginning of labor (P less than 0.001 for both comparisons). Exposure to labor did not affect the frequency of neonatal complications or later intellectual performance. Conclusions. For the fetus with uncomplicated meningomyelocele, delivery by cesarean section before the onset of labor may result in better subsequent motor function than vaginal delivery or delivery by cesarean section after a period of labor.

Cesarean Section↗

The effect of maternal hemodynamics on fetal growth in hypertensive pregnancies.

Seventy-six pregnancies in which hypertension complicated pregnancy before 28 weeks' gestation were studied. In 36, hemodynamics were characterized by increased cardiac output and low vascular resistance; in 32, hemodynamics were characterized by high resistance; in eight hemodynamics crossed over from high output to high resistance during pregnancy. High-resistance hypertension was associated with a mean birth weight 1058 gm less than that in the low-resistance group (p = 0.001). The reduction in birth weight was due to a 4-week difference in gestational age (p = 0.001) and lower percentile weights for gestational age, 19th versus 39th (p = 0.005). Infants in the crossover group had low percentile weights and a high rate of intrauterine fetal death.

Adult↗

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↗

Maternal hemodynamics in pregnancies complicated by hyperthyroidism.

The hemodynamics of six pregnant women with hyperthyroidism were studied before and after therapy. Cardiac output was measured by Doppler technique, and blood pressure by automated cuff. When compared with values in euthyroid pregnant women, blood pressure (83.6 mmHg, P less than .001), heart rate (89.2 beats per minute, P less than .001), cardiac output (11.2 L/minute, P less than .001), and stroke volume (123 mL, P less than .001) were significantly elevated. Total peripheral resistance was significantly reduced (609 dyne.second.cm-5, P less than .001). Despite normalization of thyroid indices after therapy, cardiac output remained markedly elevated (9.7 L/minute, P less than .001) and vascular resistance remained reduced (708 dyne.second.cm-5, P = .01). Although the hemodynamics of pregnant thyrotoxic women normalize with therapy, they remain significantly hyperdynamic.

Echocardiography, Doppler↗

Maternal hemodynamics and aortic diameter in normal and hypertensive pregnancies.

The aortic diameters of 89 normotensive pregnant women were compared with those of nine rigorously defined preeclamptic women and 59 women who required antihypertensive therapy. Over the course of normal pregnancy, the diameter increased significantly; it was larger in preeclamptic than in normotensive women throughout pregnancy. The aortic diameter in women with high-resistance hypertension was smaller than that in normotensive women and in those with high-output, low-resistance hypertension, but it was larger in women with low-resistance hypertension than in normotensive women. The aortic diameter increased after treatment of high-resistance hypertension with hydralazine, but decreased after treatment of high-output, low-resistance hypertension.

Aorta↗

Measurement of cardiac output in pregnancy by Doppler technique.

Doppler technique of measuring cardiac output was evaluated during pregnancy. In a study of accuracy Doppler technique correlated well with thermodilution, (r = 0.95, y = 1.05x - 0.35). In a study of interoperator variability, the technique was found to be reproducible, (r = 0.92, y = 0.91x + 0.74).

Aorta↗

Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes.

Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an approximately 2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume approximately 2400 kcal/day, whereas the calorie-restricted group consumed approximately 1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 +/- 0.8 mM wk 1 vs. 6.8 +/- 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 +/- 1.0 mM wk 1 vs. 5.4 +/- 0.5 mM wk 2, P less than 0.01). Fasting plasma insulin also declined in the calorie-restricted group (265 +/- 165 pM wk 1 vs. 145 +/- 130 pM wk 2), resulting in a significant change between groups (P less than 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of beta-hydroxybutyrate rose in the calorie-restricted group (290 +/- 240 microM wk 1 vs. 780 +/- 30 microM wk 2) but not in the control group (P less than 0.01). Finally, urine ketones increased significantly (P less than 0.02) in the calorie-restricted group, whereas they remained absent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study.

Preeclampsia is a disease unique to pregnancy that contributes substantially to maternal and fetal morbidity and mortality. The condition has been thought to be one of hypoperfusion in which increased vascular resistance characterizes the associated hypertension. This study was designed to test an alternative hypothesis, that preeclampsia is characterized by high cardiac output. In a blinded longitudinal study of nulliparas with uncomplicated pregnancies, cardiac output was measured serially by Doppler technique. Cardiac output was elevated throughout pregnancy in patients who became preeclamptic (P = .006). Six weeks postpartum, the hypertension of the preeclamptic subjects had resolved but cardiac output remained elevated (P = .001) and peripheral resistance remained lower than in the normotensive subjects (P = .001). This study demonstrates that preeclampsia is not a disease of systemic hypoperfusion and challenges most current models of the disease based on that assumption.

Adult↗

Preeclampsia: a hyperdynamic disease model.

Preeclampsia is a common disease and as such is a significant contributor to maternal and neonatal morbidity and mortality. Despite the ubiquity of the disease and its public health impact, no comprehensive mechanism has been established. Therapy has been limited to bed rest and premature delivery. The purpose of this article is to examine preeclampsia from a hemodynamic point of view and to advance a hypothesis of disease mechanism.

Adrenergic beta-Antagonists↗

Fetal and maternal considerations in the management of stage I-B cervical cancer during pregnancy.

The timing of treatment for stage I-B cervical carcinoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesarean section followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreased from 32.8% at 26-27 weeks to 2.7% at 34-35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability.

Adult↗

Antihypertensive therapy in pregnancy directed by noninvasive hemodynamic monitoring.

Invasive and noninvasive investigations suggest that the hemodynamics of pregnant hypertensive patients are heterogeneous. Nineteen pregnant patients were evaluated before changes in antihypertensive therapy. Cardiac output was measured by Doppler technique. Blood pressure was measured by automated cuff. Systemic vascular resistance was calculated. Two distinct groups were identified on the basis of differences in cardiac output (p less than 0.0001) and systemic vascular resistance (p less than 0.0001). Those with high resistances were treated with hydralazine. A modest antihypertensive effect was achieved (-6.9 mmHg, p = 0.01), but systemic vascular resistance was dramatically reduced, (-534 dyne.sec.cm-5, p less than 0.0001) and was associated with a compensatory increase in cardiac output (2.0 liters/min, p less than 0.0001). Those with a high cardiac output were treated with atenolol. An antihypertensive effect was achieved, (-17.0 mm Hg, p = 0.008), which was associated with a reduction in cardiac output (-2.8 liters/min, p less than 0.0001).

Atenolol↗

Measurement of cardiac output in pregnancy by thermodilution and impedance techniques.

To assess the value of impedance cardiography in pregnancy, simultaneous measurements of cardiac output were made with impedance and thermodilution techniques in 10 patients who required pulmonary artery catheterization. The methods correlated poorly (r = 0.17). The discrepancy between methods was particularly pronounced in hypertensive patients. Impedance cardiography does not measure cardiac output accurately in hypertensive pregnant women.

Cardiac Output↗

Hemodynamic observations during paroxysmal hypertension in a pregnancy with pheochromocytoma.

A patient with pheochromocytoma diagnosed at 17 weeks' gestation was studied at rest, during an episode of paroxysmal hypertension, and during phenoxybenzamine treatment. Cardiac output was estimated noninvasively by Doppler technique. During paroxysmal hypertension, the mean blood pressure was 102 mmHg, cardiac output fell by 40%, and systemic vascular resistance rose by 250%. Phenoxybenzamine treatment did not change the resting cardiac output or systemic vascular resistance. These observations suggest that serious fetal compromise might occur even with mild episodes of hypertension associated with pheochromocytoma.

Adrenal Gland Neoplasms↗