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Biomedical subjects

G R Saade

Publications and source records attributed to G R Saade.

104 records · Page 6Linked to original sources

The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension.

The purpose of this study was to evaluate the effects of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension. Twelve patients with pregnancy-induced hypertension were prospectively studied with transcranial pulsed Doppler and transabdominal color flow Doppler before and after infusion of a 6 gram intravenous loading dose of magnesium sulfate. The maternal vessels studied included the middle cerebral, common carotid, and internal carotid arteries. The fetal vessels studied included the middle cerebral, renal, and umbilical arteries. In addition the maternal circulation in the placental base plate was imaged. The results of this descriptive study suggest that a 6 gram loading dose of magnesium sulfate significantly vasodilates the vascular bed distal to the maternal middle cerebral artery, and increases blood velocity in this distribution. There was no significant change in pulsatility index or blood velocity in the central large vessels of the head and neck. There were no acute effects noted in the fetal or placental vessels evaluated.

Adult↗

Fetal platelet counts correlate with the severity of the anemia in red-cell alloimmunization.

OBJECTIVE: To determine whether fetal anemia secondary to maternal red-cell alloimmunization is associated with thrombocytopenia. METHODS: The records of 78 patients undergoing intrauterine transfusion for red-cell alloimmunization were reviewed. Pre-transfusion fetal platelet counts were compared between hydropic and nonhydropic fetuses. A regression analysis was performed between the fetal platelet counts and the fetal bilirubin levels, hematocrits, and reticulocyte counts taken at the initial transfusion. The hematocrits, reticulocyte counts, and bilirubin levels were adjusted for gestational age by calculating the number of standard deviations (SDs) from the mean for that age or the multiples of the mean (MOM). Student t test, Pearson coefficient, and contingency table randomization test were used to analyze the data. P < .05 was considered significant. RESULTS: Thirty-seven fetuses were hydropic and 41 were nonhydropic. Hydropic fetuses had a significantly lower platelet count than nonhydropic fetuses (197.5 +/- 86.4 versus 252.6 +/- 73.7 x 10(3)/microL; P < .01). Platelet counts correlated negatively with the reticulocyte count MOM (r = -0.652; P < .01) and the hematocrit SDs below the mean (r = -0.659; P < .01), but did not correlate with the bilirubin MOM (r = -0.183; P = .2). CONCLUSION: Hydropic and severely anemic fetuses are at increased risk for thrombocytopenia. We suggest that increased erythropoiesis diverts the hematopoietic stem cell away from thrombopoiesis.

Anemia, Hemolytic↗

The effect of magnesium sulfate on maternal retinal blood flow in preeclampsia: a randomized placebo-controlled study.

OBJECTIVES: Our purpose was to determine the effect of a 6 gm intravenous bolus of magnesium sulfate on maternal retinal blood flow velocity waveforms in patients with preeclampsia. STUDY DESIGN: Twenty-two patients were randomized to two groups and were studied with color flow Doppler before and immediately after infusion of either 6 gm of magnesium sulfate or placebo. The central retinal and posterior ciliary arteries were studied. RESULTS: Magnesium sulfate significantly reduced the pulsatility index (p < 0.005) in both vessels (change in pulsatility index = 0.26 +/- 0.23 for central retinal and -0.22 +/- 0.15 for posterior ciliary) when compared with placebo (change in pulsatility index = 0.02 +/- 0.10 for central retinal and -0.03 +/- 0.09 for posterior ciliary). CONCLUSIONS: These data suggest that magnesium sulfate dilates the vessels distal to the central retinal and posterior ciliary arteries. Changes in pulsatility index in the retinal arteries may be indicative of similar changes in other cerebral vessels.

Adult↗

Expression of receptors for corticotropin-releasing factor in the vasculature of pregnant rats.

OBJECTIVE: To identify and localize the receptor(s) responsible for modulating vascular effects of corticotropin-releasing factor (CRF) during pregnancy. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR), competitive RT-PCR, and Western blot analyses were used to study the expression of CRF receptors (CRFR(1), CRFR(2alpha), and CRFR(2beta)) in the aorta and uterine vascular bed of nonpregnant and late (day 18) and term pregnant (day 22) Sprague-Dawley rats. Immunohistochemistry was done to localize the CRF receptor in the aortic wall. There were six rats in each study group. RESULTS: Only CRFR(2beta) was identified in the aorta and uterine vascular bed by RT-PCR and Western blot analyses. The PCR product was sequenced to confirm its identity. Competitive RT-PCR and Western blot analyses showed that expression of CRFR(2beta) is not different in late pregnancy compared with the nonpregnant but is decreased at term. Immunohistochemistry showed high expression of CRFR(2beta) on the aortic endothelial surface but low expression in the smooth-muscle layer. CONCLUSION: Only CRFR(2beta) is expressed in vasculature of nonpregnant and pregnant rats and may mediate the vasorelaxant effect of CRF. This receptor is present predominantly in the vascular endothelium and to a lesser extent in the smooth muscle. The expression of CRF receptor in pregnant rat vasculature is down-regulated at term of gestation.

Animals↗

Uterine electromyography and light-induced fluorescence in the management of term and preterm labor.

OBJECTIVE: Understanding the physiology of the uterus and cervix during term and preterm parturition is crucial for developing methods to control their function and is essential to solving clinical problems related to labor. To date, only crude, inaccurate, and subjective methods are used to assess changes in uterine and cervical function in pregnancy. METHODS: In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based on recording of uterine electrical signals from the abdominal surface (uterine electromyography) and measurement of light-induced fluorescence (LIF) of cervical collagen (Collascope), respectively. Both methods are rapid and allow immediate assessment of uterine contractility and cervical ripening. RESULTS: Studies in animals and humans indicated that uterine and cervical performance can be monitored successfully during pregnancy using those approaches and that these techniques can be used during labor to better define management in a variety of conditions associated with labor. CONCLUSION: The potential benefits of the proposed instrumentation and methods include reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean rate and providing research methods to understand uterine and cervical function.

Animals↗

The nitric oxide pathway in pre-eclampsia: pathophysiological implications.

Pre-eclampsia, one of the most significant health problems in human pregnancy, complicates approximately 6-8% of all gestations and is the leading cause of fetal growth retardation, infant morbidity and mortality, premature birth and maternal death. Recent research implicates free radicals in the pathophysiology of pre-eclampsia. This review covers the biochemistry of nitric oxide (NO) and possible interactions with other free radicals. Studies in the rat show that pregnancy is associated with enhanced production and responsiveness to NO in both reproductive tissues and blood vessels. Rats infused with NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) have been used as an animal model of pre-eclampsia, and the effects of steroid hormones on blood pressure in this model have been tested. Results suggest that pre-eclampsia may be a state of NO deficiency. However, in humans there seem to be contradictions regarding the involvement of NO in maternal adaptation to pregnancy. It is suggested that NO may be one of several systems that act in concert to maintain a symbiotic relationship between mother and fetus. However, the input of each system may be genetically determined.

Animals↗

Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence.

OBJECTIVE: To report our experience with intentional puncture of the intervening membrane ('septostomy') for the treatment of the twin oligohydramnios-polyhydramnios sequence (TOPS). METHODS: 12 patients were diagnosed with TOPS based on ultrasonographic findings. A 20- to 22-gauge spinal needle was used to puncture the membrane between the twins without any attempt at amnioreduction in 9 patients, while the procedure was combined with amnioreductions in 3 patients. RESULTS: Gestational age was 23.1 +/- 3.3 weeks at the time of septostomy and 31.1 +/- 4.4 weeks at delivery. Rapid accumulation of fluid around the 'stuck' fetus occurred in all cases following a single procedure. Three of the 24 fetuses died in utero and 1 died on the fifth day of life, for a combined survival of 83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6 and 13 weeks (mean +/- SD 8.3 +/- 4.8). CONCLUSION: Amniotic septostomy is a promising new method for the management of TOPS and is associated with survival rates that are better than, or comparable to, more invasive modalities. A multicenter trial comparing septostomy to other modalities is warranted.

Amnion↗

Fetal and neonatal hematologic parameters in red cell alloimmunization: predicting the need for late neonatal transfusions.

The purpose of this study was to determine whether the need for late neonatal transfusion can be predicted in fetuses who received intrauterine transfusions. The records of 36 patients who underwent intrauterine transfusion were reviewed. Newborns who required late transfusions had a lower reticulocyte count at their last intrauterine transfusion, a longer duration between their lowest fetal reticulocyte count and delivery, and a higher umbilical cord blood hemoglobin and percent adult red cells on Kleihauer-Betke stain at delivery. The need for late transfusions appears to be related to the extent and duration of fetal bone marrow suppression.

Bilirubin↗

Iatrogenic gastroschisis decreases pulmonary hypoplasia in an ovine congenital diaphragmatic hernia model.

Pulmonary hypoplasia is a major problem in infants with congenital diaphragmatic hernia. Intrauterine reparative procedures are associated with a high complication rate. The development of less complex operations to reduce the degree of fetal lung hypoplasia may improve neonatal survival. Our objective was to investigate the effectiveness of an iatrogenic gastroschisis in reducing fetal pulmonary hypoplasia in a sheep model with an artificially created diaphragmatic hernia. A left-sided diaphragmatic hernia (Bochdalek type) was created at 75 days' gestation in an ovine fetal model during the pseudoglandular phase of lung development. At 110 days' gestational age, a left-sided gastroschisis was created by excising part of the lower abdominal wall and buttressing the opening with a rubber ring. The fetus remained in utero until 135 days' gestation, at which time it was sacrificed for autopsy. Histopathologic and morphometric studies were performed on the lungs. Ten animals had creation of a diaphragmatic hernia. Four underwent the second surgery to create a gastroschisis. One animal completed the entire protocol, 3 fetuses aborted after the second surgery. Autopsy confirmed effective decompression of the herniated abdominal contents from the chest into the amniotic cavity in all 4 cases. The lungs of the animal that completed the protocol were appropriately developed, while those fetuses that died soon after gastroschisis creation had severe pulmonary hypoplasia, mainly involving the left lung. Artificially induced diaphragmatic hernia, in the ovine fetus, causes severe pulmonary hypoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

Effects of intravascular transfusion for red cell alloimmunization on fetal arterial blood pressure.

OBJECTIVE: To evaluate the effects of intravascular transfusion (IVT) on the fetal umbilical arterial pressure (UAP) in pregnancies complicated by red cell alloimmunization. STUDY DESIGN: UAP and amniotic fluid pressures (AFP) were measured immediately before and after IVT. Mean UAP was calculated by computing 1/3 (systolic blood pressure - diastolic blood pressure) + diastolic blood pressure. The fractional increase in fetoplacental blood volume with transfusion was calculated by dividing the net volume of blood transfused by the sum of the net volume transfused and the fetoplacental volume based on the estimated fetal weight by ultrasound. Statistical techniques included paired t-test, and the Pearson product correlation. Significance was defined as p < 0.05. RESULTS: The fetal umbilical artery was punctured during a total of 27 procedures in 21 patients. Pre- and posttransfusion mean UAPs were recorded in 16 of these procedures. Mean UAP increased from 34.0 +/- 14.2 mm Hg pretransfusion to 38.6 +/- 12.8 mm Hg posttransfusion (p = 0.34). There was no correlation between the fractional change in fetoplacental blood volume and the calculated difference between pre- and posttransfusion blood pressure. Bradycardia occurred during 5 procedures (31.2%). Fetal demise occurred after 2 procedures (12.5%). CONCLUSION: IVT appears to have a minimal effect on the fetal UAP. Fetal bradycardia occurs in a significant percentage of these cases.

Blood Pressure↗

Relaxation kinetics of the aorta in N omega-nitro-L-arginine methyl ester-treated pregnant rats.

OBJECTIVE: To test the hypothesis that vascular relaxation kinetics are prolonged in pregnant rats treated chronically with N omega-nitro-L-arginine methyl ester (L-NAME). METHODS: Timed pregnant rats (on day 15 of a 22-day gestation) were implanted with infusion pumps containing vehicle (controls) or L-NAME (50 mg/d). L-NAME pumps were retained until day 22 (group 1), or removed on day 20 (group 2). All rats were killed at term. Aortic rings were mounted in organ chambers containing physiologic salt solution (PSS) for isometric tension recording, contracted with high-K+ PSS (60 mM), and allowed to relax in normal-K+ PSS. Relaxation kinetics were quantified as time for 50% and 80% relaxation. After contraction with phenylephrine, responses to cumulative concentrations of methacholine were studied in the absence and presence of L-arginine (L-Arg) (10(-3) M). RESULTS: Responses to methacholine were inhibited completely in group 1 and partially in group 2 (P < .05). The inhibition in both groups was reversed by L-Arg. The rate of relaxation was significantly slower in groups 1 and 2 (P < .05) as compared with controls. Mechanical removal of the endothelium caused prolongation of relaxation in controls and group 2 (P < .05), but not in group 1. Preincubation of aortic rings from untreated controls with L-NAME (in vitro, 10(-4) M) did not affect relaxation. CONCLUSION: The endothelium modulates the rate of vascular relaxation by a factor other than nitric oxide. N omega-nitro-L-arginine methyl ester (L-NAME) prolongs vasorelaxation by endothelium-dependent and -independent mechanisms. Prolongation of vascular relaxation kinetics may be a mechanism to elevate blood pressure and peripheral vascular resistance in preeclampsia.

Animals↗

The effects of sex steroids on human umbilical artery and vein.

OBJECTIVE: To define the vascular actions of selected sex steroids on human umbilical artery and vein and to determine whether there are any gender-specific differences in vasorelaxation between umbilical cord vessels of male and female fetuses. METHODS: Segments of umbilical artery (n = 12) and umbilical vein (n = 8) from male and female fetuses were suspended in organ baths of Krebs solution for isometric tension recording. The vessels were contracted using 60 mM potassium chloride followed by exposure to increasing concentrations (10(-7) to 10(-4) M) of sex steroid hormones (estradiol-17 beta, estriol, estrone, testosterone, and progesterone). A specific estrogen receptor antagonist (ICI 164, 384) was used to attempt to block the estradiol effect. Changes in tension were recorded. RESULTS: Of the agents tested, estradiol-17 beta had the greatest effect (25-29% relaxation at 10(-4) M concentration), which was uninhibited by a specific receptor antagonist. The other steroids tested had no significant effect, even at 10(-4) M concentration. The umbilical artery is slightly more sensitive to the effects of estradiol than the umbilical vein. There were no gender-specific differences noted in either artery or vein harvested from male or female fetuses. CONCLUSION: Estradiol-17 beta in supraphysiologic concentrations has a non-receptor-mediated vasorelaxation effect on human umbilical blood vessels.

Adult↗

Neonatal outcome after active perinatal management of the very premature infant between 23 and 27 weeks' gestation.

OBJECTIVE: To record the effect of aggressive perinatal management on neonatal outcome in the very premature infant. METHODS: A retrospective chart review of 114 infants born between 23 and 27 weeks' gestation, managed by one perinatal transport service at one hospital between July 1989 and December 1993. Fetuses > 23 weeks' gestation were considered viable and were managed with tocolytics, antibiotics, and surfactant at the discretion of the treating physician. Morbidity and mortality rates in the first 6 months, including stillbirths were analyzed. A major neurologic condition was defined as ultrasonographic evidence of grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia. RESULTS: Both neonatal mortality rate and the incidence of stillbirths decreased with advancing gestational age. Of 24 infants born at 23 weeks' gestation, 33% were stillborn and 13% were alive at 6 months. This survival rate improved to 48% for infants delivered at 24 weeks' gestation, and to 68%, 75%, and 71% for those delivered at 25, 26, and 27 weeks' gestation, respectively. The percentage of infants who survived without a major neurologic condition increased with advancing gestational age at delivery from 13% at 23 weeks' gestation to 40% at 24 weeks, 48% at 25 weeks, 70% at 26 weeks, and 71% at 27 weeks. The incidence of retinitis of prematurity, respiratory complications, and days spent in the hospital decreased with greater gestational age. CONCLUSIONS: An active plan of management for all gestations of > 23.9 weeks seems appropriate.

Adolescent↗

Relaxation kinetics of rat aorta during pregnancy.

OBJECTIVE: To examine the hypothesis that kinetics of vasorelaxation are altered during pregnancy. METHODS: Rings of aorta from rats at different stages of pregnancy (early, late, and term) and from nonpregnant female rats were precontracted with high-K+ and then allowed to relax in normal-K+ physiologic saline solution. The time to reach 50% and 80% relaxation were determined in the absence or presence of a cyclooxygenase inhibitor (indomethacin) and a nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester) or after removal of the endothelium. RESULTS: The aortic relaxation was progressively faster in later stages of gestation. N omega-nitro-L-arginine methyl ester and indomethacin had no significant effect whereas removal of the endothelium caused a slowing of relaxation in all the groups. Even in the presence of N omega-nitro-L-arginine methyl ester and indomethacin or after de-endothelization, the relaxation remained faster at term as compared with the other groups. CONCLUSION: Aortic relaxation is faster in the presence of endothelium. The effect of endothelium on relaxation is independent of nitric oxide synthase or cyclooxygenase systems. Progression of gestation is associated with acceleration of aortic relaxation, which cannot be totally ascribed to an endothelial factor and may involve a change intrinsic to the vascular smooth muscle. Faster relaxation kinetics of the vasculature during pregnancy may be a mechanism to decrease peripheral vascular resistance.

Animals↗