Biomedical subjects

George R Saade

Publications and source records attributed to George R Saade.

At least 37 records · Page 2Linked to original sources

PubMed2005

Uterine electromyography characteristics for early diagnosis of mifepristone-induced preterm labor.

OBJECTIVE: Differentiating uterine contractions leading to preterm birth from ineffective uterine activity is difficult with current tools. Uterine electromyographic activity is recordable and consists of bursts (group of action potentials) characterized by characteristics that are different during pregnancy and labor. Our aim was to identify the chronology of the changes in uterine pressure and electromyographic characteristics during mifepristone-induced preterm labor in pregnant rats and to determine the earliest characteristic to change. METHODS: On day 17 of gestation, intrauterine catheter and electromyography electrodes were implanted in the uterus. On day 18, rats were allocated for treatment with mifepristone or placebo. Intrauterine pressure and electromyography integral activities and electromyography mean were calculated before treatment and 6, 12, 18, 20, 22, and 24 hours after treatment. After mathematical transformation, burst analysis was performed by using power density spectrum energy, peak amplitude, and frequency. RESULTS: As expected, delivery rate within 24 hours was higher in the mifepristone-treated group. Changes in electromyography integral activity and mean, power density spectrum energy, and intrauterine pressure integral activity occurred late during preterm labor, in a range of 2-4 hours before delivery. Electromyography peak frequency of the power density spectrum exhibited early changes, with a shift from low to high frequencies starting at 12 hours before delivery. CONCLUSION: Electromyography peak frequency of the power density spectrum from individual bursts was the first characteristic to change after antiprogestin treatment, preceding any change in intrauterine pressure, making it a potentially useful marker for the early diagnosis of preterm labor.

Abortifacient Agents, Steroidal↗

PubMed2005

Impact of maternal age on obstetric outcome.

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.

Adult↗

PubMed2005

Burns in pregnancy.

BACKGROUND: Treatment of a major burn injury during pregnancy must incorporate modifications in management resulting from gestational physiologic changes. CASE: A 25-year-old woman, at 34 weeks of gestation, sustained a major burn injury at home. She required ventilatory support, invasive hemodynamic monitoring, and massive fluid resuscitation. Labor was augmented and a spontaneous vaginal delivery of a healthy neonate was achieved. Later, wound autografting was performed. CONCLUSION: Pregnancy-induced physiologic changes affect key factors in the management of the burned patient, including airway management and hemodynamic support. Multidisciplinary management is essential to achieve the best possible outcome.

Adult↗

PubMed2005

First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome.

OBJECTIVE: To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. METHODS: Patients at 10.3-13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12-50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency. RESULTS: There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. CONCLUSION: First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome.

Abortion, Therapeutic↗

PubMed2005

Factors influencing twins and zygosity.

Zygosity is influenced by many factors. Monozygotic twins occur spontaneously in approximately 1 in 250 births and are felt to increase twofold with ovulation induction techniques. Monozygotic twinning also increases in proportion to the number of blastocysts transferred during in vitro fertilisation. In contrast, dizygotic twinning appears to be influenced by race, genetic factors, maternal age, fertility enhancing drugs, folic acid supplementation, and maternal nutritional status.

Dietary Supplements↗

PubMed2005

Use of uterine EMG and cervical LIF in monitoring pregnant patients.

OBJECTIVES: Review the uterine electromyography (EMG) and cervical light-induced fluorescence (LIF) devices and their role in the evaluation of uterine and cervical function in comparison with present methods. DESIGN: Review of recent studies. SETTING: University of Texas Medical Branch Labour and Delivery Clinics. POPULATION: Various groups of pregnant women. METHODS: We have developed and recently improved non-invasive methods to evaluate quantitatively uterine electrical signals from the abdominal surface and cervical collagen. MAIN OUTCOME MEASURES: Uterine EMG utilised power density spectrum (PDS) peak frequency and total power (P(0)) and cervical LIF utilising LIF ratio. RESULTS: Human studies indicate that uterine and cervical performance can be successfully monitored during pregnancy using EMG and LIF, respectively, and the assessment of uterine and cervical function can both be used to influence patient management in a variety of conditions associated with labour, more than can currently available methods. CONCLUSIONS: The potential benefits of the proposed instrumentation include the following: a reduction in the rate of preterm birth, improved maternal and perinatal outcome, better monitoring of treatment, decreased caesarean section rate and better research methods for understanding uterine and cervical function.

Cervical Ripening↗

PubMed2004

Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase.

Epidemiological studies have shown increased incidence of hypertension and coronary artery disease in growth-restricted fetuses during their adult life. A novel animal model was used to test the hypothesis regarding the role of an abnormal uterine environment in fetal programming of adult vascular dysfunction. Mice lacking a functional endothelial nitric oxide synthase (NOS3-/-KO, where KO is knockout) and wild-type (WT) mice (NOS3+/+WT) were crossbred to produce homozygous NOS3-/-KO, maternally derived heterozygous (NOS3+/-mat, mother with NOS3 deficiency), paternally derived heterozygous (NOS3+/-pat, normal mother), and NOS3+/+WT litters. Number of fetuses per litter was smaller in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Adult female mice from these litters (7-8 wk old) were killed, and ring preparations of carotid and mesenteric arteries were mounted in a wire myograph to evaluate the passive and reactive vascular characteristics. Slope of the length-tension plot (a measure of vascular compliance) was increased, and optimal diameter (as calculated by Laplace equation) was decreased in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Acetylcholine caused vasorelaxation in NOS3+/-pat and NOS3+/+WT and contraction in NOS3-/-KO and NOS3+/-mat mice. Responses to phenylephrine and Ca2+ were increased in NOS3-/-KO and NOS3+/-mat compared with NOS3+/-pat and NOS3+/+WT mice. Relaxation to isoproterenol was decreased in NOS3-/-KO and NOS3+/-mat vs. NOS3+/-pat and NOS3+/+WT mice. Abnormalities in the passive and reactive in vitro vascular properties seen in NOS+/-mat that developed in a NOS3-deficient maternal/uterine environment compared with the genetically identical NOS3+/-pat mice that developed in a normal environment are the first direct evidence in support of a role for uterine environment in determining vascular function in later life.

Acetylcholine↗

PubMed2004

Side-to-side differences in transcranial Doppler parameters in normotensive and preeclamptic pregnant women.

OBJECTIVE: This study was undertaken to investigate whether women with preeclampsia demonstrate larger side-to-side velocity differences in the middle cerebral artery (MCA) compared with normotensive pregnant women. STUDY DESIGN: Forty-one preeclamptic women and 50 normotensive pregnant women were studied during the third trimester. Transcranial Doppler ultrasound was used to measure peak, end-diastolic, and mean velocities in both MCAs. An asymmetry index was calculated as 100 x Rt-Lt//(Rt+Lt)/2, for each of the following parameters: mean velocity (Vm), pulsatility index (PI), and cerebral perfusion pressure (CPP). Student t test, Pearson correlation, and regression analysis were used. Significance was taken as P<.05. RESULTS: Both normotensive and preeclamptic pregnant women showed good correlation between Rt and Lt MCA Vm (R>0.8, P<.0001), PI (R>0.6, P.0001), and CPP (R>0.8, P<.0001). There were no differences in the asymmetry index for Vm, PI, or CPP between the two groups. CONCLUSION: Preeclampsia does not appear to induce greater side-to-side velocity differences in the MCA distribution.

Adult↗

PubMed2004

Degranulation of uterine mast cell modifies contractility of isolated myometrium from pregnant women.

OBJECTIVE: This study was undertaken to test that uterine mast cell degranulation alters human myometrial contractility in vitro and to define what mediators are involved in this process. STUDY DESIGN: Longitudinal myometrial strips prepared from biopsy specimen obtained from the lower uterine segment of women at preterm and term gestation (with and without labor) were studied. Contractile responses to compound 48/80, a mast cell degranulator, were compared in the absence or presence of a mast cell stabilizer, H 1 and H 2 receptor antagonists, cyclooxygenase, and lipoxygenase inhibitors. RESULTS: Compound 48/80 increased myometrial contractility in all groups. The mast cell stabilizer cromolyn inhibited contractility, whereas the cyclooxygenase inhibitor ibuprofen, the H 1 -receptor antagonist S(+)-chlorpheniramine maleate, but not the H 2 antagonist cimetidine, only slightly attenuated this effect. The lipoxygenase inhibitor linoleyl hydroxamic acid augmented the responses to compound 48/80 in the preterm but not in the term group. CONCLUSION: Uterine mast cell degranulation, or the effects of their mediators, can modulate uterine contractility during pregnancy.

Cell Degranulation↗

PubMed2004

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice.

OBJECTIVE: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. STUDY DESIGN: Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase -/-KO and wild type (+/+WT) male mice to produce nitric oxide synthase -/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. RESULTS: Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca ++ was increased in oligoparous, but not multiparous, female offspring ( P < .05). CONCLUSION: These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy.

Animals↗

PubMed2004

Induction of premature labor and delivery by allergic reaction and prevention by histamine H1 receptor antagonist.

OBJECTIVE: The purpose of this study was to determine whether type I hypersensitivity can induce preterm labor and delivery that may be prevented by the administration of an H 1 receptor antagonist or a mast-cell stabilizer. STUDY DESIGN: At days 40 through 50 of gestation, ovalbumin-sensitized guinea pigs that had not been treated or had been pretreated with an H 1 receptor antagonist (ketotifen) or a mast-cell stabilizer (cromolyn sodium) were challenged with either ovalbumin or saline solution. Nonsensitized guinea pigs were challenged with ovalbumin. RESULTS: The duration of gestation was significantly shorter in sensitized animals that were challenged with ovalbumin than in the other groups. Pretreatment with ketotifen significantly increased the duration of pregnancy in sensitized animals, compared with untreated animals. Cromolyn sodium had no effect. CONCLUSION: An allergic reaction can induce premature labor/delivery, and pretreatment with histamine H 1 receptor antagonist can prevent it. These observations provide evidence of a novel mechanism of disease for premature labor and delivery.

Allergens↗

PubMed2003

Sex hormone effects in non-pregnant rat and human myometrium.

OBJECTIVE: To study effects of sex hormones on spontaneous contractility and on the effects of depolarizing agent potassium chloride (KCl), M-cholinoceptor and prostaglandin receptor agonists on non-pregnant rat and human uterine tissues. STUDY DESIGN: Uterine rings from ovariectomized rats treated with sex hormones or placebo, and uterine strips from premenopausal and postmenopausal women were equilibrated in Krebs buffer (t=37 degrees C, pH approximately 7.4) for isometric tension recordings. Spontaneous contractile activity and contractions in response to KCl, eicosanoids, and acetylcholine were compared. RESULTS: In tissues from ovariectomized rats, spontaneous contractility was increased, while KCl-induced contractions were decreased. Treatment with 17beta-estradiol, but not progesterone, inhibited spontaneous contractions, but potentiated KCl evoked contractions. Treatment with 17beta-estradiol did not influence responses to prostanoids in ovariectomized rats, while treatment with both sex hormones restored decreased the responses. Spontaneous contractility and responses to KCl were less in uterine tissues from postmenopausal versus premenopausal women. Hormone replacement therapy partly restored the responses to KCl, prostanoids, and acetylcholine. CONCLUSIONS: Ovarian steroids modulate spontaneous contractile activity, responses to depolarization, prostanoids and M-cholinoceptor activation in non-pregnant rat and human uterine tissues in vitro.

Acetylcholine↗

PubMed2003

A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia.

OBJECTIVE: Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia. METHODS: We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure. RESULTS: Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001). CONCLUSIONS: Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.

Anticonvulsants↗

PubMed2003

The physiology of uterine contractions.

Studies in animals and humans indicate that uterine performance can be successfully monitored during pregnancy using uterine electromyography. Uterine electromyography could be used to better define management in a variety of conditions associated with human labor. The potential benefits of the proposed instrumentation and method include: reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean-section rate, and providing research methods to better understand uterine function.

Electromyography↗

PubMed2003

Arginine flux and nitric oxide production during human pregnancy and postpartum.

OBJECTIVE: To compare second-trimester, third-trimester, and postpartum arginine flux and nitric oxide production using infusions of the stable isotope L-[(15)N(2)]-arginine in normal human gestation. METHODS: Kinetic measurements were made in pregnant volunteers with uncomplicated singleton gestations in mid gestation, late gestation, and more than 8 weeks postpartum. A bolus of 4.95 micromol/kg of labeled arginine was administered, followed by an infusion at 4.95 micromol/kg per hour for 6 hours. The isotopic enrichment of plasma arginine and nitrite or nitrate (NO(x)) was determined by gas chromatography, mass spectrometry, or both. We used the Kolmogorov-Smirnov test for normality, repeated-measures analysis of variance, and Newman-Keuls test. P <.05 denoted statistical significance. RESULTS: The rate of turnover of the intravascular NO(x) pool was significantly higher in mid gestation compared with late gestation and almost reached statistical significance when compared with postpartum values (6.2 +/- 0.9 versus 4.3 +/- 0.8 [P <.02] versus 3.7 +/- 2.1% pool/hour; P =.08). Arginine flux was significantly higher in early compared with late gestation and postpartum (107.8 +/- 13.9 versus 72.5 +/- 16.1 versus 82 +/- 8.8 micromol/kg per hour, respectively; P <.01). CONCLUSION: Arginine and nitric oxide production is higher in mid gestation. This suggests a role for nitric oxide in early cardiovascular adaptation in human gestations.

Adolescent↗

PubMed2003

Effect of histamine on phasic and tonic contractions of isolated uterine tissue from pregnant women.

OBJECTIVE: To enhance our understanding of the uterotonic effect of histamine, we compared the effects of histamine on spontaneous phasic and tonic contractile activity of uterine strips from term pregnant nonlaboring women. STUDY DESIGN: Longitudinal uterine strips were used from the lower uterine segment of term pregnant nonlaboring women undergoing elective cesarean section. The concentration-response relationship to histamine (10(-8) to 10(-4) mol/L) was determined in spontaneously contracting strips or in strips contracted tonically with a protein kinase C activator (-)-indolactam V in the presence of H(1) receptor antagonist (S[+]-chlorpheniramine maleate), H(2) receptor antagonist (cimetidine), or solvent. RESULTS: Histamine increased spontaneous phasic myometrial contractions in a concentration-dependent manner. H(1), but not H(2), receptor antagonist significantly attenuated the response to histamine. Histamine significantly reduced tonic contractions of uterine strips induced by indolactam V. H(1) histamine receptor antagonist abolished relaxation, whereas H(2) histamine receptor antagonist had no effect. CONCLUSION: Histamine increases spontaneous, but inhibits tonic, contractions of uterine strips from term pregnant nonlaboring women. Both effects are mediated through activation of H(1) receptors.

Chlorpheniramine↗

PubMed2003

Impairment of fetal growth potential and neonatal encephalopathy.

OBJECTIVE: This study was undertaken to determine the frequency of growth impairment in neonates with encephalopathy. STUDY DESIGN: In a case-control design, neonates with neonatal encephalopathy (NE) meeting criteria for an acute intrapartum hypoxic event (IHE, n = 21) and those who did not meet these criteria (n = 20) were compared with controls. The controls were 42 neonates without complications matched 2:1 for gestational age with IHE cases. The percentile of growth potential, a measure of the weight expected in the absence of pathological conditions, was calculated for each fetus. RESULTS: More neonates with NE with and without IHE were below the 10th percentile of growth potential compared with controls (7/21 [33%] and 6/20 [30%] vs 1/42 [2.4%], odds ratio [95% CI] = 20.5 [2.2-114.0] and 17.6 [1.8-102.5], respectively). These associations remained significant after controlling for gestational age and birth weight. CONCLUSION: A large proportion of neonates with NE demonstrate signs of antepartum injury reflected in the impairment of their growth. This association was similar in the presence or absence of IHE, indicating that antepartum injury has a causative rather than predisposing character in many cases of IHE.

Brain Diseases↗

PubMed2003

Proteinase-activated receptor-2 activation induces uterine contractility in term pregnant rats that is not dependent on mast cell activation and cyclo-oxygenase products.

OBJECTIVES: This study was undertaken to evaluate the effect of proteinase-activated receptor-2 (PAR-2) activation on the contractility of uterine tissues from term pregnant rats and the role of mast cells and prostaglandins in such an effect. STUDY DESIGN: Uterine rings from pregnant (day 20-21) Sprague-Dawley rats were used for isometric tension recording in organ chamber experiments (Krebs solution, 5% carbon dioxide in air, 37 degrees C, pH approximately 7.4). Responses to the PAR-2 activating peptide SLIGRL (serine-leucine-isoleucine-glycine-arginine-leucine), and to the inactive reverse peptide LRGILS (leucine-arginine-glycine-isoleucine-leucine-serine) were determined after pretreatments with compound 48/80, cromolyn, S[+]-chlorpheniramine maleate, cimetidine, combinations of histamine (H) receptor antagonists with cromolyn or ibuprofen and compared with vehicle. RESULTS: SLIGRL significantly augmented contractility of uterine tissues, and this response was not inhibited by compound 48/80, cromolyn, and ibuprofen, as well as by H(1)- and H(2)-receptor antagonists, alone or in combination with cromolyn. CONCLUSION: PAR-2 activation augments uterine contractility in tissues obtained from term pregnant rats, and this effect is independent of mast cell activation or cyclo-oxygenase pathway products.

Animals↗