Search PubMed⌕ Search

Biomedical subjects

G D Anderson

Publications and source records attributed to G D Anderson.

At least 73 records · Page 4Linked to original sources

In vivo expression and function of hybrid Ia dimers (E alpha A beta) in recombinant and transgenic mice.

We have found cell surface expression of an E alpha molecule in recombinant and transgenic mouse strains lacking an E beta molecule. Flow cytometry has shown low level expression of E alpha in B10.RQB3 (I-AqEk alpha) and B10.RFB2 (I-AfEk alpha) mice. We have also found that B10.Q (H-2q) mice can express the Ek alpha transgene. Since these strains do not have functional E beta chains, we propose that the E alpha A beta hybrid dimers are formed in low numbers and can be picked up by FACS analysis. So far we have not been able to identify these hybrid molecules by cytotoxicity or immunoprecipitation. The E alpha/A beta molecule can function in vivo during thymic selection in the clonal deletion of two V beta TCR subsets, V beta 11 and V beta 6, which have been shown to interact with the intact I-E molecule.

Animals↗

RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes.

We have identified an inbred strain of mouse, RIII S/J (H-2r), that has the largest known deletion of the TCR V beta genes by screening with mAb and TCR V beta specific probes. Upon screening of PBL with mAb F23.1, which is specific for V beta 8 TCR, RIII S/J was found to be negative. On further screening with mAb KJ 23a, which is specific for V beta 17a TCR, RIII S/J was completely negative. We next tested RIII S/J with mAb 44-22-1, which is specific for V beta 6 TCR, and found it also to be negative. The (B10 X RIII)F1 mice showed a 50% expression of V beta 6 gene, indicating a genomic rather than a clonal deletion. mAb KJ25, detecting V beta 3, was positive in RIII S/J, denoting the downstream boundary for the deletion. Southern blot analysis of liver DNA using TCR V beta-specific probes confirmed the deletion of V beta 8 gene subfamily and V beta 5 gene subfamily, along with V beta 9, V beta 11, V beta 12, and V beta 13 genes similar to the known TCR V beta deletion mutants (SWR, SJL, C57L, and C57Br). In addition, RIII S/J is missing V beta 6, V beta 15, and V beta 17 genes. Our mapping of the deletion indicates that RIII S/J has lost approximately 130 kb of V beta chromosome and with it 13 V beta genes out of the known 21 V beta genes of the TCR. The deletion is marked by the presence of V beta 10 gene upstream and V beta 3 gene downstream.

Animals↗

Influence of complement C5 and V beta T cell receptor mutations on susceptibility to collagen-induced arthritis in mice.

SWR/J mice are resistant to collagen-induced arthritis (CIA) despite having a susceptible H-2q haplotype. We have earlier demonstrated the possible role of the V beta TCR mutation of SWR in the resistance to CIA. To investigate the influence of the C5 deficiency of SWR in this resistance, crosses were made between SWR and A/J (C5 deficient, TCRwild, H-2a), and between SWR and C3H.A (C5 sufficient, TCRwild, H-2a). Upon immunization with bovine type II collagen in adjuvant, there was a similar incidence and severity of arthritis in H-2q-bearing mice in the back-crosses A x (SWR x A) ad C3H.A x (SWR x C3H.A). The absence of hemolytic complement was confirmed in the arthritic A x (SWR x A) back-cross mice by standard SRBC hemolytic assays. In addition C57L (H-2b) mice, which were C5 sufficient but had a V beta TCR deletion mutation similar to SWR, could not complement for CIA susceptibility in H-2q-bearing C57L x (SWR x C57L) back-crosses and in (C57L x SWR)F2 hybrids. These studies show that complement C5 does not play a significant role in CIA susceptibility, and further implicate the V beta TCR mutation in the resistance to CIA in SWR mice.

Animals↗

Lack of evidence of a vasodepressor role for relaxin in spontaneously hypertensive and normotensive pregnant rats.

To test the possibility that the ovarian polypeptide hormone relaxin mediates the vasodepressor effect of pregnancy, we measured changes in blood pressure in three groups of spontaneously hypertensive and Wistar-Kyoto normotensive rats: (1) pregnant, bilaterally oophorectomized rats on postmating day 13, (2) pregnant, sham-oophorectomized rats on postmating day 13, and (3) nonpregnant, sham-oophorectomized rats after 13 days. The day before parturition we also measured the pressor responsiveness to angiotensin II and norepinephrine. Systolic blood pressure fell significantly during the last week of gestation in both strains, reaching normotensive levels in the hypertensive rats by term. The pressor responsiveness to angiotensin II, but not norepinephrine, of the pregnant rats was reduced compared with that of the nonpregnant rats in both strains. Oophorectomy did not prevent the fall in blood pressure or the decrease in vascular reactivity to angiotensin II. Therefore, although ovarian relaxin secretion increases during pregnancy, it apparently does not decrease vascular sensitivity to angiotensin II or cause vasodilation.

Angiotensin II↗

Labetalol does not decrease placental perfusion in the hypertensive term-pregnant rat.

The acute effect of labetalol hydrochloride, a combined nonspecific beta-adrenergic and postsynaptic alpha 1-adrenergic blocker, on maternal hemodynamics and organ perfusion was investigated in 10 hypertensive, term-pregnant, spontaneously hypertensive rats with the use of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by the reduction of litter size to two conceptuses on day 7 of gestation. Labetalol (1 to 6 mg/kg) effectively lowered mean arterial pressure 22% by decreasing cardiac output 16%; total peripheral resistance was not significantly decreased. Thus, the blood pressure lowering effect of labetalol was due primarily to its beta-adrenergic blocking effect. Regional flows to the carcass and splanchnic circulation were decreased 19% and 15%, respectively, after labetalol administration. Uterine wall and ovarian perfusion were significantly reduced, but placental perfusion was not significantly altered. Because labetalol lowers blood pressure without reducing placental perfusion, it may be a useful alternative to hydralazine for the treatment of hypertensive emergencies in pregnancy.

Animals↗

Indomethacin reduces the risks of severe intraventricular hemorrhage.

A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.

Apgar Score↗

Plasma volume, umbilical artery Doppler flow, and antepartum fetal heart testing in high-risk pregnancies.

The purpose of this clinical study is to investigate the diagnostic value of plasma volume (PV), nonstress test (NST), contraction stress test (CST), and umbilical artery Doppler (UAD) in detecting fetal compromise in 81 patients (83 fetuses) at risk for fetal growth retardation. Neither PV nor UAD studies were used in the clinical management. There were two stillbirths and three neonatal deaths for a perinatal mortality of 6%. Twenty-seven infants (32.5%) were small for gestational age (SGA), seven (8.6%) had cord pH 7.20 or less, and five (6.2%) had 5-minute Apgar scores less than 7. Overall, PV had the highest sensitivity and NST the highest specificity regarding delivery of SGA infants. The positive and negative predictive values for infants with low cord pH and low Apgar scores were similar among the various tests. There were nine fetuses with zero or reverse diastolic flow: seven were SGA (four perinatal deaths) and all of them had both nonreactive NST and positive CST. The other two infants were appropriate for gestational age with all other tests being normal. Antepartum fetal heart rate testing appears to be similar to other tests in predicting poor fetal outcome in high-risk pregnancies.

Apgar Score↗

Clozapine and haloperidol in the amygdaloid complex: differential effects on dopamine transmission with long-term treatment.

Single-unit recording techniques and liquid chromatography with electrochemical detection were used to measure the effects of neuroleptic pretreatment on the efficacy of dopamine transmission in the amygdaloid complex. Rats received twice-daily injections of clozapine (10.0 mg/kg), haloperidol (1.0 mg/kg), or vehicle for 6 days. During withdrawal from haloperidol, but not clozapine, amygdaloid neurons were significantly more responsive to iontophoretic application of dopamine. Neither drug altered the neuronal response to norepinephrine or acetylcholine. Tolerance developed to the ability of haloperidol to increase the amygdaloid level of 3,4-dihydroxyphenylacetic acid (DOPAC), a major dopamine metabolite, but such an effect did not occur with clozapine. In fact, clozapine pretreatment led to a significant increase in both DOPAC and dopamine levels in the amygdaloid complex. These results suggest that a differential action of these drugs on dopamine transmission may explain their differential effects on postsynaptic dopamine receptors.

Acetylcholine↗

The relationship between labor and route of delivery in the preterm infant.

The purpose of this prospective study was to evaluate the effects of the active phase of labor and route of delivery on the frequency of germinal layer/intraventricular hemorrhage in 89 infants with ultrasound-estimated fetal weights less than or equal to 1750 gm. Twenty-eight infants (31.5%) had germinal layer/intraventricular hemorrhage within 1 hour after birth and an additional 15 infants (17%) had germinal layer/intraventricular hemorrhage beyond 1 hour after birth. Infants with germinal layer/intraventricular hemorrhage had a significantly lower gestational age (p less than 0.003) and birth weight (p less than 0.007). Germinal layer/intraventricular hemorrhage within 1 hour after delivery was increased in the infants of women who experienced the active phase of labor regardless of the route of delivery. However, the incidence of germinal layer/intraventricular hemorrhage beyond 1 hour after delivery and the overall incidence were similar in the vaginal delivery and cesarean delivery groups. In addition, there was an increased incidence of progression to grades III and IV hemorrhage regardless of route of delivery in the infants whose mothers experienced the active phase of labor.

Apgar Score↗

Nifedipine does not adversely affect uteroplacental blood flow in the hypertensive term-pregnant rat.

The short-term effect of the calcium channel blocker, nifedipine, on maternal hemodynamics and organ perfusion was investigated in 12 hypertensive term-pregnant, spontaneously hypertensive rats by means of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by reducing litter size to two conceptuses on day 7 of gestation. Nifedipine (200 micrograms/kg) effectively lowered mean arterial pressure 25% by decreasing total peripheral resistance 38%. Cardiac output was increased 15%. Blood flows to the splanchnic region and the reproductive organs were increased after nifedipine administration. The increase in blood flow to the reproductive organs was the result of increased ovarian and uterine wall perfusion caused by large reductions in vascular resistances. Placental blood flow was not significantly altered, but resistance was decreased. Thus, the use of nifedipine to lower maternal blood pressure in pregnancy complicated by extreme hypertension does not necessarily decrease uteroplacental perfusion.

Animals↗

Short-course antibiotic therapy for the treatment of chorioamnionitis and postpartum endomyometritis.

The development of chorioamnionitis and endomyometritis has traditionally required treatment with broad-spectrum antibiotic therapy and extended hospitalization. In the past, once parenteral antibiotic therapy was instituted, it was continued for 5 to 7 days and until the patient remained afebrile for 48 hours. To shorten the length of hospital stay, the length of parenteral antibiotic administration was reduced and an oral antibiotic was added, to complete a 7- to 10-day course of therapy. We evaluated the effectiveness of an even shorter course of parenteral antibiotics without the addition of oral antibiotics. Forty-two patients with chorioamnionitis and 64 with endomyometritis were enrolled in the study. Antibiotic therapy was continued until the patient's temperature was less than 99.5 degrees F for 12 to 24 hours. Of the 106 patients, only two were readmitted, both as a result of superficial wound separation. No patient had an infectious complication. A shorter course of parenteral antibiotics without the addition of an oral antibiotic gives results comparable to the standard extended treatment regimens, but is advantageous with respect to cost, patient compliance, and hospital stay.

Adolescent↗

How perinatologists manage the problem of the presenting breech.

A questionnaire regarding controversies in management of the breech presentation was answered by 405 maternal-fetal medicine subspecialists. Legal concerns strongly influenced clinical management in 63% of respondents. External cephalic version was considered both safe and effective in 90 and 83% of respondents, respectively. Three-quarters of those who responded usually allow a trial of labor in selected term frank breech presentations. Of the respondent subset, 43% usually augment hypotonic contractions with oxytocin. Only 57% agreed there was sufficient literature to favor cesarean section for the 28 to 31 weeks breech presentation, and only 43% so agreed for the 32 to 34 week frank breech. Nevertheless, in these situations, 94 and 83%, respectively, actually perform cesarean section in clinical practice. More than 75% agreed that a prospective study is needed to determine the correct delivery mode of the preterm breech. Ninety-two percent agreed that such data could change their current opinion regarding delivery management. Implications are discussed.

Breech Presentation↗

The benefit of cesarean section in acute myocardial infarction complicated by premature labor.

A 42-year-old woman with no known risk factors had an acute myocardial infarction at 32 weeks' gestation and went into premature labor. She required invasive hemodynamic monitoring and inotropic support. Congestive heart failure improved dramatically after cesarean section. During the acute infarction, ventricular dysfunction was out of proportion to the ultimate ventricular damage. The concept of the stunned myocardium is used to explain this finding and to justify early cesarean section. Another complication of her infarction, left ventricular thrombosis, has not previously been described in pregnancy.

Adult↗

Obstetric variables predicting survival of the immature newborn (less than or equal to 1000 gm): a five-year experience at a single perinatal center.

The immature neonate constitutes less than 3% of total births and yet accounts for almost 50% of all perinatal deaths. In a 5-year period, 476 consecutive live and inborn neonates weighing less than or equal to 1000 gm were studied. The purpose of this study was to describe our experience with these pregnancies and determine the obstetric predictors of survival. Statistical methods of univariate and multivariate analysis were used. Survival was defined as the discharge home of an alive infant. The overall survival rate without exclusions was 40.3%. The following variables were most significant and accurately predicted survivors in 76.2% and nonsurvivors in 69.2% of cases: a combination of birth weight, 5-minute Apgar score, gestational age, cervical dilatation on admission, sex, a more recent study time interval, and race. Of the factors studied, the following were directly related to advancing gestational age and birth weight: higher Apgar scores at 1 and 5 minutes, increased operative delivery rate, and increased frequency of tocolysis and glucocorticoid usage; of these factors, only the 5-minute Apgar score remained statistically significant, when controlling for gestational age and birth weight by multivariate analysis.

Adult↗

Factors responsible for preterm delivery of the immature newborn infant (less than or equal to 1000 gm).

Although there are excellent studies examining factors responsible for preterm delivery in general, there is a scarcity of data describing factors specifically associated with delivery of the immature newborn infant. Our purpose is to characterize these factors in order to determine what may be done to limit preterm delivery rate of extremely low birth weight infants. Obstetric variables responsible for the birth of 338 live in-born immature neonates in a large single perinatal center were determined. We were unable to affect 65% of these pregnancies because there was no chance for intervention prior to admission in 63% of these mothers, and 66% had nonpreventable obstetric complications responsible for delivery. The median time interval from admission to delivery was 7 hours. Mortality was significantly higher in those delivered within 7 hours. We also found that neonatal mortality was twice as high in infants born to women with a previous perinatal loss. The clinical implications of these results are discussed.

Adolescent↗

Comparison of phospholipids in vaginal and amniocentesis specimens of patients with premature rupture of membranes.

Amniotic fluid was obtained from the vaginal pool and by transabdominal amniocentesis in 28 patients who were admitted to the hospital between 26 and 35 weeks' gestation with premature rupture of the membranes. Phospholipid profiles were obtained on all specimens with the use of high-performance liquid chromatography. The lecithin/sphingomyelin ratio, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and lysolecithin were all analyzed to determine the effect of vaginal contamination. With the use of a paired t test, only lysolecithin was shown to be significantly affected by vaginal contamination (p less than 0.05). As determined by high-performance liquid chromatography, evaluation of phospholipids in vaginal fluid of patients with premature rupture of the membranes appears to be an accurate and reliable method for predicting fetal lung maturity.

Amniotic Fluid↗

Uteroplacental blood flow in the hypertensive, term pregnant, spontaneously hypertensive rat.

Carbohydrate overfeeding throughout pregnancy prevents the progressive fall in blood pressure to normotensive levels during the last week of gestation in the spontaneously hypertensive rat. Cardiac output, organ blood flows, and vascular resistances, measured with radioactive-labeled microspheres, were compared in three groups: carbohydrate-supplemented (hypertensive) term-pregnant rats, control-fed (normotensive) term-pregnant rats, and control-fed (hypertensive) nonpregnant rats. Blood pressure remained elevated in the carbohydrate-supplemented pregnant rats because the normal decrease in total peripheral resistance did not occur. There were no significant differences in organ blood flows between hypertensive and normotensive pregnant rats, with the exception of a 26% lower placental blood flow in the hypertensive versus the normotensive rats. Carbohydrate overfeeding was associated with reduced litter size but did not affect fetal growth. Both placental blood flow and litter size were inversely related to mean arterial blood pressure at term. This may be a useful model of essential hypertension during pregnancy.

Animals↗

Trial of labor in previous cesarean section patients, excluding classical cesarean sections.

The American College of Obstetricians and Gynecologists has supported the concept of a trial of labor in patients with a previous lower uterine transverse cesarean section, and its safety is generally accepted. The purpose of this report was to present the results of a year-long, prospective study in which the indications for trial of labor were liberalized. Only patients with a previous classical incision or "T" incision on the uterus were excluded. Two hundred seventy-two patients elected to undergo a trial of labor. Vaginal delivery occurred in 216 patients (76.5%). Oxytocin was used as needed, and epidural anesthesia was used in all patients who requested it. One uterine rupture occurred in a patient with a single lower transverse scar. The results of this study suggest that a trial of labor is a safe alternative for patients with a previous single or multiple lower uterine transverse incision or a lower uterine vertical incision. In addition, the use of epidural anesthesia and oxytocin appears safe in patients undergoing a trial of labor.

Anesthesia, Epidural↗