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Biomedical subjects

C Crenshaw

Publications and source records attributed to C Crenshaw.

At least 19 recordsLinked to original sources

Chorionic villus sampling: the University of Maryland experience.

The University of Maryland was the first program in the state to offer chorionic villus sampling (CVS). Since the program's beginning in 1984, 998 patients have been seen with successful sampling in 99.1 percent, using both transcervical and transabdominal approaches. The overall loss rate was quite low (2.3 percent), and no increased risk of birth defects was seen. These observations demonstrate that CVS provides a safe and accurate alternative to amniocentesis.

Abortion, Eugenic

Modulation of mannose receptor activity by proteolysis.

Macrophages express a receptor on the cell surface that functions to clear glycoproteins from the extracellular milieu. The activity of this receptor is sensitive to treatment with trypsin. In inflammatory situations, macrophages are activated and exposed to increased levels of extracellular proteases. Under these conditions, mannose receptor activity on the macrophages is diminished. We therefore decided to study the effects of trypsin treatment on the structure and activity of cell-associated and purified receptor that might contribute to the activation-associated receptor down-regulation. Trypsin treatment (1 microgram/ml for 3 h) resulted in the production of a 140 kDa, trypsin-resistant fragment from both intact cells and isolated receptor. This fragment was no longer able to bind ligand. The remaining 35 kDa fragment apparently is further degraded into smaller fragments, since no evidence of this domain was found on Coomassie Blue-stained gels. The 140 kDa fragment retained immunoreactivity and contained at least a portion of the iodinated tyrosine residues following surface labelling with Na125I. Neither calcium nor ligand protected the receptor from proteolysis. In addition, prior treatment with oxidants did not increase the susceptibility of the receptor to trypsin digestion. We conclude from these results that the macrophage mannose receptor is clipped by the serine protease trypsin at the cell surface, resulting in the release and further degradation of the binding domain, and the production of a membrane-associated 140 kDa fragment. This trypsin-mediated down-regulation of receptor activity might be important in controlling glycoprotein clearance during inflammation.

Animals

Ovarian pregnancy diagnosed after a failed midtrimester therapeutic abortion. A case report.

Ovarian pregnancy is a rare phenomenon. Its presentation often is difficult to distinguish from that of tubal ectopic pregnancy and hemorrhagic ovarian cyst. A patient had an ovarian pregnancy diagnosed following failed midtrimester therapeutic abortion in a suspected bicornuate uterus. Despite vaginal prostaglandin suppositories and intraamniotic instillation of urea and prostaglandin, neither the abortion process nor rupture of the ovarian pregnancy ensued. This is the first reported case of this most unusual presentation of ovarian pregnancy.

Abortion, Therapeutic

Reacting appropriately to thrombocytopenia in pregnancy.

The lower limit of normal for the platelet count is considered to be 150,000/cu mm in both pregnant and nonpregnant normal adults. In the absence of preeclampsia, sepsis, drugs, or other apparent causes, the finding of asymptomatic mild thrombocytopenia in pregnant women is compatible with previously unrecognized immune thrombocytopenic purpura (ITP). Because of the risk of fetal/neonatal thrombocytopenia and the subsequent risk of neonatal intracranial hemorrhage in infants born of mothers with ITP, the optimal mode of delivery for an asymptomatic but thrombocytopenic mother is problematic. Conceivably, those gravidas with mild previously unrecognized thrombocytopenia may not have ITP and thus could be spared cesarean section. From the platelet counts of 730 antepartum patients, we found a mean value of 263,900/cu mm with a standard deviation of 66,000/cu mm, yielding 95% confidence limits of 134,500 to 393,300/cu mm. The distribution is statistically indistinguishable from a normal distribution. Of 26 asymptomatic thrombocytopenic patients with no hematologic history, none had infants with hemorrhage or platelet counts less than 100,000/cu mm. Only one patient subsequently had severe glucocorticoid-resistant thrombocytopenia requiring splenectomy several months after delivery. The remaining patients continue to be asymptomatic to date, with platelet counts greater than 100,000/cu mm. We suggest a plan for managing less than normal platelet counts in asymptomatic gravidas without a history of hematologic abnormality.

Cesarean Section

The dehydroepiandrosterone loading test. III. A possible placental function test.

The dehydroepiandrosterone loading test (DLT) has been used in a small population of normal and high-risk obstetric patients, to date, in an attempt to develop a dynamic test of placental function. In spite of its limited applications, it has shown reliability in discriminating, with statistical significance, between high-risk pregnancies that result in normally grown, undistressed infants, and high-risk pregnancies that result in infants showing signs of placental insufficiency. The present report expands the study population by presenting our data on 40 loading tests performed in 37 high-risk and normal obstetric patients. Results of 19 of these DLT's have been previously reported and are included herein for statistical analysis. The DLT utilizes an excess substrate load of dehydroepiandrosterone to assess the maximum capability of the placenta to convert it to estrogen. Although our previous report did not show false positive or negative results in the conversion rates, the present results (40 DLT's) found two (2 out of 17) false positives (12%) and two (2 out of 19) false negatives (11%). The highly significant correlation between DLT result and pregnancy outcome seen previously was preserved. In addition, the data of another five DLT's in four patients are presented. This group includes a pregnancy with a fetus with multiple congenital malformations, two patients with intrauterine fetal death, and a nonpregnant woman. The results are not included in the statistical analysis, but discussion of these results has interesting pathophysiologic implications.

Dehydroepiandrosterone

O2 delivery to the pregnant uterus: its relationship to O2 consumption.

Normal sheep were studied at intervals of 3-5 days during the last weeks of pregnancy in order to evaluate variability in rate of O2 consumption (QO2) of the uterus in relation to several variables involved in delivery of O2 to the organ. Among-animal differences of uterine QO2 were statistically significant and directly related to birthweight of the lamb. Among-animal differences of uterine blood flow (UBF) and uterine arteriovenous O2 content difference [C(a-v)O2] also were statistically significant, though neither was related to birthweight, presumably since they tended to vary inversely with one another. In a given ewe relative magnitude of UBF and of C(a-v)O2 was related to maternal arterial O2 content (CaO2), day of pregnancy, and whether the animal carried singlets or twins. Variability in QO2 was most closely related to UBF, although its relations to C(a-v)O2 and CaO2 were significant also. These data suggest there are systematic relationships among variables involved in the delivery of O2 to the uterus of pregnant sheep.

Animals

Fetal lamb lung lavage and its effect on lung phosphatidylcholine.

UNLABELLED: The lungs of intrauterine 135--136-day-old lambs were lavaged with amnionic fluid, with or without meconium, to determine the effect on lung phosphatidylcholine (PC) concentration, synthesis, and function. No differences were apparent between animals lavaged with amnionic fluid or amnionic fluid with meconium. When lavaged lungs were compared to nonlavaged controls, no detectable differences were observed in histology or the quantity of saturated (SPC) and unsaturated phosphatidylcholine (UPC). However, the lavaged lungs retained a larger fraction of maximal lung volume at 5 cm H2O distending pressure and the incorporation of (32P) orthophosphate into lung PC was significantly reduced. In addition, two lavaged animals who became acidotic (pH less than 7.20) exhibited decreased incorporation of 14C) palmitate into whole lung unsaturated, and saturated phosphatidylcholine. SPECULATION: These data indicate that amnionic fluid can reduce lamb lung de novo synthesis of PC and may contribute to the alterations in lung PC found in neonatal syndromes of respiratory distress. Acidosis may accentuate this effect.

Amniotic Fluid

Acute fatty metamorphosis of the liver: a report of two patients who survived.

Two patients with acute fatty metamorphosis of the liver of pregnancy who survived are presented. Clinical and pathologic features, possible etiologic factors, and principles of treatment are discussed. Both patients subsequently were allowed to become pregnant again, both had uncomplicated second pregnancies without evidence of liver disease, and both delivered healthy babies.

Acute Disease

Whole and disaturated lung phosphatidylcholine in cortisol-treated, intrauterine growth-retarded and twin control lambs at different gestational ages.

Lambs 116--124 days gestation infused in utero for 75 h with cortisol showed, when compared to twin controls, more mature lung histology and pressure-volume relationships. 32P orthophosphate incorporation into whole lung phosphatidylcholine (PC) was increased in the four cortisol-treated lambs at 116--117 days but not at 121, 123, and 124 days gestation. 14C palmitate incorporation into PC or disaturated phosphatidylcholine (DSPC) was not enhanced at 116--117 days gestation. At 121 days in a cortisol-treated and at 128 days in a growth-retarded lamb fetus not treated with cortisol, a larger quantity of DSPC was present although the incorporation of 14C palmitate into DSPC per milligram DNA was the same. This indicated that the synthesis of DSPC had been initiated in the cortisol-treated and growth-retarded animals prior to the controls and at the time of sacrifice both were incorporating 14C palmitate at a similar rate suggesting similar rates of synthesis.

Animals

Studies on ovine placental lactogen secretion by homologous radioimmunoassay.

The concentrations of ovine placental lactogen (oPL) have been determined in maternal plasma, umbilical cord plasma, and allantoic fluid by an homologous radioimmunoassay for oPL which is sensitive to 0-1 ng hormone. Ovine placental lactogen was first detected in maternal plasma at 41-50 days of gestation and reached a peak concentration of 2547 +/- 226 (S.E.M.) ng/ml at 121-130 days in ewes with singleton gestations. The oPL concentration in cord plasma was 336-4 +/- 60-3 ng/ml and in allantoic fluid was 29-6 +/- 6-4 ng/ml. After surgical removal of the placenta, oPL disappeared from maternal plasma with a half-life of 29-1 +/- 1-3 min.

Allantois

A physiologic model of the dehydroepiandrosterone to estrogen conversion system in the fetoplacental unit. I. Development.

A physiologic model of the dynamics of fetoplacental unit dehydroepiandrosterone (HDEA) to estrogen conversion is presented. A mathematical representation of this model is included. The model is used in Part II to determine the rate constant of DHEA to estrogen conversion and to successfully identify those fetuses in jeopardy from placental insufficiency within the population studied. This presentation permits critical comprehension of the model without extensive mathematical background.

Dehydroepiandrosterone

A physiologic model of the dehydroepiandrosterone to estrogen conversion system in the fetoplacental unit. II. Preliminary clinical application--the dehydroepiandrosterone loading test.

A dehydroepiandrosterone (DHEA) loading test (DLT) is described. The results of 19 DHEA loading tests in as many third-trimester obstetric patients are presented. Analysis involves inspection of the raw data and the application of the physiologic model of the DHEA to estrogen conversion system described in the preceding paper (Part I). The DLT results show that within the population studied, the conversion rate of DHEA to estrogens is lower in patients with placental insufficiency than in normal patients (N = 5, p = 0.002) or in patients with various complications of pregnancy who deliver normally grown, undistressed infants (N = 6, p = 0.001). Routine clinical application must await more extensive evaluation to preclude the existence of forms of placental insufficiency not detected by this means, or normal states resulting in "false-positive" tests. These initial clinical results are intended primarily to demonstrate the potential clinical applicability of the physiologic model described in Part I.

Dehydroepiandrosterone

Effect of exogenous dehydroepiandrosterone upon the fetoplacental biosynthesis of estrogens and its effect upon uterine blood flow in the term pregnant ewe.

The fetoplacental unit of the ewe is capable of increasing the biosynthesis of estrogens following the exogenous administration of DHEA to the fetus. The maximum concentrations of estrogens appeared approximately 30 minutes after the administration of DHEA. Uterine blood flow in the pregnant ewe increased approximately 90 minutes after the maximum concentrations of estrogens were noted. The administration of DHEA to the nonpregnant, ovariectomized ewe did not elicit estrogen biosynthesis or changes in uterine blood flow. Isotope experiments in the pregnant ewe demonstrated the incorporation of DHEA into urinary estradiol.

Animals

Development of the sheep as an animal model to study placental lactogen physiology.

Ovine placental lactogen, purified from term sheep cotyledons, has been found to have chemical and biologic properties similar to those of human placental lactogen, ovine growth hormone, and ovine prolactin. OPL stimulates lactation in vivo and in vitro and binds to prolactin and growth hormone membrane receptors. Its binding to growth hormone receptors is approximately 20 times greater than that of hPL, suggesting that its somatotrophic potency is greater than that of hPL. Preliminary in vivo studies in the sheep indicate that oPL affects maternal carbohydrate, lipid, and protein metabolism and that its effects are, in part, similar to those of hPL and growth hormone.

Animals