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Biomedical subjects

L J Heffner

Publications and source records attributed to L J Heffner.

At least 19 recordsLinked to original sources
PubMed1996

Outcomes of severely abnormal umbilical artery doppler velocimetry in structurally normal singleton fetuses.

OBJECTIVE: To construct a management guide for preterm pregnancies complicated by severely abnormal umbilical artery Doppler velocimetry. METHODS: A retrospective chart review was conducted on all cases of absent or reversed end-diastolic flow umbilical artery Doppler velocimetry identified through an ultrasound data base. Maternal and perinatal outcome variables were retrospectively reviewed and analyzed using both parametric and nonparametric statistical techniques. Seventy-one cases were identified over a 5-year period. After excluding multiple gestations, anomalous fetuses, and two cases that were terminated before 24 weeks' gestation, 56 singleton gestations remained for analysis. RESULTS: Among the 56 subjects, there were 45 survivors and 11 deaths (five fetal and six neonatal deaths). Nonsurvivors had a significantly lower gestational age at diagnosis and delivery. Nonsurviving live-born neonates had lower Apgar scores and were significantly smaller; however, there were no differences in proportion or severity of fetal growth restriction in survivors and nonsurvivors. There were no differences in last biophysical profile before delivery or interval from diagnosis of reversed end-diastolic flow to delivery. Predictors of nonsurvival were the presence of reversed end-diastolic flow and oligohydramnios. Perinatal mortality for reversed end-diastolic flow was 333/1000 and 94/1000 for absent end-diastolic flow. Risk for perinatal death was highly gestational age dependent. For delivery at less than 26 weeks, survival was one of four; at 26-27.9 weeks, survival was seven of 12; and at 28 weeks or greater, survival was 37 of 40. CONCLUSION: Whereas severely abnormal umbilical artery blood flow poses significant risk for pregnancy, perinatal mortality is dominated by gestational age at diagnosis and delivery. This may reflect the severity of the disease or the low survival of very immature gestations. Interventions on behalf of the fetus at very early gestational ages should be undertaken with caution.

Female↗
PubMed1995

Glycosylated human prolactin: detection by immunoblotting of biological fluids is confounded by antisera crossreactivity with immunoglobulins.

Glycosylated human prolactin is found in several biological fluids and can only be detected by western immunoblotting. Glycosylated prolactin migrates at 25,000-27,000 molecular weight while prolactin migrates at 23,000. We have discovered that several anti-human prolactin sera crossreact with some light chain components of human immunoglobulins, which also migrate at 25,000 on electrophoretic gels run under reducing conditions. Evidence is provided for prolactin binding to immunoglobulins in biological fluids, which may explain why some polyclonal anti-prolactin sera demonstrate this crossreactivity.

Amniotic Fluid↗
PubMed1995

Massive chronic intervillositis associated with recurrent abortions.

Massive chronic intervillositis (MCI) is an unusual placental lesion associated with poor fetal growth and adverse pregnancy outcome; it has not previously been associated with spontaneous abortion or recurrent pregnancy loss. This article reports a patient who had 10 spontaneous abortions with repetitious massive chronic intervillositis documented in four of five gestations spanning all three trimesters. Characteristic placental histology induced massive infiltration of the maternal intervillous space by chronic inflammatory cells and fibrin, without associated chronic villitis; the cellular infiltrate was composed predominantly of LCA and CD68 immunoreactive cells with scattered CD45RO positivity, consistent with a monocyte/macrophage population with occasional T lymphocytes. Elevated maternal serum alpha-fetoprotein was documented in two pregnancies. These findings support the concept that this unusual placental lesion may have an immunologic basis, and suggest that MCI may be a histopathologically recognizable cause of recurrent spontaneous abortion.

Abortion, Habitual↗
PubMed1993

Airway responsiveness in young black and white women.

The prevalence and severity of asthma appears to be greater in blacks than in whites. To determine if racial differences in airway responsiveness may explain these findings, methacholine challenge tests from 62 black and 238 white women 20 to 35 yr of age were evaluated. Subjects served as controls for a case-control study of the relation of airway responsiveness and preterm labor. Standardized questionnaires were used to obtain information on age, obstetrical history, education, income, cigarette smoking, medication use, and respiratory illnesses and symptoms. Total serum IgE was measured using a radioimmunoassay. Methacholine challenge testing was performed on all subjects 6 wk after delivery, and the provocative dose causing a 20% decrease in FEV1 (PD20) was calculated. Black women in the study had more pregnancies and children, were younger, less well educated and more impoverished, and reported greater cigarette smoking and less medication use than did the white women. Additionally, black women had higher geometric mean serum IgE levels (blacks: 65.4 IU versus whites: 20.0 IU; p < 0.001), lower FEV1 (blacks: 2.73 +/- 0.38 SD L versus whites: 3.19 +/- 0.39 L; p < 0.001), and greater unadjusted airway responsiveness than did white women (geometric mean PD20: blacks: 28.4 mumol versus whites: 38.8 mumol; p = 0.02). After adjusting for selective demographic and smoking differences, a significant additional effect of race on mean PD20 was found. However, after adjustment for level of serum IgE and level of FEV1, racial differences were no longer apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors.

Uterine leiomyomas, which are myometrial smooth muscle tumors, secrete PRL. We investigated the actions of several hormones known to stimulate PRL secretion by the pituitary gland or decidua on PRL secretion by leiomyoma-derived smooth muscle cells (SMC) in monolayer culture. Cultures were verified to be SMC by immunostaining for smooth muscle alpha-action and desmin. Hormone treatments were performed in serum-free medium for 72 h. Medium was harvested every 24 h and assayed for PRL. 17 beta-Estradiol, progesterone, TRH, insulin-like growth factor-I, epidermal growth factor, and the GnRH agonist leuprolide did not affect PRL secretion by these SMC. Insulin caused a significant suppression of PRL secretion by 72 h, and this was accompanied by a 64% increase in total cell protein per well, which represented an increase in cell number. Cells were also plated at various densities to determine the effects of cell number on PRL secretion. The amount of PRL secreted per 1000 cells decreased significantly as cell number per well increased. Northern blot analysis identified PRL mRNA in fresh leiomyoma tissue. PRL mRNA in three independent cultures of SMC was then detected by reverse transcription and the polymerase chain reaction. Hybridization occurred only with the expected band of approximately 423 basepairs in size. We conclude that leiomyomas express PRL mRNA in vivo and that leiomyoma-derived SMC in culture continue to express the PRL mRNA and secrete PRL in the absence of ovarian steroids. PRL secretion by SMC in culture appears to be modulated primarily by changes in cell density.

Base Sequence↗
PubMed1993

Clinical and environmental predictors of preterm labor.

OBJECTIVE: To determine the magnitude of risk for preterm labor associated with specific clinical and environmental factors. METHODS: Using a case-control design, 266 women with preterm labor and 512 controls were interviewed and their medical records reviewed. Crude and adjusted odds ratios were calculated for each risk factor. Population-attributable risks were estimated. RESULTS: Third-trimester bleeding, twin gestation, and chorioamnionitis at presentation were strongly associated with preterm labor (odds ratios 11.2-48.3). A history of a prior preterm delivery, vaginal bleeding in the first or second trimester, maternal diethylstilbestrol exposure, uterine anomalies, and urinary tract infection during pregnancy were associated to a lesser extent (odds ratios 1.6-5.4), as were cigarette smoking and drug use (odds ratios 2.0 and 3.0). Cases who had preterm labor preceded by premature rupture of the membranes had a substantially higher risk of preterm labor if chorioamnionitis, vaginal bleeding early in pregnancy, or urinary tract infection was present. By contrast, women who had intact membranes at the onset of preterm labor carried higher risk when twin gestation, placental abruption, or uterine anomaly was present. The highest population-attributable risks for preterm labor were found in patients with a twin gestation or third-trimester bleeding. CONCLUSIONS: Programs to reduce the preterm delivery rate should consider the attributable risks for the factors they are intended to modify. The attributable risks we obtained suggest that medical strategies to reduce the impact of the clinical variables, especially multiple gestation, and educational programs to decrease smoking and drug use should reduce the preterm delivery rate.

Adult↗
PubMed1992

Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation.

OBJECTIVES: Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. STUDY DESIGN: Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. RESULTS: Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). CONCLUSIONS: Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment.

Analysis of Variance↗
PubMed1990

Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist.

Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion.

Antineoplastic Agents↗
PubMed1990

The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist.

The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

A glycosylated prolactin species is covalently bound to immunoglobulin in human amniotic fluid.

Western immunoblots performed during separation of glycosylated prolactin from amniotic fluid revealed that some of the glycosylated prolactin is covalently bound to another protein. Using high performance liquid chromatography and other protein isolation techniques we have demonstrated that a glycosylated prolactin species is linked to immunoglobulin by disulfide bonds in amniotic fluid.

Amniotic Fluid↗
PubMed1988

Management of isoimmunized pregnancy by use of intravascular techniques.

Twenty-two patients who had 23 pregnancies complicated by isoimmunization were managed by the use of intravascular methods on an outpatient basis. Nine patients underwent 30 percutaneous fetal blood sampling procedures to determine fetal blood type or hematocrit, without complication. Thirteen patients underwent 45 intrauterine fetal transfusions via the umbilical vessels and 16 intraperitoneal fetal transfusions. The overall survival rate in this series was 85.7%. Survival among fetuses that were hydropic at initial evaluation was 83.3%. The procedure-related perinatal mortality rate for intravascular intrauterine transfusions was 2.2%. Knowledge of fetal blood type and hematocrit allowed treatment individualized to the specific needs of each patient. In particular, the ability to transfuse blood directly into the vascular system of the hydropic fetus proved to be lifesaving in those patients.

Blood Grouping and Crossmatching↗
PubMed1988

Early amniocentesis for prenatal cytogenetic evaluation.

Early amniocentesis at 11-14 weeks gestation was evaluated in 100 consecutive patients to see how this technique compares with later amniocentesis. There were no complications as a consequence of the procedure or related pregnancy losses of chromosomally normal fetuses. Samples obtained from three (3%) patients showed insufficient cell growth; two of these patients elected a repeat procedure, which yielded a normal karyotype in each case. There were five abnormal karyotypes, one of which was a culture artifact; in the latter case, repeat amniocentesis at 15 weeks yielded a normal result. Of the 95 pregnancies with normal karyotypes, 94 were progressing normally at follow-up, and one patient elected pregnancy termination because of maternal indications. It appears that early amniocentesis may be an attractive alternative to traditional amniocentesis, in that it provides results at an earlier gestational age and may avoid certain disadvantages of chorionic villus sampling.

Amniocentesis↗
PubMed1986

Electrophoretic analyses of secreted human endometrial proteins: identification and characterization of luteal phase prolactin.

Endometrial protein synthesis and secretion throughout the menstrual cycle was studied by slab gel electrophoretic analysis of [35S]methionine incorporation into protein during short term culture of human endometrial tissue. A minimum of five protein bands that fluctuate during the menstrual cycle were identified on one-dimensional gels. Those with mol wt of 28K, 35K, 51K, and 59K decreased in the luteal phase, whereas a broad 25K band was induced in the luteal phase. This broad band was identified as two species of glycosylated PRL by antihuman PRL immunostaining and [3H]glucosamine incorporation.

Adult↗
PubMed1985

Primary management of postpartum vulvovaginal hematomas by angiographic embolization.

Three cases of large postpartum vulvovaginal hematomas are reported. After conservative measures including incision and drainage, ligation of bleeding sites, vaginal packing and replacement of volume and coagulation factors failed to control the bleeding in each, pelvic angiography was performed. Brisk arterial bleeding demonstrated on arteriography was controlled by Gelfoam embolization in all three cases. Intra- or postpartum hematologic evaluation revealed a previously undiagnosed coagulation disorder in each patient. The authors suggest that angiography be considered before hypogastric artery ligation whenever possible in patients with large postpartum hematomas and that all such patients be evaluated for coagulopathy.

Adult↗
PubMed1981

The role of calcium in maintaining motility in mouse spermatozoa.

Maintenance of mouse sperm motility requires exogenous Ca+2 in most, but not all, samples of epididymal spermatozoa. In these samples, the loss of motility with time is the same in Tris/NaCl buffer containing 1.7 mM Ca+2 (medium TNC) as it is in complete culture medium used for in vitro fertilization (medium CM) over the first 2 hours; spermatozoa in medium TNC lose motility at more rapid rate thereafter. The cation specificity for maintenance of motility is unusual in that both Sr+2 and Mg+2 substitute for Ca+2, with Mg+2 being the more effective. In the absence of Ca+2, these samples of mouse epididymal spermatozoa in Tris/NaCl buffer (medium TN) lose motility in about 30 minutes. If Ca+2 is added after incubation in TN for 15 minutes, motility is maintained as well as it is in medium TNC. If Ca+2 is added at 30 minutes, motility is partially restored. But if Ca+2 is added after 60 minutes, there is no restoration of motility. Spermatozoa suspended in medium TNC lose motility rapidly on addition of EGTA in excess of the Ca+2 present. Attempts to show uptake of Ca+2 by spectrophotometric assay, by effects of Ca+2 on oxidative metabolism, and by electron probe X-ray microanalysis were unsuccessful; motility is not maintained by entry of Ca+2 into the cells. Our results are consistent with a Ca+2 site on the plasma membrane and suggest that these sites function as oligomers of ordered subunits whose structure requires Ca+2. In the absence of Ca+2, the ability to form the oligomer is lost with time, possibly due to an irreversible conformational change.

Animals↗