Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids.

BACKGROUND: Topical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species. OBJECTIVES: To investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum. STUDY DESIGN: Prospective randomised experimental pharmacokinetic study. METHODS: Twenty-one Shetland ponies without ophthalmic disease were treated bilaterally topically every 2 hours during 24 hours to obtain steady state drug concentrations. One eye was treated with 0.15 mg of dexamethasone disodium phosphate (0.1%), and the other eye was simultaneously treated with 1.5 mg of prednisolone acetate (1%). Serum samples were taken prior to the induction of general anaesthesia. Aqueous and vitreous humour samples were taken during euthanasia at time points after administration of the last dose (t = 5 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min). Each pony was randomly assigned to one time point, and three ponies were sampled per time point. Dexamethasone and prednisolone concentrations were measured by liquid chromatography-mass spectrometry. RESULTS: The mean dexamethasone concentration in aqueous humour was 32.4 ng/mL (standard deviation [SD] 10.9) and the mean prednisolone concentration was 321.6 ng/mL (SD 96.0). In the vitreous and in serum samples concentrations of both corticosteroids were below the limit of detection (LOD 2.5 ng/mL). MAIN LIMITATIONS: The study group was limited to subjects without evidence of current ophthalmic disease. A limited number of time points were measured. CONCLUSIONS: Potentially effective dexamethasone and prednisolone concentrations were measured in the anterior chamber, but vitreal concentrations were negligible. Systemic uptake was low. Therefore, treatment with only topically administered corticosteroids is deemed insufficient in horses in cases of posterior uveitis. Further studies evaluating other routes of administration are warranted.

Papa Don't Preach? : Using Lies to Expose the Truth about Who Suppresses Female Sexuality.

The suppression of sexuality is culturally widespread, and women's sexual promiscuity, activity, and enjoyment are almost always judged and punished more harshly than men's. It remains disputed, however, to what end people suppress sexuality, and who benefits from the suppression of female sexuality. Different theories predict that women in general, men in general, women's intimate partners, or parents benefit most. Here we use the lies women and men tell-or imagine telling-about their sexual histories as an indirect measure of who is most involved in the suppression of sexuality. We asked men and women what they would reply if asked questions by their mother, father, current partner, attractive confederate, and various same- or opposite-sex friends and colleagues about their number of previous sex partners, age at first romantic kiss, age at first consensual sex, and cheating on a previous partner or spouse. By comparing the size and direction of the lies that subjects told, we tested competing predictions of several cultural and evolutionary theories concerning why female sexuality is suppressed and who is driving its suppression. We found that men and women told larger and more frequent lies to their parents, with women telling the largest and most frequent lies of all to their fathers. Additionally, the majority of lies by both men and women were in sexually conservative directions. Our findings suggest that mothers, and especially fathers, restrict female sexuality.

What drives female objectification? An investigation of appearance-based interpersonal perceptions and the objectification of women.

Previous research finds that both men and women perceive sexualized women as lacking in certain human qualities such as mental capacity and moral status. The mechanism underlying this effect, however, is unclear. The present two studies test how appearance-based judgements affect the degree to which a broad sample of women are objectified. In Study 1 (N = 279), full-body images of women wearing different clothing outfits were rated by male and female participants on perceived attractiveness, sexual intent and age. In Study 2, male and female participants (N = 1,695) viewed these same images from Study 1 and rated them on two dimensions of objectification (agency and patiency). We analyzed associations between these dimensions of objectification and the averaged appearance-based perceptions from Study 1. We find that women perceived as more open to casual sex are attributed less mental capacity and less moral status. We also find that participants tend to associate attractiveness with greater mental and moral status in women, but we find only limited evidence that perceived age influences objectification. Our findings suggest that although positive attractiveness biases may mitigate the amount a woman is objectified, greater female objectification may be prompted by observers' negative stereotypes of promiscuous women.

Fetal effects of prophylactic ephedrine and maternal hypotension during regional anesthesia for cesarean section.

The purpose of this study was to evaluate the effects of a prophylactic intravenous bolus of ephedrine on the incidence and severity of maternal hypotension and on neonatal outcome. Term healthy parturients (n = 122) scheduled for elective repeat cesarean section under regional anesthesia were studied. Ninety-two women received 10 mg ephedrine as a prophylactic intravenous bolus prior to intrathecal epidural local anesthesia. Thirty parturients who served as controls did not receive prophylactic ephedrine. Maternal blood pressures, Apgar scores, and umbilical cord blood acid-base status were evaluated. Sixty-three of 92 women (69%) who received intravenous prophylactic ephedrine prior to regional anesthesia developed hypotension compared to 21 (70%) controls. The mean (+/- SD) lowest systolic blood pressure was similar in both groups (95.6 +/- 12.9 vs. 96 +/- 8.9 mmHg; P = 0.86). The mean (+/-SD) fetal pH was significantly lower with prophylactic ephedrine than controls (7.24 +/- 0.07 vs. 7.28 +/- 0.05; P = 0.001). The frequency of umbilical artery blood pH < 7.20 was 10.6% for the ephedrine group vs. 3.2% for controls (P = 0.024). Among newborns of hypotensive mothers, the frequency of umbilical artery blood pH < 7.20 was 30.2% and 4.6% for the ephedrine and control groups, respectively (P = 0.018). Intravenous prophylaxis with ephedrine did not significantly decrease the frequency of hypotension in women receiving regional anesthesia and resulted in a greater proportion of umbilical artery blood pH values < 7.20.

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid.

OBJECTIVE: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. STUDY DESIGN: Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate matter (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients were also used. RESULTS: There were no significant differences in mean umbilical artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs 30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/- 6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. CONCLUSIONS: There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.

Genital herpes during pregnancy: no lesions, no cesarean.

OBJECTIVE: To determine the effects at our hospital of adoption of the 1988 guidelines recommended by ACOG for management of genital herpes infections during pregnancy. METHODS: Between 1984-1986, 96 pregnancies complicated by active genital herpes were delivered at Parkland Hospital. The outcome of these pregnancies were compared with 217 similar pregnancies managed after implementation of the 1988 ACOG herpes guidelines. RESULTS: Adoption of the 1988 ACOG herpes guidelines resulted in a 37% decrease in the use of cesarean delivery for women with genital herpes infections at our hospital. Most of this decrease was because the new guidelines eliminated the need for a confirmatory negative herpes culture before permitting vaginal delivery. No neonatal herpes infections occurred as a result of implementing the ACOG recommendations. CONCLUSION: The rate of cesarean delivery for women with genital herpes infections during pregnancy declined significantly at our hospital as a result of the adoption of ACOG herpes guidelines, and there were no neonatal consequences, such as increased incidence of neonatal herpes simplex virus infection.

Ex vivo human placental transfer of human immunodeficiency virus-1 p24 antigen.

OBJECTIVE: Our purpose was to determine whether human immunodeficiency virus-1 p24 antigen crosses the human placenta and, if so, to determine its clearance index relative to antipyrine. STUDY DESIGN: Eight term human placentas from uncomplicated vaginal or cesarean section deliveries were studied by ex vivo placental perfusion to determine the incidence and concentration required to obtain passage of p24 antigen into the fetal circulation. The concentration of p24 antigen was determined by antigen-capture enzyme immunoassay. RESULTS: The passage of p24 antigen into the fetal circulation was observed in three of five placentas studied when the p24 antigen concentration in the maternal circulation was 2942.8 +/- 401 pg/ml. When the p24 concentration in the maternal circulation was raised approximately fourfold to 14506 +/- 4124 pg/ml, p24 antigen passed to the fetal circulation in two of three placentas and in three of three placentas in the closed perfusion system. CONCLUSIONS: p24 antigen crossed the human placenta to the fetal circulation in what appears to be a concentration-dependent manner.

The maternal-fetal transfer of bisheteroypiperazine (U-87201-E) in the ex vivo human placenta.

OBJECTIVE: The purpose of this study was to elucidate the maternal-fetal transfer of bisheteroypiperazine (U-87201-E), a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus-1. STUDY DESIGN: Placentas from normal term deliveries were used in this study to determine the maternal-fetal transfer of bisheteroypiperazine. The studies were conducted at several concentrations with the circulation either open-open or closed-closed. RESULTS: In this study we determined that the clearance index of bisheteroypiperazine was 0.72 +/- 0.17 at maternal concentrations of 1.0 and 20.0 micrograms/ml. This is at least twice the clearance index of 3'-azido-2',3'-dideoxythymidine and more than five times greater than that of 2',3'-dideoxyinosine. CONCLUSIONS: Bisheteroypiperazine crosses the maternal-fetal membranes by simple diffusion, in some instances almost equivalent to the reference compound antipyrine. Placental tissue concentrations were equivalent at all maternal concentrations, suggesting saturation. This high rate of maternal-fetal transfer suggests that it may be an effective prophylactic drug for fetuses of human immunodeficiency virus-infected mothers.

Subcutaneous tissue: to suture or not to suture at cesarean section.

OBJECTIVE: The null hypothesis for this investigation was that there was no difference in the frequency of wound disruption between women who had their subcutaneous tissues approximated with suture and those who did not during cesarean section. METHODS: During alternating months, consecutive women delivered by cesarean section either did (N = 716) or did not (N = 693) have their subcutaneous tissues closed with suture. All data were analyzed using chi square, Student's t-test, Fisher's exact probability test, analysis of variance, or logistic regression. RESULTS: A 32% decrease in the frequency of wound disruption was observed when subcutaneous tissues were brought into apposition with suture at cesarean section (P = 0.03). CONCLUSIONS: Closure of Scarpa's and Camper's fascia with suture during cesarean section significantly decreased the frequency of wound disruption in this population.

Chorioamnionitis: association of nonreassuring fetal heart-rate patterns and interval from diagnosis to delivery on neonatal outcome.

OBJECTIVE: The purpose of this study was to determine whether selected fetal heart-rate (FHR) patterns and the interval from diagnosis to delivery in pregnancies complicated by chorioamnionitis could predict neonatal outcome. METHODS: During a 6-month period, 217 consecutive patients with acute chorioamnionitis were prospectively identified in labor. Following delivery, the fetal monitor strips and hospital courses were reviewed for both the mother and neonate. Multiple logistic regression was used to analyze the presence of a nonreassuring FHR pattern and the effect on neonatal outcome. Fisher exact tests were used to analyze the time intervals from the diagnosis of chorioamnionitis to delivery and their significance on neonatal outcome parameters. RESULTS: The overall incidence of chorioamnionitis in our population was 2.3%. None of the independent variables analyzed following the diagnosis of chorioamnionitis until delivery were significantly associated with an umbilical artery (Ua) pH < 7.20. There were no differences in cord pH, Apgar scores, sepsis, admission to special-care nursery, and oxygen requirements in neonates based on the duration of time from the diagnosis of chorioamnionitis to delivery in our study. None of the newborns had pathologic fetal acidemia (Ua pH < 7.00). None of the FHR patterns we identified after the diagnosis of acute chorioamnionitis were significantly associated with neonates with a Ua pH < 7.20. CONCLUSIONS: An interval from diagnosis to delivery of up to 12 h plays little if any role in neonatal outcome.

Prediction of the severity of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome is associated with increased neonatal morbidity and mortality. We sought to determine whether the need for neonatal mechanical ventilation or prolonged ventilation (> or = 3 days) was predictable from antepartum, intrapartum, and immediate neonatal events. STUDY DESIGN: Between 1987 and 1989, 8003 of 43,906 (18%) live infants had meconium-stained amniotic fluid; 82 of these infants had clinical and radiographic evidence of meconium aspiration, and of these 82, 39 (48%) required mechanical ventilation. Predictors of ventilation or prolonged ventilation were determined by means of stepwise logistic regression. RESULTS: Predictors of neonatal ventilation included fetal tachycardia, interval from meconium detection to delivery, low 5-minute Apgar score, respiratory distress necessitating intubation in the delivery suite, and delivery by cesarean section. Sensitivity was 72%, and specificity was 64%; the model was incorrect in 32% of the cases. Predictors of prolonged ventilation were ominous fetal heart rate tracing, umbilical arterial pH < 7.20, birth weight > 90th percentile, nulliparity, and Apgar score > 4 at 1 minute and < or = 6 at 5 minutes. Sensitivity was 67%, and specificity was 91%; prolonged ventilation was incorrectly predicted in 17% of the cases. CONCLUSIONS: Use of these models to determine the need for mechanical ventilation or prolonged ventilatory assistance will enhance identification of infants at risk of severe meconium aspiration and will lead to early transfer to the neonatal intensive care unit for intense observation and management.

Acid-base significance of meconium discovered prior to labor.

Although the significance of meconium in the amniotic fluid diagnosed during labor remains problematic, there is little information regarding the significance of meconium discovered prior to labor. The present study consisted of 40 term pregnancies with meconium found at amniocentesis for lung maturity (n = 7) or elective cesarean section (n = 33) and 40 uncomplicated, control pregnancies with clear amniotic fluid at elective cesarean section. The mean umbilical artery (UA) blood pH was 7.26 in the meconium group and 7.28 in the control group. Overall, the frequency of fetal acidemia (UA pH < 7.20) was 15% (6 of 40) of the infants in the meconium group versus 8% (3 of 40) in the control group (p = 0.24). All nine of these infants had a respiratory acidosis defined as a UA blood pH less than 7.20 with normal bicarbonate and elevated carbon dioxide pressure. Importantly, none of the neonates had metabolic acidemia and all had uncomplicated hospital courses. All of the pregnancies reported were promptly delivered because of meconium and we therefore cannot recommend nonintervention when meconium is diagnosed in the antepartum period. Meconium discovered prior to labor is not necessarily a marker of immediate or chronic fetal compromise.

The transfer of anti-human immunodeficiency virus nucleoside compounds by the term human placenta.

OBJECTIVE: The purpose of this study was to compare the maternal-fetal placental transfer of 2',3'-dideoxyinosine and 2',3'-dideoxycytidine with that of 3'-azido-2', 3-dideoxythymidine (azidothymidine). STUDY DESIGN: The perfusion system used carbon 14-labeled antipyrine as a reference compound to determine the clearance index of each compound. The inhibitor dipyridamole and the endogenous bases were used to determine if these anti-human immunodeficiency virus compounds crossed the placenta other than by simple diffusion. RESULTS: The clearance index of azidothymidine was 0.29 +/- 0.04 at maternal concentrations of 1.0 to 10 micrograms/ml, and the clearance index of 2',3'-dideoxyinosine was 0.14 +/- 0.05, which was 48% of the clearance index of azidothymidine. The clearance index of 2',3'-dideoxyinosine was essentially identical to azidothymidine in the range from 1 to 10 micrograms/ml. The results of the closed-closed studies suggest that at therapeutic peak concentrations of 1 to 2 micrograms/ml of these compounds in the maternal circulation therapeutic levels will be reached in the fetal circulation. CONCLUSION: These anti-human immunodeficiency virus inhibitors appear to cross the placenta rapidly by simple diffusion because (1) the transfer of the drugs to the fetal circulation was not saturable even at 100 micrograms/ml, (2) there was no change in clearance index with the addition of 300 mumol/L of thymidine, inosine, cytosine, or 30 mumol/L dipyridamole, and (3) there was no accumulation against the maternal fetal or fetal maternal concentration gradient.

Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.

OBJECTIVE: To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term. METHODS: Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical. RESULTS: Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity. CONCLUSIONS: The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.

Pathologic fetal acidemia.

There is no clearly established umbilical artery pH cutoff to be used for defining pathologic fetal acidemia (ie, the threshold associated with major neonatal morbidity or mortality). Classically, a pH cutoff of less than 7.20 has been used. Our goal was to define this pH cutoff more precisely. There were 3506 term newborns (2500 g or greater) with an umbilical artery pH of less than 7.20; these newborns were divided into five pH groups. Eighty-seven (2.5%) had a pH of less than 7.00, 95 (2.7%) a pH of 7.00-7.04, 290 (8.3%) 7.05-7.09, 798 (22.8%) 7.10-7.14, and 2236 (63.8%) 7.15-7.19. Two-thirds (66.7%) of the newborns with an umbilical artery pH less than 7.00 had a metabolic component in their acidemia, compared with 13.7% or less in all other pH groups. Significantly more (P less than .05) newborns in the less-than-7.00 pH group had low (less than 3) 1- and 5-minute Apgar scores compared with the other four pH groups. In addition, neonatal death was significantly more common (P = .03) in newborns with a pH less than 7.00, and seven (50%) of the 14 deaths occurred in this group. The statistically significant pH cutoff for all seizures was less than 7.05 (P = .004), and for unexplained seizures was less than 7.00 (P = .01). Eight (67%) of the 12 unexplained seizures occurred in this latter pH group. Thus, a more realistic pH cutoff for defining pathologic fetal acidemia would appear to be less than 7.00.

Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact.

Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally.

Intrapartum asphyxia in pregnancies complicated by intra-amniotic infection.

Intra-amniotic infection has been reported to be associated with intrapartum asphyxia; however, the criteria used to define asphyxia have been imprecise. In the present study of 123 women with intra-amniotic infection and 6769 women without infection, the mean umbilical artery pH was 7.28 in both groups. The frequency of acidemia (umbilical artery pH less than 7.20) was not significantly different between the infection group and controls (15 versus 10%; P = .12). Likewise, there was no significant difference between the groups when a lower umbilical artery pH value (less than 7.15) was used to define acidemia. None of the infants from infected mothers had metabolic acidemia with a pH of less than 7.15 and none had a pH of less than 7.00. Significantly more (P less than .05) infants in the infected group did have low 1-minute (20 versus 5%) and 5-minute (3 versus 1%) Apgar scores of 6 or less, criteria often used to define asphyxia. However, none of the newborns from the infected group had recently proposed criteria for the diagnosis of birth asphyxia (ie, leading to neurologic impairment) such as metabolic acidemia, seizures in the immediate newborn period, and low Apgar scores (3 or less). Birth asphyxia is rarely associated with intra-amniotic infection, and in the absence of other signs of fetal jeopardy such as an ominous fetal heart rate pattern, an immediate cesarean to prevent asphyxia does not appear justified once the diagnosis of chorioamnionitis is made.

Identification of laminin binding proteins in cell membranes of a human colon adenocarcinoma cell line.

The invasion of malignant cells through the basement membrane is a critical step in local infiltration and metastasis. Adhesion and invasion of malignant cells may be modulated by their receptor mediated binding to the basement membrane glycoprotein laminin. We studied the specific adhesion of human colon adenocarcinoma derived HT 29 cells to laminin and its proteolytic fragments. The major cell adhesion domain of laminin was localised in the central part of the cross shaped molecule. Immunoblotting experiments on separated HT 29 cell membranes using specific antibodies or radiolabelled laminin fragments revealed two major laminin-binding cell surface components with Mr of 67,000 and 69,000 D similar to the putative laminin receptor described for other tissues. Using a nitrocellulose filter disk assay, the specific interaction between cell surface binding proteins and proteolytic fragments originating from the central core of the laminin molecule could be further corroborated. In contrast, interaction of HT 29 cell membranes with the pentapeptide YIGSR (tyr-ile-gly-ser-arg), a sequence domain of the B1-chain of the laminin molecule, thought to be responsible for cell adhesion, was significantly weaker.