Vitellogenin induction by xenobiotic estrogens in the red-eared turtle and African clawed frog.

Many environmental pollutants have estrogenic activity in animals. Xenobiotic estrogens include many pesticides and industrial chemicals that biocumulate. The impact of these common pollutants on the reproductive success of wildlife may be considerable, particularly in threatened or endangered species. This research examined the use of plasma vitellogenin in males as a biomarker for estrogenic xenobiotics in reptiles and amphibians. Adult male turtles (Trachemys scripta) and frogs (Xenopus laevis) were given ip injections of estradiol-17 beta (E2), diethylstilbestrol (DES), or o,p'-DDT (1-chloro-2-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl)benzene) daily for 7 days, and plasma was collected on day 14. The estrogenic activity of each compound was determined by measuring the induction of plasma vitellogenin. Vitellogenin was identified by precipitation, electrophoresis, Western blot, and enzyme-linked immunosorbant assay (ELISA). In both species, estradiol and DES treatments induced the most vitellogenin, whereas DDT treatments induced smaller amounts of vitellogenin in a dose-dependent fashion. These data indicate that induction of plasma vitellogenin in males may be a useful biomarker of xenobiotic estrogen activity in wild populations of reptiles and amphibians.

Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy.

OBJECTIVE: To determine the contributions of uterine artery diameter and mean flow velocity to the increase in volumetric flow during human pregnancy. METHODS: Volunteers (18 pregnant and six not pregnant) were studied using both a commercially available Doppler instrument with imaging ultrasound and an improved Doppler instrument with software that can determine instantaneous true mean blood flow velocity. Diameter and mean flow velocity measurements were combined to yield volumetric flows in the common iliac, external iliac, and uterine arteries during and after pregnancy. RESULTS: Compared with the nonpregnant state, uterine artery diameter doubled by week 21 (from 1.4 +/- 0.1 to 2.8 +/- 0.2 mm; P < .05), did not change between weeks 21 and 30 (2.9 +/- 0.1 mm), and increased between weeks 30 and 36 (to 3.4 +/- 0.2 mm). Uterine artery mean flow velocity rose progressively from nonpregnant values to attain at week 36 a velocity nearly eight times faster (8.4 +/- 2.2 versus 61.4 +/- 3.0 cm/second; P < .05). Unilateral uterine artery blood flow at week 36 was 312 +/- 22 mL/minute. CONCLUSIONS: Compared with nonpregnant values, common iliac artery flow increased and external iliac artery flow decreased during pregnancy, suggesting that redistribution of pelvic flow to favor the uterus contributed to the pregnancy-associated rise in uterus artery flow. Early in pregnancy, the increase in uterine artery blood flow was due in equal parts to changes in uterine artery diameter and mean flow velocity, whereas late in pregnancy, the rise was due mainly to faster mean flow velocity.

Effect of altitude on uterine artery blood flow during normal pregnancy.

To determine whether uterine blood flow was reduced and indexes of pelvic blood flow distribution altered in normotensive pregnancy at high (3,100 m) compared with low altitude (1,600 m), we measured uterine, common iliac, and external iliac artery blood flow velocities and diameters in women during pregnancy and again postpartum. Pregnancy increased uterine artery diameter, blood flow velocity, and volumetric flow at both altitudes. Uterine artery blood flow velocity was greater (69.0 +/- 2.2 vs. 59.4 +/- 3.0 cm/s; P < 0.005) but diameter was smaller at 3,100 m than at 1,600 m (2.5 +/- 0.3 mm vs. 3.4 +/- 0.2 mm; P < 0.005), resulting in volumetric flow that was one-third lower at week 36 of pregnancy (203 +/- 48 vs. 312 +/- 22 ml/min, respectively; P < 0.01). Pregnancy increased common iliac blood flow velocity and decreased external iliac artery blood flow velocity at both altitudes. The uterine artery received a smaller percent of common iliac flow at 3,100 than at 1,600 m (46 +/- 7 vs. 74 +/- 6%; P < 0.005). Gestational age was similar but birth weight was lower at 3,100 m than at 1,600 m. Among subjects at 1,600 m, variation in uterine blood flow velocity correlated positively with infant birth weight. We concluded that reduced uterine blood flow and altered pelvic blood flow distribution during pregnancy at high altitude likely contributed to the altitude-associated reduction in infant birth weight.

Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude.

High-altitude residence during pregnancy is associated with an increased incidence of preeclampsia. To determine whether uteroplacental blood flow was reduced and pelvic blood flow distribution altered before the onset of hypertension, we measured common iliac (CI), uterine (UA), and external iliac (EI) artery flow velocities (FV), indexes of flow distribution, and blood volume (BV) at week 12, 24, and 36 of pregnancy and 6 mo postpartum in 23 normotensive, 7 preeclamptic, 5 transiently hypertensive, and 3 chronically hypertensive residents of 3,100 m. Normotensive women had a progressive increase in CIFV and UAFV, decrease in EIFV, redistribution of CIFV from the EI to the UA, and increase in BV with advancing pregnancy. Preeclamptic women attained maximal UAFV and redistribution of CIFV from the EI to the UA well before the onset of hypertension and, unlike normotensive women, showed no further increases near term. Plasma volume increment with pregnancy related to the fall in the EIFV/CIFV ratio. Transiently hypertensive women resembled normotensive subjects in the parameters measured, whereas chronically hypertensive subjects resembled preeclamptic subjects. We concluded that preeclamptic vs. normotensive pregnant residents of high altitude had less redistribution of CI flow to the UA and no increase in UA blood flow near term. That these differences were present before the onset of hypertension supports the concept that preeclampsia is characterized by an incomplete vascular adjustment to pregnancy.

Blood volume expansion, preeclampsia, and infant birth weight at high altitude.

Low blood volume (BV) during pregnancy is associated with intrauterine growth retardation and preeclampsia, which are more common at high altitude (HA) than at low altitude. We hypothesized that reduced BV expansion during pregnancy predisposed some women to develop preeclampsia and/or have lower-birth-weight infants at HA. BV was lower in 34 HA residents (3,100 m) than in 22 moderate-altitude residents (1,600 m) while nonpregnant (58.3 +/- 1.2 vs. 72.3 +/- 1.3 ml/kg; P < 0.001) and 36 wk pregnant (69.9 +/- 1.9 vs. 83.3 +/- 3.6 ml/kg; P < 0.01). BV fell between weeks 24 and 36 of pregnancy, and total BV increment with pregnancy was less in women who developed preeclampsia or transient hypertension at HA (n = 12). At HA, total blood and plasma volume expansion and arterial O2 saturation correlated negatively with the highest mean arterial pressure recorded during pregnancy (r = -0.73, P < 0.01 and r = -0.58, P < 0.01, respectively). Total BV and late pregnancy change in BV correlated positively with infant birth weight. We concluded that BV expansion in normotensive pregnancy at HA vs. moderate altitude was similar but that nonpregnant BV was less among HA women, accounting for the low BV in pregnancy. HA women who developed preeclampsia or transient hypertension had less BV expansion, particularly during the third trimester, which was associated with smaller infants.

Rapid preparation of plasma for coagulation testing.

Currently recommended minimum centrifugation of whole blood to produce platelet-poor plasma for routine coagulation assays is 1000g relative centrifugal force for 10 minutes. Many clinical laboratories centrifuge blood for routine coagulation assays from 500g to 2000g, with spin times varying from 20 to 5 minutes. Ninety blood samples, routinely submitted to our coagulation laboratory, were prospectively assayed simultaneously for the prothrombin time, activated partial thromboplastin time, and fibrinogen level, comparing centrifugation at 11,000g for 2 minutes with centrifugation at 1000g for 10 minutes. Routine and readily available equipment and supplies were used. Platelet counts were performed on the supernatant plasma in each sample to determine the efficacy of platelet depletion. Excellent correlation of methods was observed for the prothrombin time, activated partial thromboplastin time, and fibrinogen level. Platelet counts on the plasma supernatant showed no significant difference between the two centrifugation methods. We concluded that high-speed centrifugation at 11,000g with a shortened spin time of 2 minutes and with the use of routinely available equipment and supplies can significantly decrease the specimen preparation time for routine coagulation testing.

Use of complementary and alternative medicines by surgical patients.

This study examined the frequency of surgical patient use of complementary and alternative medicines prior to surgery. After conducting a literature review on the known effects of alternative medicines, we evaluated their potential interactions with anesthetics. At the University of Colorado Health Sciences Center, Denver, Colo, we surveyed 500 elective surgical outpatients about alternative medicines taken during the 2 weeks prior to surgery. Of the 500 patients surveyed, 51% preoperatively took herbs, vitamins, dietary supplements, or homeopathic medicines (range, 1-22 per patient). Substances from 2 or more categories of alternative medicines (herbs, vitamins, dietary supplements, or homeopathic medicines) were consumed by 24% of patients. Twenty-four percent of surveyed patients consumed 50 different herbs, 41% took 9 types of vitamins, 44% took 31 types of dietary supplements, and 1% of patients took the homeopathic arnica. Classification by potential adverse effects revealed that 27% of surgical patients consumed alternative medicines that may inhibit coagulation, affect blood pressure (12%), cause sedation (9%), have cardiac effects (5%), or alter electrolytes (4%). Greater communication, knowledge, and scientific research are needed to safely integrate complementary and alternative medicines in the future management of the surgical patient.

Halothane, tracheal compliance and upper-airway mechanoreceptors.

This study was designed to define the effects of halothane on the compliance of the trachea. An isolated in-situ tracheal preparation was studied in 14 mongrel dogs anesthetized with pentobarbital. Compliance of the closed tracheal segment was measured with continuous intraluminal pressure recordings during repeated injections of known volumes of air: Slow-adapting neural activity observed in paratracheal branches of the recurrent laryngeal nerve accurately reflected pressure in the tracheal segment. Halothane at 0.5--4.0 per cent concentrations caused a significant (P less than 0.001) average 10 per cent increase in the compliance of the trachea. Stimulation of the efferent vagus caused a significant (P less than 0.001) average 8 per cent decrease in compliance of the trachea. After exposure to halothane, vagal stimulation still caused a significant decrease in compliance of the trachea.

Anesthesia-related deaths during obstetric delivery in the United States, 1979-1990.

BACKGROUND: Anesthesia-related complications are the sixth leading cause of pregnancy-related death in the United States. This study reports characteristics of anesthesia-related deaths during obstetric delivery in the United States from 1979-1990. METHODS: Each state reports deaths that occur within 1 yr of delivery to the Centers for Disease Control and Prevention as part of the ongoing Pregnancy Mortality Surveillance. Maternal death certificates (with identifiers removed) matched with live birth or fetal death certificates when available from 1979-1990 were reviewed to identify deaths due to anesthesia, the cause of death, the procedure for delivery, and the type of anesthesia provided. Maternal mortality rates per million live births were calculated. Case fatality rates and risk ratios were computed to compare general to regional anesthesia for cesarean section deliveries. RESULTS: The anesthesia-related maternal mortality rate decreased from 4.3 per million live births in the first triennium (1979-1981) to 1.7 per million in the last (1988-1990). The number of deaths involving general anesthesia have remained stable, but the number of regional anesthesia-related deaths have decreased since 1984. The case-fatality risk ratio for general anesthesia was 2.3 (95% confidence interval [CI], 1.9-2.9) times that for regional anesthesia before 1985, increasing to 16.7 (95% CI, 12.9-21.8) times that after 1985. CONCLUSIONS: Most maternal deaths due to complications of anesthesia occurred during general anesthesia for cesarean section. Regional anesthesia is not without risk, primarily because of the toxicity of local anesthetics and excessively high regional blocks. The incidence of these deaths is decreasing, however, and deaths due to general anesthesia remain stable in number and hence account for an increased proportion of total deaths. Heightened awareness of the toxicity of local anesthetics and related improvements in technique may have contributed to a reduction in complications of regional anesthesia.

Lidocaine and bupivacaine differential blockade of isolated canine nerves.

In vitro studies of pharmacologic actions of local anesthetics are usually performed at room temperature using amphibian nerves exposed to local anesthetics for substantial periods of time. We performed in vitro studies of pharmacologic responses of motor A fibers and sensory C fibers to lidocaine and bupivacaine in clinically effective concentrations using a canine nerve preparation at body temperature with short exposure times to evaluate responses under clinically relevant conditions. Differential blockade of isolated, desheathed phrenic and vagus nerves was achieved with bupivacaine (0.58 mM), C fibers being blocked before A fibers (P less than 0.05). Lidocaine (2.8 mM) did not block A and C fibers differentially.

Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado.

OBJECTIVE: Our purpose was to determine the case incidences of preeclampsia at low and high altitudes and whether maternal blood pressure course during pregnancy differs between low and high altitudes. STUDY DESIGN: This was a retrospective cohort study of pregnancies in sociodemographically matched communities at low and high altitudes in Colorado; each community had a small hospital served by family practitioners and was located >100 miles from major urban areas. Included were consecutive singleton pregnancies of women without chronic disease that resulted in live-born infants at >28 weeks' gestation during an 18-month period (n = 116 at 1260 m, n = 93 at 3100 m). Clinic and hospital medical records were searched and data pertaining to hypertensive complications of pregnancy and serial blood pressure measurements were abstracted. RESULTS: Despite similar maternal risk factors, the case incidences of preeclampsia were 16% at 3100 m and 3% at 1260 m. As in sea-level pregnancies, mean blood pressure fell until week 20 in normotensive pregnancy at 1260 m. Mean pressure rose linearly, however, in normotensive women at 3100 m and in women with preeclampsia at both 1260 m and 3100 m. High altitude acted independently of known risk factors and yielded an odds ratio for preeclampsia of 3.6 (95% confidence interval 1. 1-11.9). Birth weight was 285 g lower at 3100 m despite similar gestational ages. CONCLUSION: The normal pregnancy-associated fall in blood pressure was absent at 3100 m, even in women who remained normotensive. The incidence of preeclampsia was increased at high altitude. Residence at high altitude interferes with the normal vascular adjustments to pregnancy, increasing the incidence of preeclampsia, and is perhaps analogous to other conditions that decrease uteroplacental oxygen delivery.