Atypical experiences of captive chimpanzees (Pan troglodytes) are associated with higher hair cortisol concentrations as adults.

Experiences during early development are influential on the lives of human and non-human primates into adulthood. The population of captive chimpanzees in the USA can provide insight into this relationship, as collectively they have experienced a wide range of exposure to both conspecifics (those raised in natal groups) and humans (those raised as personal pets or performers). Our study investigated chimpanzee exposure to humans using a continuous measure of categorization, the chimpanzee-human interaction index, and the relationship between this experience and cortisol concentrations in adulthood. Historical records and hair samples were collected from 60 chimpanzees which were socially housed in 13 zoos and sanctuaries. We found that more human exposure throughout the life of a chimpanzee was associated with higher hair cortisol concentrations in adulthood. Sex was also a significant factor affecting cortisol concentration, with male chimpanzees having higher cortisol concentrations than female chimpanzees. These results build upon the extensive literature about aversive effects of atypical social histories for chimpanzees and emphasize to managers the importance of monitoring potential negative health consequences and social deficits these individuals may exhibit.

Fatal fetal hemorrhage and placental pathology. Report of three cases and a new setting.

We report three cases of late third trimester fetal death in utero consequent to fetal exsanguination from the chorionic vasculature. In general, fetal hemorrhage is unusual, exsanguination is rare and the location and basis of the hemorrhage varies widely. Intragestational and intrapartum hemorrhage is far more often of maternal rather than fetal origin. Even when severe, the former is almost always manageable whilst the latter may be clinically obscure, intractable, catastrophic and fatal. In this presentation, we review and characterize fetal hemorrhage by anatomical location and on the basis of its underlying origins. In our first two cases, the chorionic vascular failure is understood on the basis of mechanical factors, such as tearing by the presenting part or an amniotomy hook. Our third case demonstrates the first reported instance in which a severe chorionic vasculopathy has damaged a placental surface vessel sufficiently to permit spontaneous rupture and fetal exsanguination.

Nutrient intake and hypertensive disorders of pregnancy: Evidence from a large prospective cohort.

OBJECTIVE: The objective of this analysis was to prospectively determine the effects of nutrient intakes on the incidences of preeclampsia and pregnancy-associated hypertension among women enrolled in the Calcium for Preeclampsia Prevention study. STUDY DESIGN: This was a prospective observational cohort study of women in a randomized clinical trial that included women seeking prenatal care at university medical centers and affiliated clinics and hospitals in 5 US communities. A total of 4589 nulliparous women were recruited between 13 and 21 weeks' gestation. Preeclampsia and pregnancy-associated hypertension were the main outcome measures. RESULTS: Preeclampsia was noted in 326 (7.6%) of the 4314 women with known pregnancy outcomes followed up until > or =20 weeks' gestation, and pregnancy-associated hypertension was noted in 747 (17.3%). As previously reported, there was no significant difference in these outcomes between cohorts randomly assigned to supplementation with calcium or placebo. By means of logistic regression a baseline risk model was constructed for preeclampsia and pregnancy-associated hypertension. After adjustment for treatment and clinical site, body mass index >26 kg/m(2) and race were significantly associated with an increased risk of preeclampsia. Body mass index > or =35 kg/m(2), race, and never smoking were significantly associated with an increased risk of pregnancy-associated hypertension. After adjustment for baseline risks, none of the 28 nutritional factors analyzed were significantly related to either preeclampsia or pregnancy-associated hypertension. CONCLUSION: We found no evidence in this study for a significant association of hypertensive disorders of pregnancy with any of the 23 nutrients measured.

Hemodynamic changes in pregnancy.

The basic mechanisms that underlie alterations in the physiology of pregnancy are virtually unknown. Basal oxygen consumption increases by some 50 mL/min in pregnant women at term. Blood volume increases gradually over gestation as does red cell mass. Cardiac output increases by some 50% by mid-third trimester. Stroke volume and heart rate increase over the course of pregnancy with heart rate increasing gradually until term. The heart of the pregnant woman remodels dramatically in the first few weeks of pregnancy; end diastolic volume increases. Stroke volume is augmented by the increase in end diastolic volume and maintenance of ejection fraction through a possible increase in contractile force. Systolic and diastolic blood pressures drop during normal pregnancy. There is evidence of blood vessel remodeling in all vessels. Venous compliance and venous blood volume are increased. Renal plasma flow increases by some 70% in pregnancy with glomerular filtration rate increasing by 50% by unknown mechanisms. The complex hormonal environment is changing throughout pregnancy. In summary, under the influence of circulating chemical mediators blood flow is redistributed to the uterus, breast, and kidney.

The sequential effects of estrogen administration and hypertension on cardiac function in ewes.

OBJECTIVE: Our objective was to study the effect of estrogen administration and moderate hypertension on left ventricular size, pump function, and contractility in chronically instrumented ewes. STUDY DESIGN: Ewes were either given 0.06 mg/kg 17beta-estradiol intramuscularly (n = 8) or were made hypertensive (n = 6) by inflation of an occluder around the aorta and were studied weekly. After 3 weeks each ewe received the opposite treatment. RESULTS: Estrogen administration caused an increase in left ventricular chamber size at a given pressure, fractional shortening (21.9% +/- 2.9% to 28.5% +/- 3.7%), and stroke volume (1.4 +/- 0.3 mL/kg to 1.6 +/- 0.3 mL/kg). Subsequent hypertension further increased left ventricular size at a given pressure but decreased fractional shortening (20.0% +/- 4.4%) and stroke volume (1.3 +/- 0.3 mL/kg). With hypertension first, there was no left ventricular enlargement, even with subsequent estrogen administration, and there were no changes in left ventricular pump function. End-systolic pressure and stress-dimension relationships did not change with either treatment. The end-systolic wall stress-fractional shortening relationship was likewise unchanged, suggesting that neither treatment changed contractility. CONCLUSIONS: The left ventricle previously exposed to hypertension does not remodel when exposed to estrogen, and cardiac pump function decreases when the estrogen enlarged heart is faced with moderate, subacute hypertension.

A regulated environmental perfusion system for the study of anoxic or hypoxic cultured neurons using microfluorescence imaging and electrophysiology.

We describe the design and performance of a newly developed regulated environmental perfusion system (REPS). This system allows study of the effects of anoxia or hypoxia in cultured cells at physiological temperature, without the use of oxygen-scavenging compounds or metabolic inhibitors. The REPS incorporates a "canoe-shaped" flow-through chamber with access from above to allow positioning of pipettes for patch-clamp, microinjection, rapid-application perfusion, or microprobes for monitoring physical parameters. The combination of laminar flow and complete washout of perfusate within the chamber, and the use of a gas-tight perfusate delivery system and pressurized reservoirs containing media with pre-stabilized oxygen tensions (pO2 values) allow rapid production of accurate perfusate pO2 within the chamber. Perfusate pO2 in the chamber declined monoexponentially with time constants of /= 2 ml/min. The perfusion chamber of the REPS is easily mounted on the stage of an inverted microscope, for use with fluorescence imaging or electrophysiological studies of cultured cells. In tests with cultured rat cortical neurons, intracellular calcium concentration increased exponentially to values exceeding 1 microM during 10 min of anoxic insult, and returned to baseline values within 1 min after restoring normoxia.

Trial of Calcium for Preeclampsia Prevention (CPEP): rationale, design, and methods.

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.

Subgaleal hematoma: the need for increased awareness of risk.

Subgaleal hematoma, also known as subaponeurotic hemorrhage, is a serious complication of birth that is associated with vacuum-assisted delivery. Despite a high rate of mortality associated with subgaleal hematoma, it has received relatively little attention in the medical literature. Lack of awareness may lead to delayed diagnosis and serious consequences for infants. This paper is a report of six cases and a literature review. Prevention and early recognition and treatment of the condition can occur only with increased practitioner awareness of this entity.

Localization of fibrillin-1 in the human term placenta.

OBJECTIVE: We determined the level of message for fibrillin-1, a single-stranded glycoprotein found in the elastic microfibrils of the extracellular matrix, in human placenta compared with other adult human tissues and localized the protein in the term human placenta. METHODS: Northern blot analysis using a cDNA specific for fibrillin-1 was used to compare message levels in several adult human tissues and placenta. Immunohistochemical staining, using a monoclonal antibody to human fibrillin-1, was used to visualize the site of fibrillin-1 in term human placenta. RESULTS: Larger amounts of message for fibrillin-1 were present in placenta than in any of the other tissues tested. Staining for fibrillin-1 was present in the villous stroma but not in the basement membranes, trophoblast cells, or in blood vessels of stem, mature intermediate, or terminal villi. CONCLUSIONS: Fibrillin-1 is distributed extensively in the villous stroma of the term human placenta and may contribute elastic properties to the placenta and basal plate required for an active uterus.

Pregnancy complicated by aortic dissection: caesarean delivery during extradural anaesthesia.

We report a case where dissection of the aorta occurred in pregnancy; only medical management was undertaken. Delivery was by Caesarean section during extradural anaesthesia and was accomplished safely several weeks after the dissection. The aetiology, association with pregnancy, diagnosis and management of acute dissection of the aorta are discussed.

Circumvallate placenta: sonographic diagnosis.

We prospectively identified 12 patients who had a shelf at the margin of the placenta consistent with the diagnosis of circumvallate placenta. Ten patients were followed to delivery and three placentas were sent for pathologic analysis. Circumvallate placenta was diagnosed by gross inspection in all three but was confirmed by microscopic analysis in only two. One of these patients had placental abruption and cesarean delivery for fetal distress at 27 weeks. Circumvallate placenta is another cause of uterine band, sheet, or shelf. The finding can be associated with a normal obstetric outcome but may predispose to placental complications.

The value of Doppler assessment of the uteroplacental circulation in predicting preeclampsia or intrauterine growth retardation.

Flow velocity waveforms of the uteroplacental arteries were analyzed at 20 and 24 weeks of gestation, by means of duplex pulsed Doppler ultrasonography, in 93 women at risk for preeclampsia or intrauterine growth retardation. The ability of an elevated resistance index to predict these conditions was tested. At 20 and 24 weeks an abnormal resistance index was significantly associated with intrauterine growth retardation but not with preeclampsia, with or without proteinuria. A low fetal abdominal circumference at 20 or 24 weeks or an increasing maternal plasma uric acid concentration at 24 weeks was as predictive as an elevated resistance index. In a second group of 43 women, screened in the same way, the only association was of an elevated resistance index at 20 weeks with intrauterine growth retardation. Although elevated resistance indices occur more commonly in women who develop intrauterine growth retardation and/or preeclampsia, the correlation is not close enough to be clinically useful as a screening test.

Substrate oxidation by adult cardiomyocytes in long-term primary culture.

In medium 199 plus 20% fetal calf serum adult rat cardiomyocytes establish a long-term culture (25 days). During the first 10 days they change their gross morphology from the typical elongated in vivo shape (day 1), to a smooth spherical intermediate form (days 2 to 5), to a spread cell type beating spontaneously (days 10 to 15). During the first 10 days in culture, protein content per cell increases and the cell population decreases. By the tenth day, protein content has doubled, and about half of the cells originally plated remain. Thereafter both the protein content and the number of cells are essentially constant for the remainder of the 25-day period investigated. On days 1, 15 and 25 adenine nucleotide contents (213, 216 and 225 nmol/10(6) cells) and values of adenylate energy charge (0.91, 0.87 and 0.88) were similar. At all times in culture, palmitate (0.1 mM) is oxidized at higher rates than lactate (1 mM) and glucose (5 mM). At all times in culture glycolytic flux is sensitive to insulin with half maximal effect seen around 10(-9) M. Oxidation rates for all exogenous substrates are maximal at 15 days in culture, indicating maximal energy demand at this time. The conversion of glucose to lactate, however, progressively increases, so that at 25 days in culture, 70% of ATP derived from degradation of exogenous glucose is glycolytic. The results of this study demonstrate that oxidative metabolism of cardiomyocytes in long-term culture resembles, in its basic characteristics, that of the intact heart. In their increased glycolytic activity, however, they are clearly different.

Determinants of cardiomyocyte development in long-term primary culture.

The influence of cell attachment to substrates and of medium composition on development of cardiomyocytes from adult rats in cultures up to 9 days old was investigated. Cardiomyocytes prevented from attaching to a culture substratum deteriorated within 3 days in medium 199 (M199) with or without fetal calf serum (FCS). Rapid attachment during the first 4 h after plating could be attained equally well on FCS or laminin coated surfaces. In M199 without FCS, attached cardiomyocytes on FCS coated dishes were able to retain their overall elongated morphology, but the number of cells remaining attached constantly decreased during the first 9 days in serum free culture. Attached on laminin the rate of loss from serum free cultures was lower. In the presence of 20% FCS, attached cardiomyocytes spread extensively after day 3, both on FCS and on laminin coated dishes. In serum containing media many cells pass through a spherical intermediate state before spreading extensively. Almost all cardiomyocytes cultured with 20% FCS on untreated tissue culture plastic gradually become spherical before attaching. With 20% FCS in culture media, the number of cells remaining in culture after 9 days was similar whether cells were rapidly attached to FCS treated or laminin coated substrata, or were plated on culture plastic, i.e., 52, 63, and 45% of the maximal number attached on day 1. By day 9 in all three culture types cells were spread and were beating spontaneously. These results indicate that adult cardiomyocytes do not establish in a stable morphological state in long-term cultures, in other than a surface attached spread cell form. For this stability the presence of yet unidentified components of fetal calf serum is required.

Rearrangement of tubulin, actin, and myosin in cultured ventricular cardiomyocytes of the adult rat.

Antitubulin, phalloidin, and antimyosin were used to study the distribution of microtubules, microfilaments, and myofibrils in cultured adult cardiomyocytes. These cells undergo a stereotypic sequence of morphological change in which myotypic features are lost and then reconstructed during a period of polymorphic growth. Microtubules, though rearranged during these events in culture, are always present in an organized network. Myosin and actin structures, on the other hand, initially degenerate. This initial degeneration is reversed when a cell attaches to the culture substratum. Upon attachment, new microtubules are laid down as a cortical network adjacent to the sarcolemma and, subsequently, as a network in the basal part of the cell. Actin and then myosin filament bundles appear next, in a pattern corresponding to the pattern of the microtubules. Finally, striated myofibrils are formed, first in the central part of the cell, and subsequently in the outgrowing processes of the cell. A mechanism is suggested by which the eventual polymorphic shape of a cell is related to the shape of its initial area of contact with the culture substratum. Finally, a model of myofibrillogenesis is proposed in which microtubules participate in the insertion of myosin among previously formed actin filament bundles to produce myofibrils.

Long-term primary cultures of adult human and rat cardiomyocytes.

An improved protocol for isolating and culturing adult mammalian cardiomyocytes is presented. Problems of establishing and maintaining cultured adult human and rat cardiomyocytes, and some of their properties, are discussed.

Evidence for functional sodium and calcium ion channels in the membrane of cultured cardiomyocytes of the adult rat.

Characteristics are reported for electrical activity of adult rat cardiomyocytes in long-term primary culture. Cells in vitro for 12 to 28 days have mean membrane potential of -53 mV, are electrically excitable, and some are spontaneously contractile. The action potential of these cells has a slow rate of depolarization and is abolished by methoxyverapamil (D-600) but not by tetrodotoxin (TTX). When cells are hyperpolarized by passage of an inward current, spontaneous action potentials cease and action potentials evoked by depolarizing pulses are then TTX sensitive. Fetal bovine serum is a constituent of the culture medium. Its temporary removal causes spontaneous contractility to cease but the cells remain electrically excitable.