Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age.

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P<0.0001). There were small (1-5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P<0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data.

Characterization of dioxin exposure in firefighters, residents, and chemical workers in the Irkutsk Region of Russian Siberia.

The goal of this study was to characterize body burdens of polychlorinated dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in three groups of Siberians living in the Irkutsk Region of Russia. These groups included firefighters exposed to a mixture of toxic substances extinguishing a large fire at the Shelekhovo Cable Factory in 1992, chemical workers from the Khimprom chemical plant, and residents living in proximity to large chemical factories in Sayansk and Angarsk. Blood samples from all groups were obtained in the fall of 1998. Dioxin analyses of samples were performed in Germany, Canada, and in a Russian dioxin laboratory in Ufa, Bashkortostan Republic. The average levels of dioxin toxic equivalents (TEQs) are 23.6 parts per trillion (ppt) total TEQ (PCDD/F only) in the disabled firefighters, 25.0 in the non-disabled firefighters, 28.7 in residents, and 45.6 in the Khimprom workers blood. Two workers did have elevated total TEQs of 91.4 and 102.2 ppt. Dibenzofurans and coplanar PCBs substantially contribute to the total elevated TEQ seen here. The average TEQs suggest levels of dioxin exposure in this part of the former Soviet Union not dissimilar to levels measured in industrialized countries of Europe and Northern America.

Levels of dioxins and dibenzofurans in breast milk of women residing in two cities in the Irkutsk Region of Russian Siberia compared with American levels.

The presence of dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs) in human tissue, food, and environmental samples from Russia has been monitored since 1988 as part of a research collaboration between a number of countries including Finland, the United States, Germany, the former Soviet Union, and Canada. Although elevated TCDD and PnCDD levels have previously been found in blood of male and female Russian chemical manufacturing workers and in their children, dioxin levels in the general population have usually been found to be lower than in Americans and Europeans. This study continues earlier work in the Irkutsk region of Russian Siberia, where we report levels of dioxin, dibenzofurans, and PCBs in human milk samples taken from general population women living in the industrialized cities of Angarsk and Usolye-Sibirskoye, near Lake Baikal. Total polychlorinated dibenzo-p-dioxin (PCDD) toxic equivalents (TEQs) compared in this paper for the industrialized regions of Siberia, Ukraine, and the US are similar, ranging from 6.1 to 7 parts per trillion (ppt). Recent 1998 milk samples from Angarsk and Usolye-Sibirskoye have total mean polychlorinated dibenzofuran (PCDF) TEQs of 10 and 21.7 ppt, respectively, with the other industrialized countries ranging from 2.3 to 6.7 ppt. Although dioxin-like PCBs were not measured for the city of Usolye-Sibirskoye (1998), total mean PCDD/F TEQ from Angarsk and Usolye-Sibirskoye (1998) were the two highest levels in this study, with 26.9 and 28.5 ppt, respectively, followed by 1993-1994 Ukraine samples with 24 ppt, 1989 Siberian samples with 13.6 ppt, and 1996 USA with 11.4 ppt total TEQ. In this study, higher levels of dioxins are noted in milk from Angarsk and Usolye-Sibirskoye than found in earlier Russian studies, with mean levels also exceeding 1996 and 1999 US breast milk dioxin levels.

Multicenter study of noninvasive monitoring systems as alternatives to invasive monitoring of acutely ill emergency patients.

BACKGROUND: Recent reports showed lack of effectiveness of pulmonary artery catheterization in critically ill medical patients and relatively late-stage surgical patients with organ failure. Since invasive monitoring requires critical care environments, the early hemodynamic patterns may have been missed. Ideally, early noninvasive hemodynamic monitoring systems, if reliable, could be used as the "front end" of invasive monitoring to supply more complete descriptions of circulatory pathophysiology. OBJECTIVES: To evaluate the accuracy and reliability of noninvasive hemodynamic monitoring consisting of a new bioimpedance method for estimating cardiac output combined with arterial BP, pulse oximetry, and transcutaneous PO2 and PCO2; we compared this system of noninvasive monitoring with simultaneous invasive measurements to evaluate circulatory deficiencies in acutely ill patients shortly after hospital admission where invasive monitoring was not readily available. We also preliminarily explored early differences in temporal hemodynamic patterns of survivors and nonsurvivors. DESIGN AND SETTING: Prospective comparison of simultaneous invasive and noninvasive measurements of circulatory function with retrospective analysis of data in university-run county hospitals, university hospitals and affiliated teaching hospitals, and a community private hospital. PATIENTS: We studied 680 patients, including 139 severely injured or hemorrhaging patients in the emergency department (ED), 129 medical (nontrauma) patients on admission to the ED, 274 high-risk surgical patients intraoperatively, and 138 patients recently admitted to the ICU. RESULTS: A new noninvasive impedance device provided cardiac output estimations under conditions in which invasive thermodilution measurements were not usually applied. There were 2,192 simultaneous bioimpedance and thermodilution cardiac index measurements; the correlation coefficient, r = 0.85, r2 = 0.73, p < 0.001. The precision and bias was -0.124+/-0.75 L/min/m2. Both invasive and noninvasive monitoring systems provide similar information and identified episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous O2, high transcutaneous CO2, and low oxygen consumption before and during initial resuscitation. The limitations of noninvasive systems were described. CONCLUSIONS: Noninvasive monitoring systems gave continuous displays of physiologic data that provided information allowing early recognition of low flow and poor tissue perfusion that were more pronounced in the nonsurvivors. Noninvasive systems may be acceptable alternatives where invasive monitoring is not available.

Early physiologic patterns in acute illness and accidents: toward a concept of circulatory dysfunction and shock based on invasive and noninvasive hemodynamic monitoring.

The aim of the present study was to explore methods, concepts, and techniques that provide recognition of circulatory deficiencies at the earliest possible time in the patient's illness. We used both the standard invasive pulmonary artery thermodilution catheter and noninvasive hemodynamic monitoring systems consisting of a new bioimpedance cardiac output device, pulse oximetry, transcutaneous oxygen (PtCO2) and carbon dioxide tensions as well as the transcutaneous oxygen tension/fraction of inspired oxygen ratio (PtCO2/FIO2). These three noninvasive systems were used to evaluate cardiac function, pulmonary function, and tissue perfusion, respectively. This approach to early noninvasive monitoring is based on recent evidence suggesting that poor tissue perfusion and oxygenation initiate circulatory dysfunction that leads to shock and organ failure. We studied 303 acute episodes of circulatory dysfunction and shock in 261 patients in a university-run county hospital; 75 were acute traumatic injuries and 109 acute nontrauma medical emergencies on admission to the emergency department, and 77 ICU patients with an acute illness or exacerbation of their current illness. The study was a prospective, descriptive study to identify early abnormal circulatory patterns reflecting the cardiac, pulmonary, and perfusion functions associated with death and with survival. We described noninvasively monitored patterns in individual illustrative cases, in common etiologic groups, and in physiologic categories representing various abnormal functional patterns. We found that hypotensive shock usually was preceded by episodes of high flow followed by low flow and inadequate tissue perfusion indicated by reduced PtCO2; this frequent pattern was modified by associated co-morbid conditions, especially hypovolemia, limited cardiac reserve capacity, age, hypertensive states, and increased body metabolism from infection, trauma, stress, exercise, temperature, and endocrine disorders. Reduced pulmonary function occurred in 18% of emergency patients; these were usually patients with thoracic trauma, severe hypovolemia, head injuries, chronic obstructive pulmonary disease, asthma, drug overdose, and central nervous system failure (massive stroke and coma). We concluded that noninvasive measurements identify early circulatory problems reliably and provide objective criteria for physiologic analysis as well as for definition of therapeutic goals and titration of therapy.

Application of an artificial intelligence program to therapy of high-risk surgical patients.

We developed an artificial intelligence program from a large computerized database of hemodynamic and oxygen transport measurements together with prior studies defining survivors' values, outcome predictors, and a branched-chain decision tree. The artificial intelligence program was then tested on the data of 100 survivors and 100 nonsurvivors not used for the development of the program or other analyses. Using the predictor as a surrogate outcome measure, the therapy recommended by the program improved the predicted outcome 3.16% per therapeutic intervention while the actual therapy given increased outcome 1.86% in surviving patients; the artificial intelligence-recommended therapy improved outcome 7.9% in nonsurvivors, while the actual therapy given increased predicted outcome -0.29% in nonsurvivors (p < .05). There were fewer patients whose predicted outcome decreased after recommended treatment (14%) than after the actual therapy given (37%). Review of therapy recommended by the program did not reveal instances of inappropriate or potentially harmful recommendations.