Detection of heterogeneous drug-protein binding by frontal analysis and high-performance affinity chromatography.

This study examined the use of frontal analysis and high-performance affinity chromatography for detecting heterogeneous binding in biomolecular interactions, using the binding of acetohexamide with human serum albumin (HSA) as a model. It was found through the use of this model system and chromatographic theory that double-reciprocal plots could be used more easily than traditional isotherms for the initial detection of binding site heterogeneity. The deviations from linearity that were seen in double-reciprocal plots as a result of heterogeneity were a function of the analyte concentration, the relative affinities of the binding sites in the system and the amount of each type of site that was present.

Temporal trends in neonatal outcomes following iatrogenic preterm delivery.

Background: Preterm birth rates have increased substantially in the recent years mostly due to obstetric intervention. We studied the effects of increasing iatrogenic preterm birth on temporal trends in perinatal mortality and serious neonatal morbidity in the United States.

Methods: We used data on singleton and twin births in the United States, 1995-2005 (n = 36,399,333), to examine trends in stillbirths, neonatal deaths, and serious neonatal morbidity (5-minute Apgar ≤3, assisted ventilation ≥30 min and neonatal seizures).

The Canadian Perinatal Network: a national network focused on threatened preterm birth at 22 to 28 weeks' gestation.

Objective: The Canadian Perinatal Network (CPN) maintains an ongoing national database focused on threatened very preterm birth. The objective of the network is to facilitate between-hospital comparisons and other research that will lead to reductions in the burden of illness associated with very preterm birth.

Methods: Women were included in the database if they were admitted to a participating tertiary perinatal unit at 22+0 to 28+6 weeks' gestation with one or more conditions most commonly responsible for very preterm birth, including spontaneous preterm labour with contractions, incompetent cervix, prolapsing membranes, preterm prelabour rupture of membranes, gestational hypertension, intrauterine growth restriction, or antepartum hemorrhage.

Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, pre-eclampsia and chronic hypertension with superimposed pre-eclampsia. Pre-eclampsia complicates about 3% of pregnancies, and all hypertensive disorders affect about five to 10% of pregnancies. Secular increases in chronic hypertension, gestational hypertension and pre-eclampsia have occurred as a result of changes in maternal characteristics (such as maternal age and pre-pregnancy weight), whereas declines in eclampsia have followed widespread antenatal care and use of prophylactic treatments (such as magnesium sulphate).

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.

Background: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder.

Timing of delivery for pregnancies with congenital diaphragmatic hernia.

A recent report has suggested that delivery at early term ages may be associated with lower mortality among infants with congenital diaphragmatic hernia. We sought to confirm this finding by examining gestational age-specific mortality in the USA in term infants with isolated congenital diaphragmatic hernia, delivered following the spontaneous onset of labour. In the final population of 928 infants, neonatal and infant mortality decreased with advancing gestation, from 25 and 36% at 37 weeks of gestation, respectively, to 17 and 20% at 40 weeks of gestation, respectively.

Optimal timing of delivery in pregnancies with pre-existing hypertension.

Objective: To determine the optimal timing of delivery in pregnancies with pre-existing (chronic) hypertension by quantifying the gestational age-specific risks of stillbirth associated with ongoing pregnancy and the gestational age-specific risks of neonatal mortality or serious neonatal morbidity following the induction of labour.

Design: Population-based cohort study.

Setting: USA.

Temporal trends and regional variations in severe maternal morbidity in Canada, 2003 to 2007.

Objective: To identify temporal trends and regional variations in severe maternal morbidity in Canada using routine hospitalization data.

Methods: We used a previously identified set of International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10CA) and Canadian Classification of Interventions (CCI) codes to estimate rates of severe maternal morbidity in Canada (excluding Quebec) for 2003 to 2007 using the Discharge Abstract Database of the Canadian Institute for Health Information (CIHI). Rates and 95% confidence intervals were calculated by year and within each province and territory and contrasted using the chi-square or Fisher exact test.

Severe maternal morbidity in Canada, 2003 to 2007: surveillance using routine hospitalization data and ICD-10CA codes.

Objective: To examine the feasibility of using routine labour and delivery hospitalization data and international classification of diseases (ICD-10CA) codes for carrying out surveillance of severe maternal morbidity in Canada.

Methods: We identified ICD-10CA diagnosis codes and Canadian Classification of Interventions (CCI) procedure codes associated with severe maternal illness. Severe maternal morbidity rates in Canada (excluding Quebec) for the period 2003 to 2007 were estimated using the Discharge Abstract Database of the Canadian Institute for Health Information.

Binding of tolbutamide to glycated human serum albumin.

The presence of elevated levels of glucose in blood during diabetes can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). This study examined the changes that occur in binding of the sulfonylurea drug tolbutamide to HSA as the level of glycation for this protein was increased. High-performance affinity chromatography was used in this work along with columns containing various preparations of in vitro glycated HSA.

Single umbilical artery risk factors and pregnancy outcomes.

Objective: To identify risk factors for fetuses and neonates with single umbilical artery and isolated single umbilical artery (single umbilical artery in the absence of chromosomal abnormalities and structural abnormalities) and to assess whether there is an increased risk for complications during pregnancy, labor, and delivery, and for perinatal morbidity and mortality.

Methods: A population-based retrospective cohort analysis of deliveries in Nova Scotia, Canada, between 1980 and 2002 was conducted using the Nova Scotia Atlee Perinatal Database. Risk factors and outcomes for single umbilical artery and isolated single umbilical artery pregnancies were compared with three-vessel-cord pregnancies.

Chromatographic analysis of acetohexamide binding to glycated human serum albumin.

Acetohexamide is a drug used to treat type II diabetes and is tightly bound to the protein human serum albumin (HSA) in the circulation. It has been proposed that the binding of some drugs with HSA can be affected by the non-enzymatic glycation of this protein. This study used high-performance affinity chromatography to examine the changes in acetohexamide-HSA binding that take place as the glycation of HSA is increased.

Biointeraction analysis of carbamazepine binding to alpha1-acid glycoprotein by high-performance affinity chromatography.

Interactions of the drug carbamazepine with the serum protein alpha(1)-acid glycoprotein (AGP) were examined by high-performance affinity chromatography. Frontal analysis studies with an immobilized AGP column and control column indicated carbamazepine had both low-affinity interactions with the support and high-affinity interactions with AGP. When a correction was made for binding to the support, the association equilibrium constant measured at pH 7.

The effects of glycation on the binding of human serum albumin to warfarin and L-tryptophan.

Diabetes leads to elevated levels of glucose in blood which, in turn, can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). It has been suggested that this increase in glycation can alter the ability of HSA to bind to drugs and other small solutes. This study used high-performance affinity chromatography (HPAC) to see if there is any significant change related to glycation in the binding of HSA to warfarin and l-tryptophan, which are often used as probe compounds for Sudlow sites I and II of HSA in drug binding studies with this protein.

Decreased term and postterm birthweight in the United States: impact of labor induction.

Objective: We sought to assess recent trends in falling mean birthweight (BW) and gestational age (GA) among US non-Hispanic white singleton live births >or=37 weeks of gestation and the contribution of increased rates of induction to these trends.

Study Design: This was an ecological study based on US vital statistics from 1992 through 2003.

Results: From 1992 through 2003, mean BW fell by 37 g, mean GA by 3 days, and macrosomia rates by 25%.

Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography.

Sulfonylurea drugs are often prescribed as a treatment for type II diabetes to help lower blood sugar levels by stimulating insulin secretion. These drugs are believed to primarily bind in blood to human serum albumin (HSA). This study used high-performance affinity chromatography (HPAC) to examine the binding of sulfonylureas to HSA.

Influence of ultrasound-to-delivery interval and maternal-fetal characteristics on validity of estimated fetal weight.

Objectives: To explore the effects of ultrasound-to-delivery interval and maternal-fetal characteristics on the distribution of measurement error in estimated fetal weights (EFWs), and to determine the predictive ability of EFW for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) among infants delivered within 1 day of an ultrasound examination.

Methods: Percentage differences between EFW and birth weights were calculated in 3697 pregnancies. Linear regression was used to compare the accuracy of EFW for births on each of the 6 days after an ultrasound scan with the accuracy observed among births on the same day.

Effect of domperidone on the composition of preterm human breast milk.

Objective: Domperidone is increasingly prescribed to improve breast milk volume despite a lack of evidence regarding its effects on breast milk composition. We examined the effect of domperidone on the nutrient composition of breast milk.

Patients And Methods: Forty-six mothers who had delivered infants at <31 weeks' gestation, who experienced lactation failure, were randomly assigned to receive domperidone or placebo for 14 days.

Co-bedding as a Comfort measure For Twins undergoing painful procedures (CComForT Trial).

Background: Co-bedding, a developmental care strategy, is the practice of caring for diaper clad twins in one incubator (versus separating and caring for each infant in separate incubators), thus creating the opportunity for skin-to-skin contact and touch between the twins. In studies of mothers and their infants, maternal skin-to-skin contact has been shown to decrease procedural pain response according to both behavioral and physiological indicators in very preterm neonates. It is uncertain if this comfort is derived solely from maternal presence or from stabilization of regulatory processes from direct skin contact.

Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group.

Background: Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Several recent publications have noted an increasing trend in incidence over time. The international PPH collaboration was convened to explore the observed trends and to set out actions to address the factors identified.

Prenatal corticosteroid prophylaxis for women delivering at late preterm gestation.

Objective: We studied patterns of prenatal corticosteroid use, respiratory distress syndrome, and associated mortality rates to assess the congruence between knowledge and clinical practice related to such prophylaxis.

Methods: We used data on all live births in the United States (for the years 1989-1991, 1995-1997, and 2002-2004) and Nova Scotia, Canada (for the years 1988-2007). Gestational age-specific temporal trends in infant deaths resulting from respiratory distress syndrome were quantified in the United States, and gestational age-specific temporal trends in corticosteroid use and morbidity (respiratory distress syndrome and intraventricular hemorrhage) were quantified in Nova Scotia.

Cognitive elements in clinical decision-making: toward a cognitive model for medical education and understanding clinical reasoning.

Physician cognition, metacognition and affect may have an impact upon the quality of clinical reasoning. The purpose of this study was to examine the relationship between measures of physician metacognition and affect and patient outcomes in obstetric practice. Reflective coping (RC), proactive coping, need for cognition (NFC), tolerance for ambiguity, state-trait anxiety and metacognitive awareness were assessed for obstetricians (n = 12) who provided intra-partum care to 4,149 women.