Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P

Chopper, a new death domain of the p75 neurotrophin receptor that mediates rapid neuronal cell death

The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75(NTR)) has been found to be necessary and sufficient to initiate neural cell death. The region was named Chopper to distinguish it from CD95-like death domains. A 29-amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and nonneural cell types and was not inhibited by signaling through Trk (unlike killing by full-length p75(NTR)). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner, blocking p75(NTR)-mediated death both in vitro and in vivo. Removal of the ectodomain of p75(NTR) increased the potency of Chopper activity, suggesting that it regulates the association of Chopper with downstream signaling proteins.

Community structure of Quaternary coral reefs compared with Recent life and death assemblages

This paper assesses the reliability with which fossil reefs record the diversity and community structure of adjacent Recent reefs. The diversity and taxonomic composition of Holocene raised fossil reefs was compared with those of modern reef coral life and death assemblages in adjacent moderate and low-energy shallow reef habitats Of Madang Lagoon, Papua New Guinea. Species richness per sample area and Shannon-Wiener diversity (H') were highest in the fossil reefs, intermediate in the life assemblages, and lowest in the death assemblages. The taxonomic composition of the fossil reefs was most similar to the combination of the life and death assemblages from the modern reefs adjacent to the two fossil reefs. Depth zonation was recorded accurately in the fossil reefs. The Madang fossil reefs represent time-averaged composites of the combined life and death assemblages as they existed at the time the reef was uplifted. Because fossil reefs include overlapping cohorts from the life and death assemblages, lagoonal facies of fossil reefs are dominated by the dominant sediment-producing taxa, which are not necessarily the most abundant in the life assemblage. Rare or slow-growing taxa accumulate more slowly than the encasing sediments and are underrepresented in fossil reef lagoons. Time-averaging dilutes the contribution of rare taxa, rather than concentrating their contribution. Consequently, fidelity indices developed for mollusks in sediments yield low values in coral reef death and fossil assemblages. Branching corals dominate lagoonal facies of fossil reefs because they are abundant, they grow and produce sediment rapidly, and most of the sediment they produce is not exported. Fossil reefs distinguished kilometer-scale variations in community structure more clearly than did the modern life assemblages. This difference implies that fossil,reefs may provide a better long-term record of community structure than modern reefs. This difference also suggests that modern kilometer-scale variation in coral reef community structure may have been reduced by anthropogenic degradation, even in the relatively unimpacted reefs of Madang Lagoon. Holocene and Pleistocene fossil reefs provide a time-integrated historical record of community composition and may be used as long-term benchmarks for comparison with modern, degraded, nearshore reefs. Comparisons between fossil reefs and degraded modern reefs display gross changes in community structure more effectively than they demonstrate local extinction of rare taxa.

Low-affinity neurotrophin receptor with targeted mutation of exon 3 is capable of mediating the death of axotomized neurons

1. In vivo studies have shown that the low-affinity 75 kDa neurotrophin receptor (p75NTR) is involved in axotomy-induced cell death of sensory and motor neurons. To further examine the importance of p75NTR in mediating neuronal death in vivo , we examined the effect of axotomy in the p75NTR-knockout mouse, which has a disrupted ligand-binding domain. 2. The extent of sensory and motor neuron loss in the p75NTR-knockout mouse following axotomy was not significantly different to that in wild-type mice. This suggests that disruption of the ligand-binding domain is insufficient to block the cell death process in axotomized neurons. 3. Immunohistochemical studies showed that axotomized neurons continue to express this mutant receptor with its intracellular death-signalling moiety intact. 4. Treatment with antisense oligonucleotides targeted against p75NTR resulted in significant reduction in the loss of axotomized neurons in the knockout mouse. 5. These data suggest that the intracellular domain of p75NTR is essential for death-signalling and that p75NTR can signal apoptosis, despite a disrupted ligand-binding domain.

Effects of age and alcohol exposure during early life on pyramidal cell numbers in the CA1-CA3 region of the rat hippocampus

We have previously shown that exposing rats to a relatively high dose of ethanol during early postnatal life can result in an alteration in spatial learning ability. The hippocampal formation is known to be involved in the control of this ability. The purpose of the present study was to determine whether exposure of rats to ethanol during early postnatal life had either immediate or delayed effects on the numbers of pyramidal cells in the CA1-CA3 subregion of the hippocampus. Wistar rats were exposed to a relatively high daily dose of ethanol at postnatal day 10-15 by placing them for 3 h/day in a chamber containing ethanol vapor. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anesthetized and killed at 16 and 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volumes of the CA1 and CA2+CA3 regions. The physical disector method was used to estimate the numerical density of neurons in each of the subdivisions. The total number of pyramidal cells was calculated by multiplying the appropriate estimates of the numerical density by the volume. There were significant age-related reductions in the total numbers of pyramidal cells at 16-30 days of age irrespective of the groups examined. Ethanol treated rats were found to have slightly but significantly fewer pyramidal cell neurons than either the MRC or SC groups. These observations indicate that pyramidal cells in the hippocampus may be vulnerable to a relatively high dose of ethanol exposure during this short period of early postnatal life. (C) 2003 Wiley-Liss, Inc.

How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis m patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance-that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including die possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients mid for patients with heart failure at all stages of disease.

Effects of maternal glycemia on fetal heart rate in pregnancies complicated by pregestational diabetes mellitus

Objective: To investigate the influence of maternal glycemia on fetal heart rate (FHR) parameters analyzed by computerized cardiotocography in fetuses of diabetic mothers in the third trimester. Study design: Thirty-nine pregnant women with pregestational diabetes mellitus were studied prospectively. The inclusion criteria were a diagnosis of pregestational diabetes, singleton pregnancy between 36 and 40 weeks, and absence of fetal abnormalities. Computerized cardiotocography (System 8002) was performed over a period of 60 min and capillary glycemia was measured immediately before and 30 and 60 min after the beginning of the exam. The evaluations were done 2 h after lunch. Results: Nineteen patients (48.7%) presented mean glycemia >= 120 mg/dL The mean basal FHR was 136.7 +/- 10.0 bpm in the group with glycemia <120 mg/dL and 144.8 +/- 9.4 bpm in the group with glycemia >= 120 mg/dL (p = 0.013, Student`s t test). There was a significant positive correlation (Pearson`s test, p = 0.0001, r = 0.57) between basal FHR and mean glycemia. A significant negative correlation was observed between short-term variation and mean glycemia (Pearson`s test, p = 0.003, r = -0.47). No significant differences were observed between the other indices evaluated by computerized cardiotocography and glycemia. Conclusions: Maternal hyperglycemia at the time of cardiotocography is associated with elevated FHR. It seems to be important to understand how FHR parameters are influenced by maternal glycemic status at the time of fetal assessment in pregnancies complicated by diabetes. (C) 2009 Published by Elsevier Ireland Ltd.

Morphometric Study on the Anatomy of the Fetal Cricoid Cartilage and Comparison Between Its Inner Diameter and Endotracheal Tube Sizes

Objectives: The high incidence of respiratory disorders is one of the main problems in perinatal medical care. With the increased use of intubation, the incidence of laryngeal injury causing stenosis has also increased. The principal constriction point in the infant`s larynx is the midcricoid area. We sought to provide detailed morphometric data on the anatomy of the cricoid cartilage and its relationship with growth and body characteristics of fetuses at 5 to 9 months of gestational age. Methods: Nineteen larynges obtained from 17 stillborn infants and 2 newborn infants ranging in gestational age from 5 to 9 months were studied. Measurements of the cricoid cartilage were made with a millimeter-graded caliper. Results: Weight was the variable most correlated with cricoid measurements. The cricoid lumen configuration showed an almost elliptic shape and did not change with gestational age. The mean inner subglottic cricoid area was 19.27 +/- 9.62 mm(2) and was related to weight and body surface area. Cricoid growth was more pronounced at the outer portion of the cartilage. Conclusions: The cricoid lumen configuration was elliptic, and its mean area was smaller than that of available endotracheal tubes. This lumen area was most influenced by weight and height.

Risk factors for sudden unexpected cardiac death in Tasmanian men

Background: Sudden unexpected cardiac death (SUCD) accounts for approximately 25% of deaths from ischaemic heart disease (IHD) but is relatively poorly understood because of the difficulties involved in researching aetiology. Clinical differences between instances of SUCD and those cases of acute chest pain that survive long enough to be proven as myocardial infarction but are eventually fatal might reflect differences in aetiology. Aims: To determine the risk factors for sudden unexpected cardiac death in Tasmanian men. Methods: A population-based case-control method was used with the study population, an estimated 125,225 men aged 25-74 years living in the island State of Tasmania, Australia. The case group of 102 men who had a SUCD was validated using necropsy reports, hospital records and information provided by the usual general practitioner. Cases were matched with 204 community controls. Spouses or partners of eligible subjects answered a detailed questionnaire. Multi-variate odds ratios (ORs) for risk factors were calculated using stepwise analysis. Results: Risk factors measured included: smoking habit, treated hypertension, hypercholesterolaemia, diabetes mellitus, family history of LHD, alcohol intake and exercise habits. Independent risk factors for SUCD were: history of diabetes mellitus (OR=4.2, 95% CI: 1.39, 12.81), current smoking status (OR=3.5, 95% CI: 1.80, 6.82), and family history of IHD (OR=2.6, 95% CI: 1.34, 4.92). Conclusions: Some accepted risk factors for acute myocardial infarction (AMI) also predict sudden death in men with no history of coronary disease. Efforts to reduce smoking, the incidence of diabetes mellitus and mean blood pressure must be continued as SUCD is, by definition, untreatable but is potentially avoidable in many instances.

Limiting conditional distributions for birth-death processes

In a recent paper [16], one of us identified all of the quasi-stationary distributions for a non-explosive, evanescent birth-death process for which absorption is certain, and established conditions for the existence of the corresponding limiting conditional distributions. Our purpose is to extend these results in a number of directions. We shall consider separately two cases depending on whether or not the process is evanescent. In the former case we shall relax the condition that absorption is certain. Furthermore, we shall allow for the possibility that the minimal process might be explosive, so that the transition rates alone will not necessarily determine the birth-death process uniquely. Although we shall be concerned mainly with the minimal process, our most general results hold for any birth-death process whose transition probabilities satisfy both the backward and the forward Kolmogorov differential equations.

Pregnancy outcome in juvenile systemic lupus erythematosus: A Brazilian multicenter cohort study

Objective. To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). Methods. A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients` medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. Results. A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria >= 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. Conclusion. We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.