Determination of T1pH relaxation rates in charred and uncharred wood and consequences for NMR quantitation

The performance of three different techniques for determining proton rotating frame relaxation rates (T1pH) in charred and uncharred woods is compared. The variable contact time (VCT) experiment is shown to over-estimate T1pH, particularly for the charred samples, due to the presence of slowly cross-polarizing C-13 nuclei. The variable spin (VSL) or delayed contact experiment is shown to overcome these problems; however, care is needed in the analysis to ensure rapidly relaxing components are not overlooked. T1pH is shown to be non-uniform for both charred and uncharred wood samples; a rapidly relaxing component (T1pH = 0.46-1.07 ms) and a slowly relaxing component (T1pH = 3.58-7.49) is detected in each sample. T1pH for each component generally decreases with heating temperature (degree of charring) and the proportion of rapidly relaxing component increases. Direct T1pH determination (via H-1 detection) shows that all samples contain an even faster relaxing component (0.09-0.24 ms) that is virtually undetectable by the indirect (VCT and VSL) techniques. A new method for correcting for T1pH signal losses in spin counting experiments is developed to deal with the rapidly relaxing component detected in the VSL experiment. Implementation of this correction increased the proportion of potential C-13 CPMAS NMR signal that can be accounted for by up to 50% for the charred samples. An even greater proportion of potential signal can be accounted for if the very rapidly relaxing component detected in the direct T1pH determination is included; however, it must be kept in mind that this experiment also detects H-1 pools which may not be involved in H-1-C-13 cross-polarization. (C) 2002 Elsevier Science (USA).

Growth hormone-binding protein in normal and pathologic gestation: Correlations with maternal diabetes and fetal growth

To date, measurements of GH-binding protein (GHBP) during human pregnancy have been carried out using;assays susceptible to interference by the elevated levels of human placental GH typical of late gestation. We recruited a large cohort of pregnant women (n = 140) for serial measurements of GHBP and used the ligand immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90 nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and 0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP levels in pregnancies complicated by noninsulin-dependent diabetes mellitus (NIDDM) were substantially elevated at all gestational ages. The mean value in the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01). In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed reduced GHBP concentrations at 36-38 weeks. The correlation between body mass index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks gestation, GHBP was significantly elevated (P < 0.01) in those women whose neonates had low birth weight (

Effect of restricted feed intake on early reproductive development in Large White gilts

Forty-five Large White gilts were used to study the effect of energy intake from 28 to 176 d of age on body composition and reproductive development. From 28 to 60 d, the gilts were fed ad libitum a 16.6 MJ DE/kg, 24% crude protein and 1.3% total lysine diet. From 61 d of age three dietary treatments were used; 1) ad libitum access to feed (15.6 MJ DE/kg, 21% crude protein and 1.07% total lysine) (H), 2) feed offered at 75% (M) of the previous days intake of H, and 3) feed offered at 60% (L) of the previous days intake of H. ADG from 61 to 176 d of age was (p <0.05) affected by treatment. Although live weight at 176 d of age did not differ (p >0.1) the H gilts had higher (p <0.08) carcass weights than the M or L gilts. Back fat depths were similar (p >0.1) for all treatments at 115 d of age, however by 176 d of age M and H gilts were fatter (p <0.1) than L gilts. The mean lipid deposition (LD) from 115 to 176 d of age for L gilts (78.9 g/d) was less (p <0.05) than for M gilts (143.6 g/d) and H gilts (135.6 g/d). There were no differences between treatments for protein deposition (PD) over the same period. More (p <0.05) H gilts (n=8) attained puberty (first observed estrus) than either M gilts or L gilts (n=4 for both). Follicle numbers were similar (p >0.1) across treatments. For gilts that attained puberty, H gilts had fewer (p <0.05) follicles (13.5) than M gilts (19.7) and L gilts (21.3). For gilts with follicular development, H gilts had the heaviest (458.7 g) reproductive tract weight (RTW). However, for those that attained puberty, L gilts had the heaviest RTW. RTW were lowest for those with no follicular development. Energy restriction had a negative impact on puberty attainment, i.e. it took longer to reach puberty. However, for gilts that attained puberty, the number of follicles was greater for those on lower feed intakes. It would appear that rate of fat deposition, but not necessarily the total amount of fat, plays an important role in puberty attainment.

Aerobic cultivation of Streptococcus zooepidemicus and the role of NADH oxidase

A metabolic flux model was developed for Streptococcus zooepidemicus to compare the metabolism of glucose and maltose during aerobic batch cultivation. Lactic acid was the main product of glucose metabolism whereas acetic acid was the main product of maltose metabolism. This difference was chiefly attributed to the two-fold higher flux through NADH oxidase in maltose-grown cells that enabled the ATP generation rate to remain high despite a slower maltose consumption rate. The two-fold higher flux was matched by a two-fold increase in NADH oxidase activity, 2.53 +/- 0.1 mumol NADH min(-1) mg(-1) protein on maltose versus 1.07 +/- 0.04 Rmol NADH min(-1) mg(-1) protein on glucose, indicating that NADH oxidase activity is regulated by the energy status of the cell. Surprisingly, the energy status of the cell had little impact on hyaluronic acid (HA) yield and molecular weight. (C) 2003 Elsevier Science B.V. All rights reserved.

A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia

Based on the epidemiological finding that individuals with schizophrenia tend to be born in winter/spring when compared to the general population, we examined (1) the strength and timing of this effect in Northern Hemisphere sites, and (2) the correlation between the season of birth effect size and latitude. Studies were located via electronic data sources, published citations, and letters to authors. Inclusion criteria were that studies specify the diagnostic criteria used, that studies specify the counts of schizophrenia and general population births for each month, and that subjects and the general population be drawn from the same birth years and catchment area. We extracted data from eight studies based on 126,196 patients with schizophrenia and 86,605,807 general population births and drawn from 27 Northern Hemisphere sites. Comparing winter/spring versus summer/autumn births, we found a significant excess for winter/spring births (pooled odds ratio = 1.07; 95% confidence interval 1.05, 1.08; population attributable risk = 3.3%). There was a small but significant positive correlation between the odds ratios for the season of birth comparison and latitude (r = 0.271, p < 0.005). Furthermore, the shape of the seasonality in schizophrenia births varied by latitude band. These variations may encourage researchers to generate candidate seasonally fluctuating exposures.

Mode II delamination testing in uniaxially oriented PVC pipes

The mode II fracture toughness of an oriented PVC pipe was measured using an End Notched Flexure test geometry. A relatively low value of G(IIC) was found of 1.07 kJ m(-2) and this indicates that it is energetically more favorable for a crack to propagate in the tangential direction rather than radially through the wall of the pipe. Examination of the mechanism of crack advanced showed that although the crack was propagating globally in mode II, micro-cracks were opening ahead of the crack in mode I or in mixed mode. Growth of the crack occurred by linking up of these micro-cracks. This is similar to the mechanism found for mode II cracking in carbon fibre epoxy composites. (C) 2004 Kluwer Academic Publishers.

Effect of pravastatin on cardiovascular events in people with chronic kidney disease

Background - Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. Methods and Results - We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin ( 40 mg daily) versus placebo. Of 19 700 subjects, 4491 ( 22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m(2) body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome ( adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome ( HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function ( HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD ( adjusted HR 0.86, 95% CI 0.74 to 1.00, P = 0.045). Conclusions - Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

Cold periods and coronary events: an analysis of populations worldwide

Study objective: To investigate the association between cold periods and coronary events, and the extent to which climate, sex, age, and previous cardiac history increase risk during cold weather. Design: A hierarchical analyses of populations from the World Health Organisation's MONICA project. Setting: Twenty four populations from the WHO's MONICA project, a 21 country register made between 1980 and 1995. Patients: People aged 35 - 64 years who had a coronary event. Main results: Daily rates of coronary events were correlated with the average temperature over the current and previous three days. In cold periods, coronary event rates increased more in populations living in warm climates than in populations living in cold climates, where the increases were slight. The increase was greater in women than in men, especially in warm climates. On average, the odds for women having an event in the cold periods were 1.07 higher than the odds for men (95% posterior interval: 1.03 to 1.11). The effects of cold periods were similar in those with and without a history of a previous myocardial infarction. Conclusions: Rates of coronary events increased during comparatively cold periods, especially in warm climates. The smaller increases in colder climates suggest that some events in warmer climates are preventable. It is suggested that people living in warm climates, particularly women, should keep warm on cold days.

Population pharmacokinetics of metformin in late pregnancy

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes, 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method, A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in'NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0. 1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 ka (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, ea, effects on neonatal obesity and insulin resistance, remain unknown.

Hearing sensitivity and bone mineral density in older adults: the Health, Aging and Body Composition Study

Bone mineral density (BMD) may be associated with hearing loss in older adults. Demineralization of the cochlear capsule has been associated with hearing loss in those with Paget's disease of the bone and otosclerosis. Osteoporosis may also result in cochlear capsule demineralization. We hypothesized that lower hip BMD and lower heel ultrasound measurements would be associated with hearing loss in a population-based sample of 2,089 older black and white men and women. Bone parameters and hearing function were measured at the fourth clinical follow-up visit. Audiometric threshold testing was used to measure air- and bone-conduction hearing sensitivity. BMD of the hip and its subregions was measured using dual-energy X-ray absorptiometry. Calcaneal bone measurements [broadband ultrasound attenuation (BUA), speed of sound (SOS) and the quantitative ultrasound index (QUI)] were obtained using heel ultrasound. After adjusting for known hearing loss risk factors, no association was found between hearing and any of the bone measurements in whites and black women. In black men, however, lower hip BMD was associated with higher odds of hearing loss; for each standard deviation decrease in total hip BMD, the odds of hearing loss were 1.41 (95% confidence interval 1.08, 1.83), 1.39 (95% CI 1.07, 1.82) for femoral neck BMD and 1.65 (95% CI 1.26, 2.16) for trochanter BMD. Conductive hearing loss was associated with lower heel ultrasound measurements, though only among white men. The results of this study are mixed and inconclusive. Lower BMD of the hip and its subregions was associated with hearing loss among black men, but not among whites or black women. Lower measurements on heel ultrasound were associated with conductive hearing loss, though only among white men. These results suggest that axial and appendicular bone parameters may be modestly associated with hearing loss in older men, but not in women.

Reduced between-hospital variation in short term survival after acute myocardial infarction: the result of improved cardiac care?

Objectives: To re-examine interhospital variation in 30 day survival after acute myocardial infarction ( AMI) 10 years on to see whether the appointment of new cardiologists and their involvement in emergency care has improved outcome after AMI. Design: Retrospective cohort study. Setting: Acute hospitals in Scotland. Participants: 61 484 patients with a first AMI over two time periods: 1988 - 1991; and 1998 - 2001. Main outcome measures: 30 day survival. Results: Between 1988 and 1991, median 30 day survival was 79.2% ( interhospital range 72.1 - 85.1%). The difference between highest and lowest was 13.0 percentage points ( age and sex adjusted, 12.1 percentage points). Between 1998 and 2001, median survival rose to 81.6% ( and range decreased to 78.0 - 85.6%) with a difference of 7.6 ( adjusted 8.8) percentage points. Admission hospital was an independent predictor of outcome at 30 days during the two time periods ( p< 0.001). Over the period 1988 - 1991, the odds ratio for death ranged, between hospitals, from 0.71 ( 95% confidence interval ( CI) 0.58 to 0.88) to 1.50 ( 95% CI 1.19 to 1.89) and for the period 1998 - 2001 from 0.82 ( 95% CI 0.60 to 1.13) to 1.46 ( 95% CI 1.07 to 1.99). The adjusted risk of death was significantly higher than average in nine of 26 hospitals between 1988 and 1991 but in only two hospitals between 1998 and 2001. Conclusions: The average 30 day case fatality rate after admission with an AMI has fallen substantially over the past 10 years in Scotland. Between-hospital variation is also considerably less notable because of better survival in the previously poorly performing hospitals. This suggests that the greater involvement of cardiologists in the management of AMI has paid dividends.