bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivery of singleton preterm infants in New South Wales, 1990–1997
Authors: Roberts Christine L. , Algert Charles S. , Raynes‐Greenow Camille , Peat Brian , Henderson‐Smart David J. 
Published: March 2003

AbstractObjective: To examine trends in the maternal characteristics and delivery of singleton preterm infants in an Australian population.Design: Population‐based descriptive study.Setting: New South Wales (NSW), Australia.Population: The population included 37 500 singleton preterm births from 1 January 1990 to 31 December 1997.Methods: Data were obtained from the NSW Midwives’ Data Collection (MDC) and rates over time were calculated. Preterm birth by Caesarean section before the onset of labour or where labour was induced were considered to be medically indicated.Main outcome measures: Preterm rates, medically indicated preterm birth rates, mode of delivery and neonatal outcomes, and trends over time.Results: Among singleton infants, there was no significant change over time in the rate of preterm birth (annual average 5.5%), preterm births that were medically indicated (annual average 29.3%) or neonatal outcomes of preterm births. The rate of indicated preterm birth varied by gestational age and was highest (39.7%) at 29–32 weeks’ gestation. Instrumental preterm births declined over time from 9.5 to 7.8% with a shift from forceps to vacuum use and episiotomy rates declined from 19.7 to 14.8%.Conclusions: Increases in the reported overall preterm rate (singletons and multiples) were not due to increased delivery of singleton infants. Changes in the management of singleton preterm births were similar to changes observed in term births such as decreasing forceps and episiotomy usage. It may be to time to reassess whether Australian clinicians would be willing to randomise patients to clinical trials of the best method of delivery for preterm infants.
Outpatient management of abnormal smears
Authors: Ward Bruce G , Broe Stephen J 
Published: March 2003

AbstractObjectives: To review the results of the first 403 women treated at the Abnormal Smear and Colposcopy Unit with special reference to the utility, efficacy, acceptability and economy of in‐office treatment of cervical lesions by large loop or Fischer cone excision.Design: Retrospective chart review of consecutive patients treated following, referral with an abnormal smear or abnormal cervical morphology, between 1 September 1996 and 1 August 2001.Setting: Inner city private practice.Sample: A total of 403 consecutive General Practitioner referred women.Methods: Details of referral smear result, colposcopically directed biopsy result, subsequent treatment type and histological result including assessability, number of specimens submitted, complications and follow‐up assessment were extracted at chart review. Costs of public hospital inpatient and outpatient care, supplied by the Casemix and Clinical Benchmarking Service, Mater Miseraecordae Public Hospitals (with permission to publish), were compared with Medicare rebates.Main outcome measures: A total of 187 women were treated by large loop excision of the transformation zone, and 216 by Fischer cone excision. The number of women who were treated as outpatients under local anaesthetic were 395, while eight patients were treated under general anaesthesia as inpatients. There was poor correlation between referring smear, biopsy and subsequent treatment results. Eight patients had abnormal cytology at follow‐up, of whom two have been retreated. Three patients had primary or secondary bleeding requiring treatment and two developed cervical stenosis. Outpatient private practice treatment of women with abnormal smears allows significant savings to the public purse over public or private hospital care.Conclusions: Outpatient treatment of women with abnormal smears, using the Fischer cone technique, is safe, well accepted, effective and the most cost efficient solution to this public health problem.
Prediction of serious complications in patients admitted to a surgical ward
Authors: Veltkamp S C , Kemmeren J M , van der Graaf Y , Edlinger M , van der Werken C 
Published: March 2003

AbstractBackgroundPrediction of complications is an essential part of risk management in surgery. Knowing which patients are at high risk of developing complications will contribute to the quality and cost reduction of surgery.MethodsAll patients admitted to a general surgical ward during a 1-year interval were followed until 30 days after discharge. Complications and data on potential risk factors were recorded prospectively. Relative risks were calculated for each risk factor and predictive values for the development of a serious or minor complication were computed using logistic regression analysis. The predictive values of different combinations of variables were expressed as receiver operating characteristic curves.ResultsOf 3075 patients, 375 suffered one or more serious complications and 319 experienced a minor complication. A model was developed for prediction of serious complications, consisting of 11 variables, with an area under the curve (AUC) of 0·79 (95 per cent confidence interval (c.i.) 0·76 to 0·81). The prognostic value of the model for minor complications (seven variables) was lower (AUC 0·68 (95 per cent c.i. 0·65 to 0·71)).ConclusionSerious complications in patients admitted to a surgical ward can be predicted using a model consisting of 11 variables. The risk score can be used in the decision-making process before surgery.
Effect ofin vivoadministration of anti-CTLA-4 monoclonal antibody and IL-12 on the induction of low-dose oral tolerance
Authors: BARONE K S , HERMS B , KARLOSKY L , MURRAY S , QUALLS J 
Published: March 2003

SummaryOral tolerance has been characterized as an immunological hyporesponsiveness to fed antigen. Previous studies have suggested that high-dose oral tolerance involves the preferential interaction of B7 with CTLA-4 on the T cell. To determine whether similar mechanisms are involved in the induction of low-dose oral tolerance, mice were treated with anti-CTLA-4 monoclonal antibody (MoAb), with or without IL-12, at the time of feeding. Results showed that anti-CTLA-4 MoAb alone failed to restore cellular proliferation, antibody titres and IFN-γ levels; however, IL-4 cytokine levels in OVA-fed mice were partially restored. In contrast, administration of IL-12 along with anti-CTLA-4 MoAb to mice during feeding completely prevented the suppression of Th1 immune responses, as shown by increased serum IgG2a titres, IFN-γ production and cell proliferation. These results suggest that blocking B7-CTLA-4 interactions in the presence of IL-12 prevents the induction of low-dose oral tolerance at the Th1 cell level.
Leaf dark respiration as a function of canopy position in Nothofagus fusca trees grown at ambient and elevated CO2 partial pressures for 5 years
Authors: Griffin K. L. , Tissue D. T. , Turnbull M. H. , Schuster W. , Whitehead D. 
Published: March 2003

Summary

Mass‐based and area‐based rates of respiration, leaf nitrogen content, leaf total protein content, non‐structural carbohydrates and leaf mass per unit area (LMA) all decreased with depth in the canopy of Nothofagus fusca (Hook. F.) Oerst. (Red beech) trees grown for 5 years at ambient (36 Pa) or elevated (66 Pa) CO2 partial pressures.
Elevated CO2 partial pressure had a strong effect on dark respiration, decreasing both mass‐based and area‐based rates at all canopy positions, but had little or no effect on leaf physical and biochemical properties.
Leaf sugars, starch, protein, N and LMA were all correlated with respiration rate, and are therefore strong predictors of area‐based dark respiration rates. The y axis intercept of regressions of respiration rate on mean leaf N, protein, starch and LMA was lower for plants grown at elevated compared to ambient CO2 partial pressures because of the differential effect of growth at elevated CO2 partial pressure on leaf gas‐exchange, chemical and physical characteristics.
The lower respiration rates for leaves from trees grown at elevated CO2 partial pressure resulted in a significant increase in the ratio of light‐saturated net photosynthesis to respiration, increasing the potential carbon‐use efficiency of these leaves.
Interspecific variation in potential water‐use efficiency and its relation to plant species abundance in a water‐limited grassland
Authors: Tsialtas J. T. , Handley L. L. , Kassioumi M. T. , Veresoglou D. S. , Gagianas A. A. 
Published: March 2003

Summary Interspecific and temporal variations in presumed water‐use efficiency, as measured by carbon isotope discrimination (Δ), were examined in a Greek semiarid herbaceous grassland, and the hypothesis tested that competition for water is a factor in determining vegetation structure. Experiments were conducted for 3 years in an upland grassland consisting of exclusively C3perennial species. The most abundant species were the grassesPoa pratensisL.,Lolium perenneL. andFestuca valida(Uechtr.) Penzes; the forbsAchillea millefoliumL.,Plantago lanceolataL. andTaraxacum officinaleWeber ex Wigg; and the legumeTrifolium repensL. Rooting depth did not explain plant Δ in this shallow‐soil site, where soil moisture was concentrated in the top of the profile. Although temporal variation for Δ was significant within most species, changes in ranking of species were slight throughout three growing seasons. Δ Was negatively related to species biomass production, which means that species’ abundances were positively related to species’ water‐use efficiencies. Δ Was positively related to leaf N content, which we interpret as an autocorrelation with water availability. The results of this study are consistent with the notion that, in an environment where water is scarce, plants may compete effectively by increasing their potential water‐use efficiency as measured by Δ, and that species abundance is regulated by competition‐driven water depletion.
A self‐assembling model of resource dynamics and plant growth incorporating plant functional types
Authors: Colasanti R. L. , Hunt R. , Askew A. P. 
Published: March 2003

Summary

We explored the ecological properties of a self‐assembling, cellular automaton model by simulating the behaviour of distinct plant functional types.
Types differed according to three fundamental traits: size of plant modules; longevity of modules in the absence of resources; and propensity to flowering.
When expressed at three levels apiece, the three traits were able to approximate the essential biology of seven important types within a well known system of plant functional types (the C‐S‐R system, based on disturbance and resource availability).
The seven types, when grown in real experiments with virtual communities, reproduced classical community‐level behaviour to the extent of demonstrating smooth, competitive replacements along gradients of resource or disturbance, or both.
In complex communities simulated over a wide range of environmental conditions, the seven types produced a clearly ‘humpbacked’ curve linking plant diversity to community productivity. The mixtures of species resulting from these experiments together represented all parts of C‐S‐R space.
These outcomes emerged solely from the ‘bottom‐up’ processes inherent in self‐assembling cellular automata. No community‐level specifications were inserted into the model, yet the community‐level consequences agreed with both the underlying predictions of C‐S‐R theory and field observations.
This work confirms that the dynamics of herbaceous plant communities can be emergent from the resource‐handling properties of the organs of the constituent species, and that a simple rule base can, to a first approximation, be sufficient to reproduce such dynamics.
Effects of low‐dose oral hydrocortisone replacement versus short‐term reproduction of physiological serum cortisol concentrations on insulin action in adult‐onset hypopituitarism
Authors: McConnell E. M. , Bell P. M. , Ennis C. , Hadden D. R. , McCance D. R. , Sheridan B. , Atkinson A. B. 
Published: March 2003

Summaryobjective Hypercortisolism is associated with impaired glucose tolerance and insulin resistance. For many years hydrocortisone 30 mg was the standard total daily replacement dose in adult hypopituitarism. The use of this conventional dose has now been shown to result in mild biochemical hypercortisolism and might contribute to the increased cardiovascular risk reported in hypopituitarism. The use of lower doses of hydrocortisone replacement therapy might prevent some of the adverse metabolic effects seen with conventional doses.patients In a randomized crossover study we assessed peripheral and hepatic insulin action in 15 ACTH‐deficient patients with normal glucose tolerance on two occasions while receiving either a low‐dose oral hydrocortisone replacement (LOR) therapy (15 mg at 0800, 5 mg at 1700) or a physiological hydrocortisone infusion (PHI), which achieved physiological serum cortisol concentrations.results Exogenous glucose infusion rates required to maintain euglycaemia were similar for the LOR and the PHI protocols (26·2 ± 0·4 vs. 23·8 ± 0·6 µmol/kg/min, respectively). Endogenous glucose production was also similar (12·0 ± 2·5 vs. 11·6 ± 2·4 µmol/kg/min, respectively) and in the post‐absorptive state suppressed to a similar extent following insulin (4·5 ± 2·0 vs. 5·1 ± 3·1 µmol/kg/min).conclusion Hydrocortisone replacement therapy at a dose of 15 mg with breakfast, 5 mg with evening meal does not increase peripheral or hepatic insulin resistance when compared to a hydrocortisone infusion designed to simulate physiological serum cortisol concentrations.
Correlation between midazolam and lignocaine pharmacokinetics and MEGX formation in healthy volunteers
Authors: Swart Eleonora L. , van der Hoven Ben , Johan Groeneveld A. B. , Touw Daniel J. , Danhof Meindert 
Published: March 2003

Aims  The objectives of the present investigation were: (a) to determine the correlation between lignocaine and midazolam pharmacokinetics following intravenous administration in healthy volunteers, (b) to determine the effects of treatment with an inhibitor of CYP3A4 (erythromycin) on this correlation and (c) to assess the precision of the MEGX‐test as a sole predictor of lignocaine and midazolam pharmacokinetics.Methods  The study was conducted in four male and four female healthy volunteers, aged between 21 and 26 years, who received 1 mg kg−1 lignocaine HCl i.v. on days 1, 3, 5, 9 and 10 of the investigation. On days 5 and 10 they also received midazolam, 0.075 mg kg−1 i.v. and from days 6–10 they took erythromycin 500 mg orally, four times daily. Following administration of lignocaine and midazolam, frequent venous blood samples were obtained for determination of the concentrations of lignocaine, MEGX and midazolam.Results  In the absence of erythromycin a statistically significant linear correlation was observed between the clearance of lignocaine and midazolam (CLmidazolam= 0.41×CLlignocaine+1.2; r2 = 0.857; P < 0.001). Erythromycin cotreatment resulted in a loss of the correlation between the two clearances (r2 = 0.39; P = 0.1). Erythromycin caused a statistically significant reduction in midazolam clearance from the original value of 3.8 to 2.5 (95% CI for the difference −2.27, −0.35) ml kg−1 min−1. Interestingly there was no significant change in the clearance of lignocaine (6.4 vs 5.8 (95% CI for the difference −2.74, −1.51) ml kg−1 min−1). Furthermore no correlation at all was observed between the MEGX‐test and lignocaine or midazolam clearances. Considering the data on day 1, 3 and 5 the intra‐individual coefficient of variation in the MEGX‐test was 45.3% at 15 min and 23.5% at 30 min, respectively.Conclusions  It is concluded that there is a significant correlation between lignocaine and midazolam clearances but this correlation is lost after CYP3A4 inhibition by erythromycin. The MEGX‐test is of no value in assessing intra‐ and inter‐individual variability in midazolam clearance.
Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man
Authors: Daley‐Yates Peter T. , Price Alison C. , Sisson Jonathan R. , Pereira Adrian , Dallow Nigel 
Published: March 2003

Aims  To assess the absolute bioavailability, pharmacokinetics and metabolism of beclomethasone dipropionate (BDP) in man following intravenous, oral, intranasal and inhaled administration.Methods  Twelve healthy subjects participated in this seven‐way cross‐over study where BDP was administered via the following routes: intravenous infusion (1000 µg), oral (4000 µg, aqueous suspension), intranasal (1344 µg, aqueous nasal spray) and inhaled (1000 µg ex‐valve, metered dose inhaler). The contribution of the lung, nose and gut to the systemic exposure was assessed by repeating the inhaled, intranasal and oral dosing arms together with activated charcoal, to block oral absorption. Blood samples were collected for 24 h postdose for the measurement of BDP, beclomethasone‐17‐monopropionate (B‐17‐MP) and beclomethasone (BOH) in plasma by liquid chromatography tandem mass spectrometry.Results  Intravenous administration of BDP (mean CL 150 l h−1, Vss 20 l, t½ 0.5 h) was associated with rapid conversion to B‐17‐MP which was eliminated more slowly (t1/2 2.7 h). In estimating the parameters for B‐17‐MP (mean CL 120 l h−1, Vss 424 l) complete conversion of BDP to B‐17‐MP was assumed. The resultant plasma concentrations of BOH were low and transient. BDP was not detected in plasma following oral or intranasal dosing. The mean absolute bioavailability (%F, 90% CI; nominal doses) of inhaled BDP was 2% (1–4%) and not reduced by coadministration of charcoal. The mean percentage F of the active metabolite B‐17‐MP was 41% (31–54%), 44% (34–58%) and 62% (47–82%) for oral, intranasal and inhaled dosing without charcoal, respectively. The corresponding estimates of nasal and lung absorption, based on the coadministration of charcoal, were < 1% and 36% (27–47%), respectively.Conclusions  Unchanged BDP has negligible oral and intranasal bioavailability with limited absorption following inhaled dosing due to extensive (95%) presystemic conversion of BDP to B‐17‐MP in the lung. The oral and intranasal bioavailabilities of the active metabolite B‐17‐MP were high and similar, but direct absorption in the nose was insignificant. The total inhaled bioavailability of B‐17‐MP (lung + oral) was also high (62%) and approximately 36% of this was due to pulmonary absorption. Estimates of oral bioavailability and pulmonary deposition based on total BOH were approximately half those found for B‐17‐MP.
Effect of OROS® controlled‐release delivery on the pharmacokinetics and pharmacodynamics of oxybutynin chloride
Authors: Sathyan Gayatri , Chancellor Michael B. , Gupta Suneel K. 
Published: March 2003

Aims  Dry mouth is a common side‐effect seen with immediate‐release oxybutynin (IR‐Oxy). Ditropan XL®[(Oxy‐XL), a controlled‐release formulation of oxybutynin chloride, is a once‐daily oral dosage form that incorporates the OROS® technology. Dry mouth as the pharmacodynamic measure was compared between Oxy‐XL and IR‐Oxy administration. The steady state stereospecific pharmacokinetics were also established for the two formulations and the kinetic‐dynamic relationship of oxybutynin was examined.Methods  This was a randomized, repeated‐dose, double‐blind, two‐treatment, two‐period, crossover study. After a baseline assessment day, volunteers were randomly assigned to one of two treatment sequences and received 4 days of each treatment with a washout period of 7 days between treatments. The treatments were: 1) Oxy‐XL 10 mg in the morning and placebo 8 h later, and 2) IR‐Oxy 5 mg in the morning and again 8 h later. Volunteers assessed dry mouth severity subjectively using a 100 mm visual analogue scale, VAS (Baseline, treatment days 1 and 4) and objectively by collecting saliva (Baseline and treatment day 4) before dosing and every hour after the morning dose for ∼16 h. Several blood samples were collected during each treatment, with frequent sampling on day 4 to analyse for plasma R‐ and S‐oxybutynin and R‐ and S‐desethyloxybutynin concentrations.Results  Relatively constant plasma concentrations of oxybutynin and its metabolite were seen over 24 h following Oxy‐XL administration with the degree of fluctuation being much lower (P = 0.001; 66% to 81% reduction for the various analytes) than IR‐Oxy. Compared with IR‐Oxy, Oxy‐XL yielded higher (131% and 158% for the R‐ and S‐isomer, respectively) oxybutynin and lower (62% and 78% for the R‐ and S‐isomer, respectively) desethyloxybutynin bioavailability, suggesting reduced first‐pass metabolism. Saliva output (area under the effect curve) was significantly higher [P = 0.001; 37% (95% confidence interval: 24, 51%)] with Oxy‐XL than with IR‐Oxy and, accordingly, dry mouth severity (VAS) integrated over the day was significantly lower with Oxy‐XL. The decrease in saliva output and the consequent increase in dry mouth severity correlated with the metabolite R‐desethyloxybutynin concentration, and no apparent relationship was observed with the R‐oxybutynin concentration. This suggests that the metabolite may contribute to the dry mouth. Therefore, the reduction in metabolite exposure with Oxy‐XL may be a possible explanation for the observed decrease in dry mouth severity with OXY‐XL compared with IR‐Oxy.Conclusions  Oxy‐XL maintains relatively constant plasma drug and metabolite concentrations and minimizes first‐pass metabolism of oxybutynin. The metabolite appears to contribute to dry mouth associated with oxybutynin, and following Oxy‐XL metabolite exposure is reduced compared with IR‐Oxy. Consequently less dry mouth was observed with Oxy‐XL as compared with IR‐Oxy.
The glucuronidation of mycophenolic acid by human liver, kidney and jejunum microsomes
Authors: Bowalgaha Kushari , Miners John O. 
Published: March 2003

Aims  To estimate the relative contribution of liver, kidney and jejunum to MPA elimination via glucuronidation from in vitro kinetic data.Methods  The kinetics of MPA glucuronidation by human liver, kidney and jejunum microsomes were characterized. Mycophenolic acid glucuronide (MPAG) concentrations in microsomal incubations were determined using a specific h.p.l.c. procedure. Non‐specific microsomal binding of MPA was excluded using an equilibrium dialysis approach.Results  Microsomes from all three tissues catalysed the conversion of MPA to MPAG. Mean microsomal intrinsic clearances for MPAG formation by liver, kidney and jejunum microsomes were 46.6, 73.5 and 24.5 µl (min mg)−1, respectively. When extrapolated to the whole organ, however, hepatic intrinsic clearance was 21‐ and 38‐fold higher than the respective intrinsic clearances for kidney and small intestine.Conclusions  The data suggest that the liver is the organ primarily responsible for the systemic clearance of MPA, with little contribution from the kidney, and that the small intestine would be expected to contribute to first‐pass extraction to a minor extent only.