bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of prostaglandin synthesis does not affect contractile responses to noradrenaline, serotonin, angiotensin II nor endothelin‐1 in human forearm isolated veins
Authors: CHIN JAYE P. F. , HURLSTON ROBYN M. , DART ANTHONY M. 
Published: July 2012

The functional role of endogenous cyclo‐oxygenase products was examined in the human forearm isolated vein.
Six healthy normal adult males (age > 18 years old) were recruited. Forearm veins were biopsied and ring segments mounted in standard organ baths for recording of isometric force.
Noradrenaline (‐log molar EC50: 7.75 ± 0.19; –log molar threshold concentration: 8.80 ± 0.20), 5‐hydroxytryptamine (–log molar EC50: 7.52 ± 0.17; –log molar threshold concentration: 9.50 ± 0.64), angiotensin II (–log molar threshold concentration: 9.00 ± 0.28) and endothelin‐1 (–log molar threshold concentration: 9.13 ± 0.47) were equipotent in this preparation. Indomethacin (10 μ) had no effect on either the threshold concentration or EC50 of noradrenaline, 5‐hydroxytryptamine nor the threshold concentration of angiotensin II nor endothelin‐1.
Sodium nitroprusside (1 N‐10 μ) relaxed noradrenaline‐precontracted preparations. Evidence of minimal endothelial influence was confirmed by the lack of relaxant response to acetylcholine (1 N‐10 μ). Histology using silver staining confirmed that endothelial cells were absent over greater than 90% of the lumen surface.
We conclude that endogenous prostanoids derived from smooth muscle cells, either released basally or agonist‐stimulated, do not play a role in the regulation of vascular tone in the human forearm isolated vein.
A comparison of the acute haemodynamic effects of nisoldipine and nifedipine during treatment with atenolol in patients with coronary artery disease
Authors: DONALDSON KIRSTEEN M. , DAWKINS KEITH D. , WALLER DEREK G. 
Published: July 2012

The acute haemodynamic effects of intravenous nisoldipine (1, 2, 4 μg kg−1) and nifedipine (2.5, 5, 10 μg kg−1) were compared in a randomised, within‐patient crossover study. Fifteen male patients with stable angina pectoris treated with atenolol were studied after undergoing routine cardiac catheterisation.
Nisoldipine caused a dose‐related fall in systemic vascular resistance (maximum 22%) associated with an increase in heart rate and cardiac index (18%) and a fall in mean arterial pressure (7%).
By contrast, nifedipine was associated with a significant increase in heart rate but systemic vascular resistance, cardiac index and mean arterial pressure remained unaltered.
At doses with equivalent effects on heart rate (2 μg kg−1 nisoldipine; 10 μg kg−1 nifedipine) acute dosing with nisoldipine caused a significantly greater fall in systemic vascular resistance and increase in cardiac index, whilst nifedipine caused a greater reduction in stroke volume index and left ventricular stroke work index.
The results suggest that, when combined with atenolol, acute dosing with nisoldipine may have a more complementary haemodynamic profile than nifedipine. The implications of this finding for chronic oral dosing in patients with impaired left ventricular function should be evaluated.
The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension
Authors: BAINBRIDGE A. D. , MACFADYEN R. J. , STARK S. , LEES K. R. , REID J. L. 
Published: July 2012

The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double‐blind, double dummy placebo controlled, randomised, crossover study in 20 patients (mean age 55.4 years; range 46–69) with uncomplicated mild to moderate hypertension (supine diastolic >90 mmHg <115 mmHg after 4 weeks of single‐blind wash‐out on placebo). The four randomised, double‐blind, crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo, monotherapy with each drug and the combination. Noninvasive ambulatory blood pressure monitoring (Spacelabs 90207) was performed for 24 h at the end of each phase.
The mean 24 h ambulatory blood pressure (mmHg) was 147.9/92.0 following placebo, 141.3/87.8 following monotherapy with ramipril 2.5 mg, 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg. All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo. The antihypertensive efficacy of the combination was additive.
The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER.
Post‐exercise reduction in blood pressure in hypertensive subjects: effects of angiotensin converting enzyme inhibition
Authors: BEAULIEU MARC , NADEAU ANDRÉ , LACOURCIÈRE YVES , CLÉROUX JEAN 
Published: July 2012

Much attention has been given to the effects of various classes of antihypertensive drugs on blood pressure and haemodynamics. The effects of a single bout of exercise on post‐exercise blood pressure have also been studied by several investigators. However, the combined effects of prior exercise and antihypertensive medication has drawn less attention.
We examined the separate and combined effects of a single bout of exercise and of angiotensin converting enzyme (ACE) inhibition with a new ACE inhibitor (fosinopril, 20 mg day−1) on post‐exercise blood pressure and systemic and regional haemodynamics. Ten patients with mild‐to‐moderate hypertension were studied with a double‐blind, randomized crossover, placebo‐ and rest period‐controlled study design.
At rest, mean arterial pressure (MAP, −10 ± 2 mm Hg), total peripheral resistance (TPR, −11 ± 5%) and forearm vascular resistance (FVR, −17 ± 8%) were significantly (P < 0.05) reduced during ACE inhibition as compared with the placebo phase.
During the placebo phase, MAP (–3 ± 1 mm Hg), TPR (–10 ± 4%) and FVR (–9 ± 4%) were lower after exercise as compared with the control rest period.
During ACE inhibition, MAP (–3 ± 1 mm Hg) and TPR (–8 ± 4%) were lower, but FVR (+32 ± 15%) was increased after exercise as compared with the control rest period.
Thus, blood pressure and TPR decreased similarly after exercise during the placebo phase and during ACE inhibition. However, differences in post‐exercise forearm haemodynamics during the placebo phase and during ACE inhibition indicate that underlying regional haemodynamics are modified.
Differential effects of misoprostol and ranitidine on the pharmacokinetics of diclofenac and gastrointestinal symptoms
Authors: DAMMANN H. G. , SIMON‐SCHULTZ J. , STEINHOFF I. , DAMASCHKE A. , SCHMOLDT A. , SALLOWSKY E. 
Published: July 2012

The effects of oral misoprostol (800 μg day−1) and ranitidine (300 mg day−1) on the pharmacokinetics of diclofenac (100 mg) were assessed in a three‐way randomized crossover study in 18 healthy male subjects.
Subjects were studied over three 8 day periods, during which they received twice‐daily placebo, misoprostol, or ranitidine. A single dose of diclofenac was given orally on days 1 and 8, and plasma diclofenac concentrations were measured by h.p.l.c. over 24 h.
Misoprostol caused a non‐significant 19% increase in the mean Cmax value of diclofenac on both days 1 and 8. After 8 days of dosing with misoprostol there was a significant (P = 0.04) 20% decrease in the AUC of diclofenac.
Ranitidine had no statistically significant effects on the pharmacokinetics of diclofenac.
Co‐administration of misoprostol and diclofenac was associated with a higher frequency and severity of gastrointestinal symptoms and frequency of bowel opening, and a decrease in faecal consistency when compared with either placebo or ranitidine plus diclofenac (P < 0.01).
Intramuscular picenadol in patients with postoperative pain
Authors: BRUNELLE ROCCO L. , GOLDSTEIN DAVID J. , GEORGE RICHARD E. , ZIMMERMAN DENNIS M. 
Published: July 2012

The analgesic efficacy and safety of a single 50 mg intramuscular dose of rac‐picenadol, a centrally acting agonist‐antagonist opioid analgesic, were compared with pethidine (meperidine) 100 mg and placebo in 60 patients with moderate to severe postoperative pain using hourly pain intensity and relief measurements for up to 6 h following injection of the study medications.
Both picenadol and pethidine were statistically significantly (P < 0.05) more effective than placebo in reducing pain intensity and in increasing total relief. Patients receiving picenadol and pethidine had higher frequency of somnolence than patients receiving placebo. In addition, patients receiving picenadol 50 mg experienced a higher incidence of confusion (30%), speech disorders (30%), and tremors (25%) than the patients receiving either pethidine or placebo.
These results were compared with those of a similar study which investigated the effects of a 25 mg intramuscular dose of picenadol vs pethidine and placebo. This comparison suggests that 25 mg of picenadol is a more acceptable dosage since both 25 and 50 mg were effective dosages.
Effect of peginterferon alfa‐2a (40KD) on cytochrome P450 isoenzyme activity
Authors: Brennan Barbara J. , Xu Zhi‐Xin , Grippo Joseph F. 
Published: July 2012

AimPegylated interferon‐based therapy is recommended for treatment of hepatitis C virus (HCV) infection. Because interferons are known to down‐regulate hepatic cytochrome P450 (CYP) enzymes, which are involved in drug metabolism and clearance, there is a need to investigate the effect of peginterferon (PEG‐IFN) alfa‐2a (40KD) on the activity of these enzymes in vivo.MethodsFourteen healthy, male volunteers aged 18 to 45 years were recruited into an open label, two period, single centre study in which CYP enzyme activity was measured by administration of the selectively metabolized probe drugs theophylline (CYP1A2), tolbutamide (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6) and dapsone (CYP3A4) on day 1 of the study. PEG‐IFN alfa‐2a (40KD) 180 μg was given subcutaneously each week from day 15 to 36, and probe drugs were re‐administered on day 37. Probe drugs and metabolites were quantified in plasma or urine samples and used to derive pharmacokinetic parameters.ResultsPEG‐IFN alfa‐2a (40KD) significantly increased the area under the serum drug concentration vs. time curve (AUC(0,∞)) for theophylline by 24%, with a reduction in the mean oral clearance of theophylline of 20%. There were no effects on the pharmacokinetics of any of the other probe drugs. The incidence of adverse events was as expected in subjects receiving pegylated interferon.ConclusionThese results suggest there may be an inhibitory effect of PEG‐IFN alfa‐2a (40KD) on CYP1A2. PEG‐IFN alfa‐2a (40KD) had no effect on CYP2C9, CYP2C19, CYP2D6 or CYP3A4 in healthy subjects.
Human eosinophils release IL‐1ß and increase expression of IL‐17A in activated CD4+ T lymphocytes
Authors: Esnault S. , Kelly E. A. B. , Nettenstrom L. M. , Cook E. B. , Seroogy C. M. , Jarjour N. N. 
Published: July 2012

SummaryBackgroundDifferentiation and activation of CD4+ T cells is controlled by various cytokines produced by innate immune cells. We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4+ cells, but their influence on IL‐17A (IL‐17) has not been established.ObjectiveThe purpose of this study is to determine the effect of EOS on IL‐17 production by lymphocytes.MethodsPre‐activated CD4+ T cells were cultured in the presence of either autologous EOS or EOS culture supernatants. Expression of IL‐17 was determined by real‐time quantitative PCR (qPCR) after 5 h and protein level was measured after 48 h. To determine the effect of allergen‐induced airway EOS on IL‐17, subjects with mild allergic asthma underwent bronchoscopic segmental bronchoprovocation with allergen (SBP‐Ag) after a treatment with an anti‐IL‐5 neutralizing antibody (mepolizumab) to reduce airway eosinophilia. IL‐17 mRNA was measured in bronchoalveolar lavage (BAL) cells by qPCR.ResultsIn vitro, EOS significantly increased IL‐17 production by CD4+ T cells. Addition of exogenous IL‐1ß increased expression of IL‐17 mRNA by CD4+ T cells. EOS expressed and released IL‐1ß. Furthermore, levels of IL‐1ß in EOS supernatants highly correlated with their ability to increase IL‐17 expression by CD4+ T cells, and neutralizing antibody to IL‐1ß reduced expression of IL‐17 mRNA. In vivo, reduction of EOS in the airway using mepolizumab was associated with diminished IL‐17 expression after SBP‐Ag.Conclusions and clinical relevanceOur data demonstrate that EOS can promote IL‐17 production through the release of IL‐1ß. Enhanced IL‐17 cytokine production is another mechanism by which EOS may participate in pathogenesis of allergic airway inflammation in asthma.
A passive low‐frequency seismic experiment in the Albertine Graben, Uganda
Authors: Martini F. , Lokmer I. , Jonsdottir K. , De Barros L. , Möllhoff M. , Bean C. J. , Hauser F. , Doherty J. , Ryan C. , Mongan J. 
Published: July 2012

ABSTRACTA passive seismic experiment was conducted in April/May 2010 in the Albertine Graben region in Uganda to record low‐frequency seismic signals and explore the possibility of their exploitation in this area as a direct hydrocarbon indicator (DHI). Recordings were made at locations directly overlying both hydrocarbon and water‐bearing strata within the sedimentary basin as well as reference sites external to the basin, directly on the basement. Contrary to findings published in some literature to date, we found that spatial variations in the analysed wavefield parameters correlate with the underlying geology rather than the presence or absence of hydrocarbons. Inversion of the surface‐wave (fundamental mode) dispersion curve as well as the observed horizontal‐to‐vertical spectral ratio of both surface and body waves provide evidence that the observed spectral variations can be explained solely by a simple layered/gradient velocity model, without the presence of any kind of anomaly that could be attributed exclusively to a hydrocarbon reservoir.Consequently, it is recommended that knowledge of the geological and velocity structure is sought when analysing passive low‐frequency seismic data sets. This is a fundamental prerequisite in order to guard against misinterpretation of the spatial variation of seismic derived attributes as DHIs.
Two‐dimensional fast generalized Fourier interpolation of seismic records
Authors: Naghizadeh Mostafa , Innanen Kristopher A. 
Published: July 2012

ABSTRACTThe fast generalized Fourier transform algorithm is extended to two‐dimensional data cases. The algorithm provides a fast and non‐redundant alternative for the simultaneous time‐frequency and space‐wavenumber analysis of data with time‐space dependencies. The transform decomposes data based on local slope information and therefore making it possible to extract the weight function based on dominant dips from alias‐free low frequencies. By projecting the extracted weight function to alias‐contaminated high frequencies and utilizing a least‐squares fitting algorithm, a beyond‐alias interpolation method is accomplished. Synthetic and real data examples are provided to examine the performance of the proposed interpolation method.
Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis
Authors: Martinowitz U. , Shapiro A. , Quon D. V. , Escobar M. , Kempton C. , Collins P. W. , Chowdary P. , Makris M. , Mannucci P. M. , Morfini M. , Valentino L. A. , Gomperts E. , Lee M. 
Published: July 2012

SummaryIB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double‐blind, non‐inferiority, cross‐over study conducted in participants aged ≥12 years weighing ≥40 kg, with severe or moderately severe haemophilia B (FIX activity ≤2 IU dL
−1). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4–18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8–59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg−1 or nonacog alfa. The lower limit of the one‐sided 95% confidence interval for the ratio of AUC0‐t and AUC0‐∞ (IB1001/nonacog alfa) was 0.90, establishing non‐inferiority. Terminal phase half‐lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non‐inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B.
Guidelines for the management of hemophilia
Authors: Srivastava A. , Brewer A. K. , Mauser‐Bunschoten E. P. , Key N. S. , Kitchen S. , Llinas A. , Ludlam C. A. , Mahlangu J. N. , Mulder K. , Poon M. C. , Street A. ,   Treatment Guidelines Working Group The World Federation Of Hemophilia
Published: July 2012

SummaryHemophilia is a rare disorder that is complex to diagnose and to manage. These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.
Impact of birth complications on breastfeeding duration: an internet survey
Authors: Brown Amy , Jordan Sue 
Published: July 2012

AbstractAimTo explore reasons underlying cessation of breastfeeding in mothers with uncomplicated vaginal deliveries and those experiencing complications during childbirth.BackgroundInterventions during labour and childbirth can have a negative impact on breastfeeding. Explanations include adverse reactions to medication, delayed breastfeeding initiation, and disruption of the normal endocrinology of childbirth. However, reasons for breastfeeding cessation linked to birth experience have not been fully examined. Increasing breastfeeding duration and, consequently, improving infant and maternal health in the UK depend on understanding why women stop breastfeeding.DesignAn exploratory cross‐sectional survey.MethodBetween January–May 2009, 284 mothers attending community groups in Swansea, Wales, and mothers participating in online parenting forums, who initiated breastfeeding but discontinued before 6 months postpartum, reported their birth experience, including complications and reasons for breastfeeding cessation in an internet survey.ResultsMothers who experienced birth complications breastfed for a significantly shorter duration than those who did not. Specifically, caesarean deliveries, foetal distress, failure to progress, and postpartum haemorrhage were each associated with a shorter breastfeeding duration. Mothers who experienced complications were more likely to discontinue breastfeeding for reasons of pain and difficulty than mothers who did not experience complications, yet no difference was seen between groups for social reasons such as embarrassment or a lack of support.ConclusionCertain complications during labour may increase risk of specific physical difficulties with breastfeeding, possibly due to their association with medications received. Maternity health professionals should be alert to this possibility to offer enhanced attention and care to overcome these issues and prolong breastfeeding duration.
Fertility‐awareness knowledge, attitudes, and practices of women seeking fertility assistance
Authors: Hampton Kerry D. , Mazza Danielle , Newton Jennifer M. 
Published: July 2012

AbstractAimsTo report a descriptive study of fertility‐awareness knowledge, attitudes, and practice of infertile women seeking fertility assistance.BackgroundPrevious research has suggested that poor fertility‐awareness may be a contributing cause of infertility among women seeking fertility assistance at assisted reproductive technology clinics. The actual practices and attitudes towards fertility‐awareness in this particular group of women are unknown.DesignA cross‐sectional questionnaire‐based survey.MethodsThe study was conducted over 6 months, from 2007–2008, of women on admission to two assisted reproductive technology clinics in a major city in Australia.ResultsTwo hundred and four of 282 distributed questionnaires were completed (response rate = 72·3%). Eighty‐three per cent had attempted conception for 1 year or more, 86·8% actively tried to improve their fertility‐awareness from one or more sources of the information, 68·2% believed they had timed intercourse mainly within the fertile window of the menstrual cycle in their attempts at conception, but only 12·7% could accurately identify this window. Ninety‐four per cent believe that a woman should receive fertility‐awareness education when she first reports trouble conceiving to her doctor.ConclusionsMost women seeking assistance at assisted reproductive technology clinics attempt timed intercourse within the fertile window of the menstrual cycle. However, few accurately identify this window, suggesting that poor fertility‐awareness may be a contributing cause of infertility.
Semi‐automated vectorial analysis of anorectal motion by magnetic resonance defecography in healthy subjects and fecal incontinence
Authors: Noelting J. , Bharucha A. E. , Lake D. S. , Manduca A. , Fletcher J. G. , Riederer S. J. , Joseph Melton L. , Zinsmeister A. R. 
Published: July 2012

AbstractBackground  Inter‐observer variability limits the reproducibility of pelvic floor motion measured by magnetic resonance imaging (MRI). Our aim was to develop a semi‐automated program measuring pelvic floor motion in a reproducible and refined manner.Methods  Pelvic floor anatomy and motion during voluntary contraction (squeeze) and rectal evacuation were assessed by MRI in 64 women with fecal incontinence (FI) and 64 age‐matched controls. A radiologist measured anorectal angles and anorectal junction motion. A semi‐automated program did the same and also dissected anorectal motion into perpendicular vectors representing the puborectalis and other pelvic floor muscles, assessed the pubococcygeal angle, and evaluated pelvic rotation.Key Results  Manual and semi‐automated measurements of anorectal junction motion (r = 0.70; P < 0.0001) during squeeze and evacuation were correlated, as were anorectal angles at rest, squeeze, and evacuation; angle change during squeeze or evacuation was less so. Semi‐automated measurements of anorectal and pelvic bony motion were also reproducible within subjects. During squeeze, puborectalis injury was associated (P ≤ 0.01) with smaller puborectalis but not pelvic floor motion vectors, reflecting impaired puborectalis function. The pubococcygeal angle, reflecting posterior pelvic floor motion, was smaller during squeeze and larger during evacuation. However, pubococcygeal angles and pelvic rotation during squeeze and evacuation did not differ significantly between FI and controls.Conclusion & Inferences  This semi‐automated program provides a reproducible, efficient, and refined analysis of pelvic floor motion by MRI. Puborectalis injury is independently associated with impaired motion of puborectalis, not other pelvic floor muscles in controls and women with FI.