bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: gastro‐oesophageal reflux disease as a functional gastrointestinal disorder
Authors: Kahrilas P. J. 
Published: December 2004

SummaryGastro‐oesophageal reflux disease encompasses a family of disorders united by a common pathogenesis: the excessive reflux of gastric contents. The best defined disorder is oesophagitis, but it is now evident that proton pump inhibitor therapy can resolve oesophagitis in virtually every case. The same cannot be said for gastro‐oesophageal reflux disease symptoms, however, thus moving the frontier to symptom control. Endoscopy‐negative reflux disease is a heterogeneous group, no longer bound by the common denominator of endoscopic findings. In fact, three distinct patient subgroups emerge: (i) individuals who in essence have oesophagitis, but are either in remission or simply fail to meet the endoscopic criteria; (ii) patients with hypersensitivity to oesophageal stimuli; and (iii) patients with ‘functional heartburn’ whose symptoms are not related to reflux. Given this heterogeneity, it is not surprising that the efficacy of antisecretory drugs is less impressive. This has led to new therapeutic approaches beyond acid control: mucosal protective agents, either central nervous system or peripherally acting compounds aimed at normalizing hyperalgesia, and reflux inhibitors and serotonergic agents, such as tegaserod.
Review article: gastric emptying in functional gastrointestinal disorders
Authors: Quigley E. M. M. 
Published: December 2004

SummaryAlthough delayed gastric emptying has been described in several functional gastrointestinal disorders, and appears to be especially common in functional dyspepsia, the relationship of this finding to symptoms and basic pathophysiology is difficult to define. The delineation of the interactions between delayed gastric emptying, on the one hand, and symptom pathogenesis, on the other, has been hampered by several factors. These include the limitations of the methodology itself, the extent of overlap between the various functional disorders and the sensitivity of gastric emptying to factors external to the stomach, be they elsewhere within the gastrointestinal tract, in the central nervous system or in the environment. In many instances, delayed gastric emptying is an epiphenomenon, reflecting the overlap between inadequately defined functional syndromes, shared pathophysiology or the activation of physiological interactions between the various organs of the gut. In others, it may imply a truly diffuse motor disorder. The disappointments attendant on attempts to alleviate symptoms through approaches designed to accelerate gastric emptying should therefore not come as a surprise. Pending the definition of the true significance of delayed gastric emptying in all functional gastrointestinal disorders, caution should be exerted in the interpretation of this finding in a patient with functional symptoms.
Population pharmacokinetics of raltitrexed in patients with advanced solid tumours
Authors: Blair Elaine Y. L. , Rivory Laurent P. , Clarke Stephen J. , McLachlan Andrew J. 
Published: December 2004

AimsTo investigate the population pharmacokinetics of raltitrexed in patients with advanced solid tumours and to identify patient covariates contributing to the interpatient variability in the pharmacokinetics of raltitrexed.MethodsPatient covariate and concentration–time data were collected from patients receiving 0.1–4.5 mg m−2 raltitrexed during the early clinical trials of raltitrexed. Data were fitted using nonlinear mixed effects modelling to generate population mean estimates for clearance (CL) and central volume of distribution (V). The relationship between individual estimates of the pharmacokinetic parameters and patient covariates was examined and the influence of significant covariates on the population parameter estimates and their variance was investigated using stepwise multiple linear regression. The performance of the developed model was tested using an independent validation dataset. All patient data were pooled in the total cohort to refine the population pharmacokinetic model for raltitrexed.ResultsA three‐compartment pharmacokinetic model was used to fit the concentration–time data of raltitrexed. Estimated creatinine clearance (CLCR) was found to influence significantly the CL of raltitrexed and explained 35% of variability in this parameter, whilst body weight (WT) and serum albumin concentrations (ALB) accounted for 56% of the variability in V. Satisfactory prediction (mean prediction error 0.17 µg l−1 and root mean square prediction error 4.99 µg l−1) of the observed raltitrexed concentrations was obtained in the model validation step. The final population mean estimates were 2.17 l h−1[95% confidence interval (CI) 2.06, 2.28] and 6.36 l (95% CI 6.02, 6.70) for CL and V, respectively. Interpatient variability in the pharmacokinetic parameters was reduced (CL 28%, V 25%) when influential covariates were included in the final model. The following covariate relationships with raltitrexed parameters were  described  by  the  final  population  model:  CL  (l h−1) = 0.54 + 0.02  CLCR (ml min−1) and V (l) = 6.64 + 0.08 WT (kg) − 0.16 ALB (g l−1).ConclusionsA population pharmacokinetic model has been developed for raltitrexed in patients with advanced cancer. Pharmacokinetic parameters of raltitrexed are markedly influenced by the patient's renal function, body weight and serum albumin levels, which may be taken into account in dose individualization. The use of influential covariates to guide anticancer dosage selection may result in less variability in drug exposure and potentially a better clinical outcome.
Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects
Authors: Jiang Xuemin , Williams Kenneth M. , Liauw Winston S. , Ammit Alaina J. , Roufogalis Basil D. , Duke Colin C. , Day Richard O. , McLachlan Andrew J. 
Published: December 2004

AimThe aim of this study was to investigate the effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin.MethodsThis was an open‐label, three‐way crossover randomized study in 12 healthy male subjects, who received a single 25‐mg dose of warfarin alone or after 14 days’ pretreatment with St John's wort, or 7 days’ pretreatment with ginseng. Dosing with St John's wort or ginseng was continued for 7 days after administration of the warfarin dose. Platelet aggregation, international normalized ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S‐7‐hydroxywarfarin concentration in urine were measured. Statistical comparisons were made using anova and 90% confidence intervals are reported.ResultsINR and platelet aggregation were not affected by treatment with St John's wort or ginseng. The apparent clearances of S‐warfarin after warfarin alone or with St John's wort or ginseng were, respectively, 198 ± 38 ml min−1, 270 ± 44 ml min−1 and 220 ± 29 ml min−1. The respective apparent clearances of R‐warfarin were 110 ± 25 ml min−1, 142 ± 29 ml min−1 and 119 ± 20 ml min−1. The mean ratio and 90% confidence interval (CI) of apparent clearance for S‐warfarin was 1.29 (1.16, 1.46) and for R‐warfarin it was 1.23 (1.11, 1.37) when St John's wort was coadministered. The mean ratio and 90% CI of AUC0−168 of INR was 0.79 (0.70, 0.95) when St John's wort was coadministered. St John's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers.ConclusionsSt John's wort significantly induced the apparent clearance of both S‐warfarin and R‐warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac‐warfarin. Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S‐warfarin or R‐warfarin.
The I1‐imidazoline agonist moxonidine decreases sympathetic tone under physical and mental stress
Authors: Wenzel René R. , Mitchell Anna , Siffert Winfried , Bührmann Sandra , Philipp Thomas , Schäfers Rafael F. 
Published: December 2004

AimsMoxonidine is an I1‐imidazoline receptor agonist that reduces blood pressure by inhibition of central sympathetic activity. The effects of the drug under physical and mental stress have not been studied in detail.MethodsWe investigated the effects of 0.4 mg moxonidine orally on sympathetic activity, blood pressure and heart rate in a double‐blind, placebo‐controlled crossover study in 12 healthy volunteers. The subjects underwent physical exercise test using bicycle ergometry and a mental stress test using an adaptive reaction test device. Potential association of parameters with the GNB3 C825T polymorphism was also assessed.ResultsUnder resting conditions, moxonidine decreased plasma noradrenaline (NA: −66.1 ± 12 pg ml−1; P < 0.01 vs placebo) and adrenaline (A: −18.8 ± 6 pg ml−1; P < 0.05 vs placebo). Physical exercise evoked a significant increase in plasma NA and A (NA: 760 ± 98 pg ml−1; A: 97 ± 9 pg ml−1; P < 0.001 vs baseline), which was significantly reduced after pretreatment with moxonidine (NA: 627 ± 68 pg ml−1; P < 0.05 vs placebo; A: 42.8 ± 4 pg ml−1; P < 0.01 vs placebo). Maximal physical exercise capacity was not limited by moxonidine (NS). During the mental stress test, increases in NA (placebo: 146 ± 24 pg ml−1, moxonidine: 84 ± 26 pg ml−1; P < 0.01 vs placebo) and A (placebo: 22.8 ± 9 pg ml−1, moxonidine: 8.0 ± 8 pg ml−1; P < 0.01 vs placebo) were significantly reduced after pretreatment with moxonidine. Increases in blood pressure during mental stress were significantly lower after pretreatment with moxonidine (P < 0.05 vs placebo). There was no association of the response to moxonidine with GNB3 genotypes (NS).ConclusionsMoxonidine decreases total sympathetic tone under basal conditions as well as during physical exercise and mental stress without limiting absolute exercise capacity. Thus, moxonidine appears suitable for the treatment of patients with high SNS activity and hypertension induced by physical or mental stress. As the drug does not reduce exercise capacity, it may be considered as an alternative to β‐adrenoceptor blockers in selected patients.
Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers
Authors: Hua Teng C. , Pan Alan , Chan Clark , Poo Yeo K. , Skinner Michael H. , Knadler Mary P. , Gonzales Celedon R. , Wise Stephen D. 
Published: December 2004

AimTo investigate the effect of duloxetine on the pharmacokinetics and tolerability of tolterodine and its active 5‐hydroxymethyl metabolite (5‐HM).MethodsSixteen healthy subjects received two 5‐day treatment regimens in a randomized, double‐blinded, crossover fashion: tolterodine (2 mg, BID) + duloxetine (40 mg, BID), tolterodine (2 mg, BID) + duloxetine placebo (BID). Plasma concentrations of tolterodine and 5‐HM were measured on day 5. Adverse events, clinical safety laboratory data and vital signs were assessed during the study.ResultsDuloxetine increased the AUCτ,ss of tolterodine by 71%[geometric mean, 95% confidence interval (CI) 31, 123], and its Cmax,ss by 64% (CI 30, 106), and prolonged its t1/2 by 14% (CI 1, 28). Duloxetine did not affect the plasma concentrations or t1/2 of 5‐HM. Laboratory data and vital signs did not reveal any clinically significant changes or abnormalities.ConclusionsDuloxetine exhibited minor inhibitory effects on the pharmacokinetics of tolterodine but not 5‐HM. Coadministration of these drugs was well tolerated and demonstrated no significant safety findings in the studied population. These findings suggest that there should not be a need for routine adjustment of tolterodine dosage in the presence of duloxetine.
An investigation of components of variance and tachyphylaxis in a placebo‐controlled intravenous tyramine study
Authors: Cantarini M. V. , Watkins C. L. , Growcott J. , Hughes A. M. 
Published: December 2004

Aims  To explore inter‐ and intra‐volunteer variability for the dose of intravenous tyramine eliciting a 20 mmHg increase in systolic blood pressure from baseline (TYR20) and to evaluate potential tachyphylaxis.Methods  Twelve healthy volunteers received blinded placebo‐controlled ascending and descending sequences of intravenous tyramine injections on two separate occasions. The TYR20 was derived by linear interpolation, using three interventions to deal with missing data.Results  Analysis of covariance (ancova) demonstrated no significant difference in TYR20 between sequences, regardless of the missing data methodology applied. Inter‐volunteer variability was 2.4–3.4 times larger than within‐volunteer variability. No evidence of tachyphylaxis was seen using either the sign test or generalized additive models.Conclusions  Since inter‐volunteer variability was greater than intra‐volunteer variability, a crossover study design would be a more efficient study design, and the descending sequence of injections could be omitted since tachyphylaxis was not demonstrated.
Recombinant factor VIIa reverses the anticoagulant effect of the long‐acting pentasaccharide idraparinux in healthy volunteers
Authors: Bijsterveld Nick R. , Vink Roel , Van Aken Benien E. , Fennema Hein , Peters Ron J. G. , Meijers Joost C. M. , Büller Harry R. , Levi Marcel 
Published: December 2004

SummaryWe investigated whether the anticoagulant effect of idraparinux, a selective long‐acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo‐controlled trial, comparing idraparinux [7·5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 μg/kg intravenous (i.v.)] (n = 6), or idraparinux (7·5 mg s.c) followed after 1 week by rFVIIa (90 μg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre‐idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux‐inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.
Does anthracycline administration by infusion in children affect late cardiotoxicity?
Authors: Levitt G. A. , Dorup I. , Sorensen K. , Sullivan I. 
Published: December 2004

SummaryThe severity of late cardiotoxicity after anthracycline treatment for childhood cancer relates mainly to the cumulative anthracycline dose received, but all dose ranges cause some cardiac dysfunction. Anthracycline administration by infusion in order to lower peak drug concentration has been used in an attempt to reduce cardiotoxicity. Cardiac performance was assessed by echocardiography in children who were relapse‐free survivors of treatment for acute lymphoblastic leukaemia (ALL). They received the same cumulative anthracycline dose (daunorubicin 180 mg/m2) either by bolus injection (UKALL X protocol, n = 40) or by infusion (UKALL XI protocol, n = 71) with a follow‐up duration of 5·3 ± 2·0 and 5·4 ± 1·0 years respectively. On analysis, both the bolus administration and infusion groups showed similar mild impairment of cardiac performance, characterized by increased left ventricular end systolic stress and impaired left ventricular function. In conclusion, subclinical abnormality of left ventricular performance was confirmed in both groups despite the relatively modest cumulative anthracycline dose received. We were unable to demonstrate an advantage of anthracycline administration by 6‐h infusion with respect to late cardiotoxicity at this dose.
Incidence of novel N‐glycosylation sites in the B‐cell receptor of lymphomas associated with immunodeficiency
Authors: Forconi Francesco , Capello Daniela , Berra Eva , Rossi Davide , Gloghini Annunziata , Cerri Michaela , Muti Giuliana , Morra Enrica , Paulli Marco , Magrini Umberto , Lucioni Marco , Rambaldi Alessandro , Lauria Francesco , Carbone Antonino , Stevenson Freda K. , Gaidano Gianluca 
Published: December 2004

SummaryNovel N‐glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B‐cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency‐related non‐Hodgkin's lymphomas (NHL) include post‐transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome‐related NHL (AIDS‐NHL). Most PTLD derive from B cells that carry mutated VH genes and that have completed the GC reaction. All AIDS‐NHL carry mutated VH genes and variable features of GC or post‐GC cells. To determine if N‐glycosylation is a feature of immunodeficiency‐related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS‐NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells (P = 0·15). AIDS‐NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N‐glycosylation sites in PTLD, consistent with post‐GC features. The variable incidence of N‐glycosylation sites in AIDS‐NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development.
Initial design for a fish bioenergetics model of Pacific saury coupled to a lower trophic ecosystem model
Authors: ITO SHIN‐ICHI , KISHI MICHIO J. , KURITA YUTAKA , OOZEKI YOSHIOKI , YAMANAKA YASUHIRO , MEGREY BERNARD A. , WERNER FRANCISCO E. 
Published: December 2004

AbstractA fish bioenergetics model coupled with an ecosystem model was developed to reproduce the growth of Pacific saury. The model spatially covers three different oceanographic spatial domains corresponding to the Kuroshio, Oyashio, and interfrontal (mixed water) regions. In this coupled model, three (small, large, and predatory) zooplankton densities which were derived from the lower trophic level ecosystem model were input to the bioenergetics model of saury as the prey densities. Although certain model parameters were imposed from other species’ bioenergetics, several model parameters were estimated from observational data specific to Pacific saury. The integrated model results reproduced appropriate growth rates of Pacific saury. Model sensitivities to water temperature and prey density are examined and observational methods to evaluate the model parameters are discussed.
Variations in patterns of daily changes in otolith increment widths of 0+ Pacific saury, Cololabis saira, off Japan by hatch date in relation to the northward feeding migration during spring and summer
Authors: KURITA YUTAKA , NEMOTO YUTAKA , OOZEKI YOSHIOKI , HAYASHIZAKI KEN‐ICHI , IDA HITOSHI 
Published: December 2004

AbstractDaily changes in otolith increment widths from the core to the edge in 0+ Pacific saury, Cololabis saira, were examined. There appeared a first peak of increment width at 22.9 ± 9.6 (73) [mean ± SD (sample number)] days old, followed by the bottom of the first trough [88.6 ± 25.3 days old (73)] and a second peak [143.8 ± 24.6 days old (62)]. The ages at the second peak formation were strongly related to the estimated hatch dates from 30 October to 7 April (N = 62, r2 = 0.661) with a negative coefficient of elapsed days from 30 September, corresponding to the beginning of the spawning season. Thus, fish hatched earlier in the spawning season formed the second peak at an older age. The second peak was estimated to occur from 23 April to 14 August, mainly in June and July, at 152.5–216.8 mm (excluding one exception of 96.9 mm) in the earlier period (before 15 June) and at 87.5–177.5 mm in the later period (after 17 June). The peak of otolith increment width is concluded to approximate the peak of daily growth because the relationship between otolith radius and body size was expressed as an allometric curve. The occurrence of the second peak of increment width (growth) can be theoretically explained by descending temperature and ascending feeding condition, which Pacific saury experiences through the northward feeding migration from the warm and food‐poor Kuroshio (subtropical) waters to the cold and food‐rich Oyashio (subarctic) waters during spring and summer. The clear relationship between the age at the second peak and hatch date suggests the possibility of estimating hatch dates even of fish that have translucent zones in their otoliths by examining the increment widths from the core to the inner edge of the first translucent zone and specifying the age at the second peak.
Movement of juvenile walleye pollock, Theragra chalcogramma, from a spawning ground to a nursery ground along the Pacific coast of Hokkaido, Japan
Authors: HONDA SATOSHI , OSHIMA TATSUKI , NISHIMURA AKIRA , HATTORI TSUTOMU 
Published: December 2004

AbstractThe movement of juvenile walleye pollock, Theragra chalcogramma, from the Funka Bay spawning ground to the Doto nursery ground along the Pacific coast of Hokkaido was observed during spring through summer of 2000 and 2001. A positive relationship between the size of the juveniles and the position of the eastern front of their distribution indicated a relationship between the hatching period and the timing of the eastward movement of juveniles toward the Doto area. Based on the bathymetric distribution of juvenile pollock on the continental shelf in Hidaka Bay, the coastal current is suggested to play a role in the easterly movement of juveniles. However, further supporting evidence from physical and biological oceanographic studies is necessary to confirm this hypothesis.
Loneliness as a predictor of quality of life among older caregivers
Authors: Ekwall Anna K. , Sivberg Bengt , Hallberg Ingalill R. 
Published: December 2004

Aim.  This paper reports a study investigating quality of life in relation to loneliness, caregiving, social network, gender, age and economic status among caregiving men and women in a population‐based sample aged 75 years or older.Background.  Because of demographic changes, in the future more care for older people will be given by informal caregivers who are themselves older. Being old and caring for another older person may affect various aspects of life, such as physical and emotional health and decreased time for respite, which may affect social life and quality of life.Method.  A postal questionnaire including the Short Form Health Survey was used. The sample consisted of 4278 people, aged 75 years and over, living in Sweden. Of these, 783 (18%) were caregivers.Findings.  Caregivers had a larger social network and reported feelings of loneliness less often than non‐caregivers. Forty per cent of caregivers helped every day. There were gender differences in experiences of loneliness during the last year, with the frequency of intense feelings of loneliness being higher among women. Loneliness and a small or non‐existent network were significantly associated with low quality of life among caregivers, as well as in the total sample. The results showed significant association between loneliness, weak social network and low mental quality of life.Conclusions.  The fact that loneliness was the most important factor predicting low quality of life among caregivers, as well as older people in general, indicates that it is crucial in the care of older people. From a nursing perspective, the findings indicate the advantage of helping older people to keep up and develop their social networks. Nursing care should involve steps to maintain the social network before an older person becomes too weak, since decreased health status makes social contacts more difficult.