bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain
Authors: Reznikov Igor , Pud Dorit , Eisenberg Elon 
Published: August 2005

AimsPrevious research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short‐acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer‐related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non‐opioid analgesics.MethodsThe study population consisted of 224 patients, including 142 in the opioid‐treated group and 82 in the non‐opioid‐treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (°C), as well as suprathreshold tonic heat pain intensity (46.5 °C for 1 min) measured by 0–10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients.ResultsNo differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI −8.8, 42.8), P = 0.19), pressure (2.2 mmHg (−28.7, 33.2), P = 0.89) and heat (−0.3 °C (−1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities −0.4 NPS units (95% CI −1.2, 0.4), P = 0.31). Pearson correlations within the opioid‐treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the ‘weak’ opioid‐treated subgroup and the ‘strong’ opioid‐treated subgroup again revealed insignificant results.ConclusionsThese results suggest that the administration of ‘commonly used’ dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients receiving non‐opioid analgesia.
Ziprasidone decreases cortisol excretion in healthy subjects
Authors: Meier Andreas , Neumann Anna‐Catharina , Jordan Wolfgang , Huether Gerald , Rodenbeck Andrea , Rüther Eckart , Cohrs Stefan 
Published: August 2005

AimsTo determine the influence of the atypical antipsychotic ziprasidone on cortisol excretion.MethodsIn a double‐blind, placebo‐controlled, randomized cross‐over design 11 healthy male subjects were studied twice for 2 consecutive nights (N1, undisturbed sleep conditions; N2, exposure to acoustic stress) 5 days apart. Placebo or ziprasidone 40 mg was administered orally 2 h before bedtime on N1 and N2. Urine was collected during three fractionated collection periods (evening; night; morning) for the later determination of cortisol concentrations by standard radioimmunoassays.ResultsZiprasidone decreased the total amount of cortisol excreted by 4.9 (95% CI 3.3, 6.5) µg during N1 and by 10.8 (95% CI 5.7, 15.8) µg during N2 (P < 0.002). This effect was still detectable in the morning (P < 0.02), with decreases of 5.8 (95% CI −2.8, 14.4) µg after N1 and by 12.1 (95% CI 2.8, 21.4) µg after N2. The effect subsided in the evening. A significant intervention–condition interaction (P < 0.02), was found. The significant increase in cortisol excretion during acoustic stress observed with placebo was absent after treatment with ziprasidone.ConclusionsThe significant decrease in nocturnal cortisol excretion following ziprasidone reflects a decreased activity of the HPA‐axis in healthy subjects. This effect may be an important contributor to the mode of action of ziprasidone in different patient populations, particularly in the treatment of depression and in cognitive impairment in schizophrenia.
Population pharmacokinetics of indinavir alone and in combination with ritonavir in HIV‐1‐infected patients
Authors: Kappelhoff Bregt S. , Huitema Alwin D. R. , Sankatsing Sanjay U. C. , Meenhorst Pieter L. , Van Gorp Eric C. M. , Mulder Jan W. , Prins Jan M. , Beijnen Jos H. 
Published: August 2005

AimsThe aim of the study was to characterize the population pharmacokinetics of indinavir, define the relationship between the pharmacokinetics of indinavir and ritonavir, and to identify the factors influencing the pharmacokinetics of indinavir alone or when given with ritonavir.MethodsHIV‐1‐infected patients being treated with an indinavir‐containing regimen were included. During regular visits, 102 blood samples were collected for the determination of plasma indinavir and ritonavir concentrations. Full pharmacokinetic curves were available from 45 patients. Concentrations of indinavir and ritonavir were determined by liquid chromatography coupled with electrospray tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed effect modelling (NONMEM).ResultsThe disposition of indinavir was best described by a single compartment model with first order absorption and elimination. Values for the clearance, volume of distribution and the absorption rate constant were 46.8 l h−1 (24.2% IIV), 82.3 l (24.6% IIV) and 02.62 h−1, respectively. An absorption lag‐time of 0.485 h was detected in patients also taking ritonavir. Furthermore this drug, independent of dose (100–400 mg) or plasma concentration, decreased the clearance of indinavir by 64.6%. In contrast, co‐administration of efavirenz or nevirapine increased the clearance of indinavir by 41%, irrespective of the presence or absence of ritonavir. Female patients had a 48% higher apparent bioavailability of indinavir than males.ConclusionsThe pharmacokinetic parameters of indinavir were adequately described by our population model. Female gender and concomitant use of ritonavir and non‐nucleoside reverse transcriptase inhibitors strongly influenced the pharmacokinetics of this drug. The results support the concept of ritonavir boosting, maximum inhibition of indinavir metabolized being observed at 100 mg.
Diversity‐dependent productivity in semi‐natural grasslands following climate perturbations
Authors: KAHMEN A. , PERNER J. , BUCHMANN N. 
Published: August 2005

SummaryThe consequences of globally declining biodiversity and climate change for ecosystem functions are intensively debated topics in ecological research. However, few studies have investigated potential interactions, or the combined effects of both scenarios, for ecosystem functioning. In the work presented here we tested the hypothesis that increasing plant diversity acts as insurance for ecosystem functions during extreme weather events which are predicted by climate change scenarios.We measured the effect of plant diversity on above‐ and below‐ground productivity in semi‐natural grasslands following experimentally induced early summer drought. To test the insurance hypothesis directly, we determined in each community the range of δ13C values of individual plant species as drought stress indicators.Increasing plant diversity significantly enhanced below‐ground productivity as a consequence of simulated drought, while above‐ground productivity was reduced independently of plant diversity.Plants shifting carbon allocation to below‐ground compartments during drought maintain various aspects of ecosystem services and functions. Although we were not able to detect physiological evidence for the insurance hypothesis, we conclude from our below‐ground results that plant diversity is an essential entity of ecosystems for maintaining ecosystem functions in a changing climate.
Factors affecting the expression of inducible defences in Euplotes: genotype, predator density and experience
Authors: DUQUETTE S. L. , ALTWEGG R. , ANHOLT B. R. 
Published: August 2005

Summary

Inducible defences alter the strength of interaction in food webs. Their effectiveness depends both on the maximum level of induction and the speed at which induction happens. Maximum level and speed of induction should therefore evolve in concert.
We examined the effect of genotype, number of predators and previous exposure to predators on speed and maximum level of induction in a morphological defence expressed by eight clones in three species of the ciliate Euplotes.
Both speed and maximum level of induction, and the reaction to predator density varied among genotypes. These results show that there is genetic variance for all aspects of this inducible defence and the potential for complex evolutionary change under selection.
Higher predator densities led to higher maximum levels of defence and, for one measure of induction speed, more rapid induction. Previous exposure to predators had no detectable effect on either speed or maximum level of induction.
Our results demonstrate that Euplotes can precisely and rapidly adjust their morphological defence to the magnitude of predation risk. The speed of induction and the maximum level of defence varied among genotypes and this will lead to variation in defence level and vulnerability under natural conditions. Variation in prey vulnerability is a key factor promoting stability in food webs.
Competition increasingly dominates the responsiveness of juvenile beech and spruce to elevated CO2 and/or O3 concentrations throughout two subsequent growing seasons
Authors: Kozovits Alessandra R. , Matyssek Rainer , Blaschke Helmut , Göttlein Axel , Grams Thorsten E. E. 
Published: August 2005

AbstractSaplings of Fagus sylvatica and Picea abies were grown in mono‐ and mixed cultures in a 2‐year phytotron study under all four combinations of ambient and elevated ozone (O3) and carbon dioxide (CO2) concentrations. The hypotheses tested were (1) that the competitiveness of beech rather than spruce is negatively affected by the exposure to enhanced O3 concentrations, (2) spruce benefits from the increase of resource availability (elevated CO2) in the mixed culture and (3) that the responsiveness of plants to CO2 and O3 depends on the type of competition (i.e. intra vs. interspecific).Beech displayed a competitive disadvantage when growing in mixture with spruce: after two growing seasons under interspecific competition, beech showed significant reductions in leaf gas exchange, biomass development and crown volume as compared with beech plants growing in monoculture. In competition with spruce, beech appeared to be nitrogen (N)‐limited, whereas spruce tended to benefit in terms of its plant N status.The responsiveness of the juvenile trees to the atmospheric treatments differed between species and was dominated by the type of competition: spruce growth benefited from elevated CO2 concentrations, while beech growth suffered from the enhanced O3 regime. In general, interspecific competition enhanced these atmospheric treatment effects, supporting our hypotheses. Significant differences in root : shoot biomass ratio between the type of competition under both elevated O3 and CO2 were not caused by readjustments of biomass partitioning, but were dependent on tree size.Our study stresses that competition is an important factor driving plant development, and suggests that the knowledge about responses of plants to elevated CO2 and/or O3, acquired from plants growing in monoculture, may not be transferred to plants grown under interspecific competition as typically found in the field.
Glia maturation factor‐β is produced by thymoma and may promote intratumoral T‐cell differentiation
Authors: Yamazaki H , Tateyama H , Asai K , Fukai I , Fujii Y , Tada T , Eimoto T 
Published: August 2005

Aims : To investigate whether Glia maturation factor‐β (GMFB) is expressed in thymomas and is associated with T‐cell development.Methods and results : We investigated the expression of GMFB by immunohistochemistry in 86 cases of thymoma classified into five type A, 35 type AB, 11 type B1, 26 type B2, and nine type B3 thymomas according to the World Health Organization classification system. Immunoblotting and in situ hybridization (ISH) studies were also performed in selected cases. The results of the immunoblot analysis were in accordance with those of immunohistochemical scoring. The ISH study ascertained the tumour cells producing the protein. Immunohistochemically, GMFB expression was observed in one (20%) of type A, 32 (80%) of type AB, all (100%) of type B1 and B2, and eight (89%) of type B3 thymoma with statistically significant differences between type A and type AB, type B1, or type B2 thymoma, and between type B3 and type AB or type B2 thymoma. There was a significant correlation between GMFB expression and the amount of accompanying non‐neoplastic T cells. GMFB promoted T‐cell differentiation into CD4–/CD8+ cells when analysed by two‐colour flow cytometry.Conclusions : The present study suggests that T‐cell development in thymoma may be maintained partly by GMFB produced by the tumour cells.
Reconstruction of the colonization of southern Madagascar by introducedRattus rattus
Authors: Hingston Melanie , Goodman Steven M. , Ganzhorn Jörg U. , Sommer Simone 
Published: August 2005

AbstractAim Description of the genetic differentiation ofRattus rattuspopulations in southern Madagascar. Reconstruction of the colonization pattern ofR. rattusin southern Madagascar and of the origin of introducedR. rattus.Location Southern Madagascar.Methods We analysed the variation in the non‐coding hypervariable region 1 (HVR I) of the mitochondrial control region in 93 individuals from six different sampling sites. The origin of the introduced individuals was examined by comparing MalagasyR. rattussequences to data available from outside Madagascar.Results Thirteen distinct mtDNA control region haplotypes (H1–H13) were distinguished. Only 11 sites (2.6%) were variable within a 419‐bp sequence. Three haplotypes were shared between the sampling areas, though only one haplotype was ubiquitous accounting for 63.4% of all individuals. Population genetic differences (ΦST) between sampling sites ranged from 0.13 to 0.31.amovaresults showed that the majority of variation (86.1%) was assigned to diversity within populations. Except for twoR. rattussequences from India, all other outgroup samples (New York, Great Britain, France and French Polynesia) belonged to an identical haplotype.Main conclusions The spatial distribution and frequency of haplotypes and associated phylogenetic analysis provisionally suggest the Tolagnaro harbour as the place of the founder population from whichR. rattusspread into southern Madagascar. Given currently available samples, these populations are most closely related to rats from the Indian subcontinent. Corroboration of each of these hypotheses will require additional geographical sampling, particularly from northern Madagascar and Africa.
Cigarette smoking and the risk of goitre and thyroid nodules amongst parous women
Authors: GALANTI M. R. , GRANATH F. , CNATTINGIUS S. , EKBOM‐SCHNELL A. , EKBOM A. 
Published: August 2005

Abstract.Objectives.  To clarify the mechanisms by which smoking is associated to toxic and nontoxic goitre and thyroid nodules.Design.  Cohort study.Setting.  Sweden.Subjects.  A cohort of 874 507 parous women identified through the Medical Birth Registry, with smoking behaviour assessed through self‐reported information at the first pre‐natal visit, and follow‐up between 1983 and 1997.Main outcome measures.  Hospital diagnoses of toxic and nontoxic goitre and thyroid nodules, identified by record‐linkage with the national Inpatient Registry. Cox regression was employed to estimate the hazard ratio (HR) of smokers compared with nonsmokers and the corresponding 95% confidence limits (CL).Results.  There was a significantly increased risk of goitre and nodules amongst smokers. The positive association was stronger for toxic (age adjusted HR = 1.94, CL = 1.74–2.16) than for nontoxic goitre and nodules (age‐adjusted HR = 1.26; CL = 1.14–1.38). There was generally no clear risk trend with regard to amount smoked (below and above 10 cigarettes per day). Elevated body mass attenuated these associations, whilst being born in Swedish areas of endemic goitre enhanced the association with nontoxic goitre and nodules.Conclusions.  Smoking enhances the risk of thyroid goitre and nodules requiring hospital admission. Iodine deficiency and body weight are likely to be important modifiers of the risk of thyroid hyperplastic diseases amongst smokers.
NmlR ofNeisseria gonorrhoeae: a novel redox responsive transcription factor from the MerR family
Authors: Kidd Stephen P. , Potter Adam J. , Apicella Michael A. , Jennings Michael P. , McEwan Alastair G. 
Published: August 2005

SummaryA MerR‐like regulator (NmlR –NeisseriamerR‐likeRegulator) identified in theNeisseria gonorrhoeaegenome lacks the conserved cysteines known to bind metal ions in characterized proteins of this family. Phylogenetic analysis indicates that NmlR defines a subfamily of MerR‐like transcription factors with a distinctive  pattern  of  conserved  cysteines  within their primary structure. NmlR regulates itself and three other genes inN. gonorrhoeaeencoding a glutathione‐dependent dehydrogenase (AdhC), a CPx‐type ATPase (CopA) and a thioredoxin reductase (TrxB). AnnmlRmutant lacked the ability to survive oxidative stress induced by diamide and cumene hydroperoxide. It also had >  50‐fold lower NADH‐S‐nitrosoglutathione oxidoreductase activity consistent with a role for AdhC in protection against nitric oxide stress. The upstream sequences of the NmlR regulated genes contained typical MerR‐like operator/promoter arrangements consisting of a dyad symmetry located between the −35 and −10 elements of the target genes. The NmlR target operator/promoters were cloned into a β‐galactosidase reporter system and promoter activity was repressed by the introduction of NmlRin trans. Promoter activity was activated by NmlR in the presence of diamide. Under metal depleted conditions NmlR did not repress PAdhC(or PCopA) promoter activity, but this was reversed in the presence of Zn(II), indicating repression was Zn(II)‐dependent. Analysis of mutated promoters lacking the dyad symmetry revealed constitutive promoter activity which was independent of NmlR. Gel shift assays further confirmed that NmlR bound to the target promoters possessing the dyad symmetry. Site‐directed mutagenesis of the four NmlR cysteine residues revealed that they were essential for activation of gene expression by NmlR.
A non‐RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis
Authors: MacGurn Jason A. , Raghavan Sridharan , Stanley Sarah A. , Cox Jeffery S. 
Published: August 2005

SummaryThe Snm secretion system is a crucial virulence determinant of Mycobacterium tuberculosis. Genes encoding all known components of this alternative secretion pathway are clustered at the same genetic locus, known as RD1. Here, we show that a mutant M. tuberculosis strain containing a transposon insertion in the Rv3615c gene, which is situated outside the RD1 locus, results in loss of Snm secretion. Complementation analysis revealed that both Rv3615c and the downstream gene Rv3614c are required for Snm secretion. Thus, we have renamed the two genes snm9 and snm10 respectively. The snm9::Tn mutant phenocopies bona fide snm mutants, exhibiting attenuation in mice, macrophage growth defects and failure to suppress cytokine induction. Furthermore, yeast two‐hybrid analysis revealed a physical interaction between Snm10 and Snm7 (Rv3882c), suggesting that Snm10 may function in complex with other Snm proteins during secretion. Thus, snm9 and snm10 are the first genes located outside the RD1 locus identified as critical components of Snm secretion. These data indicate that Snm secretion consists of an elaborate network of interactions that likely arose from multiple  duplication  events  during  the  evolution  of M.  tuberculosis.
An investigation of folate‐related genetic factors in the determination of birthweight
Authors: Relton Caroline L. , Pearce Mark S. , Burn John , Parker Louise 
Published: August 2005

SummaryRecent evidence suggests that maternal folate status in early gestation is a significant determinant of infant birthweight. Folate metabolism is known to be controlled by genetic factors, with a number of polymorphic variations in folate metabolising genes identified, several of which have well‐documented functional effects. The current study investigated whether folate‐related polymorphic variation, in association with low maternal folate status, influences birthweight. Red blood cell (RBC) folate analysis and genotyping of five polymorphisms in folate‐related genes [Methylenetetrahydrofolate reductase (MTHFR) 677C>T; MTHFR 1298A>C; cystathionine‐β‐synthase (CβS) 844ins68bp; serine hydroxymethyltransferase (SHMT) 1420C>T; reduced folate carrier‐1 (RFC‐1) 80G>A] were undertaken in mothers and infants from 998 pregnancies. These data were analysed in relation to infant birthweight, adjusted for gender and gestational age (z‐score).Low maternal RBC folate status was associated with reduced infant birthweight. None of the genetic variants studied showed an independent association with infant birthweight. However, two genetic variants were shown to have a significant effect on birthweight when found in association with low maternal RBC folate status. When individuals with variant genotypes and mothers with folate in the lowest quintile were compared with wild‐type individuals and mothers with folate in the highest quintile, the following differences in mean birthweight (z‐score) were observed; maternal MTHFR 677C>T (−0.56 [95% CI −1.00, −0.12]P = 0.01) and infant CβS 844ins68bp (−0.71 [95% CI −1.97, −0.07]P = 0.03). The findings of this study suggest that folate‐related genetic polymorphisms do not directly influence infant birthweight. However, when placed on a background of deficient maternal nutritional status, they may detrimentally affect fetal growth.
Changing patterns of inequality in birthweight and its determinants: a population‐based study, Scotland 1980–2000
Authors: Fairley Lesley 
Published: August 2005

SummaryBirthweight is used as an indicator of individual and population health and is known to be strongly correlated with adult cardiovascular disease. This paper uses routinely collected maternity discharge data from Scotland between 1980 and 2000 to look at birthweight trends and the changes in the distribution of maternal risk factors for birthweight. We also examine the contributions of each of the risk factors to birthweight trends and investigate whether there has been a reduction in inequality in birthweight over time. Data from 1 282 172 singleton live births were used in the analysis. Both mean birthweight and low birthweight (LBW: < 2500 g) were used as outcomes. The risk factors studied were maternal age, parity, maternal height, marital status and occupational social class of the father. The slope and relative indices of inequality were used to measure the change in inequalities over time.Mean birthweight increased from 3320 g in 1980 to 3410 g in 2000, while the percentage LBW decreased slightly from 5.7% in 1980 to 5.4% in 2000. The prevalence of many risk factors changed; there has been an increase in the proportion of older mothers, single mothers, taller mothers and mothers with undetermined social class. Although most risk factors had a significant change in effect over time, the inequalities in birthweight between groups did not appear to diminish over time. Both the slope and relative index of inequality had a quadratic relationship over time, with the inequalities in birthweight being greatest in the early 1980s and late 1990s.