bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organizational assessment in general practice: a systematic review and implications for quality improvement
Authors: Rhydderch Melody , Edwards Adrian , Elwyn Glyn , Marshall Martin , Engels Yvonne , Van den Hombergh Pieter , Grol Richard 
Published: July 2005

AbstractBackground  Quality improvement of organizational aspects in general practice is receiving increasing attention. In particular, the impact of effective organization on preventative care has been recognized. Organizational assessments are typically used as part of professionally led accreditation schemes where there is a tension between externally led quality assurance and internally led quality improvement. The aim of this article is to inform the debate by reviewing the international‐peer‐reviewed literature on organizational assessments used in  general  practice  settings.  Design  Systematic literature review.Methods  The literature was searched for articles relating to organizational assessment. Titles and abstracts were examined by two independent reviewers and relevant articles obtained. Bibliographies were examined for follow‐up references. Data were extracted on the development and use of assessment methods.Results  Thirteen papers describing five organizational assessment instruments were included for detailed appraisal.Conclusion  This review discovered a developing field containing different approaches to the measurement of organizational aspects of general practice. Whilst professionally led accreditation is well‐developed and dependent on externally led quality assurance, approaches to internally led quality improvement are less well‐developed. There is a need for organizational assessment tools designed for the purpose of stimulating internal development.
Factors that influence prescribing within a therapeutic drug class
Authors: Nutescu Edith A. , Park Hayley Y. , Walton Surrey M. , Blackburn Juan C. , Finley Jamie M. , Lewis Richard K. , Schumock Glen T. 
Published: July 2005

AbstractRationale, aims and objectives  The decision to prescribe one drug instead of another within the same therapeutic class may be influenced by a variety of drug‐related, direct, or indirect factors; but little is known about which considerations are most important in such choices. The low‐molecular‐weight heparins (LMWHs) represent a class of drugs that are commonly used and for which therapeutic equivalence has been debated in the literature. The purpose of this study was to identify and compare factors perceived by doctors and clinical pharmacists to be influential in prescribing decisions among LMWHs.Methods  Doctors and clinical pharmacists were interviewed to elicit information and to rank factors that influence the prescribing and use of LMWHs in community hospitals in the United States. For each factor, the mean and median of the rating were determined along with the frequency distribution across ratings. The non‐parametric Mann–Whitney U‐test was used to examine differences between doctors and clinical pharmacists.Results  Both groups considered efficacy, formulary status, and policies restricting drug use to be highly influential in the decision to use one LMWH instead of another. Compared to clinical pharmacists, doctors rated personal experience as more influential, whereas they rated drug cost and prescribing guidelines lower.Conclusions  These findings suggest that doctors and clinical pharmacists differentiate between LMWHs based on differences between products and because of hospital administrative programs (such as drug formularies). This information may be of value in designing programs to alter medication use.
The impact of practice guidelines and funding policies on the use of new drugs in advanced non‐small cell lung cancer*
Authors: Dranitsaris George , Evans William K. , Milliken Debbie , Zanke Brent 
Published: July 2005

AbstractBackground  Cancer Care Ontario's (CCO) Program in Evidence‐based Care has provided a credible basis for policy development and the funding of new and expensive anticancer drugs in the province of Ontario. In November 1997, vinorelbine was approved for the first‐line treatment of advanced non‐small cell lung cancer (NSCLC) on the basis of evidence‐based practice guidelines generated by the Provincial Lung Disease Site Group. In June 1998, gemcitabine was approved as an alternative to vinorelbine for use in selected patients (e.g. significant venous access problems, peripheral neuropathy, severe toxicity to vinorelbine). A provincial drug database was used to determine the impact that these new policies had on the rate of vinorelbine and gemcitabine uptake within the CCO new drug funding programme.Methods  Drug utilization data for vinorelbine and gemcitabine from October 1997 to June 1999 were obtained from the CCO drug database. Individual patient data consisted of age, gender, first‐line agent used, number of treatments, duration of therapy, treatment location (regional cancer centre vs. other) and total cost. Demographic and drug utilization data were analysed descriptively as means, medians, or proportions. Multivariable logistic regression analysis was then used to identify factors associated with the selection of gemcitabine over vinorelbine, as a first‐line therapy.Results  Following the approval of the first policy in November 1997, there was a rapid adoption of vinorelbine use in new NSCLC patients. When the gemcitabine policy was approved in June 1998, there was a rapid uptake in its use reaching a stable plateau of approximately 15% of all NSCLC patients within 9 months. The logistic regression analysis identified patient age greater than 65 years [odds ratio (OR) = 1.90, P = 0.001] and treatment in a non‐regional cancer setting (OR = 1.71, P = 0.008) as significant predictors of gemcitabine utilization. Overall, the mean drug cost per patient treated with first‐line gemcitabine was significantly higher than vinorelbine ($Can2590 vs. $Can1030, P < 0.001).Conclusions  The new funding policies were associated with a rapid increase in drug utilization reaching a stable plateau within 9 months. Factors contributing to the usage of these new drugs for NSCLC included patient characteristics, such as age and treatment location.
Kisspeptins: Regulators of Metastasis and the Hypothalamic‐Pituitary‐Gonadal Axis
Authors: Murphy K. G. 
Published: July 2005

AbstractThe kisspeptins are the peptide products of the KiSS‐1 gene and the endogenous agonists for the GPR54 receptor. Although KiSS‐1 was initially discovered as a metastasis suppressor gene, recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. Disrupted GPR54 signalling causes hypogonadotrophic hypogonadism in rodents and man. Central or peripheral administration of kisspeptin potently stimulates the hypothalamic‐pituitary‐gonadal axis, increasing circulating gonadotrophin concentrations in a number of animal models. These effects appear likely to be mediated via the hypothalamic gonadotrophin‐releasing hormone system, although kisspeptins may have direct effects on the anterior pituitary gland. Hypothalamic KiSS‐1 expression is regulated by circulating sex steroids. The precise physiological role of the kisspeptin system in the regulation of reproductive function remains to be elucidated.
Perinatal Influences of Melatonin on Testicular Development and Photoperiodic Memory in Siberian Hamsters
Authors: Tuthill C. R. , Freeman D. A. , Butler M. P. , Chinn Tori , Park J. H. , Zucker I. 
Published: July 2005

AbstractWe assessed the influence of perinatal melatonin on reproductive development and adult responsiveness to melatonin. Testicular growth in an intermediate day length (14 : 10 h light/dark cycle) was substantially reduced in Siberian hamsters gestated by pinealectomised compared to pineal‐intact females; gonadal development was normalised in offspring of pinealectomised dams that were pinealectomised at 3–4 days of age. Hamsters deprived of melatonin only during gestation, or both pre‐ and postnatally, underwent testicular involution during treatment with melatonin in adulthood. Photoperiodic histories acquired prenatally did not endure as long as those acquired by adult hamsters. Hamsters first exposed to melatonin in adulthood were not more proficient in acquiring photoperiodic histories than were normal males. These findings indicate that pre‐ versus postnatal differences in melatonin signal duration determine rates of testicular development. Exposure to melatonin perinatally does not appear to organise the neuroendocrine substrate that mediates effects of day length and melatonin on the gonads of adult hamsters.
Altered Mesencephalic Dopaminergic Populations in Adulthood as a Consequence of Brief Perinatal Glucocorticoid Exposure
Authors: McArthur S. , McHale E. , Dalley J. W. , Buckingham J. C. , Gillies G. E. 
Published: July 2005

AbstractEarly exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological ‘programming’ are unclear. This study tested the hypothesis that inappropriate exposure to glucocorticoid stress hormones (GCs) during critical periods of development permanently alters the mesencephalic dopaminergic populations in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Using a rat model, the synthetic GC dexamethasone was added to the maternal drinking water during gestational days 16–19 or over the first week of postnatal life. In adulthood, the effects upon tyrosine hydroxylase immunopositive (TH+) cell numbers in the midbrain, and monoamine levels in the forebrain, of the adult offspring were assessed and compared with control offspring whose dams received normal drinking water. In the VTA, both prenatal and postnatal dexamethasone treatment increased TH+ cell numbers by approximately 50% in males and females. Although prenatal dexamethasone treatment also increased TH+ cell numbers in the SNc by 40–50% in males and females, postnatal treatment affected females only by increasing TH+ cell numbers by approximately 30%. In comparison, similar changes were not detected in the monoamine levels of the dorsolateral striatum, nucleus accumbens or infralimbic cortex of either males or females, which is a feature likely to reflect adaptive changes in these pathways. These studies demonstrate that the survival or phenotypic expression of VTA and SNc dopaminergic neurones is profoundly influenced by brief perinatal exposure to GCs at times when endogenous levels are normally low. These findings are the first to demonstrate permanent changes in the cytoarchitecture within midbrain dopamine nuclei after perinatal exposure to stress hormones and implicate altered functionality. Thus, they have significance for the increasing use of GCs in perinatal medicine and indicate potential mechanisms whereby perinatal distress may predispose to the development of a range of psychiatric conditions in later life.
Evidence that the Type‐2 Gonadotrophin‐Releasing Hormone (GnRH) Receptor Mediates the Behavioural Effects of GnRH‐II on Feeding and Reproduction in Musk Shrews
Authors: Kauffman A. S. , Wills A. , Millar R. P. , Rissman E. F. 
Published: July 2005

AbstractGonadotrophin‐releasing hormone (GnRH) is a regulatory neuropeptide of which there are multiple structural variants. In mammals, a hypothalamic form (GnRH‐I) controls gonadotrophin secretion whereas a midbrain form (GnRH‐II) appears to have a neuromodulatory role affecting feeding and reproduction. In female musk shrews and mice, central administration of GnRH‐II reinstates mating behaviour previously inhibited by food restriction. In addition, GnRH‐II treatment also decreases short‐term food intake in musk shrews. GnRH‐II can bind two different mammalian GnRH receptors (type‐1 and type‐2), and thus it is unclear which receptor subtype mediates the behavioural effects of this peptide. Adult female musk shrews implanted with i.c.v. cannula were food restricted or fed ad lib and then tested for sexual behaviour or food intake. One hour before testing, animals were pretreated with vehicle or Antide, a potent type‐1 GnRH receptor antagonist (at a dose that blocks GnRH‐I or ‐II mediated ovulation). Twenty minutes before testing, females were infused a second time with either GnRH‐II or vehicle. Additional females were tested after an infusion of 135‐18, a type‐1 receptor antagonist that displays agonist actions at the primate type‐2 receptor. GnRH‐II treatment increased sexual behaviour in underfed female shrews; pretreatment with Antide did not block this action, suggesting that the effects of GnRH‐II are not mediated via the type‐1 receptor. Similarly, the inhibitory effects of GnRH‐II on short‐term food intake were not prevented by pretreatment with Antide. The behavioural effects of the type‐2 receptor agonist 135‐18 were similar to those seen in GnRH‐II‐treated females, with 135‐18 promoting sexual behaviour and decreasing food intake. Collectively, these results indicate that GnRH‐II does not act via the type‐1 GnRH receptor to regulate mammalian behaviour but likely activates the type‐2 GnRH receptor.
Stress‐Induced Changes in Spatial Memory are Sexually Differentiated and Vary Across the Lifespan
Authors: Bowman R. E. 
Published: July 2005

AbstractStress exposure, depending on intensity and duration, elicits adaptive or maladaptive physiological changes. The same general pattern of advantageous versus deleterious stress effects appears to exist for some cognitive functions, particularly spatial learning and memory performance. This article reviews sex differences in response to stress on a variety of spatial tasks. In general, females are more resistant than males to stress‐induced impairments on spatial tasks, including the radial arm maze and object placement. In young adulthood, chronic stress (restraint, 6 h per day for 21 days) impairs male performance on both tasks but leads to behavioural enhancements in females. Furthermore, these sex‐dependent stress effects are influenced by both organisational and activational oestrogenic effects. Additionally, sex‐specific stress responses vary depending on developmental age at the time of stress exposure. Male behavioural stress responses appear fixed across the lifespan (i.e. stress‐induced cognitive impairments) whereas female stress responses appear more variable (i.e. stress‐induced enhancements observed in young adulthood are different in response to prenatal stress and diminished following stress exposure at old age). These findings underscore the point that many effects obtained in males cannot be generalised to females and highlight the need to investigate the stress response at different ages and in both sexes.
Prostaglandin E2 Mediates Cellular Effects of Interleukin‐1β on Parvocellular Neurones in the Paraventricular Nucleus of the Hypothalamus
Authors: Ferri C. C. , Ferguson A. V. 
Published: July 2005

AbstractInterleukin‐1β (IL‐1β) is involved in hypothalamic regulation of corticotrophin‐releasing hormone secretion, autonomic activation and consequent downstream modulation of the neuroimmune response. Previously, we have shown that IL‐1β depolarises parvocellular neurones in the paraventricular nucleus (PVN) of the hypothalamus, and these effects are dependent on attenuation of γ‐amino butyric acid (GABA)‐ergic input. In the present study, using whole‐cell patch clamp recordings of rat neurones in a slice preparation of the PVN, we show that the effects of IL‐1β are abolished in the presence of a cyclooxygenase (COX)‐2 inhibitor, NS‐398, indicating a dependence on prostaglandin (PG) synthesis and activation. In response to 1 µM PGE2, 64% of parvocellular neurones tested exhibited a clear depolarisation, which was abolished in the presence of tetrodotoxin (TTX). Furthermore, neurones responsive to both IL‐1β and PGE2 exhibited a decrease in the frequency of inhibitory post‐synaptic potentials, suggesting that effects of these modulators are mediated via a decrease in GABA‐ergic input to these neurones. A proportion (44% and 40%, respectively) of putative GABA‐ergic neurones in the halo region surrounding the PVN demonstrated hyperpolarising responses to 1 nM IL‐1β and 1 µM PGE2, and these effects were maintained in TTX. Furthermore, direct hyperpolarising effects of IL‐1β were blocked in the presence of NS‐398. Together, these data suggest that PGE2, synthesised in response to IL‐1β‐activation of COX‐2 expressing cells, directly hyperpolarises putative GABA‐ergic neurones in the halo zone surrounding and projecting to the PVN, resulting in a decrease in GABA‐ergic input to parvocellular neurones and consequent depolarisation. These data further elucidate the cellular mechanisms by which IL‐1β exerts its neuroimmune‐related actions in the PVN.
Oestrogens Prevent Loss of Dopamine Transporter (DAT) and Vesicular Monoamine Transporter (VMAT2) in Substantia Nigra of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Mice
Authors: Jourdain S. , Morissette M. , Morin N. , Di Paolo T. 
Published: July 2005

AbstractPrevious results from our laboratory have shown that 17β‐oestradiol prevents 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) striatal dopamine depletion. 17β‐oestradiol, oestriol and oestrone are the naturally occurring oestogens in humans. Using various dopamine markers, the present study investigated whether oestrone and oestriol such as 17β‐oestradiol have neuroprotective activity in MPTP‐treated mice. Male mice were treated with 17β‐oestradiol, oestriol or oestrone for 5 days before and after MPTP administration, and were compared with nonlesioned mice receiving the same treatment. Striatal concentrations of dopamine and its metabolites, 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assayed by high‐performance liquid chromatography. Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) specific binding were measured by autoradiography. DAT, VMAT2 and tyrosine hydroxylase mRNA levels were measured byin situhybridisation. MPTP induced a loss of DAT and VMAT2 specific binding in the striatum and substantia nigra, as well as a decrease of VMAT2 mRNA in the substantia nigra. 17β‐oestradiol treatment prevented the loss of these dopaminergic markers, as well as striatal concentrations of dopamine, DOPAC and HVA. Mice receiving oestriol and oestrone showed catecholamine concentrations comparable to MPTP mice. Oestriol treatment had no effect on dopaminergic markers in MPTP mice whereas oestrone prevented striatal DAT loss and the decrease of VMAT2 mRNA in the substantia nigra. In nonlesioned mice, 17β‐oestradiol,oestriol or oestrone had no effect on all the dopaminergic markers investigated. In conclusion, a weak or a lack of effect of oestriol and oestrone was observed compared to 17β‐oestradiol in MPTP mice and none of these steroids had an effect in nonlesioned mice. A DAT and VMAT2 specific binding decrease after MPTP in the striatum and substantia nigra, as well as a decrease of substantia nigra VMAT2 mRNA, was observed and could be prevented by oestradiol.
Responses of net ecosystem CO2 exchange in managed grassland to long‐term CO2 enrichment, N fertilization and plant species
Authors: AESCHLIMANN URS , NÖSBERGER JOSEF , EDWARDS PETER J. , SCHNEIDER MANUEL K. , RICHTER MICHAEL , BLUM HERBERT 
Published: July 2005

ABSTRACTThe effects of elevated pCO2 on net ecosystem CO2 exchange were investigated in managed Lolium perenne (perennial ryegrass) and Trifolium repens (white clover) monocultures that had been exposed continuously to elevated pCO2 (60 Pa) for nine growing seasons using Free Air CO2 Enrichment (FACE) technology. Two levels of nitrogen (N) fertilization were applied. Midday net ecosystem CO2 exchange (mNEE) and night‐time ecosystem respiration (NER) were measured in three growing seasons using an open‐flow chamber system. The annual net ecosystem carbon (C) input resulting from the net CO2 fluxes was estimated for one growing season. In both monocultures and at both levels of N supply, elevated pCO2 stimulated mNEE by up to 32%, the exact amount depending on intercepted PAR. The response of mNEE to elevated pCO2 was larger than that of harvestable biomass. Elevated pCO2 increased NER by up to 39% in both species at both levels of N supply. NER, which was affected by mNEE of the preceding day, was higher in T. repens than in L. perenne. High N increased NER compared to low N supply. According to treatment, the annual net ecosystem C input ranged between 210 and 631 g C m−2 year−1 and was not significantly affected by the level of pCO2. Low N supply led to a higher net C input than high N supply. We demonstrated that at the ecosystem level, there was a long‐term stimulation in the net C assimilation during daytime by elevated pCO2. However, because NER was also stimulated, net ecosystem C input was not significantly increased at elevated pCO2. The annual net ecosystem C input was primarily affected by the amount of N supplied.
Stomatal, mesophyll conductance and biochemical limitations to photosynthesis as affected by drought and leaf ontogeny in ash and oak trees
Authors: GRASSI GIACOMO , MAGNANI FEDERICO 
Published: July 2005

ABSTRACTGas exchange measurements were carried out on ash and oak trees in a forest plantation during three whole growing seasons characterized by different water availability (2001, 2002 and 2003). A quantitative limitation analysis was applied to estimate the effects of drought and leaf ontogeny on stomatal (SL) and non‐stomatal limitations (NSL) to light‐saturated net photosynthesis (Amax), relative to the seasonal maximum rates obtained under conditions of optimal soil water content. Furthermore, based on combined gas exchange and chlorophyll fluorescence measurements, NSL was partitioned into a diffusive (due to a decrease in mesophyll conductance, MCL) and a biochemical component (due to a decrease in carboxylation capacity, BL). During the wettest year (2002), the seasonal pattern of both Amax and stomatal conductance (gsw) was characterized in both species by a rapid increase during spring and a slight decline over the summer. However, with a moderate (year 2001) or a severe (year 2003) water stress, the summer decline of Amax and gsw was more pronounced and increased with drought intensity (30–40% in 2001, 60–75% in 2003). The limitation analysis showed that during the spring and the autumn periods SL, MCL and BL were of similar magnitude. By contrast, from the summer data it emerged that all the limitations increased with drought intensity, but their relative contribution changed. At mild to moderate water stress (corresponding to values of gsw > 100 mmol H2O m−2 s−1) about two‐thirds of the decline in Amax was attributable to SL. However, with increasing drought intensity, NSL increased more than SL and nearly equalled it when the stress was very severe (i.e. with gsw < 60 mmol H2O m−2 s−1). Within NSL, MCL represented the main component, except at the most severe water stress levels when it was equalled by BL. It is concluded that diffusional limitations (i.e. SL + MCL) largely affect net assimilation during most of the year, whereas biochemical limitations are quantitatively important only during leaf development and senescence or with severe droughts.