bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost‐effectiveness of increasing kidney transplantation and home‐based dialysis
Authors: HOWARD KIRSTEN , SALKELD GLENN , WHITE SARAH , MCDONALD STEPHEN , CHADBAN STEVE , CRAIG JONATHAN C , CASS ALAN 
Published: February 2009

SUMMARYBackground:  Renal replacement therapy (RRT) consumes sizable proportions of health budgets internationally, but there is considerable variability in choice of RRT modality among and within countries with major implications for health outcomes and costs. We aimed to quantify these implications for increasing kidney transplantation and improving the rate of home‐based dialysis.Methods:  A multiple cohort Markov model was used to assess costs and health outcomes of RRT for new end‐stage kidney disease (ESKD) patients in Australia for 2005–2010, using a health‐care funder perspective. Patient characteristics and current practice patterns were based on the ANZDATA Registry. Two proposed changes were modelled: (i) increasing kidney transplants by between 10% and 50% by 2010; and (ii) increasing home haemodialysis (HD) and peritoneal dialysis (PD) to the highest rates observed among Australian centres. We assessed costs (Australian dollars), survival and quality‐adjusted survival, and cost‐effectiveness.Results:  The number of new ESKD patients in 2010 was estimated to be 2700, with annual RRT costs of about $A700 million; cumulative costs (2005–2010) were $A5 billion. Increasing transplants by 10–50% saves between $A5.8 and $A26.2 million, and increases quality‐adjusted life years (QALYs) by 130–658 QALYs. Switching new patients from hospital HD to (i) home HD saves $A46.6 million by 2010; or (ii) PD saves $A122.1 million.Conclusions:  These clinical practice changes reduce costs, improve patient quality of life and, in the case of transplantation, increase survival. Planning for RRT services should incorporate efforts to maximize rates of transplantation and to encourage home‐based over hospital‐based dialysis to optimize cost‐effectiveness in RRT service delivery.
Advantages of delaying the onset of rehabilitative reaching training in rats with incomplete spinal cord injury
Authors: Krajacic Aleksandra , Ghosh Mousumi , Puentes Rocio , Pearse Damien D. , Fouad Karim 
Published: February 2009

AbstractWe have previously reported that rehabilitative reaching training initiated 4 days following an incomplete cervical spinal cord injury (SCI) in adult rats promotes plasticity and task‐specific recovery. This training, however, also resulted in impairments in an untrained task. Here we examined whether delaying the rehabilitative training following cervical SCI is still effective in promoting task‐specific recovery, but circumvents impairments in an untrained task, comparable to what has been reported in stroke models. Therefore, reaching training for a period of 6 weeks was initiated at Day 12 following a cervical dorso‐lateral quadrant lesion. Thereupon the rats’ ability to reach and to walk on a horizontal ladder (i.e. the untrained task) was assessed, and 8 weeks post‐injury cortical map changes were investigated through microstimulation. Further, we examined changes in phospho protein kinase A (pPKA) levels following an immediate and a delayed onset of reaching training in rats with cervical SCI. We found that delayed rehabilitative training was comparably effective as immediate training in promoting task‐specific recovery and sprouting of injured axons. Importantly, delayed training did not impair the performance on horizontal ladder walking. Strikingly, only delayed reaching training restored cortical PKA levels that had dropped significantly over 2 weeks post‐injury. Additionally, delayed training did not influence cortical map changes following injury, but decreased white matter damage. In conclusion, our results show that a short delay in the onset of training in a forelimb task significantly alters our outcome measures, which should be considered in future rehabilitative approaches.
Differential regulation of psychostimulant‐induced gene expression of brain derived neurotrophic factor and the immediate‐early geneArcin the juvenile and adult brain
Authors: Banerjee Partha S. , Aston James , Khundakar Ahmad A. , Zetterström Tyra S. C. 
Published: February 2009

AbstractPsychostimulant drugs are widely used in children for the treatment of attention‐deficit/hyperactivity disorder. Recent animal studies have suggested that exposure to these agents in early life could be detrimental to brain development. Here, for the first time, the effect of methylphenidate (MPH) andd‐amphetamine (AMPH) on the expression of two key genes for neuronal development and plasticity, brain‐derived neurotrophic factor (bdnf) and the effector immediate early gene activity‐regulated, cytoskeletal‐associated protein (Arc), was examined in both juvenile and adult rats. Both MPH [2 mg/kg, intraperitoneal (i.p.)] and AMPH (0.5 mg/kg, i.p.) induced marked decreases ofbdnfmRNA in hippocampal and cortical brain regions of juveniles, whereas effects in adults were significantly less (hippocampus) or opposite (frontal cortex). In comparison,ArcmRNA was decreased (hippocampus and parietal cortex), largely unaffected (frontal cortex) or increased (striatum) in juveniles, whereas in adults,ArcmRNA increased in most brain regions. MPH‐induced locomotion was also measured, and showed a much smaller increase in juveniles than in adults. In summary, our data show that the effects of MPH and AMPH on expression of the neurodevelopmentally important genes,bdnfandArc, differ markedly in juvenile and adult rats, with juveniles showing evidence of brain region‐specific decreases in both genes. These age‐dependent effects on gene expression may be linked with the reported long‐term harmful effects of psychostimulants in animal models.
Actions of propofol on substantia gelatinosa neurones in rat spinal cord revealed byin vitroandin vivopatch‐clamp recordings
Authors: Takazawa Tomonori , Furue Hidemasa , Nishikawa Koichi , Uta Daisuke , Takeshima Kaori , Goto Fumio , Yoshimura Megumu 
Published: February 2009

AbstractPropofol, an intravenous general anaesthetic, exerts anaesthetic actions through interaction with γ‐aminobutyric acid type A (GABAA) receptors in the supraspinal nervous system. However, whether propofol has any significant effects on synaptic transmission at the spinal level and whether it exhibits antinociceptive action is still not fully clarified. Spontaneous activity and stimulus‐evoked responses of substantia gelatinosa (SG) neurones to noxious pinch stimuli were recorded using spontaneously breathing rats under propofol anaesthesia usingin vivowhole‐cell patch‐clamp techniques. Precise actions of propofol on GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) as well as excitatory postsynaptic currents (EPSCs) in SG neurones were also analyzed in spinal cord slice preparations. At clinical doses (5 mg/kg), propofol reversibly depressed action potentials elicited by noxious mechanical stimuli applied to the skin in the majority (6/8) of SG neurons recorded underin vivoconditions. This depression may have been caused by interactions of propofol with GABAAreceptors, as decay time of GABAergic sIPSCs was prolonged after propofol injection (128 ± 11% of control,n = 5) with minimal effect on EPSCs. Although prolongation of IPSCsin vivowas reversible, IPSCs were progressively prolonged even after washout of propofol when the effect was tested using spinal cord slices. Propofol had a mild depressant effect on Aδ‐ and C‐afferent‐mediated EPSCs. We conclude that systemic bolus injection of propofol reversibly depressed nociceptive transmission, at least in part, by enhancing postsynaptic GABAAreceptor‐mediated responses in the SG.
Age‐dependent effect of prenatal stress on hippocampal cell proliferation in female rats
Authors: Koehl Muriel , Lemaire Valerie , Le Moal Michel , Abrous Djoher N. 
Published: February 2009

AbstractStressors occurring during pregnancy can alter the developmental trajectory of offspring and lead to, among other deleterious effects, cognitive deficits and hyperactivity of the hypothalamo‐pituitary‐adrenal axis. A recent feature of the prenatal stress (PS) model is its reported influence on structural plasticity in hippocampal formation, which sustains both cognitive functions and stress responsiveness. Indeed, we and others have previously reported that males exposed to stress in utero are characterized by a decrease in hippocampal cell proliferation, and consequently neurogenesis, from adolescence to senescence. Recent studies in females submitted to PS have reported conflicting results, ranging from no effect to a decrease in cell proliferation. We hypothesized that changes in cell proliferation in PS female rats are age dependent. To address this issue, we examined the impact of PS on hippocampal cell proliferation in juvenile, young, middle‐aged and old females. As hypothesized, we found an age‐dependent effect of PS in female rats as cell proliferation was significantly decreased only when animals reached senescence, a time when adrenal gland weight also increased. These data suggest that the deleterious effects of PS on hippocampal cell proliferation in females are either specific to senescence or masked during adulthood by protective factors.
Development of the light sensitivity of the clock genes Period1 and Period2, and immediate‐early gene c‐fos within the rat suprachiasmatic nucleus
Authors: Matějů Kristýna , Bendová Zdena , El‐Hennamy Rehab , Sládek Martin , Sosniyenko Serhiy , Sumová Alena 
Published: February 2009

AbstractThe molecular mechanism underlying circadian rhythmicity within the suprachiasmatic nuclei (SCN) of the hypothalamus has two light‐sensitive components, namely the clock genes Per1 and Per2. Besides, light induces the immediate‐early gene c‐fos. In adult rats, expression of all three genes is induced by light administered during the subjective night but not subjective day. The aim of the present study was to ascertain when and where within the SCN the photic sensitivity of Per1, Per2 and c‐fos develops during early postnatal ontogenesis. The specific aim was to find out when the circadian clock starts to gate photic sensitivity. The effect of a light pulse administered during either the subjective day or the first or second part of the subjective night on gene expression within the rat SCN was determined at postnatal days (P) 1, 3, 5 and 10. Per1, Per2 and c‐fos mRNA levels were assessed 30 min, 1 and 2 h after the start of each light pulse by in situ hybridization histochemistry. Expression of Per1 and c‐fos was light responsive from P1, and the responses began to be gated by the circadian clock at P3 and P10, respectively. Expression of Per2 was only slightly light responsive at P3, and the response was not fully gated until P5. These data demonstrate that the light sensitivity of the circadian clock develops gradually during postnatal ontogenesis before the circadian clock starts to control the response. The photoinduction of the clock gene Per2 develops later than that of Per1.
Galantamine protects against oxidative stress induced by amyloid‐beta peptide in cortical neurons
Authors: Melo Joana B. , Sousa Carla , Garção Pedro , Oliveira Catarina R. , Agostinho Paula 
Published: February 2009

AbstractGalantamine is currently used in the treatment of patients with mild‐to‐moderate Alzheimer’s disease (AD). Although its action is mostly directed at the regulation of cholinergic transmission, galantamine can also afford neuroprotection against amyloid‐beta peptide (Aβ), which is involved in AD pathogenesis. In this study, we used cultured rat cortical neurons treated with two forms of Aβ1–40, fresh and previously aged (enriched in fibrils). First, we confirmed that galantamine prevented neurodegeneration induced by both peptide forms in a concentration‐dependent manner. Moreover, we observed that when neurons were co‐incubated with fresh Aβ1–40 plus galantamine, the amount of amyloid aggregates was reduced. As oxidative conditions influence Aβ aggregation, we investigated whether galantamine prevents oxidative stress induced by this peptide. The data show that either fresh or aged Aβ1–40 significantly increased the amount of reactive oxygen species and lipoperoxidation, these effects being prevented by galantamine. In Aβ1–40‐treated neurons, the depletion of reduced glutathione (GSH) seems to be related to the decrease in glutathione peroxidase and glutathione reductase activities. These alterations in the GSH antioxidant system were prevented by galantamine. Overall, these results constitute the first evidence that galantamine can prevent the neuronal oxidative damage induced by Aβ, providing an in vitro basis for the beneficial actions of galantamine in the AD neurodegenerative process.
Development of the representation of auditory space in the superior colliculus of the rat
Authors: Vachon‐Presseau Etienne , Martin Alex , Lepore Franco , Guillemot Jean‐Paul 
Published: February 2009

AbstractThe aims of the present study were, first, to determine the time of the emergence of the topographic map in the superior colliculus (SC) of the rat and, second, to examine the spatial changes in auditory neurons’ receptive fields (RFs) throughout the developmental period. For these purposes, recording sessions were conducted on rats of different age groups (P15–18; P21–24; P27–29 and P60–80). Results show that SC auditory neurons’ RFs go through multiple changes during early development before the establishment of the adult‐like auditory topographic map (P27). These modifications include, first, the refining of directional RFs tuning between P18 and P27 and, second, a shift of sensitivity towards 90° in the contralateral hemispace after P15–18. In addition, data indicate that the neuronal response latencies are shorter in the adult group than in the P15–18 or P21–24 groups. Finally, a diminution in spontaneous firing rate was observed between the P15–18 group and the P60–80 group. The results of the present study revealed that the neural organization representing auditory space in the deep layers of the SC of the rat is not innate, but rather emerges at about P27–29. Moreover, they bring new evidence supporting a two‐step process involved in the development of the representation of auditory space. Hence, the development of the auditory space representation follows a logical temporal maturation sequence whereby the RF organization must be completed before a stable topographic map can be formed.
Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long‐acting glucagon‐like peptide‐1 mimetic, in healthy subjects
Authors: Bush M. A. , Matthews J. E. , De Boever E. H. , Dobbins R. L. , Hodge R. J. , Walker S. E. , Holland M. C. , Gutierrez M. , Stewart M. W. 
Published: February 2009

Aims:  Albiglutide is a glucagon‐like peptide‐1 (GLP‐1) mimetic generated by genetic fusion of a dipeptidyl peptidase‐IV‐resistant GLP‐1 dimer to human albumin. Albiglutide was designed to retain the therapeutic effects of native GLP‐1 while extending its duration of action. This study was conducted to determine the pharmacokinetics and initial safety/tolerability profile of albiglutide in non‐diabetic volunteers.Methods:  In this single‐blind, randomized, placebo‐controlled trial, 39 subjects (18–60 years, body mass index 19.9–35.0 kg/m2) received placebo (n = 10) or escalating doses of albiglutide (n = 29) on days 1 and 8 in the following sequential cohorts: cohort 1: 0.25 + 1 mg; cohort 2: 3 + 6 mg; cohort 3: 16 + 24 mg; cohort 4: 48 + 60 mg; and cohort 5: 80 + 104 mg. Dose proportionality was evaluated based on area under the plasma drug concentration versus time curve [area under the curve (AUC(0–7 days))] and maximum plasma drug concentration (Cmax) for cohorts 2–5 during week 1.Results:  Albiglutide had a terminal elimination half‐life (T1/2) of 6–8 days and time to maximum observed plasma drug concentration (Tmax) of 3–4 days. A greater‐than‐dose proportional increase in albiglutide exposure was observed. Albiglutide demonstrated a dose‐dependent trend in reductions of glucose weighted mean AUC and fructosamine levels in healthy subjects. The incidence and severity of adverse events (AEs) was similar between placebo and albiglutide groups. Headache was the most frequent drug‐related AE, followed by constipation, flatulence and nausea.Conclusions:  Albiglutide has a half‐life that favours once weekly or less frequent dosing with an acceptable safety/tolerability profile in non‐diabetic subjects.
The safety profile of tadalafil as prescribed in general practice in England: results from a prescription‐event monitoring study involving 16 129 patients
Authors: Hazell Lorna , Cornelius Victoria , Wilton Lynda V. , Shakir Saad A.W. 
Published: February 2009

OBJECTIVESTo examine the safety of tadalafil as used in general practice in England, and to compare the mortality rate due to ischaemic heart disease (IHD) in tadalafil users with that in the male population in England.PATIENTS AND METHODSPatients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by general practitioners (GPs) from February 2003 to November 2004. Demographic and outcome data (clinical events) were requested from patients’ GPs using a postal questionnaire. A standardized mortality ratio (SMR) was calculated using indirect standardization for deaths from IHD in the cohort (where age was known) over a 1‐year observation period compared to that in the English male population (2003). A sensitivity analysis was carried out to investigate the effects of missing data for age and cause of death.RESULTSClinical information was obtained for 16 129 patients (median age 60 years, interquartile range 52–67); the age was not specified for 3212 (19.9%) patients. At least a third of the patients had diabetes mellitus and 29% had hypertension. Comparison of the mortality rate due to IHD for the patients of known age with that in the English male population provided an SMR of 0.57 (95% confidence interval 0.38–0.83) indicating fewer observed deaths in the cohort than expected. The results of the sensitivity analyses investigating the effect of missing data for age and cause of death produced similar SMR estimates. One confirmed case of non‐arteritic anterior ischaemic optic neuropathy (NAION) was reported during tadalafil therapy in a patient with other risk factors for this condition.CONCLUSIONThe results from this prescription‐event monitoring study suggest that tadalafil is generally well tolerated when used in general practice in England. The most frequently reported adverse clinical events were in keeping with clinical trial data and include headache, dyspepsia and back pain. There was no evidence of a greater mortality rate due to IHD in the tadalafil cohort than in the general male population. However, these results are limited by the use of an external comparator group and might be explained by a ‘healthy cohort effect’. One event of NAION was reported, and although a causal relationship was not established it indicates that NAION occurs rarely in patients prescribed tadalafil.
Stone measurement by volumetric three‐dimensional computed tomography for predicting the outcome after extracorporeal shock wave lithotripsy
Authors: Bandi Gaurav , Meiners Ryan J. , Pickhardt Perry J. , Nakada Stephen Y. 
Published: February 2009

OBJECTIVETo evaluate the efficacy of stone volume measured using a three‐dimensional (3D) reconstruction of preoperative non‐contrast computed tomography (NCCT) as an independent predictor of success after extracorporeal shock wave lithotripsy (ESWL) of upper urinary tract calculi.PATIENTS AND METHODSWe evaluated preoperative NCCT in 94 patients who had ESWL for solitary upper urinary tract calculi of 4–20 mm in diameter. Axial images were used to measure the skin‐to‐stone distance (SSD), Hounsfield Unit (HU) density and axial stone diameter. Stone volume was calculated on a volume‐rendered 3D image for each stone. Maximum stone length was determined by comparative measurements of each stone in coronal, sagittal and axial planes, and was also measured on a plain abdominal film before ESWL. For ESWL we used the DoliS lithotripter (Dornier Medical Systems, Marrietta, GA, USA). A plain film at 6 weeks was used to categorize patients as stone‐free (SF) or with residual stone.RESULTSIn all, 58 (62%) patients were SF and 36 (38%) had RS; the mean stone volume was significantly different between these groups (274 vs 464 µL, P = 0.002). Logistic regression analysis showed that stone volume was the strongest predictor of SF status (P < 0.001), compared to peak HU (P = 0.015), mean HU (P = 0.04) and axial stone diameter (P = 0.006). The body mass index, SSD and maximum stone length on NCCT or a plain film did not predict success. A stone volume of <500 µL best predicted treatment success (P < 0.001) with 72% of patients with a stone volume of <500 µL having a successful outcome, vs only 27% with a stone volume of >500 µL.CONCLUSIONOur study suggests that stone volume is an optimal predictor of SF status after ESWL of solitary upper urinary tract calculi.
Mutations in the lamin B1 gene are not present in multiple sclerosis
Authors: Brussino A. , D’Alfonso S. , Cagnoli C. , Di Gregorio E. , Barberis M. , Padovan S. , Vaula G. , Pinessi L. , Squadrone S. , Abete M. C. , Collimedaglia L. , Guerini F. R. , Migone N. , Brusco A. 
Published: February 2009

Background:  Whole gene duplication of the lamin B1 gene (LMNB1), encoding for a protein of the nuclear lamina, causes an adult‐onset autosomal dominant leukodystrophy (ADLD). Clinical features of ADLD (onset in adult life, dysautonomic symptoms, followed by pyramidal and cerebellar dysfunctions) partially resemble those of multiple sclerosis (MS), particularly the primary‐progressive form. Our aim was to test whether LMNB1 gene mutations were present amongst patients with a diagnosis of MS.Methods:  One hundred eighty‐two MS patients were screened for copy number variations of the LMNB1 gene using a qPCR assay. Point mutations in the LMNB1 gene were searched by denaturing high‐performance liquid chromatography and direct sequencing in a subgroup of 16 patients with familial MS.Results:  No duplication/deletion of the lamin B1 gene was found amongst MS patients, and no point mutation was identified in the familial cases.Conclusion:  Our work indicates that lamin B1 defects are probably not responsible for signs and symptoms resembling multiple sclerosis.
Comparison of the characteristics for in‐hospital and out‐of‐hospital ischaemic strokes
Authors: Park H. J. , Cho H. J. , Kim Y.‐D. , Lee D. W. , Choi H.‐Y. , Kim S. M. , Heo J. H. 
Published: February 2009

Background and purpose:  Patients who are being admitted to a hospital due to diseases other than stroke may develop a stroke (in‐hospital stroke; IHS).Methods:  We enrolled 111 consecutive patients who developed IHS outside a neurology ward during a 5‐year period at a single hospital. The frequency, characteristics, and outcomes for IHS patients were compared with patients who develop ischaemic stroke outside of the hospital (out‐of‐hospital stroke; OHS).Results:  Forty‐six percent of IHS occurred in the department of cardiology or cardiovascular surgery and 60% were associated with surgery or procedures. In comparison with the OHS patient group, the IHS patient group showed an increased frequency of cardiac disease, leukocytosis, and anemia. Cardioembolism, stroke of other determined etiologies, and an incomplete evaluation were more common in the IHS group, whereas large artery atherosclerosis was more frequent in the OHS group. The IHS group had up to a 10‐fold higher mortality than the OHS group, with sepsis being the most common cause of death in the IHS group.Conclusions:  IHS has distinct etiologies and stroke mechanisms from OHS. The prevention and management of infection could decrease mortality in IHS patients.