bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered synaptic plasticity in the mossy fibre pathway of transgenic mice expressing mutant amyloid precursor protein
Authors: Witton Jonathan , Brown Jon T , Jones Matthew W , Randall Andrew D 
Published: November 2010

Abstract
Aβ peptides derived from the cleavage of amyloid precursor protein are widely believed to play an important role in the pathophysiology of Alzheimer's disease. A common way to study the impact of these molecules on CNS function is to compare the physiology of transgenic mice that overproduce Aβ with non-transgenic animals. In the hippocampus, this approach has been frequently applied to the investigation of synaptic transmission and plasticity in the perforant and Schaffer collateral commissural pathways, the first and third components of the classical hippocampal trisynaptic circuit, respectively. Similar studies however have not been carried out on the remaining component of the trisynaptic circuit, the mossy fibre pathway. Using transverse hippocampal slices prepared from ~2 year old animals we have compared mossy fibre synaptic function in wild-type mice and their Tg2576 littermates which age-dependently overproduce Aβ. Input-output curves were not altered in slices from Tg2576 mice, but these animals exhibited a significant loss of the prominent frequency-facilitation expressed by the mossy fibre pathway. In addition to this change in short term synaptic plasticity, high frequency stimulation-induced, NMDA-receptor-independent LTP was absent in slices from the transgenic mice. These data represent the first description of functional deficits in the mossy fibre pathway of Aβ-overproducing transgenic mice.
On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study
Authors: Klopotowska Joanna E , Kuiper Rob , van Kan Hendrikus J , de Pont Anne-Cornelie , Dijkgraaf Marcel G , Lie-A-Huen Loraine , Vroom Margreeth B , Smorenburg Susanne M 
Published: November 2010

Abstract
Introduction
Patients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting.

Methods
A prospective study compared a baseline period with an intervention period. During the intervention period, an ICU hospital pharmacist reviewed medication orders for patients admitted to the ICU, noted issues related to prescribing, formulated recommendations and discussed those during patient review meetings with the attending ICU physicians. Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians.

Results
During the 8.5-month study period, medication orders for 1,173 patients were reviewed. The ICU hospital pharmacist made a total of 659 recommendations. During the intervention period, the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74%. The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period: 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days, respectively (P < 0.001). Preventable ADEs (patient harm, National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period (P = 0.25). Per monitored patient-day, the intervention itself cost €3, but might have saved €26 to €40 by preventing ADEs.

Conclusions
On-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm (preventable ADEs) at acceptable costs per monitored patient-day.

Trial registration number
ISRCTN92487665
Acidemia does not affect outcomes of patients with acute cardiogenic pulmonary edema treated with continuous positive airway pressure
Authors: Aliberti Stefano , Piffer Federico , Brambilla Anna Maria , Bignamini Angelo A , Rosti Valentina D , Maraffi Tommaso , Monzani Valter , Cosentini Roberto 
Published: November 2010

Abstract
Introduction
A lack of data exists in the literature evaluating acidemia on admission as a favorable or negative prognostic factor in patients with acute cardiogenic pulmonary edema (ACPE) treated with non-invasive continuous positive airway pressure (CPAP). The objective of the present study was to investigate the impact of acidemia on admission on outcomes of ACPE patients treated with CPAP.

Methods
This was a retrospective, observational study of consecutive patients admitted with a diagnosis of ACPE to the Emergency Department of IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, between January 2003 and December 2006, treated with CPAP on admission. Two groups of patients were identified: subjects with acidemia (acidotic group), and those with a normal pH on admission (controls). The primary endpoint was clinical failure, defined as switch to bi-level ventilation, switch to endotracheal intubation or inhospital mortality.

Results
Among the 378 patients enrolled, 290 (77%) were acidotic on admission. A total of 28 patients (9.7%) in the acidotic group and eight patients (9.1%) among controls experienced a clinical failure (odds ratio = 1.069, 95% confidence interval = 0.469 to 2.438, P = 0.875). Survival analysis indicates that, among acidotic patients, the time at which 50% of patients reached the 7.35 threshold was 173 minutes (95% confidence interval = 153 to 193). Neither acidemia (P = 0.205) nor the type of acidosis on admission (respiratory acidosis, P = 0.126; metabolic acidosis, P = 0.292; mixed acidosis, P = 0.397) affected clinical failure after adjustment for clinical and laboratory factors in a multivariable logistic regression model.

Conclusions
Neither acidemia nor the type of acidosis on admission should be considered risk factors for adverse outcomes in ACPE patients treated with CPAP.
Alemtuzumab Treatment of Intermediate-1 Myelodysplasia Patients Is Associated With Sustained Improvement in Blood Counts and Cytogenetic Remissions
Authors: Sloand Elaine M. , Olnes Matthew J. , Shenoy Aarthie , Weinstein Barbara , Boss Carol , Loeliger Kelsey , Wu Colin O. , More Kenneth , Barrett A. John , Scheinberg Phillip , Young Neal S. 
Published: November 2010

Purpose Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and progression to leukemia. Clinical and experimental evidence suggests an immune-mediated pathophysiology in some patients, in whom immunosuppressive therapy (IST) with horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) can be effective. Because of the toxicities associated with h-ATG/CsA, we investigated an alternative regimen with alemtuzumab in MDS. Patients and Methods We conducted a nonrandomized, off-label, pilot, phase I/II study of alemtuzumab monotherapy in patients with MDS who were judged likely to respond to IST based on the following criteria: HLA-DR15–negative patients whose age plus the number of months of RBC transfusion dependence (RCTD) was less than 58; and HLA-DR15–positive patients whose age plus RCTD was less than 72. In total, 121 patients with MDS were screened, of whom 32 met eligibility criteria to receive alemtuzumab 10 mg/d intravenously for 10 days. Primary end points were hematologic responses at 3, 6, and 12 months after alemtuzumab. Results Seventeen (77%) of 22 evaluable intermediate-1 patients and four (57%) of seven evaluable intermediate-2 patients responded to treatment with a median time to response of 3 months. Four of seven evaluable responders with cytogenetic abnormalities before treatment had normal cytogenetics by 1 year after treatment. Five (56%) of nine responding patients evaluable at 12 months had normal blood counts, and seven (78%) of nine patients were transfusion independent. Conclusion Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.
Impact of Androgen-Deprivation Therapy on Physical Function and Quality of Life in Men With Nonmetastatic Prostate Cancer
Authors: Alibhai Shabbir M.H. , Breunis Henriette , Timilshina Narhari , Johnston Calvin , Tomlinson George , Tannock Ian , Krahn Murray , Fleshner Neil E. , Warde Padraig , Canning Sarah Duff , Klotz Lawrence , Naglie Gary 
Published: November 2010

Purpose This prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. Patients and Methods Men with nonmetastatic prostate cancer (PC) starting continuous ADT were enrolled in this matched cohort study. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the timed-up-and-go (TUG) test, representing endurance and upper and lower extremity strength, respectively. Quality of life (QOL) was measured with the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Subjects were assessed at baseline, 3, 6, and 12 months. Two control groups (PC without ADT; no PC), matched on age, education, and baseline function were enrolled. Mixed effects regression models were fitted, adjusting for baseline covariates. Results We enrolled 87 patients on ADT, 86 PC controls, and 86 healthy controls; groups were similar in age (mean, 69.1 years; range, 50 to 87) and physical function. The 6MWT distance remained stable in the ADT group (P = .96) but improved in both control groups (P < .05). Grip strength declined in the ADT group (P = .04), remained stable in PC controls (P = .31), and improved in healthy controls (P = .008). TUG scores remained stable over time and across groups (P > .10). The SF-36 physical function summary score declined in the ADT group (P < .001), but increased in both control groups (P < .001). Negative effects on outcomes were observed within 3 months of starting ADT and were generally independent of age. Conclusion Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.
Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study
Authors: Kocher Martin , Soffietti Riccardo , Abacioglu Ufuk , Villà Salvador , Fauchon Francois , Baumert Brigitta G. , Fariselli Laura , Tzuk-Shina Tzahala , Kortmann Rolf-Dieter , Carrie Christian , Hassel Mohamed Ben , Kouri Mauri , Valeinis Egils , van den Berge Dirk , Collette Sandra , Collette Laurence , Mueller Rolf-Peter 
Published: November 2010

PurposeThis European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.Patients and MethodsPatients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.ResultsOf 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.ConclusionAfter radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.
Impact of Androgen-Deprivation Therapy on Cognitive Function in Men With Nonmetastatic Prostate Cancer
Authors: Alibhai Shabbir M.H. , Breunis Henriette , Timilshina Narhari , Marzouk Shireen , Stewart Diane , Tannock Ian , Naglie Gary , Tomlinson George , Fleshner Neil , Krahn Murray , Warde Padraig , Canning Sarah Duff 
Published: November 2010

Purpose To evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC). Patients and Methods The following three groups of men age 50 years or older and matched on age and education were enrolled: patients with PC starting continuous ADT (n = 77), patients with PC not receiving ADT (PC controls, n = 82), and healthy controls (n = 82). A battery of 14 neuropsychological tests, examining eight cognitive domains, was administered at baseline, 6 months, and 12 months. Changes in cognitive scores over time were analyzed using the following three approaches: multivariable linear regression; the proportion of participants per group with 1 standard deviation (SD) or greater declines, and the proportion of participants who declined by at least 1.5 SD on two or more tests. Results The mean age and education level of participants were 68.9 years (range, 50 to 87 years) and 15.4 years of education (range, 8 to 24 years), respectively. Adjusted for age and education, all three cohorts had similar cognitive scores at baseline other than in one test of working memory. In adjusted regressions, ADT use was not associated with significant changes in the domains of attention/processing speed, verbal fluency, verbal memory, visual memory, or cognitive flexibility at either 6 months (all P > .05) or 12 months (all P > .05). One test each of immediate memory (P = .029), working memory (P = .031), and visuospatial ability (P = .034) were worse among ADT users than controls at 12 months, but these findings were not confirmed using other analytic approaches. Conclusion There is no consistent evidence that 12 months of ADT use has an adverse effect on cognitive function in elderly men with PC.
Subacromial impingement syndrome: a prospective comparison of ultrasound-guided versus unguided injection techniques
Authors: Panditaratne Nalinda , Wilkinson Christopher , Groves Clare , Chandramohan Muthusamy 
Published: November 2010

Objectives To evaluate the hypothesis that ultrasound-guided subacromial steroid injection produces greater reduction in morbidity than unguided injection. Design All patients underwent either ultrasound-guided subacromial injection with 80 mg Depo-Medrone at Bradford Royal Infirmary (group 1) or unguided injection (group 2) by a general practitioner with a specialist interest in musculoskeletal medicine (GPwSI). Patients were clinically and ultrasonically diagnosed with subacromial impingement syndrome. Setting Patients in group 1 included both hospital and GP referrals. Patient in group 2 were GP referrals to GPwSI. Main outcome measures Comparison was made of pre-injection and six week post-injection Oxford shoulder score and a 0–10 pain score. Results Forty-one patients received guided injections (group 1) and 17 unguided (group 2). Group 1 showed a significant mean reduction in the Oxford shoulder score of 9.10 (95% CI 7.07–11.13, P < 0.0001) and a significant change in the mean 0–10 pain score of −3.26 (95% CI −2.51 to −3.88, P < 0.0001). Group 2 also showed significant reduction in the mean Oxford shoulder score of 9.94 (95% CI 6.41–13.47, P < 0.0001) and significant change in the mean 0–10 pain score of −2.94 (−1.95 to −3.93, P < 0.0001). Comparison of groups 1 and 2 for each outcome measure revealed no significant differences. Conclusion Our data confirm the efficacy of steroid injection in the management of subacromial impingement, although no significant difference is found when comparing the two groups. We recommend the continued use of unguided injections, with ultrasound used for more practically difficult cases and where there is diagnostic uncertainty.
Karyotype and Identification of All Homoeologous Chromosomes of AllopolyploidBrassica napusand Its Diploid Progenitors
Authors: Xiong Zhiyong , Pires J Chris 
Published: November 2010

AbstractInvestigating recombination of homoeologous chromosomes in allopolyploid species is central to understanding plant breeding and evolution. However, examining chromosome pairing in the allotetraploid Brassica napus has been hampered by the lack of chromosome-specific molecular probes. In this study, we establish the identification of all homoeologous chromosomes of allopolyploid B. napus by using robust molecular cytogenetic karyotypes developed for the progenitor species Brassica rapa (A genome) and Brassica oleracea (C genome). The identification of every chromosome among these three Brassica species utilized genetically mapped bacterial artificial chromosomes (BACs) from B. rapa as probes for fluorescent in situ hybridization (FISH). With this BAC-FISH data, a second karyotype was developed using two BACs that contained repetitive DNA sequences and the ubiquitous ribosomal and pericentromere repeats. Using this diagnostic probe mix and a BAC that contained a C-genome repeat in two successive hybridizations allowed for routine identification of the corresponding homoeologous chromosomes between the A and C genomes of B. napus. When applied to the B. napus cultivar Stellar, we detected one chromosomal rearrangement relative to the parental karyotypes. This robust novel chromosomal painting technique will have biological applications for the understanding of chromosome pairing, homoeologous recombination, and genome evolution in the genus Brassica and will facilitate new applied breeding technologies that rely upon identification of chromosomes.
Estrogen and HER-2 Receptor Discordance Between Primary Breast Cancer and Metastasis
Authors: Pusztai Lajos , Viale Giuseppe , Kelly Catherine M. , Hudis Clifford A. 
Published: November 2010

Abstract
Discordance in estrogen receptor and human epidermal growth factor receptor 2 receptor status between the primary tumor and recurrence is frequently reported in the literature. This is frequently interpreted as evidence for a change in the biology of breast cancer during the course of the disease. This commentary discusses some of the caveats of this interpretation. Discordant receptor results can be caused by any of 3 factors: (a) a genuine switch in the biology of the disease, (b) sampling error in focally receptor-positive cancers, and (c) limited accuracy and reproducibility of receptor assays. The relative contribution of each of these factors to discordant results is unknown. A switch in molecular class between primary and recurrent cancer (or residual cancer after therapy) appears to be a rare event based on the available limited molecular profiling data. Small pockets of strongly focally receptor-positive tumor nests in a larger receptor-negative cancer are also relatively infrequently seen. Discordance resulting from inherent limitations in assay reproducibility is evident from the frequently discordant receptor results even when the same samples are assessed in different laboratories (e.g., central versus local laboratory). A repeat tumor biopsy is clearly justified when it is suspected, on clinical grounds, that the original receptor results may have been false negative or when the diagnosis of metastatic disease is in question. However, routine repeat biopsy for receptor re-evaluation does not necessarily improve diagnostic accuracy and have a potential to harm through a false-negative result. For patients with clinical courses consistent with hormone responsiveness, or with prior positive hormone receptor results, a course of endocrine therapy is reasonable regardless of the most recent hormone receptor assay result.
Inclusion of Rituximab in Treatment Protocols for Non-Hodgkin's Lymphomas and Risk for Progressive Multifocal Leukoencephalopathy
Authors: Tuccori Marco , Focosi Daniele , Blandizzi Corrado , Pelosini Matteo , Montagnani Sabrina , Maggi Fabrizio , Pistello Mauro , Antonioli Luca , Fornai Matteo , Pepe Pasquale , Rossi Giuseppe , Petrini Mario 
Published: November 2010

Abstract

Learning Objectives
After completing this course, the reader will be able to: Evaluate the application of risk estimates of progressive multifocal leukoencephalopathy to your patients with non-Hodgkin's lymphoma previously treated with rituximab.Include progressive multifocal leukoencephalopathy in the differential diagnosis for neurological symptoms in your patients with non-Hodgkin's lymphoma previously treated with rituximab.
This article is available for continuing medical education credit at CME.TheOncologist.com.

Objectives.
Rituximab is an anti-CD20 monoclonal antibody that promotes better treatment outcomes in patients with non-Hodgkin's lymphoma (NHL). Case series of progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab within polychemotherapy regimens have led to the introduction of a black box warning, but no risk estimation has ever been provided.

Methods.
We performed a retrospective, monocentric cohort study on 976 NHL patients diagnosed in 1994–2008, including 517 patients who received at least one dose of rituximab.

Results.
Inclusion of rituximab into standard chemotherapy regimens for NHL caused a significantly higher incidence of PML cases (rate difference, 2.2 every 1,000 patient-years; 95% confidence interval, 0.1–4.3).

Interpretation.
Based on this finding, clinical surveillance of PML-related symptoms is recommended in NHL patients exposed to rituximab.