bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mevalonate Prevents Lovastatin-Induced Apoptosis in Medulloblastoma Cell Lines
Authors: Wang Wei , Macaulay Robert J.B. 
Published: December 2014

Background:3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors for cholesterol biosynthesis and the production of non-steroidal mevalonate derivatives that are involved in a number of growth-regulatory processes. We have reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only inhibits medulloblastoma proliferationin vitro, but also induces near-complete cell death via apoptosis. The present study explores some of the pathways which may be involved in lovastatin-induced apoptosis.Methods:Medulloblastoma cell lines were exposedin vitroto lovastatin with or without mevalonate, and document the effects using morphology, flow cytometry, DNA electrophoresis and Northern analysis.Results:1) Mevalonate prevents apoptosis when co-incubated with lovastatin, or when administered to lovastatin-pretreated cells. 2) Mevalonate restores the lovastatin-arrested cell cycle, allowing S phase entry. 3) Mevalonate does not prevent lovastatin-induced apoptosis after a critical duration of lovastatin pretreatment. For cell lines Daoy and UW228 this was 24 hours, and for D283 Med and D341 Med it was 48 hours. 4) Increases in HMG-CoA reductase mRNA levels induced by lovastatin are abrogated by co-incubation with lovastatin and mevalonate.Conclusion:These results confirm that lovastatin inhibition of this enzyme results in blockage of the mevalonate pathway, and that such a block is a critical step in the mechanism of lovastatin-induced apoptosis.
Reversible Paraneoplastic Encephalomyelitis Associated with a Benign Ovarian Teratoma
Authors: Taylor R. Blaine , Mason Warren , Kong Kester , Wennberg Richard 
Published: December 2014

Background:Paraneoplastic encephalomyelitis (PEM) is a well characterized, and typically irreversible, paraneoplastic syndrome, usually associated with small cell lung cancer or other malignancy. We describe a case of a young woman with a benign ovarian teratoma who presented with a reversible PEM.Case report:A 24-year-old woman presented with a three week history of memory impairment, unusual behavior, personality changes, auditory hallucinations, hypersomnolence and binocular diplopia. On admission she was disoriented and inattentive with impaired short term memory. Small doses of lorazepam (1 mg), given for episodic agitation, repeatedly induced multidirectional bilateral nystagmus and a skew deviation, but her neurological examination was otherwise normal. A left-sided pelvic mass was palpable. Brain MRI pre- and post-gadolinium was normal. There was a mild CSF pleocytosis and an EEG showed minimal bilateral background activity irregularities. There were no other laboratory abnormalities. Two weeks after admission, she clinically deteriorated developing central respiratory failure and a flaccid paraplegia. Repeat MRI showed an area of increased T2 weighted signal in the medulla and three similar areas in the spinal cord. Following removal of her tumor, treatment with high dose corticosteroids and intravenous immunoglobulin, she ultimately made a full recovery. Pathology revealed the tumor to be a benign ovarian cystic teratoma.Conclusion:This is the first report of a reversible PEM seen in association with a benign tumor, in this case a mature ovarian teratoma. Presumably, an immune response directed against neural elements of the teratoma cross-reacted with normal brain, brainstem and spinal cord antigens to cause neurologic symptoms. Tumor removal was followed by neurologic recovery.
High-Dose Methylprednisolone Reduces Cytokine-Induced Adhesion Molecules on Human Brain Endothelium
Authors: Gelati Maurizio , Corsini Elena , Dufour Anna , Massa Giorgio , Giombini Sergio , L.Solero Carlo , Salmaggi Andrea 
Published: December 2014

Objective:We investigated the in vitro effects of low- and high-dose methylprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs).Methods:Brain endothelium was obtained from microvessels included in the apparently normal white matter of surgical specimens of nine patients. Cells were stained with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and analysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated.Results:3-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-3-induced ICAM-1 and VCAM-1 expression.Conclusion:The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through the blood brain barrier and consequently the perivascular infiltrates. The results add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.
High Dose Tamoxifen and Radiotherapy in Patients with Glioblastoma Multiforme: A Phase IB Study
Authors: Muanza Thierry , Shenouda George , Souhami Luis , Corns Robert , Leblanc Richard , Mohr Gerard , Langleben Adrian 
Published: December 2014

Purpose:To assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM).Material and Methods:Twelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly.Results:Median follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 51/2 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1- 43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively.Conclusion:Our study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results.
Dementia Caregiving: The Role of the Primary Care Physician
Authors: Cohen Carole A. , Pringle Dorothy , LeDuc Linda 
Published: December 2014

Background:Family and friends play an important role in caring for individuals with dementia living in the community. In preparation for the Canadian Consensus Conference on Dementia held in Montreal, Canada in February 1998, the subject of dementia caregiving was reviewed in order to provide primary care physicians with some guidelines for their practice. The review was updated in June 2000 in preparation for this article.Method:Pertinent English-language publications and resources from the Alzheimer Society of Canada were reviewed from 1985 onwards. Findings related to the consequences of caregiving, services for caregivers and recommendations regarding the role of the primary care physician were reviewed.Findings:Dementia caregivers experience many positive and negative consequences of caregiving. Some comprehensive services for caregivers have been shown to delay institutionalization and reduce negative consequences of caregiving. The primary care physician has a role to play in working with families and should address the following issues: 1) education about dementia; 2) psychological support for caregivers; 3) assistance mobilizing caregiver social support networks.Conclusion:Primary care physicians have an important role to play in acknowledging and supporting the caregiving provided by family and friends to individuals with dementia.
Recommendations for the Management of Behavioral and Psychological Symptoms of Dementia
Authors: Herrmann Nathan 
Published: December 2014

Background:The behavioral and psychological symptoms of dementia (BPSD) are common, serious problems that impair the quality of life for both patient and caregiver. In order to provide recommendations based upon the best available evidence, a qualitative literature review was performed.Methods:A search of the English language medical literature published between 1966 and 2000 was performed. The quality of the studies was assessed by considering the subjects, trial design, analysis and results. Final recommendations were based upon the quality of available evidence.Results:The management of BPSD begins with a thorough assessment to search for underlying causes of behaviour change. Concomitant medical illness should be treated and sensory impairment ameliorated. Nonpharmacological approaches should be instituted prior to medication use. These interventions include music, light, changes in level of stimulation and specific behavioral techniques. Antipsychotics are the best studied pharmacological intervention for agitation and aggression and have demonstrated modest but consistent efficacy. Antidepressants such as trazodone and selective serotonin re-uptake inhibitors, as well as anticonvulsants such as carbamazepine and valproic acid have also demonstrated efficacy. Benzodiazepines can be used for short-term treatment as p.r.n. agents when necessary. Pharmacotherapy must be monitored closely for both effectiveness and side effects, with consideration of medication withdrawal when appropriate.Conclusion:The management of BPSD can significantly improve the quality of life for the patient and caregiver. Their assessment and management are essential components of the treatment of dementia.
The Use of Medications for Cognitive Enhancement
Authors: Pryse-Phillips William , Sternberg Shelley , Rochon Paula , Naglie Gary , Strong Howard , Feightner John 
Published: December 2014

Objective:To provide Canadian physicians and allied health care professionals with the evidence they need to help them make treatment decisions in the management of patients with Alzheimer’s disease or other dementias.Options:The full range and quality of diagnostic and therapeutic modalities available to Canadian physicians for the management of dementia.Outcomes:Improvement in the treatment of dementias, leading to reduced suffering, increased functional capacity and decreased economic burden.Evidence and values:The creation of these evidence-based consensus statements involved literature reviews of the subject by the authors; comparison of alternative clinical pathways and description of the methods whereby published data were analyzed; definition of the level of evidence for data in each case; evaluation and revision in a conference setting (involving primary care physicians, neurologists, psychiatrists, geriatricians, psychologists, consumers and other interested parties); insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all authors.Benefits, harms, and costs:A rational plan for the therapy of dementias is likely to lead to substantial benefits in both human and economic terms.Recommendations:Treatment decisions should be made taking into account the severity or stage of the disease, the availability of caregivers, the presence of disease affecting other bodily systems and the ability of the subject to pay the cost of the medications. Donepezil is considered to have positive effects upon certain tests of neuropsychological function and may produce some improvement in Alzheimer’s disease of mild to moderate severity as measured by rating scales. Its ability to improve quality of life remains uncertain. No other drug treatments* (apart from symptomatic therapies) are at present approved for the treatment of Alzheimer’s disease.Validation:These recommendations were created by a writing committee, evaluated and revised at a consensus conference and further reviewed and revised by the writing committee prior to publication.
Identification of the Temporal Components of Seizure Onset in the Scalp EEG
Authors: O'Neill Nora S. , Koles Zoltan J. , Javidan Manouchehr 
Published: December 2014

Background:The identification of the earliest indication of rhythmical oscillations and paroxysmal events associated with an epileptic seizure is paramount in identifying the location of the seizure onset in the scalp EEG. In this work, data-dependent filters are designed that can help reveal obscure activity at the onset of seizures in problematic EEGs.Methods:Data-dependent filters were designed using temporal patterns common to selected segments from pre-ictal and ictal portions of the scalp EEG. Temporal patterns that accounted for more variance in the ictal segment than in the pre-ictal segment of the scalp EEG were used to form the filters.Results:Application of the filters to the scalp EEG revealed temporal components in the seizure onset in the scalp recording that were not obvious in the unfiltered EEG. Examination of the filtered EEG enabled the onset of the seizure to be recognized earlier in the recording. The utility of the filters was confirmed qualitatively by comparing the scalp recording to the intracranial recording and quantitatively by calculating correlation coefficients between the scalp and intracranial recordings before and after filtering.Conclusion:The data-dependent approach to EEG filter design allows automatic detection of the basic frequencies present in the seizure onset. This approach is more effective than narrow band-pass filtering for eliminating artifactual and other interference that can obscure the onset of a seizure. Therefore, temporal-pattern filtering facilitates the identification of seizure onsets in challenging scalp EEGs.
The Carbohydrate and Caloric Content of Concomitant Medications for Children with Epilepsy on the Ketogenic Diet
Authors: Lebel Denis , Morin Caroline , Achim Nathalie , Laberge Micheline , Carmant Lionel 
Published: December 2014

Background:The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population.Methods:We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet.Results:We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe.Conclusion:We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically.
New Insights into the Neuropathogenesis of Molybdenum Cofactor Deficiency
Authors: Salman Michael S. , Ackerley Cameron , Senger Christof , Becker Laurence 
Published: December 2014

Background:Molybdenum cofactor deficiency (MOCOD) is a rare, progressive neurodegenerative disorder caused by sulphite oxidase enzyme deficiency. The neuropathological findings are consistent with a toxic insult to the brain that causes severe neuronal loss, reactive astrogliosis and spongiosis. The mechanisms responsible for these changes are unknown.Methods:The case is a male infant with MOCOD who died at nine months of age from pneumonia. At autopsy, a complete neuropathological examination was performed including conventional immunohistochemical staining. In addition, brain sections were stained cytochemically with shikata and orcein which stain for disulphide bonds. The elemental composition of cortical cells was then analyzed in the scanning electron microscope using backscatter electron imaging and energy dispersive X-ray spectrometry.Results:Neurons demonstrated cytoplasmic staining with shikata and orcein cytochemically when compared to control sections. Energy dispersive X-ray spectrometry analysis of these neurons confirmed the presence of excess sulphur and unexpectedly revealed excess magnesium accumulation. None of these findings was found in an age-matched control.Conclusions:In MOCOD we found abnormal accumulation of sulphur and magnesium in neurons. It is postulated that sulphur-containing compound(s) that are formed as a result of MOCOD cause excitotoxic neuronal injury in the presence of excess magnesium.
Assessing Health-Related Quality of Life in Patients with Migraine
Authors: Becker W.J. 
Published: December 2014

Background:The place of health-related quality of life (HRQoL) instruments in clinical research trials and clinical practice as compared to more traditional clinical outcome measures such as headache intensity and frequency is unclear.Objectives:To review the current status of HRQoL measurement in migraine.Methods:A literature search was done for HRQoL and migraine. Selected articles dealing with migraine and commonly used HRQoL instruments and HRQoL measures used in recent clinical trials were reviewed.Results:Several general and migraine specific HRQoLinstruments can detect changes over time in response to at least major changes in migraine therapy. Both also show a correlation with clinical headache features. However, their sensitivity to detect clinically significant changes over time is not clear.Conclusion:The SF-36, a general HRQoLmeasure and several migraine-specific HRQoL instruments are useful endpoints for migraine clinical trials. Their role in clinical practice is yet to be established.
Doctor-Patient Communication: Principles and Practices
Authors: Kurtz Suzanne M. 
Published: December 2014

Background:In a formal needs assessment, conducted prior to the Canadian Headache Society's recent national continuing education workshop, participants expressed particular enthusiasm for enhancing their own communication skills or their teaching of those skills.Objectives:Responding to both interests, this paper offers a practical conceptual framework for thinking systematically about how to improve physician-patient communication to a professional level of competence.Methods:The three-part, evidence-based framework first defines communication in medicine in terms of five underlying assumptions about communication and the learning of communication skills. It then discusses three categories of communication skills (content, process, and perceptual skills) and six goals that physicians and patients work to achieve through their communication with each other. The second part of the framework explores “first principles” of effective communication and includes a brief look at the historical context that has significantly influenced our thinking about, and practice of communication in health care. Part three of the framework describes one approach for delineating and organizing the specific skills that research supports for communicating effectively with patients - the Calgary Cambridge Guide.Results:It is clear from the literature that better physician communication skills improve patient satisfaction and clinical outcomes and that good communication skills can be taught and learned.Conclusions:It is important that physicians learn the principles of good physician-patient communication and apply them in clinical practice. Medical education programs at all levels should include teaching of physician-patient communication.
Why Do You Prescribe Methylprednisolone for Acute Spinal Cord Injury? A Canadian Perspective and a Position Statement
Authors: Hurlbert R.J. , Moulton R. 
Published: December 2014

Objective:To determine the practice patterns for methylprednisolone administration for patients with acute spinal cord injury (SCI) within the spinal surgery community across Canada, and the reasons behind these patterns.Methods:Canadian neurological and orthopedic spine surgeons were surveyed at their respective annual meetings with a questionnaire asking seven questions with respect to their practice standards.Results:Sixty surgeons completed the survey representing approximately two-thirds of surgeons treating acute SCI within Canada. The NASCIS III dosing regimen is the most commonly prescribed steroid protocol. However, one-quarter of surgeons do not administer steroids at all. Of those who administer methylprednisolone, most do so because of peer pressure or out of fear of litigation.Conclusion:The vast majority of spine surgeons in Canada either do not prescribe methylprednisolone for acute SCI, or do so for what might be considered the wrong reasons. These results demonstrate the need for an evidence-based practice guideline. The Candian Spine Society and the Canadian Neurosurgical Society fully endorse the recommendations of the steroid task force (see preceding paper).
Electronic Case-Report Forms of Symptoms and Impairments of Peripheral Neuropathy
Authors: Dyck Peter J. , Turner David W. , Davies Jenny L. , O’Brien Peter C. , Dyck P. James B. , Rask Cynthia A. ,   and the rhNGF group
Published: December 2014

Background and objective:For the conduct of controlled clinical trials, epidemiologic surveys or even of medical practice of varieties of peripheral neuropathy, the usefulness, error rate and cost-effectiveness of scannable case-report forms has not been studied. Materials andMethods:The overall performance, the frequency of the problems identified and corrected, and the time saved from use of a standard paper case report form was evaluated in multicenter treatment trials, single center epidemiologic surveys and in our neurologic practice. The paper case report form (Clinical Neuropathy Assessment [CNA]) for pen entry at study medical centers for patient, disease and demographic information (Lower Limb Function [LLF] and Neuropathy Impairment Score [NIS]) can be faxed to a core Reading and Quality Assurance Center where the form and data is electronically and interactively evaluated and corrected, if needed, by participating medical centers before electronic entry into database.Observations and conclusions:1) The approach provides a standard, scannable paper case report form for pen entry of neuropathy symptoms, impairments and disability at the bedside or in the office which is retained as a source document at the participating medical center but a facsimile can be transferred instantaneously, its data can be programmed, interactively evaluated, modified and stored while maintaining an audit trail; 2) it allowed efficient and accurate reading, transfer, analysis, and storage of data of more than 15,000 forms used in multicenter trials; 3) in 500 consecutive CNA evaluations, software programs identified and facilitated interactive corrections of omissions, discrepancies, and disease and study inconsistencies, introducing only a few readily identified and corrected entry errors; and 4) use of programmed, as compared to non-programmed assessment, was more accurate than double keyboard entry of data and was approximately five times faster.