MedWorm: ALS

Trophos Completes Patient Enrolment In Pivotal Phase 3 Efficacy Study Of Olesoxime In Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)

Health News from Medical News Today — Fri, 19 Mar 2010 08:00:00 +0100

Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology, announced today the completion of patient enrolment with over 500 patients recruited into the pivotal phase 3 efficacy study of olesoxime in Amyotrophic Lateral Sclerosis (ALS). The study is supported by the EU FP7 MitoTarget project (see below). The trial protocol has benefited from EMEA Scientific Advice procedure. Efficacy results are expected in the 4th quarter of 2011... (Source: Health News from Medical News Today)

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Trophos Completes Patient Enrolment In Pivotal Phase 3 Efficacy Study Of Olesoxime In Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)

Muscular Dystrophy News From Medical News Today — Fri, 19 Mar 2010 08:00:00 +0100

Mechanisms Underlying Inflammation in Neurodegeneration

Cell — Fri, 19 Mar 2010 04:00:10 +0100

Christopher K. Glass, Kaoru Saijo, Beate Winner, Maria Carolina Marchetto, Fred H. Gage. Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discu.... (Source: Cell)

Critical Drug Information Not Reaching Prescribers; Guidance for REMS; Stem Cell Trial for ALS Scheduled; Orphan Drug Status for a Gene Therapy; Safe Use Initiative from FDA; Antigenics Withdraws European Oncophage Application

Biotechnology Law Report — Fri, 19 Mar 2010 00:21:06 +0100

Biotechnology Law Report Dec 2009, Vol. 28, No. 6: 717-718. (Source: Biotechnology Law Report)

The Link Between Bipolar Disorder and Creativity

Psych Central — Thu, 18 Mar 2010 18:49:26 +0100

People with bipolar disorder experience episodes of both mania (an exceptionally elevated, irritable, or energetic mood) and depression. These episodes may be separate or depressed and manic symptoms may occur at the same time. The frequency of episodes varies. At least four depressive, manic, hypomanic (mild form of mania) or mixed episodes within a year is known as rapid-cycling bipolar disorder. During the early stages of a manic episode, people can be very happy, productive and creative. They have less need for sleep and don’t feel tired. There is some evidence that many well-known creative people suffer or have suffered from bipolar disorder. But this link may be caused by an unknown third factor, such as temperament. Bipolar disorder has been slightly romanticized by its assoc...

ALS Therapy Development Institute And Aestus Therapeutics, Inc. Collaborate To Investigate Potential Treatments For ALS

Muscular Dystrophy News From Medical News Today — Thu, 18 Mar 2010 11:00:00 +0100

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ALS Therapy Development Institute And Aestus Therapeutics, Inc. Collaborate To Investigate Potential Treatments For ALS

Health News from Medical News Today — Thu, 18 Mar 2010 11:00:00 +0100

The ALS Therapy Development Institute (ALS TDI) and Aestus Therapeutics, Inc., announced their plans today to test several potential small-molecule compounds to slow or stop the progression of Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig's disease). "Aestus is a key, strategic drug discovery partner in the effort to identify potential therapeutics for ALS. This collaborative effort will substantially increase our ability to identify several new existing compounds related to the information gained through our gene expression profiling and proteomics efforts... (Source: Health News from Medical News Today)

Improving Binding Specificity of Pharmacological Chaperones That Target Mutant Superoxide Dismutase-1 Linked to Familial Amyotrophic Lateral Sclerosis Using Computational Methods

Journal of Medicinal Chemistry — Tue, 16 Mar 2010 12:33:02 +0100

Journal of Medicinal Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Medicinal Chemistry)

Discovery Of Chemical That May Protect Hearts Of Muscular Dystrophy Patients

Health News from Medical News Today — Tue, 16 Mar 2010 11:00:00 +0100

Researchers at the University of Minnesota Medical School have discovered a chemical that may, over the long term, protect the hearts of Duchenne muscular dystrophy patients - a fatal and most common form of muscular dystrophy in children. The chemical, which Medical School scientists have termed a "molecular band-aid," seeks out tiny cuts in diseased heart muscle. When injected into the bloodstream, the molecular band-aid finds these microscopic cuts and protects them from harmful substances so the heart muscle cells can survive and function normally... (Source: Health News from Medical News Today)

Discovery Of Chemical That May Protect Hearts Of Muscular Dystrophy Patients

Muscular Dystrophy News From Medical News Today — Tue, 16 Mar 2010 11:00:00 +0100

Researchers at the University of Minnesota Medical School have discovered a chemical that may, over the long term, protect the hearts of Duchenne muscular dystrophy patients - a fatal and most common form of muscular dystrophy in children. The chemical, which Medical School scientists have termed a "molecular band-aid," seeks out tiny cuts in diseased heart muscle... (Source: Muscular Dystrophy News From Medical News Today)

Analysis of the genome content of Lactococcus garvieae by genomic interspecies microarray hybridization

BMC Microbiology - Latest articles — Tue, 16 Mar 2010 00:00:00 +0100

Conclusions: In this study, we identified 267 genes that were potentially present in L. garvieae CECT 4531. Some of the identified genes could be involved in the pathogenesis of L. garvieae infections. These results provide the first insight into the genome content of L. garvieae. (Source: BMC Microbiology - Latest articles)

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Radiometric survey of teletherapy treatment rooms in Brazil

Radiation Protection Dosimetry — Mon, 15 Mar 2010 15:24:05 +0100

The Brazilian national regulatory authority, National Commission of Nuclear Energy, requires that dose rates in the vicinity of teletherapy treatment rooms do not exceed the permissible limits for workers as well as members of the public, depending on the place considered. At the end of 2005, the Brazilian national regulatory authority reduced the permissible dose limit for controlled areas from 1000 to 400 µSv week–1. Therefore, the aim of this work is to verify the adequacy of structural shielding to this new limit for telecobalt units that had their sources changed and clinic linear accelerators (ALs) installed before the end of 2005. Considering the ALs, measurements of dose rates in controlled areas did not exceed the new permissible limit, excepting for a single case. In ...

De novo truncating FUS gene mutation as a cause of sporadic amyotrophic lateral sclerosis

Human Mutation — Mon, 15 Mar 2010 00:00:00 +0100

Mutations in the gene encoding fused in sarcoma (FUS) were recently identified as a novel cause of amyotrophic lateral sclerosis (ALS), emphasizing the genetic heterogeneity of ALS. We sequenced the genes encoding superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TARDBP) and FUS in 99 sporadic and 17 familial ALS patients ascertained at Mayo Clinic. We identified two novel mutations in FUS in two out of 99 (2.0%) sporadic ALS patients and established the de novo occurrence of one FUS mutation. In familial patients, we identified three (17.6%) SOD1 mutations, while FUS and TARDBP mutations were excluded. The de novo FUS mutation (g.10747A>G; IVS13-2A>G) affects the splice-acceptor site of FUS intron 13 and was shown to induce skipping of FUS exon 14 leading to the C-terminal truncati...

Blutung nach Embolisation einer zerebralen AVM

Klinische Neuroradiologie — Sun, 14 Mar 2010 11:30:22 +0100

Zusammenfassung Bericht über einen 36-jährigen Patienten mit einer links temporal gelegenen arteriovenösen Malformation (AVM). Nach interdisziplinärem Konsil wurde eine kombinierte Behandlung mit endovaskulärer Embolisation und anschließender stereotaktischer Bestrahlung empfohlen. 2 h nach komplikationslos verlaufener Embolisation kam es zu einer Blutung links temporal mit Ventrikeleinbruch. Nachdem die Akutphase mit Anlage externer Drainagen und späterer Implantation eines Shuntsystems überstanden war, behielt der Patient ein hirnorganisches Psychosyndrom zurück. Sein Rechtsanwalt verklagte die Klinik wegen fehlerhafter Behandlung und unzureichender Aufklärung. Das Gericht hat die Klage als unbegründet abgewiesen und sich dabei maßgeblich auf die Ausführungen...

Army Of New Care Advisors Joins The Fight Against Muscle Disease, UK

Health News from Medical News Today — Sun, 14 Mar 2010 08:00:00 +0100

An army of 19 new and newly secured care advisors will be joining the fight against muscle disease across the UK with the Muscular Dystrophy Campaign. Thanks to the hard work of campaigning patients in 10 UK regions and the Muscular Dystrophy Campaign, babies, children and adults living with muscle disease will now have access to 19 regional care advisors, who provide vital care co-ordination, advice and guidance on services, equipment and funding. They are also an important point of contact for families to answer their questions about these rare and devastating conditions... (Source: Health News from Medical News Today)

Army Of New Care Advisors Joins The Fight Against Muscle Disease, UK

Muscular Dystrophy News From Medical News Today — Sun, 14 Mar 2010 08:00:00 +0100

An army of 19 new and newly secured care advisors will be joining the fight against muscle disease across the UK with the Muscular Dystrophy Campaign... (Source: Muscular Dystrophy News From Medical News Today)

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Glutamate receptors, neurotoxicity and neurodegeneration.

Pflugers Archiv : European Journal of Physiology — Sun, 14 Mar 2010 00:00:00 +0100

Authors: Lau A, Tymianski M Glutamate excitotoxicity is a hypothesis that states excessive glutamate causes neuronal dysfunction and degeneration. As glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), the implications of glutamate excitotoxicity are many and far-reaching. Acute CNS insults such as ischaemia and traumatic brain injury have traditionally been the focus of excitotoxicity research. However, glutamate excitotoxicity has also been linked to chronic neurodegenerative disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and others. Despite the continued research into the mechanisms of excitotoxicity, there are currently no pharmacological interventions capable of providing significant neuroprotection in the...

All you need is flow!

Resuscitation — Sat, 13 Mar 2010 14:14:41 +0100

Sudden cardiac arrest is a leading cause of death in Europe, with approximately 275,000 arrests each year. Survival rates average 10%, but this varies a lot between different sites, and depends on factors like the quality and effectiveness of the local chain of survival. Return of spontaneous circulation (ROSC) is achieved only in approximately 1/3 of all arrested patients where Advanced Life Support (ALS) has been initiated. This may be due to too long response times, absence of bystander CPR, long time to first defibrillation or bad quality ALS with long pauses without sufficient vital circulation. (Source: Resuscitation)

Chlamydia pneumoniae IgG and IgA antibody titers and prognosis in patients with coronary heart disease: results from the CLARICOR trial

Diagnostic Microbiology and Infectious Disease — Fri, 12 Mar 2010 16:32:52 +0100

Abstract: The association observed between coronary heart disease (CHD) and Chlamydia (Chlamydophila) pneumoniae antibodies prompted, during the 1990s, several primary and secondary prevention trials with various antibiotics. In our CLARICOR trial, a randomized placebo-controlled trial in 4372 patients with stable CHD, a brief clarithromycin regimen was followed, unexpectedly, by increased long-term mortality. We now compare C. pneumoniae antibody levels at entry with population levels, with the patients' individual histories, and with their subsequent outcomes. IgG antibody levels were somewhat raised, but elevated IgA and IgG titers were unrelated to entry data (including prior acute myocardial infarction), except for an association with smoking and with not using statins. Hazards of mor...

Recent advances in cancer therapy: an overview.

Current Pharmaceutical Design — Fri, 12 Mar 2010 15:18:05 +0100

Authors: Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, Capellá G The landscape of cancer treatment has dramatically changed over the last four decades. The age when surgery and radiotherapy were the only effective way to fight tumour growth has ended. A complex scenario where the molecular features of tumours seem to be the cornerstone of any therapy is now emerging. Here we provide an overview on the different approaches to cancer treatment. This review will help the reader to acknowledge the pivotal role of some classic cancer therapies, including surgery, radiation, chemotherapy and endocrine therapy, now better understood in the mechanims underpinning their efficacy. Following, we focus on the understanding of the value of systemic treatment and on an up-d...

Kathoden-Elektrolyse als neuer Weg zum Auffinden und zum Verschluß des Netzhautrisses

Ophthalmologica — Thu, 11 Mar 2010 23:00:00 +0100

Zeitschrift für Augenheilkunde 1934;83:322-323 (DOI:10.1159/000298107) (Source: Ophthalmologica)

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Diary Note: East Of England Muscle Disease Conference

Health News from Medical News Today — Thu, 11 Mar 2010 15:00:00 +0100

What Families living with muscle disease in the East of England are joining forces with clinicians and MPs at an inaugural conference for the region, organised by the Muscular Dystrophy Campaign. The conference will be an opportunity for families to learn more about fighting for better muscle disease services in their region and to find out how local campaigning can make a real difference. There will be talks from leading clinicians and local MPs about recent care developments and how best to make your voice heard on healthcare issues... (Source: Health News from Medical News Today)

Diary Note: East Of England Muscle Disease Conference

Muscular Dystrophy News From Medical News Today — Thu, 11 Mar 2010 15:00:00 +0100

What Families living with muscle disease in the East of England are joining forces with clinicians and MPs at an inaugural conference for the region, organised by the Muscular Dystrophy Campaign. The conference will be an opportunity for families to learn more about fighting for better muscle disease services in their region and to find out how local campaigning can make a real difference... (Source: Muscular Dystrophy News From Medical News Today)

US FDA grants "orphan drug" status for CK-2017357 for the treatment of amyotrophic lateral sclerosis

NeLM - News — Thu, 11 Mar 2010 00:00:00 +0100

Source: BioSpace Area: News According to a report by BioSpace, the US Food and Drug Administration has granted "orphan drug" designation for CK-2017357, a skeletal muscle troponin activator for the potential treatment of amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig's Disease. ALS is a progressive, neurodegenerative disease that afflicts 20,000 to 30,000 people in the United States. The average life expectancy of an ALS patient is approximately three to five years and only 10% of patients survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. (Source: NeLM - News)

Die Schlafgewohnheiten der Österreicher

Somnologie - Schlafforschung und Schlafmedizin — Wed, 10 Mar 2010 15:39:46 +0100

Zusammenfassung Hintergrund Schlafstörungen und Schlafmangel sind in unserer modernen Gesellschaft weit verbreitet. Zwar hat das mediale Interesse an der Funktion und Bedeutung des Schlafs beträchtlich zugenommen, doch stellt sich die Frage, wie sehr der Stellenwert gesunden und ausreichenden Schlafs im Allgemeinen und das Schlafverhalten im Einzelnen dadurch beeinflusst bzw. verändert wird. Methode In einer für die österreichische Bevölkerung repräsentativen Umfrage (n=1000, 478 Männer, 522 Frauen) wurden neben allgemeinen Schlafmerkmalen auch die subjektive Schlafqualität, Schlafgewohnheiten und Hinweise auf Schlafstörungen in Zusammenhang mit demographischen und gesundheitlichen Aspekten untersucht. Ergebnisse Rund 76% de...

Cytokinetics Announces Orphan Drug Designation Granted to CK-2017357 for the Treatment of Amyotrophic Lateral Sclerosis

HSMN NewsFeed — Wed, 10 Mar 2010 15:35:13 +0100

SOUTH SAN FRANCISCO, CA - (HSMN NewsFeed) - Cytokinetics, Incorporated (NASDAQ:CYTK ) announced today that its fast skeletal muscle troponin activator, CK-2017357, has been granted orphan-drug designation by the U.S. Food and Drug Administration (FDA) for ... Biopharmaceuticals, Neurology, FDACytokinetics, CK-2017357, amyotrophic lateral sclerosis (Source: HSMN NewsFeed)

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Ameliorating Amyotrophic Lateral Sclerosis

New England Journal of Medicine — Wed, 10 Mar 2010 00:00:00 +0100

A newly implicated molecular pathway in skeletal muscle regulates the formation of the neuromuscular junction and is implicated in a mouse model of amyotrophic lateral sclerosis. (Source: New England Journal of Medicine)

A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What have we Learned in the Last Decade?

CNS Neuroscience and Therapeutics — Wed, 10 Mar 2010 00:00:00 +0100

Authors: Bellingham MC Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009. A systematic review of this literature found that riluzole had a wide range of effects on factors influencing neural activity in general, and the neuromotor system in particular. These effects occurred over a large dose range (<1 muM to >1 mM). Reported neural effects of riluzole included (in approximate ascending order of dose...

Spectrometric study of the interaction between Alpinetin and bovine serum albumin using chemometrics approaches.

Analytica Chimica Acta — Tue, 09 Mar 2010 23:04:44 +0100

Authors: Ni Y, Wang S, Kokot S The binding interaction of Alpinetin (APT) with bovine serum albumin (BSA) was studied by fluorescence, UV-visible and synchronous fluorescence spectroscopy (SFS) under simulated physiological conditions. The measured complex spectra were resolved by multivariate curve resolution-alternating least squares (MCR-ALS), yielding a host of data and information, which otherwise would have been impossible to obtain. The extracted profiles corresponded to the spectra of the single species in the APT/BSA mixture. In addition, the presence of the APT-BSA complex was demonstrated, and it was shown that the associated quenching of the fluorescence from the BSA protein resulted from the formation of APT-BSA complex via a static mechanism. The binding constant (K(a(ave...

Children’s launches new stem cell Web site

Thrive, Children's Hospital Boston — Tue, 09 Mar 2010 15:21:24 +0100

By Jonathan Kraft, president of The Kraft Group and New England Patriots As a long-time supporter of stem cell research, I’m proud to announce the launch of a new Children’s Hospital Boston Web site that we hope will demystify the science of stem cells and answer some of the public’s questions about them. For the past three and a half years, my wife, Patti, and I have served as co-chairs of Children’s Hospital Boston’s Stem Cell Task Force because we believe that stem cells hold incredible promise for the future of health care. During this time I’ve gotten to know Len Zon and George Daley, the two physician-scientists who head up the hospital’s Stem Cell Research Program, and I believe that the work they are doing will revolutionize health care.They’ve expl...

Is Prenatal Screening For Rare Diseases Like Spinal Muscular Atrophy Too Costly?

Health News from Medical News Today — Tue, 09 Mar 2010 10:00:00 +0100

Spinal Muscular Atrophy (SMA) is one of many serious disorders for which prenatal testing is available. SMA affects approximately 1 in 10,000 live births and is the leading genetic cause of infant mortality and the second most common autosomal recessive disorder, after cystic fibrosis. Although the American College of Medical Genetics recommends carrier testing for all couples, the American College of Obstetricians and Gynecologists has issued a recommendation to the contrary, citing lack of information about the costs and benefits of screening for SMA... (Source: Health News from Medical News Today)

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Is Prenatal Screening For Rare Diseases Like Spinal Muscular Atrophy Too Costly?

Muscular Dystrophy News From Medical News Today — Tue, 09 Mar 2010 10:00:00 +0100

MitoTarget Launches New Online Resource for Physicians and Sufferers from Rare Illness ALS

World Pharma News — Tue, 09 Mar 2010 00:00:00 +0100

Trophos, the pharmaceutical company specialising in therapies for orphan diseases including ALS (also known as Lou Gehrig's disease), announces, on behalf of the MitoTarget consortium, the launch of MitoTarget Online. The multilingual web-based resource aims to be the first point of call for all of those affected by ALS. (Source: World Pharma News)

Aberrant RNA processing events in neurological disorders.

Brain Research — Tue, 09 Mar 2010 00:00:00 +0100

Authors: Anthony K, Gallo JM The importance of aberrant RNA processing in neurodegeneration is becoming increasingly clear; a recent example being the identification of the splicing factor TDP-43 as the major component of inclusions characteristic of a number of neurodegenerative conditions including amyotrophic lateral sclerosis (ALS). Due to the enormous diversity generated by alternative splicing and its importance in the nervous system, it is no surprise that defective alternative splicing in disease has been particularly well documented. However, in addition to splicing, other RNA processing events such as RNA editing, polyadenylation and mRNA stability are also disrupted in some neurological disorders. For instance: the editing efficiency of specific ionotropic receptors is reduc...

Gray matter perfusion correlates with disease severity in ALS

Neurology — Mon, 08 Mar 2010 20:59:33 +0100

Conclusion: Amyotrophic lateral sclerosis (ALS) severity is correlated with brain perfusion as measured by arterial spin labeling (ASL) perfusion. This correlation appears to be independent of brain atrophy. ASL perfusion may be a useful tool for monitoring disease progression and assessing treatment effects in ALS. (Source: Neurology)

6. Impaired autonomic cardiac control in patients with amyotrophic lateral sclerosis and it’s prognostic significance

Clinical Neurophysiology — Mon, 08 Mar 2010 18:13:02 +0100

Purpose: To assess autonomic cardiac control in ALS patients and the impact of autonomic dysfunction on outcome. Methods: Fifty five patients with sporadic ALS (28 women, 27 men; average age 56,00±10,34) were compared to 30 healthy controls (17 women, 13 men; average age 42,87±11,91). Ewing‘s cardiovascular reflex tests, short-term power spectrum analysis of heart rate variability (HRV), real time beat-to-beat ECG monitoring with HRV analysis and baroreceptor function analysis (BRS) were performed at the beginning of the study. Cardiovascular responses to 5-min hyperventilation were also assessed. Time domain parameters of HRV were obtained from 24-h ECG monitoring. The follow-up period was 38 months. Kaplan–Meier method and Cox proportional hazard model were used to assess survival...

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2. Corticospinal dysfunction and the development of amyotrophic lateral sclerosis following electrical injury

Clinical Neurophysiology — Mon, 08 Mar 2010 18:13:01 +0100

The pathophysiology of Amyotrophic Lateral Sclerosis (ALS) is not entirely understood, although 5–10% of cases are familial with the remainder termed sporadic. While there have been case reports of ALS developing following electrical trauma, a recent systematic review suggested that there was no convincing evidence for a causal relationship. Herein, we describe a 25-year-old male patient who developed ALS with initial onset in the right upper limb, soon after sustaining a severe electrical injury to the same region, associated with the development of structural abnormalities involving the motor pathways evident on magnetic resonance imaging. Assessment of cortical excitability with transcranial magnetic stimulation demonstrated a relatively inexcitable motor cortex, with a significant in...

An auditory oddball brain–computer interface for binary choices

Clinical Neurophysiology — Mon, 08 Mar 2010 18:12:59 +0100

Conclusions: With this study, the viability of the paradigm was shown for healthy participants and will next be evaluated with individuals diagnosed with ALS or locked-in syndrome (LIS) after stroke.Significance: The here presented BCI offers communication with binary choices (yes/no) independent of vision. As it requires only little time per selection, it may constitute a reliable means of communication for patients who lost all motor function and have a short attention span. (Source: Clinical Neurophysiology)

Motor neuron disease: systematic reviews of treatment for ALS and SMA

British Medical Bulletin — Mon, 08 Mar 2010 15:36:34 +0100

Introduction There is no curative treatment for the common motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Nevertheless, there is an increasing volume of published studies. This review assesses the current evidence for treatment of these conditions. Sources of data Primarily, the systematic reviews of the Cochrane Collaboration, with additional reference to other systematic reviews and online sites. Areas of agreement Riluzole remains the only medication with demonstrated efficacy and regulatory approval for the treatment of ALS. Areas of controversy, growing points and areas timely for developing research The design of clinical trials and the publication of unsatisfactory studies, in both human and animal models, continue to cause confusion in ad...

Extracorporeal cardiac mechanical stimulation: precordial thump and precordial percussion

British Medical Bulletin — Mon, 08 Mar 2010 15:36:34 +0100

Introduction External cardiac mechanical stimulation is one of the fastest resuscitative manoeuvres possible in the emergency setting. Precordial thump (PT), initially reported for treatment of atrio-ventricular block, has been subsequently described to cardiovert also ventricular tachycardia (VT) and fibrillation (VF). PT efficacy, mechanics and mechanisms remain poorly characterized. Sources of data Appropriate MESH and free terms were searched on PubMed, Embase and the Cochrane Library. Cross-referencing from articles and reviews, and forward search using SCOPUS and Google scholar have also been performed. Pre-set inclusion and exclusion criteria were applied to retrieved references on PT, which were then reviewed, summarized and interpreted. Areas of agreement PT is not effective in ...

ISIS Initiates Phase 1 Clinical Trial Of ISIS-SOD1Rx In Patients With ALS

Health News from Medical News Today — Sat, 06 Mar 2010 09:00:00 +0100

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced that it has initiated a Phase 1 study of ISIS-SOD1Rx in patients with an inherited, aggressive form of Lou Gehrig's disease also known as familial amyotrophic lateral sclerosis (ALS). Approximately 20 percent of all familial ALS cases are caused by a mutant form of superoxide dismutase, or SOD1. ISIS-SOD1Rx is an antisense drug designed to inhibit the production of SOD1. The ALS Association and the Muscular Dystrophy Association are providing funding for the development of ISIS-SOD1Rx... (Source: Health News from Medical News Today)

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ISIS Initiates Phase 1 Clinical Trial Of ISIS-SOD1Rx In Patients With ALS

Muscular Dystrophy News From Medical News Today — Sat, 06 Mar 2010 09:00:00 +0100

Phosphoinositide-dependent Protein Kinase (PDK) Activity Regulates Phosphatidylinositol 3,4,5-Trisphosphate-dependent and -independent Protein Kinase B Activation and Chemotaxis [Signal Transduction]

Journal of Biological Chemistry — Fri, 05 Mar 2010 14:37:12 +0100

Chemotactic cells must sense shallow extracellular gradients and produce localized intracellular responses. We previously showed that the temporal and spatial activation of two protein kinase B (PKB) homologues, PkbA and PkbR1, in Dictyostelium discoideum by phosphorylation of activation loops (ALs) and hydrophobic motifs had important roles in chemotaxis. We found that hydrophobic motif phosphorylation depended on regulation of TorC2 (target of rapamycin complex 2); however, the regulation of AL phosphorylation remains to be determined at a molecular level. Here, we show that two PDK (phosphoinositide-dependent protein kinase) homologues, PdkA and PdkB, function as the key AL kinases. Cells lacking both PdkA and PdkB are defective in PKB activation, chemotaxis, and fruiting body formation...

New ALS treatment enters Phase 1 Clinical Trial

Hope Center News — Fri, 05 Mar 2010 12:38:37 +0100

A new hope nears fruition as Tim Miller’s research on SOD1 leads to clinical trial for new ALS drug. (Source: Hope Center News)

Measures of bulbar and spinal motor function, muscle innervation, and mitochondrial function in ALS rats.

Behavioural Brain Research — Fri, 05 Mar 2010 00:00:00 +0100

Authors: Smittkamp SE, Spalding HN, Brown JW, Gupte AA, Chen J, Nishimune H, Geiger PC, Stanford JA Symptom onset in amyotrophic lateral sclerosis (ALS) may occur in the muscles of the limbs (spinal onset) or those of the head and neck (bulbar onset). Most preclinical studies have focused on spinal symptoms, despite the prevalence of and increased morbidity and mortality associated with bulbar disease. We measured lick rhythm and tongue force to evaluate bulbar disease in the SOD1-G93A rat model of familial ALS. Body weight and grip strength were measured concomitantly. Testing spanned the early (maturation), middle (pre-symptomatic), and late (symptomatic and end-stage) phases of the disease. We measured a persistent tongue motility deficit that became apparent in the early phase of t...

V. Dermoidkystom als freie Geschwulst in der Bauchhöhle

Gynecologic and Obstetric Investigation — Thu, 04 Mar 2010 23:00:00 +0100

Monatsschrift für Geburtshilfe und Gynäkologie 1920;52:180-185 (DOI:10.1159/000295885) (Source: Gynecologic and Obstetric Investigation)

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Interleukin-17 and interleukin-23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?

Acta Neurologica Scandinavica — Thu, 04 Mar 2010 00:00:00 +0100

Conclusions [ndash] Our findings suggest that these molecules may be involved in the pathogenetic mechanisms acting as potential markers of Th17 cells activation in ALS. (Source: Acta Neurologica Scandinavica)

III. Ein zunächst als Enzephalitis lethargica diagnostizierter Hypophysentumor

Ophthalmologica — Wed, 03 Mar 2010 23:00:00 +0100

Zeitschrift für Augenheilkunde 1925;54:286-292 (DOI:10.1159/000295369) (Source: Ophthalmologica)

Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis

Acta Neuropathologica — Wed, 03 Mar 2010 08:50:27 +0100

Abstract Abnormal TDP-43 aggregation is a prominent feature in the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Mutations in TARDBP, the gene encoding TDP-43, cause some cases of ALS. The normal function of TDP-43 remains incompletely understood. To better understand TDP-43 biology, we generated mutant mice carrying a genetrap disruption of Tardbp. Mice homozygous for loss of TDP-43 are not viable. TDP-43 deficient embryos die about day 7.5 of embryonic development thereby demonstrating that TDP-43 protein is essential for normal prenatal development and survival. However, heterozygous Tardbp mutant mice exhibit signs of motor disturbance and muscle weakness. Compared with wild type control littermates, Tardbp +/− animals hav...

No Implants Needed: Movement-Generating Brain Waves Detected and Decoded Outside the Head

Scientific American Topic - Medical Technology — Wed, 03 Mar 2010 00:30:00 +0100

Our bodies are wired to move, and damaged wiring is often impossible to repair. Strokes and spinal cord injuries can quickly disconnect parts of the brain that initiate movement with the nerves and muscles that execute it, and neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis (ALS) draw the process out to the same effect. Scientists have been looking for a way to bypass damaged nerves by directly connecting the brain to an assistive device--like a robotic limb--through brain-computer interface (BCI) technology. Now, researchers have demonstrated the ability to nonintrusively record neural signals outside the skull and decode them into information that could be used to move a prosthetic. [More] (Source: Scientific American Topic - Medical Technology)

No Implants Needed: Movement-Generating Brain Waves Detected and Decoded Outside the Head

Scientific American - Official RSS Feed — Wed, 03 Mar 2010 00:30:00 +0100

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Association of Laparoscopic Surgeons of Great Britain and Ireland (ALS) Tonbridge, Kent, United Kingdom, 26–27 November 2009

Surgical Endoscopy — Tue, 02 Mar 2010 10:01:41 +0100

Content Type Journal ArticleDOI 10.1007/s00464-010-0974-5 Journal Surgical EndoscopyOnline ISSN 1432-2218Print ISSN 0930-2794 (Source: Surgical Endoscopy)

In vitro activation of GAT1 transporters expressed in spinal cord gliosomes stimulates glutamate release that is abnormally elevated in the SOD1/G93A(+) mouse model of amyotrophic lateral sclerosis

Journal of Neurochemistry — Tue, 02 Mar 2010 00:00:00 +0100

J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06628.x The effect of GABA on glutamate release from astrocytes has been studied in healthy mice and in a murine transgenic model of amyotrophic lateral sclerosis (ALS), using mouse spinal cord gliosomes labeled with [3H]d-aspartate ([3H]d-ASP). GABA concentration-dependently evoked the release of [3H]d-ASP. The effect of GABA was not mimicked by GABAA or GABAB receptor agonists or counteracted by antagonists, excluding receptor involvement. However, it was prevented by the GABA transport inhibitor N-(4,4-phenyl-3-butenyl)-nipecotic acid (SKF 89976A), suggesting participation of GABA transporters type 1 (GAT1) placed on glutamate-releasing astrocyte-derived gliosomes. Accordingly, GAT1 co-expressed with glutamate[ndash]aspartate transporter (GL...

Lipid rafts: keys to neurodegeneration.

Brain Research Bulletin — Tue, 02 Mar 2010 00:00:00 +0100

Authors: Schengrund CL The increase in life expectancy seen in many countries has been accompanied by an increase in the number of people living with dementia and a growing need for health care. The large number of affected individuals emphasizes the need to identify causes for the phenotypes associated with diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, Huntington's, and those caused by prions. This review addresses the hypothesis that changes in lipid rafts induced by alterations in their ganglioside and/or cholesterol content or the interaction of mutant proteins with them provide the keys to understanding the onset of neurodegeneration that can lead to dementia. The biological function(s) of raft-associated gangliosides and cholesterol are discussed prior...

Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology

Neurology — Mon, 01 Mar 2010 21:00:04 +0100

(Source: Neurology)

Latest developments at GANIL for stable and radioactive ion beam production

Review of Scientific Instruments — Mon, 01 Mar 2010 17:24:27 +0100

P. Jardin, C. Barue, O. Bajeat, C. Canet, E. Clement et al. In the frame of the SPIRAL II (Systeme de Production d'Ions Radioactifs Acceleres en Ligne Partie II) project, several developments of stable and radioactive ion production systems have been started up. In parallel, GANIL has the ambition to preserve the existing stable and radioactive beams and als ... [Rev. Sci. Instrum. 81, 02A909 (2010)] published Fri Feb 26, 2010. (Source: Review of Scientific Instruments)

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Epidemiology of amyotrophic lateral sclerosis in Isfahan, Iran

European Journal of Neurology — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions: The incidence and prevalence of ALS in the Iranian population seems to be lower compared to other populations and the survival of patients was longer than previously reported. (Source: European Journal of Neurology)

A pioneer in neuropathology: Alix Joffroy (1844–1908), J.-M Charcot’s pupil

Neuromuscular Disorders — Mon, 01 Mar 2010 00:00:00 +0100

The nosography developed in the mid XIXth century was that of neuromuscular diseases. Many disorders were confused among the vast group of muscular atrophies. Gradually, the following diseases were distinguished among others: infantile paralysis, amyotrophic lateral sclerosis, labio-glosso-laryngé paralysis… French doctors Charcot, Duchenne de Boulogne… and other European doctors: Eulenburg, Meryon… participated in this heroic march forward of neurology. One name remains unknown to these neurologists and anatomopathologists: Alix Joffroy (1844–1908). The anatomopathologist tradition developed at the turn of the XXth century. Joffroy was one whose work led to a big advance in neurology by contributing to the establishment of the first foundations of modern spinal anatomopathology. ...

Web2OHS: A Web2.0-Based Omnibearing Homecare System

Information Technology in Biomedicine, IEEE Transactions on - new TOC — Mon, 01 Mar 2010 00:00:00 +0100

This study presents a Web2.0-based Omnibearing Homecare System (Web2OHS) that uses our proposed Application Layer Somecast (ALS) protocol for real-time interactions. Web2OHS provides omnibearing homecare and patientcare services for medical staff and caregivers, which are capable of assisting families, physicians, and nurses to obtain patients’ physiological information using healthcare sensors, as well as monitor their behaviors using monitoring-based services. Web2OHS is a three-tier architecture that consists of Web2OHS clients, the Web2.0-based Patientcare Service Platform (WPSP), and the Medicine-based Active Database (MADB). Users can interact with Web2OHS using various appliances and retrieve the latest physiological and monitoring data using really simple syndication (RSS) a...

Med Sci Monit 2010; 16(3):RA73-78 "Statins and ALS: The possible role of impaired LXR signaling"

Medical Science Monitor — Fri, 26 Feb 2010 19:37:00 +0100

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are commonly used in the therapy of cardiovascular diseases. Recent studies suggest that statins may induce amyotrophic lateral sclerosis (ALS) in some patients, but no pathogenic mechanism has been proposed for this association. Herein the hypothesis is proposed that statins may induce or aggravate ALS by impairing liver X receptor (LXR) signaling. The hypothesis is supported by the following observations: 1) statins inhibit the synthesis of endogenous LXR agonists, oxysterols, and decrease the expression of LXR target genes in many cells, 2) mice lacking LXRβ exhibit sn ALS-like phenotype, 3) statins increase the concentration of plant sterols in plasma and tissues, partially by impairing LXR-dependent signaling, wh...

Statins: Do they cause ALS?

MayoClinic.com Full Feed — Fri, 26 Feb 2010 06:00:00 +0100

Statins can cause muscle injury in some people. But can they also trigger ALS? (Source: MayoClinic.com Full Feed)

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Statins: Do they cause ALS?

MayoClinic.com - Ask a Specialist — Fri, 26 Feb 2010 06:00:00 +0100

Statins can cause muscle injury in some people. But can they also trigger ALS? (Source: MayoClinic.com - Ask a Specialist)

Transient oxidative stress evokes early changes in the functional properties of neonatal rat hypoglossal motoneurons in vitro

European Journal of Neuroscience — Fri, 26 Feb 2010 00:00:00 +0100

Oxidative stress of motoneurons is believed to be an important contributor to neurodegeneration underlying the familial (and perhaps even the sporadic) form of amyotrophic lateral sclerosis (ALS). This concept has generated numerous rodent genetic models with inborn oxidative stress to mimic the clinical condition. ALS is, however, a predominantly sporadic disorder probably triggered by environmental causes. Thus, it is interesting to understand how wild-type motoneurons react to strong oxidative stress as this response might cast light on the presymptomatic disease stage. The present study used, as a model, hypoglossal motoneurons from the rat brainstem slice to investigate how hydrogen peroxide could affect synaptic transmission and intrinsic motoneuron excitability in relation to their ...

VI. Über die rationelle Abortusbehandlung als die beste Prophylaxis gegen die artefizielle Uterusperforation

Gynecologic and Obstetric Investigation — Thu, 25 Feb 2010 23:00:00 +0100

Monatsschrift für Geburtshilfe und Gynäkologie 1916;43:247255 (DOI:10.1159/000292239) (Source: Gynecologic and Obstetric Investigation)

Schlaf und Arbeitsleben

Somnologie - Schlafforschung und Schlafmedizin — Thu, 25 Feb 2010 17:58:30 +0100

Zusammenfassung Hintergrund Gestörter und nichterholsamer Nachtschlaf beeinträchtigt die Arbeitsleistung und die Stresstoleranz und gilt als einer der Risikofaktoren für Burn-out. Eine weitere Folge ist vermehrte Tagesmüdigkeit, die neben einer verminderten Aufmerksamkeits- und Konzentrationsleistung auch als eine Ursache für Arbeits- und Verkehrsunfälle angesehen wird. Methode In der vorliegenden Studie werden die Daten einer Umfrage der Bundesarbeitskammer Österreich an 4214 Arbeitnehmern (BAK-Studie) in Hinblick auf Schlafprobleme (des Ein- und Durchschlafens) und arbeitsbedingte Müdigkeit untersucht. Geklärt werden soll, wie sich gestörter Schlaf auf den allgemeinen Gesundheitszustand, die Arbeitsfähigkeit und die Arbeitszufriedenheit ausw...

Erhöhte Tagesschläfrigkeit in Österreich

Somnologie - Schlafforschung und Schlafmedizin — Thu, 25 Feb 2010 17:58:29 +0100

Zusammenfassung Hintergrund Die Prävalenz von erhöhter Tagesschläfrigkeit wurde in vielen Ländern untersucht, wobei sich die Ergebnisse je nach gewählter Definition und Methodik stark unterschieden. Die vorliegende Untersuchung wurde durchgeführt, um die Häufigkeit von erhöhter Tagesschläfrigkeit in der österreichischen Bevölkerung und den Zusammenhang mit verschiedenen schlaf- und gesundheitsbezogenen Faktoren zu erheben. Methoden Die Daten stammen aus einer Umfrage der Österreichischen Gesellschaft für Schlafmedizin und Schlafforschung (ÖGSM). Befragt wurden 1000 Personen aus allen österreichischen Bundesländern, die Stichprobe war für die österreichische Bevölkerung repräsentativ. Ergebnisse Von den Befragten be...

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DJ-1 forms complexes with mutant SOD1 and ameliorates its toxicity

Journal of Neurochemistry — Thu, 25 Feb 2010 00:00:00 +0100

In this study, we showed the up-regulation of DJ-1 protein levels in mutant SOD1 transgenic mice through the lifespan were observed in the motor neurons. We demonstrated biochemically DJ-1 formed complexes with mutant SOD1 in the cell lysates. Furthermore, DJ-1 over-expression resulted in increased cell viability and reduced cell toxicity in mutant SOD1-transfected neuronal cells, because of improvement in apoptotic pathway and reduction in oxidative stress levels. We also evaluated DJ-1 levels in CSF collected from sporadic ALS patients and controls subjects. The CSF DJ-1 levels were significantly higher in patients with sporadic ALS than in control subjects. These results show that DJ-1 may be associated with sporadic and familial ALS pathogenesis. Therefore, insight into the effects of ...

A pilot trial of telemedicine-assisted, integrated care for patients with advanced amyotrophic lateral sclerosis and their caregivers

Journal of Telemedicine and Telecare — Wed, 24 Feb 2010 22:33:05 +0100

Patients with amyotrophic lateral sclerosis (ALS) need a care programme as the disease progresses. We used telemedicine-assisted integrated care (TAIC) in 40 patients with ALS, for a mean duration of 8.6 months (range 1–12). A nurse-tutor played the key role, supported by respiratory physicians, neurologists and psychologists. Each patient used a portable pulse oximeter during the daily telephone contacts to assess clinical/oxygen variations. Patients also completed a satisfaction questionnaire. During the study period, each patient used TAIC at least five times per month. There were 1907 scheduled telephone calls (86% of the total) and 317 unscheduled calls. Of the unscheduled calls, 84% were managed by the nurse-tutor and only 16% of them required specialist intervention. The most ...

Self-modeling curve resolution techniques applied to comparative analysis of volatile components of Iranian saffron from different regions.

Analytica Chimica Acta — Wed, 24 Feb 2010 20:35:19 +0100

Authors: Jalali-Heravi M, Parastar H, Ebrahimi-Najafabadi H Volatile components of saffron from different regions of Iran were extracted by ultrasonic-assisted solvent extraction (USE) and were analyzed by gas chromatography-mass spectrometry (GC-MS). Self-modeling curve resolution (SMCR) was proposed for resolving the co-eluted GC-MS peak clusters into pure chromatograms and mass spectra. Multivariate curve resolution-objective function minimization (MCR-FMIN) and multivariate curve resolution-alternating least square (MCR-ALS) were successfully used for this purpose. The accuracy of the qualitative and quantitative results was improved considerably using SMCR techniques. Comparison of the results of saffron from different regions of Iran showed that their volatile components are diff...

Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS

Bioinformatics — Wed, 24 Feb 2010 12:48:51 +0100

Motivation: Epistasis, the presence of gene–gene interactions, has been hypothesized to be at the root of many common human diseases, but current genome-wide association studies largely ignore its role. Multifactor dimensionality reduction (MDR) is a powerful model-free method for detecting epistatic relationships between genes, but computational costs have made its application to genome-wide data difficult. Graphics processing units (GPUs), the hardware responsible for rendering computer games, are powerful parallel processors. Using GPUs to run MDR on a genome-wide dataset allows for statistically rigorous testing of epistasis. Results: The implementation of MDR for GPUs (MDRGPU) includes core features of the widely used Java software package, MDR. This GPU implementation allows fo...

TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration [Neuroscience]

Proceedings of the National Academy of Sciences — Wed, 24 Feb 2010 05:51:53 +0100

Neuronal cytoplasmic and intranuclear aggregates of RNA-binding protein TDP-43 are a hallmark feature of neurodegenerative diseases such as amyotrophic lateral... (Source: Proceedings of the National Academy of Sciences)

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Preemie’s pain threshold lower than previously thought

Thrive, Children's Hospital Boston — Tue, 23 Feb 2010 18:00:35 +0100

More than four million babies are born in the United States every year. Of those, 13 percent will be born prematurely. For these infants, their time spent in the Neonatal Intensive Care Unit (NICU) is critical to the future of their well-being. A recent study finds that routine tests performed on infants in the NICU can increase their pain response. It was once believed that newborns don’t feel pain from routine tests. However, some infants undergo many of these routine tests daily and this study shows that “repeated exposure to pain and stress early in life may have lasting effects, including increased pain sensitivity later in life,” according to Reuters. Studies have shown that once a premature infant reaches school age, they have shown to be at significantly higher risk for atten...

Preemies’ pain threshold lower than previously thought

Thrive, Children's Hospital Boston — Tue, 23 Feb 2010 18:00:35 +0100

Diary Note: Nottingham Muscle Group Meeting, UK

Health News from Medical News Today — Tue, 23 Feb 2010 08:00:00 +0100

What Families affected by muscle disease in Nottingham and the East Midlands are meeting to hear how care and services in their region will be improved. Speaking at the meeting will be Kate Caston and Christine Richardson from the East Midlands NHS Specialised Commissioning Group. They were called to Parliament in January to explain to the All Party Parliamentary Group on Muscular Dystrophy (APPG) why East Midlands services for muscle disease patients had not improved as much as in other areas of the UK... (Source: Health News from Medical News Today)

Diary Note: Nottingham Muscle Group Meeting, UK

Muscular Dystrophy News From Medical News Today — Tue, 23 Feb 2010 08:00:00 +0100

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

BMC Neuroscience - Latest articles — Tue, 23 Feb 2010 00:00:00 +0100

Conclusions: In this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. This shows that G-CSF exerts potent anti-apoptotic activities towards motoneurons in vivo and suggests that the protection offered by G-CSF in ALS mouse models is due to its direct neuroprotective activity. (Source: BMC Neuroscience - Latest articles)

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Illness Perceptions After Myocardial Infarction: Relations to Fatigue, Emotional Distress, and Health-Related Quality of Life.

The Journal of Cardiovascular Nursing — Mon, 22 Feb 2010 06:10:35 +0100

CONCLUSIONS:: Patients' illness perceptions influence health outcomes after an MI. Supporting MI patients in increasing their perception of personal control could be a primary nursing strategy in rehabilitation programs aimed at facilitating health behavior, decreasing experiences of fatigue, and increasing HRQoL. PMID: 20168186 [PubMed - as supplied by publisher] (Source: The Journal of Cardiovascular Nursing)

Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders

European Journal of Neuroscience — Mon, 22 Feb 2010 00:00:00 +0100

Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150[ndash]200 [mu]m expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1G93A mutant mimicking amyotrophic la...

William Hague Lends Muscle To Yorkshire And Humber Muscle Group, UK

Health News from Medical News Today — Sun, 21 Feb 2010 09:00:00 +0100

A group of campaigning muscle disease patients from Yorkshire and Humber are proud to announce the Rt. Hon. William Hague MP as their new patron. The Yorkshire and Humber Muscle Group asked Mr Hague, as MP for Richmond and a Rotherham-born local lad, to be patron of their organisation and are pleased that he has accepted this post. Muscular dystrophy patients and their families living in Yorkshire and Humber make up the regional campaigning group for better local muscle disease health services... (Source: Health News from Medical News Today)

William Hague Lends Muscle To Yorkshire And Humber Muscle Group, UK

Muscular Dystrophy News From Medical News Today — Sun, 21 Feb 2010 09:00:00 +0100

A group of campaigning muscle disease patients from Yorkshire and Humber are proud to announce the Rt. Hon. William Hague MP as their new patron. The Yorkshire and Humber Muscle Group asked Mr Hague, as MP for Richmond and a Rotherham-born local lad, to be patron of their organisation and are pleased that he has accepted this post... (Source: Muscular Dystrophy News From Medical News Today)

Amyotrophic lateral sclerosis: sonographic evaluation of dysphagia

La Radiologia Medica — Sat, 20 Feb 2010 06:56:57 +0100

Conclusions VUS can be integrated into the diagnostic protocol for evaluating swallowing in patients with ALS, as it has higher sensitivity than VFS in assessing the dynamic factors that represent the early signs of dysphagia. Content Type Journal ArticleCategory Gastrointestinal Radiology/Radiologia GastrointestinaleDOI 10.1007/s11547-010-0523-2Authors S. Tamburrini, UOC Diagnostica per Immagini PO dei Pellegrini Via Boezio 19 80124 Napoli ItalyA. Solazzo, Seconda Università di Napoli Sezione di Radiologia, Dipartimento Magrassa-Lanzara Napoli ItalyA. Sagnelli, Seconda Università di Napoli II Clinica Neurologica Napoli ItalyL. Del Vecchio, Seconda Università di Napoli Sezione di Radiologia, Dipartimento Magrassa-Lanzara Napoli ItalyA. Reginelli, Seconda Universit...

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Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis

Neuroradiology — Sat, 20 Feb 2010 06:48:01 +0100

Conclusion The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA. Content Type Journal ArticleCategory Diagnostic NeuroradiologyDOI 10.1007/s00234-010-0653-1Authors Kanako Sato, University of Tokyo Department of Radiology, Graduate School of Medicine 7-3-1 Hongo Bunkyō Tokyo Japan 113-8655Shigeki Aoki, Juntendo University Department of Radiology 2-1-1 Hongo Bunkyō Tokyo Japan 113-8421Nobue K. Iwata, University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyō Tokyo Japan 113-8655Yoshitaka Masutani, University of Tokyo Department of Radiology, Graduate School of Medicine 7-3-1 Hongo Bunkyō Tokyo Japan 113-8655Takeyuki Watadani, University of Tokyo Department of Radiology, Graduate School ...

Human angiogenin presents neuroprotective and migration effects in neuroblastoma cells.

Molecular and Cellular Biochemistry — Sat, 20 Feb 2010 00:00:00 +0100

In this study, we investigate whether human wild type ANG (wANG) and its variant K40I (mANG) maintain their divergent functional capacities in neuronal cells. To evaluate this, SH-SY5Y neuroblastoma cells were transfected with wANG and mANG DNA and identified both wild and mutant ANG are localized to nuclei and have no effects on proliferation. We have shown that human wANG prevented cell death under H(2)O(2)-induced oxidative stress in both SH-SY5Y and NSC-34 cells, tested by MTT assay. These effects were more enhanced in motor neuron cell NSC-34. wANG also played a role in cell migration, while mANG decreased these functional activities. Immunoblot analysis revealed that the intracellular signaling of ERK1/2 (at Thr183/Tyr185) was increased following transfection of the wANG gene, and si...

Selected Update: Proteases: Unraveling the therapeutic activity of activated protein C

Nature Signaling Update — Fri, 19 Feb 2010 15:29:33 +0100

Two new studies shed further light on the beneficial roles and mechanisms of action of activated protein C (APC) in two disease conditions: amyotrophic lateral sclerosis and sepsis. (Source: Nature Signaling Update)

TDP-43 Is a Developmentally Regulated Protein Essential for Early Embryonic Development [Neurobiology]

Journal of Biological Chemistry — Fri, 19 Feb 2010 14:39:21 +0100

In this study, we show that TDP-43 is a nuclear protein with persistent high-level expression during embryonic development and with progressively decreased protein levels during postnatal development. In mice where the TDP-43 gene (Tardbp) was disrupted using a gene trap that carries a β-galactosidase marker gene, heterozygous (Tardbp+/–) mice are fertile and healthy, but intercrosses of Tardbp+/– mice yielded no viable homozygotic null (Tardbp–/–) mice. Indeed, Tardbp–/– embryos die between 3.5 and 8.5 days of development. Tardbp–/– blastocysts grown in cell culture display abnormal expansion of their inner cell mass. The pattern of β-galactosidase staining at E9.5 Tardbp+/– embryos is predominantly restricted to the neuroepi...

Characterization of the Human Ventricular Cerebrospinal Fluid Proteome Obtained from Hydrocephalic Patients.

Journal of Proteomics — Fri, 19 Feb 2010 00:00:00 +0100

Authors: Waybright T, Avellino AM, Ellenbogen RG, Hollinger BJ, Veenstra TD, Morrison RS The continuing expansion of proteomic technology has been fueled by the potential for discovering novel biomarkers that may be used for the early detection of disease. It has been proposed that human cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord from traumatic injury, may be a valuable target for the diagnosis of a variety of conditions such as Alzheimer's disease, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson's disease. The immense complexity of biofluids, however, still requires that considerable development be made in the analytical techniques used so that comprehensive coverage of the proteins present in such samples is achieved. Using a...

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Effects of prolonged repetitive stimulation of median, ulnar and peroneal nerves

Muscle and Nerve — Thu, 18 Feb 2010 00:00:00 +0100

In this study we describe the changes in CMAP with prolonged RNS among commonly tested normal nerves. Our findings have important implications with regard to RNS. Muscle Nerve, 2010 (Source: Muscle and Nerve)

Differences in quality of life modalities give rise to needs of individual support in patients with ALS and their next of kin.

Palliative and Supportive Care — Thu, 18 Feb 2010 00:00:00 +0100

Authors: Olsson AG, Markhede I, Strang S, Persson LI Objective:The aim of this study was to examine health-related quality of life (HRQoL), individual QoL, anxiety and depression in patients with amyotrophic lateral sclerosis (ALS) and their next of kin in relation to patients' physical function over time.Methods:35 patients and their next of kin were studied using the Short Form-36 Health Survey (SF-36), Schedule for Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), and Hospital Anxiety and Depression Scale (HADS) and patients also by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and the Norris scale every fourth to sixth month, one to four times.Results:Changes were found over time in both patients and their next of kin in the SF-36 but not in...

Effects of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) at Age 8 Years: Preliminary Data

Clinical Pediatrics — Wed, 17 Feb 2010 07:22:39 +0100

The current study reports the effects of NIDCAP (Newborn Individualized Developmental Care and Assessment Program) at 8 years of age for a randomized controlled trial of 38 very early born (≤29 weeks postmenstrual age), high-risk preterm infants. It was hypothesized that the experimental group at school age in comparison with the control group would perform significantly better neuropsychologically and neuroelectrophysiologically. Twenty-two (11 control, 11 experimental) children of the original 38 (18 control, 20 experimental) participants were studied at school age with a detailed neuropsychological battery and with EEG spectral coherence measures. Results indicated significantly better right hemisphere and frontal lobe function in the experimental group than the control group, both n...

Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosis

Acta Neurologica Scandinavica — Wed, 17 Feb 2010 00:00:00 +0100

Conclusions [ndash] These data suggest that changes of TDP-43 in ALS skin are likely to be related to the disease process and that metabolic alterations of TDP-43 may take place in the skin of patients with ALS. (Source: Acta Neurologica Scandinavica)

ALS care at Mayo Clinic named Center of Excellence — the first in Florida

News from Mayo Clinic — Tue, 16 Feb 2010 15:41:36 +0100

A specialized center that treats a common neuromuscular disease, located within the Mayo Clinic campus in Florida, has for the 5th year been given the highest certification possible by the national ALS (Amyotrophic Lateral Sclerosis) Association. (Source: News from Mayo Clinic)

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ALS care at Mayo Clinic named Center of Excellence — the first in Florida

Mayo Clinic Research News — Tue, 16 Feb 2010 15:41:36 +0100

ALS care at Mayo Clinic named Center of Excellence — the first in Florida

Mayo Clinic Jacksonville News — Tue, 16 Feb 2010 15:41:36 +0100

Clive Svendsen Of Cedars-Sinai To Receive ALS Research Award From American Academy Of Neurology

Health News from Medical News Today — Tue, 16 Feb 2010 08:00:00 +0100

Clive Svendsen, Ph.D., director of the Cedars-Sinai Regenerative Medicine Institute, is receiving the American Academy of Neurology Sheila Essey Award for his research on ALS (amyothrophic lateral sclerosis). ALS, often referred to as Lou Gehrig's disease, is a progressive neurodegenerative disease in which nerve cells called motor neurons degenerate in the brain and spinal cord. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. There is currently no treatment or cure that halts or reverses ALS... (Source: Health News from Medical News Today)

Clive Svendsen Of Cedars-Sinai To Receive ALS Research Award From American Academy Of Neurology

Muscular Dystrophy News From Medical News Today — Tue, 16 Feb 2010 08:00:00 +0100

Clive Svendsen, Ph.D., director of the Cedars-Sinai Regenerative Medicine Institute, is receiving the American Academy of Neurology Sheila Essey Award for his research on ALS (amyothrophic lateral sclerosis). ALS, often referred to as Lou Gehrig's disease, is a progressive neurodegenerative disease in which nerve cells called motor neurons degenerate in the brain and spinal cord... (Source: Muscular Dystrophy News From Medical News Today)

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

Brain — Tue, 16 Feb 2010 03:54:46 +0100

The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 seq...

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Induction of Molecular Chaperones as a Therapeutic Strategy for the Polyglutamine Diseases.

Current Pharmaceutical Biotechnology — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Nagai Y, Fujikake N, Popiel HA, Wada K Protein misfolding and aggregation in the brain have been implicated as a common molecular pathogenesis of various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and the polyglutamine (polyQ) diseases. The polyQ diseases are a group of nine hereditary neurodegenerative diseases, including Huntington's disease (HD) and various types of spinocerebellar ataxia (SCA), which are caused by abnormal expansions of the polyQ stretch (> 35-40 repeats) in unrelated disease-causative proteins. The expanded polyQ stretch is thought to trigger misfolding of these proteins, leading to their aggregation and accumulation as inclusion bodies in affected neurons, eventually resulting in neuro...

Heat Shock Proteins: Therapeutic Drug Targets for Chronic Neurodegeneration?

Current Pharmaceutical Biotechnology — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Sajjad MU, Samson B, Wyttenbach A Intra- and extracellular protein misfolding and aggregation is likely to contribute to a number of age-related central nervous system diseases ("proteinopathies"). Therefore, molecular chaperones, such as heat shock proteins (HSPs), that regulate protein folding, misfolding and adaption to cellular stress are emerging as therapeutic targets. Here we review the current knowledge of HSP-modulating drugs and discuss the opportunities and difficulties of their therapeutic use to treat proteinopathies such as Alzheimer's- and Parkinson's disease, the polyglutamine- and prion disorders and Amyotrophic Lateral Sclerosis. PMID: 20166961 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology)

Heat Shock Proteins as Suppressors of Accumulation 0f Toxic Prefibrillar Intermediates and Misfolded Proteins in Neurodegenerative Diseases.

Current Pharmaceutical Biotechnology — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Arawaka S, Machiya Y, Kato T The most characteristic feature of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, is the occurrence of extra- or intracellular fibrillar aggregates containing misfolded proteins with beta-sheet conformation. These aggregates are composed of distinct proteins in each neurodegenerative disease. However, mutations in genes encoding major constituents of aggregates, such as Abeta, tau, alpha-synuclein, SOD1 and huntingtin, have been identified to causally associate with familial forms of the diseases. Biochemical studies demonstrate that these mutant and some wild-type proteins tend to be misfolded or form aggregates. It has been proposed that these diseases are ca...

Cedars-Sinai Regenerative Medicine Institute to receive ALS Research Award

EurekAlert! - Medicine and Health — Mon, 15 Feb 2010 05:00:00 +0100

(Cedars-Sinai Medical Center) Clive Svendsen, Ph.D., director of the Cedars-Sinai Regenerative Medicine Institute, is receiving the American Academy of Neurology Sheila Essey Award for his research on ALS (amyothrophic lateral sclerosis). (Source: EurekAlert! - Medicine and Health)

Common genetic variation of insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, and acid labile subunit in relation to serum IGF-I levels and mammographic density

Breast Cancer Research and Treatment — Sun, 14 Feb 2010 06:51:42 +0100

Abstract Mammographic density is strongly related to increased breast cancer risk. Accumulating evidence indicates that a role for the IGF-pathway in mammographic density and breast cancer development. Here, we investigate whether common genetic variation in this pathway influences insulin-like growth factor-I (IGF-I) levels and mammographic density. In 1,916 premenopausal women within the Prospect-EPIC cohort, we examined associations of 14 haplotype tagging SNPs in the ALS, IGFBP1, and IGFBP3 genes with IGF-I circulating levels and mammographic density. In 657 women, who became postmenopausal during follow-up, we investigated how these SNPs were related with the decrease in density over menopause. Linear regression models were used for statistical analysis. None of the A...

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Intoxikationen als Ursachen von Bewusstseinsstörungen

Intensivmedizin und Notfallmedizin — Sat, 13 Feb 2010 06:46:06 +0100

Zusammenfassung Störungen des Bewusstseins sind das häufigste Leitsymptom bei Vergiftungen. Sie können sich als Verwirrung, Delir und Agitiertheit oder Somnolenz, Sopor und Koma zeigen. Viele Intoxikationen lösen zusätzlich zur Bewusstseinsstörung auch epileptiforme zerebrale Krampfanfälle aus. Daneben können muskuläre Symptome, v. a. ein vermehrter Muskeltonus oder auch ein Faszikulieren der Muskulatur, auf bestimmte Vergiftungen hinweisen. Es ist möglich, die Diagnose anhand dieser unterschiedlichen Symptomatik so einzugrenzen, dass ein gezielter Giftnachweis geführt werden kann. Bei schweren Vergiftungen ist die richtige Diagnose wegen einer gezielten Antidot- und Entgiftungstherapie bedeutend. Content Type Journal ArticleCategory LeitthemaDOI 10.1007/...

Validating population-based registers for ALS: how accurate is death certification?

Journal of Neurology — Fri, 12 Feb 2010 07:08:14 +0100

Abstract The purpose of this study was to determine the accuracy of death certification for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) as recorded by the Central Statistics Office in the Republic of Ireland, and to examine its utility in capture-recapture analysis. The database of the Irish Central Statistics Office (CSO) was searched for death certificates of individuals over 15 years of age for whom ALS/MND (ICD9) was listed as a primary, secondary or tertiary cause of death from 2002 to 2006. This dataset was compared with mortality data from the Irish Register for ALS/MND for the same period. Three hundred ninety-eight cases with a diagnosis of ALS were identified through the CSO. The cause of death as identified by the CSO was 318 out of 398 (...

Timing of drug administration during CPR and the role of simulation

Resuscitation — Thu, 11 Feb 2010 14:16:04 +0100

The role of drugs in cardiopulmonary resuscitation (CPR) remains unclear. To date no randomised controlled study has demonstrated that the routine use of any vasopressor at any stage during cardiac arrest increases the rate of neurologically intact survival to hospital discharge in humans. The favourable outcome of initial return of spontaneous circulation (ROSC) and increased survival seen with vasopressors in animal studies have not been consistently shown in human studies. The large prospective observational study of more than 10000 cardiac arrests in Sweden found the use of adrenaline was an independent predictor of poor outcomes. The introduction of advanced life support (ALS) trained paramedics in the OPALS study failed to change survival rates in over 4000 cardiac arrest victims. Re...

Requests for euthanasia: origin of suffering in ALS, heart failure, and cancer patients

Journal of Neurology — Thu, 11 Feb 2010 11:47:50 +0100

This study provided consultation reports and questionnaires filled out by the attending physicians from 3,337 consultations conducted by SCEN physicians in situations where a patient requested EAS. For this study we selected data on all ALS patients (n = 51), all heart failure patients (n = 61), and a random sample of 73 cancer patients. The most frequently reported reasons for unbearable suffering were: fear of suffocation (45%) and dependency (29%) in ALS patients, pain (46%) and fatigue (28%) in cancer patients, and dyspnea (52%) and dependency (37%) in heart failure patients. Somatic complaints were reported more frequently as a reason for EAS by cancer patients [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.09–0.46] and heart failure patients [OR 0.16...

Sandra Gidley MP Flexes Political Muscle To Call For New Muscle Disease Care Advisor, UK

Muscular Dystrophy News From Medical News Today — Thu, 11 Feb 2010 11:00:00 +0100

Sandra Gidley MP is backing the fight for better muscle disease healthcare in Hampshire by calling on NHS bosses to fund specialist staff. Last month the South Central Muscle Group, a patients' forum for families in the region living with muscular dystrophy, met in Southampton where MP for Romsey Sandra Gidley spoke to them about making their voices heard by politicians... (Source: Muscular Dystrophy News From Medical News Today)

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Sandra Gidley MP Flexes Political Muscle To Call For New Muscle Disease Care Advisor, UK

Health News from Medical News Today — Thu, 11 Feb 2010 11:00:00 +0100

Prevalence of depression in amyotrophic lateral sclerosis and other motor disorders

European Journal of Neurology — Thu, 11 Feb 2010 00:00:00 +0100

Background: Research suggests the prevalence of severe depression in ALS is (Source: European Journal of Neurology)

An antibody-based affinity chromatography tool to assess Cu, Zn superoxide dismutase (SOD) G93A structural complexity in vivo.

Biotechnology Journal — Thu, 11 Feb 2010 00:00:00 +0100

Authors: Palacios F, Cota G, Horjales S, Lima A, Battistoni J, Sotelo-Silveira J, Marín M 'Conformational diseases' are a group of diverse disorders that have been associated with misfolding of specific proteins, leading to their aggregation in particular cell tissues. Despite their relevance, the mechanisms involved in neurodegenerative processes remains poorly understood. Mutations in Cu,Zn superoxide dismutase (SOD1) are implicated in death of motor neurons in amyotrophic lateral sclerosis. Among others, the SOD1(G93A) mutation is known to weaken the structure and this could lead to conformational variations of the protein. As an approach to understand the tissue-specific propensity of protein aggregation, we developed an experimental procedure allowing rapid extraction of vari...

I. Die Eklampsie als Vergiftung

Gynecologic and Obstetric Investigation — Wed, 10 Feb 2010 23:00:00 +0100

Monatsschrift für Geburtshilfe und Gynäkologie 1904;20:12681282 (DOI:10.1159/000286289) (Source: Gynecologic and Obstetric Investigation)

Geschwisterrelationen als Funktionsmuster der (therapeutischen) Gruppen

Psychotherapy and Psychosomatics — Wed, 10 Feb 2010 23:00:00 +0100

Psychother Psychosom 1966;14:251263 (DOI:10.1159/000285829) (Source: Psychotherapy and Psychosomatics)

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Der Vereinsamte als Patient

Psychotherapy and Psychosomatics — Wed, 10 Feb 2010 23:00:00 +0100

Psychother Psychosom 1966;14:186198 (DOI:10.1159/000285824) (Source: Psychotherapy and Psychosomatics)

Neurologische Ursachen von Bewusstseinsstörungen

Intensivmedizin und Notfallmedizin — Tue, 09 Feb 2010 17:35:44 +0100

Zusammenfassung Neurologische Ursachen von Bewusstseinsstörungen sind häufig und erfordern in der Regel eine rasche Therapie. Kritisch für den optimalen Behandlungserfolg ist daher die schnelle und dennoch möglichst zuverlässige Differenzialdiagnose. Ein strukturiertes Vorgehen bei der Untersuchung in der Notfallsituation erleichtert dies. Bewusstseinsstörungen werden häufig in quantitative und qualitative Störungen eingeteilt. Wesentliche Komponente einer quantitativen Bewusstseinsstörung ist die Vigilanzminderung. Qualitative Bewusstseinsstörungen führen z. B. zu Verwirrtheitszuständen oder einem Delir. Für die Identifikation neurologischer Ursachen ist die sorgfältige Untersuchung von Begleitsymptomen kritisch. Da die Vigilanz wesentlich vom aszendiere...

Upregulation of persistent sodium conductances in familial ALS

Journal of Neurology, Neurosurgery & Psychiatry — Tue, 09 Feb 2010 15:00:05 +0100

Conclusions Taken together, these studies suggest that persistent Na+ conductances are upregulated in FALS and that this upregulation is intrinsically associated with axonal degeneration. (Source: Journal of Neurology, Neurosurgery & Psychiatry)

Amyloid oligomers: dynamics and toxicity in the cytosol and nucleus

FEBS Journal — Tue, 09 Feb 2010 00:00:00 +0100

The accumulation of misfolded proteins in the cytosol and nucleus of neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by polyglutamine-expanded proteins, whereas mutations in superoxide dismutase 1 lead to amyotrophic lateral sclerosis. These structurally unstable mutant species perturb essential interactions between normal proteins and tend to aggregate because of the presence of exposed hydrophobic surfaces. Accumulating evidence suggests that soluble species, including misfolded monomers and oligomers, are more toxic than large insoluble aggregates or inclusions. Spectroscopic analysis, including fluorescence recovery after photobleaching and fluorescence loss in photobleaching, in living cells revealed that protein aggregates of misfolded proteins ...

PI3K/Akt/mTOR signaling regulates glutamate transporter 1 in astrocytes.

Biochemical and Biophysical Research communications — Tue, 09 Feb 2010 00:00:00 +0100

Authors: Wu X, Kihara T, Akaike A, Niidome T, Sugimoto H Reduction in or dysfunction of glutamate transporter 1 (GLT 1) is linked to several neuronal disorders such as stroke, Alzheimer's disease, and amyotrophic lateral sclerosis. However, the detailed mechanism underlying GLT 1 regulation has not been fully elucidated. In the present study, we first demonstrated the effects of mammalian target of rapamycin (mTOR) signaling on GLT 1 regulation. We prepared astrocytes cultured in astrocyte-defined medium (ADM), which contains insulin and several growth factors including epidermal growth factor (EGF) and insulin. The levels of phosphorylated Akt (Ser473) and mTOR (Ser2448) increased, and GLT 1 levels were increased in ADM-cultured astrocytes. Treatment with a phosphatidylinositol 3-kina...

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Human adipose-derived stem cells enhance the glutamate uptake function of GLT1 in SOD1(G93A)-bearing astrocytes.

Biochemical and Biophysical Research communications — Tue, 09 Feb 2010 00:00:00 +0100

Authors: Gu R, Hou X, Pang R, Li L, Chen F, Geng J, Xu Y, Zhang C Impaired glutamate uptake function of astrocytes associated with accumulation of extracellular glutamate is a well-documented feature of amyotrophic lateral sclerosis (ALS). Enhancing the uptake function of astrocytic glutamate transport 1 (GLT1) may be a potential treatment for this disease. Human adipose-derived stem cells (hADSCs) are capable of secreting a large number of cytokines which exhibit diverse pharmacological effects. Therefore, we investigate the influence of the soluble factors released by hADSCs on the GLT1 in primary astrocytes cultured from SOD1(G93A) mice, a widely studied mutant human SOD1 transgenic model of ALS. Our data indicate that soluble factors from hADSCs significantly upregulate the express...

FUS Mutations in Familial Amyotrophic Lateral Sclerosis in the Netherlands [Original Contribution]

Archives of Neurology — Mon, 08 Feb 2010 20:51:02 +0100

Conclusions We discovered FUS mutations in Dutch patients with FALS and the occurrence of benign variations in the gene. Therefore, caution is warranted when interpreting results in a clinical setting. Although the phenotype associated with FUS mutations is variable, most patients predominantly demonstrate loss of lower motor neurons and have short disease survival. (Source: Archives of Neurology)

Progress on Progranulin [Editorial]

Archives of Neurology — Mon, 08 Feb 2010 20:51:01 +0100

(Source: Archives of Neurology)

The Spectrum of Mutations in Progranulin: A Collaborative Study Screening 545 Cases of Neurodegeneration [Original Contribution]

Archives of Neurology — Mon, 08 Feb 2010 20:51:01 +0100

Conclusions Pathogenic mutations were found only in FTD-spectrum cases and not in other related neurodegenerative diseases. Haploinsufficiency of GRN is the predominant mechanism leading to FTD. (Source: Archives of Neurology)

Metabolische Ursachen von Bewusstseinsstörungen

Intensivmedizin und Notfallmedizin — Mon, 08 Feb 2010 17:28:47 +0100

Zusammenfassung Eine Vielzahl metabolischer Entgleisungen manifestiert sich mit einer primären Bewusstseinsstörung (metabolische Enzephalopathie). Die Pathomechanismen sind vielfältig. Das klinische Bild ist meist unspezifisch, umfasst sowohl quantitative (Vigilanzminderung) als auch qualitative Veränderungen (Bewusstseinstrübung) und ist variabel im Verlauf. Die klinische Untersuchung fokussiert auf mentale, kognitive Symptome, Hirnnervenfunktion, motorische Defizite und Zeichen der vegetativen Instabilität. Orientierende Laboruntersuchungen sind wegweisend. Eine zerebrale Bildgebung ist bei Unklarheiten großzügig indiziert. Die wichtigsten metabolischen Enzephalopathieformen umfassen Elektrolytstörungen (insbesondere Hyponatriämie), glykämische Entgleisungen, a...

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ALS model mirrors human disorder

Hope Center News — Mon, 08 Feb 2010 11:38:05 +0100

A new mouse model of amyotrophic lateral sclerosis (ALS) closely resembles the paralyzing disorder in humans, researchers at the School of Medicine reported in the November 3, 2009 issue of Proceedings of the National Academy of Sciences. (Source: Hope Center News)

Researchers Report That TÎ²4 Increases Skeletal Muscle And May Have A Role In The Treatment Of Duchenne Muscular Dystrophy

Muscular Dystrophy News From Medical News Today — Mon, 08 Feb 2010 11:00:00 +0100

Regenerx Biopharmaceuticals, Inc. (NYSE Amex:RGN) announced today that a research team in Washington, D.C. has found that dystrophin-deficient Mdx mice, treated twice a week for six months with TÎ²4, showed a significant increase in skeletal muscle regenerating fibers compared to untreated mice. No effects related to muscle function or fibrosis and no adverse reactions were observed in the mice... (Source: Muscular Dystrophy News From Medical News Today)

Researchers Report That TÎ²4 Increases Skeletal Muscle And May Have A Role In The Treatment Of Duchenne Muscular Dystrophy

Health News from Medical News Today — Mon, 08 Feb 2010 11:00:00 +0100

Regenerx Biopharmaceuticals, Inc. (NYSE Amex:RGN) announced today that a research team in Washington, D.C. has found that dystrophin-deficient Mdx mice, treated twice a week for six months with TÎ²4, showed a significant increase in skeletal muscle regenerating fibers compared to untreated mice. No effects related to muscle function or fibrosis and no adverse reactions were observed in the mice. Mdx mice are used as models for Duchenne muscular dystrophy to evaluate potential therapeutic compounds... (Source: Health News from Medical News Today)

AVI BioPharma's Drug Candidate AVI-5038 Receives European Orphan Drug Designation For Duchenne Muscular Dystrophy

Health News from Medical News Today — Sun, 07 Feb 2010 08:00:00 +0100

AVI BioPharma, Inc. (NASDAQ: AVII), a developer of RNA-based drugs, announced that it received an orphan drug designation from the Committee for Orphan Medical Products of the European Medicines Agency (EMEA) for AVI-5038, a drug candidate being developed by AVI for the treatment of Duchenne Muscular Dystrophy (DMD). DMD is a genetic muscle-wasting disease caused by failure to produce dystrophin. The orphan drug designation potentially may provide AVI up to 10 years of market exclusivity if the drug candidate is approved for marketing in the European Union (EU)... (Source: Health News from Medical News Today)

AVI BioPharma's Drug Candidate AVI-5038 Receives European Orphan Drug Designation For Duchenne Muscular Dystrophy

Muscular Dystrophy News From Medical News Today — Sun, 07 Feb 2010 08:00:00 +0100

AVI BioPharma, Inc. (NASDAQ: AVII), a developer of RNA-based drugs, announced that it received an orphan drug designation from the Committee for Orphan Medical Products of the European Medicines Agency (EMEA) for AVI-5038, a drug candidate being developed by AVI for the treatment of Duchenne Muscular Dystrophy (DMD). DMD is a genetic muscle-wasting disease caused by failure to produce dystrophin... (Source: Muscular Dystrophy News From Medical News Today)

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Recent Advancements in Stem Cell and Gene Therapies for Neurological Disorders and Intractable Epilepsy.

Neuropharmacology — Sun, 07 Feb 2010 00:00:00 +0100

Authors: Naegele JR, Maisano X, Yang J, Royston S, Ribeiro E The potential applications of stem cell therapies for treating neurological disorders are enormous. Many laboratories are focusing on stem cell treatments for CNS diseases, including spinal cord injury, Amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, stroke, traumatic brain injury, and epilepsy. Among the many stem cell types under testing for neurological treatments, the most common are fetal and adult brain stem cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. An expanding toolbox of molecular probes is now available to allow analyses of neural stem cell fates prior to and after transplantation. Concomitantly, protocols are being developed...

California Stem Cell And ALS Therapy Development Institute Extend Their Collaboration To Advance Potential Stem Cell Assisted Therapy For ALS

Health News from Medical News Today — Sat, 06 Feb 2010 09:00:00 +0100

California Stem Cell, Inc. (CSC) and ALS Therapy Development Institute (ALS TDI) are pleased to announce an extension and expansion of their collaboration aimed at advancing a potential stem cell therapy for ALS (amyotrophic lateral sclerosis). This effort will build on work that has already been completed as part of this on-going partnership to understand how stem cells, and their derivatives, may be applied to treatment of this fatal neurodegenerative disease... (Source: Health News from Medical News Today)

California Stem Cell And ALS Therapy Development Institute Extend Their Collaboration To Advance Potential Stem Cell Assisted Therapy For ALS

Muscular Dystrophy News From Medical News Today — Sat, 06 Feb 2010 09:00:00 +0100

The Insulin-like Growth Factor-1 Binding Protein Acid-labile Subunit Alters Mesenchymal Stromal Cell Fate [Lipids]

Journal of Biological Chemistry — Fri, 05 Feb 2010 14:38:39 +0100

Age-related osteoporosis is accompanied by an increase in marrow adiposity and a reduction in serum insulin-like growth factor-1 (IGF-1) and the binding proteins that stabilize IGF-1. To determine the relationship between these proteins and bone marrow adiposity, we evaluated the adipogenic potential of marrow-derived mesenchymal stromal cells (MSCs) from mice with decreased serum IGF-1 due to knockdown of IGF-1 production by the liver or knock-out of the binding proteins. We employed 10–16-week-old, liver-specific IGF-1-deficient, IGFBP-3 knock-out (BP3KO) and acid-labile subunit knock-out (ALSKO) mice. We found that expression of the late adipocyte differentiation marker peroxisome proliferator-activated receptor was increased in marrow isolated from ALSKO mice. When induced with a...

Einzelhaft als Risikofaktor für psychiatrische Hospitalisierung

Psychopathology — Thu, 04 Feb 2010 23:00:00 +0100

Psychiatria clin. 1983;16:365377 (DOI:10.1159/000284167) (Source: Psychopathology)

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ALS Therapy Development Institute And Oxford BioMedica Begin Second Phase Of Collaboration To Develop Gene Therapies For ALS, UK

Health News from Medical News Today — Thu, 04 Feb 2010 03:00:00 +0100

The ALS Therapy Development Institute and Oxford BioMedica announced today the extension of their collaboration following successful completion of the first phase. The extended collaboration, which is funded by the Muscular Dystrophy Association, aims to advance the development of Oxford BioMedica's preclinical gene therapy candidate, MoNuDin®, and to evaluate other gene-based strategies for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). "ALS is a debilitating disease that takes so many of our best and brightest from us without warning and without reason... (Source: Health News from Medical News Today)

ALS Therapy Development Institute And Oxford BioMedica Begin Second Phase Of Collaboration To Develop Gene Therapies For ALS, UK

Muscular Dystrophy News From Medical News Today — Thu, 04 Feb 2010 03:00:00 +0100

The ALS Therapy Development Institute and Oxford BioMedica announced today the extension of their collaboration following successful completion of the first phase... (Source: Muscular Dystrophy News From Medical News Today)

FUS mutations in sporadic amyotrophic lateral sclerosis.

Neurobiology of Aging — Thu, 04 Feb 2010 00:00:00 +0100

Authors: Lai SL, Abramzon Y, Schymick JC, Stephan DA, Dunckley T, Dillman A, Cookson M, Calvo A, Battistini S, Giannini F, Caponnetto C, Mancardi GL, Spataro R, Monsurro MR, Tedeschi G, Marinou K, Sabatelli M, Conte A, Mandrioli J, Sola P, Salvi F, Bartolomei I, Lombardo F, , Mora G, Restagno G, Chiò A, Traynor BJ Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS m...

Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications

Apoptosis — Wed, 03 Feb 2010 17:58:29 +0100

We describe the intricate nature of the ubiquitin/proteasome pathway and discuss the paradox of protein aggregation, i.e. its potential toxic/protective effect in neurodegeneration. The relations between some of the dysfunctional components of the pathway and neurodegeneration are presented. We highlight possible ubiquitin/proteasome pathway-targeting therapeutic approaches, such as activating the proteasome, enhancing ubiquitination and promoting SUMOylation that might be important to slow/treat the progression of neurodegeneration. Finally, a model time line is presented for neurodegeneration starting at the initial injurious events up to protein aggregation and cell death, with potential time points for therapeutic intervention. Content Type Journal ArticleCategory Apoptosis in...

Zinc induces depletion and aggregation of endogenous TDP-43.

Free Radical Biology and Medicine — Wed, 03 Feb 2010 00:00:00 +0100

Authors: Caragounis A, Price KA, Soon CP, Filiz G, Masters CL, Li QX, Crouch PJ, White AR Ubiquitinated neuronal aggregates containing TDP-43 are pathological hallmarks in the spectrum of frontotemporal lobar dementia and amyotrophic lateral sclerosis. In affected neurons, the TDP-43 undergoes C-terminal fragmentation, phosphorylation and ubiquitination and forms aggregates in the cytoplasm or nucleus. While in vitro studies have been able to re-capitulate these features using transfected cell culture models, little is known about the biochemical mechanisms that underlie pathological changes to endogenous TDP-43. As altered metal ion homeostasis and increased oxidative stress are central features of neurodegeneration, including FTLD and ALS, we sought to determine the affects of these ...

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Association of ALS with head injury, cigarette smoking and APOE genotypes

Journal of the Neurological Sciences — Wed, 03 Feb 2010 00:00:00 +0100

Conclusions: Our results add to the body of evidence suggesting that head injuries may be a risk factor for multiple neurodegenerative diseases, including ALS. We hypothesize that the strength of association between head injuries and ALS may depend upon APOE genotype. (Source: Journal of the Neurological Sciences)

Mutant SOD1 knockdown in all cell types ameliorates disease in G85R SOD1 mice with a limited additional effect over knockdown restricted to motor neurons

Journal of Neurochemistry — Tue, 02 Feb 2010 00:00:00 +0100

J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06594.x Approximately 10% of patients with amyotrophic lateral sclerosis (ALS) have familial ALS (FALS), and 20% of FALS is caused by mutant Cu/Zn superoxide dismutase type 1 (MTSOD1). Previous studies have convincingly demonstrated that MTSOD1 expression in other cell types besides motor neurons (MNs) contributes to disease in MTSOD1 FALS transgenic mice. Using Cre/LoxP methods, we knocked down G85R SOD1 mRNA by 66% in all cell types in 3-month-old FALS transgenic mice, delaying disease onset and lengthening disease duration. Surprisingly, the effect on onset and early disease duration was similar to that seen in FALS transgenic mice with [sim]25% knockdown prenatally in G85R SOD1 mRNA restricted to MNs and some interneurons. These results dem...

The Science of Small Clinical Trials Lecture Series: Methods of Particular Interest for Small Clinical Trials (Part 2 of 2)

Videocast - All Events — Mon, 01 Feb 2010 21:14:00 +0100

Over two lectures, Drs. Coffey & Wittes will describe some clinical trial design and analysis methods that are of particular interest in instances of small study populations, including: cross-over, n-of-1, factorial, sequential, adaptive, play-the-winner, risk-based allocation, and case-control, illustrated by case studies of Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease) and Mucopolysaccaridosis type VI (Maroteaux-Lamy Syndrome).Air date: 3/2/2010 10:00:00 AM (Source: Videocast - All Events)

The Science of Small Clinical Trials Lecture Series: Methods of Particular Interest for Small Clinical Trials (Part 1 of 2)

Videocast - All Events — Mon, 01 Feb 2010 21:13:00 +0100

Over two lectures, Drs. Coffey & Wittes will describe some clinical trial design and analysis methods that are of particular interest in instances of small study populations, including: cross-over, n-of-1, factorial, sequential, adaptive, play-the-winner, risk-based allocation, and case-control, illustrated by case studies of Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's Disease) and Mucopolysaccaridosis type VI (Maroteaux-Lamy Syndrome).Air date: 2/24/2010 10:00:00 AM (Source: Videocast - All Events)

Genetic contribution of FUS to frontotemporal lobar degeneration

Neurology — Mon, 01 Feb 2010 21:02:05 +0100

Conclusions: In a first analysis of FUS in patients with frontotemporal lobar degeneration (FTLD), we identified a novel FUS missense mutation, M254V, in 1 patient with pure FTLD. At this point, the biologic relevance of this mutation remains elusive. Screening of additional FTLD patient cohorts will be needed to further elucidate the contribution of FUS mutations to FTLD pathogenesis. (Source: Neurology)

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FUS: A new actor on the frontotemporal lobar degeneration stage

Neurology — Mon, 01 Feb 2010 21:02:04 +0100

(Source: Neurology)

ALS Young Investigators Meeting 2010 (2010-07-28)

Institute of Psychiatry | Events — Mon, 01 Feb 2010 17:57:11 +0100

The 8th European ALS Young Investigator Meeting is being held July 28, 29, 30 2010 in London, England. It has been organised by an international scientific committee of world class researchers from the field of ALS/MND research.<br /> <br />Our aim is to bring together established clinicians and researchers with younger scientists, encouraging new ways of thinking and providing a platf (Source: Institute of Psychiatry | Events)

3-Year Mission To Understand And Treat Neurodegenerative Disease

Health News from Medical News Today — Mon, 01 Feb 2010 09:00:00 +0100

Project A.L.S. (New York, NY) and the Robert Packard Center for ALS Research at Johns Hopkins University (Baltimore, MD) announced that they will partner on P2 ALS, a $15 million initiative designed to advance ALS (Lou Gehrig's disease) research exponentially over the next three years. Project A.L.S... (Source: Health News from Medical News Today)

3-Year Mission To Understand And Treat Neurodegenerative Disease

Multiple Sclerosis News From Medical News Today — Mon, 01 Feb 2010 09:00:00 +0100

Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene

Journal of Neuroscience Research — Mon, 01 Feb 2010 00:00:00 +0100

Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression increased in the spinal mo...

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N.J. Law Allows Limited Medical Marijuana Use

Internal Medicine News — Mon, 01 Feb 2010 00:00:00 +0100

New Jersey has become the 14th state in the nation to allow the medical use of marijuana, although its program will be the country's most restrictive. Outgoing Gov. Jon S. Corzine (D) signed the “Compassionate Use Medical Marijuana Act” into law on Jan. 18, shortly before leaving office; the law will take effect in 6 months. The new law will remove legal penalties for the possession and use of marijuana for medical purposes. Under the law, the drug must be recommended by a licensed state physician for a qualifying medical condition such as cancer, HIV/AIDS, multiple sclerosis, amyotrophic lateral sclerosis, or Crohn's disease. (Source: Internal Medicine News)

Caring for the Patient with ALS: It Takes a Village (404)

Journal of Pain and Symptom Management — Mon, 01 Feb 2010 00:00:00 +0100

Describe an interdisciplinary treatment approach to common symptoms and functional loss in ALS. (Source: Journal of Pain and Symptom Management)

N.J. Law Allows Limited Medical Marijuana Use

Family Practice News — Mon, 01 Feb 2010 00:00:00 +0100

New Jersey recently became the 14th state to allow the medical use of marijuana, though its law is the country's most restrictive. Last month, outgoing Gov. Jon S. Corzine (D) signed the “Compassionate Use Medical Marijuana Act” (A804/S119) into law. The new law will remove legal penalties for the possession and use of marijuana for medical purposes. Under the law, the drug must be recommended by a licensed state physician for a qualifying medical condition such as cancer, HIV/AIDS, multiple sclerosis, amyotrophic lateral sclerosis, or Crohn's disease. (Source: Family Practice News)

Power Wheelchair Prescription, Utilization, Satisfaction, and Cost for Patients With Amyotrophic Lateral Sclerosis: Preliminary Data for Evidence-Based Guidelines

Archives of Physical Medicine and Rehabilitation — Mon, 01 Feb 2010 00:00:00 +0100

Conclusions: We obtained first-hand knowledge from 32 patients with ALS/MND who are current PWC users on their use and satisfaction with their PWCs from initial to current use. Based on this survey, patients with ALS/MND seen for their wheelchair evaluation with experienced clinicians exhibit high use and satisfaction with their PWCs. (Source: Archives of Physical Medicine and Rehabilitation)