Symptoms Of Mesothelioma - Early Detection Of A Deadly Cancer
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In most cases, people usually ignore the symptoms of Mesothelioma due to their generic nature. This is because the early symptoms of mesothelioma can also be the indication of other common Read more...
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Titan pharmaceuticals announces spheramine® initial phase iib results
Titan Pharmaceuticals, Inc. (AMEX:TTP) announced initial analyses show that Spheramine® did not meet the Phase IIb clinical study's primary or key secondary endpoints, with no significant differences detected between the Spheramine and sham surgery arms of the study after 12 months of follow-up. (Source: Parkinson's Disease News From Medical News Today) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Treatment challenges in parkinson's disease.
Parkinson's disease is a degenerative disease of the central nervous system that affects approximately 1% of the U.S. population over 65 years of age. Prompt identification of symptom reemergence due to medication wearing off is crucial.Page: 32DOI: 10.1097/01.NPR.0000325979.75451.32Authors: Welsh, Mickie RN, DNSc (Source: Nurse Practitioner, The)
Unmasking psychiatric symptoms after stn deep brain stimulation in parkinson's disease.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18439220">Related Articles</a></td></tr></table>
<p><b>Unmasking psychiatric symptoms after STN deep brain stimulation in Parkinson's disease.</b></p>
<p>Acta Neurol Scand Suppl. 2008;188:41-5</p>
<p>Authors: Lilleeng B, Dietrichs E</p>
<p>BACKGROUND: Stereotactic implantation of electrodes for deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established treatment for Parkinson's disease. The treatment gives stable effect over years on the motor symptoms of Parkinson's disease. Psychiatric effects of STN-DBS have attracted increasing attention, with a growing number of reports on psychiatric side effects or exacerbations of known psychiatric disease. However, little is known about the possible unmasking of hidden psychiatric symptoms after surgery. AIMS: The aim of this clinical commentary is to illustrate unmasking of psychiatric disease by STN-DBS through the presentation of a case from our clinic. PATIENT: A patient with Parkinson's disease underwent implantation of STN stimulation electrodes with good results on his motor symptoms. He did not disclose his previous psychiatric history. Soon after the onset of stimulation he developed affective symptoms with manic, aggressive and depressive behaviour, and also an attempted suicide. The stimulation was reduced and his dopaminergic medication increased after the attempted suicide. His previous history of depression and anxiety was now revealed. He received psychiatric attention, and the affective symptoms resolved. The effect of the stimulation on motor symptoms remained stable. CONCLUSIONS: The unmasking of previous psychiatric problems after STN stimulation may be an underestimated problem. It is necessary to fully penetrate the psychiatric anamnesis, especially in patients with a strong wish to be operated and a consequent reluctance to reveal previous problems. Patients with a previous history of a psychiatric disorder are not the best candidates for implantation of STN electrodes.</p>
<p>PMID: 18439220 [PubMed - in process]</p> (Source: Acta Neurologica Scandinavica. Supplementum)
Evidence-based efficacy comparison of tolcapone and entacapone as adjunctive therapy in parkinson's disease.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18482101">Related Articles</a></td></tr></table>
<p><b>Evidence-based efficacy comparison of tolcapone and entacapone as adjunctive therapy in Parkinson's disease.</b></p>
<p>CNS Neurosci Ther. 2008;14(1):83-93</p>
<p>Authors: Lees AJ</p>
<p>The relative efficacy has not been adequately established for the two catechol-O-methyltransferase (COMT) inhibitors that are currently available for adjunctive therapy in Parkinson's disease; tolcapone and entacapone. A recent Cochrane meta-analysis of 14 studies in 2566 patients, conducted to assess the efficacy and safety of tolcapone and entacapone, found both to be statistically superior to placebo in increasing ON time and decreasing OFF time. The meta-analysis also showed that the weighted mean difference from baseline to endpoint in tolcapone-treated patients was twice that in entacapone-treated patients for both placebo-corrected ON time and OFF time. Withdrawal rates were generally lower for tolcapone. Two additional studies have examined the switch between tolcapone and entacapone. In 40 Parkinson's disease patients with fluctuations who were switched from tolcapone to entacapone, improvements in ON time and reductions in OFF time were approximately twice the magnitude for tolcapone than for entacapone. In a second study examining the switch from entacapone to tolcapone, the results for several exploratory variables also suggested that tolcapone has greater efficacy than entacapone. These findings indicate that tolcapone should be considered in all patients with entacapone-refractory motor fluctuations.</p>
<p>PMID: 18482101 [PubMed - in process]</p> (Source: CNS Neuroscience and Therapeutics)
Pe2i: a radiopharmaceutical for in vivo exploration of the dopamine transporter.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18482099">Related Articles</a></td></tr></table>
<p><b>PE2I: a radiopharmaceutical for in vivo exploration of the dopamine transporter.</b></p>
<p>CNS Neurosci Ther. 2008;14(1):47-64</p>
<p>Authors: Emond P, Guilloteau D, Chalon S</p>
<p>The membrane dopamine transporter (DAT) has a pivotal role in the regulation of dopamine (DA) neurotransmission involved in a number of physiological functions and brain disorders. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT), are relevant tools to explore the DAT, and we developed the cocaine derivative N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl) nortropane (PE2I) that has proved to be a very potent radiopharmaceutical to image the DAT by these techniques. Several methods are available to obtain PE2I labeled with iodine-123 or -125, carbon-11 and tritium. The pharmacological properties of PE2I have demonstrated that it has good affinity for the DAT (4 nM) and is one of the most selective DAT ligands. [(125)I]PE2I characterized postmortem in human brains has revealed very intense and selective binding in the basal ganglia. Ex vivo autoradiography in rats has shown that high level of [(125)I]PE2I accumulates in the striatum and also in the substantia nigra and ventral tegmental area. [(125)I]PE2I accumulation in the rat striatum is rapid, high, and selective, providing a maximum striatum/cerebellum ratio of 10 during the first 30 min post injection. Using SPECT or PET, rapid, high, and selective accumulation of PE2I was found in the caudate nucleus and putamen in monkeys, whereas rapid wash out from the cerebellum was observed. In vivo investigations in healthy humans have demonstrated that PE2I has high striatal uptake, low nonspecific binding, low radiation exposure, and a fairly short scanning time. A number of findings in various animal models of Parkinson's disease in rats and monkeys have demonstrated the high efficacy of PE2I for detection of reduction in the density of DAT, thus showing the potential value of PE2I for early diagnosis and evaluation of treatment of this disease. The excellent properties of PE2I are basis for the development of new DAT tracers for use in future PET explorations using fluor-18.</p>
<p>PMID: 18482099 [PubMed - in process]</p> (Source: CNS Neuroscience and Therapeutics)
Characterization of supraventricular tachycardia in infants: clinical and instrumental diagnosis.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18393871">Related Articles</a></td></tr></table>
<p><b>Characterization of supraventricular tachycardia in infants: clinical and instrumental diagnosis.</b></p>
<p>Curr Pharm Des. 2008;14(8):729-35</p>
<p>Authors: Vignati G, Annoni G</p>
<p>Supraventricular tachycardia (SVT) is the most common symptomatic arrhythmias in children. Re-entry tachycardias are the most common form, on the contrary automatic tachycardias are relatively rare. There are four types or re-entry: along anomalous pathway with bi-directional (Wolff-Parkinson-White) or unidirectional conduction, intranodal re-entry, intra-atrial re-entry that is common after surgical procedure, and finally the uncommon sinus node re-entry. Automatic tachycardias may be atrial or junctional. The different types of tachycardia have a different incidence according to the age: in the first year of age re-entry along anomalous pathway is the dominant form, while intranodal reentry becomes common during adolescence. The age at the beginning of tachycardia is important for long term prognosis. When SVT starts in the first months of life it disappears in 80% of cases within the first year of life; on the contrary, if tachycardia starts later spontaneous remission is detected in only 15%-20% of patients. In infancy heart failure is the more common presenting symptom, thereafter palpitations become the principal cause of recognition of SVT. Syncope is reported in about 8% of cases and in another 15% usually neonates and infants, the SVT has an occasional detection. Electrocardiogram (ecg) usually allows the precise diagnosis of various types of SVT, and every effort should be made to record ecg during tachycardia. The parameters that should be evaluated are: heart rate, P wave axis, PR and RP interval, and finally presence or absence of AV block. Short lasting episodes should be difficult to be recorded; in these cases cardio-call and trans-telephonic transmission represent useful techniques to obtain SVT demonstration. Patients with SVT require a complete evaluation with others diagnostic techniques: echocardiogram, Holter monitoring, stress test, that should be chosen according the type of tachycardia. Electrophysiologic evaluation is now rarely performed for diagnostic purpose; trans-esophageal atrial stimulation being less invasive than intracardiac evaluation is more extensively employed when diagnosis of SVT is uncertain. Transesophageal stimulation is useful in the following situations: 1) evaluation of patients with symptoms suggestive of paroxistic tachycardia but without ecg documentation, 2) to assess the mechanism responsible for re-entry tachycardia: macro re-entry versus intranodal re-entry 3) to evaluate characteristics of anomalous pathway with bi-directional conduction, and 4)to terminate re-entrant SVT.</p>
<p>PMID: 18393871 [PubMed - indexed for MEDLINE]</p> (Source: Current Pharmaceutical Design) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
A2a adenosine receptor and its modulators: overview on a druggable gpcr and on structure-activity relationship analysis and binding requirements of agonists and antagonists.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18537675">Related Articles</a></td></tr></table>
<p><b>A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists.</b></p>
<p>Curr Pharm Des. 2008;14(15):1525-52</p>
<p>Authors: Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D</p>
<p>Since the discovery of the biological effects of adenosine, the development of potent and selective agonists and antagonists of adenosine receptors has been the subject of medicinal chemistry research for several decades, even if their clinical evaluation has been discontinued. Main problems include side effects due to the ubiquity of the receptors and the possibility of side effects, or to low brain penetration (in particular for the targeting of CNS diseases), short half-life of compounds, lack of effects. Furthermore, species differences in the affinity of ligands make difficult preclinical testing in animal models. Nevertheless, adenosine receptors continue to represent promising drug targets. A(2A) receptor has proved to be a promising pharmacological target for small synthetic ligands, and while A(2A) agonists are undergoing clinical trials for myocardial perfusion imaging and as anti-inflammatory agents, A(2A) antagonists represent an attractive field of research to discover new drugs for the treatment of neurodegenerative disorders, such as Parkinson's disease. Furthermore, the information coming from bioinformatics and molecular modeling studies for the A(2A) receptor has made easier the understanding of ligand-target interaction and the rational design of agonists and antagonists for this subtype. The aim of this review is to show an overview of the most significant steps and progresses in developing A(2A) adenosine receptor agonists and antagonists.</p>
<p>PMID: 18537675 [PubMed - in process]</p> (Source: Current Pharmaceutical Design)
Adenosine a2a receptor antagonists and parkinson's disease: state of the art and future directions.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18537671">Related Articles</a></td></tr></table>
<p><b>Adenosine A2A receptor antagonists and Parkinson's disease: state of the art and future directions.</b></p>
<p>Curr Pharm Des. 2008;14(15):1475-89</p>
<p>Authors: Simola N, Morelli M, Pinna A</p>
<p>Adenosine A(2A) receptors present in the central nervous system have been implicated in the modulation of motor functions. Accordingly, adenosine A(2A) receptor antagonists currently constitute an attractive non-dopaminergic option for use in the treatment of Parkinson's disease (PD). The highly enriched distributions of adenosine A(2A) receptors in striatopallidal neurons, and their ability to form functional heteromeric complexes with dopamine D(2) and metabotropic glutamate mGlu5 receptors, render A(2A) receptor antagonists of particular interest in the modulation of motor behavior, whilst at the same time displaying a low predisposition to inducing non-motor side effects. Furthermore, adenosine A(2A) receptor antagonists appear to exert a marked efficacy on PD tremor and in reducing the progress of underlying neurodegeneration and maladaptive neuroplasticity that complicates standard dopamine replacement treatments in PD. Finally, recent evidence has illustrated an improvement of cognitive function as well as enhancement of attention in rodents following administration of A(2A) receptor antagonists. This article is aimed at examining preclinical studies describing these findings as well as reports from clinical trials, in order to provide a comprehensive review of the evidence suggesting that this class of drugs may represent an advance in the treatment of PD.</p>
<p>PMID: 18537671 [PubMed - in process]</p> (Source: Current Pharmaceutical Design)
Cyclooxygenase-2 in synaptic signaling.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18537667">Related Articles</a></td></tr></table>
<p><b>Cyclooxygenase-2 in synaptic signaling.</b></p>
<p>Curr Pharm Des. 2008;14(14):1443-51</p>
<p>Authors: Yang H, Chen C</p>
<p>Cyclooxygenase-2 (COX-2), a rate-limiting enzyme converting arachidonic acid to prostaglandins and a key player in neuroinflammation, has been implicated in the pathogenesis of neurodegenerative diseases such as multiple sclerosis, Parkinson's and Alzheimer's diseases, and in traumatic brain injury- and ischemia-induced neuronal damage, and epileptogenesis. Accumulated information suggests that the contribution of COX-2 to neuropathology is associated with its involvement in synaptic modification. Inhibition or elevation of COX-2 has been shown to suppress or enhance excitatory glutamatergic neurotransmission and long-term potentiation (LTP). These events are mainly mediated via PGE(2), the predominant reaction product of COX-2, and the PGE(2) subtype 2 receptor (EP(2))-protein kinase A pathway. Recent evidence shows that endogenous cannabinoids are substrates for COX-2 and can be oxygenated by COX-2 to form new classes of prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides). These COX-2 oxidative metabolites of endocannabinoids, as novel signaling mediators, modulate synaptic transmission and plasticity and cause neurodegeneration. The actions of these COX-2 metabolites are likely mediated by mitogen-activated protein kinase (MAPK) and inositol 1,4,5-trisphosphate (IP(3)) signal transduction pathways. These discoveries suggest that the contributions of COX-2 to neurotransmission and brain malfunction result not only from its conversion of arachidonic acid to classic prostaglandins but also from its oxidative metabolism of endocannabinoids to novel prostaglandins. Thus, elucidation of COX-2 in synaptic signaling may provide a mechanistic basis for designing new drugs aimed at preventing, treating or alleviating neuroinflammation-associated neurological disorders.</p>
<p>PMID: 18537667 [PubMed - in process]</p> (Source: Current Pharmaceutical Design)
Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and parkinson's disease.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18537665">Related Articles</a></td></tr></table>
<p><b>Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson's disease.</b></p>
<p>Curr Pharm Des. 2008;14(14):1428-34</p>
<p>Authors: Asanuma M, Miyazaki I</p>
<p>A number of experimental studies using parkinsonian models have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have neuroprotective properties against dopaminergic neurotoxicity not only by their cyclooxygenase-inhibiting effect but also by other specific properties or some unknown pharmacological effects. This article reviews heterogeneous pharmacological properties of NSAIDs including inhibitory effect against nitric oxide synthesis, agonistic action for peroxisome proliferator-activated receptor gamma, or possible suppressive effects against dopamine quinone generation, and also reviews their neuroprotective effects in the experimental parkinsonian models and pathogenesis of Parkinson's disease. Several epidemiological studies recently clarified that the use of nonaspirin NSAIDs but not aspirin was associated with a lower prevalence of Parkinson's disease, in contrast with neuroprotective effects of aspirin in the experimental studies. It also discusses the discrepancy between results in the experimental parkinsonian models and epidemiological data in prevalence of Parkinson's disease on the effects of NSAIDs.</p>
<p>PMID: 18537665 [PubMed - in process]</p> (Source: Current Pharmaceutical Design)
Collateral effects of antiarrhythmics in pediatric age.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18393879">Related Articles</a></td></tr></table>
<p><b>Collateral effects of antiarrhythmics in pediatric age.</b></p>
<p>Curr Pharm Des. 2008;14(8):782-7</p>
<p>Authors: Ali KM</p>
<p>Although there are numerous reports of antiarrhythmic use in children, controlled, comparison trials of antiarrhythmic agents in children are virtually nonexistent and most data are obtained from case series of children treated. Effective and safe pharmacological therapy requires that the physicians attempt to identify a drug with the most appropriate profile to attack the most vulnerable parameter of the mechanisms of the cardiac arrhythmia with the least pro arrhythmic/collateral effects. Digoxin in patients with Wolf-Parkinson -White syndrome, verapamil in infants and intravenous quinidine should be avoided as there is clear evidence that they can cause serious side effects. Collateral effects of other antiarrhythmic drugs are discussed in details in this review. Well-designed, controlled trials are needed to further evaluate the comparative efficacy of antiarrhythmics in children, as well as to evaluate dosing and toxicity in various age groups.</p>
<p>PMID: 18393879 [PubMed - indexed for MEDLINE]</p> (Source: Current Pharmaceutical Design) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
"pacemaker for the brain" shows new potential
Dr. Douglas Anderson was among the earliest neurosurgeons in the nation to treat Parkinson's disease with a treatment called deep brain stimulation. Dr. Anderson has treated approximately 50 Parkinson's patients with the therapy, known as DBS. His first patient was a middle-aged woman who used a wheelchair due to her Parkinson's. Dr. Anderson implanted an electrode that delivered mild electrical signals deep in her brain. (Source: Parkinson's Disease News From Medical News Today)
New parkinson?s drug - spheramine ? fails to meet primary and secondary endpoints in study
PharmaTimes reports that an investigational drug for Parkinson?s disease has failed to meet primary or secondary endpoints in a Phase IIb study. The STEPS trial involved 71 patients with advanced Parkinson?s disease, randomised to either spheramine, or a sham surgical procedure which involves the drilling of a burr hole into the skull at the site of injection. No significant differences were detected between the injected spheramine and sham surgery arms of the study after 12 months of follow-up. Spheramine is a novel cell therapy consisting of retinal pigment epithelial cells that are injected into the central nervous system to produce dopamine, into both hemispheres.
According to PharmaTimes, following the results of the study, Bayer has announced that it will end its collaboration with Titan Pharmaceuticals on the development of this drug. (Source: NeLM Headline News)
Titan parkinson's treatment fails trial, likely to be dropped by bayer schering
Titan Pharmaceutical Inc.'s potential cell-based treatment for Parkinson's Disease failed in a Phase IIb study, the company said Wednesday, and likely won't be continued by partner Bayer Schering Pharma. (Source: bizjournals.com Health Care:Pharmaceuticals headlines)
Titan parkinson's treatment fails trial, likely to be dropped by bayer schering
Titan Pharamceutical Inc.'s potential cell-based treatment for Parkinson's Disease failed in a Phase IIb study, the company said Wednesday, and likely won't be continued by partner Bayer Schering Pharma. (Source: bizjournals.com Health Care:Pharmaceuticals headlines)
$950,000 in seed grants awarded by the parkinson's disease foundation
The Parkinson's Disease Foundation (PDF) is pleased to announce awards of $950,000 toward its 2008-2009 International Research Grants and Fellowship Program (IRGFP). The funding will support the research of 19 Parkinson's scientists, chosen on April 11 from a group of almost 100 candidates by a scientific review committee led by Stanley Fahn, M.D., PDF's Scientific Director. (Source: Health News from Medical News Today) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Spotlight placed on putamen puzzle in parkinson and pure autonomic failure.
Page: 1,11DOI: 10.1097/01.NT.0000326094.40093.a1Authors: HURLEY, DAN (Source: Neurology Today)
Prion diseases: a riddle wrapped in a mystery inside an enigma.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18587704">Related Articles</a></td></tr></table>
<p><b>Prion diseases: a riddle wrapped in a mystery inside an enigma.</b></p>
<p>Folia Neuropathol. 2008;46(2):93-116</p>
<p>Authors: Liberski PP</p>
<p>It is now widely accepted that many structurally diverse proteins can misfold and cause so-called "conformational diseases", including the most common neurodegenerations, Alzheimer's disease and Parkinson's disease. The conversion of largely a-helical or random coil proteins into cross-b-pleated sheet conformations that form first oligomers and then fibrils underlies these disorders. However, this a- to b-structure transition seems to be a generic propensity of all globular proteins, not only those involved in neurodegenerations, not to mention "prion diseases". Metaphorically, all these neurodegenerations are "infectious" in the sense that misfolded b-sheeted conformers are formed in a nucleation process in which preformed metastable oligomer acts as a seed (a nucleus) to convert a normal into an abnormal protein. However, in none but transmissible spongiform encephalopathies (TSEs) has infectivity in a microbiological sense ever been observed, and even in TSEs the formation of misfolded protein is not necessarily accompanied by the generation of infectivity de novo. Furthermore, certain "prion diseases" are not TSEs but just "proteinopathies" caused by accumulation of abnormally misfolded PrPd. The presence of a massive amount of PrP-amyloid and no infectivity casts doubts on whether TSEs are really infectious amyloidoses. The misfolding of PrP may yet prove to be an epiphenomenon secondary to infection with a still unknown infectious agent. If, on the other hand, the purely proteinaceous character of the replicating unit of TSE infectivity is ultimately found to be correct, the critical issues become 1) the mechanism by which a misfolded PrP template induces normal protein molecules to adopt the same pathologically misfolded conformation, and 2) the intracellular conditions that are responsible for strain differences in these molecules.</p>
<p>PMID: 18587704 [PubMed - as supplied by publisher]</p> (Source: Folia Neuropathologica)
Cross-diagnostic validity of the nottingham health profile index of distress (nhpd)
Background:
The Nottingham Health Profile index of Distress (NHPD) has been proposed as a generic undimensional 24-item measure of illness-related distress that is embedded in the Nottingham Health Profile (NHP). Data indicate that the NHPD may have psychometric advantages to the 6-dimensional NHP profile scores. Detailed psychometric evaluations are, however, lacking. Furthermore, to support the validity of the generic property of outcome measures evidence that scores can be interpreted in the same manner in different diagnostic groups are needed. It is currently unknown if NHPD scores have the same meaning across patient populations. This study evaluated the measurement properties and cross-diagnostic validity of the NHPD as a survey instrument among people with Parkinson's disease (PD) and peripheral arterial disease (PAD).
Methods:
Data from 215 (PD) and 258 (PAD) people were Rasch analyzed regarding model fit, reliability, differential item functioning (DIF), unidimensionality and targeting. In cases of cross-diagnostic DIF this was adjusted for and the impact of DIF on the total score and person measures was assessed.
Results:
The NHPD was found to have good overall and individual item fit in both disorders as well as in the pooled sample, but seven items displayed cross-diagnostic DIF. Following adjustment for DIF some aspects of model fit were slightly compromised, whereas others improved somewhat. DIF did not impact total NHPD scores or resulting person measures, but the unadjusted scale displayed minor signs of multidimensionality. Reliability was >0.8 in all within- and cross-diagnostic analyses. Items tended to represent more distress (mean, 0 logits) than that experienced by the sample (mean, -1.6 logits).
Conclusions:
This study supports the within- and cross-diagnostic validity of the NHPD as a survey tool among people with PD and PAD. We encourage others to reassess available NHP data within the NHPD framework to further evaluate the strengths and weaknesses of this simple patient-reported index of illness-related distress. (Source: BioMed Central)
New treatment options for parkinson's disease show promise
Phase 2 results with a new nonergot compound called pardoprunox appear promising, but adverse effects may be an issue. In a separate study, transdermal delivery of a levodopa prodrug increased levodopa levels in a small number of patients, raising hopes for a levodopa patch. Medscape Medical News (Source: Medscape Medical News Headlines)
Inverse independent component analysis facilitates clarification of the accessory conductive pathway of wolf?parkinson?white syndrome electrocardiogram
Abstract Our aim was to demonstrate a digital analyzing method that could extract the potential of early excitation derived from accessory
conductive pathway (ACP) from fusion of the QRS complex wave of the electrocardiogram of Wolf-Parkinson-White (WPW) syndrome.
A 13-year-old boy with WPW syndrome received successful catheter ablation therapy. ECG was recorded and analyzed using independent
component analysis (ICA) and inverse independent component analysis (I-ICA), at pretherapy and posttherapy. We identified
the ACP potential and the following potential spread to the ventricle. Results agreed with those of intracardiac mapping,
locating the ACP in the left posterior side of the heart. ICA and I-ICA might be useful for noninvasive analysis of WPW syndrome
ECG and other electrocardiac abnormalities.
Content Type Journal ArticleCategory Case ReportDOI 10.1007/s00246-008-9250-zAuthors
Seika Yanai, Sapporo Social Insurance General Hospital Department of Pediatrics Sapporo Hokkaido JapanYasuhiro Ishikawa, Ishikawa Medical Clinic Saitama JapanShigeto Fuse, East Japan NTT Sapporo Hospital Department of Pediatrics Sapporo Hokkaido JapanHiroyuki Tsutsumi, Sapporo Medical University School of Medicine Department of Pediatrics Sapporo Hokkaido Japan
Journal Pediatric CardiologyOnline ISSN 1432-1971Print ISSN 0172-0643 (Source: Pediatric Cardiology) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
A critical reappraisal of current staging of lewy-related pathology in human brain
Abstract Sporadic Parkinson disease (sPD) or brainstem-predominant type of Lewy body (LB) disease, and dementia with Lewy bodies (DLB),
the two most frequent ?-synucleinopathies, are progressive multisystem neurodegenerative disorders with widespread occurrence
of ?-synuclein (AS) deposits in the central, peripheral, and autonomic nervous system. For both LB-related disorders, staging/classification
systems based on semiquantitative assessment of the distribution and progression pattern of Lewy-related/AS pathology are
used that are considered to be linked to clinical dysfunctions. In PD, a six-stage system (Braak) has been suggested to indicate
a predictable sequence of lesions with ascending progression from medullary and olfactory nuclei to the cortex, the first
two presymptomatic stages being related to incidental LB disease, stages 3 and 4 with motor symptoms, and the last two (cortical)
stages may be frequently associated with cognitive impairment. DLB, according to consensus pathologic guidelines, by semiquantitative
scoring of AS pathology (LB density and distribution) in specific brain regions, is distinguished into three phenotypes (brainstem,
transitional/limbic, and diffuse neocortical), also considering concomitant Alzheimer-related pathology. Retrospective clinico-pathologic
studies, although largely confirming the staging system, particularly for younger onset PD with long duration, have shown
that between 6.3 and 43% of the cases did not follow the proposed caudo-rostral progression pattern of AS pathology. There
was sparing of medullary nuclei in 7?8.3% of clinically manifested PD cases with AS inclusions in midbrain and cortex corresponding
to Braak stages 4 and 5, whereas mild parkinsonian symptoms were already observed in stages 2 and 3. There is considerable
clinical and pathologic overlap between PD (with or without dementia) and DLB, corresponding to Braak LB stages 5 and 6, both
frequently associated with variable Alzheimer-type pathology. Dementia often does not correlate with progressed stages of
LB pathology, but may also be related to concomitant Alzheimer lesions or mixed pathologies. There is no relationship between
Braak LB stage and the clinical severity of PD, and the predictive validity of this concept is doubtful, since large unselected,
retrospective autopsy series in 30?55% of elderly subjects with widespread AS/Lewy-related pathology (Braak stages 5 and 6)
reported no definite neuropsychiatric symptoms, suggesting considerable cerebral compensatory mechanisms. Applying the original
criteria to large dementia samples, 49% of positive cases were not classifiable. Therefore, modified criteria for the categorization
of Lewy-related pathology were proposed for patients with a history of dementia. The causes and molecular basis of the not
infrequent deviations from the current staging schemes of AS pathology in PD and DLB, its relation to the onset of classical
parkinsonian symptoms and for the lack of definite clinical deficits despite widespread AS pathology in the nervous system
remain to be elucidated.
Content Type Journal ArticleCategory ReviewDOI 10.1007/s00401-008-0406-yAuthors
Kurt A. Jellinger, Institute of Clinical Neurobiology Kenyongasse 18 1070 Vienna Austria
Journal Acta NeuropathologicaOnline ISSN 1432-0533Print ISSN 0001-6322 (Source: Acta Neuropathologica)
The parkinson's disease foundation awards $950,000 in seed grants
(Parkinson's Disease Foundation) The Parkinson's Disease Foundation is pleased to announce awards of $950,000 toward its 2008-2009 International Research Grants and Fellowship Program. The funding will support the research of 19 Parkinson's scientists around the world. The IRGFP is part of PDF's four-pronged approach to funding Parkinson science. In fiscal year 2009, PDF will contribute more than $4.8 million to support Parkinson's disease research. (Source: EurekAlert! - Biology)
Central and systemic il-1 exacerbates neurodegeneration and motor symptoms in a model of parkinson's disease
Parkinson's disease is a neurodegenerative disorder with uncertain aetiology and ill-defined pathophysiology. Activated microglial cells in the substantia nigra (SN) are found in all animal models of Parkinson's disease and patients with the illness. Microglia may, however, have detrimental and protective functions in this disease. In this study, we tested the hypothesis that a sub-toxic dose of an inflammogen (lipopolysaccharide) can shift microglia to a pro-inflammatory state and exacerbate disease progression in an animal model of Parkinson's disease. Central lipopolysaccharide injection in a degenerating SN exacerbated neurodegeneration, accelerated and increased motor signs and shifted microglial activation towards a pro-inflammatory phenotype with increased interleukin-1β (IL-1β) secretion. Glucocorticoid treatment and specific IL-1 inhibition reversed these effects. Importantly, chronic systemic expression of IL-1 also exacerbated neurodegeneration and microglial activation in the SN. In vitro, IL-1 directly exacerbated 6-OHDA-triggered dopaminergic toxicity. In vivo, we found that nitric oxide was a downstream molecule of IL-1 action and partially responsible for the exacerbation of neurodegeneration observed. Thus, IL-1 exerts its exacerbating effect on degenerating dopaminergic neurons by direct and indirect mechanisms. This work demonstrates an unequivocal association between IL-1 overproduction and increased disease progression, pointing to inflammation as a risk factor for Parkinson's disease and suggesting that inflammation should be efficiently handled in patients to slow disease progression. (Source: Brain)
Sensory deficit in parkinson's disease: evidence of a cutaneous denervation
Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction. (Source: Brain)
Racial disparities in the development of dysphagia after stroke: analysis of the california (mircal) and new york (sparcs) inpatient databases.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18586139">Related Articles</a></td></tr></table>
<p><b>Racial disparities in the development of dysphagia after stroke: analysis of the California (MIRCal) and New York (SPARCS) inpatient databases.</b></p>
<p>Arch Phys Med Rehabil. 2008 Jul;89(7):1358-65</p>
<p>Authors: Gonzalez-Fernandez M, Kuhlemeier KV, Palmer JB</p>
<p>OBJECTIVES: To determine whether the proportion of patients with stroke experiencing dysphagia differs among racial groups and whether this relation can be explained by stroke type or severity. DESIGN: Case-control study using California's Medical Information Reporting and New York's Statewide Planning and Research Cooperative System databases for 2002. Cases had primary diagnosis of cerebrovascular disease (International Classification of Disease, 9th Revision [ICD-9] codes 430-438.9, excluding transient [435-435.9] and late-effects [438-438.9]), and self-identified race was white, black, or Asian. Two comparison groups were selected: (1) Parkinson's disease (ICD-9 codes 332-332.1) and (2) oral cancer (ICD-9 codes 141-149). SETTING: Inpatient admissions in the respective states. PARTICIPANTS: Cases with primary diagnosis of cerebrovascular disease whose self-identified race was white, black, or Asian. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Dysphagia, defined by ICD-9 codes 787.2 (dysphagia), 507.0 (aspiration pneumonia), or presence of a feeding tube in the absence of a diagnosis of coma (Current Procedural Terminology codes 432.46 or 437.50 without ICD-9 code 780.01). RESULTS: In the stroke group, the adjusted odds ratio (OR) with 95% confidence interval (CI) for dysphagia was significantly higher for Asians than whites in New York (OR=1.64; 95% CI, 1.50-1.79) and California (OR=1.69; 95% CI, 1.34-2.13). The adjusted OR was slightly but significantly higher for blacks than whites in New York (OR=1.15; 95% CI, 1.03-1.28), but not in California (OR=1.08; 95% CI, 0.97-1.19). No statistically significant differences among racial groups were found in patients with Parkinson's disease or oral cancer. Other factors strongly associated with dysphagia included hemiplegia (OR=2.19; 95% CI, 2.07-2.32) and aphasia (OR=1.97; 95% CI, 1.83-2.11). CONCLUSIONS: Asians were more likely to have dysphagia after stroke. This association was statistically significant after adjusting for age, sex, stroke severity indicators, comorbidities, and stroke type.</p>
<p>PMID: 18586139 [PubMed - in process]</p> (Source: Archives of Physical Medicine and Rehabilitation) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of dj-1.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18591768">Related Articles</a></td></tr></table>
<p><b>Pyrroloquinoline Quinone Prevents Oxidative Stress-Induced Neuronal Death Probably through Changes in Oxidative Status of DJ-1.</b></p>
<p>Biol Pharm Bull. 2008 Jul;31(7):1321-6</p>
<p>Authors: Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H</p>
<p>Pyrroloquinoline quinone (PQQ) has been shown to play a role as an anti-oxidant in neuronal cells and prevent neuronal cell death in a rodent stroke model. DJ-1, a causative gene product for a familial form of Parkinson's disease, plays a role in anti-oxidative stress function by self-oxidation of DJ-1. In this study, the expression level and oxidation status of DJ-1 were examined in SHSY-5Y cells and primary cultured neurons treated with 6-hydroxydopamine (6-OHDA) or H(2)O(2) in the presence or absence of PQQ. The pI shift of DJ-1 to an acidic point, which was observed in SHSY-5Y cells treated with 6-OHDA, was inhibited by PQQ. TOF-MS analyses showed that while the level of a reduced form of DJ-1, one of the active forms of DJ-1, was decreased in SHSY-5Y cells treated with 6-OHDA or H(2)O(2), PQQ increased the level of the reduced form of DJ-1. These results suggest that PQQ prevents oxidative stress-induced changes in oxidative status of DJ-1. Therefore, the neuroprotective effects of PQQ on oxidative stress-induced neuronal death may be at least in part involved in increased level of an active form of DJ-1.</p>
<p>PMID: 18591768 [PubMed - in process]</p> (Source: Biol Pharm Bull)
Motor cortex stimulation in patients with parkinson disease: 12-month follow-up in 4 patients.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18590444">Related Articles</a></td></tr></table>
<p><b>Motor cortex stimulation in patients with Parkinson disease: 12-month follow-up in 4 patients.</b></p>
<p>J Neurosurg. 2008 Jul;109(1):133-9</p>
<p>Authors: Arle JE, Apetauerova D, Zani J, Deletis DV, Penney DL, Hoit D, Gould C, Shils JL</p>
<p>Object Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders. Methods A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS. Results Although there were benefits seen within the first 6 months in Unified Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months. Conclusions Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.</p>
<p>PMID: 18590444 [PubMed - in process]</p> (Source: Journal of Neurosurgery)
Parkinson's disease does not mean no life or no hope
Being diagnosed at the age of 36 with a disease that usually affects older people was a devastating blow, Bryn Williams tells Claire Smith (Source: Scotsman.com News - Health)
Association, expression, pathobiology: is too much tau in pd a blueprint for genetic association?
(Source: Neurology)
Haplotypes and gene expression implicate the mapt region for parkinson disease: the genepd study
Background: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum.
Methods: Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR.
Results: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT.
Conclusions: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk. (Source: Neurology) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Gout and risk of parkinson disease: a prospective study
(Source: Neurology)
The 6-hydroxydopamine model: news from the past.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18595767">Related Articles</a></td></tr></table>
<p><b>The 6-hydroxydopamine model: News from the past.</b></p>
<p>Parkinsonism Relat Disord. 2008 Jun 30;</p>
<p>Authors: Blandini F, Armentero MT, Martignoni E</p>
<p>The investigation of pathogenic and pathophysiological mechanisms of Parkinson's disease relies on experimental models reproducing, in the animal, the pathological and behavioural features of the disease. Despite the availability of innovative models, 6-hydroxydopamine (6-OHDA) remains the most widely used tool to induce a nigrostriatal lesion in the animal (rat). This is due to (1) the relatively low complexity and cost of the procedure, (2) the fact that the 6-OHDA-induced lesion is highly reproducible, and (3) the versatility of the procedure, which can yield varying degrees of nigrostriatal lesions that develop with different temporal profiles, depending on the site chosen for the toxin injection.</p>
<p>PMID: 18595767 [PubMed - as supplied by publisher]</p> (Source: Parkinsonism and Related Disorders)
Molecular pathways of programmed cell death in experimental parkinson's disease.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18595766">Related Articles</a></td></tr></table>
<p><b>Molecular pathways of programmed cell death in experimental Parkinson's disease.</b></p>
<p>Parkinsonism Relat Disord. 2008 Jun 30;</p>
<p>Authors: Vila M, Perier C</p>
<p>Dysfunction of mitochondrial complex I leads to degeneration of dopaminergic neurons of the substantia nigra pars compacta, as seen in Parkinson's disease, through activation of mitochondria-dependent programmed cell death pathways. In this scenario, complex I blockade increases the soluble pool of cytochrome c in the mitochondrial intermembrane space through oxidative mechanisms, whereas activation of pro-cell death protein Bax triggers neuronal death by permeabilizing the outer mitochondrial membrane and releasing cytochrome c into the cytosol. Targeting either Bax transcriptional or post-translational activation results in a marked attenuation of dopaminergic cell death caused by complex I inhibition.</p>
<p>PMID: 18595766 [PubMed - as supplied by publisher]</p> (Source: Parkinsonism and Related Disorders)
Mild cognitive impairment is common in parkinson's disease patients with normal mini-mental state examination (mmse) scores.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18595765">Related Articles</a></td></tr></table>
<p><b>Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores.</b></p>
<p>Parkinsonism Relat Disord. 2008 Jun 30;</p>
<p>Authors: Mamikonyan E, Moberg PJ, Siderowf A, Duda JE, Have TT, Hurtig HI, Stern MB, Weintraub D</p>
<p>PURPOSE: Cognitive impairment occurs in the majority of Parkinson's disease (PD) patients, but little is known about detection of mild cognitive impairment (MCI) in this population. We report on the frequency and characteristics of cognitive deficits in PD patients with intact global cognition based on Mini-Mental State Examination (MMSE) performance. METHODS: One hundred and six PD patients with normal age- and education-adjusted MMSE scores (mean [SD] score=29.1 [1.1]) were administered standardized neuropsychological tests assessing memory, executive function, and attention. Impairment on a cognitive domain was a low score (i.e., >/=1.5 SD below the published normative mean) on at least two measures or tests (for memory and executive abilities) or a single measure (for attention). RESULTS: Mild cognitive impairment was found in 29.2% of PD patients, with 17.9% demonstrating single domain and 11.3% multiple domain impairment. Memory and attention impairment were most common (15.1% and 17.0%, respectively), followed by executive impairment (8.5%). Depending on the measure of disease severity chosen, increasing age and disease severity, anti-anxiety medication use, and a suggestion for increasing severity of daytime sleepiness were independent predictors of cognitive impairment. CONCLUSIONS: Cognitive deficits are common in PD patients with "normal" cognition based on MMSE performance, suggesting that MCI is under-recognized in clinical practice due to routine use of insensitive screening instruments. In contrast with some previous reports, early memory impairment may be as common as either executive or attentional deficits in PD. In addition, psychiatric medication use and daytime sleepiness may be reversible or treatable contributors to cognitive impairment.</p>
<p>PMID: 18595765 [PubMed - as supplied by publisher]</p> (Source: Parkinsonism and Related Disorders)
Driving assessment in parkinson's disease-a novel predictor of performance? - cordell r, lee hc, granger a, vieira b, lee ah.
Clinical symptoms of Parkinson's disease (PD) can make driving hazardous. The removal of the privilege to drive reduces independence; nevertheless, to protect public safety, medical practitioners require reliable screening tools to decide whether a PD driv... (Source: SafetyLit: All (Unduplicated)) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Replication of association between
elavl4
and parkinson disease: the
gene
pd study
Abstract Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations.
In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously
studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene.
Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-008-0526-4Authors
Anita L. DeStefano, Boston University School of Public Health Department of Biostatistics 715 Albany Street, Crosstown Center, 3rd floor Boston MA 02118 USAJeanne Latourelle, Boston University School of Medicine Department of Neurology Boston MA 02118 USAMark F. Lew, University Southern California School of Medicine Department of Neurology Los Angeles CA 90033 USAOksana Suchowersky, University of Calgary Department of Clinical Neuroscience Calgary AB Canada T2N-4N1Christine Klein, University of Lübeck Department of Neurology 23538 Lübeck GermanyLawrence I. Golbe, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School Department of Neurology New Brunswick NJ 08903 USAMargery H. Mark, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School Department of Neurology New Brunswick NJ 08903 USAJohn H. Growdon, Massachusetts General Hospital Department of Neurology Boston MA 02114 USAG. Fredrick Wooten, University of Virginia Health System Department of Neurology Charlottesville VA 22908 USARay Watts, University of Alabama at Birmingham Department of Neurology Birmingham AL 35233 USAMark Guttman, University of Toronto Department of Medicine Toronto Canada L6B-1C9Brad A. Racette, Washington University School of Medicine Department of Neurology Saint Louis MO 63110 USAJoel S. Perlmutter, Washington University School of Medicine Department of Neurology Saint Louis MO 63110 USALynn Marlor, Barrow Neurological Institute Phoenix AZ 85013 USAHolly A. Shill, Sun Health Research Institute Sun City AZ 85351 USACarlos Singer, University of Miami Department of Neurology Miami FL 33136 USAStefano Goldwurm, Parkinson Institute, Istituti Clinici di Perfezionamento 39100 Milan ItalyGianni Pezzoli, Parkinson Institute, Istituti Clinici di Perfezionamento 39100 Milan ItalyMarie H. Saint-Hilaire, Boston University School of Medicine Department of Neurology Boston MA 02118 USAAudrey E. Hendricks, Boston University School of Public Health Department of Biostatistics 715 Albany Street, Crosstown Center, 3rd floor Boston MA 02118 USAAdam Gower, Boston University Department of Bioinformatics Boston MA 02215 USASally Williamson, Boston University School of Medicine Department of Neurology Boston MA 02118 USAMichael W. Nagle, Boston University School of Medicine Department of Neurology Boston MA 02118 USAJemma B. Wilk, Boston University School of Medicine Department of Neurology Boston MA 02118 USATiffany Massood, Boston University School of Medicine Department of Neurology Boston MA 02118 USAKaren W. Huskey, Boston University School of Public Health Department of Biostatistics 715 Albany Street, Crosstown Center, 3rd floor Boston MA 02118 USAKenneth B. Baker, Cleveland Clinic Foundation Departments of Neurology and Neuroscience Cleveland OH 44195 USAIlia Itin, Cleveland Clinic Foundation Departments of Neurology and Neuroscience Cleveland OH 44195 USAIrene Litvan, University of Louisville School of Medicine Department of Neurology Louisville KY 40202 USAGarth Nicholson, University of Sydney ANZAC Research Institute, Concord Hospital Neurology Department Sydney AustraliaAlastair Corbett, University of Sydney ANZAC Research Institute, Concord Hospital Neurology Department Sydney AustraliaMartha Nance, Struthers Parkinson?s Center Minneapolis MN 55427 USAEdward Drasby, Port City Neurology Scarborough ME 04074 USAStuart Isaacson, Parkinson?s Disease and Movement Disorder Center of Boca Raton Boca Raton FL 33486 USADavid J. Burn, Newcastle University Institute for Ageing and Health/Regional Neurosciences Centre NE4 6BE Newcastle upon Tyne UKPatrick F. Chinnery, Newcastle University Institute for Ageing and Health/Regional Neurosciences Centre NE4 6BE Newcastle upon Tyne UKPeter P. Pramstaller, General Regional Hospital Bolzano Department of Neurology 39100 Bolzano ItalyJomana Al-hinti, University of Arkansas for Medical Sciences Department of Neurology Little Rock AR 72205 USAAnette T. Moller, Aarhus University Hospital Department of Neurology 8000 Aarhus DenmarkKaren Ostergaard, Aarhus University Hospital Department of Neurology 8000 Aarhus DenmarkScott J. Sherman, University of Arizona Department of Neurology Tucson AZ 85724 USARichard Roxburgh, Auckland City Hospital Department of Neurology Auckland New ZealandBarry Snow, Auckland City Hospital Department of Neurology Auckland New ZealandJohn T. Slevin, University of Kentucky College of Medicine Department of Neurology Lexington KY 40536 USAFranca Cambi, University of Kentucky College of Medicine Department of Neurology Lexington KY 40536 USAJames F. Gusella, Harvard Medical School Boston Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital MA 02114 Boston USARichard H. Myers, Boston University School of Medicine Department of Neurology Boston MA 02118 USA
Journal Human GeneticsOnline ISSN 1432-1203Print ISSN 0340-6717 (Source: Human Genetics)
Ectopic atrial rhythm is a preablation predictor of atrioventricular nodal reentrant tachycardia in children
Abstract
Background Supraventricular tachycardia (SVT) is a common tachyarrhythmia among pediatric patients. Usually, non-preexcited SVT is attributable
to either atrioventricular nodal reentry tachycardia (AVNRT) or unidirectional retrograde accessory pathway (URAP), but these
cannot be differentiated on a baseline electrocardiogram (ECG). The ability to identify the SVT mechanism in children may
guide decision-making about treatment and counseling regarding electrophysiology study (EPS). Clinical experience suggested
that ectopic atrial rhythm (EAR) is more frequently observed on preablation ECGs of pediatric patients with AVNRT. This study
aimed to determine whether EAR is predictive of AVNRT. Methods A 10-year single-center retrospective review was conducted with patients who underwent ablation for SVT from 1997 through
2006. All pediatric patients with documented AVNRT or URAP during EPS were included. The exclusion criteria specified prior
ablation, Wolff-Parkinson-White syndrome, or complex congenital heart disease. A patient was considered to have EAR if a preablation
ECG had a p-wave axis less than 0° or greater than 90° or a wandering atrial pacemaker with at least three different p-wave
morphologies. Results The review found 457 eligible patients ages 0.5 to 21 years: 285 with AVNRT and 172 with URAP. Patients with congenital heart
defects represented 5.6% of the AVNRT group and 2.9% of the URAP group. Ectopic atrial rhythm was seen in 45 (16%) of 285
patients with AVNRT compared with 10 (6%) of 172 URAP patients (p = 0.001). The sensitivity and specificity of EAR for AVNRT was 16% and 94%, respectively, and the positive predictive value
was 82%. There was no difference in heart rate or QRS duration between the two groups. Conclusion On preablation ECG for pediatric SVT patients, EAR is a reasonably specific marker for AVNRT.
Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00246-008-9255-7Authors
Christina Y. Miyake, Children?s Hospital Boston Department of Cardiology 300 Longwood Avenue Boston MA 02115 USAFrank Cecchin, Children?s Hospital Boston Department of Cardiology 300 Longwood Avenue Boston MA 02115 USAEdward P. Walsh, Children?s Hospital Boston Department of Cardiology 300 Longwood Avenue Boston MA 02115 USACharles I. Berul, Children?s Hospital Boston Department of Cardiology 300 Longwood Avenue Boston MA 02115 USA
Journal Pediatric CardiologyOnline ISSN 1432-1971Print ISSN 0172-0643 (Source: Pediatric Cardiology)
The coffee diterpene kahweol induces heme oxygenase-1 via the pi3k and p38/nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress.
<table border="0" width="100%"><tr><td align="left"/></tr></table>
<p><b>The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress.</b></p>
<p>FEBS Lett. 2008 Jun 28;</p>
<p>Authors: Hwang YP, Jeong HG</p>
<p>In this study, we investigated the mechanisms of kahweol protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with kahweol significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Kahweol also up-regulated heme oxygenase-1 (HO-1) expression, which conferred neuroprotection against 6-OHDA-induced oxidative injury. Moreover, kahweol induced PI3K and p38 activation, which are involved in the induction of Nrf2, HO-1 expression, and neuroprotection. These results suggest that regulation of the anti-oxidant enzyme HO-1 via the PI3K and p38/Nrf2 signaling pathways controls the intracellular levels of ROS.</p>
<p>PMID: 18593583 [PubMed - as supplied by publisher]</p> (Source: FEBS Letters)
Orally disintegrating selegiline allows parkinson's disease patients to lower dopamine agonist dose
Dopaminergic adverse effects are reduced without worsening of the Parkinson's disease with selegiline, a study finds. Medscape Medical News (Source: Medscape Today Headlines)
Emea recommends new warnings and contraindications for ergot-derived dopamine agonists, europe
The European Medicines Agency has recommended updating the product information for ergot-derived dopamine agonists with new warnings and contraindications in relation to the risk of fibrosis. Ergot-derived dopamine agonists are mainly used to treat Parkinson's disease. The class comprises bromocriptine, cabergoline, dihydroergocryptine, lisuride and pergolide, all five of which are authorised at the level of the Member States. (Source: Pharma Industry News From Medical News Today) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Detection of walking periods and number of steps in older adults and patients with parkinson's disease: accuracy of a pedometer and an accelerometry-based method
The aim of this study was to examine if walking periods and number of steps can accurately be detected by a single small body-fixed device in older adults and patients with Parkinson's disease (PD). Results of an accelerometry-based method (DynaPort MicroMod) and a pedometer (Yamax Digi-Walker SW-200) worn on each hip were evaluated against video observation. Twenty older adults and 32 PD patients walked straight-line trajectories at different speeds, of different lengths and while doing secondary tasks in an indoor hallway. Accuracy of the instruments was expressed as absolute percentage error (older adults versus PD patients). Based on the video observation, a total of 236.8 min of gait duration and 24,713 steps were assessed. The DynaPort method predominantly overestimated gait duration (10.7 versus 11.1%) and underestimated the number of steps (7.4 versus 6.9%). Accuracy decreased significantly as walking distance decreased. Number of steps were also mainly underestimated by the pedometers, the left Yamax (6.8 versus 11.1%) being more accurate than the right Yamax (11.1 versus 16.3%). Step counting of both pedometers was significantly less accurate for short trajectories (3 or 5 m) and as walking pace decreased. It is concluded that the Yamax pedometer can be reliably used for this study population when walking at sufficiently high gait speeds (>1.0 m/s). The accelerometry-based method is less speed-dependent and proved to be more appropriate in the PD patients for walking trajectories of 5 m or more. (Source: Age and Ageing)
Proteasomal inhibition reduces parkin mrna in pc12 and sh-sy5y cells.
<table border="0" width="100%"><tr><td align="left"/><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18586549">Related Articles</a></td></tr></table>
<p><b>Proteasomal inhibition reduces parkin mRNA in PC12 and SH-SY5Y cells.</b></p>
<p>Parkinsonism Relat Disord. 2008 Jun 27;</p>
<p>Authors: Koch A, Lehmann-Horn K, Dächsel JC, Gasser T, Kahle PJ, Lücking CB</p>
<p>Mutations in the gene encoding the E3 ubiquitin-protein ligase parkin have been shown to be a common genetic cause of familial early-onset Parkinson's disease (PD). In addition to its function in the ubiquitin-proteasome system (UPS), parkin has been ascribed general neuroprotective properties. Stress and mutation induced decreases in parkin solubility leading to compromised cytoprotection have recently been reported. We systematically investigated whether PD-related stresses including MG132 and epoxomicin (proteasomal impairment), tunicamycin (unfolded protein stress), and rotenone (mitochondrial dysfunction) resulted in expressional changes of parkin and other E3 ubiquitin ligases (dorfin, SIAH-1). Rotenone and tunicamycin did not change parkin mRNA levels, whereas proteasomal inhibition resulted in a reduction of parkin mRNA in PC12 cells as well as in SH-SY5Y cells. Therefore, surprisingly, cells did not react with a compensatory parkin upregulation under proteasomal inhibition, although, in parallel, parkin protein shifted to the insoluble fraction, reducing soluble parkin levels in the cytosol. Since the mRNA of the parkin-coregulated gene PACRG paralleled the parkin mRNA at least partly, we suspect a promoter-driven mechanism. Our study, therefore, shows a link between proteasomal impairment and parkin expression levels in cell culture, which is intriguing in the context of the described and debated proteasomal dysfunction in the substantia nigra of PD patients.</p>
<p>PMID: 18586549 [PubMed - as supplied by publisher]</p> (Source: Parkinsonism and Related Disorders)
Emea recommends new warnings and contraindications for ergot-derived dopamine agonists
The European Medicines Agency (EMEA) has recommended updating the product information for ergot-derived dopamine agonists (bromocriptine, cabergoline, dihydroergocryptine, lisuride and pergolide) with new warnings and contraindications relating to fibrosis, a known side effect of these agents.
Following a safety review which included new scientific data showing that fibrosis can start to develop long before the occurrence of symptoms, the advisory committee to the EMEA recommended that the marketing authorisations should be maintained, but that new warnings and contraindications should be added to reduce the risk of fibrosis as follows:
? For cabergoline and pergolide, for which the prescribing information currently includes a contraindication for patients with evidence of valve problems and a restriction to second-line use in patients with Parkinson?s disease, patients must be monitored for signs of fibrosis with echocardiography before treatment is started and regularly during treatment. In addition, the maximum recommended dose should be reduced to 3 mg per day and cardiac fibrosis listed as a very common side effect.
? For bromocriptine and dihydroergocryptine, a contraindication for patients with pre-existing valve problems should be added.
? The maximum dose of bromocriptine should be restricted to 30 mg per day.
? A warning on the possible risk of fibrosis in patients taking bromocriptine, dihydroergocryptine and lisuride at high doses for long periods should be added.
Doctors are advised to prescribe ergot-derived dopamine agonists according to the updated prescribing information and monitor for the development of fibrosis in the heart and elsewhere in the body throughout treatment. (Source: NeLM news - Cardiology)
Roco kinase activity is controlled by internal gtpase function.
<table border="0" width="100%"><tr><td align="left"><a href="http://stke.sciencemag.org/cgi/pmidlookup?view=long&pmid=18544747"><img src="http://www.ncbi.nlm.nih.gov/entrez/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-sigtrans_full.gif" border="0"/></a> </td><td align="right"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=PubMed_PubMed&from_uid=18544747">Related Articles</a></td></tr></table>
<p><b>ROCO kinase activity is controlled by internal GTPase function.</b></p>
<p>Sci Signal. 2008;1(23):pe27</p>
<p>Authors: Weiss B</p>
<p>Small guanosine triphosphatases (GTPases) have long been known to control the activities of downstream protein kinases. Some members of a rather new multidomain protein family contain not only a GTPase domain of the ROC (Ras of complex protein) subtype but also a protein kinase domain, and both domains seem to cooperate with each other in the same polypeptide. Data now show that the kinase activity of one of these ROCO proteins depends on whether guanosine diphosphate or guanosine triphosphate (GTP) is bound and that the activity is controlled by the adjacent GTPase, which suggests a novel mechanism of intrinsic control. This ROCO family member, leucine-rich repeat kinase 2 (LRRK2), is of special interest because mutations within both its protein kinase and its GTPase domains are associated with Parkinson's disease (PD). These mutations lead to abnormally enhanced protein kinase activity, which is believed to cause or at least contribute to neuronal damage. The crystal structure of the GTPase domain of LRRK2 has now been resolved and shows that the ROC GTPase domain is responsible for LRRK2 homodimerization in a surprising way. The structure not only offers insights into the molecular effects of some of the PD-associated mutations of LRRK2, but may also help to improve our understanding of the intrinsic control mechanism between a GTPase and a protein kinase within the same protein.</p>
<p>PMID: 18544747 [PubMed - in process]</p> (Source: Science Signaling)
Dopaminergic therapy for parkinson's disease raises risk for impulse control disorders
Large multicenter study confirms association, identifies possible risk factors for compulsive behaviors. Medscape Medical News (Source: Medscape Today Headlines) <p> </p><p><b><i>MedWorm Sponsored Message:</i></b> Find out how you can <a href="http://www.medworm.com/rss/medicalsponsorship.php" target="_self">get your message across here</a> by sponsoring this MedWorm news feed.</p>
Bioalvo sa filed patents covering first drug products
Showing the efficacy of its HTS screening systems and successful
collaboration with Academia, Bioalvo managed to file its first IP on
products eight months after having the technology platform up and running.
Bioavlo filed two PCT patent applications covering the therapeutic use of a compound identified using its
proprietary drug screening technology, already protected by two earlier filed PCT
applications.
Relevant data regarding toxicity, efficacy and physiological behaviour (like ability to
cross the blood brain barrier - BBB), that were key information for the IP filing,
were obtained under the aegis of a successful collaboration with Professor Miguel
Castanho's team at UL.
The PCTs were filed covering therapeutic use for indications such as pain and CNS
diseases.
Bioalvo acquired full commercial and IP rights regarding the products to UL, who
will receive royalties on Bioalvo's net revenues regarding the product sales.
The relevance of the existing data already attracted the attention of key
international players in the fields of pain and CNS.
Helena Vieira, Bioalvo's CEO said, "We are very happy we've been able to show
that industry and academia can work quite well together in Portugal and that is the
way to value the good science we have within our universities. Filing our first IP
around products give us a great feeling of accomplishment since this is a relevant
landmark in the planned roadmap for the company development. These are the first
of many that will follow, technology is up and running successfully as we have reassured
with this IP filing, so it is only a question of time and resources."
Luis Amado, Bioalvo's CBDO mentioned, "Having products with relevant data as in
this case is a great asset to foster partnerships and licensing deals, not only on
product front but also for the use of technology that can see its value considerably
increased by those."
Professor Miguel Castanho declared, "this is an important step in technology
transfer and industry-academia partnerships in Portugal. It is certainly an
encouraging event to cross the old boundaries that still separate the two sectors. It
is also inspiring to have the perspective that our academic work may one day revert
in direct favour of suffering patients. Without a strong and committed industrial
partner like Bioalvo this goal would be elusive.
About Bioalvo S.A.
Bioalvo is the first Portuguese biotech company working on early stages of drug
discovery.
Bioalvo designs and develops innovative drug development programmes that
generate potent and efficient drugs aimed at central nervous system and
neurodegenerative disorders.
Through its proprietary innovative platforms Bioalvo can accelerate and increase
the efficiency of drug discovery through HTS and generate true and potent drug
candidates for its pipeline and of its partners that will ultimately lead to treatments
and cures for human diseases with dramatic social impacts such as amyloidosis,
Huntington's, Alzheimer's, Parkinson's or cancer. The company operates an
alliance-based R&D business model and relies on partnerships to fill its pipeline and
bring its products to the market.
Bioalvo is fully committed in building value by developing a diverse pipeline of
products to address un-met healthcare needs. (Source: Drug Development Technology)
Parkinson's drugs increase risk of impulse disorders
A common class of drugs prescribed to control Parkinson's disease symptoms increases the risk of gambling, excess shopping and compulsive sexual behaviour, a new study finds. (Source: CTV Health)
Adagio results music to the ears of parkinson's patients
(Source: Inpharma)
Neurosearch successfully completes phase i with acr325 and
announces the decision to progress development into phase ii
proof-of-concept studies in parkinson's disease and bipolar
disorder
COPENHAGEN, Denmark, June 26, 2008 - NeuroSearch (NEUR.CO)
has completed Phase I evaluation of its drug candidate, ACR325,
with a highly positive outcome. The results of double-blinded,
placebo controlled single and multiple dose studies in... (Source: Drugs.com - Clinical Trials)
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