Parkinson Disease: Pennsylvania

Price A, Filoteo JV, Maddox WT. · Department of Psychology, Elizabethtown College, Elizabethtown, PA 17022, United States. · Neuropsychologia. · Pubmed #19428385 links to  free full text

Abstract: Measures of explicit rule-based category learning are commonly used in neuropsychological evaluation of individuals with Parkinson's disease (PD) and the pattern of PD performance on these measures tends to be highly varied. We review the neuropsychological literature to clarify the manner in which PD affects the component processes of rule-based category learning and work to identify and resolve discrepancies within this literature. In particular, we address the manner in which PD and its common treatments affect the processes of rule generation, maintenance, shifting and selection. We then integrate the neuropsychological research with relevant neuroimaging and computational modeling evidence to clarify the neurobiological impact of PD on each process. Current evidence indicates that neurochemical changes associated with PD primarily disrupt rule shifting, and may disturb feedback-mediated learning processes that guide rule selection. Although surgical and pharmacological therapies remediate this deficit, it appears that the same treatments may contribute to impaired rule generation, maintenance and selection processes. These data emphasize the importance of distinguishing between the impact of PD and its common treatments when considering the neuropsychological profile of the disease.

Dadabhai A, Friedenberg FK. · Temple University Hospital, Temple University School of Medicine, Gastroenterology Section, Parkinson Pavilion, 8th Floor, 3401 North Broad Street, PA 19140, Philadelphia, USA. · Expert Opin Drug Saf. · Pubmed #19236223 No free full text.

Abstract: Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of approximately 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.

McGuckin J, Parkinson K. · Vascular Access Centers, Philadelphia Vascular Institute, Philadelphia, PA, USA. · Tech Vasc Interv Radiol. · Pubmed #19100949 No free full text.

Abstract: Minimally-invasive medicine has continually progressed from its beginning in the 1960's. Evolution of technology and techniques have led to treatment of new disease states in minimally-invasive therapies. Now the venue of those therapies is shifting outpatient procedures from the hospital and into outpatient centers.

Richter JE. · Department of Medicine, Temple University School of Medicine, 3401, North Broad Street, 801 Parkinson Pavilion, Philadelphia, PA 19140, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072391 No free full text.

Abstract: Achalasia cannot be cured. Instead, our goal is to relieve symptoms of dysphagia and regurgitation, improve esophageal emptying and prevent the development of megaesophagus. The most definitive therapies are pneumatic dilation and surgical myotomy. The overall success of grade pneumatic dilation is 78%, with women and older patients performing best. Laparoscopic myotomy has an overall success rate of 85%, but can be complicated by the sequelae of severe acid reflux disease. Young patients, especially men, are the best candidates for surgical myotomy. There are no prospective, randomized studies comparing these two procedures. Botulinum toxin injections into the esophagus and smooth muscle relaxants are reserved for older patients or those with major comorbid illnesses. Some patients with end-stage achalasia will require esophagectomy.

Grace AA. · Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Mov Disord. · Pubmed #18781673 No free full text.

Abstract: Dopamine (DA) neurons exist in two activity states; either spontaneously firing or quiescent and nonfiring. When faced with a behavioral demand, the quiescent DA neurons can be activated to facilitate normal motor output. Levodopa appears to increase DA output by activating these nonfiring neurons; as a consequence, DA release is increased, but behavioral demand can now overwhelm the system, potentially leading to the inactivation and on/off phenomena. Levodopa administered in a pulsatile manner may also lead to the induction of synaptic plasticity within the DA systems. In the ventral mesolimbic system, this could lead to the loss of behavioral flexibility, impulsive behavior, and cognitive impairment, whereas in the dorsal nigrostriatal system, this may underlie Levodopa-induced dyskinesia. Continuous administration of Levodopa may circumvent this sensitization process, enabling a therapeutic response without limbic and motor side effects.

Vosler PS, Brennan CS, Chen J. · Department of Neurology, University of Pittsburgh School of Medicine, S-507, Biomedical Science Tower, Pittsburgh, PA 15213, USA. · Mol Neurobiol. · Pubmed #18686046 No free full text.

Abstract: Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.

Howland RH. · University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. · J Psychosoc Nurs Ment Health Serv. · Pubmed #18595454 No free full text.

Abstract: Placebo and nocebo effects are interesting and complex phenomena. In this article, I discuss some findings about the psychological and neurobiological processes that may underlie these effects on the basis of studies of pain, Parkinson's disease, and depression. From a psychological perspective, expectancy and conditioning theories have been used to explain placebo and nocebo effects. These psychological processes may be translated into physiological effects through overlapping brain circuits that are important for cognitive information processing, analgesia, and reward expectations. These brain circuits may represent a fundamentally important common underlying pathway that mediates placebo and nocebo effects in many conditions. Understanding these effects is important for designing clinical treatment studies and interpreting their results and is highly relevant for clinical practices.

Rothman JR, Jaffe WI. · Department of Urology, Temple University, 3401 North Broad Street, 3rd Floor, Parkinson Pavilion, Suite 350, Philadelphia, PA 19140, USA. · Curr Urol Rep. · Pubmed #18519014 No free full text.

Abstract: Prostatitis accounts for almost 2 million office visits to urologists and primary care physicians. The label "prostatitis" refers to a diverse constellation of symptoms and disease processes. The diagnosis and treatment of this disorder present numerous challenges for the physician, including a lack of abnormal findings on physical examination, laboratory tests, and radiographic images. In this article, we offer a review of the current literature and recommendations for the evaluation and diagnosis of the patient presenting with prostatitis.

Weintraub D, Comella CL, Horn S. · Department of Psychiatry and Neurology, University of Pennsylvania, 3615 Chestnut St, Philadelphia, PA 19104, USA. · Am J Manag Care. · Pubmed #18402509 links to  free full text

Abstract: The nonmotor neuropsychiatric symptoms of Parkinson's disease, particularly depression, psychosis, and cognitive impairment/dementia, are major contributors to disability and a decline in quality of life. Their effect on patients may be more disabling than motor symptoms. Increasing awareness of the importance of recognizing and treating neuropsychiatric symptoms of this disease in the medical community is a focus of specialists and organizations. This article looks at useful screening measures to help clinicians recognize neuropsychiatric symptoms and offers suggestions for their effective treatment.

Weintraub D, Comella CL, Horn S. · Department of Neurological Sciences, University of Pennsylvania, 330 S 9th St, Philadelphia, PA 19107, USA. · Am J Manag Care. · Pubmed #18402508 links to  free full text

Abstract: In the absence of a cure, the primary goals in managing Parkinson's disease (PD) are to preserve functionality and health-related quality of life. Meeting these goals can minimize healthcare-resource utilization and long-term healthcare costs. Although effective treatment of motor symptoms of the disease is a central consideration to facilitate improved outcomes, management of nonmotor symptoms is now recognized as an equally important target of intervention, since nonmotor symptoms can contribute greatly to disability. The article addresses the current treatment options of choice for reducing motor symptoms of PD and their most rational use. Cost-effectiveness is a major consideration for managed care and is also analyzed for many available treatment options.

Weintraub D, Comella CL, Horn S. · University of Pennsylvania, Philadelphia, PA, USA. · Am J Manag Care. · Pubmed #18402507 links to  free full text

Abstract: Parkinson's disease (PD) is a chronic neurodegenerative disease associated with substantial morbidity, increased mortality, and high economic burden. Of importance to managed care is that the number of cases of PD are on the rise, paralleling the advancing age of the population, and misdiagnosis is common. Effective management of PD can minimize disability and potentially improve long-term outcomes, which would minimize long-term healthcare costs and medical resource utilization. This article provides a brief review of the epidemiology, pathophysiology, clinical course, and burden of PD.

Doty RL. · Smell and Taste Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Parkinsonism Relat Disord. · Pubmed #18267240 No free full text.

Abstract: It has become increasingly apparent that Parkinson's disease (PD) can no longer be considered purely a motor disease, as numerous sensory alterations accompany this disorder either before or early in its clinical progression. Most notable among such disturbances are decrements in smell function. Such anomalies have been documented in approximately 90% of patients with early-stage sporadic PD and appear to progress little, if at all, with the development of the more classic PD-related motor symptoms. In this paper, I briefly review the nature of the olfactory dysfunction observed in PD and current theories as to its pathological basis.

Doty RL. · Smell and Taste Center and Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Ann Neurol. · Pubmed #18232016 No free full text.

Abstract: Environmental agents, including viruses, prions, and toxins, have been implicated in the cause of a number of neurodegenerative diseases, most notably Alzheimer's and Parkinson's diseases. The presence of smell loss and the pathological involvement of the olfactory pathways in the formative stages of Alzheimer's and Parkinson's diseases, together with evidence that xenobiotics, some epidemiologically linked to these diseases, can readily enter the brain via the olfactory mucosa, have led to the hypothesis that Alzheimer's and Parkinson's diseases may be caused or catalyzed by agents that enter the brain via this route. Evidence for and against this concept, the "olfactory vector hypothesis," is addressed in this review.

Abel T, Zukin RS. · Department of Biology, University of Pennsylvania, 204G Lynch Laboratories, 433 South University Avenue, Philadelphia, PA 19104-6018, USA. · Curr Opin Pharmacol. · Pubmed #18206423 links to  free full text

Abstract: Epigenetic chromatin remodeling and modifications of DNA represent central mechanisms for regulation of gene expression during brain development and in memory formation. Emerging evidence implicates epigenetic modifications in disorders of synaptic plasticity and cognition. This review focuses on recent findings that HDAC inhibitors can ameliorate deficits in synaptic plasticity, cognition, and stress-related behaviors in a wide range of neurologic and psychiatric disorders including Huntington's disease, Parkinson's disease, anxiety and mood disorders, Rubinstein-Taybi syndrome, and Rett syndrome. These agents may prove useful in the clinic for the treatment of the cognitive impairments that are central elements of many neurodevelopmental, neurological, and psychiatric disorders.

Pollard JR. · Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. · Curr Opin Investig Drugs. · Pubmed #18183537 No free full text.

Abstract: UCB SA was developing the high-affinity synaptic vesicle glycoprotein 2A ligand, seletracetam, an analog of levetiracetam, for the potential oral treatment of epilepsy. Phase II epilepsy trials were underway, but in July 2007, the company stated that development of seletracetam had been put on hold and it is unknown whether planned phase IIb/III trials will begin.

Giasson BI, Van Deerlin VM. · Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104-6084, USA. · Neurosignals. · Pubmed #18097165 No free full text.

Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of late-onset Parkinson's disease (PD). Clinical and pathological studies have demonstrated that in the majority of cases LRRK2 mutations lead to PD with classical clinical and pathological features. However, in some patients the pathological features can be distinct and/or more extensive than typically seen in PD. Collectively, these findings provide important clues into the mechanisms by which LRRK2 mutations can lead to demise of dopaminergic neurons. The understanding of LRRK2 protein function and its gene regulation and the consequences of mutations are still at their infancy, but scientific findings are progressing at a rapid pace. Although more detailed information on LRRK2 is still needed in the quest for therapeutic intervention that could halt or slow the progression of disease, here we summarize the current information on the biological and pathological properties of LRRK2.

Kranick SM, Duda JE. · Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. · Neurosignals. · Pubmed #18097158 No free full text.

Abstract: Prior to the onset of the cardinal motor features of idiopathic Parkinson's disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.

Goldmann Gross R, Siderowf A, Hurtig HI. · Parkinson's Disease and Movement Disorders Center, Department of Neurology, University of Pennsylvania Health System, Philadelphia, PA, USA. · Neurosignals. · Pubmed #18097157 No free full text.

Abstract: Parkinson's disease (PD) is classically thought of as a movement disorder characterized by tremor, rigidity and postural instability. Nevertheless, there is growing recognition of prominent cognitive impairment in PD and related disorders, which is responsible for substantial disability in these patients. This review will focus on cognitive impairment associated with Lewy body pathology, including PD with dementia (PDD) and dementia with Lewy bodies (DLB). We will review the epidemiology, clinical evaluation, underlying mechanisms and treatment of cognitive impairment in these patients. Despite differences between PDD and DLB, there is clinical, neuropathological and radiological overlap between these disorders, supporting the view that they represent a spectrum of disease. These observations suggest that common targets for diagnosis and treatment of these disorders can be identified.

Miller L, Vegesna A, Kalra A, Besetty R, Dai Q, Korimilli A, Brasseur JG. · Department of Gastroenterology, Temple University Hospital, Gastroenterology Section, 8th Floor, Parkinson Pavilion, Philadelphia, PA 19043, USA. · Gastroenterol Clin North Am. · Pubmed #17950440 No free full text.

Abstract: The use of high-frequency ultrasound transducers combined with manometry in the gastrointestinal (GI) tract has yielded important findings concerning the anatomy, physiology, and pathophysiology of the high-pressure zone of the gastroesophageal junction and the sphincteric muscles within. These transducers have made previously invisible portions of the GI tract accessible to investigation. Three distinct high-pressure zones have been identified and correlated with anatomic structures: the extrinsic sphincter (crural diaphragm) and the two components of the intrinsic sphincter (an upper LES and a lower LES [the gastric sling fiber/clasp fiber complex]). This article discusses the possible underlying pathophysiology of gastroesophageal reflux disease; the biomechanics of the gastroesophageal junction high-pressure zone; and the mechanism of action of standard surgical and newer endoscopic therapies for gastroesophageal reflux disease.

Richter JE. · The Richard L. Evans Chair, Department of Medicine, Temple University School of Medicine, 3401 North Broad Street, 801 Parkinson Pavilion, Philadelphia, PA 19140, USA. · Gastroenterol Clin North Am. · Pubmed #17950439 No free full text.

Abstract: Gastroesophageal reflux disease (GERD) is a common problem that is expensive to diagnose and treat. The disease is increasing in prevalence in the Western world, with important risk factors being obesity and the eradication of Helicobacter pylori. Heartburn and acid regurgitation are classic symptoms of GERD, but their sensitivity is poor. Ambulatory esophageal pH testing is the most sensitive test for GERD, whereas endoscopy is the most specific test. Medical treatment with proton pump inhibitors (PPIs) has revolutionized the treatment of GERD and its complications, but long-term side effects do exist. Laparoscopic anti-reflux surgery and PPIs have similar efficacy in the few available long-term trials. This article reviews the presentation, evaluation, and treatment of GERD.

Parkman HP, Orr WC. · Gastroenterology Section, Department of Medicine, Temple University School of Medicine, Parkinson Pavilion, 8th Floor, 3401 North Broad Street, Philadelphia, PA 19140, USA. · Gastroenterol Clin North Am. · Pubmed #17950436 No free full text.

Abstract: Abnormalities of gastrointestinal (GI) motor function contribute directly or indirectly to a number of common clinical problems and account for significant health care-related expenditure. Proper evaluation of patients who have suspected GI motility disorders is important to ensure a correct diagnosis and to embark on an appropriate plan of treatment. The GI motility laboratory serves as an important area for patient evaluation in gastroenterology and is an essential element in any comprehensive digestive disease program. This article addresses important concepts in setting up and running an efficient and practical GI motility laboratory.

Kung HF, Kung MP, Wey SP, Lin KJ, Yen TC. · Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. · Nucl Med Biol. · Pubmed #17921030 No free full text.

Abstract: In the past 10 years, significant progress has been made in using a technetium-99m dopamine transporter imaging agent, [99mTc]TRODAT, for routine clinical studies. Developing a molecular imaging agent from bench to the bedside is more than a simple scientific venture. Currently, Taiwan is the only place where [99mTc]TRODAT is approved for routine clinical use in the diagnosis of Parkinson's disease. The trials and tribulations of developing [99mTc]TRODAT for routine clinical use in Taiwan provide an interesting case study in how to (critics may say, how not to) develop a molecular imaging agent.

Weintraub D, Hurtig HI. · Department of Psychiatry, University of Pennsylvania, 3535 Market St., Rm. 3003, Philadelphia, PA 19104, USA. · Am J Psychiatry. · Pubmed #17898337 links to  free full text

This publication has no abstract.

Oldfield V, Keating GM, Perry CM. · Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA. · Drugs. · Pubmed #17683172 No free full text.

Abstract: Rasagiline (Azilect) is a novel, selective, irreversible second-generation inhibitor of monoamine oxidase type B (MAO-B). It is administered orally once daily and is approved in the US, Canada, Mexico, Israel and the EU for use as monotherapy and as adjunct therapy in the treatment of Parkinson's disease.Results of well designed clinical studies indicate that rasagiline is effective as initial monotherapy and improves Parkinson's symptomatology in patients with early Parkinson's disease. In addition, when administered in conjunction with levodopa, in patients with moderate to advanced disease and motor fluctuations, rasagiline reduces mean daily 'off' time and increases daily 'on' time without troublesome dyskinesias, compared with controls. Rasagiline is generally well tolerated as monotherapy and adjunctive therapy and is administered once daily. Thus, rasagiline, administered as a simple and convenient dosage regimen, is a well tolerated and effective option for monotherapy in patients with early Parkinson's disease and for adjunctive therapy in patients with moderate to advanced disease.

Richter JE. · Department of Medicine, Temple University School of Medicine, 3401 North Broad Street, 801 Parkinson Pavilion, Philadelphia, PA 19140, USA. · Best Pract Res Clin Gastroenterol. · Pubmed #17643904 No free full text.

Abstract: Gastrooesophageal reflux disease, GERD, is a common problem which is expensive to diagnose and treat. The disease is increasing in prevalence in the Western world with important risk factors being obesity and the eradication of Helicobacter pylori. Increasing research points to transient LES relaxation and spatial separation of the diaphragm and LES (hiatal hernia in chest) being the critical mechanisms of acid reflux. Heartburn and acid regurgitation are classic symptoms of GERD, but their sensitivity is poor. Ambulatory oesophageal pH testing is the most sensitive test for GERD, while endoscopy is the most specific test. Medical treatment with PPIs has revolutionized the treatment of GERD and its complications, but long-term side effects do exist. Laparoscopic antireflux surgery and PPIs have similar efficacy in the few available long-term trials. Currently, endoscopic treatments for GERD should not be a clinical alternative outside of research trials. New drug therapies should be directed at modulating transient LES relaxation.