Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The US Food and Drug Administration (FDA) has approved several new drugs in the past 2 years. This article provides an overview of some of the newer drugs that are likely to find wider use in the future. The drugs reviewed in this article can be used to treat cardiovascular system problems, diabetes mellitus, multiple sclerosis, hepatitis B infection, hyponatremia, Parkinson's disease, rheumatoid arthritis, pain, constipation, and insomnia. Another drug discussed can be used to help a patient stop smoking. The article also discusses Gardasil, the recombinant vaccine against human papilloma virus (types 6, 11, 16, and 18).
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PMID:What's new in clinical pharmacology and therapeutics. 1859 82

Constipation has always been a common problem but recently it appears to be on the rise in the western world. Its prevalence in the general population is estimated at around 20% with reports suggesting significantly higher levels in the elderly, especially above the age of 65. There have also been reports of females being affected more then males, Higgins et al reporting a male to female ratio of 1: 2.2. Constipation can be classified as either primary or secondary. Primary constipation is either due to prolonged transient time through the colon (colonic inertia) or a disturbance in defecation with normal transient time. Secondary constipation is either due to medications or other medical diseases for example hypothyroidism, diabetes or Parkinson's disease. In the past several years advances have been made in understanding the physiological and pathophysiological processes of normal and abnormal defecation. This has led to the understanding of transient time, sensation and pressure build-up in the rectum and anus as well as the key role of synchronization between contraction and relaxation of the involved muscles and sphincters. Disturbance in any one of the above mentioned processes can lead to constipation. The obstructed defecation syndrome has been shown to be the result of an abnormal function of the muscles involved in defecation or an anatomical abnormality of the pelvic organs. Obstructed defecation syndrome is estimated to be prevalent in 7% of the adult population and is judged to be the cause of one third of all cases of constipation. Due to the fact that surgery is an emerging treatment of choice for these patients suffering from obstructed defecation syndrome, it is highly important that we should not only be able to diagnose the cause of constipation in patients but accurately identify those suffering specifically from obstructed defecation syndrome. Therefore, this paper reviews the definitions, symptoms, pathophysiology, diagnosis and treatments of obstructed defecation syndrome.
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PMID:[Obstructed defecation syndrome]. 1869 23

Four patients, aged 67, 52, 56 and 64 years, respectively, undergoing percutaneous colostomy or jejunostomy are presented to illustrate current options for percutaneous endoscopic access to the digestive tract. The first patient had Parkinson's disease and required percutaneous jejunostomy for continuous post-pyloric administration of medication. The second patient had impaired gastric emptying due to gastric graft-versus-host disease following bone marrow transplantation. He was successfully treated with percutaneous jejunostomy, which was removed 2 years later after full recovery. The third patient had severe constipation due to the use ofmorphinomimetic analgesics. She received percutaneous caecostomy for colonic lavage and desufflation. The fourth patient had combined constipation and sphincteric insufficiency. Although the percutaneous endoscopic colostomy was clinically successful, the catheter had to be removed due to local pain and abscess formation.
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PMID:[Current options for percutaneous endoscopic access to the digestive tract]. 1878 74

The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW-6002) is an adenosine A(2A) receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12-week, multicenter, double-blind, placebo-controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti-Parkinson's medications. Istradefylline-treated subjects had significant placebo-corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline-treated and 7 (6.1%) placebo-treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations.
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PMID:Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations. 1883 30

Constipation is associated with future risk of Parkinson's disease (PD) and with incidental Lewy bodies (LB) in the locus ceruleus or substantia nigra (SN). Our purpose is to examine the independent association between bowel movement frequency in late-life and postmortem SN neuron density. Bowel movement frequency was assessed in the Honolulu-Asia Aging Study from 1991 to 1993 in 414 men aged 71 to 93 years with later postmortem evaluations. Brains were examined for LB in the SN and locus ceruleus and neurons were counted in four quadrants from a transverse section of SN. In nonsmokers, neuron densities (counts/mm(2)) for men with >1, 1, and <1 bowel movement daily were 18.5, 18.8, 10.1 (P < 0.001) for dorsomedial; 15.3, 16.4, 10.2 (P < 0.03) for ventromedial; and 18.6, 18.3, 10.9 (P = 0.011) for ventrolateral quadrants. Relationships were not significant in the dorsolateral quadrant or in any quadrant among smokers. After adjustment for age, time to death, coffee drinking, tricep skinfold thickness, excessive daytime sleepiness, cognitive function, PD, and incidental LB, density ratios in nonsmokers with 1 or more bowel movement(s) daily were significantly higher compared to those with <1 daily. Constipation is associated with low SN neuron density independent of the presence of LB.
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PMID:Bowel movement frequency in late-life and substantia nigra neuron density at death. 1900 91

Botulinum toxin (BoNT) has been used for over a quarter of century for the treatment of well over 100 different indications. Many of the symptoms for which BoNT has been found to be effective occur in a variety of neurological disorders. One neurodegenerative disorder in which BoNT has been used extensively to treat various symptoms is Parkinson's disease (PD). This review will highlight the following therapeutic applications of BoNT in conditions associated with PD: limb dystonia, blepharospasm and lid apraxia, bruxism, cervical dystonia (anterocollis), camptocormia, hand and jaw tremor, rigidity (painful shoulder), freezing of gait, sialorrhea, dysphagia (achalasia), seborrhea, hyperhidrosis, overactive bladder, and constipation.
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PMID:Disease-oriented approach to botulinum toxin use. 1907 3

Emerging evidences suggest that the enteric nervous system (ENS) is affected by the degenerative process in Parkinson's disease (PD). In addition lesions in the ENS could be associated with gastrointestinal (GI) dysfunctions, in particular constipation, observed in PD. However, the precise alterations of the ENS and especially the changes in the neurochemical phenotype remain largely unknown both in PD and experimental Parkinsonism. The aim of our study was thus to characterize the neurochemical coding of the ENS in the colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, a well-characterized model of PD. In the myenteric plexus, there was a significant increase in the number of neurons per ganglia (identified with Hu), especially nitric oxide synthase immunoreactives (IR) neurons in MPTP-treated monkeys compared to controls. A concomitant 72% decrease in the number of tyrosine hydroxylase-IR neurons was observed in MPTP-treated monkeys compared to controls. In contrast no change in the cholinergic or vasoactive intestinal peptide-IR population was observed. In addition, the density of enteric glial cells was not modified in MPTP-treated monkeys. Our results demonstrate that MPTP induces major changes in the myenteric plexus and to a lesser extent in the submucosal plexus of monkeys. They further reinforce the observation that lesions of the ENS occur in the course of PD that might be related to the GI dysfunction observed in this pathology.
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PMID:Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental Parkinsonism. 1907 45

Rapid eye movement sleep behaviour disorder (RBD) may serve as a useful indicator to approach Parkinson's disease (PD); however, PD patients do not always exhibit RBD. We wondered whether the presence of RBD would be reflected in the expansion of PD lesions and represent the same PD entity. We examined the clinical differences between PD with and without RBD and studied the frequency of RBD-like symptoms (RBD-s) and clinical differences in 150 PD patients, including 81 patients (54.0%) who satisfied the International Classification of Sleep Disorders, Revised, minimum clinical criteria for RBD. RBD-s preceding the appearance of parkinsonism were found in 44.4% of patients. Statistically, the presence of RBD-s was associated with ages above 65 years, male gender, constipation, dopa-induced dyskinesia and 'sleep attack', with odds ratios of 3.709, 2.469, 2.184, 5.046 and 6.562, respectively. No differences were found between the 2 groups with regard to symptoms at PD onset, disease duration, Hoehn-Yahr stage, hallucination, dementia, wearing-off, orthostatic hypotension, cerebral blood flow and antiparkinsonism drugs. In the early stage, RBD and autonomic system dysfunction are important factors in the progression of PD.
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PMID:Parkinson's disease with and without REM sleep behaviour disorder: are there any clinical differences? 1912 3

Upper and lower gastrointestinal dysautonomia symptoms (GIDS)--sialorrhea, dysphagia, and constipation are common in Parkinson's disease (PD) and often socially as well as physically disabling for patients. Available invasive quantitative measures for assessing these symptoms and their response to therapy are time-consuming, require specialized equipment, can cause patient discomfort and present patients with risk. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. Six clinical researchers and a biostatistician systematically searched the literature for scales of sialorrhea, dysphagia, and constipation, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated "Recommended" if the scale was used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and clinimetric studies have established that it is a valid, reliable, and sensitive. "Suggested" scales met at least part of the above criteria, but fell short of meeting all. Based on the systematic review, scales for individual symptoms of sialorrhea, dysphagia, and constipation were identified along with three global scales that include these symptoms in the context of assessing dysautonomia or nonmotor symptoms. Three sialorrhea scales met criteria for Suggested: Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale, and Sialorrhea Clinical Scale for PD (SCS-PD). Two dysphagia scales, the Swallowing Disturbance Questionnaire (SDQ) and Dysphagia-Specific Quality of Life (SWAL-QOL), met criteria for Suggested. Although Rome III constipation module is widely accepted in the gastroenterology community, and the earlier version from the Rome II criteria has been used in a single study of PD patients, neither met criteria for Suggested or Recommended. Among the global scales, the Scales for Outcomes in PD-Autonomic (SCOPA-AUT) and Nonmotor Symptoms Questionnaire for PD (NMSQuest) both met criteria for Recommended, and the Nonmotor Symptoms Scale (NMSS) met criteria for Suggested; however, none specifically focuses on the target gastrointestinal symptoms (sialorrhea, dysphagia, and constipation) of this report. A very small number of rating scales have been applied to studies of gastrointestinal-related dysautonomia in PD. Only two scales met "Recommended" criteria and neither focuses specifically on the symptoms of sialorrhea, dysphagia, and constipation. Further scale testing in PD among the scales that focus on these symptoms is warranted, and no new scales are needed until the available scales are fully tested clinimetrically.
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PMID:Dysautonomia rating scales in Parkinson's disease: sialorrhea, dysphagia, and constipation--critique and recommendations by movement disorders task force on rating scales for Parkinson's disease. 1920 66

Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility in PD include early satiety and weight loss from delayed gastric emptying and constipation from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the parkinsonian neurotoxin and mitochondrial complex I inhibitor rotenone causes delayed gastric emptying and enteric neuronal dysfunction when administered chronically to rats in the absence of major motor dysfunction or CNS pathology. When examined 22-28 days after initiation of rotenone infusion by osmotic minipump (3 mg/kg/day), 45% of rotenone-treated rats had a profound delay in gastric emptying. Electrophysiological recording of neurally-mediated muscle contraction in isolated colon from rotenone-treated animals confirmed an enteric inhibitory defect associated with rotenone treatment. Rotenone also induced a transient decrease in stool frequency that was associated with weight loss and decreased food and water intake. Pathologically, no alterations in enteric neuron numbers or morphology were apparent in rotenone-treated animals. These results suggest that enteric inhibitory neurons may be particularly vulnerable to the effects of mitochondrial inhibition by parkinsonian neurotoxins and provide evidence that parkinsonian gastrointestinal abnormalities can be modeled in rodents.
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PMID:Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease. 1940 96


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