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

Spinal cavernous hemangioma is rare, and it is extremely rare for cavernous hemangioma to develop in the cauda equina. There has been only one report of hydrocephalus associated with cavernous hemangioma in the cauda equina. We report a case of cavernous hemangioma in the cauda equina diagnosed on the basis of the headaches due to hydrocephalus. A 67-year-old man was being treated for Parkinson's disease because of tremor of both upper extremities for several years. In December 1991 he complained of occasional headaches. On February 15, 1992 the headaches became severe and frequent, with nausea and vomiting, and his gait became unsteady. Four days later he came to our hospital. Neurological examination revealed fine finger tremor and truncal ataxia. Computerized tomography scanning and magnetic resonance imaging of the head revealed ventricular enlargement, but there were no mass lesions obstructing the cerebrospinal fluid pathway. Lumbar puncture at the L3-L4 level yielded bloody cerebrospinal fluid, and the pressure had increased to 410 mmH2O. Cerebral angiography showed no abnormal findings. Magnetic resonance imaging of the lumbar spine demonstrated an intradural tumor at the level of vertebral body L2. Spinal angiography showed no evidence of abnormal vascularity in the mass at the L2 level. On March 10, 1992, laminectomy at three levels, L1 to L3 was performed, and a well-defined blueberry-like intra-cauda equina tumor 1 cm. in diameter, was removed. One spinal nerve root passed through the tumor. The pathological diagnosis was cavernous hemangioma. After removal of the tumor, the patient's headaches improved, and a follow-up computerized tomography scan six months later showed normal ventricle size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cauda equina cavernous hemangioma associated with hydrocephalus--case report]. 754 25

Eleven patients with levodopa-related motor fluctuations were scored before and after intranasal apomorphine monotherapy, and the motor responses were compared with those with levodopa/carbidopa in this openlabel study. Oral trimethobenzamide was used to prevent apomorphine-induced nausea. Three measures of motor performance were employed: (a) the Unified Parkinson's Disease Rating Scale (UPDRS) motor battery; (b) a timed hand-tapping test; and (c) the Webster's step-seconds test. The magnitude of the motor-score improvement after apomorphine administration was very similar to that after the usual doses of levodopa/carbidopa in the 10 patients completing the study; this was true for all three outcome measures. A major advantage of apomorphine was the rapid onset of clinical response, which typically occurred in < 10 min, as well as the ease of administration. Major side effects, beyond those experienced with levodopa/carbidopa, were limited to nausea and vomiting (three patients) and orthostatic hypotension (one patient); however, only a single patient dropped out of the study as a consequence. These results indicate that intranasal apomorphine is effective in rapidly relieving parkinsonian "off" states and that, for most patients, trimethobenzamide is an effective and well-tolerated antiemetic for use with apomorphine.
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PMID:Intranasal apomorphine rescue therapy for parkinsonian "off" periods. 872 38

Ropinirole is a novel, non-ergoline dopamine agonist chemical name with a very high specificity for dopamine D2-like receptors, currently being investigated for the symptomatic treatment of Parkinson's disease. The efficacy of ropinirole has been investigated in three placebo-controlled studies: one using ropinirole as monotherapy in early Parkinson's disease and two using it as an adjunct to L-dopa in patients who are experiencing fluctuations in motor response. Ropinirole therapy for 12 weeks was an effective symptomatic therapy in both patient groups, as measured by either a significant improvement in the motor score of the UPDRS, reduction of awake time spent "off" or a reduction in the dose of L-dopa. Ropinirole therapy was generally well tolerated, the most frequent adverse events being nausea and vomiting which are typical of all dopamine agonists, but unlike other dopamine agonists, CNS side-effects were of the same magnitude as found patients receiving placebo.
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PMID:Ropinirole in the symptomatic treatment of Parkinson's disease. 874 30

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

BAM-1110 [(5R,8R,10R)-6-methyl-8-(1,2,4-triazol-l-ylmethyl) ergoline maleate] is a newly synthesized dopamine agonist that produces little anorexic side effects (nausea and vomiting). The current study examines the effects of BAM-1110 on parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model of Parkinson's disease. First, a significant antiparkinsonian effect of apomorphine hydrochloride (0.3 mg/kg given subcutaneously) was confirmed in these animals. BAM-1110 (0.1, 0.3, and 1 mg/kg subcutaneously) relieved parkinsonian symptoms in a dose-dependent manner. Significant effects were observed at doses of 0.3 and 1 mg/kg and lasted for at least 3 h. BAM-1110, at a dose of 0.3 mg/kg that produced the submaximal antiparkinsonian effect, did not induce significant abnormal behaviors such as hyperactivity and stereotyped behaviors. Significant stereotyped behaviors were observed at 1 mg/kg of BAM-1110. Apomorphine induced hyperactive and stereotyped behaviors in parallel with its antiparkinsonian effect. BAM-1110 appears to be a potentially useful dopamine agonist to treat Parkinson's disease because of its relatively weak drug-induced hyperactive disturbances and anorexic side effects.
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PMID:Antiparkinsonian effects of BAM-1110, a novel ergoline derivative, in MPTP-treated cynomolgus monkeys. 957 83

N-0923, a novel aminotetralin dopamine D2 agonist, was shown to effectively reverse parkinsonian symptoms in nine dopa/agonist-responsive Parkinson's disease patients. The drug was given up to 4.5 hours by continuous intravenous (i.v.) infusion using an i.v. pump. The onset of anti-parkinsonian effect was seen within minutes of the initiation of the infusion and was absent within 90 minutes of cessation of the infusion. The short elimination half-life of N-0923 (90 min) would allow for the rapid initiation of drug effect when necessary and at the same time permit the effect to be terminated quickly if necessary. The drug would be useful in situations where oral medication is not feasible or is associated with erratic absorption. The patients tolerated the drug well. Dose escalation load was limited by nausea and vomiting. It should be noted that the doses were increased until these symptoms occurred, but therapeutic effects were noted well before the side effects occurred. Using a modified Columbia scale, maximum improvement consisted of a 27-95% drop in score. Maximum response was obtained at infusion rates varying from 2-16 microg/kg per hour and at blood levels of 0.11-1.49 microg/mL.
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PMID:N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism. 975 44

After 3-5 years of continuous use of 1-dopa preparations for Parkinson's disease, 25%-50% of patients develop side-effects such as the "on-off" phenomenon and involuntary movements that markedly impair function. One cause of these manifestations is evidently a disturbance in the absorption of 1-dopa. We attempted to avoid this problem by using subcutaneous injections. Apomorphine is a rapid-acting dopamine agonist which causes a return from "off" to "on" within minutes. We present the results of a trial of subcutaneous injections of apomorphine in 22 Parkinsonian patients (12 males, 10 females) with severe motor fluctuations. During 5 days prior to the apomorphine all received Motilium (domperidone, 60 mg/d) to prevent nausea and vomiting. All were hospitalized initially to determine optimal dosage and to teach them the technique of self-injection. 2 to 4 mg of apomorphine were injected 1 to 3 times daily for 2 to 12 months. In 17 patients (80%) "off" periods were reduced without significant side-effects. Apomorphine seems to be effective, tolerable treatment for shortening 1-dopa induced "off" periods.
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PMID:[Apomorphine for treatment of "off-periods" in Parkinson's disease]. 1095 39

Levodopa is the most effective drug available for the symptomatic treatment of Parkinson's disease (PD) and is the gold standard with which other therapies must be compared. Levodopa improves most parkinsonian symptoms and is associated with an apparent decrease in mortality rate. However levodopa usage is also associated with both acute and chronic side effects which compromise treatment. Levodopa is metabolized by both decarboxylase and catechol-O-methyl transferase enzymes. It is routinely administered in combination with a decarboxylase inhibitor to prevent the peripheral accumulation of dopamine and associated side effects such as nausea and vomiting. More recent studies suggest that combination of levodopa with an inhibitor of catechol-O-methyl transferase prolongs the duration of effect of the drug and can prolong the duration of motor response in fluctuating patients. This article will review the safety and efficacy of levodopa treatment.
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PMID:Levodopa in the treatment of Parkinson's disease. 1114 6

Idiopathic Parkinson's disease (PD) is a common chronic progressive neuro-degenerative disorder associated with the progressive loss of dopaminergic neurons in the substantia nigra. The natural course of the disease may lead to severe disability despite a variety of pharmacological and surgical treatment options. Levodopa is still the most effective symptomatic treatment for PD; however, long term use can cause a number of adverse effects including motor complications, nausea and vomiting, postural hypotension and changes in mental status. The onset of motor complications marks a crucial point in the management of PD. They may present as changes between akinetic and mobile phases (motor fluctuations) or as abnormal involuntary movements (dyskinesias). After levodopa treatment for 3 to 5 years, motor complications occur in approximately 50% of patients, and after 10 years in >80% of patients. Treatment options have recently expanded as new drugs have been licensed and surgical procedures refined. Patients with motor complications present a demanding task in disease management, and often multiple drugs and high dosages are necessary to achieve only suboptimal control, resulting in increased healthcare utilisation. Costs increase considerably in patients with motor fluctuations and dyskinesias compared with patients without these symptoms. In a French study, 6-month direct medical costs per patient increased from 1648 euros (EUR) to EUR3028 in patients without and with motor fluctuations, respectively. In a recent French study a significant difference in monthly direct medical costs was found in patients with and without dyskinesias (EUR560 vs 170). Unfortunately, no data are available on the effect of motor complications on indirect costs. Several studies have shown that health-related quality of life (HR-QOL) is reduced when motor fluctuations occur. This may also be true of dyskinesias, but because of the limited number of studies a definite conclusion is not yet possible. Recently, surgical treatment options have been used to deal with advanced PD and late stage complications. Although their effect on motor complications and HR-QOL is well documented, they result in increased costs (total medical cost: EUR28920) compared with drug treatment alone and are increasingly restricted by healthcare providers. The purpose of this article is to review the available data from pharmacotherapeutic. surgical and economic studies on HR-QOL and healthcare expenditure in patients with PD, with a major focus on the impact of motor fluctuations and dyskinesias.
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PMID:Health-related quality of life and healthcare utilisation in patients with Parkinson's disease: impact of motor fluctuations and dyskinesias. 1173 71

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.
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PMID:Spectrum of use and tolerability of 5-HT3 receptor antagonists. 1551 6


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