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)

Memantine is a 1-amino-adamantane derivative which has been proposed to be useful in the treatment of Parkinson's disease. Its beneficial effect has been related to its novel properties as an NMDA receptor blocker which can neutralize the effect of glutamate at striatal and subthalamic levels. In the present study, conducted in an open-fashion, 14 parkinsonian patients with motor fluctuations taking L-dopa, were given a supplement of memantine 30 mg/day. After one month, 10 patients completed the treatment (4 discontinued it due to abdominal pain, psychomotor agitation, confusion and dizziness). In 5 patients, the main parkinsonian features improved significantly (1 point or more on the Webster scale). In 6 patients, "off" episodes improved (from daily mean of 273 minutes, to 172 minutes). In summary, memantine addition to parkinsonian features, could form a basis for novel therapeutic strategies directed to neutralize the effects of glutamate at striatal and subthalamic levels.
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PMID:Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease. 138 98

Fifty Thai patients with Parkinson's disease of all staging were allocated for 10 mg/day L-deprenyl therapy as the monotherapy (6 patients) and adjunctive therapy for at least two months. The assessment of this open study included the activities of daily living using Schwab/England Scale, Hoehn and Yahr staging and Unified Parkinson Disease Rating Scale (UPDRS) by comparison of the initial and after two month of treatment scores. There was improvement of both Schwab/England Scale and UPDRS in Hoehn and Yahr stage I, II and III patients. In stage IV and V patients there was no benefit of L-deprenyl therapy of both clinical and statistical analyses. Adverse effects of L-deprenyl were not serious. There were dry mouth (20%), anorexia (10%), nausea and vomiting (8%), insomnia (6%), lightheadedness (4%) constipation (4%), abdominal pain (2%), generalised ache (2%). We conclude that L-deprenyl therapy is effective, safe, but costly. It is more effective in early Parkinsonism. The effectiveness of L-deprenyl is less in more advanced states of Parkinson's disease. Thus, selection of the appropriate Parkinsonian patient for L-deprenyl therapy is vital.
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PMID:L-deprenyl therapy in Thai patients with Parkinson's disease: before and after, clinical trial of 50 patients. 212 33

We report a case of generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder. A 74-year-old female was admitted with abdominal pain and biochemical findings of acute renal failure (ARF). She had recently complained of macrohematuria. She had a past history of radiotherapy for uterine cervical cancer and Parkinson's disease treated with levodopa and amantadine. We diagnosed this case as intraperitoneal rupture of the bladder by cystogram. Biochemical findings of ARF might have resulted from urine reabsorption. Intraperitoneal rupture of the bladder should be considered in all cases of peritonitis, especially in patients with urological symptoms and features of ARF.
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PMID:Generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder. 896 1

Ropinirole is a novel, nonergoline, selective D2-type dopamine agonist developed to treat Parkinson's disease. Safety data from therapeutic studies involving 1364 patients receiving ropinirole are reported (mean daily dose 8.7 mg, early therapy; 8.2 mg adjunct therapy). In early therapy, the emergent adverse experiences more common with the ropinirole group compared with placebo were nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and hallucinations. In adjunct therapy, they were dyskinesia, nausea, hallucinations, and confusion. Most adverse experiences were mild and associated with a similar withdrawal rate compared with the placebo group. Except for hallucinations, the incidence of emergent adverse experiences decreased with time, despite increasing doses. Long-term adverse experiences particularly associated with ergoline-type dopamine agonists have so far not been observed with ropinirole. Only 1.2% of patients receiving ropinirole developed dyskinesia compared with 11.2% receiving L-dopa in early therapy over a mean period of 17 months. There were no clinically significant changes in cardiovascular parameters or laboratory data. The incidence of adverse experiences in the bromocriptine group was low, possibly because of a slow titration scheme and low average dose. Overall, the safety profile of ropinirole appears similar to that of other dopamine agonists. Clinical studies are continuing to assess the long-term safety and efficacy of ropinirole.
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PMID:The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson's disease. 961 8

Tolcapone is a potent, reversible catechol-O-methyltransferase (COMT) inhibitor with both peripheral and central activity. It has been demonstrated to improve motor function and allow levodopa dose reductions in Parkinson's disease (PD) patients who are experiencing either a stable response or motor fluctuations while on levodopa/dopa decarboxylase inhibitor therapy. Because striatal dopamine is metabolized by COMT and monoamine oxidase (MAO), central COMT inhibition alone or in combination with MAO inhibition might provide symptomatic benefit for patients not receiving levodopa. We conducted a pilot study to evaluate the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in early untreated PD patients. Patients were randomized to receive 200 mg tolcapone three times a day or placebo for the 8 weeks of the study. Open-label oral selegiline (5 mg in the morning and midday) was administered to all patients during the second 4 weeks of the study. There was no difference between treatment groups according to the investigator's assessment of tolerability at week 4. Ninety-five percent of tolcapone-treated patients and 98% of placebo-treated patients experienced excellent or good tolerability during the first 4 weeks (95% confidence interval [CI]: -10.3, 5.7; p = 0.57). A decrease in tolerability occurred in the tolcapone group during the second 4 weeks of the study following the addition of selegiline. The most commonly reported side effects were diarrhea (31% tolcapone, 7% placebo), nausea (21% tolcapone, 2% placebo), urine discoloration (12% tolcapone, 0% placebo), dizziness (12% tolcapone, 5% placebo), headaches (12% tolcapone, 10% placebo), and abdominal pain (10% tolcapone, 5% placebo). We did not identify symptomatic benefit associated with tolcapone alone or in combination with oral selegiline in this group of otherwise untreated PD patients.
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PMID:A pilot evaluation of the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in untreated Parkinson's disease patients. Tolcapone De Novo Study Group. 968 68

Patients with gastroparesis frequently present challenging clinical, diagnostic, and therapeutic problems. Data from 146 gastroparesis patients seen over six years were analyzed. Patients were evaluated at the time of initial diagnosis and at the most recent follow-up in terms of gastric emptying and gastrointestinal symptomatology. The psychological status and physical and sexual abuse history in female idiopathic gastroparesis patients were ascertained and an association between those factors and gastrointestinal symptomatology was sought. Eighty-two percent of patients were females (mean age: 45 years old). The mean age for onset of gastroparesis was 33.7 years. The etiologies in 146 patients are: 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson's disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction, and 6% miscellaneous causes. Subgroups were identified within the idiopathic group: 12 patients (23%) had a presentation consistent with a viral etiology, 48% had very prominent abdominal pain. Other subgroups were gastroesophageal reflux disease and nonulcer dyspepsia (19%), depression (23%), and onset of symptoms immediately after cholecystectomy (8%). Sixty-two percent of women with idiopathic gastroparesis reported a history of physical or sexual abuse, and physical abuse was significantly associated with abdominal pain, somatization, depression, and lifetime surgeries. At the end of the follow-up period, 74% required continuous prokinetic therapy, 22% were able to stop prokinetics, 5% had undergone gastrectomy, 6.2% went onto gastric electrical stimulation (pacing), and 7% had died. At some point 21% had required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition. A good response to pharmacological agents can be expected in the viral and dyspeptic subgroups of idiopathics, Parkinson's disease, and the majority of diabetics, whereas a poorer outcome to prokinetics can be expected in postgastrectomy patients, those with connective tissue disease, a subgroup of diabetics, and the subset of idiopathic gastroparesis dominated by abdominal pain and history of physical and sexual abuse. Appreciation of the different etiologies and psychological status of the patients may help predict response to prokinetic therapy.
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PMID:Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. 982 25

We report a 73-year-old Japanese woman with familial Parkinson's disease. The patient was well until her 67 years of the age, when she noted rest tremor in her right hand. Soon after her gait became short stepped. She visited our clinic on October 6, 1992 when she was 68 years old. She was alert and well oriented without dementia. She showed masked face, small voice, small stepped gait, retropulsion, resting tremor in her right hand, rigidity in the neck, and bradykinesia. She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment. On August 26, 1998, she developed abdominal pain, diarrhea, and vomiting. She was admitted to another hospital, where abdominal plain x-ray revealed an evidence of intestinal obstruction (ileus). She was treated with nasogastric suction and intravenous fluid. Her condition did not improve and she was transferred to our hospital on August 29, 1998. Her family history revealed no consanguineous marriage. She had two elder brothers and three elder sisters. One of her brothers had been diagnosed as Parkinson's disease. Her husband also suffered from Parkinson's disease, however, her parents apparently did not have Parkinson's disease. On admission, she appeared to be drowsy. Her blood pressure was 102/70 mmHg, body temperature 36.2 degrees C. The lungs were clear and no cardiac murmur was present. Abdomen was flat and bowel sound was audible. No abnormal mass was palpable. Neurologic examination revealed mild consciousness disturbance, masked face, and small voice. No motor paralysis was noted. Muscle tone was hypotonic. No abnormal involuntary movement was noted. Abnormal laboratory findings on admission were as follows; WBC 11,300/microliter, amylase 1,373 IU/l, CK 446 IU/l, BUN 50 mg/dl, creatinine 1.17 mg/dl, CRP 22.7 mg/ dl, Na 134 mEq/l, K 3.1 mEq/l, and Cl 81 mEq/l. A chest x-ray film revealed pneumonic shadows in both lower lung fields. She was treated by nasointestinal suction, intravenous fluids, and chemotherapy for her infection. Her BP started to drop on September 2 and she developed cardiac arrest on the same day. She was discussed in a neurological CPC. The chief discussant arrived at the conclusion that the patient had a form of autosomal dominant familial Parkinson's disease. As parents did not have Parkinson's disease, some of the participants raised the possibility of autosomal recessive inheritance. But the age of onset was too late for autosomal recessive inheritance. Majority thought that the mode of inheritance was autosomal dominant with low penetrance. alpha-Synuclein mutation causes an autosomal dominant familial Parkinson's disease, but this type is very rare in non-Greek populations and the penetrance is high. Chromosome 2-linked autosomal dominant familial Parkinson's disease shows low penetrance. There are many other autosomal dominant forms of familial Parkinson's disease linked to yet unknown chromosome loci. Majority thought that this patient also had a form of Lewy-body positive autosomal dominant familial Parkinson's disease of unknown chromosome locus. Post mortem examination revealed ischemic intestinal lesion with strangulation. This was thought to be the cause of her death. In the central nervous system, the brain appeared to be normal by inspection. In the coronal sections, the substantia nigra and the locus coeruleus showed marked depigmentation. Histologic examination revealed marked neuronal loss and Lewy body formation in the remaining neurons. Pathologic examination was consistent with Parkinson's disease. Mutational analysis for the parkin gene was negative.
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PMID:[A 73-year-old woman with familial Parkinson's disease]. 1065 9

Besides the classic motor swings, many non motor fluctuations may occur in Parkinson's disease, but the clinical spectrum and the frequency of these symptoms are not well recognized. A total of 47 parkinsonian outpatients were questioned about any symptoms associated with off state. Nine patients had no fluctuations, 16 referred only to motor fluctuations and 22 to motor fluctuations associated with non motor symptoms. Overall, these patients referred to 54 symptoms (average 2.3/patients, range 1-6). These symptoms were classified as: autonomic (3 difficulty in swallowing, 7 hot, 11 sweat, 2 cold, 1 pallor, 1 abdominal bloating, 1 abdominal pain, 1 abdominal and genital pain, 5 bladder dysfunction, 2 feet oedema); sensory (7 sensory dyspnoea, 1 pain in lower limbs, 1 internal tremor); cognitive (3 depression, 4 anxiety, 2 panic, 1 drowsiness, 1 confusion). In patients without off periods, the length, severity and the average dosages of levodopa were fewer than in patients with fluctuations. No significant differences were found between patients with motor off and patients with associated non motor off regarding age (71.2+/-9.6 years vs 71.6+/-10.7 years), length of the disease (83.2+/-38.5 months vs 95.9+/-58.1 months), the Hoehn-Yahr (3.06+/-0.96 vs 3.02+/-0.96) and Webster (15.5+/-6.99 vs 15.1+/-5.9) scale, the dosages of levodopa (680.9+/-238.9 mg/die vs 679.7+/-289.6 mg/die), the number (2.3+/-1.7 vs 2.8+/-1.5) and length (6.8+/-5.2 h vs 7.2+/-7.1 h) of motor off. The non motor fluctuations were recognized in about 60% of patients with motor fluctuations: usually they were mild and less important than motor off, but sometimes these problems were disabling and led to unnecessary tests and therapies.
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PMID:Non motor off in Parkinson's disease. 1169 27

In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of fife, was better tolerated, and had a more favorable adverse-event profile than pergolide.
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PMID:Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations. 1174 15

Gastrointestinal symptoms such as nausea, abdominal pain, and bloating are frequent complaints of patients with Parkinson's disease (PD). It has been postulated that impaired gastrointestinal function may contribute to the development of motor fluctuations such as delay on and no on in patients with PD. Gastrointestinal impaired function and symptoms may be associated with the disease itself or secondary to levodopa treatment. Thus, we assessed gastric emptying (GE) and gastric motility in PD patients to examine the association between clinical status and gastric function. GE and antral contraction (frequency and amplitude) were evaluated by scintigraphy in 29 patients with mild PD (Hoehn and Yahr [H&Y] stage 1.0-2.0); 22 patients with moderate PD (H&Y stage 2.5-3.0); and 22 healthy volunteers, following the ingestion of a labeled standard meal. Gastric emptying (mean +/- SD of T(1/2)) and antral contraction were not significantly different between patients with mild PD (63.4 +/- 28.8 minutes) and moderate PD (54.7 +/- 25.5 minutes). In the control group, GE was 43.4 +/- 10.8 minutes (range 29.0 - 61.0 minutes). The prevalence of delayed emptying (>61 minutes) was not significantly different in patients with mild disease (48.3%) as compared with patients with moderate disease (36.4%). Antral contraction, both frequency and amplitude, were not significantly different between patients with mild and moderate PD throughout the entire 100 minutes of the study. Untreated patients (n = 28) had mean GE T(1/2) of 59 +/- 30.6 minutes. Patients with smooth response to levodopa showed slower GE (n = 10; 73.6 +/- 25.3 minutes), while treated patients with motor response fluctuations when tested at the on state (n = 13), had much faster GE (49.3 +/- 16.2 minutes). This shortened GE in the on state was similar to the GE of normal volunteers. We conclude that gastric emptying time in patients with PD was delayed compared with control volunteers. It was even slower in patients treated with levodopa. This effect of levodopa treatment was reversed to pseudonormalization (normal GE) at the advanced stages of the disease, when patients developed motor response fluctuation. Other clinical features of PD were not associated with delayed gastric emptying.
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PMID:Gastric emptying time and gastric motility in patients with Parkinson's disease. 1174 35


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