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Biomedical subjects

J K Tsui

Publications and source records attributed to J K Tsui.

At least 19 recordsLinked to original sources
PubMed2001

Transdermal dopaminergic D(2) receptor agonist therapy in Parkinson's disease with N-0923 TDS: a double-blind, placebo-controlled study.

N-0923 is a non-ergot, dopaminergic D(2) agonist designed to be transdermally available. It has anti-parkinsonian effects when infused intravenously. An adhesive matrix patch was developed to deliver N-0923 transdermally (N-0923 TDS). In this phase II trial, we evaluated the effectiveness of various doses of N-0923 TDS at replacing levodopa. Eighty-five Parkinson's disease (PD) patients were randomized to placebo or one of four doses of N-0923 TDS for 21 days. Change in daily levodopa dose was the primary efficacy measure. Significantly greater reductions in levodopa dose were achieved as compared to placebo for the two highest doses of N-0923 TDS. Patients treated with 33.5 mg and 67 mg N-0923 TDS decreased levodopa use by 26% and 28%, vs. 7% for placebo. N-0923 TDS was safe and well tolerated.

Administration, Cutaneous↗
PubMed2001

The long-term response to levodopa in dopa-responsive dystonia.

We report the long-term response to levodopa in 20 patients with dopa-responsive dystonia (DRD). We found an inverse correlation between the daily dose of levodopa and duration of treatment (r=-0.59, P<0.01). Mild dyskinesias were present in 20% of our patients. Dyskinetic patients were on a higher dose of levodopa than non-dyskinetics. Dyskinesias responded to a reduction in levodopa, with no deterioration in motor function. We propose that the dopamine turnover might decrease with time, which would lead to a decrease in the requirement for levodopa and the occurrence of dyskinesias late in the course of DRD.

Adolescent↗
PubMed2001

Angiotensin regulates endothelin-B receptor in rat inner medullary collecting duct.

Our recent studies showed that endothelin (ET)(B) receptors are downregulated in congestive heart failure. These changes in ET(B) receptor density can be prevented by angiotensin-converting enzyme inhibitors, suggesting a possible role for angiotensin. Using isolated inner medullary collecting ducts (IMCD), we examined the possibility that angiotensin-induced downregulation of ET(B) receptors is accompanied by a decrease in ET(B) receptor mRNA. Binding studies showed that overnight incubation with angiotensin II induced a downregulatiion of ET(A) and ET(B) receptors' density in IMCD by 39% and 29%, respectively. This downregulation in ET receptor density was abolished when IMCD was coincubated with angiotensin II and its receptor antagonist saralasin. Furthermore, when the cells were exposed to phorbol myristate acetate (PMA), it resulted in a reduction in ET(A) and ET(B) receptor binding sites by 41% and 34%, respectively, suggesting the involvement of protein kinase C (PKC). In isolated IMCD, ET-1 induced an increase in cyclic guanosine monophosphate (cGMP) accumulation (705 + 63 to 1,015 + 88 fmol/microg protein/5min, P <.01), and the ET-1-induced accumulation was attenuated in the presence of angiotensin II (641 + 45 to 809 + 46 fmol/microg protein/5min, P <.01). Using competitive polymerase chain reaction (PCR) method, we also observed downregulation of ET(A) and ET(B) receptors mRNA in IMCD treated with angiotensin II (ET(A), 1.09+0.11 v 0.77 + 0.07 amol/microg of total RNA, P <.01; ET(B), 14.80 + 1.95 v 8.65 + 0.67 amol/microg of total RNA, P <.01). The addition of a PKC inhibitor abolished the downregulation of ET(A) and ET(B) receptor mRNA induced by angiotensin II (ET(A), 1.25 + 0.07 v 1.19 + 0.06 amol/microg of total RNA, not significant [NS]; ET(B), 14.36 + 0.83 to 13.68 + 0.64 amol/microg of total RNA, NS). These results suggest that angiotensin II-induced downregulation of ET(A) and ET(B) receptors mRNA is mediated by a mechanism involving PKC.

Angiotensin II↗
PubMed2000

Botulinum toxin A as treatment for drooling saliva in PD.

The authors evaluated intraparotid injections of botulinum toxin A in reducing salivary secretions and drooling in nine patients with PD. There was a marked objective reduction in secretion, and two thirds of the patients had subjective improvement in drooling. No side effects were observed. The authors conclude that botulinum toxin A promises to be a simple and effective treatment for the common problem of drooling saliva in chronic neurologic disease.

Aged↗
PubMed2000

Post-traumatic cervical dystonia: a distinct entity?

BACKGROUND/OBJECTIVE: The incidence of head/neck trauma preceding cervical dystonia (CD) has been reported to be 5-21%. There are few reports comparing the clinical characteristics of patients with and without a history of injury. Our aim was to compare the clinical characteristics of idiopathic CD (CD-I) to those with onset precipitated by trauma (CD-T). METHODS: We evaluated 114 consecutive patients with CD over a 9-month period. All patients were interviewed using a detailed questionnaire and had a neurological examination. Their clinical charts were also reviewed. RESULTS: Fourteen patients (12%) had mild head/neck injury within a year preceding the onset of CD. Between the two groups (CD-I and CD-T), the gender distribution (F:M of 3:2), family history of movement disorders (32% vs. 29%), the prevalence of gestes antagonistes (65% vs. 64%), and response to botulinum toxin were similar. There were non-specific trends, including an earlier age of onset (mean ages 43.3 vs. 37.6), higher prevalence of neck pain (86% vs. 100%), head tremor (67% vs. 79%), and dystonia in other body parts (23% vs. 36%) in CD-T. CONCLUSIONS: CD-I and CD-T are clinically similar. Trauma may be a triggering factor in CD but this was only supported by non-significant trends in its earlier age of onset.

Adult↗
PubMed2000

Vasopressin regulates endothelin-B receptor in rat inner medullary collecting duct.

Previous studies have shown that endothelin (ET) antagonizes the actions of arginine vasopressin (AVP) in the renal collecting ducts. On the other hand, the effects of AVP on ET function within the collecting ducts of the kidney have not been investigated extensively. Using isolated inner medullary collecting ducts (IMCD), we examined the possibility that a decrease in ET(B) receptor mRNA accompanied AVP-induced downregulation of ET(B) receptors. Binding studies revealed that overnight incubation of rat IMCD cells with AVP significantly reduced the maximal binding capacity (B(max)) of ET. Activation of adenylate cyclase by forskolin decreased the total ET(B) receptor density by approximately 42% but did not affect the density of ET(A) receptors. The Rp diastereoisomer of adenosine 3', 5'-cyclic monophosphothionate, Rp-cAMPS (a specific inhibitor of protein kinase A), blocked the AVP-induced reduction in ET receptor density. Using competitive PCR method, we also observed downregulation of ET(B) receptor mRNA in IMCD treated with AVP. Additional studies were done with IMCD to determine whether AVP inhibited the ET-induced accumulation of cGMP. We saw a reduction in ET-induced cGMP accumulation when IMCD was incubated overnight with AVP. This inhibition of ET-induced accumulation of cGMP was blocked by Rp-cAMPS. These results suggest that AVP regulates ET(B) receptor expression in IMCD.

Animals↗
PubMed2000

Head tremor in cervical dystonia.

OBJECTIVE: To compare the clinical characteristics, natural history, and therapeutic outcome of patients with cervical dystonia (CD) with head tremor (HT+) and without head tremor (HT-). METHODS: We prospectively evaluated 114 consecutive patients of CD over a 9-month period with a detailed questionnaire. Chi-square and t-tests were employed for statistical analysis. RESULTS: Seventy-eight (68.4%) patients had head tremor and 27 of them (34.6%) had tremor as one of the first symptoms. Age at onset of symptoms were similar in HT+ and HT- groups; however there was a higher prevalence in women in the former group (66.7% vs. 41.7%; p=0.01). HT+ patients had more frequent positive family history of essential-like hand/head tremor (21.8% vs. 5.5%; p<0.05), associated neck pain (92.3% vs. 77.8%: p<0.05), and essential-like hand tremor (40% vs. 8.3%; p<0.001). They also appeared to have more frequent history of preceding head/neck trauma (14.1% vs. 8.3%), frequent head rotation (88.5% vs. 69.4%) and antecollis (12.8% vs. 5.5%) but less often head tilt (37.2% vs. 47.2%) and gestes antagonistes (60.2% vs. 75%) than the HT- patients; however these differences were not statistically significant. The frequency of prior psychiatric illnesses, the incidence of dystonias in other parts of the body, frequency of retrocollis and shoulder elevation, and spontaneous remission were similar in the two groups. CONCLUSION: Head tremor is common in CD and is more commonly associated with hand tremor and family history of tremor or other movement disorders. This supports a possible genetic association between CD and essential tremor (ET). Linkage studies are required to evaluate the genetic association between CD and ET.

Adult↗
PubMed1999

Unilateral pallidotomy for reduction of parkinsonian pain.

OBJECT: The goal of this study was to determine whether unilateral pallidotomy reduces parkinsonian pain. METHODS: Twenty-one patients suffering from Parkinson's disease (PD) were followed prospectively for 1 year after they had undergone a unilateral pallidotomy to assess the procedure's effect on pain related to PD. Pain unrelated to PD was not studied. Patients scored the level of their PD pain on an ordinal scale (0-10 points) preoperatively and 6 weeks and 1 year postoperatively. The results were analyzed using Wilcoxon's paired-ranks test (with Bonferroni correction) and showed a significant reduction in overall pain scores at 6 weeks (p < 0.001) and 1 year (p = 0.001) following pallidotomy. Various types of PD pain are described and their possible pathophysiological mechanisms are presented. CONCLUSIONS: Unilateral pallidotomy significantly reduces pain attributable to Parkinson's disease.

Cohort Studies↗
PubMed1996

Botulinum toxin as a therapeutic agent.

Botulinum toxin is a presynaptic neuromuscular blocking agent that, when injected intramuscularly in minute quantities, can produce selective muscle weakness. This property is employed therapeutically to provide symptomatic relief in conditions related to excessive muscle activities in strabismus, blepharospasm, hemifacial spasm, cervical dystonia, spasmodic dysphonia (adductor type), and jaw closing dystonia. It is investigational for a long list of medical conditions. It is a marketed drug in a number of countries in the world, but its use has only been approved by different regulatory agencies for use in a limited number of conditions. The long-term effects, appropriate dose for children, and in pregnancy, and maximum dose without causing toxicity remain unclear.

Anti-Dyskinesia Agents↗
PubMed1994

Clinical observations on the rate of progression of idiopathic parkinsonism.

The time course of evolution of clinical deficits has been a traditional guide to the nature of the aetiopathogenesis of neurological disease. We studied the influence of ageing and duration of disease on the natural history of idiopathic parkinsonism (IP). Two hundred and thirty-eight patients with IP were examined while off medication. Bradykinesia scores were analysed against patients' age and duration of disease by multiple regression. There was no significant interaction between the effects of age and of duration (P = 0.923). We conclude that age and duration of symptoms influence the natural history of IP additively and independently. Furthermore, the rate of neuronal death is more rapid in the earlier stages of evolution of the pathology; subsequently, the velocity of progression slows down to approach the rate of attrition produced by normal ageing. This time course has implications for possible models of pathogenesis.

Aged↗
PubMed1993

Botulinum toxin in the treatment of writer's cramp: a double-blind study.

We treated 20 patients with writer's cramp in a double-blind, placebo-controlled study. Each patient received two treatments in tandem, one with botulinum-A toxin (BTX-A) injections and another with normal saline, separated by 3 months. Treatment order was randomized and unknown to the patient and physician. Patients were assessed before each treatment and 2 and 6 weeks after each treatment by objective measurements of pen control. Twelve patients had improvement in pen control after treatment with BTX-A, but only four had significant improvement in writing. BTX-A injections are effective in relieving symptoms in selected cases of writer's cramp, particularly in those with significant wrist-joint deviation.

Adult↗
PubMed1992

Cerebral glucose metabolism in Parkinson's disease with and without dementia.

Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.

Aged↗
PubMed1992

Future treatment of Parkinson's disease.

New methods of drug delivery and slowing down the progression of Parkinson's disease (PD) are the major goals of research. More steady drug levels in the blood are possible by means of controlled-release preparations of levodopa and long-acting dopamine agonists, as well as transcutaneous duodenal tubes and pumps for controlled subcutaneous infusion. Patches containing dopamine agonists absorbed through the skin may be developed. The role of D1 agonists as compared with D2 agonists remains to be elucidated. Agonists on autoreceptors of dopaminergic neurons may potentially reduce excessive stimulation of the intact neurons and this may slow down the rate of neuronal death in PD. Monoamine oxidase-B inhibitors may have a potentially protective action on neurons. Investigations are being carried out to evaluate this claim. Catechol-o-methyl-transferase inhibitors may be helpful in theory. There is also recent interest in inhibitors of excitatory amino acids, which may contribute to neuronal loss in PD.

Animals↗
PubMed1990

Treatment of spasticity with botulinum toxin: a double-blind study.

We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions.

Adult↗
PubMed1990

Decreased efficacy of levodopa with carbidopa in parkinsonian patients after adrenal-to-caudate implants.

We studied 6 parkinsonian patients 6 weeks after unilateral adrenal-to-caudate implants. We withheld medications the night before each of 2 study days and gave the patients a single test dose of either a combination of levodopa and carbidopa, or levodopa alone in double-blind random order. We administered the modified Columbia scale, objective measurements of rigidity and movement velocity, and the pegboard test at regular intervals after the single test dose. The results revealed that the improvements in performance recorded by the Columbia scale and the pegboard test were significantly less on the side contralateral to the operation when patients received carbidopa, whereas there was no significant difference in performance between the 2 observations on the ipsilateral side. Carbidopa apparently crossed the disrupted blood-brain barrier and lowered the efficacy of levodopa.

Adrenal Medulla↗
PubMed1989

Optimal indices for testing parkinsonian rigidity.

We assessed parkinsonian rigidity objectively at the wrist to determine the optimal angular velocity and displacement for detecting abnormality. The wrist was moved passively with a torque motor and the average work done for one complete cycle was computed. This objective rigidity score (ORS) was compared with a clinical rigidity score (CRS). ORS was more pronounced at faster movement velocities in parkinsonian patients, whereas in normal subjects there was only a modest increase in the score. Angular velocities of 140 to 190 degrees/second and displacements of +/- 25 to +/- 30 degrees were most sensitive for detecting parkinsonian rigidity and had good correlation with the CRS.

Adult↗
PubMed1989

The effect of dietary protein on the efficacy of L-dopa: a double-blind study.

We randomly placed 10 parkinsonian patients on high- and low-protein diets that tasted and looked alike, each for 1 week. All patients were taking L-dopa and carbidopa with or without other antiparkinson medications; medications remained unchanged. A "blind" physician recorded the modified Columbia scores, objective measurements of rigidity, movement velocity, and pegboard tests three times a day for 5 days during each week. The patients recorded fluctuations hour to hour. We measured serial blood L-dopa levels on day 4 of each week. Performance was significantly better while the patients were on low-protein diets. These results did not correlate with blood L-dopa levels, which had higher peaks in three patients while they were on high-protein diets despite inferior performance and increased number of "off" hours. Thus, high dietary protein probably affects the efficacy of L-dopa at a central level.

Antiparkinson Agents↗