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A H Rajput

Publications and source records attributed to A H Rajput.

At least 37 records · Page 2Linked to original sources
PubMed1997

Concordance of common movement disorders among familial cases.

Multicase families are frequently utilized in studies of movement disorders (MDs). We report families with two or more MD cases seen at the Movement Disorder Clinic, Saskatoon (MDCS). In 30% of the MD probands, there was either a history or documentation of at least one secondary MD case in the family. Only those MD cases that were seen at the MDCS were considered in this study. A total of 56 probands and 77 secondary MD cases were seen at the MDCS between 1968 and 1996. In 24 (31.2%) of the secondary cases, the diagnosis was different from that in the proband. In 46 families (82%), only one secondary case was seen, and the diagnosis was concordant with the proband in 71.7%. In the remaining 10 families with two or more secondary cases, the diagnosis was concordant in 64.5% of cases. The largest subgroup was Parkinson's disease (PD)--40 probands and 53 secondary cases. of these secondary cases, 73.6% had PD. The concordance rate was 91% in essential tremor, but only 12.5% if the proband had essential tremor + parkinsonism. Considering that a large proportion of secondary cases have a diagnosis discordant with the proband, we recommend that, whenever possible, MD diagnosis in secondary cases be based on clinical assessment.

Age of Onset↗
PubMed1997

Tolcapone improves motor function in parkinsonian patients with the "wearing-off" phenomenon: a double-blind, placebo-controlled, multicenter trial.

We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on levodopa therapy. After 3 months, patients receiving tolcapone had a significant decrease in mean daily levodopa dose requirement compared with placebo-treated patients (p < 0.01). In patients treated with tolcapone 200 mg tid, daily "off" time, measured using patient diaries, was reduced from baseline by 3.25 hours; this reduction was significantly different from that seen in the placebo group (p < 0.01). Moreover, the number of daily levodopa intakes was reduced significantly in each tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor function and overall efficacy in the tolcapone groups (p < 0.01). The most frequent adverse events were associated with levodopa treatment. Dyskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving 200 mg tid, with most cases occurring within the first 30 days of the study. Diarrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17% on tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that tolcapone as an adjunct offers promise for the relief of the "wearing-off" phenomenon in levodopa-treated parkinsonian patients.

Aged↗
PubMed1996

GTP-cyclohydrolase I gene mutations in hereditary progressive amd dopa-responsive dystonia.

Recently, mutations of the GTP-cyclohydrolase I (GTP-CH I) gene, which catalyzes the first step in the tetrahydrobiopterin (BH4) biosynthesis, were discovered in Japanese patients with hereditary progressive dystonia/dopa-responsive dystonia (HPD/DRD). However, it has not been confirmed that non-Japanese patients also contain mutations in the same gene, or whether these mutations are specific to HPD/DRD. In this study, two novel nonsense mutations in exon I of the GTP-CH I gene and a new mutation at the splice acceptor site of intron I were identified in an autopsied case of English-Irish descent and 2 Japanese patients with HPD/DRD. In the latter, cerebrospinal fluid (CSF) neopterin levels (which may reflect the GTP-CH I activity in the brain) were reduced to 18% and 37% of controls. A therapeutic trial of oral BH4 was ineffective, however, in a genetically proven patient. In contrast, no mutations in any exons of the GTP-CH I gene were found in 2 patients with early-onset parkinsonism with dystonia (EOP-D) who developed dopa-responsive parkinsonism and dystonia at 6 and 8 years old, respectively. Neopterin levels in CSF were well preserved in 6 EOP-D patients. These data suggest that, among patients of different racial backgrounds, the pathogenesis of HPD/DRD, unlike EOP-D, involves partial reduction of the brain GTP-CH I activity consequent to mutations in the GTP-CH I gene. Measurement of CSF neopterin concentration may be useful for the differential diagnosis between HPD/DRD and EOP-D.

Adolescent↗
PubMed1996

Inhibition of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes by deprenyl.

Intracellular concentrations of cyclic nucleotides is regulated by cyclic nucleotide phosphodiesterases and calmodulin-dependent cyclic nucleotide phosphodiesterases (CaMPDE), one of the most intensively studied and best characterized phosphodiesterases. In the present study, the effect of an antiparkinsonian agent, deprenyl (selegeline hydrochloride) which is believed to be a selective inhibitor of monoamine oxidase-B, on bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) isozymes have been investigated. The findings indicated that deprenyl inhibited brain 60 kDa isozyme, however the inhibition for brain 63 kDa CaMPDE was observed to a lesser extent. The inhibition of brain 60 kDa CaMPDE was overcome by increasing the concentration of calmodulin suggesting that deprenyl may be calmodulin antagonist or act specifically and reversibly on the action of calmodulin. The 60 kDa CaMPDE isozyme is predominantly expressed in brain and its inhibition can result in increased intracellular levels of cAMP. The increased intracellular levels of cAMP have a protective role for dopaminergic neurons. Therefore, deprenyl may be a valuable tool to investigate the physiological roles of brain CaMPDE isozymes in progression of Parkinson's disease and gives a new insight into the action of this drug.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Amantadine treatment is an independent predictor of improved survival in Parkinson's disease.

Amantadine has been used for more than 20 years in the symptomatic treatment of Parkinson's disease (PD). Several recent discoveries suggest that amantadine could also have a neuroprotective effect in PD. We studied survival in all parkinsonism (including PD and other parkinsonian syndromes) patients attending a single clinic, employing standard survival curves and a Cox regression model, to identify independent predictive variables for survival (while taking into account factors potentially associated with both outcome and treatment selection). Amantadine-treated patients (n = 250) were similar to the patients not treated with amantadine (n = 586) in terms of age, gender, type of parkinsonism, Hoehn and Yahr stage and dementia status at initial neurological visit. Amantadine use was an independent predictor of improved survival (p < 0.01). Improved survival was also associated with a higher 10-year expected survival (based on age, gender, and birth year), absence of dementia, type of parkinsonism = PD, and low Hoehn and Yahr stage (I or II) at initial neurologic visit (all p < 0.01); these additional factors occurred in statistically similar proportions in the groups that were and were not treated with amantadine. The association of improved survival with amantadine use may stem from symptomatic benefit or may reflect a "neuroprotective" effect, mediated through N-methyl-D-aspartate (NMDA) receptor antagonism, dopamine uptake blockade activity, or other mechanisms. Our preliminary findings suggest that a prospective, controlled, randomized trial of amantadine's effects on PD progression is warranted.

Aged↗
PubMed1995

Prevalence of movement disorders in institutionalized elderly.

The proportion of the population over age 65 years is steadily increasing in Canada and the elderly who are unable to live independently are frequently institutionalized in chronic care facilities. We report our observations on movement disorders (MD) in an institutionalized elderly population of Saskatchewan. A representative sample of 67 subjects aged > or = 65 years had a detailed neurological evaluation on three separate occasions. MD were detected in 13 (19%) cases. The majority, 11 (16%), were females. Seven (10%) had essential tremor, 4 (6%) Parkinson's disease and 2 (3%) had drug-induced parkinsonism.

Aged↗
PubMed1994

Dopa-responsive dystonia: pathological and biochemical observations in a case.

We report the first neuropathological and neurochemical study of a patient with dopa-responsive dystonia. She had onset of foot dystonia at age 5 years and by age 8 years it was generalized with prominent right leg and arm involvement. On levodopa 750 mg daily she had complete symptomatic improvement that was sustained for 11 years until death. Pathological studies revealed normal numbers of hypopigmented substantia nigra neurons, normal tyrosine hydroxylase (TH) immunoreactivity and TH protein in the SN, no inclusion bodies or gliosis, and no evidence of a degenerative process in the striatum. Biochemical studies revealed reduced dopamine in the substantia nigra and striatum (8% in the putamen and 18% of control in the caudate) with a similar but not identical subregional distribution as in idiopathic Parkinson's disease. In the striatum, TH protein and TH activity was reduced, with the loss more pronounced in the putamen than the caudate. The GBR 12935 binding to DA transporter was normal in the caudate and at the lower end of the range of control values in the putamen. We conclude that disturbed dopamine synthetic capacity or a reduced arborization of striatal dopamine terminals may be the major disturbance in dopa-responsive dystonia.

Adult↗
PubMed1994

Pulmonary embolism: an under-recognized yet frequent cause of death in parkinsonism.

There are very few detailed reports on the cause of death in patients with Parkinson syndrome, and most reports lack postmortem verification. Pulmonary embolism has been reported as an infrequent terminal event. We reviewed the results of 60 complete autopsies performed on patients with Parkinson syndrome personally cared for at our institution. Pulmonary embolism was second only to pneumonia as the most common cause of death overall.

Adult↗
PubMed1994

Prevalence of movement disorders in elderly community residents.

We studied movement disorders (MD) in community residents of Saskatchewan aged > or = 65 years. A representative sample of 70 individuals had detailed neurological evaluation. Those who had definite and possible MD at first examination had a second neurological assessment by a senior neurologist. The most prevalent MD was essential tremor (ET) (14%) followed by Parkinson's disease (PD) (3%). The marked difference in prevalence ratios for PD and ET are attributed to: (a) higher incidence of ET in the general population; (b) a greater possibility that most, if not all, ET cases would reside in the community whereas a sizable proportion of elderly PD cases may be institutionalized, and (c) shortened survival in PD but a normal life expectancy in ET.

Aged↗
PubMed1993

Significance of parkinsonian manifestations in essential tremor.

Parkinsonian features, notably resting tremor may be seen in some essential tremor patients but the significance of those is unknown. The reported risk of parkinsonism in essential tremor patients varies from being unchanged to 35 times higher than expected. We studied 9 patients with essential tremor who had autopsies. In 6 of the 9 (66%) resting tremor was noted and in 3 (33%) cases fully developed parkinsonism was noted. The parkinsonism was consequent to neuroleptic usage in 2 and to basal ganglia status lacunaris and cribrosus in one case but no consistent abnormalities were noted in 3 essential tremor only and 3 essential tremor plus resting tremor cases. We conclude that resting tremor is an age-related natural evolution in some essential tremor patients. We recommend that the additional diagnosis of parkinsonism in the essential tremor be made only when resting tremor, bradykinesia and rigidity are all evident. The risk of ideopathic Parkinson's disease in essential tremor cases is similar to the general population.

Aged↗
PubMed1993

Prognostic significance of the onset mode in parkinsonism.

Early recognition of the prognosis in parkinsonism is important for both the management and studies aimed at preventing progression of disease. Less favorable prognosis is reported in early-onset postural instability and gait difficulty (PIGD) than in the tremor-onset cases, but the reasons for this are unknown. In 70 autopsy-verified cases, 11 (15.7%) had PIGD, and 34 (49%) had tremor onset. Improvement on levodopa was more common in the tremor-than the PIGD-onset cases (p < 0.05). The majority of tremor-onset cases had Lewy body disease, while the majority of PIGD-onset cases had other forms of pathology. Survival was shorter in the PIGD- than the tremor-onset cases (p < 0.05).

Adult↗
PubMed1993

Diagnosis of PD.

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Humans↗