PubMed Health⌕ Search

Biomedical subjects

C H Adler

Publications and source records attributed to C H Adler.

At least 19 recordsLinked to original sources
PubMed2006

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia.

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.

Botulinum Toxins↗
PubMed2005

Is the functional decline of Parkinson's disease similar to the functional decline of Alzheimer's disease?

Since many Parkinson's disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE (rho=-0.814, P<0.001; rho=-0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE (rho=-0.675, P<0.001; rho=-0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD.

Activities of Daily Living↗
PubMed2004

Ropinirole for restless legs syndrome: a placebo-controlled crossover trial.

The authors performed a double-blind, placebo-controlled, crossover study of ropinirole (0.5 to 6.0 mg/day) for restless legs syndrome (RLS). The RLS Rating Scale score improved (p < 0.001) from a mean (SD) of 25 (7) during placebo treatment to 13 (12) during ropinirole treatment. Eight of the 22 patients had complete resolution of symptoms on ropinirole. Adverse events included nausea and dizziness. Ropinirole was effective and well tolerated for treating the symptoms of RLS.

Adult↗
PubMed2003

Parkinson's disease patients undershoot target size in handwriting and similar tasks.

OBJECTIVES: Previous research suggested that people with Parkinson's disease are able to increase handwriting stroke size up to 1.5 cm without an increase of stroke duration; whereas age matched individuals in normal health are able to modulate stroke size without changes in stroke duration for sizes up to 2 cm. This study was designed to test this finding by examining whether sizes larger than 1.5 cm show different relationships with stroke duration for patients with Parkinson's disease as compared with age matched controls. METHODS: The study included 13 subjects with Parkinson's disease and 13 age matched controls. Participants were required to write a cursive "llllllll" pattern, or a cursive "lililili" pattern without the dots, at a comfortable speed and also as fast as possible, in five different sizes (1.0, 1.5, 2.0, 3.0, and 5.0 cm). The participants wrote with a ballpoint pen on a digitiser tablet. The target pattern was displayed at its required size on a screen, but disappeared as soon as the pen touched the surface of the digitiser tablet. Online visual monitoring of the hand was prevented by a cover over the digitiser. After each trial, the recorded movement of the tip of the pen was displayed with two lines to indicate whether the size requirement had been met. The writing conditions were presented in random order and consisted of 12 trials for each participant. RESULTS: The results demonstrated that stroke size and duration produced by the participants with Parkinson's disease were independently modulated up to 1.5 cm; sizes over 1.5 cm resulted in progressive undershooting by patients with Parkinson's disease (PD). It was also shown that these participants modulated acceleration measures inefficiently as compared with controls. CONCLUSIONS: The findings suggest that individuals with Parkinson's disease writing at speed produce inadequate stroke sizes when these should equal or exceed 1.5 cm.

Aged↗
PubMed2002

Loss of response to levodopa in Parkinson's disease and co-occurrence with dementia: role of D3 and not D2 receptors.

Previous data suggest a relationship between the loss of response to levodopa in Parkinson's disease (PD) patients with the co-occurrence of dementia, but the role of alterations in the dopamine system has not been explored. We measured the extent of striatal DA loss and changes in striatal DA D(2) and D(3) receptors in postmortem striatum of PD patients who historically had or had not lost their clinical response to dopaminergic drugs and/or had an additional diagnosis of dementia. Clinical evaluation and retrospective chart reviews for PD and dementia, and neuropathological diagnoses were obtained. All PD cases (+/-dementia), regardless of response to dopaminergic drugs, exhibited a significant and similar degree and pattern of loss of tyrosine hydroxylase immunocytochemistry and DA transporter binding in striatum, and loss of tyrosine hydroxylase-immunoreactive neurons and brain-derived neurotrophic-immunoreactive neurons from the ventral midbrain. D(2) receptor concentrations were modestly elevated in the rostral striatum of all the PD cases (+/-dementia), whether or not they continued to respond to dopaminergic drugs. In contrast, loss of D(3) receptor concentration correlated with loss of response to dopaminergic drugs, independent of the presence or absence of dementia. A maintained response to dopaminergic drugs correlated with an elevation of D(3) receptors. Dementia with PD was highly correlated with a loss of response to dopaminergic drugs, and was also correlated with reduced D(3) receptors. The alterations in D(3) receptor concentrations were greatest in the nucleus accumbens, caudal striatum, and globus pallidus. Thus, loss of dopamine D(3) receptors may be a more important contributing factor to a loss of response to dopaminergic drugs than changes in the D(2) receptor.

Aged↗
PubMed2002

Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics.

The authors studied the pharmacokinetics of levodopa (LD) with and without pramipexole (PPX) in men and postmenopausal women with PD. Patients on stable dose of carbidopa/LD were randomized to receive escalating doses of placebo or PPX over 7 weeks. LD and PPX pharmacokinetics were performed after a single test dose 25/100 of carbidopa/LD, before initiation of PPX or placebo, at 1.5 mg/d and 4.5 mg/d of PPX or placebo. Compared to men, women had greater LD bioavailability. PPX did not alter LD bioavailability, and PPX pharmacokinetics were equivalent in men and women.

Aged↗
PubMed2002

Motor unit number estimates in idiopathic Parkinson's disease.

We previously reported changes in motor unit morphology in patients with Parkinson's disease (PD) using subjective and computerized quantitative electromyography. Now, we present data on motor unit number estimates (MUNE) to address the hypothesis of motor neuron dropout in PD. Twenty patients with PD and 20 age-matched control subjects were screened by clinical criteria and nerve conduction studies to exclude those with neuropathy. Motor unit number estimates in the extensor digitorum brevis and hypothenar group were assessed by three different MUNE techniques. The MUNE technique types included (1) the statistical method developed by Daube, (2) a threshold method, and (3) an F-wave method. The overall multivariate comparison for the six MUNE measurements was significantly lower for the patients than the controls (P=0.02). The only significant difference in the individual measures was found in the threshold MUNE method of the hypothenar group (P<0.05). These results are consistent with those of our previous work, and both support the hypothesis that mild motor neuron dropout occurs in idiopathic PD. However, MUNE methods characteristically have large standard deviations which make it difficult to detect small changes. Progress in decreasing the variance of MUNEs will facilitate their use in detecting small motor unit number changes in neurodegenerative disease.

Aged↗
PubMed2002

Dosing with ropinirole in a clinical setting.

OBJECTIVES: To determine the optimal dose of ropinirole (ReQuip) for treatment of early Parkinson's disease (PD). MATERIALS AND METHODS: Six-month data were gathered from three trials of monotherapy in patients with PD. RESULTS: Seventy-five percent of patients who experienced a therapeutic response did so at <or= 7.5 mg/day. Patients whose dose was increased by more than four titration levels from weeks 4-24 (mean total increase 14.8 mg/day) tended to show greater improvements than those whose dose increase was smaller (mean increase 3.4 mg/day) (17.4% vs 10.8%, respectively). Mean doses continued to increase throughout the 3- and 5-year trials (3-year trial at endpoint, 10.4 mg/day; 5-year trial at 3 years and at endpoint, 14.1 and 14.9 mg/day, respectively). CONCLUSION: Although a therapeutic response may be expected at <or= 7.5 mg/day, these data suggest a benefit for continued dose titration in most patients with early PD. For some patients, the maximum recommended dose (24 mg/day) may be necessary.

Adult↗
PubMed2002

Adaptation of handwriting size under distorted visual feedback in patients with Parkinson's disease and elderly and young controls.

OBJECTIVE: The ability to use visual feedback to control handwriting size was compared in patients with Parkinson's disease (PD), elderly people, and young adults to better understand factors playing a part in parkinsonian micrographia. METHODS: The participants wrote sequences of eight cursive l loops with visual target sizes of 0.5 and 2 cm on a flat panel display digitiser which both recorded and displayed the pen movements. In the pre-exposure and postexposure conditions, the display digitiser showed the actual pen trace in real time and real size. In the distortion exposure conditions, the gain of the vertical dimension of the visual feedback was either reduced to 70% or enlarged to 140%. RESULTS: The young controls showed a gradual visuomotor adaptation that compensated for the visual feedback distortions during the exposure conditions. They also showed significant after effects during the postexposure conditions. The elderly controls marginally corrected for the size distortions and showed small after effects. The patients with PD, however, showed no trial by trial adaptations or after effects but instead, a progressive amplification of the distortion effect in each individual trial. CONCLUSION: The young controls used visual feedback to update their visuomotor map. The elderly controls seemed to make little use of visual feedback. The patients with Parkinson's disease rely on the visual feedback of previous or of ongoing strokes to programme subsequent strokes. This recursive feedback may play a part in the progressive reductions in handwriting size found in parkinsonian micrographia.

Aged↗
PubMed2001

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor.

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.

Aged↗
PubMed2001

Serum leptin concentrations and satiety in Parkinson's disease patients with and without weight loss.

We compared serum leptin and satiety measures in 18 Parkinson's disease (PD) patients with unintended weight loss (WL) and 18 PD patients whose weight was stable (WS). Mean serum leptin concentrations tended to be lower in WL than WS patients, but this did not reach statistical significance. Body mass index correlated with serum leptin concentrations. Ratings of hunger, satiety, fullness, and thirst did not differ between groups. However, the mean sensation of fullness before meals correlated with serum leptin in the entire cohort of patients, particularly in the WL group. The results indicate that unintended weight loss in PD patients is unlikely to be due to abnormal serum leptin concentrations.

Aged↗
PubMed2000

Electrophysiological observations in hereditary parkinsonism-dementia with Lewy body pathology.

We studied the only two living affected individuals who are part of a previously reported kindred that expresses a hereditary parkinsonism-dementia syndrome with Lewy body pathology. The electrophysiological characteristics of the hyperkinetic movement disorders in these patients were examined to provide physiological insights into the clinical phenotype of this syndrome. Evaluation of both patients showed 7-9 Hz electromyographic discharges in upper extremity muscles during postural activation, and one patient showed a 4-5 Hz discharge pattern correlating to a rest tremor. Brief (<50 ms) myoclonic electromyographic discharges were seen in both patients, and a time-locked relationship to a focal cortical premovement electroencephalographic potential was elicited in one patient. Somatosensory evoked potentials were not enlarged and long latency reflexes were not enhanced. Electroencephalography was normal in one patient but showed pathologic slow frequencies in the other. The electrophysiological findings show evolution which correlates with an apparent characteristic evolution of hyperkinetic movement disorders that accompanies the severe progression of parkinsonism-dementia in this kindred. These results have implications for the future study of this and similar syndromes.

Adult↗
PubMed2000

Motor unit changes in sporadic idiopathic Parkinson's disease.

We studied motor unit changes in 20 patients with Parkinson's disease (PD) and 20 age-matched control subjects to look for evidence of motorneuron degeneration in sporadic idiopathic PD. Patients and control subjects were screened by clinical criteria and nerve conduction studies to exclude those with peripheral neuropathic processes. Changes in motor unit morphology were investigated with subjective and computerized quantitative electromyography (QEMG) of the anterior tibialis (AT) and first dorsal interosseous. Multivariate comparisons showed a significant difference in the QEMG analysis for motor unit enlargement in patients with PD versus control subjects. Some of the univariate comparisons for both the subjective and QEMG analyses of the AT were also significant. These results demonstrate that motorneuron drop-out with reinnervation occurs in sporadic idiopathic PD. In summary, our findings provide evidence that clinically silent motorneuron disease occurs in typical cases of sporadic idiopathic PD, suggesting that it may be a normal part of the pathologic picture of PD. Any hypothesis concerning the pathogenic mechanism of PD would need to take into account such a finding.

Aged↗
PubMed2000

Amantadine is beneficial in restless legs syndrome.

Twenty-one patients (mean age 70 yrs) with restless legs syndrome (RLS) were treated with amantadine in an open-label trial. Amantadine was started at 100 mg per day and was increased every 3-5 days by 100 mg (up to a maximum of 300 mg per day) until significant relief of symptoms or intolerable side effects were experienced. Patients were rated pre- and posttreatment using an RLS rating scale (0-10). Each patient also rated the degree of response in a continuous scale from 0% (no improvement) to 100% (complete improvement). Eleven of 21 (52%) had subjective benefit to amantadine, with degree of response ranging from 25%-100% (mean 69%) among responders. Six had 95%-100% improvement. The RLS score for all 21 patients dropped from a mean (+/- standard deviation) of 9.8 +/- 0.6 (range, 8-10) pretreatment to 6.6 +/- 3.8 (range, 0-10) posttreatment (p = 0.001). The duration of response was 0-13 months (mean, 3.6 +/- 4.5), with nine responders still remaining on the drug as of last follow up. The mean effective dose was 227 mg per day. The most common side effects were drowsiness (3), fatigue (2), and insomnia (2); only two stopped amantadine because of side effects. We conclude that amantadine is an effective and well-tolerated drug for RLS.

Aged↗
PubMed2000

Disruptions in the reach-to-grasp actions of Parkinson's patients.

Previous research has shown that Parkinson's-disease (PD) patients produce irregular movement paths during a rapid arm pointing task. The aim of this study was to investigate the movement paths of PD patients during a prehensile action to objects requiring different levels of precision. Thus, we sought to determine if movement-accuracy requirements affect the control of movement path. Thirteen PD patients and 13 age-matched controls served as participants. In addition to having prolonged movement times, PD patients showed differences in the kinematic patterns of the transport and grasp components. For the transport component, relative time to maximum deceleration and relative time to maximum elbow velocity occurred earlier for the PD patients than the controls. Analyses of wrist paths indicated that, when accuracy requirements were increased, patients produced paths that appeared more segmented than controls. For PD patients, reaches to a small object resulted in wrist paths that were significantly less smooth, as reflected by higher jerk values, and were less continuous, as indicated by larger standard deviations in curvature. A temporal analysis of movement-initiation patterns in the vertical and horizontal planes indicated that control participants had a minimal offset between initial movement in the vertical plane and initial movement in the horizontal plane regardless of accuracy constraints. However, PD patients had a significantly longer interval between initial movement in the vertical plane and subsequent movement in the horizontal plane when reaching to the small object. Higher accuracy constraints also resulted in PD patients achieving relative time to maximum elbow velocity significantly earlier than controls. For the grasp component, PD patients produced movement patterns in which the amplitude of and relative time to maximum aperture were less sensitive to object size. In addition, patients exhibited greater variability in the time to maximum aperture. Additional analyses of the grasp component indicated that control participants exhibited a stable position, relative to object location, in which aperture began to close. Conversely, PD patients showed little consistency in where aperture began to close with respect to object location. Irregularities in the transport component suggest that PD patients have a reduced capability to precisely coordinate joint segments, particularly under high accuracy requirements. Variability in where aperture began to close and disruptions in transport-grasp coordination suggests that the basal-ganglia dysfunction, as exhibited in PD, affects the specification of these movement parameters used to produce a consistent pattern of coordination between prehensile components.

Adult↗