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Biomedical subjects

W C Koller

Publications and source records attributed to W C Koller.

At least 127 records · Page 7Linked to original sources

Treating motor fluctuations with controlled-release levodopa preparations.

A major problem in the long-term treatment of Parkinson's disease with chronic, intermittent levodopa therapy is fluctuations in motor response. Both peripheral and central pharmacokinetic properties of levodopa are important in determining the duration of response. The "wearing-off" phenomenon or "end-of-dose" deterioration is related directly to the level of plasma levodopa. Therefore, a principal strategy for the treatment of motor fluctuations has been the attempt to prolong levodopa plasma levels with the use of long-acting, controlled-release levodopa preparations. This paper reviews the available data on the two compounds that are commercially available: benserazide-levodopa hydrodynamically balanced system (Madopar HBS) and controlled-release carbidopa-levodopa (Sinemet CR).

Delayed-Action Preparations↗

Interactive video conferencing: a means of providing interim care to Parkinson's disease patients.

Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC.

Aged↗

Is there a relationship between Parkinson's disease and essential tremor?

The issue of whether there is a relationship between essential tremor (ET) and Parkinson's disease (PD) is controversial partly due to the confusion regarding the accurate diagnosis of these conditions. The presence of postural tremor, which often occurs in PD, by itself is insufficient for the diagnosis of ET. Most epidemiological studies have shown that there is no association between these two conditions. Some studies, but not others have found a higher prevalence of tremor in family members of PD patients. Clinical, positron emission tomography scan, and neuropathological data have failed to show any relationship between these two conditions. It is concluded that there is no relationship between ET and PD and that when these two conditions are seen in the same patient, this represents a chance occurrence of two common diseases.

Humans↗

Effects of selegiline dosing on motor fluctuations in Parkinson's disease.

To examine selegiline's dosing effects, we studied 16 Parkinson disease patients with motor fluctuations in a double-blind, crossover trial of selegiline at 0, 5, and 10 mg daily. Patients' motor diaries, disability scores, and walking speed were marginally improved, with no advantage of 10 mg over 5 mg found. We conclude that in patients with motor fluctuations, selegiline provides modest symptomatic effects, with daily dosing of 5 mg being indistinguishable from 10 mg.

Aged↗

Personality and depression in Parkinson's disease.

The Parkinson's disease (PD) patient has been characterized as having a distinctive personality with introverted features. These personality traits are said to predate motor symptoms and are theorized to serve as a subtle clue to latent PD. To examine this hypothesis, we compared remote and current personality features in 35 PD subjects and 35 controls. Subjects' spouses completed a personality inventory (PI) characterizing patients' premorbid and current status. The premorbid PI of PD subjects differed from that of controls in being more "quiet," "generous," "cautious," and "even-tempered," and less "flexible." The characterization of the PD subjects' current personality differed greatly from reported premorbid personality features, i.e., significant change in 13 of 24 PI items. Personality inventory responses regarding both the PD subjects' premorbid and current personality correlated to symptoms of depression and disease severity. Cognition, tobacco use, alcohol consumption, and rural versus urban residency did not correlate with PI responses. We conclude that PD patients are apt to be viewed as introverts premorbidly, and, with disease onset, more striking personality changes are recognized. These perceptions appear to be closely linked to depressed affect and correlate with motor impairment to a lesser extent.

Alcohol Drinking↗

Essential tremor and dystonia.

We reviewed the database of the Dystonia Clinic at the University of Kansas Medical Center for patients with dystonia and tremor. Of 296 patients with idiopathic dystonia, 24 had dystonic tremor, 20 with cervical dystonia had an isolated head-nodding tremor, two patients with writer's cramp had ipsilateral hand tremor, and two patients with generalized dystonia had arm tremor. Eight patients, all with cervical dystonia, had essential tremor that preceded the onset of their dystonia.

Dystonia↗

Clinical experience with controlled-release carbidopa/levodopa in Parkinson's disease.

We converted 158 Parkinson's disease (PD) patients on stable doses of standard carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%) preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients elected to continue L-CR, and we performed the primary data analysis on this group. Following conversion to L-CR, patients reported an increase in length of benefit from each dose and an increased "kick-in" time. There was a decrease in the total number of doses, "off" periods, sleep interruptions per night, dose failures, and sleep disturbances. Conversion to L-CR resulted in a significant increase in total levodopa dose. There was no significant change in the dyskinesias. However, early-morning dystonia resolved in eight of 14 patients. Our findings suggest that L-CR is particularly effective in decreasing motor fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures in PD.

Adult↗

Identical twins with similar onset of Parkinson's disease: a case report.

The role of heredity in Parkinson's disease (PD) is controversial. We report a pair of monozygotic twins (confirmed by DNA fingerprints) concordant for PD. Their disease began when they were 62 and 63 years old. Both patients presented with left-side bradykinesia. One of the twins had a long history of depression. Both patients had typical manifestations of PD, which were responsive to dopaminergic therapy. The similar age of onset along with the similar clinical characteristics of these twins suggests that hereditary or genetic susceptibility may be important in the etiology of PD.

Diseases in Twins↗

Risk factors for Parkinson's disease.

Parkinson's disease (PD) has been associated with rural living, well-water consumption, and pesticide exposure; however, the individual risk contribution of these variables has not been established. We examined social and medical histories of predominantly rural populations to determine relative risk factors for PD. Patients and controls were surveyed regarding residency, occupation, medical history, and social and dietary habits. An initial multiple logistic regression model was confounded by excessive variable colinearity. Principal factor analysis yielded three factors: rural living (including years of rural residency and ground-water use), pesticide use, and male lifestyle (male gender, head trauma, male-dominated occupations). Other variables did not load in factor analysis and were entered separately, with the three factor scores, in a second multiple logistic regression model. Significant predictors of PD emerged (in order of strength): pesticide use, family history of neurologic disease, and history of depression. The predicted probability of PD was 92.3% (odds ratio = 12.0) with all three predictors positive. Pesticide use (distinguishable from rural living) can be considered a risk factor for the development of PD, with family history of neurologic disease and history of depression serving as weaker predictors of PD.

Adult↗

Hemiballism and tremor due to ependymal cyst.

A 21-year-old woman was admitted with right hemiballism and tremor. She had tremor since the age of 6 years. At age 12, an intracerebral, left paraventricular space-occupying lesion was found and treated with 4,500 rads. Increasing tremor was associated with mass enlargement. By age 20, there was insidious presentation of right hemiballism. At age 21, she had craniotomy and a large septate cyst was opened and drained. Biopsy of the cyst wall revealed that it was consistent with ependymal cyst. Postoperatively the hemiballism resolved and the tremor improved. This case is unusual due to the presentation of hemiballism caused by ependymal cyst.

Adult↗

Classification of essential tremor.

Classification of essential tremor was attempted using tremor frequency; tremor duration; family history of tremor; responsiveness to alcohol, propranolol, and primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one patients were evaluated. The majority of patients had a tremor frequency less than 7.0 Hz, a positive family history, and a positive response to alcohol. Approximately 46% of patients had a beneficial response with propranolol and 71% with primidone. Tremor frequency was inversely correlated with age and directly correlated with an antagonist pattern of muscle contraction. Enhanced long-latency reflexes were not found. Other characteristics of essential tremor were not significantly correlated. It is concluded that essential tremor can not be classified into subtypes.

Aged↗

Olfactory function in essential tremor.

Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD.

Female↗

Metabolism of glucurolactone to glucarate in Parkinson's disease.

The metabolism of oral glucurolactone to serum D-glucarate by the hepatic cytochrome P450 enzyme system was no different in 20 untreated Parkinson's disease (PD) patients as compared with 20 age- and sex-matched controls. There was no evidence for a deficit in hepatic enzymes in PD.

Administration, Oral↗

Initiating treatment of Parkinson's disease.

Treatment of Parkinson's disease (PD) can be divided into two categories: symptomatic therapy (restoring dopamine levels toward normal and reversing functional disability) and preventive therapy (interfering with the pathophysiologic mechanism of PD to prevent or decrease the rate of progression of the disease). Regarding symptomatic treatment, although anticholinergic preparations generally are considered effective for the symptoms of tremor and rigidity without altering bradykinesia, their effectiveness is limited and adverse reactions are common; their role should be restricted to use as adjuvants to levodopa therapy. Amantadine has been shown to be as effective as anticholinergics, but it lacks long-term efficacy. Dopamine agonists--bromocriptine, pergolide mesylate and lisuride in Europe--are not as effective as levodopa and therefore rarely are used as initial therapy; their proposed role, too, is as adjuvants to levodopa therapy. Levodopa is the most effective drug presently available for the treatment of PD; its introduction is accompanied by rapid and dramatic reduction of symptoms and signs. Initial adverse reactions are not usually a major problem; and although there is speculation that initiation of therapy should be delayed because of possible long-term complications, clinically distinguishing these from problems related to disease progression itself is difficult. The possibility that nigral cell death is mediated by oxidative mechanisms provides the basis for considering antioxidant therapy as protective treatment; selegiline, an antioxidant, has been found to delay the need for symptomatic therapy. It is suggested that initial treatment of Parkinson's disease begin with both preventive therapy with selegiline and symptomatic treatment with the sustained-release preparation of levodopa, which may be associated with fewer long-term complications.

Amantadine↗

When does Parkinson's disease begin?

A long preclinical or asymptomatic period may occur in Parkinson's disease (PD). Many long-latency parkinsonian syndromes exist. The presence of early-life risk factors is consistent with a long prodromal period. Marked degeneration of the substantia nigra and loss of striatal dopamine are necessary before clinical symptoms develop. Lewy bodies, the histological hallmark of PD, occur in 10% of normal individuals over age 50. Clinical symptoms develop slowly and are often intermittent in early PD. Nonmotor signs, eg, depression or sensory changes, often precede motor signs by many years. Reduction of striatal dopamine can be detected with PET in "at-risk" asymptomatic individuals. Individual sensitivity to drug-induced parkinsonism also suggests a preclinical state. Biologic markers may eventually be able to detect preclinical PD.

Aging↗

How accurately can Parkinson's disease be diagnosed?

The clinical picture of Parkinson's disease (PD) can be so varied that absolute clinical diagnosis may not always be possible. Several diverse entities (including toxins, pharmacologic agents, and multisystem atrophies and other degenerative diseases) can produce clinical syndromes almost indistinguishable from those of PD. Nevertheless, a sufficient number of guiding criteria--such as the presence of at least two of three motor signs (tremor, bradykinesia, and rigidity), persistence of these signs for several years, and responsiveness to levodopa--may serve to clarify and specify diagnosis, at least until such time as a biologic marker of PD is discovered. However, currently the clinical diagnosis of PD remains difficult.

Atrophy↗