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Biomedical subjects

F H McDowell

Publications and source records attributed to F H McDowell.

At least 19 recordsLinked to original sources
PubMed1994

Neurorehabilitation.

Explore the source record for details and available documents.

Cerebrovascular Disorders↗
PubMed1991

"Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson's disease.

We reviewed the histories of patients seen in a large Parkinson's disease clinic from 1983 to 1989 to determine if there is a relationship between the timing of initiation of levodopa therapy and the development of motor response fluctuations, dyskinesias, and dementia. There were no factors predisposing to the development of response fluctuations or dementia. Younger age at disease onset predisposed to the development of dyskinesia. Dyskinesias occurred in a greater proportion of patients in whom the initiation of levodopa therapy was delayed by more than 2 years from disease diagnosis than among those in whom treatment was started earlier. We thus failed to identify any adverse consequences of early levodopa treatment in our patient population.

Aged↗
PubMed1991

Activation of rehabilitation.

Following the demonstration that catecholamine levels in the cerebral hemispheres were considerably reduced with stroke, efforts were made to change this situation in experimental animals. It was found that the use of amphetamine (CAS 300-62-9) greatly enhanced the recovery time of animals following experimental stroke, and that agents which block the release or function of catecholamines in the central nervous system seem to delay recovery. These observations have been used to determine whether or not the same conditions exist for humans with stroke. To date in one study there is evidence that use of amphetamine early after a stroke may enhance the rehabilitation process. The rehabilitation process can be impaired by a number of situations, the most common of which is depression. It has been shown that treatment of depression for patients with stroke in rehabilitation may improve the outcome as well as the speed of outcome. Prognosis for patients with stroke who enter rehabilitation programs is related to the degree of central nervous system damage. Those patients with only motor dysfunction tend to do much better in programs than those who have in addition sensory or visual disturbances. Usually maximum improvement of function following stroke and rehabilitation care occurs in the first three months. Carefully planned rehabilitation programs for patients following stroke with realistic goals can greatly improve the patients' function and enable them to remain as independent as possible.

Animals↗
PubMed1990

Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR).

35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer "off" periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease.

Antiparkinson Agents↗
PubMed1990

An examination of male-female differences in progression and mortality of Parkinson's disease.

We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person-years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease.

Disability Evaluation↗
PubMed1989

The use of glutethimide for treatment of essential tremor.

Two patients with long-standing intention tremor that was interfering with their ability to maintain employment were treated with glutethimide. In both patients, this agent successfully suppressed tremor at doses of 1,000 mg and 4,000 mg per day. Glutethimide has been taken for as long as 14 years in one patient without evidence of side effects.

Functional Laterality↗
PubMed1989

A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance.

Fourteen Parkinsonian patients with fluctuations in therapeutic response to levodopa completed a double-blind, crossover trial of controlled-release levodopa/carbidopa (Sinemet CR4) vs standard Sinemet 25/100 (STD). Significant increases in mean interdose interval and per cent of the waking day spent "on", as well as reductions in the number of daily medication doses and number of "off" episodes were noted. In the double-blind part of the study, relative to open treatment with STD, ten patients rated themselves as improved while taking CR4, whereas only three considered themselves improved with STD. Difficulties using CR4 included an increased "lag-time" to the onset of antiparkinson effect, a tendency to produce increasingly severe dyskinesia late in the day, and a somewhat lessened predictability of motor response. Nonetheless, since the overall level of motor function through the day was equal to or better than that attained with STD, but with fewer medication administrations, Sinemet CR4 should prove a useful antiparkinsonian agent.

Carbidopa↗
PubMed1989

Effect of age at onset on progression and mortality in Parkinson's disease.

We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinson's disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.

Aging↗
PubMed1989

A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100).

Seventeen patients with advanced Parkinson's disease who had fluctuations in motor performance while taking standard Sinemet (STD) 25/100 underwent daylong pharmacokinetic and clinical observation studies while taking both STD and Sinemet CR, a new controlled-release formulation containing 50 mg carbidopa and 200 mg levodopa. During treatment with Sinemet CR, there was an increase in the interdose interval, a reduction in the number of medication doses taken each day, an increase in total "on" time, and a reduction in the number of "off" episodes. Total daily levodopa intake was greater with Sinemet CR, although the bioavailability of levodopa and carbidopa from the two preparations was equivalent. The variability in plasma levodopa levels was significantly less with Sinemet CR. The slower release of drug from Sinemet CR was reflected in a prolongation of the Tmax for levodopa and a prolongation of the interval from Tmax to the succeeding trough levodopa level. Clinically, peak antiparkinsonian effect occurred later and lasted longer with the CR preparation.

Antiparkinson Agents↗
PubMed1988

Clinical significance of the relationship between O-methyldopa levels and levodopa intake.

A recent clinical trial of controlled-release carbidopa/levodopa preparation afforded us the opportunity to examine the effects of chronically increasing circulating 3-O-methyldopa (OMD) levels on the clinical response to levodopa. In patients taking standard Sinemet, both mean plasma OMD levels and the area under the plasma concentration-versus-time curve (AUC) obtained during 8-hour periods of blood sampling correlated highly with the total daily intake of levodopa. In patients taking the controlled-release formulation, the mean daily intake of levodopa was doubled. This, in turn, led to a doubling of the mean OMD level and its AUC, whereas the AUC for levodopa was unchanged. Despite the increase in circulating OMD there was no reduction in mobility in either the "on" or "off" conditions. Thus, doubling plasma OMD levels did not seem to interfere with brain uptake of levodopa sufficiently to cause a deterioration in its therapeutic efficacy in these patients.

Animals↗
PubMed1988

Controlled-release levodopa/carbidopa. III: Sinemet CR5 treatment of response fluctuations in Parkinson's disease.

Five patients with advanced Parkinson's disease and fluctuations in therapeutic response to levodopa participated in, and four completed, an open label study of the efficacy of Sinemet CR5. Reductions in the number of daily doses and "off" periods as well as the increase in interdose interval and percent "on" time versus standard Sinemet were comparable to those achieved with Sinemet CR4 in these same patients. As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced. Sinemet CR5 appears to offer no advantages over Sinemet CR4 in the treatment of response fluctuations in Parkinson's disease.

Aged↗
PubMed1987

Multi-center study of Parkinson mortality with early versus later dopa treatment.

Four geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person-years of observation, Group 1 had an observed-to-expected mortality ratio of 1.43; Group 2, 2.44; and Group 3, 2.95 (p less than 0.05). This result confirmed that increased duration of disease was associated with increased mortality risk. To examine the effect of the time of initiation of dopa treatment, duration of disease was held constant at 17 years for all three groups. Observed-to-expected mortality ratios were 1.43 for Group 1; 2.66 for Group 2; 2.63 for Group 3. This statistically significant advantage for Group 1 (p less than 0.0001) led to the conclusion that early treatment with dopa has a beneficial effect on life expectancy. After 17 years of disease, causes of death in Group 1 were less likely (p = 0.027) to be due to Parkinson's disease than was found in the other groups.

Aged↗