Albert Goodgold

Bromocriptine in Parkinson disease Further studies

Bronnocriptine was administered to 66 patients with advanced Parkinson disease (PD) and increasing disability despite optimal treatment with levodopakarbidopa (Sinemet®). Forty-five patients tolerated at least 25 mg per day of bromocriptine (the “adequately treated” group) in addition to Sinemet and had significantly decreased rigidity, tremor, bradykinesia, gait disturbance, and total score, but increased involuntary movements. Twenty-five of these 45 patients improved by at least one stage. Among the 45 patients, 27 had “on-off” effects, and in 19 the “on-off” effects decreased on bromocriptine. The mean dose ofbromocriptine in adequately treated patients was 47 mg, permitting a 10 percent reduction in the dose of levodopa. Twelve adequately treated patients received bromocriptine for at least 1 year, and 8 continued for longer than this. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). All adverse effects were reversible. Despite adverse effects, expense, and scarcity, bromocriptine, when added to levodopa, is useful in patients with advanced disease who no longer respond satisfactorily to levodopa, and for whom no other treatment is available.

Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease

A double-blind study comparing the effects of carbidopa and levodopa combined in a single tablet with levodopa alone was undertaken in 50 patients with Parkinsons disease. After 6 months, there was a statistically significant improvement over baseline in total score, rigidity, and tremor only in the patients randomized to carbidopa/levodopa. In addition, 40 percent of the patients treated with carbidopa/levodopa showed obvious clinical improvement (a greater than 50 percent reduction in their total score) over treatment with levodopa alone. However, after 2 years, only 20 percent continued to show this improvement. Nausea, vomiting, and anorexia developed in 56 percent of patients on levodopa but in only 27 percent of patients on carbidopa/levodopa. However, abnormal involuntary movements, observed in 48 percent of patients on levodopa, were present in 77 percent of patients on carbidopa/levodopa. Despite the increase in abnormal involuntary movements, carbidopa/levodopa is more effective than levodopa.

Treatment failures with levodopa in parkinsonism

Since the initial reports establishing the efficacy of levodopa in the management of Parkinson’s disease and sufficiently large numbers of patients have been treated to permit certain observations as to the type and degree of response that may be expected with levodopa in any series of patients. I t has been found, for example, that approximately 10 to 30 percent of patients treated with levodopa show little or no beneficial response to the drug and that during the course of therapy 30 to 50 percent of patients will develop mental changes, abnormal involuntary movements, and cardiovascular and other side effects limiting the rap^.^ ,5 This report evaluates patients showing little or no response to levodopa therapy and of a representative number of patients who initially responded but developed side effects necessitating dosage reduction or drug discontinuance. In addition, two of these patients underwent special studies to determine the metabolic fate of C1 -dopa. These studies were compared with those of four patients who showed a satisfactory response to levodopa and with one patient with amyotrophic lateral sclerosis who, during treatment with levodopa, developed adventitious movements but did not improve clinically.

Lergotrile in Parkinson disease Further studies

Lergotrile was administered to 53 patients with advanced Parkinson disease (PD), who had increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet®). Thirty-nine patients who could tolerate at least 20 mg per day lergotrile (thus considered “adequately treated”) had significant decreases in rigidity, tremor, bradykinesia, gait disturbance, and total score without increased involuntary movements. Twenty-one of these 39 patients improved by at least one stage. Among the 39 patients, 23 had “on-off” effects, and in 13 of these the “on-off” effects decreased on lergotrile. The mean daily dose of lergotrile in adequately treated patients was 49 mg, permitting a 10 percent reduction in the dose of levodopa. Lergotrile was discontinued in 33 of the 53 patients because of adverse effects, including hepatotoxicity (11 patients), mental changes (12 patients) and orthostatic hypotension (8 patients). Although lergotrile, when added to levodopa, has a definite antiparkinsonian effect, the incidence of adverse effects, particularly hepatotoxicity, makes it unlikely that this ergot alkaloid will become widely available for the treatment of PD. Analogues of lergotrile have been synthesized, and it is hoped that they will duplicate the antiparkinsonian effect of this drug without its toxicity.

Computer processing of narrative medical data: A critical evaluation of results in 100 cases of head injuries

UTILIZATION OF COMPUTERS for storage, analysis, and retrieval of narrative medical data has far-reaching implications for clinical research and medical record keeping. We have directed our attention toward two problems in this area: first, collecting and storing narrative data in computer-acceptable form with minimal effort on the part of the physician, and second, computer search, analysis and retrieval of specific items from narrative clinical data. Critical evaluation of the advantages and limitations of presently available techniques will determine the direction of future developments. A solution to the first problem, that of a physician introducing narrative and numerical data in computeracceptable form, is described elsewhere.1-4 This account deals with quantitative analysis of the effectiveness of retrieval of narrative data from clinical research protocols which have been stored on magnetic tape. We have undertaken to compare the results of analysis of 100 narrative documents on patients with head injury admitted to the Neurology Services of New York University, Bellevue Medical Center.5 Comparison of techniques includes determination of the incidence of various diagnostic categories, enumeration of certain clinical findings, and tabulation of abnormal laboratory test rewlts. Three techniques of analysis were evaluated utilizing: [A] a relatively large computer system, [B] a small computer system, and [C] a visual survey by physicians recorded with “pencil and paper.” Results to date suggest that the computer techniques developed thus far give unmistakable promise for significant advance in storing, analyzing, and re-