Emerging perspectives in Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to A Lieberman.
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We compared the results of treatment with selegiline (deprenyl, Eldepryl) in 17 patients with advanced Stage 4 Parkinson Disease (PD) who were on levodopa (as Sinemet) with 65 Stage 2 or 3 patients with early PD who were also on levodopa. The first group consisted of 17 patients with advanced Stage 4 PD without response fluctuations ("wearing off" or "on off" phenomena). Their mean age was 72.1 +/- 7.5 years, their mean duration of PD was 7.4 +/- 3.2 years. The second group consisted of 65 patients with Stage 2 or 3 PD who had recently been started on levodopa. Their mean age was 63 +/- 12.1 years, their mean duration of PD was 7.4 +/- 3.2 years. The mean dose of selegiline was 10.0 +/- 1.8 mg per day (range 5-20 mg). The mean duration of treatment was 1.5 +/- 0.8 years. During the four years of observation 55.3 +/- 8.0% of the Stage 2 or 3 patients improved while only 14.3 +/- 13.5% of the Stage 4 patients improved. This difference was significant (p less than 0.05). During this time 22.0 +/- 6.7% of the Stage 2 or 3 patients worsened and 60.7 +/- of the Stage 4 patients worsened. This degree of worsening was significant (p less than 0.05). Adverse effects were minor and reversible. Our observations suggest that selegiline is more effective (higher percent of patients improving, lower percent of patients worsening) when it is added earlier with patients on levodopa than when it is added later.
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Chest pain is a frequent complaint requiring evaluation. The differential diagnosis is extensive and includes diseases of the respiratory, cardiac, gastrointestinal, neurologic, or musculoskeletal systems. This report describes an adolescent patient with chest pain secondary to spontaneous pneumomediastinum. The work-up and etiology is discussed.
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Sinemet-controlled release (CR4) consisting of 50 mg carbidopa/200 mg levodopa was compared with Sinemet 25/100 in 24 Parkinson's disease (PD) patients during a 16-week double-blind cross-over study. The mean age of the patients was 66.2 years, their mean duration of PD was 9.3 years. All of the patients had response fluctuations consisting mainly of the 'wearing-off' phenomenon. Some of the patients also experienced the 'on-off' phenomenon. All patients were evaluated using the unified Parkinson disease rating scale. The following significant differences were noted on Sinemet CR4. More patients noted a decrease in dyskinesias and response fluctuations; more patients experienced a decrease in stage when 'on'; more patients were 'on' longer during the day, and more patients were globally improved. The mean number of doses per day were significantly less on Sinemet CR4 (mean 5.0, range 3-8) than on Sinemet 25/100 (mean 6.2, range 4-11 doses/day). The mean dose of levodopa in Sinemet CR4 was 1,186 +/- 458 mg and the mean dose of carbidopa was 797 +/- 115 mg. The mean dose of levodopa in Sinemet 25/100 was 873 +/- 304 mg and the mean dose of carbidopa was 218 +/- 76 mg. This study indicates that Sinemet CR4 is a useful addition for patients with response fluctuations.
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The efficacy of cefaclor and of trimethoprim-sulfamethoxazole (TMP-SMX) in the management of recurrent otitis media was evaluated in a randomized single-blind controlled trial. The median age of the patients was 12 months (range 5-37); there were 37 boys and 19 girls. All had received 1 or more courses of antibacterials for acute otitis media in the previous 2-3 weeks. 27 were treated with oral cefaclor suspension, 40 mg/kg/day in 3 divided doses, and 29 with 1 mg/kg/day of TMP-SMX (trimethoprim 8 mg, sulfamethoxazole 40 mg) in 2 divided doses, each group for 10 days. 70% of the cefaclor group and 90% of the TMP-SMX group were cured after the 10 days of therapy (0.1 greater than p greater than 0.05). Results were not better on the 21st day as compared with the 10th. Our data indicate a mild preference for TMP-SMX (although p was not less than 0.05), since it needs to be given only twice a day and costs less than cefaclor.
With the advent of molecular biology techniques the prenatal diagnosis of many inherited diseases is now possible. In our Division of Transplantation Immunology we provide prenatal diagnosis for phenylketonuria (PKU), cystic fibrosis (CF) and congenital adrenal hyperplasia (CAH). In CF and PKU the chromosome carrying the disease gene is identified by the molecular probe, while in CAH it can also be determined by HLA phenotyping. Accurate diagnosis of a disease is dependent on the physical distance on the chromosome between the probe and the disease gene. Chorionic villous sampling allows evaluation of embryos at 9-10 weeks of gestation and also identification of carriers. DNA prepared from white blood cells of members of 4 families with CAH was digested with restriction endonucleases. Southern transfers were hybridized with the probe for 21-hydroxylase, and with 3 HLA probes mapped to both sides of the gene for 21-OH. In 2 families the embryo was found to be normal and in 2 diseased. Using the same techniques, but with probe and endonucleases specific for PKU, prenatal diagnosis was provided for 11 families with that condition. An embryo with PKU was found in each of 2 families, normal ones in 7, and in the remaining 2 families the testing was not informative. As of the present, 6 normal and 2 diseased children have been born, all as predicted. In 8 families with CF, DNA was examined with 5 probes mapped to both sides of the CF gene. Carriers and healthy sibs were identified, and in 1 family prenatal diagnosis was provided.
Flat affect is a major component of schizophrenia and is often also seen in neurological disorders. A preliminary set of comparisons were conducted to delineate neuropsychological mechanisms underlying flat affect in schizophrenia, and new measures are described for the assessment of affective deficits in clinical populations. Subjects were schizophrenic with flat affect (SZs), right brain-damaged (RBD), Parkinson's Disease (PDs), and normal control (NC) right-handed adults. Subjects were administered affective measures of expression and perception in both facial and vocal channels. For both perceptual and expressive tasks the SZs performed significantly less accurately than the NCs and the PDs but did not differ from the RBDs. This was the case for both face and voice. This finding lends support to the speculation that right hemisphere mechanisms, especially cortical ones, may be compromised among schizophrenics with flat affect.
Open autologous adrenal medullary to caudate nucleus transplantation was performed in 12 patients with advanced Parkinson's disease (PD). Ten of these patients had diurnal response fluctuations including "wearing off" and "on/off" phenomena. All of the patients were no longer satisfactorily responding to levodopa/carbidopa and dopamine agonists. The mean age of the patients was 55.1 years (range 37-65 yrs); mean duration of PD was 11.7 years (range 4-40 yrs); mean stage "on" was 3.3 (range 2-4); mean stage "off" was 4.8 (range 4-5). Mean duration of follow up from surgery was 10.4 months (range 2-17 months). Three patients improved dramatically with major changes in their lifestyle. The course of improvement in these 3 patients was different in each, implying that different mechanisms were responsible for the improvement. One of the patients died unexpectedly. In this patient, there were no surviving adrenal cells. Three patients improved moderately. Patients reported that they were "on" longer and had to take medication less often and were less dependent on individual doses of levodopa/carbidopa. The improvement has been sustained in two patients. However, in one of these patients there had to be frequent changes in scheduling to maintain the improvement. Two patients after technically successful implants did not improve. One of these patients subsequently died. In this patient there were a few surviving adrenal medullary cells. Four patients suffered major complications. One patient had a cerebral infarction and two had cerebral hemorrhages. One of these patients has shown a good recovery. One patient with autonomic insufficiency had a cardiac arrest with cerebral anoxia one week after surgery. This patient has shown a partial recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Right-hemisphere stroke rehabilitation inpatients were assessed by: (1) CT scans; (2) neurological exam; and (3) cognitive and affective psychometric measures. Damage to temporal, parietal, and occipital regions was associated with visual-spatial impairments. Surprisingly, parietal damage was no more related than temporal and occipital damage to severity of visual inattention. While the neurologist's ratings of lability and depression were related to CT-scan measures, patients' self-report of depression was not so related. These findings support a less specific and probably greater interlobule organization of the right, as compared with left, hemisphere, and highlight the need for multifaceted affective assessment in such a brain-damaged group.
MK 458 is a potent and selective D2 receptor agonist. MK 458 consists of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in a hydroxypropyl-methylcellulose-lactose matrix. MK 458, mean dose 8.1 mg (range 2.5 to 13.5 mg), was administered to 14 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The duration of the study was 4 weeks with a titration to maximum dose in 2 weeks. The addition of MK 458 resulted in a mean reduction in levodopa of 41% (range 0 to 81%). This degree of levodopa reduction was not seen in previous studies with other DA agonists. While the reduction in signs of PD was comparable to those on levodopa, MK 458 did not induce dyskinesias or dystonias. It is postulated that MK 458 may be able to replace levodopa as the primary treatment for PD.
Stimulation of rat astrocytes in vitro by calcium ionophore A23187 and/or lipopolysaccharide results in the generation of a cytotoxic factor that is functionally similar to the previously described macrophage-derived cytotoxic factor, tumor necrosis factor. Like the macrophage product, the astrocyte cytotoxic factor kills murine L 929 cell targets. In addition, it kills rat oligodendrocytes, the myelin-producing cells of the central nervous system. Human recombinant tumor necrosis factor also has cytotoxic activity directed against rat oligodendrocytes.
Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours "on" increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa.
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