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Biomedical subjects

A Lieberman

Publications and source records attributed to A Lieberman.

At least 19 recordsLinked to original sources
PubMed1992

An integrated approach to patient management in Parkinson's disease.

New concepts about the pathogenesis and pathophysiology of Parkinson's disease have emerged. For these concepts to be useful, they must be understood, and for them to be applied, the psychology of the patient and the patient's family must be understood. The initial consultation is crucial in establishing a successful relationship between a patient, family, and physician. This consultation is analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is placed on imaginitive questioning using the format of the ADL portion of the UPDRS in establishing the diagnosis and following treatment. The rational for starting treatment with selegiline at this time is discussed in the context of the role that increased MAO-B activity plays in the progression of Parkinson's disease. After making the diagnosis and starting treatment with selegiline, deciding when to start levodopa is the next crucial decision. Often as important as deciding when to start levodopa is overcoming the resistance of the patient to accept this treatment. The next crucial decision occurs after the patient develops response fluctuations on levodopa. A format for assessing the fluctuations is presented, and the merits of different treatments, including selegiline, dopamine agonists (bromocriptine and pergolide), and sustained-release or controlled-release levodopa preparations (Sinemet CR), discussed. The management of patients with depression, sleep problems, and advanced disease including postural instability and mental changes are reviewed.

Activities of Daily Living↗
PubMed1992

Dopamine agonists used as monotherapy in de novo PD patients: comparisons with selegiline.

Studies indicate that selegiline, a monoamine oxidase type B inhibitor, slows progression of Parkinson's disease (PD) and delays the need for levodopa. While dopamine agonists also delay the need for levodopa because of their symptomatic, antiparkinsonian effect, only recently has it been proposed that agonists may also have a protective effect. When dopamine agonists are used as monotherapy in newly diagnosed PD patients, fewer patients improve than on levodopa, but fewer patients develop response fluctuations. This might indicate that dopamine agonists have a protective, as well as a symptomatic, effect, as the lack of response fluctuations may indicate that dopamine agonists protect nigral neurons. Response fluctuations may result from destruction of nigral neurons.

Bromocriptine↗
PubMed1992

The role of the regulatory enzymes of catecholamine synthesis in Parkinson's disease.

The major neuropathology of Parkinson's disease (PD) is the degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa. The symptomatic treatment of PD consists of replenishing DA by administering L-dopa, which is enzymatically converted to DA in the striatum. The increase of TH activity by modification of the enzyme leads to an increased synthesis of striatal L-dopa, and thereby replenishes the missing DA more efficiently. The activity of TH is increased by protein kinase-dependent phosphorylation of the enzyme or by inhibition of dephosphorylation with specific phosphatase inhibitors. Thus, modification of TH results in an activated form of the enzyme, which might provide a basis for developing new strategies in the treatment of PD. The extraneuronal enzyme, catechol-O-methyl transferase (COMT), inactivates catecholamines by O-methylation, and its inhibition leads to increased levels of striatal DA. The availability of selective and nontoxic COMT inhibitors makes it possible to assess their therapeutic role in treatment of PD. The intraneuronal enzymes, monoamine oxidase (MAO)-A and MAO-B, inactivate catecholamines and other biogenic amines, such as serotonin, by deamination. Inhibition of these enzyme activities leads to increased levels of striatal DA. The irreversible MAO-B inhibitor selegiline was shown to exert antiparkinsonian activity, especially in the early stages of parkinsonism. Selegiline also prevents the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in MPTP-treated mice and monkeys. Its role in the prevention of the disease is under investigation in several clinical centers.

Catechol O-Methyltransferase↗
PubMed1992

Long-term experience with selegiline and levodopa in Parkinson's disease.

Between 1982 and 1989, 197 patients with Parkinson's disease were treated with selegiline and levodopa for at least 0.3 years. Two groups of patients were included: a group of 65 patients (stage 2 or 3 on the Hoehn and Yahr Scale) who recently had been started on levodopa and were not experiencing response fluctuations, and a group of 132 patients on levodopa who were experiencing fluctuations. More nonfluctuating than fluctuating patients improved, although the differences were not significant; a higher percentage of fluctuating patients worsened, compared with nonfluctuating patients, and these differences were significant. The percentage of patients who were stable was similar between the two groups, and adverse effects were minor and reversible. Our study suggests that among patients on levodopa, fewer patients worsen when selegiline is added earlier than when it is added later.

Aged↗
PubMed1991

Experience with selegiline and levodopa in advanced Parkinson's disease.

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.

Aged↗
PubMed1990

Spontaneous pneumomediastinum in an adolescent patient.

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.

Adolescent↗
PubMed1990

Randomized double-blind cross-over study of Sinemet-controlled release (CR4 50/200) versus Sinemet 25/100 in Parkinson's disease.

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.

Aged↗
PubMed1989

[Cefaclor and trimethoprim-sulfamethoxazole for recurrent otitis media].

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.

Acute Disease↗
PubMed1989

[Carrier detection and prenatal diagnosis in phenylketonuria, cystic fibrosis and adrenal hyperplasia use of molecular biology techniques].

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.

Adrenal Hyperplasia, Congenital↗
PubMed1989

A preliminary comparison of flat affect schizophrenics and brain-damaged patients on measures of affective processing.

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.

Adult↗
PubMed1989

Adrenal medullary transplants as a treatment for advanced Parkinson's disease.

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)

Adrenal Medulla↗
PubMed1988

Relationship among CT scans, neurological exam, and neuropsychological test performance in right-brain-damaged stroke patients.

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.

Brain↗
PubMed1988

MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease.

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.

Adult↗