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Biomedical subjects

A N Lieberman

Publications and source records attributed to A N Lieberman.

At least 37 records · Page 2Linked to original sources
PubMed1985

The use of pergolide and lisuride, two experimental dopamine agonists, in patients with advanced Parkinson disease.

Pergolide, an experimental dopamine agonist, was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily responding to levodopa, including 45 patients with diurnal oscillations in performance: "on-off" phenomena. Lisuride, an experimental dopamine agonist was administered to 63 patients with advanced Parkinson disease. Pergolide or lisuride, when added to levodopa, resulted in a significant decrease in disability in both the "on" and the "off" period, and an increase in the number of hours in which patients were "on". Forty-one of 56 patients (73%) improved on Pergolide. Thirty-seven of 63 patients (59%) improved on lisuride. Mean dose of pergolide was 2.5 mg. (range 0.2 to 10.0 mg.). Mean dose of lisuride was 2.6 mg. (range 0.2 to 5.0 mg.). Pergolide was discontinued in 18 patients because of adverse effects, including an organic confusional syndrome (six patients), dyskinesias (four patients) and cardiovascular abnormalities (three patients). Lisuride was discontinued in 26 patients because of adverse effects, including an organic confusional syndrome (15 patients), dyskinesias (five patients) and vasospasm (two patients). Pergolide was discontinued in nine patients and lisuride in 12 because of a lack of effect or a declining effect. Both drugs are equally useful in patients with advanced Parkinson disease.

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PubMed1985

Bromocriptine in Parkinson disease.

Bromocriptine is an ergopeptine derivative and dopamine agonist that predominantly stimulates the striatal D2 non-adenyl cyclase-linked dopamine receptors. Bromocriptine, unlike other dopamine agonists, has mixed "agonist-antagonist" properties at these receptors. The striatal dopamine receptors exist in two different affinity states: a low and a high affinity state. Bromocriptine, unlike other dopamine agonists, does not differentiate between the low and the high affinity state of the D2 receptors, and bromocriptine does not induce a conformational change in these receptors. Bromocriptine, in low doses, is effective in patients with mild to moderate Parkinson's disease, while bromocriptine in higher doses is needed in patients with advanced disease. Both in low doses and in high doses, bromocriptine combined with levodopa is usually more effective than bromocriptine alone. The efficacy of low dose (5-30 mg/day) and high dose (31-100 mg/day) bromocriptine alone and with levodopa was examined in 27 studies encompassing 790 patients. Forty-six % of the studies were done in a double blind manner. In four studies of 79 patients, low dose bromocriptine (16 mg/day) without levodopa resulted in improvement in 58% of the patients. Only 9% of the patients experienced adverse effects. Most of the patients (63%) and mild or moderate Parkinson disease. In seven studies of 143 patients, high dose bromocriptine (56 mg/day) without levodopa resulted in improvement in 62% of patients, but with 27% having adverse effects. Most of these patients (77%) had mild or moderate disease. Diurnal oscillations in performance, the "wearing off" or "on-off" effect, were not seen during treatment with bromocriptine alone. In nine studies of 201 patients, low dose bromocriptine (23 mg/day) and levodopa resulted in improvement in 71% of patients with 26% having adverse effects. Most of these patients (66%) had advanced disease, and many had diurnal oscillations in performance. In seven studies of 367 patients, high dose bromocriptine (48 mg/day) and levodopa resulted in improvement in 58% with 37% having adverse effects. Most of these patients (85%) had advanced disease. The increased effectiveness of bromocriptine in combination with levodopa may be explained as follows. Bromocriptine by itself does not discriminate between the low and the high affinity states of the dopamine receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1984

Should dopamine agonists be given early or late? A review of nine years experience with bromocriptine.

Experience with bromocriptine in 106 patients treated over nine years was reviewed. Most of the patients were already being treated with levodopa (combined with a peripheral decarboxylase inhibitor). These patients, after having initially achieved a good response to levodopa, were no longer responding satisfactorily. Most of the patients were also experiencing diurnal oscillations in performance: "wearing off" and "on-off" phenomena. In these patients previous attempts at changing the dose (increasing or decreasing) or changing the scheduling of levodopa had been unsuccessful. Bromocriptine was added to levodopa beginning at a dose of 5 mg/day, and each week was increased by another 5 mg/day. At a dose of bromocriptine of at least 25 mg/day, there was a decrease in disability in the majority of patients with a decrease in the severity of the diurnal oscillations in performance (especially "wearing off" phenomena). In most patients, the addition of bromocriptine resulted in an approximately 10% reduction in the dose of levodopa. The majority of patients sustained their improvement at least one year. In some patients improvement was sustained for up to five years. The therapeutic efficacy of bromocriptine was limited in many patients by the occurrence of adverse effects including mental changes, dyskinesias, orthostatic hypotension, and nausea. These adverse effects could often be minimized by reducing the dose of bromocriptine or levodopa. All adverse effects were reversible upon stopping the drug. We have found bromocriptine to be a valuable adjunct in the treatment of these patients.

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PubMed1984

Long-term treatment with pergolide: decreased efficacy with time.

We studied the effect of pergolide (combined with levodopa) in 17 patients with Parkinson's disease, including 15 with "wearing off" or on-off phenomena, who had been taking pergolide for at least 2 years. Mean duration of the study was 27.8 months. All 17 patients improved initially, but the improvement later faded. Mean disability score, which decreased initially by 60% (significant), was decreased only by 20% after 2 years (not significant). Wearing off and on-off phenomena, which improved initially, became prominent again. Four patients lost all the improvement, nine patients lost much of the improvement, and four maintained much of the improvement. Mean dose of pergolide was 2.2 mg (range, 0.8 to 5.0 mg).

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PubMed1984

Combined use of benserazide and carbidopa in Parkinson's disease.

The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. Although many patients respond better to one drug than the other, we sought to exploit the differences in pharmacokinetics by giving both drugs to the same patient. Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, including 22 patients with diurnal oscillations in performance, "wearing off" or on-off phenomena. Previous attempts to change the dose, sequence, or ratio of levodopa to carbidopa in these patients had been unrewarding. Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. The mean dose of levodopa:carbidopa before benserazide was 910:100 (9 to 1 ratio); the mean dose of levodopa:benserazide was 355:90 (4 to 1 ratio). The mean dose of levodopa:carbidopa + benserazide was 925:155 (6 to 1 ratio). The combination of carbidopa with benserazide is useful in some parkinsonian patients.

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PubMed1984

Pergolide and lisuride in advanced Parkinson's disease.

In a retrospective study, treatment with lisuride was compared to pergolide in 25 patients with advanced PD in whom the response to levodopa had diminished. Sixteen patients had wearing off and/or ON-OFF phenomena. Lisuride or pergolide, when added to levodopa, resulted in comparable and significant decreases in disability in both ON and OFF periods; pergolide resulted in a greater increase in the number of hours in which patients were ON. Adverse reactions were comparable on both drugs. However, patients who developed an adverse reaction on one drug did not necessarily develop the same reaction on the other drug. Both lisuride and pergolide are effective anti-Parkinson drugs.

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PubMed1983

Transient neurologic disturbances, brain tumors, and normal computed tomography scans.

During a 4-year period, four patients presented with transient disturbances in neurologic function that were diagnosed as seizures in two and transient ischemic attacks in the other two. Computed tomography (CT scan), both with and without contrast, was normal in all four patients. Isotopic brain scans (3 patients), cerebral angiograms (4 patients), and lumbar punctures (4 patients) were normal. Electroencephalograms (EEG) were normal in two patients and abnormal in two patients (consisting of focal slowing). Within 4.5 months, all patients developed symptoms and signs of a brain tumor, and in all four, CT scan now revealed a large mass lesion which at surgery was shown to be a malignant astrocytoma. These four patients constituted 4% of the total number of patients with malignant astrocytomas that were seen at the NYU Medical Center during this same time period. It is stressed that the CT scan may be normal early in the course of patients with brain tumors, particularly if they present with a transient disturbance in neurologic function. The first evidence of the tumor in such patients may be a slow-wave abnormality on the EEG. Patients who are suspected of having a brain tumor should, if the initial CT scan is normal, have the scan repeated later.

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PubMed1983

Bromocriptine and lisuride in Parkinson disease.

Lisuride was compared with bromocriptine in 25 parkinsonian patients in whom the response to levodopa had diminished; 19 had "wearing off," "on-off" phenomena, or both. At the time bromocriptine was added to levodopa, the mean age of the patients was 62.7 years and mean disease duration was 8.9 years. Disability decreased by 34% in the on period and by 20% in the off period, and the number of hours the patients were on increased from 9.6 to 12.8. All these changes were significant (p less than or equal to 0.01 to 0.05). Bromocriptine, however, had to be discontinued in 11 patients because of adverse effects. In the remaining 14 patients, bromocriptine was eventually discontinued because of decreased efficacy. Mean dose of bromocriptine was 55 mg (range, 20 to 100 mg). At the time lisuride was added to levodopa the patients were older (65.4 years), had had the disease longer (11.4 years), and were more disabled. Nonetheless, disability decreased in the on period by 33% and in the off period by 17%, and the number of hours the patients were on increased from 3.9 to 8.9. All these changes were significant (p less than or equal to 0.01 to 0.05). The mean dose of lisuride was 2.8 mg (range, 0.6 to 5.0 mg). Lisuride was discontinued in 8 patients because of adverse effects. Both bromocriptine and lisuride are useful in managing patients with advanced Parkinson disease whose response to levodopa has diminished. While it is presently not possible to state which of the drugs is more effective, ultimately their usage will probably be determined by their relative cost.

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PubMed1983

Further studies with lisuride in Parkinson's disease.

Lisuride was administered to 63 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The group included 40 patients with 'on-off' phenomena. Lisuride alone (13 patients) or combined with levodopa (50 patients) resulted in a 34% decrease in PD disability as assessed in the 'on' period, a 16% decrease in disability as assessed in the 'off' period, and a 96% increase in the numbers of hours in which patients were 'on' (from 5.5 to 10.8 h). All of these changes were significant (p less than or equal to 0.001). 37 of the 63 patients (59%) improved at least one-stage on lisuride. The major adverse effect limiting the use of lisuride was the occurrence of an organic confusional syndrome. This was related, in part, to the presence of an underlying dementia and to the concurrent use of anticholinergic drugs.

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PubMed1983

The effects of pergolide on the cardiovascular system of 40 patients with Parkinson's disease.

The effect of pergolide, a semisynthetic ergot alkaloid, on the cardiovascular system of 40 patients with Parkinson's disease (PD) was evaluated. The mean daily dose of pergolide was 2.4 mg (range, 0.1 to 10 mg). The mean duration of follow-up was 6 months (range, 2 weeks to 20 months). The 40 patients were selected only on the basis of severe PD. All 13 patients in the first part of the study underwent 1 to 5 days of Holter monitoring before starting pergolide. Monitoring was then carried out for an additional period of between 2 and 10 weeks while the patients were on pergolide. Seven of the 13 patients manifested repetitive ventricular rhythms. These were isolated and unassociated with increases in premature ventricular contractions. The dose at which the RVRs occurred was a function of the presence or absence of heart disease. The changes occurred below 3 mg/day in patients with heart disease and above 3 mg/day in patients without heart disease. Pergolide was discontinued in three of the patients with heart disease. It was concluded that pergolide may, in the diseased heart, predispose to RVRs. In the second part of the study, Holter monitoring was carried out only at the discretion of the cardiologist, and five patients were so monitored. None of these patients was rejected from the study. Only one patient (with heart disease) of the 27 patients in the second part of the study experienced an arrhythmia. This consisted of an increase in PVCs on 4 mg/day of pergolide. Pergolide was discontinued. Eight of the 40 patients in these early dose-ranging studies experienced orthostasis, two with syncope, immediately on addition of pergolide (0.1 to 0.4 mg) to levodopa. The orthostasis could be eliminated in all but two patients by reducing or discontinuing levodopa.

Adult↗
PubMed1983

Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson's disease.

Treatment with pergolide was compared with bromocriptine in 25 patients, all of whom were also receiving levodopa and in all of whom the response to levodopa had diminished. All 25 patients had "on-off" phenomena. At the time bromocriptine was added to levodopa, the mean age of the patients was 61.8 years, mean duration of disease was 9.0 years, and mean duration of levodopa treatment was 6.1 years. For the group as a whole, disability as determined in the "on" period decreased by 36%, from 28.7 to 18.5; and 11 patients improved at least one stage. Disability as determined in the "off" period decreased by 25%, from 59.5 to 44.4. The number of hours in which patients were "on" increased by 62%, from 7.1 to 11.5. All of these changes were significant (p less than or equal to 0.05). Bromocriptine had to be discontinued in nine patients (eight because of mental changes). In the remaining 16 patients, bromocriptine was eventually discontinued because of diminishing efficacy. Mean dose of bromocriptine was 50 mg (range, 10-100 mg), and mean duration of treatment was 23 months (range, 2-65 months). At the time of their treatment with pergolide, the patients were older, 65.5 years, had the disease longer, 12.7 years, and were more disabled. Nonetheless, for the group as a whole, disability score as determined in the "on" period decreased significantly by 40%, from 43.5 to 26.3, and 14 patients improved at least one stage. Disability as determined in the "off" period decreased significantly by 21%, from 69.0 to 54.8. The number of hours in which patients were "on" increased significantly by 224%, from 3.4 to 11.0 hr. The mean dose of pergolide was 2.1 mg (range, 0.1-10.0 mg), and the mean duration of treatment was 6.2 months (range, 0.5-20 months). Pergolide was discontinued in eight patients: three because of asymptomatic tachyarrhythmias of unknown clinical significance (detected only by Holter monitoring); two because of orthostatic hypotension; and two because of mental changes. Although pergolide appears to be more potent than bromocriptine because of its greater effect in a larger number of patients at a more advanced stage of their disease, both drugs are useful, and both enhance our ability to manage patients with PD.

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PubMed1982

Prolonged persistence of a large pericardial effusion and hemodynamic evidence of cardiac tamponade during treatment of myxedema.

We describe clinical, echocardiographic, and catheterization findings that were present initially and during therapy in a myxedematous patient with a large pericardial effusion and tamponade. Treatment with thyroxine resulted in a marked improvement of most of the clinical features of hypothyroidism and some improvement in cardiac function. However, the pericardial effusion as well as clinical and laboratory evidence of tamponade persisted for 2 months after full replacement doses of T4 had been achieved. The tamponade was finally relieved by fenestration of the parietal pericardium. These findings are consistent with evidence of an abnormality of pericardial drainage that persists for months after other thyroid hormone dependent functions are normalized by thyroxine replacement. Therefore prompt surgical drainage rather than dependence on medical therapy alone is indicated in myxedematous patients who have cardiac tamponade.

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