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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 559 records · Page 31Linked to original sources
PubMed1982

Further studies with pergolide in Parkinson disease.

Pergolide was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily responding to levodopa. The group included 45 patients with on-off phenomena. Pergolide, when combined with levodopa, resulted in a 44% decrease in disability as assessed in the on period, a 15% decrease in disability as assessed in the off period, and a 148% increase in the number of hours in which patients were on (from 4.6 +/- 0.3 hours to 11.4 +/- 0.6 hours). All these changes were significant at 1%. Forty-one of the 56 patients (59%) improved when pergolide was added to levodopa. Mean dose of pergolide was 2.5 mg (range, 0.2 to 10.0 mg). Mean duration of the study was 13 months (range, 1 day to 34 months). Maximum improvement occurred within 2 months and began to decline, usually after 6 months. The major adverse effects necessitating discontinuing pergolide were the occurrence of an organic confusional syndrome (six patients), increased dyskinesias (four patients), and cardiovascular abnormalities (three patients). Nine patients discontinued pergolide because of a lack of effect or declining effect.

Adult↗
PubMed1982

Effect of potassium on distal nephron hydrogen ion secretion in the dog.

The purpose of these investigations was to determine whether potassium might influence the DNHS and, if so, to gain insight into the mechanisms involved. Since DNHS is decreased by ECF volume expansion, dogs were studied in both normovolemic and ECF volume-expanded states. DNHS was assessed in vivo by examining the U-B PCO2. In dogs with an expanded ECF volume, the U-B PCO2 at comparable urine bicarbonate concentrations was almost 50% lower than in the normovolemic dogs. Despite hyperkalemia and kaluresis, the U-B PCO2 was minimally affected by potassium infusion in the dogs with an expanded ECF volume. In contrast, in the normovolemic dogs, the U-B PCO2 was much higher before potassium administration and it decreased after potassium infusion to levels comparable to those observed in the dogs with ECF volume expansion. The U-B PCO2 in the normovolemic dogs was inversely related to the rate of potassium excretion when this rate was less than 150 muEq/min. Amiloride, an agent that decreases the electrical gradient favoring DNHS, caused only a small fall in the U-B PCO2 in potassium-loaded dogs with either a normal or an expanded ECF volume. Although other explanations are possible, we favor the hypothesis that the secretion of potassium into the distal nephron led to a reduced rate of hydrogen ion secretion provided that there was a significant avidity for sodium reabsorption.

Absorption↗
PubMed1982

Evaluation of mitral stenosis by the study of the left ventricular diastolic phase.

The left ventricular relaxation period has been studied by digitized monodimensional echocardiography in 14 patients with symptomatic pure mitral stenosis and in 11 normal subjects. The maximal relaxation rate and the maximal circumferential relaxation rate differed significantly in both groups (p less than 0.001) with a marked reduction in the patients with mitral stenosis; it was, however, not possible to trace a significant correlation between mitral valve area and the indices of diastolic phase, excepted a slightly significant one for the mean relaxation rate (r = 0.7). In spite of the fact that these results show a delayed left ventricular filling in mitral stenosis, the correlation with the mitral valve area was poor and suggests that it is not satisfactory to estimate the left ventricular filling only by the variation of the ventricular transverse diameter, and that a more accurate evaluation of the mitral valve area should include, in addition to the measurement of the ventricular relaxation rate, at least an indirect estimation of the transmitral pressure gradient, for instance by Doppler echocardiography of the transmitral flow.

Diastole↗
PubMed1981

The regulation of striatal DOPA synthesis by alpha 2-adrenoreceptors.

The administration of alpha 2-adrenoreceptor antagonists SKF 64139 or SKF 72223 (TIQ derivatives) elicits an increase in striatal DOPA synthesis. The findings that the enhanced DOPA synthesis is reversed by pretreatment of the animals with clonidine or with the D beta H inhibitor FLA-63 suggest that action of the TIQ derivatives is related to their ability to block alpha-adrenoreceptors. It is being postulated that the enhanced striatal DOPA synthesis elicited by the TIQ derivatives is a result of inhibition of dopaminergic neurotransmission.

Adrenergic beta-Antagonists↗
PubMed1981

Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by partial ergoline.

The capacity of the ergoline, pergolide, and of the partial ergoline, LY 141865, to stimulate pre- and postsynaptic dopamine (DA) receptors was investigated. Binding studies have revealed that pergolide has a high affinity, while the partial ergoline, LY 141865, has a low affinity for the postsynaptic striatal DA receptors in vitro. Two behavioral animal models were used to assess the DA agonist potencies of these compounds for the postsynaptic DA receptors in vivo. Pergolide induced turning behavior in rats with 6-hydroxydopamine (6-OH-DA) lesions, and relief of tremor in monkeys with ventromedial tegmental lesions, at a lower dose and for a longer duration than LY 141865. An in vivo and an in vitro biochemical test was use to measure the ability of these compounds to stimulate presynaptic DA receptors. In the in vitro test, pergolide and LY 141865 were found to have low inhibitory activity for synaptosomal tyrosine hydroxylase, while in the in vivo test, both drugs were effective even in low doses in reversing the gamma-butyrolactone elicited increased accumulation of striatal DOPA. These results suggest that pergolide has a high affinity for pre- and postsynaptic DA receptors, while its partial ergoline analogue has a high affinity for the presynaptic, but not for the postsynaptic DA receptors. The data also suggest that dopamine synthesis in vitro and in vivo may be regulated by different presynaptic DA receptors.

Animals↗
PubMed1981

Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.

Different brain regions were removed post mortem from three patients with the Lesch-Nyhan syndrome and were examined for alterations in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), adenine phosphoribosyl transferase, and biochemical indexes of norepinephrine, dopamine, serotonin, gamma-aminobutyric acid (GABA), and acetylcholine neuron function, as compared with age-matched controls. The level of HGPRT activity in the material from patients with the Lesch-Nyhan syndrome was less than 1 per cent of control levels, whereas adenyl phosphoribosyl transferase was not significantly altered. All biochemical aspects of the function of dopamine-neuron terminals in the striatum (except dihydroxyphenylacetic acid levels) were decreased to 10 to 30 per cent of the control values. Serotonin and 5-hydroxyindoleacetic acid levels were increased, striatal choline acetyltransferase levels were low, and striatal glutamic acid decarboxylase and guanylate cyclase activities were unaltered. The disruption of the balance between the functions of GABA, dopamine, and acetylcholine neurons in the extrapyramidal system probably accounts for some of the symptoms observed in the Lesch-Nyhan syndrome (e.g., choreoathetosis).

Acetylcholine↗
PubMed1981

Presence of avian pancreatic polypeptide-like immunoreactivity in catecholamine and methionine-enkephalin-containing neurones within the central nervous system.

Using single and double staining immunohistochemical procedures it has been demonstrated that an avian pancreatic polypeptide-like immunoreactivity (APP-LI) co-exists with catecholamines in neurones within the A1/A3, A2 and A6 (locus coeruleus) cell groups, and also with methionine-enkephalin in cell bodies of the sacral parasympathetic system. Axonal and terminal immunoreactivity was observed in axons and nerve terminals in particularly high density within the dorsal horn of the spinal cord and originated in part from intrinsic cell bodies. Intense terminal labelling was also found around sacral and caudal lumbar motor neurones, and thoracic lateral sympathetic column neurones. Immunoreactive material was present in fibres around neurones of the periaqueductal grey, caudal raphe and the locus coeruleus and in neurones in the arcuate nucleus.

Animals↗
PubMed1981

Immunohistochemical identification of two types of dopamine neuron in the rat olfactory bulb as seen by serial sectioning.

Several neurons around the glomeruli in the rat olfactory bulb contain the enzyme tyrosine hydroxylase as revealed by light and electron microscopic immunohistochemistry. Electron microscopic analysis of serial sections reveal that both superficial tufted cells and small periglomerular neurons were labelled. These results give further support for the view that dopamine neurons in the rat olfactory bulb, from a neuroanatomical point of view, do not represent a homogeneous cell population. Furthermore, taken together with previous results in the literature our findings indicate that, from a transmitter histochemical point of view, neither tufted cells nor periglomerular neurons represent a homogeneous cell population.

Animals↗
PubMed1981

Keratophakia update.

Since October 1977, the authors have attempted 32 keratophakias (refractive corneal surgery using an interlamellar homograft disc). Twenty-nine of these were primary and three secondary on aphakic eyes. These cases were divided into two series. In the first series, the dioptric correction was 28.5% less than the amount calculated to correct the aphakic error. In the second series, only 6.5% of the calculated dioptric power remained uncorrected. Keratophakia is an alternative to other modalities of secondary full-time correction of aphakia since the internal eye is not compromised by this secondary procedure as it is with a secondary intraocular implant. Further improvements in instrumentation techniques and mathematic programs will broaden the application of refractive keratoplasty techniques.

Adult↗
PubMed1981

Cardiac effects of pergolide.

We examined the effect of pergolide, a semisynthetic ergot alkaloid, alone or combined with carbidopa and levodopa (Sinemet), on the cardiac rhythm of 12 patients with Parkinson's disease. The patients were selected on the basis of severe Parkinson's disease and stable cardiac rhythm as determined by 1 to 5 days of Holter monitoring. Monitoring was then carried out for an additional period of between 2 and 10 wk while the patients were on pergolide. Seven of the 12 patients had repetitive ventricular rhythms (RVRs). These were isolated, infrequent, and not associated with increases in premature ventricular contractions. The dose at which the RVRs occurred may be a function of the presence or absence of heart disease, but the significance of RVRs remains to be determined.

Aged↗
PubMed1981

Lisuride combined with levodopa in advanced Parkinson disease.

Lisuride, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was combined with levodopa in 20 patients with advanced Parkinson disease who were no longer responding satisfactorily to levodopa, including 14 patients with "on-off' phenomena. Every patient who completed the 8-week trial improved significantly (p greater than or equal to 0.01), with a decrease in all symptoms. The mean dose of lisuride was 2.4 mg per day. The dose of levodopa (mg of levodopa in Sinemet) was reduced from 1030 to 920 mg. Among the patients with "on-off' phenomena, there was a significant increase in the time in which they were 'on' (mobile) from 4.6 to 9.6 hours. In 5 of 10 patients who have been on lisuride for at least 1 year, there has been no decline in efficacy.

Adult↗
PubMed1981

Treatment of advanced Parkinson disease with pergolide.

Pergolide mesylate, a semisynthetic ergoline and a potent, long-acting central dopamine agonist, was tested in 13 patients with advanced Parkinson disease and diurnal oscillations in performance ("wearing-off" or "on-off" phenomena or both) whose response to levodopa had diminished considerably. Among all nine patients who completed the initial clinical trial, pergolide alone (two patients) or combined with levodopa (seven patients) had a marked antiparkinson effect. There was a significant reduction (p less than 0.05) in rigidity, bradykinesia, gait disorder and total Parkinson disease disability score. Pergolide had a marked effect in all the patients with "wearing-off" or "on-off" phenomena or both, resulting in a significant increase (p less than 0.01) in the duration of the time patients were "on." the number of hours in which patients were "on" increased from 3.8 +/- 0.5 (SEM) to 11.4 +/0 ).8 (SEM). The main daily dose of pergolide was 2.4 mg (range, 2 to 5 mg). Ten months later, all nine patients are doing well. Pergolide is an effective drug in patients with advanced Parkinson disease and reduces "on-off" phenomena.

Aged↗