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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 541 records · Page 30Linked to original sources
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.

Aged↗
PubMed1982

A new approach to quantitate the density and antigen contents of high densities of transmitter-identified terminals. Immunocytochemical studies on different types of tyrosine hydroxylase immunoreactive nerve terminals in nucleus caudatus putamen of the rat.

By means of a semi-automatic image analyzer plugged into an Apple II computer and suitable computer programs it is possible to analyze transmitter-identified nerve terminals. Thus, a densitometric approach is applied on the original photograph followed by systematic sampling which is carried out by means of a grating of circles. This procedure allows the study quantitatively of density and intensities of different types of densely packed tyrosine hydroxylase (TH) immunoreactive nerve terminals of the nuc. caudatus putamen. It is shown that the islandic TH immunoreactive nerve terminals have a higher density, but a TH content similar to the diffuse types of TH immunoreactive nerve terminals in the nuc. caudatus putamen.

Animals↗
PubMed1982

Lowering of blood pressure in hypertensive rats by SKF 64139 and SKF 72223.

The effects of a centrally acting phenylethanolamine N-methyl-transferase (PNMT) inhibitor, SKF 64139, and of its analog, SKF 72223, which is devoid of PNMT inhibitory activity on blood pressure and heart rate, were investigated in spontaneously hypertensive rats (SHR) and in DOCA-salt hypertensive rats. SKF 64139 lowers blood pressure and decreases pulse rate, while SKF 72223 lowers blood pressure and transiently increases pulse rate in SH-rats and in DOCA-salt hypertensive rats. SKF 72223 has no effect on blood pressure or heart rate in normotensive Wister-Kyoto rats. These results suggest that the antihypertensive action elicited by these two tetrahydroisoquinoline (TIQ) derivatives is not due to lowering of central epinephrine (E) levels. To determine whether the cardiovascular response elicited by SKF 72223 is due to stimulation of presynaptic alpha 2-adrenoreceptors, or to blockade of alpha 1-adrenoreceptors, we have examined its effect in combination with the partial alpha 2-agonist clonidine, or with the alpha 1-antagonist prazosin. The administration of clonidine slightly decreases the antihypertensive action of SKF 72223. The clonidine induced reduction in pulse rate is reversed by SKF 72223. In animals pretreated with prazosin, SKF 72223 elicits an additional decrease in blood pressure. Since SKF 64139 and SKF 72223 interact with alpha 2-adrenoreceptors, it is suggested that blockade of peripheral vascular alpha 2-adrenoreceptors might be in part responsible for their antihypertensive action. However, the antihypertensive action of these two drugs might also be due to some central mechanisms.

Adrenergic alpha-Antagonists↗
PubMed1982

Effects of ibotenic acid-induced neuronal degeneration in the medial preoptic area and the lateral hypothalamic area on sexual behavior in the male rat.

It is well known that electrolytic lesions in the medial preoptic area (MPOA) and the lateral hypothalamic area (LHA) seriously impair masculine sexual behavior in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO), in the MPOA were as effective as electrolytic lesions in eliminating copulation whereas no behavioral effects were detected following similar infusions in the LHA. Histological examination of MPOA and LHA following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Also, immunohistochemical studies suggested that the serotonergic innervation of the MPOA remained largely intact in spite of IBO treatment; similarly, the damage inflicted by IBO in LHA on tyrosine hydroxylase-immunoreactive fibers in the medial forebrain bundle was insignificant. These data suggest that: (i) the functional integrity of MPOA nerve cell bodies is necessary for the expression of sexual behavior, and (ii) disruption of mating produced by electrolytic LHA lesions is due to disruption of medial forebrain bundle fiber systems. Behavioral observations of non-copulating males suggested that the MPOA injury did not interfere with all aspects of their sexual interaction with the estrous female; rather, they appeared specifically unable to perform the reflexive pelvic thrust pattern normally associated with mounting. We here report, however, that the ability to perform mounts with pelvic thrusts was temporarily restored in the vast majority of MPOA-injured males by the i.p. administration of the ergot derivative, lisuride. About 50% of these MPOA-damaged males even ejaculated, often after a low number of intromissions and short ejaculation latencies. On the other hand, injections of naloxone (an opiate receptor antagonist) failed to activate mounting in MPOA-lesioned or castrated rats. On the basis of these findings the possible ways in which steroid hormone-sensitive brain areas might interact with monoamine-containing pathways are discussed.U

Animals↗
PubMed1982

The effect of GTP on benzodiazepine receptors.

GTP decreases the specific binding of [3H]flunitrazepam to cerebral cortical membrane sites. Scatchard analysis data show that GTP does not alter the maximum binding sites (Bmax), but increases the dissociation constant (KD) for [3H]flunitrazepam. GTP also inhibits the specific binding of the benzodiazepine antagonist [3H]CGS-8216. The specific binding of [3H]CGS-8216 displaceable by clonazepam is inhibited to a greater extent by GTP than that displaceable by the benzodiazepine antagonists, CGS-8216 or beta-CCE.

Animals↗
PubMed1982

Relatively high levels of dopamine in nucleus accumbens of levodopa treated patients with Parkinson's disease.

The dopamine levels were found to be low in the putamen and relatively high in the nucleus accumbens in two Parkinson disease patients treated with levodopa up to the time of their deaths. Tyrosine hydroxylase immunocytochemistry revealed a severe degeneration of the nigro-striatal dopamine neuronal system in both postmortem brains. The relatively high dopamine levels in the nucleus accumbens may be responsible for the occurrence of dyskinesias.

Aged↗
PubMed1982

The use of pergolide, a potent dopamine agonist, in Parkinson's disease.

Pergolide, a semisynthetic ergoline and a potent long-acting adenylcyclase-linked dopamine agonist, was given to 40 patients with advanced Parkinson's disease whose response to levodopa had diminished considerably. The group included 31 patients with marked diurnal oscillations in performance ("wearing off" and/or "on-off" phenomena). Pergolide alone (7 patients) or combined with levodopa (33 patients), resulted in a reduction in disability (P less than or equal to 0.01) as assessed in both the patients' "on" and "off" periods. Pergolide also resulted in an increase (P less than or equal to 0.001) in the number of hours in which patients were on from 3.8 (+/-0.4) to 11.9 (+/-0.9). The mean daily dose of pergolide was 2.4 mg (range 0.1 to 10.0). The mean duration of the study was 12 mo (range 1 to 24). Pergolide is effective in Parkinson's disease and will change the management of patients whose response to levodopa has diminished.

Adult↗
PubMed1982

Development of the adrenergic phenotype: increase in adrenal messenger RNA coding for phenylethanolamine-N-methyltransferase.

Mechanisms regulating the developmental increase in the activity of adrenal phenylethanolamine-N-methyltransferase (PNMTase), an index of the adrenergic phenotype, were examined. Immunotitration indicated that the increase in catalytic activity in rat adrenal from birth to adulthood was attributable to increased numbers of PNMTase molecules, not enzyme activation. To determine whether the ontogenetic increase in PNMTase protein was associated with elevation of mRNA coding for PNMTase, cell-free translation was performed on total cellular mRNA obtained from adrenals at different ages. Translation in wheat-germ and reticulocyte lysate systems, followed by immunoprecipitation of the PNMTase product, NaDodSO4 gel electrophoresis, and fluorography, showed an 8-fold increase in the proportion of specific PNMTase mRNA relative to total mRNA in rat adrenals from birth to adulthood. Moreover, bovine adrenal medullae exhibited a 100-fold increase in PNMTase mRNA levels between embryonic life and adulthood. Consequently, the ontogenetic increase in adrenal PNMTase appears to be due to a developmental rise in specific mRNA coding for the protein.

Adrenal Medulla↗
PubMed1982

Organizational principles in the peripheral sympathetic nervous system: subdivision by coexisting peptides (somatostatin-, avian pancreatic polypeptide-, and vasoactive intestinal polypeptide-like immunoreactive materials).

Sympathetic ganglia and some peripheral tissues of adult guinea pig and cat were analyzed by the indirect immunofluorescence technique with antisera to catecholamine-synthesizing enzymes and some peptides. In the guinea pig, noradrenergic neurons could be subdivided into three populations containing respectively (i) somatostatin-like immunoreactive material, (ii) avian pancreatic polypeptide (APP)-like immunoreactive material, and (iii) apparently only noradrenaline (NA; norepinephrine). A fourth population of sympathetic neurons was nonadrenergic and contained vasoactive intestinal polypeptide (VIP)-immunoreactive material. In the cat many noradrenergic neurons with APP and some without this peptide were seen, but no somatostatin-immunoreactive neurons were observed. Also a population of non-adrenergic, presumably cholinergic, neurons containing a VIP-like peptide was observed. These neuron populations seemed to innervate different tissues with some target specificity. For example, in the nasal mucosa of the cat, nerves containing NA/APP-like immunoreactive material (called NA/APP nerves) were found around small arteries and arterioles, whereas venules and sinusoids were surrounded by nerves containing only NA (called NA nerves). Also in the submandibular salivary gland of the cat, the NA/APP nerves surrounded arteries and arterioles, whereas NA nerves were seen in relation to acini and ducts. The sympathetic (cholinergic) VIP-containing neurons innervated blood vessels and exocrine tissue in the cat sweat glands. In the coeliac-superior mesenteric ganglion complex of the guinea pig and cat, a dense network of VIP-immunoreactive fibers was seen preferentially around noradrenergic ganglionic cell bodies lacking APP-immunoreactive material. Thus, adult peripheral sympathetic neurons can be subdivided into several categories on the basis of specific peptides. These subdivisions may innervate specific targets and may receive peptide-specific neuronal inputs.

Animals↗
PubMed1982

Elevation of the blood lactate concentration by alkali therapy without requiring additional lactic acid accumulation: theoretical considerations.

A patient presented with lactic acidosis and severe acidemia; sodium bicarbonate was administered to titrate the very large hydrogen ion load. Coincident with this therapy, the blood lactate concentration rose from 21 to 27 mmole/L. In order to evaluate whether this rise in lactate could have occurred without requiring additional net lactic acid production, the effect of the hydrogen ion concentration on lactate distribution was evaluated. Data obtained from animal studies support the established hypothesis that lactate is distributed like other weak organic acids at steady-state; hence, alkalemia should favor a shift of lactate from the intracellular fluid (ICF) to the extracellular fluid (ECF). The authors calculated that the blood lactate concentration could rise by 50% without requiring net lactic acid accumulation when the severe acidemia was corrected by alkali therapy. Thus, an increase in lactate concentration of the magnitude observed during alkali therapy need not indicate a worsening of the metabolic picture in lactic acidosis.

Alkalies↗
PubMed1982

The use of lisuride, a potent dopamine and serotonin agonist, in the treatment of progressive supranuclear palsy.

Seven patients with progressive supranuclear palsy were treated with lisuride. Mean age was 62 years (range, 52 to 68 years), and duration of disease was 4.4 years (range, 1 to 7 years). All seven had been treated with levodopa/carbidopa and three with bromocriptine; four had, at one time, shown a partial response to levodopa. One patient had also shown a partial response to bromocriptine. Lisuride was used alone in four patients, and combined with levodopa/carbidopa in three patients. Mean dose of lisuride was 2.5 mg (range, 1.5 to 5.0 mg). Mean duration of treatment was 4 months (range, 1 to 10 months). While two patients showed a reduction in rigidity, one in tremor and two in bradykinesia, in only one of them was there an overall improvement. It is postulated that the relative lack of response to lisuride may be due to a loss of both the dopaminergic and serotonergic receptors in progressive supranuclear palsy.

Aged↗