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Biomedical subjects

R J Polinsky

Publications and source records attributed to R J Polinsky.

At least 55 records · Page 3Linked to original sources
PubMed1987

Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure.

Plasma epinephrine (EPI), norepinephrine (NE), beta-endorphin, and corticotropin (ACTH) responses were measured during insulin-induced hypoglycemia in normal subjects and in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). In normal subjects, there was a striking rise in EPI, NE, beta-endorphin, and ACTH following the nadir of hypoglycemia. Both beta-endorphin and ACTH responses were significantly lower than normal in patients with MSA, in contrast to normal levels in IOH patients. No correlation was observed between the degree of adrenergic insufficiency and the beta-endorphin and ACTH responses. The normal peptide responses in IOH are consistent with involvement limited to the peripheral sympathetic nervous system, whereas lesions in the central nervous system in MSA interfere with release of beta-endorphin and ACTH in response to hypoglycemia. The strong correlation between beta-endorphin and ACTH levels is consistent with their common origin. Peripheral adrenergic activity is not essential for beta-endorphin and ACTH release in humans.

Adrenal Glands↗
PubMed1987

Dominantly inherited Alzheimer's disease: cerebral glucose metabolism.

Cerebral glucose metabolic rate (CMRGlu), measured by positron emission tomography, was bilaterally and symmetrically reduced in two patients with autosomal dominant Alzheimer's disease. Supramarginal gyri and temporal lobes were most severely affected. An isolated reduction of CMRGlu in the left supramarginal gyrus was observed in one asymptomatic at-risk subject.

Adult↗
PubMed1987

MRI in autonomic failure.

A significant rank correlation between rigidity and putaminal signal dropout on magnetic resonance imaging (MRI) in patients with multiple system atrophy suggests that putaminal degeneration may cause this clinical finding. Absence of putaminal abnormalities on MRI in patients with pure autonomic failure may prove useful in differentiating these two autonomic disorders.

Aged↗
PubMed1987

Adrenergic dysfunction in hereditary adult-onset leukodystrophy.

We studied the pressor response to norepinephrine infusion in patients with an autosomal dominant adult-onset leukodystrophy. We also examined cardiovascular and catecholamine responses to insulin-induced hypoglycemia. A parallel shift to the left of the norepinephrine dose response curve, in conjunction with low baseline plasma norepinephrine levels, was consistent with denervation supersensitivity, suggesting a distal lesion of sympathetic noradrenergic neurons. Absence of the epinephrine response to insulin-induced hypoglycemia indicated that autonomic neuropathy was attended by severe adrenal medullary dysfunction.

Adult↗
PubMed1987

Interconversion of O-methylated norepinephrine metabolites in humans.

Levo-norepinephrine labeled with tritium was used to study urinary norepinephrine metabolites as an index of whole body norepinephrine turnover. Six healthy volunteers were given intravenous infusions of [ring-2,5,6-3H] levo-norepinephrine, followed by collection of urine for 24 hours. Specific activities were determined by high-performance liquid chromatography for each of the three O-methylated metabolites of norepinephrine in the urine samples, and were then used to calculate the fraction of 4-hydroxy-3-methoxymandelic acid (VMA) formed from 4-hydroxy-3-methoxyphenylglycol (MHPG) and from normetanephrine. These values were used, in conjunction with total excretion of each of these metabolites, to calculate the fraction of MHPG and normetanephrine converted to VMA. The fraction of VMA formed from MHPG was 0.821 +/- 0.020, and that from normetanephrine was 0.179 +/- 0.020. Whereas fractional conversion of normetanephrine to VMA was 0.634 +/- 0.030, that of MHPG to VMA was only 0.507 +/- 0.025. Similar results were obtained when the experiment was repeated in three of the subjects using [8-14C] levo-norepinephrine, suggesting that isotope, specific activity, and position of the label were not determinants of the values obtained. The present results confirm the extent of conversion of MHPG to VMA described by others, and suggest that a higher percentage of normetanephrine than previously reported is converted to VMA.

Adult↗
PubMed1986

Insulin-induced hypotension and neurogenic orthostatic hypotension.

Insulin-induced hypoglycemia induced a fall in blood pressure (BP) in patients with idiopathic orthostatic hypotension (IOH) and multiple system atrophy (MSA), but not in control subjects. Only in IOH was there a correlation between plasma norepinephrine (NE) levels and maintenance of BP during the test. The hypotension was not affected by pretreatment with propranolol. Hypotension during insulin-induced hypoglycemia is manifested in patients who lack an adequate NE response. The hypotension, however, may be due to a central action of insulin because not all MSA patients with impaired NE release become hypotensive.

Aged↗
PubMed1985

Decreased sympathetic neuronal uptake in idiopathic orthostatic hypotension.

The disappearance rates from plasma of intravenously administered levo-norepinephrine (l-NE), dextro-norepinephrine (d-NE), and isoproterenol (ISO) were measured in normal subjects and in patients with either multiple-system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). The two isomers, l-NE and d-NE, were removed at similar rates in all groups. In normal subjects, the d and l isomers of norepinephrine were cleared more rapidly than ISO. In patients with IOH, the initial rates of disappearance of the NE isomers from plasma were slower than normal and similar to the rate for ISO disappearance. Plasma NE levels, NE clearance, and the apparent release rate of NE into plasma from sympathetic neurons were significantly lower in patients with IOH than in normal subjects. Only the apparent NE secretion rate was related to the baseline plasma NE level. Sympathetic neuronal dysfunction in IOH is attended by a reduction in the clearance of NE. The very low plasma NE levels, in association with the striking reduction in NE clearance, suggest that in IOH there is a marked decrease in NE release. NE clearance and apparent NE secretion rate are normal in MSA, consistent with a central nervous system dysfunction in regulating the sympathetic nervous system. Neuronal uptake of NE in humans does not appear to be stereoselective.

Adult↗
PubMed1985

Parkinson's disease and Alzheimer's disease: hypersensitivity to X rays in cultured cell lines.

Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death.

Adolescent↗
PubMed1984

Disposition and metabolism of MHPG in humans: application to studies in depression.

MHPG is formed from norepinephrine metabolized throughout the body; its levels in plasma reflect total norepinephrine metabolism. Over half of the MHPG, is converted to VMA. Less than 20% of MHPG is derived from brain norepinephrine and urinary excretion of this metabolite cannot be used as a measure of brain norepinephrine metabolism. Because unconjugated MHPG is readily diffusable, there is a free exchange of this metabolite among plasma, cerebrospinal fluid, and nerve tissues (including brain and spinal cord). The CSF MHPG levels, after appropriately correction for the plasma contribution of the metabolite, reflect its rate of formation in the central nervous system.

Adrenal Gland Diseases↗
PubMed1984

Hypersensitivity to DNA-damaging agents in cultured cells from patients with Usher's syndrome and Duchenne muscular dystrophy.

Lymphoblastoid lines from nine Usher's syndrome (recessively inherited retinitis pigmentosa and congenital sensorineural deafness) patients (representing eight kindreds) and from ten Duchenne muscular dystrophy patients (representing seven kindreds) showed a small but statistically significant hypersensitivity to the lethal effects of X-rays, as measured by the cellular ability to exclude the vital dye trypan blue, when compared with lines from 26 normal control subjects. Fibroblast lines from the Usher's syndrome patients, treated with X-rays or the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine, also showed a statistically significant hypersensitivity when compared to normal fibroblast lines. These findings are consistent with the possibility that defective DNA repair mechanisms may be involved in the pathogenesis of these degenerative diseases.

Adolescent↗
PubMed1984

Speech symptoms associated with early signs of Shy Drager syndrome.

Speech disturbances reflecting impaired laryngeal control were found in ten patients whose autonomic dysfunction was associated with central neurological disease (Shy Drager Syndrome). In contrast, ten patients with progressive autonomic failure without evidence of CNS involvement had no difficulties on speech function tasks in comparison with normal controls. Presence of speech symptoms may aid in the clinical differentiation between patients with pure autonomic dysfunction and those with central neurological involvement.

Adult↗
PubMed1984

Chronic autonomic failure: CSF and plasma 3-methoxy-4-hydroxyphenylglycol.

We measured CSF and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in patients with orthostatic hypotension. Total CSF MHPG levels were significantly lower than normal in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). Only IOH patients had low plasma levels of MHPG. Correction of CSF MHPG levels for the contribution from plasma free MHPG provides an index of central norepinephrine metabolism. In MSA, abnormal function of central noradrenergic pathways seems to cause the low CSF MHPG levels. In IOH, the decreased CSF MHPG results from the diminished plasma MHPG levels.

Adult↗
PubMed1984

Alpha-adrenergic receptors in orthostatic hypotension syndromes.

Alpha-adrenergic receptor function was measured in platelets from patients with orthostatic hypotension and normotensive controls. Patients with idiopathic orthostatic hypotension (IOH) or multiple system atrophy (MSA) had more alpha-receptors than controls. Patients with IOH, but not MSA, produced less prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) than controls. Patients with sympathotonic orthostatic hypotension (SOH) were similar to controls in receptor number and cAMP production. The percent norepinephrine (NE) inhibition of PGE1-stimulated cAMP production was similar in patients and controls. An increase in alpha-receptor number may result from decreased peripheral NE secretion in IOH and MSA. Increased alpha-receptor number and decreased cAMP production, which accompany essential hypertension, may contribute to the supine hypertension of IOH, and an increase in alpha-receptor number may contribute to the supine hypertension of MSA. SOH patients appear to have no abnormalities of alpha-receptor function.

Adolescent↗
PubMed1984

Multiple system atrophy. Clinical aspects, pathophysiology, and treatment.

Progressive autonomic failure is a clinical syndrome of autonomic dysfunction that may occur in isolation as in idiopathic orthostatic hypotension (IOH) or in association with a central neurologic disorder, multiple system atrophy (MSA). MSA and IOH can be distinguished on the basis of biochemical and pharmacologic tests. Plasma norepinephrine levels are low in IOH and normal in MSA; neither group increases the plasma norepinephrine level adequately in response to postural change. Both MSA and IOH manifest an exaggerated pressor response to administered norepinephrine. However, only patients with IOH have true adrenergic receptor supersensitivity. The autonomic dysfunction in IOH primarily involves the peripheral autonomic neurons whereas the defect in MSA is the failure to activate appropriately an intact distal sympathetic nervous system. Neuropathologic studies reveal a multisystem degeneration in MSA; the few postmortem examinations of the central nervous system in IOH reveal lesions confined to the intermediolateral columns of the spinal cord. Orthostatic hypotension may be treated with a number of medications although supine hypertension limits the usefulness of these drugs. Further development and testing of a sympathetic neural prosthesis may help to resolve this therapeutic dilemma. Only the parkinsonian features in MSA respond to treatment with anticholinergic drugs.

Arrhythmia, Sinus↗
PubMed1983

Sympathetic neural prosthesis for managing orthostatic hypotension.

A prototype electromechanical analogue of the sympathetic division of the baroreceptor reflex arc was used to maintain blood pressure automatically in two patients with neurogenic orthostatic hypotension. The device prevented significant and sustained reductions in mean blood pressure when the patients were tilted up to 85 degrees. Upon achieving the preset mean blood pressure, the device maintained this pressure with a standard error of less than 2 mm Hg. Similar results were obtained when the patients were walking. The device did not cause supine hypertension during the trials.

Adult↗