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Biomedical subjects

R J Polinsky

Publications and source records attributed to R J Polinsky.

88 records · Page 5Linked to original sources
PubMed1980

Gilles de la Tourette syndrome: clinical and family study of 50 cases.

Fifty patients with Tourette syndrome were evaluated; data included family history, clinical characteristics, response to haloperidol, and side effects during haloperidol therapy. Sixteen patients had a family history of Tourette syndrome, and another 16 had a family history of tics. Twenty-four families had more than 2 members with Tourette syndrome or tics. There was no preponderance of families with a Jewish, Eastern European background in this sample. Thirty-four patients had obsessive-compulsive behavior. Among the 50 patients there was a high frequency of sleep disturbance, learning disability, self-destructive behavior, inappropriate sexual activity, and antisocial behavior. Family history was significantly related to the occurrence of sleep disturbance, obsessive-compulsive behavior, haloperidol response, and the frequency of side effects caused by haloperidol. The precise mode of genetic transmission in familial Tourette syndrome remains to be determined.

Female↗
PubMed1980

Dissociation between central and peripheral noradrenergic activity in essential hypertension.

1. Eleven patients with essential hypertension and nine healthy normotensive volunteer subjects, all without a neurological disorder, had blood drawn and cerebrospinal fluid sampled for analysis of noradrenaline (NA). 2. Cerebrospinal fluid NA levels were elevated (P < 0.01) in the hypertensive patients but plasma levels of NA were similar between groups. 3. The results suggest there is noradrenergic hyperactivity in the central nervous system which is not reflected in abnormal peripheral sympathetic nervous system function in this group of patients.

Adult↗
PubMed1980

The adrenal medullary response to hypoglycemia in patients with orthostatic hypotension.

The epinephrine response to insulin-induced hypoglycemia has been studied in patients with orthostatic hypotension and in control subjects. Normal subjects had a brisk increase in plasma epinephrine and norepinephrine levels which occurred at the nadir of plasma glucose levels. After the nadir of hypoglycemia, glucose recovery was biphasic, with an initial rapid rise in glucose, followed by a more gradual return to normoglycemia. In a group of 16 patients with orthostatic hypotension, 12 had deficient plasma catecholamine responses to hypoglycemia, and of these, 7 had almost no plasma epinephrine response. Comparison of the plasma epinephrine responses and the course of plasma glucose elevations indicated that a mean plasma epinephrine level of over 200 pg/ml is necessary for the rapid initial phase of glucose recovery. There does not appear to be any relationship between the etiological basis of the autonomic dysfunction and deficient epinephrine response.

Adrenal Medulla↗
PubMed1979

The trial use of clozapine for abnormal involuntary movement disorders.

Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind, placebo-controlled trial. The cohort consisted of individuals with Gilles de la Tourette's syndrome, Huntington's disease, and atypical persistent dyskinesia that was drug induced. Two subjects were dropped from the protocol due to complications. Two patients with Huntington's disease showed a marked decrease in movements; other individuals obtained no significant therapeutic benefits. Seven of the 10 patients completing the trial experienced moderate or marked side effects.

Adolescent↗
PubMedDate not supplied

Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical.

A group of fibroblast lines from three patients with the sporadic form of Alzheimer disease (AD) showed a small but statistically significant hypersensitivity to the lethal effects of the DNA-damaging chemical N-methyl-N'-nitro-nitrosoguanidine (MNNG) when compared with lines from eight normal control subjects. A fibroblast line from a patient with a dominantly inherited form of familial AD had a hypersensitivity similar to that of the three sporadic AD lines. However, fibroblast lines from a group of five patients with spinal muscular atrophy (SMA) were not hypersensitive to the chemical, demonstrating that not every primary neuronal degeneration manifests hypersensitivity to this chemical. These findings are consistent with the possibility that a defect in DNA-repair mechanisms may be the cause of the in vitro hypersensitivity, as well as the premature death of neurons in vivo, in both the sporadic and familial forms of AD.

Alzheimer Disease↗
PubMedDate not supplied

Familial Alzheimer's disease: progress and problems.

This paper reexamines recent epidemiologic and molecular genetic studies on the genetic basis of Alzheimer's Disease (AD). Careful analysis of the available epidemiologic data strongly suggests that at least a proportion of AD results from the inheritance of an autosomal dominant gene defect. However, studies of isolated families, of concordance rates in twins, and of risk for AD in relatives of AD probands yield conflicting data. While it is likely that much of the conflict can be ascribed to methodologic differences, it remains premature to conclude that all AD is transmitted as an autosomal dominant trait. Molecular genetic techniques hold the promise of isolation and characterization of the genetic defect(s) in familial AD (FAD). Recently, chromosome 21 has been implicated as the potential site of an autosomal dominant defect in some but not necessarily all FAD pedigrees. However, the results of recent genetic epidemiologic studies suggest that progress in the molecular genetic approach to AD will be difficult.

Adult↗
PubMedDate not supplied

Serum- and bradykinin-induced calcium transients in familial Alzheimer's fibroblasts.

The calcium-sensitive photoprotein, aequorin, was used to examine serum- and bradykinin-induced transient increases in free cytosolic calcium ions in skin fibroblasts from 10 individuals with early onset familial AD (FAD), including four who were biopsied before their clinical symptoms would allow a diagnosis of AD, 2 individuals with late onset FAD, 8 at-risk but nonsymptomatic individuals, and 13 controls. The data show that (a) among controls, the peaks of the calcium transients increase in height as a function of donor age; (b) transients induced by 10% serum, 10 nM bradykinin (BK) or 100 nM BK were generally lower in FAD fibroblasts, including those from donors in the early stages of the disease, than in age-matched control cells; (c) such transients are reduced in cells from a proportion of the nonsymptomatic, at-risk individuals. Thus, serum- and BK-induced calcium transients are reduced in fibroblasts from both early and more advanced stage FAD donors and perhaps even from donors who are presymptomatic carriers of the defective gene. The data also suggest that changes in calcium transients in FAD fibroblasts neither mimic nor exaggerate the effects of normal aging.

Adult↗
PubMedDate not supplied

Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer's disease.

Rivastigmine (ENA 713, or carbamoylatine) is an acetylcholinesterase (AChE) inhibitor with brain-region selectivity and a long duration of action. Both preclinical studies and studies in human volunteers have shown that rivastigmine induces substantially greater inhibition of AChE in the central nervous system (CNS) compartment than in the periphery (40% inhibition of central AChE compared with 10% inhibition of plasma butylcholinesterase in healthy volunteers). Moreover, rivastigmine preferentially inhibits the G1 enzymatic form of AChE, which predominates in the brains of patients with Alzheimer's disease (AD). Evidence from animal studies also suggests that rivastigmine is a more potent inhibitor of AChE in the cortex and hippocampus, the brain regions most affected by AD. Absorption of rivastigmine is rapid and almost complete (>96% of the administered dose). Extensive, saturable first-pass metabolism, however, leads to bioavailability of approximately 35% of the administered dose and nonlinear pharmacokinetics. The principal metabolite of rivastigmine has at least 10-fold lower activity against AChE compared with the parent drug. Rivastigmine is completely metabolized; the major route of elimination of the metabolites is renal. Although patients with AD demonstrate 30% to 50% higher plasma concentrations of rivastigmine and its principal metabolite than do healthy elderly patients, there is no evidence of drug accumulation, which is consistent with rivastigmine's short pharmacokinetic half-life. Distribution of rivastigmine into the CNS is extensive, and inhibition of AChE in the cerebrospinal fluid is detectable 1.2 hours after oral dosing in both healthy volunteers and patients with AD. Peak activity is reached somewhat more slowly in AD patients than in healthy subjects, and the inhibitory effects have a longer duration (6.0 vs 2.4 hours and 12.0 vs 8.5 hours, respectively). Rivastigmine is inactivated during the process of interacting with and inhibiting AChE, and, in contrast to other AChE inhibitors, the hepatic cytochrome P-450 (CYP-450) system is not involved in the metabolism of rivastigmine. This reduces its propensity to interact with drugs metabolized by specific CYP-450 isoenzymes. Consistent with rivastigmine's pharmacokinetic and pharmacodynamic profiles, Phase II and III trials have demonstrated that the drug is a well-tolerated and effective treatment for AD.

Alzheimer Disease↗
PubMedDate not supplied

The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene.

Amyloid beta-protein (AP) is a peptide of relative molecular mass (Mr) 42,000 found in the senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles of patients with Alzheimer's disease and Down's syndrome (trisomy 21). Recent molecular genetic evidence has indicated that AP is encoded as part of a larger protein by a gene on chromosome 21 (refs 5-7). The defect in the inherited autosomal dominant form of Alzheimer's disease, familial Alzheimer's disease (FAD), has been mapped to the same approximate region of chromosome 21 by genetic linkage to anonymous DNA markers, raising the possibility that this gene product, which could be important in the pathogenesis of Alzheimer's disease, is also the site of the inherited defect in FAD (ref. 5). We have determined the pattern of segregation of the AP gene in FAD pedigrees using restriction fragment length polymorphisms. The detection of several recombination events with FAD suggests that the AP gene is not the site of the inherited defect underlying this disorder.

Alzheimer Disease↗
PubMedDate not supplied

Relationship between plasma norepinephrine and sympathetic neural activity.

For circulating norepinephrine (NE) to reflect sympathetic activity validly, plasma NE should show an intensity-dependent increase during sympathetic stimulation and decrease during sympathetic inhibition, and circulating NE should correlate with more directly obtained measures of sympathetic activity. Review of published evidence indicates that NE in peripheral plasma satisfies these criteria. However, models used to explain the relationship between circulating NE and sympathetic activity must take into account processes intervening between the synaptic cleft and free NE in the circulation and, since sympathetic outflow is regionalized, the contributions of specific vascular beds to circulating NE. In this report a model is presented where removal processes for NE are viewed as acting in series to produce a gradient in NE concentrations from synapse to plasma, and where the relative contributions of specific vascular beds are calculated from the arteriovenous difference in plasma NE across those beds and the percentage of cardiac output distributed to them. In general, venous plasma NE provides a useful estimation of average sympathetic outflow.

Animals↗