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Biomedical subjects

L Tune

Publications and source records attributed to L Tune.

25 records · Page 2Linked to original sources

Cerebrospinal fluid acetylcholinesterase activity in senile dementia of the Alzheimer type.

Acetylcholinesterase (AChE) activity was measured in cerebrospinal fluid (CSF) samples from 36 individuals, including 12 persons with Alzheimer's disease, 12 normal controls, and 12 patients with other dementias. AChE activity also was measured in 47 normal subjects whose ages ranged from 20 to 84 to evaluate the effect of age on AChE activity. CSF from patients with senile dementia of the Alzheimer type showed significantly lower mean AChE activity than in age-matched controls and patients with other dementia syndromes. No correlation was found between duration of illness, age, or severity of illness (as measured by the Mini-Mental State Examination score) and CSF AChE activity in Alzheimer's disease. AChE increased significantly over the age range of 20 to 84. CSF AChE activity may prove to be a useful diagnostic test to confirm the clinical diagnosis of moderate to severe Alzheimer's disease.

Acetylcholinesterase↗

Serum neuroleptic concentrations and clinical response: a radioreceptor assay investigation of acutely psychotic patients.

Twenty-two acutely psychotic patients were rigorously assessed for psychopathology at baseline and after 14 days of neuroleptic treatment. The neuroleptic radioreceptor assay (NRRA) was used to determine serum neuroleptic concentrations. Serum neuroleptic concentration was significantly, nonlinearly related to changes in BPRS Total Score, and BPRS Factor Scores for Thought Disturbance and Anxiety-Depression. Clinical improvement was associated with intermediate (11-50, 51-126 ng/ml haloperidol equivalents) while poor clinical outcome was related to both low (less than or equal to 10 ng/ml) or high (greater than 125 ng/ml) serum levels. The results are discussed in terms of a possible "therapeutic window" for the neuroleptics and the implications this might have for clinical practice.

Adolescent↗

Acute extrapyramidal side effects: serum levels of neuroleptics and anticholinergics.

An assay technique for measuring anticholinergic drugs in human serum based upon their inhibition of the specific binding of [3H]-quinuclidinyl benzilate to rat brain muscarinic receptors is described. The assay was validated by demonstrating a close correlation (r = 0.99) between serum levels of nortriptyline measured by the radioenzymatic assay and a GLC technique. The assay measures free anticholinergics, and under standard assay conditions, approximately 95% of benztropine is bound to serum protein. Marked variation in serum anticholinergic levels in patients receiving the same oral dose was observed, and in individual patients there was a non-linear relationship between increasing oral dose and serum anticholinergic levels. In a cross-sectional study of 109 patients receiving concurrently neuroleptics and anticholinergics, there was no correlation (r = 0.029) between serum neuroleptic levels measured by radioreceptor assay and extrapyramidal side effects (EPS). In the patients whose serum anticholinergic levels were also determined, there was a significant inverse correlation (r = 0.44) between anticholinergic levels of EPS. In this cohort of patients, there was no significant correlation between serum anticholinergic and serum neuroleptic levels (r = 0.16) and the ratio of serum anticholinergic to serum neuroleptic was a poor predictor of EPS (r = 0.26). The results suggest a marked variation in sensitivity of patients to the EPS-inducing of neuroleptics; nevertheless, the incidence of EPS decreases with increasing serum levels of anticholinergics. An optimal serum anticholinergic level of 10 pmole atropine equivalent per ml was associated with a low incidence of EPS and is relevant to drug action at the striatal muscarinic receptor.

Acute Disease↗

Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects.

A simple, sensitive, and specific radioreceptor assay has been developed for the measurement of anticholinergic drugs in human serum. The assay is based on the competitive inhibition by free anticholinergic drugs in a 0.2-mL sample of serum with the specific binding of the potent muscarinic antagonists, tritiated quinuclidinyl benzilate, to solubilized brain muscarinic receptors. Anticholinergic activity could be detected regardless of drug structure and was quantified against atropine standards. Although the serum levels of anticholinergic drugs varied considerably in 35 patients receiving both neuroleptic and anticholinergic drugs, there was a highly significant inverse correlation between the presence of acute extrapyramidal side effects due to neuroleptics and the serum levels of anticholinergics.

Adult↗

Tricyclic antidepressant radioreceptor assay.

A radioreceptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-quinuclidinyl benzilate (3H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that in can detect, for example, 2 ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects.

Animals↗

Neuroleptic treatment of late-life schizophrenia.

There is a paucity of studies on the use of neuroleptic medication for treatment of the core symptoms of schizophrenia in elderly patients. The studies that are available have significant methodologic problems, including the mixing of early- and late-onset patients, inadequate outcome criteria, and the lack of control groups. Studies of conventional neuroleptics suggest that older patients have a moderate therapeutic response but are likely to develop side effects. The few studies of atypical antipsychotics now available suggest efficacy for treatment of behavioral disturbance in the elderly and a more favorable side-effect profile. The usefulness of all neuroleptics for the treatment of the core symptoms of late-life schizophrenia may depend on the duration and severity of the symptoms, with a poor response associated with greater severity and duration. It appears that patients with later-onset symptoms may respond better to all neuroleptics.

Aged↗