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Biomedical subjects

W E Fann

Publications and source records attributed to W E Fann.

At least 19 recordsLinked to original sources

Three-dimensional mapping of local cerebral perfusion in alcoholic encephalopathy with and without Wernicke-Korsakoff syndrome.

Seventeen severe chronic alcoholic patients with and without Wernicke-Korsakoff syndrome (WKS) were examined prospectively after being treated by withdrawal from alcohol. The WKS patients also received thiamine supplements. Three-dimensional measurements of local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were made utilizing xenon contrast computed tomography (Xe CT-CBF). Results were displayed as color-coded brain maps before and after treatment and these were correlated with neurological and cognitive examinations. Before treatment chronic alcoholics without WKS (n = 10) showed diffuse reductions of LCBF values throughout all gray matter including hypothalamus, vicinity of nucleus basalis of Meynert, thalamus, and basal ganglia. Similar, but more severe, reductions were seen in patients with WKS (n = 7), however, white matter perfusion was also reduced. In WKS, most prominent reductions of LCBF were also seen in hypothalamus and basal forebrain nuclei but thalamus, basal ganglia, and limbic systems were severely reduced. After treatment, both groups with alcoholic encephalopathy showed marked clinical improvement and cerebral perfusion was restored toward normal. Chronic alcohol abuse, in the absence of thiamine deficiency, reduces CBF by direct neurotoxic effects. If thiamine deficiency is also present, more severe and localized hemodynamic reductions are superimposed.

Adult

Abstinence improves cerebral perfusion and brain volume in alcoholic neurotoxicity without Wernicke-Korsakoff syndrome.

Twenty severe chronic alcoholic patients with signs of neurotoxicity but without Wernicke-Korsakoff syndrome were treated by abstinence from alcohol and examined prospectively at intervals thereafter. Serial examinations included detailed medical histories, neurological examinations, cognitive capacity screening examinations, computed tomography scans with measurements of sulcal and ventricular volume, and measurements of regional CBF. All sedatives were withdrawn before CBF measurements were made. Before treatment, gray matter blood flow values were significantly reduced compared with those of age-matched normal volunteers, but white matter blood flow values were normal and the ventricles were enlarged. After abstinence from alcohol, mean gray matter blood flow values and brain volume both increased significantly.

Adult

Noradrenergic and cholinergic agents in Korsakoff's syndrome.

Subjects suffering from memory disorders associated with Korsakoff's syndrome were treated with noradrenergic and cholinergic drugs in two phases. In the acute phase, tests of short- and long-term memory were conducted shortly after the administration of methylphenidate, physostigmine, an oral placebo, and an intramuscular placebo. In the chronic phase, the memory tests were given after the subjects had been administered each of the following for 1-week periods: methylphenidate, choline chloride, methylphenidate plus choline chloride, and an oral placebo. Significant improvements were seen in long-term memory scores of patients receiving chronic methylphenidate treatment. Significant improvement was not found in short-term memory measures with any of the drug treatments.

Aged

Cerebral atrophy and hypoperfusion improve during treatment of Wernicke-Korsakoff syndrome.

Nineteen patients with sudden onset of impaired recent memory, cerebellar ataxia, peripheral neuropathy, and other signs of Wernicke-Korsakoff syndrome (WKS) were treated and examined prospectively for 3 months. Serial studies included histories, neurological examinations, cognitive capacity screening examinations (CCSE), computed tomography (CT) scans, and measurements of regional CBF. Patients were detoxified and withdrawn from sedatives before CBF measurements were examined. Treatment included alcohol withdrawal, nutritious diet, and 300 mg thiamine daily. Before treatment CCSE scores and blood flow values of both white and gray matter were reduced, particularly within both temporoparietal regions. After treatment of compliant patients (n = 10), white and gray matter blood flow increased concurrently with improved CCSE scores. Abnormal eye signs, ataxia, peripheral neuropathy, and performance of activities of daily living also improved. Cerebral atrophy and ventricular enlargement measured by CT decreased. Early recognition and treatment of WKS in compliant patients permit rapid reversals of cognitive and neurological impairments associated with increased blood flow of gray and white matter and improvements of brain atrophy measured by CT scanning.

Adult

Alprazolam in older depressed inpatients.

Alprazolam, a triazolobenzodiazepine first developed as an anxiolytic, has been shown to be effective in the treatment of depression in several comparison studies with tricyclic antidepressants. This open label study examined the efficacy and safety of alprazolam in patients aged 56-78. Of 18 patients with evaluable data, 12 were responders (improvement greater than or equal to 50% on the Hamilton Depression Rating Scale); 4 patients were partial responders (HAM-D improvement of 25%-49%); and 2 patients were nonresponders. Initial drowsiness was the only side effect observed.

Aged

A method for the determination of amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma using stable isotope dilution and gas chromatography-chemical ionization mass spectrometry (GC-CIMS).

A gas chromatography--mass spectrometry (GC-MS) method has been developed to measure amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma. Deuterated analogs of each compound were synthesized as internal standards. Isobutane was used as both gas chromatography (GC) carrier gas and chemical ionization (CI) reagent gas. In order to obtain compounds with satisfactory GC and mass spectrometry (MS) properties, the two alcohol metabolites were dehydrated without loss of label during sample preparation. Selective ion monitoring of the MH+ ions of the protio- and deuterio- compounds gave ion ratios which were converted to plasma concentrations using standard curves. For amitriptyline and nortriptyline, which are assayed using multiple deuterated analogs as internal standards, the curves are straight lines. For 10-hydroxyamitriptyline and 10-hydroxynortriptyline, which are assayed using monodeuterated analogs as internal standards, the curves are nonlinear and are analyzed using an iterative computer procedure. Assay sensitivity is 0.5 ng/ml for amitriptyline, nortriptyline, and 10-hydroxyamitriptyline and 1 ng/ml for 10-hydroxynortriptyline. Assay precision and accuracy in terms of percent error are both less than 5%. Following oral administration of a single 75-mg dose of amitriptyline to two subjects, the mean plasma levels of amitriptyline, nortriptyline, 10-hydroxyamitriptyline, conjugated 10-hydroxyamitriptyline, 10-hydroxynortriptyline, and conjugated 10-hydroxynortriptyline were 36, 8, 10, 66, 16, and 46 ng/ml, respectively, at 2 hr after dosing and 3, 4, 0.5, 1, 6, and 17 ng/ml, respectively, at 72 hr after dosing. Analyses of plasma samples from 12 subjects who had been receiving 50 mg amitriptyline therapy three times a day for an average +/- SD of 32 +/- 5 days gave a mean concentration of 81 +/- 40 ng/ml for amitriptyline, 71 +/- 57 ng/ml for nortriptyline, 12 +/- 5 ng/ml for 10-hydroxyamitriptyline, 91 +/- 30 ng/ml for conjugated 10-hydroxyamitriptyline, 82 +/- 27 ng/ml for 10-hydroxynortriptyline, and 176 +/- 64 ng/ml for conjugated 10-hydroxynortriptyline.

Amitriptyline

Clinical research techniques in tardive dyskinesia.

The authors have developed standardized assessment and control techniques designed to provide objective measures of tardive dyskinesia in patients progressing through an experimental treatment program. Standardized videotaping is carried out and blind ratings on the Abnormal Involuntary Movement Scale are made by a team of psychiatrists and neurologists. Other assessments include several measurements of vocal function and a quantitative acceleration profile standardized on normal subjects. Such measures allow quantifiable determination of response to drug treatment and may provide clues to the etiology and definition of the dyskinetic syndrome.

Central Nervous System

Deanol acetamidobenzoate (Deaner) in tardive dyskinesia.

A total of twenty-nine patients have thus far been treated with deanol in various dosage levels for periods ranging from five to thirty days. Clinical response has been pronounced, even dramatic, in seven patients, moderate but significant in nine patients, and slight to insignificant in thirteen others. Videotape rating and quantitative accelerometry, to the extent that they constitute novel and stress-inducing experiences may not be representative of global clinical changes. Deanol did not produce the anticipated elevation in choline levels postulated to be one mechanism of its action. The failure of deanol to achieve this effect may most probably be attributed to interval after last dose, to inadequate level of deanol or to some alteration in choline metabolism in the presence of deanol. The etiology of tardive dyskinesia at biochemical and structural levels is complex. For some patients improvement has been dramatic and clearly associated with deanol. Others appear to exhibit minimal response which cannot be differentiated from placebo or environmental effects. Our present strategy, in common with that of other authors includes the administration of a "challenge" dose of rapid acting injectable cholinomimetic agents (e.g. physostigmine) and dopamine-blocking agents (e.g. haloperidol) with placebo controls. In this manner therapy may be more rationally selected for long-term use and may logically include deanol. The correlation of such predictive challenges with response to long-term treatment is an area for much more well controlled study.

Choline

Pharmacotherapy in older depressed patients.

Treatment of depression in elderly patients is not generically different from treatment of depression in younger age cohorts. Because of certain age-related physical, physiological, and biochemical factors, however, drug prescription for geriatric patients must be modified in several respects. Tricyclic antidepressants are the principal agents in treatment, but their side effects tend to be magnified in the elderly. Dosage should initially be lower than with younger patients and increased in gradual increments. Lithium, MAO inhibitors, and neuroleptics are appropriate in some cases, but additional precautions are necessary. Because the elderly are liable to multiple system decompensation, they are likely to be prescribed multiple pharmacological agents. Drug-drug interactions involving antidepressant medication present a variety of therapeutic problems and can threaten life. Depression in late life can be treated pharmacologically, but both the therapeutic and deleterious activities of the drugs can be altered by compromised organ systems.

Adjustment Disorders