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Biomedical subjects

W J Burke

Publications and source records attributed to W J Burke.

At least 19 recordsLinked to original sources
PubMed1992

Validation of a telephone version of the mini-mental state examination.

OBJECTIVE: To assess the construct validity of a telephone-administered version of the Mini-Mental State Examination (MMSE). DESIGN: Validity testing by comparing a telephone version of the MMSE administered first to a face-to-face evaluation done several days later. SETTING: Outpatient geriatric assessment center. SUBJECTS: 100 of 175 consecutive referrals. MAIN OUTCOME MEASURES: MMSE and a brief neuropsychological screening test (BNPS) face-to-face and a telephone version of the MMSE as part of the Adult Lifestyles and Function Interview (ALFI-MMSE). RESULTS: Test scores of the two MMSE versions correlated strongly for all subjects (Pearson's r = 0.85, P = 0.001) and remained significant for the cognitively intact (P = 0.02) and questionably (P = 0.002), mildly (P = 0.0001), and moderately (P = 0.003) demented. Comparison of the two versions' equivalent 22 items revealed no significant difference for scores of all subjects (P = 0.07) but with a trend toward higher scores in the original version. Diminished hearing, reported either by the subject (P = 0.003) or by the collateral source (P = 0.02) was associated with lower scores on the telephone version. Five individual test items were biased by the route of test administration. Sensitivity and specificity relative to the BNPS were 67% and 100% for the ALFI-MMSE and 68% and 100% for the MMSE, respectively. CONCLUSION: The scores on the ALFI-MMSE correlated strongly with the scores of the original version given face-to-face in subjects undergoing geriatric assessment. The results indicate that the ALFI-MMSE could be a useful and economical tool to screen for cognitive impairment.

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PubMed1992

A prospective evaluation of the Geriatric Depression Scale in an outpatient geriatric assessment center.

OBJECTIVE: To prospectively evaluate the Geriatric Depression Scale (GDS) in cognitively intact and impaired patients undergoing outpatient geriatric assessment. SUBJECTS: One hundred ninety-four geriatric patients evaluated in a 1-year period. SETTING: The outpatient Geriatric Assessment Center of the University of Nebraska Medical Center. MEASUREMENTS: The 30-item GDS was completed by all patients. The patients were then evaluated by one of three geriatric psychiatrists who were blind to the GDS results. The prospective clinical diagnosis of major depression was compared to the GDS results. Patients were categorized as cognitively impaired or intact on the basis of the Mini-Mental State Examination. Data were analyzed using ROC curves. An optimal cutoff was identified which was the total score on the GDS with the highest combined sensitivity and specificity. RESULTS: ROC curve analyses showed good agreement between the clinical diagnosis and the GDS in both cognitively intact and impaired subjects. Cognitively intact, euthymic patients reported a mean of 8.4 symptoms, while cognitively impaired, euthymic patients, reported a mean of 8.7. Cognitively intact, depressed patients reported a mean of 14.7 symptoms, while cognitively impaired, depressed patients reported a mean of 15.0. CONCLUSIONS: This study provides further evidence that the GDS is as accurate a screening test for depression in cognitively impaired as in intact patients.

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PubMed1991

Degeneration of the cholinergic innervation of the locus ceruleus in Alzheimer's disease.

Choline acetyltransferase (Acetyl-CoA: choline O-acetyltransferase: EC 2.3.1.6) (ChAT) enzyme activity and neuron density were measured in the locus ceruleus (LC) of autopsied brains of neurologically normal individuals and patients who had Alzheimer's disease. Neuron density in the LC of individuals with Alzheimer's was significantly reduced to approximately 50% of normal values. ChAT activity was also reduced by about 50%. Furthermore, the number of pigmented neurons in the LC was highly correlated with presynaptic ChAT activity. These findings were specific for the LC, since deficits in ChAT and neuron density were not found in two adrenergic brainstem nuclei (C1 and C2). We measured mitogen activity in LC extracts in order to determine whether loss of cholinergic afferents to the LC, as evidenced by loss of ChAT, was related to putative trophic factors. Mitogen activity was significantly reduced (50%) in the Alzheimer's group as compared to normals. Mitogen activity was significantly correlated with ChAT activity and the density of neurons in the LC. The loss of cholinergic nerve terminals in the LC in Alzheimer's disease may be functionally significant, since acetylcholine has important effects on LC physiology. The highly significant relationships between ChAT, neuron density and mitogen activity has important implications for our understanding of mechanisms of neurodegeneration in Alzheimer's disease.

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PubMed1991

Effect of pre- and postmortem variables on specific mRNA levels in human brain.

The method of polymerase chain reaction was used to investigate the pre- and postmortem factors which affect the stability of specific mRNAs in the C1 region of human autopsy brain. Eight premortem and 4 postmortem factors were correlated to levels of phenylethanolamine N-methyltransferase (PNMT), three splice forms of amyloid precursor protein (APP) and actin mRNAs in 10 control brains using Pearson's correlation coefficient. Significant negative correlations were found between hypoxia and PNMT mRNA, and between postmortem and storage intervals and APP751 and beta-actin mRNAs. A positive correlation was found between death-refrigeration interval and total APP and APP695 mRNAs. There was also a positive correlation between seizure activity and APP770 mRNA. The results indicate that a variety of pre- and postmortem factors can affect mRNA levels. The possible effect of pre- and postmortem factors on specific mRNA levels should be investigated prior to comparing mRNA levels in different disease states.

Adult↗
PubMed1991

Neuroleptic drug use in the nursing home: the impact of OBRA.

In 1990 the new OBRA legislation affecting nursing home care went into effect. This legislation and the regulations written to interpret it introduce specific rules concerning the use of neuroleptic medication in the care of nursing home residents. This article examines this legislation and the new regulations, and reviews neuroleptic drug use, including appropriate indications, side effects and prescribing guidelines. Physicians who care for nursing home patients should be familiar with the regulations.

Antipsychotic Agents↗
PubMed1990

Evidence for decreased transport of tryptophan hydroxylase in Alzheimer's disease.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin and a specific marker for serotonergic neurons. These neurons are affected in Alzheimer's disease (AD) in several ways: serotonin is decreased in axon terminals, serotonin neurons accumulate neurofibrillary protein, and these neurons are lost in AD brains. One subcellular mechanism which may underlie degeneration of neurons in AD is decreased axonal transport with accumulation of enzymes and their potentially toxic metabolites in the cell body. To determine whether there is a defect in axonal transport in serotonin neurons in AD we measured TPH activity, serotonin and its oxidative metabolite 5-hydroxyindoleacetic acid (5-HIAA) in dorsal raphe cell bodies from Alzheimer and control cases. TPH activity is increased 4.7-fold in raphe neuron cell bodies in Alzheimer brains. Serotonin and 5-HIAA are increased by 4.0- and 2.0-fold, respectively in Alzheimer compared to control raphe cell bodies. In contrast, in synaptic terminals of the amygdala 5-HT and 5-HIAA were decreased by 41% and 50%, respectively in the same AD cases. We propose that the accumulation of TPH and its products in the raphe perikarya in AD results from a diminished transport of TPH to axon terminals. The accumulation of oxidative metabolites of serotonin may contribute to the degeneration of serotonergic neurons in AD.

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PubMed1990

Does the Williams Manual Test predict service use among subjects undergoing geriatric assessment?

This study examines the utility of the Williams Manual Test (WMT) in predicting those older patients who will eventually require formal services. One hundred seventeen older subjects underwent comprehensive geriatric assessment that included administration of the WMT and questionnaires assessing current service use. Study participants returned at 6 and 12 months for repeat measurement of study variables. The WMT was found to be a significant predictor of additional service use at 12 months (chi 2 = 6.4, P less than .01). The test had high specificity (83%) but relatively low sensitivity (40%). The lack of sensitivity in this study group was likely due to high levels of stress among caregivers whose relative was otherwise not predicted to need services. When the WMT was repeated after 6 and 12 months, the results were highly reproducible. The WMT appears to be a useful predictor of increasing formal service use. However, in certain study groups, its predictive ability may be affected by high levels of caregiver stress.

Activities of Daily Living↗
PubMed1990

Evidence for decreased transport of PNMT protein in advanced Alzheimer's disease.

Phenylethanolamine N-methyltransferase (PNMT) is the rate-limiting enzyme in the synthesis of epinephrine and a specific marker for adrenergic neurons. PNMT protein is decreased in axon terminals in brains from patients with Alzheimer's disease due to retrograde degeneration of epinephrine neurons. To determine the subcellular mechanism underlying retrograde degeneration, the distribution of PNMT between axon terminal and cell body was calculated in early and advanced Alzheimer cases compared with age-matched controls. In early Alzheimer's disease there is a decrease in PNMT in axon terminals and in total PNMT in epinephrine cell bodies and terminals compared with control values. There is no difference in the ratio of PNMT in cell body/axon terminal compared with controls. In contrast, in advanced Alzheimer's disease, PNMT activity increases by 124% in epinephrine neuronal cell bodies compared with controls. Immunochemical titration shows that this increased enzyme activity is due to an increase in PNMT protein. The cell body/axon terminal ratio of PNMT is increased 2.5-fold in advanced Alzheimer's disease compared with controls. These findings are consistent with the hypothesis that in early Alzheimer's disease there is a decreased synthesis or increased degradation of PNMT. However, in advanced Alzheimer's disease we propose that the accumulation of this enzyme in the perikarya results from a diminished transport of PNMT to axon terminals. We further postulate that epinephrine, the product of PNMT, and its further metabolites are endogenous neurotoxins. Therefore, the accumulation of PNMT in epinephrine cell bodies may contribute to the degeneration of these neurons in Alzheimer's disease.

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PubMed1990

Use of psychostimulants for the elderly.

As the number of people over age 65 continues to grow, a clear understanding of the usefulness and limitations of psychostimulants in treating elderly persons becomes more important. The authors review the limited literature and discuss the use of psychostimulants for treating "senility," including their effects on cognition, amotivational syndromes, and depression. They conclude that early studies of "senile" patients suffered from a lack of clear diagnostic standards and did not address the issue of whether measurements of the target symptoms being assessed were reliable or valid. The authors suggest that future studies more clearly define age groups, diagnostic criteria, and scales to measure the effects of psychostimulants.

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PubMed1989

Detection of 3,4-dihydroxyphenylglycolaldehyde in human brain by high-performance liquid chromatography.

The monoamine oxidase A metabolite of noradrenaline, 3,4-dihydroxyphenylglycolaldehyde, is the precursor of 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylglycol, metabolites of noradrenaline. Owing to difficulties in purifying this aldehyde, it has not been previously characterized or identified in biological sources. This paper describes an enzymatic synthesis, purification, and characterization of 3,4-dihydroxyphenylglycolaldehyde. The aldehyde metabolite is identified in postmortem human brain using high-performance liquid chromatography and electrochemical detection. We estimate the concentration in human hippocampus to be 0.164 +/- 0.05 nmol/g. The importance of this aldehyde metabolite of noradrenaline is discussed.

Adsorption↗
PubMed1989

The neurological features of early and 'latent' human immunodeficiency virus infection.

Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.

AIDS Dementia Complex↗
PubMed1989

Use of the Geriatric Depression Scale in dementia of the Alzheimer type.

The Geriatric Depression Scale (GDS) has been shown to be an effective screening test for depression in selected geriatric populations. However, it has not been evaluated as a screening test for depression among elderly adults with dementia of the Alzheimer type. Over a two-year period 283 patients were seen in a geriatric assessment center and were screened for depression using the Geriatric Depression Scale. They also received a clinical psychiatric diagnosis by one of two geropsychiatrists. Patients with a Clinical Dementia Rating (CDR) of 0 (cognitively intact) (n = 70) and those with mild Alzheimer's disease (CDR of 1) (n = 72) were selected for comparison. The data were analyzed using Receiver Operating Characteristic Curves (ROCs) in order to compare the utility of the Geriatric Depression Scale in these two groups. ROC curves, which plot sensitivity against false positives, have come into increasing use as a method of examining the clinical performance of tests. The area lying beneath the curve (AUC) can be estimated and used as a quantitative measure of test performance (equivalent to the Wilcoxon rank sum). In the intact group, the Geriatric Depression Scale produced a ROC curve with an AUC of 0.85 (percent score = 1), which is significant (z = 7.28, P less than .0001). In the group composed of those with Alzheimer's disease, the Geriatric Depression Scale yielded a ROC curve with an AUC of 0.66, which was not significantly different from chance (z = 1.92, P = NS). This study provides empirical evidence that while the Geriatric Depression Scale is an accurate screening test for depression in cognitively intact geriatric populations, it does not maintain its validity in populations that contain large numbers of patients with dementia of the Alzheimer type.

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PubMed1989

Musical hallucinations. The sounds of silence?

Hallucinations may occur in any sensory modality. Auditory hallucinations, usually ascribed to psychiatric illness, take various forms including the perception of voices, cries, noises, or rarely, music. Formed musical hallucinations, (ie, the perception of either vocal or instrumental melodies), reported in the English literature to date have typically been associated with marked hearing loss, advanced age (average 67.8 years), female sex (71%), lack of response to treatment, and general lack of associated psychopathology. We have collected data on seven additional patients with musical hallucinations. The average age of these patients was 72.9 years; all were women. Six had significant hearing problems. All reported onset of musical hallucinations after the age of 60. Interestingly, all seven had major psychiatric illnesses. Four had major depression, two had late-onset schizophrenia, and one had multi-infarct dementia. Of the five who had CT scans, one was normal and the rest demonstrated varying degrees of brain pathology. Neuroleptics were used with varying results in three cases; antidepressants were used in two depressed patients and were temporally related to the onset of musical hallucinations in one patient. Electroconvulsive therapy (ECT) was very effective in treating depression and musical hallucinations in the three patients for whom it was used, usually providing relief from hallucinations after only two treatments. Our collection of cases demonstrates that musical hallucinations can occur in association with psychiatric illness, and perhaps unlike the hallucinations associated with isolated hearing loss, may respond to conventional treatments for the underlying psychiatric disorder. Hearing loss is neither a necessary nor sufficient condition for the occurrence of musical hallucinations.

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PubMed1988

Effect of dopamine on tyrosine hydroxylase in cultured rat adrenal medulla.

Explants of rat adrenal medulla were cultured in defined medium for up to 22 hr. Addition of dopamine to the medium led to a diminution in the activity of tyrosine hydroxylase (tyrosine 3-monooxygenase; EC 1.14.16.2) in the tissue. The enzyme activity was inversely proportional to the concentration of dopamine in the culture medium. The extent of loss of tyrosine hydroxylase, as measured by immunochemical titration, corresponded to the degree of loss in enzyme activity under the same conditions. The decreased amount of enzyme protein was due to a decrease in the rate of synthesis of tyrosine hydroxylase. However, this effect was not specific in that the relative rate of tyrosine hydroxylase synthesis was not decreased. Metabolites of dopamine when added to the medium did not affect tyrosine hydroxylase activity. Two other adrenal medullary enzymes, monoamine oxidase (EC 1.4.3.4) and acid phosphatase (EC 3.1.3.2), were not affected by addition of dopamine to the medium. The results indicate that elevated cytoplasmic levels of dopamine decrease the concentration of tyrosine hydroxylase by inhibiting protein synthesis.

Adrenal Medulla↗
PubMed1988

Reliability of the Washington University Clinical Dementia Rating.

There is a growing need for methods for measuring and staging the natural history of dementia of the Alzheimer type. One instrument, designed with that purpose in mind, is the Washington University Clinical Dementia Rating. We tested its reliability using multiple clinicians in a videotape-design study, and it proved reliable under these study conditions.

Aging↗
PubMed1988

Mild senile dementia of the Alzheimer type: 2. Longitudinal assessment.

Forty-three subjects with mild senile dementia of the Alzheimer type (SDAT, so-called probable Alzheimer's disease) were studied longitudinally by serial administration of several tests to rate dementia. Comparison was made with 58 healthy elderly controls. The clinical diagnosis was confirmed in all 16 autopsies. At 5 years after entry into the study, the cumulative rate of nursing home placement was 73%, and of death, 30%, rising at 7 years to 84% and 44%, respectively. Four of six clinical measures of dementia were found to correlate with the natural history of SDAT. Several measures are better than a single one in carrying out longitudinal studies of the disorder.

Aged↗