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Biomedical subjects

L Volicer

Publications and source records attributed to L Volicer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prenatal protein malnutrition effects on the serotonergic system in the hippocampal formation: an immunocytochemical, ligand binding, and neurochemical study.

Prenatally protein malnourished rats born to dams maintained on a 6% casein diet during pregnancy and then fostered at birth to females on a 25% casein diet show adult alterations in hippocampal kindling and long-term potentiation and behavioral changes that all suggest dysfunction of hippocampal formation (HF). In the present investigation, compared to well-nourished controls, 220 day malnourished rats exhibited a decrease in the 5-HT fiber density in the dentate gyrus (DG) and CA3 subfield and, a 15-25% decrease 5-HT uptake sites assayed with [3H]-citalopram in CA3 and CA1. In malnourished rats, 5-HT1A receptors assayed with [3H]8-OH-DPAT were decreased by 20% in CA3. Because most hippocampal subfields showed no 5-HT changes, hippocampal 5-HT levels determined via HPLC methods were similar in adult malnourished and control rats. These results suggest that there are localized changes in the 5-HT afferent system in the hippocampal formation of the 220 day prenatally protein malnourished rat. Considering the 5-HT afferent input to inhibitory intrahippocampal neurons, the decreased 5-HT plexus may result in increased inhibition within specific hippocampal subfields despite overall normal levels of 5-HT in the total HF.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Measurement of severity in advanced Alzheimer's disease.

BACKGROUND: In late stages of dementia of the Alzheimer type (DAT), most scales measuring only cognitive or functional deficits lose their sensitivity to detect further disease progression. METHODS: By combining ratings of cognitive (speech, eye contact) and functional deficits (dressing, eating, ambulation) with occurrence of pathological symptoms (sleep-wake cycle disturbance, muscle rigidity/contractures), a scale was developed (BANS-S) which does not lose its sensitivity until the patient reaches a vegetative state. BANS-S was tested on three Special Care Dementia Units. RESULTS: Data from 74 patients with the clinical diagnosis of DAT indicated that BANS-S has good reliability and reproducibility. BANS-S scores correlated with scores of Mini-Mental State Examination, Katz ADL, Test for Severe Impairment, and Language Assessment. In 25 patients with the diagnosis of DAT confirmed by autopsy, BANS-S scores determined within 3 months of death correlated with density of neurofibrillary tangles in CA2 and CA3 areas of the hippocampus. CONCLUSION: BANS-S may be a useful tool for the evaluation of different treatment strategies in severe DAT and for the correlation of clinical and pathological findings.

Aged↗
PubMed1994

Impact of special care unit for patients with advanced Alzheimer's disease on patients' discomfort and costs.

OBJECTIVE: To compare outcomes in patients with the clinical diagnosis of probable dementia of the Alzheimer type (DAT) cared for in a Dementia Special Care Unit (DSCU) with those in traditional long-term care (TLTC). DESIGN: Two-year prospective cohort study. SETTING: Two Veterans Administration Hospitals. The DSCU concentrated on assuring patients' comfort instead of promoting maximal survival; in some patients this excluded transfer to acute medical settings, the use of antibiotics, and tube feeding. MEASUREMENTS: Data were collected regarding disease severity, patient discomfort, use of medical resources, and mortality rate. RESULTS: Patients at both settings were similar on baseline measures, and most were severely demented. The monthly levels of observed discomfort were lower in DSCU than in TLTC patients. The costs of medications, radiology, and laboratory procedures were lower in DSCU than in TLTC patients. DSCU patients were also transferred less frequently to an acute medical setting. The average 3-month cost for a DSCU patient was $1477 less than the cost of care for a TLTC patient. However, DSCU patients with lower severity of DAT had a higher mortality rate then TLTC patients. CONCLUSIONS: These results suggest that management of patients with advanced DAT on a DSCU using a palliative care philosophy may result in less patient discomfort and lower costs than management on a TLTC.

Aged↗
PubMed1993

Non-age related differences in thrombin responses by platelets from male patients with advanced Alzheimer's disease.

Alzheimer's Disease(AD), characterized by a deposition of beta-amyloid peptide (beta/A4) in the brain and in the cerebral microvasculature of affected individuals, is derived from its precursor protein (beta APP) via proteolytic processing by enzyme(s) which have not yet been characterized or localized. Since platelets carry APP in one of their granules, they have been implicated as a source of the beta/A4 deposits in the microvasculature of AD patients, attributable to either an abnormality in the platelets' stimulus response, in the quantity or nature of the APP they release upon activation and/or in the processing of that protein. We show here that platelets from patients with severe AD have abnormal stimulus responses to alpha-thrombin. Specifically, these cells hyperacidify. While it is not clear why this abnormality occurs, it may contribute to aberrant granule secretion since we have demonstrated earlier that release of platelet granule contents is partially controlled by the cytoplasmic pH.

Adult↗
PubMed1993

Heterogeneity of brain gene expression in Alzheimer's disease.

We have examined the expression of several genes whose transcripts have increased levels in Alzheimer's disease and have found heterogeneity in these levels in different patients with this condition. The level of expression of these genes was compared to different clinical and pathological aspects of the disease. A case with markedly elevated alpha 1-antichymotrypsin mRNA levels demonstrated prominent neuronal accumulation of this protein. Many of the neurons which demonstrated alpha 1-antichymotrypsin staining did not have neurofibrillary tangles, and vice versa. This suggests that alpha 1-antichymotrypsin staining might identify a different facet of the pathology of Alzheimer's disease than does neurofibrillary tangle staining and may provide new information in the study of this condition.

Aged↗
PubMed1993

Palliative fever management in Alzheimer patients. quality plus fiscal responsibility.

Aggressive medical treatment of infections does not affect the progressive course of dementia of the Alzheimer type (DAT) and has limited effect on the mortality rate. Utilization of health care resources and discomfort during a fever episode were compared in three differing treatment conditions: in 18 patients in a dementia special care unit (DSCU) who received palliative management, 26 patients in a DSCU who were treated aggressively, and 17 DAT patients in traditional long-term care units who were treated aggressively. Both groups of patients in the DSCU had lower discomfort scores, lower utilization of high-cost health care resources, and higher utilization of analgesics and narcotics. A nursing model of care incorporating hospice concepts into the DSCU is suggested.

Aged↗
PubMed1993

Predicting short-term survival for patients with advanced Alzheimer's disease.

OBJECTIVE: The purpose of this study was to develop a statistical model for predicting short term survival in patients with dementia of the Alzheimer type (DAT). DESIGN: A prospective cohort study. SETTING: Three 25-bed intermediate medical care units using a structured approach to patient care management including palliative care options and patients from a second, traditional long-term care setting. PARTICIPANTS: Of 104 patients with advanced DAT monitored for 34 months, 68 patients (97% white male) who had at least one fever episode were included in the model development phase. Data from 71 additional DAT patients with at least one fever episode were used to test the statistical model. MAIN OUTCOME MEASURES: Six-month survival following a fever episode. RESULTS: Older age and higher severity of DAT at the time of the fever episode, palliative care, and hospital admission for long-term care within 6 months prior to the fever were found to be positively associated with likelihood of mortality within 6 months of the fever onset. Adjusted odds ratios for each of these variables were statistically significant. The model performed well in subsequent testing on an independent sample of patients. CONCLUSION: Results provide a formula which can be used to predict likelihood of dying within 6 months following onset of a fever in DAT patients. This statistical prediction is recommended for use in combination with clinical judgment to certify DAT patients for Medicare hospice coverage.

Age Factors↗
PubMed1993

Is hospice care appropriate for Alzheimer patients?

Hospice care can benefit late-stage Alzheimer's patients, but caregivers and families must first be aware of the complications and treatment difficulties that often accompany Alzheimer's disease. From this awareness they can determine whether and when hospice care is appropriate for their patients or loved ones.

Aged↗
PubMed1992

Increased levels of neuronal thread protein in cerebrospinal fluid of patients with Alzheimer's disease.

Neuronal thread protein is a recently characterized, approximately 20-kd protein that accumulates in brains with Alzheimer's disease (AD) lesions. This study examined whether concentrations of neuronal thread protein (NTP) were also increased in the cerebrospinal fluid (CSF) of individuals with probable (clinically diagnosed) and definite (histopathologically proved) AD. Using a highly sensitive three-site monoclonal antibody-based immunoradiometric assay, we measured NTP concentrations in CSF from 84 patients with probable AD and mild dementia (duration, 4.05 +/- 0.36 years), 45 with Parkinson's disease and minimal or no dementia (duration, 4.73 +/- 0.78 years), 73 with multiple sclerosis, and 73 nondemented control subjects. NTP concentrations were also measured in postmortem ventricular fluid and temporal lobe neocortex extracts from 31 subjects with histopathologically proved AD and 14 age-matched control subjects. The mean concentration of NTP in the CSF was higher in AD (4.15 +/- 0.25 ng/ml; 95% confidence interval [CI] limits, 3.65-4.65) than in Parkinson's disease (1.96 +/- 0.16 ng/ml; 95% CI, 1.65-2.27), multiple sclerosis (1.6 +/- 0.14 ng/ml; 95% CI limits, 1.33-1.88), or control subjects (1.27 +/- 0.06 ng/ml; 95% CI limits, 1.15-1.40) (p < 0.001). In addition, 70% of the patients with probable AD had concentrations of NTP in CSF that were higher than 2.5 ng/ml (> upper 99% CI limit in the control group), compared with 23% of Parkinson's disease patients, 11% of multiple sclerosis patients, and 4% of control subjects. The mean concentrations of NTP in the ventricular fluid and brain tissue from individuals with documented AD and end-stage dementia were threefold higher than the levels detected in the CSF from the remaining patients with probable AD and mild dementia. Moreover, of 9 patients with AD, postmortem brain and CSF manifested 5- to 50-fold higher levels of NTP compared with the CSF samples obtained an average of 6 years earlier. These findings demonstrate that NTP levels are elevated in the CSF of individuals with AD and that NTP levels in the CSF increase strikingly with progression of dementia and neuronal degeneration.

Adult↗
PubMed1992

Assessment of discomfort in advanced Alzheimer patients.

An objective scale for measuring discomfort in noncommunicative patients with advanced Alzheimer's disease was empirically generated from the perspectives of nursing staff practicing on special care Alzheimer units and was judged to have content validity. On the basis of a pilot test, the discomfort scale was reduced to nine items. Quantifiable scoring procedures and a rater training program were developed. The scale (DS-DAT) was tested longitudinally for 6 months with 82 subjects at two sites. Psychometric properties, measurement issues, and recommendations for use in practice and research are discussed.

Alzheimer Disease↗
PubMed1992

Neurochemical changes in the rat brain after intraventricular administration of tryptamine-4,5-dione.

Tryptamine-4,5-dione (4,5-DKT) a neurotoxic derivative of serotonin (5-HT), was injected into the lateral ventricle of the rat in order to evaluate its biochemical effects. The levels of 8 substances in the hippocampus, striatum and prefrontal cortex were examined 3, 7 and 14 days after treatment with 4,5-DKT. 5-Hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in all three regions by days 7 and 14, respectively. Tryptamine-4,5-dione had no significant effect on dopaminergic or adrenergic systems or on the levels of L-tryptophan and L-tyrosine, in any of the three areas of brain examined. Reduced activity of tryptophan hydroxylase in the cortex was observed 14 days after administration of 4,5-DKT. However, administration of 4,5-DKT did not alter the binding of [3H]paroxetine, a specific antagonist of the uptake of 5-HT, to nerve terminals. These results indicate that 4,5-DKT produced depletion of 5-HT without eliminating serotoninergic nerve terminals.

Animals↗
PubMed1992

Prenatal protein malnutrition in rats enhances serotonin release from hippocampus.

The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism.

Animals↗
PubMed1992

Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease.

OBJECTIVE: The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders. METHOD: Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity. RESULTS: Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement. CONCLUSIONS: Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.

Aged↗
PubMed1992

A single-case-study method for treating resistiveness in patients with Alzheimer's disease.

A single-case-study approach was used to identify the best medication for treating resistiveness to care in patients with moderately advanced dementia. The double-blind research design incorporated three medications, placebo washout periods, multiple baselines, frequent ratings by nurses of patients' resistiveness, and visual and statistical analysis of results to find the optimal drug, one that provided a stable response at a low dose. Six patients completed the trials. Thiothixene was more effective than oxazepam and diphenhydramine. Important features of the design were its avoidance of polypharmacy and high doses and its use of frequent ratings (each nursing shift) of patients' resistiveness. Although the single-case-study method is labor intensive, it can be beneficial when adapted for clinical use.

Aged↗