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L Volicer

Publications and source records attributed to L Volicer.

At least 19 recordsLinked to original sources
PubMed1996

Neurotoxicity of free-radical-mediated serotonin neurotoxin in cultured embryonic chick brain neurons.

Exposure of serotonin (5-HT) to oxygen-derived free-radical-generating system, xanthine oxidase-hypoxanthine or to a Fenton reaction results in the formation of the neurotoxin, tryptamine-4,5-dione. In cultured embryonic chick brain neurons, incubation of tryptamine-4,5-dione or its ethyl carbonate derivative resulted in a dose-dependent neurotoxicity (1-100 microM). The addition of sulfhydryl compound, glutathione at 2 or 10 microM significantly enhanced the toxicity induced by 10 microM tryptamine-4,5-dione. On the contrary, glutathione at 10 microM decreased the neurotoxic effect caused by 10 microM 5,6- and 5,7-dihydroxytryptamine in the cultured neurons. The toxicity resulted from 5,6- and 5,7-dihydroxytryptamine could be fully prevented by a 5-HT uptake inhibitor, fluoxetine. However, the toxicity caused by tryptamine-4,5-dione and glutathione conjugate could not be blocked by fluoxetine (10 or 100 microM) or by a glutathione transferase inhibitor, boric acid/serine. The results indicate a different molecular mechanism among 5-HT derived neurotoxins and suggest that tryptamine-4,5-dione and/or its glutathione conjugate would cause neuronal damage, if they are formed in vivo.

5,6-Dihydroxytryptamine↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility.

Adult↗
PubMed1995

Allele epsilon 4 of apolipoprotein E shows a dose effect on age at onset of Pick disease.

Pick disease is a rare progressive dementing illness characterized by severe atrophy of the frontal and temporal lobes. Clinically, Pick disease may be difficult to distinguish from Alzheimer disease (AD). The fact that Pick disease is often familial, and the evidence suggesting that the epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for AD and possibly other dementias, prompted us to study ApoE isoforms in Pick disease. ApoE genotypes were evaluated in an autopsy series of 21 AD and 12 Pick cases and compared with published data for a large group of adults participating in the Framingham Study. The distributions of ApoE genotypes in the AD and Pick patients and the controls were significantly different from one another. The frequency of epsilon 4 was 50.0, 20.0, and 13.6% in these respective groups. Linear regression analysis showed that the number of epsilon 4 alleles was inversely related to age at onset of Pick disease (P < 0.03) and accounted for 40% of the variation in age at onset. These results suggest that epsilon 4 may be a susceptibility factor for dementia and not specifically for AD. Experiments using a monoclonal antibody against ApoE suggest that neurons and Pick bodies are immunoreactive with ApoE. The dose effect of the epsilon 4 allele on age at onset of dementias other than AD and the association of ApoE immunoreactivity with neurons and Pick bodies support a broader role for ApoE in the pathogenesis of neuronal degeneration through interactions with the neuronal cytoskeleton.

Age of Onset↗
PubMed1995

Effect of prenatal malnutrition on release of monoamines from hippocampal slices.

The effect of prenatal protein malnutrition on release of monoamine neurotransmitters, their precursors and metabolites, from hippocampal slices was investigated in 15, 30, 90 and 220 days old male rats. The release of dopamine and its metabolites, tryptophan, and 5-hydroxyindoleacetic acid from hippocampal slices of malnourished rats was greater than release from control slices at all ages studied. Malnutrition also significantly increased the release of normetanephrine but only in the 220 day age group. Potassium-induced depolarization increased release of tyrosine, normetanephrine and 5-hydroxyindoleacetic acid less from slices of malnourished than from control rats. The release of norepinephrine, normetanephrine, serotonin and 5-hydroxyindoleacetic acid increased significantly with age while the release of tyrosine, 3,4-dihydroxyphenylacetic acid and homovanillic acid decreased significantly with age. Age was also significantly associated with the effectiveness of potassium-induced depolarization in increasing release of tyrosine, norepinephrine, normetanephrine, tryptophan, serotonin and 5-hydroxyindoleacetic acid.

Age Factors↗
PubMed1995

Reaching consensus: the process of recommending treatment decisions for Alzheimer's patients.

Observational and interview data obtained from nurse caregivers and family members of patients with late-stage Alzheimer's disease were analyzed to explicate the nursing role in advance proxy planning. A four-phase model, Achieving Consensus: Decision Making to Determine Treatment Options for Patients with Alzheimer's Disease, was developed. Patient decline, family coping, professional development of nursing staff, and nursing unit philosophy were community characteristics found to be important antecedents to the process of reaching consensus. Achieving consensus constructs included interactive process components of patient, family, and staff adjustment, caring, and knowing. Timing and trust were influential catalysts to family and staff readiness factors for achieving consensus. Outcomes were the advice provided by staff and the family conference where treatment options were determined. Consequences included the advance proxy plan and patient care.

Adaptation, Psychological↗
PubMed1995

Sundown syndrome in severely demented patients with probable Alzheimer's disease.

A retrospective review of 71 patients with probable Alzheimer's disease was analyzed with respect to nursing evaluations of sundowning status (recurring confusion or agitation in the late afternoon or early evening). The prevalence of sundowning (including probable sundowners) was 24%. Sundowners and non-sundowners differed with regard to number of sedatives received daily, particularly chloral hydrate, and the number of days on the inpatient unit. There were no differences between sundowners and non-sundowners with respect to other types of medications, medical diagnoses, current age, age of onset of Alzheimer's disease, or Mini-Mental State Exam. Restlessness was the most common sundowning behavior, although multiple behavioral disturbances were seen. This survey suggests that the sundown syndrome is a common problem in severely demented Alzheimer's patients and requires further study.

Age of Onset↗
PubMed1994

Stability of o-phthalaldehyde-sulfite derivatives of amino acids and their methyl esters: electrochemical and chromatographic properties.

RP-HPLC coupled with 16-channel coulometric electrode array detection was used to monitor the decomposition of five amino acid o-phthalaldehyde (OPA)-sulfite derivatives (Ala, Arg, Glu, Ser, Tyr) and their methyl ester derivatives as well. At fixed OPA and sulfite concentrations inclusion of methanol and EDTA in the derivatization media has increased most effectively the room temperature stability of both derivatives measured at pH 9.2 (amino acids) and pH 8.2 (methyl esters). Decreases in product concentrations by 6% have occurred after more than 15 h for amino acid derivatives and 8 h for methyl ester derivatives. The oxidation potential maxima for OPA-sulfite derivatives of amino acids were found at 600 mV while the same methyl ester derivatives had 60-120 mV higher maxima with the exception of tyrosine. The detector responses were found to be linear in the studied 0.1-10 microM concentration range for both derivative forms and their detection limit was 100-200 fmol injected on the column. The RP-HPLC retention of amino acid methyl ester OPA-sulfite derivatives was very similar to the amino acid OPA-2-mercaptoethanol ones while the more polar amino acid OPA-sulfite derivatives were eluted earlier (k' < 1) under the same chromatographic conditions.

Alanine↗
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↗