Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Policy research into the service needs of persons with dementia had its origin looking at challenges confronting caregivers--extended hours of instrumental task assistance, social isolation, fatigue, depression--and how public policy might support informal care-giving while saving public expenditures from nursing home care. This paper, drawing on the experience of the Medicare Alzheimer's Disease Demonstration and other work, provides suggestions for extending care and financing considerations to include health care use and the medical management of chronic health conditions. Basic research is needed to document current use and risk factors, as is experimentation with clinical and other interventions designed to achieve desired quality of care and cost outcomes. This section of the paper will be of direct interest to both US and international readers. The second half of the paper reviews the US state role in regulating and financing nursing homes, home and community-based care, and residential care. All these sectors have high rates of staff turnover, staff shortages, and concerns with quality of care. The international community and US states provide naturally occurring opportunities for delivery system experimentation and innovation. Research taking advantage of these opportunities could greatly inform public policy.
 ...
PMID:Health and long-term care for people with Alzheimer's disease and related dementias: policy research issues. 1151 91

For clinical use of event-related potentials (ERPs), issues to be solved included individual variations in their latencies and amplitudes, inconsistencies in the abnormalities of these parameters in dementia patients among research institutes, etc. In normal groups, variations in the latency and amplitude of P300 (P3), a representative ERP component, can be resolved by the standardization of several of its biological determinants. The determinants included 1) natural factors, e.g. circadian rhythm, the season, 2) induced factors, e.g. exercise, fatigue, drugs, and 3) constitutional factors, e.g. age, sex. The inconsistency of data among dementia patients is mostly due to differences in the severity or stage of dementia. However, clinically the most important issue is to develop an ERP test to identify mild cognitive dysfunction at an early stage of dementia, which differs from that at an advanced stage. For example, in familial Alzheimer's disease, a test for verbal memory is reported to be the most sensitive. On the other hand, mismatch negativity, one of the early ERP components, is a pre-attentive automatic response to changes in auditory stimuli. Since this component can be evoked without any attention or task, one of its advantages is that it can be recorded in infants or small children, or in demented or comatose patients. Other clinically useful ERP components are also introduced.
 ...
PMID:[Clinically useful event-related potentials]. 1223 29

Amyloid beta-peptide [Abeta(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress, including membrane lipid peroxidation. Abeta(1-42) causes oxidative stress in and neurotoxicity to neurons in mechanisms that are inhibited by Vitamin E and involve the single methionine residue of this peptide. In particular, Abeta induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). These alkenals covalently bind to synaptosomal protein cysteine, histidine, and lysine residues by Michael addition to change protein conformation and function. HNE or acrolein binding to proteins introduces a carbonyl to the protein, making the protein oxidatively modified as a consequence of lipid peroxidation. Immunoprecipitation of proteins from AD and control brain, obtained no longer than 4h PMI, showed selective proteins are oxidatively modified in the AD brain. Creatine kinase (CK) and beta-actin have increased carbonyl groups, and Glt-1, a glutamate transporter, has increased binding of HNE in AD. Abeta(1-42) addition to synaptosomes also results in HNE binding to Glt-1, thereby coupling increased Abeta(1-42) in AD brain to increased lipid peroxidation and its sequelae and possibly explaining the mechanism of glutamate transport inhibition known in AD brain. Abeta also inhibits CK. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. The epsilon-4 allele of the lipid carrier protein apolipoprotein E (APOE) allele is a risk factor for AD. Synaptosomes from APOE knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. Further, synaptosomes from allele-specific APOE knock-in mice have tiered vulnerability to Abeta(1-42)-induced oxidative stress, with APOE4 more vulnerable to Abeta(1-42) than are those from APOE2 or APOE3 mice. These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by Abeta(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE allele-related risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress in AD neurodegeneration.
 ...
PMID:Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. 1239 66

Preschool teachers are at risk for developing voice problems such as vocal fatigue and vocal nodules. The purpose of this report was to study preschool teachers' voice use during work. Ten healthy female preschool teachers working at daycare centers (DCC) served as subjects. A binaural recording technique was used. Two microphones were placed on both sides of the subject's head, at equal distance from the mouth, and a portable DAT recorder was attached to the subject's waist. Recordings were made of a standard reading passage before work (baseline) and of spontaneous speech during work. The recording technique allowed separate analyses of the level of the background noise, and of the subjects' voice sound pressure level, mean fundamental frequency, and total phonation time. Among the results, mean background noise level for the ten DCCs was 76.1 dBA (range 73.0-78.2), which is more than 20 dB higher than what is recommended where speech communication is important (50-55 dBA). The subjects spoke on an average of 9.1 dB louder (p < 0.0001), and with higher mean fundamental frequency (247 Hz) during work as compared to the baseline (202 Hz) (p < 0.0001). Mean phonation time for the group was 17%, which was considered high. It was concluded that preschool teachers do have a highly vocally demanding profession. Important steps to reduce the vocal loading for this occupation would be to decrease the background noise levels and include pauses so that preschool teachers can rest their voices.
 ...
PMID:Vocal behavior and vocal loading factors for preschool teachers at work studied with binaural DAT recordings. 1239 88

An increase in fundamental frequency (F(0)) and in sound pressure level (SPL) has been reported both after vocal loading tests and after a teacher's working day. This increase has been found to be greater among teachers with fewer voice complaints. The present study investigated speech changes during a teacher's working day (a) in ordinary conditions and (b) when using electric sound amplification while teaching. Five Icelandic teachers (mean age 51 years) volunteered as subjects. Classroom speech was recorded with a portable DAT recorder and a head-mounted microphone first in ordinary conditions, and the next week while using electrical sound amplification. Recordings were made during the first and the last lesson of the hardest working day of the week. F(0) and SPL were analyzed. The subjects' comments were gathered by questionnaire. An increase in F(0) and SPL was found during the working day in both teaching conditions but the change was larger and for F(0) statistically significant when amplification was used. All 5 teachers reported less tiredness of the vocal mechanism when using amplification. The results support the suggestion that a vocal loading-related increase in F(0) and SPL is not merely a sign of vocal fatigue but may even reflect an adequate adaptation to loading. Situational factors cannot be ignored, however.
 ...
PMID:Changes in teachers' speech during a working day with and without electric sound amplification. 1241 98

The tolerability and safety of donepezil HCI in patients with mild to moderate Alzheimer's disease (AD) were examined in an integrated analysis of phase II/III placebo-controlled trials. Patients with mild to moderately severe AD (n=1,920) were randomised to receive donepezil (n=1,291) or placebo (n=629). Adverse events, physical examinations and clinical laboratory tests were assessed. A high completion rate (79%) was achieved in these trials. Of the 1,291 patients receiving donepezil only, 142 (11%) withdrew because of an adverse event compared with 43 of the 629 (7%) placebo patients. The most common adverse events included nausea, diarrhoea, headache, insomnia, dizziness, rhinitis, vomiting, asthenia/fatigue and anorexia. Donepezil had no clinically significant effect on any laboratory evaluations and was not associated with hepatotoxicity. These results demonstrate that donepezil is well tolerated and has a favourable safety profile at clinically effective, once-daily doses of 5 mg and 10 mg.
 ...
PMID:Donepezil: tolerability and safety in Alzheimer's disease. 1246 88

Oxidative stress, manifested by protein oxidation, lipid peroxidation, DNA oxidation and 3-nitrotyrosine formation, among other indices, is observed in Alzheimer's disease (AD) brain. Amyloid beta-peptide (1-42) [Abeta(1-42)] may be central to the pathogenesis of AD. Our laboratory and others have implicated Abeta(1-42)-induced free radical oxidative stress in the neurodegeneration observed in AD brain. This paper reviews some of these studies from our laboratory. Recently, we showed both in-vitro and in-vivo that methionine residue 35 (Met-35) of Abeta(1-42) was critical to its oxidative stress and neurotoxic properties. Because the C-terminal region of Abeta(1-42) is helical, and invoking the i + 4 rule of helices, we hypothesized that the carboxyl oxygen of lle-31, known to be within a van der Waals distance of the S atom of Met-35, would interact with the latter. This interaction could alter the susceptibility for oxidation of Met-35, i.e. free radical formation. Consistent with this hypothesis, substitution of lle-31 by the helix-breaking amino acid, proline, completely abrogated the oxidative stress and neurotoxic properties of Abeta(1-42). Removal of the Met-35 residue from the lipid bilayer by substitution of the negatively charged Asp for Gly-37 abrogated oxidative stress and neurotoxic properties of Abeta(1-42). The free radical scavenger vitamin E prevented A(beta (1-42)-induced ROS formation, protein oxidation, lipid peroxidation, and neurotoxicity in hippocampal neurons, consistent with our model for Abeta-associated free radical oxidative stress induced neurodegeneration in AD. ApoE, allele 4, is a risk factor for AD. Synaptosomes from apoE knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. We also studied synaptosomes from allele-specific human apoE knock-in mice. Brain membranes from human apoE4 mice have greater vulnerability to Abeta(1-42)-induced oxidative stress than brain membranes from apoE2 or E3, assessed by the same indices, consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Using immunoprecipitation of proteins from AD and control brain obtained no longer than 4h PMI, selective oxidized proteins were identified in the AD brain. Creatine kinase (CK) and beta-actin have increased carbonyl groups, an index of protein oxidation, and Glt-1, the principal glutamate transporter, has increased binding of the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE). Abeta inhibits CK and causes lipid peroxidation, leading to HNE formation. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. Other oxidatively modified proteins have been identified in AD brain by proteomics analysis, and these oxidatively-modified proteins may be related to increased excitotoxicity (glutamine synthetase), aberrant proteasomal degradation of damaged or aggregated proteins (ubiquitin C-terminal hydrolase L-1), altered energy production (alpha-enolase), and diminished growth cone elongation and directionality (dihydropyrimindase-related protein 2). Taken together, these studies outlined above suggest that Met-35 is key to the oxidative stress and neurotoxic properties of Abeta(1-42) and may help explain the apoE allele dependence on risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress and neurodegeneration in AD.
 ...
PMID:Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. 1260 22

The aim of the present study was to investigate the effects of a group structured intervention on the mental and physical discomfort and immune function of 20 family caregivers. A structured intervention for caregivers consists of five sessions, each of which lasts 90 min. This was a modified version of the program that had been originally developed for cancer patients. All the family caregivers were female and ranged in age from 47 to 66 years (mean: 54.7 +/- 4.4). The period of care at home ranged from 1 to 12 years (mean: 5.8 +/- 2.7). Concerning the original diseases of the care-receivers, 10 had vascular dementia and eight had Alzheimer's disease. Nine out of 20 caregivers had no care support, and seven utilized no public resources such as day-care centers. Only five caregivers felt that they were healthy. Two psychometries, that is, Profile of Mood States (POMS) and General Health Questionnaire-30 (GHQ-30) were administered and blood samples were drawn before and after intervention. Comparison of results showed that there was significant improvement (P < 0.05) in the scores of depression, anger-hostility, fatigue and confusion in the POMS, and physical symptoms, anxiety-mood disorder, suicidality-depression in the GHQ-30. Also, there was significant (P = 0.0325) augmentation of natural-killer cell activity. The present study suggests that this kind of intervention was effective for relieving emotional and physical discomfort, and also for improving immune function.
 ...
PMID:Structured intervention in family caregivers of the demented elderly and changes in their immune function. 1266 60

The present study investigated changes in the voice quality of teachers during a working day (a). in ordinary conditions and (b). when using electrical sound amplification while teaching. Classroom speech of 5 teachers was recorded with a portable DAT recorder and a head-mounted microphone during the first and the last lesson of a hard working day first in ordinary conditions and the following week using amplification. Long-term average spectrum and sound pressure level (SPL) analyses were made. The subjects' comments were gathered by questionnaire. Voice quality was evaluated by 2 speech trainers. With amplification, SPL was lower and the spectrum more tilted. Voice quality was evaluated to be better. The subjects reported less fatigue in the vocal mechanism. Spectral tilt decreased and SPL increased during the day. There was a tendency for perceived asthenia to decrease. No significant changes were observed in ordinary conditions. The acoustic changes seem to reflect a positive adaptation to vocal loading. Their absence may be a sign of vocal fatigue.
 ...
PMID:Changes in teachers' voice quality during a working day with and without electric sound amplification. 1293 Oct 60

Previous epidemiological and clinical studies of humans exposed to polychlorinated biphenyls (PCBs) indicate that the majority of patients have neurological complaints (e.g., headache, vertigo, paresthesias, poor memory and concentration, fatigue, depression). Since only a small minority of PCB-exposed patients demonstrate abnormalities on objective neurological measures (e.g., CT-scans, EEC, nerve conduction velocity), it is particularly unfortunate that objective neuropsychological data has not been published to substantiate patient complaints. The present study provides neuropsychological test data on two patients exposed to PCBs. In both cases, PCB exposure is documented by an analysis of PCB levels in the patients' work environments. Despite the absence of abnormalities on CT-scans and EEC, both patients displayed a variety of cognitive deficits and emotional disturbance. Serial assessment of one patient with high blood levels of PCBs revealed a dementia (sharing certain features with Alzheimer's disease) and an organic affective syndrome. Assessment of a second patient exposed to PCBs (but with no detectable blood levels of PCBs) suggested that his cognitive impairments were not due to PCB exposure. The present study provides data which points to the importance and sensitivity of neuropsychological examination in cases of PCB-exposure.
 ...
PMID:Dementia as a neuropsychological consequence of chronic occupational exposure to polychlorinated biphenyls (PCBs). 1458 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>