Burring cheek teeth in rabbits.
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Animals↗
Biomedical subjects
M P Lawton
Publications and source records attributed to M P Lawton.
An overview of the social and behavioral consequences of Alzheimer's disease.
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Aged↗
The physical environment of the person with Alzheimer's disease.
A conceptual structure based on a set of 11 universal human needs is used as the basis for organizing a view of research methods appropriate to designing environments for people with dementia. The advantages and disadvantages of four general approaches are discussed: consumer surveys, direct behavior observation, expert judgments, and experimental designs. All are found wanting, though clearly worth pursuing. Systematic qualitative observational methods are suggested as a mode for generating and organizing user-friendly data for designing environments for people with dementia.
Aged↗
Valuation of life: a concept and a scale.
OBJECTIVES: The objective was to derive and test the psychometric characteristics of a scale to measure Valuation of Life (VOL). METHODS: Four samples were used in successive phases of exploratory factor analysis, confirmatory factor analysis, reliability and validity testing, and exploration of response-error effects. Estimates of Years of Desired Life were obtained under a variety of hypothetical quality-of-life (QOL)-compromising conditions of poor health. RESULTS: Confirmed 13-item (Positive VOL) and 6-item (Negative VOL) factors were obtained. A significant relationship between VOL and most Years of Desired Life estimates remained when demographic, health, quality of life, and mental health measures were controlled. Analysis of Negative VOL revealed that some respondents misunderstand the meaning of an agree response to negatively phrased items. DISCUSSION: VOL is a cognitive-affective schema whose function as a mediator and moderator between health and end-of-life decisions deserves further research.
Factor Analysis, Statistical↗
Characterization of transgenic mouse strains using six human hepatic cytochrome P450 probe substrates.
1. Transgenic mice were evaluated with six human cytochrome P450 (CYP) selective probe substrates, as little is known about their metabolism in the mouse. Mouse strains characterized include C57BL/SJL, FVB/N, mdr 1a/1b (-/-), ob/ob and ACCA. 2. Human CYP probe substrates used for characterization of mouse CYP activities included bufuralol, testosterone, dextromethorphan, phenacetin, diclofenac and S-mephenytoin. Activities were compared with those obtained in human liver microsomes and in human recombinant enzyme preparations. All transgenic mouse strains showed similar apparent K(m) with bufuralol, testosterone and dextromethorphan which compared favourably with those observed in human liver microsomes. 3. K(m) for phenacetin O-deethylase and S-mephenytoin 4'-hydroxylation were more variable across strains and in some cases demonstrated biphasic kinetics. Phenacetin O-deethylase activity was low in all mouse strains except FVB/N and mdr 1a/1b (-/-). Diclofenac 4-hydroxylation did not occur to any significant extent in the five strains of mouse evaluated here. 4. The findings suggest the validity of using five of the probes for transgenic mouse hepatic CYP characterization and gross comparison with data generated with human CYP.
Animals↗
The psychosocial preferences of older adults: a pilot examination of content and structure.
Individualizing care for older persons depends on knowing about a care recipient's psychosocial preferences. Currently, however, no comprehensive, empirically derived instruments exist to assess these preferences. As part of an effort to develop such an instrument, this pilot study examined the content and structure of psychosocial preferences in older adults using the statistical technique known as concept mapping. Results suggest two underlying dimensions to psychosocial preferences (Enrichment-Self-Maintenance and Extrapersonal-Intrapersonal) and six distinct content domains (Social Contact, Growth Activities, Leisure Activities, Self-Dominion, Support Aids, and Caregivers and Care). Both the dimensions and the content domains provide valuable information for the construction of psychosocial preference instruments. They also might assist formal and informal caregivers in tailoring their interventions to provide individualized care that enhances quality of life for older adults.
Activities of Daily Living↗
Two transitions in daughters' caregiving careers.
Daughters and daughters-in-law of presently unmarried elders were studied longitudinally, and the data were analyzed to determine how two transitions in caregiving status affected the women of the younger generation. One transition compared noncaregivers who had become caregivers 1 year later ("caregiving entrants," n = 33) with continuing noncaregivers (n = 56) and with veteran continuing caregivers (n = 78) over the same period. The second transition followed Time 1 new caregivers as they became "new veteran" caregivers (n = 69), comparing them with "old veteran" caregivers (n = 189) over the same year. The transition to caregiving was marked by a decrease in the care receiver's competence and an increase in the amount of care received, but caregiving entrants' quality of life did not change significantly over 1 year, as compared with either continuing noncaregivers or veteran caregivers. Although longitudinal study shows little positive evidence for the wear-and-tear model of caregiving, methodological improvements are needed before discarding the hypothesis that caregiving erodes mental health.
Adaptation, Psychological↗
The relationship between external events and affect states in older people.
Long-term and moderately short-term effects of bereavement and marriage on psychological well-being (PWB) among older people were investigated. The aspect of PWB that was examined was the prevalence of six affects, rated in terms of their frequency during the past year. Affect frequency of four groups was tested: Recently widowed, recently married, and widowed and married elders unselected for length of time in those marital statuses. As predicted, both length of time in the marital status and congruence between the positive event (marriage) and positive affect and between congruence of the negative event (bereavement and negative affect) were associated with group differences. Depressive affect was greatest among the recently bereaved but the recently-married, long-married, and longer-bereaved groups did not differ in depression. Positive affect was greatest among the recently married and other groups did not differ in this respect. Hostility, anxiety, shyness, and contentment were not predicted to differ among groups; in fact, contentment was least in the bereaved; shyness was least among the recently-married, and hostility was lowest among the long-widowed. Results are discussed in terms of the joint influences of time since a life event and the differential relevance of positive and negative affect states to positive and negative events. Continued research attention to the covariation of these factors in relation to the affective aspects of PWB is needed to understand the conditions of stability and change.
Adaptation, Psychological↗
Molecular cloning, expression, and characterization of CYP2D17 from cynomolgus monkey liver.
The cynomolgus monkey is a species used in drug-safety evaluation and biotransformation studies by the pharmaceutical industry. Relatively little is known, however, about the catalytic activities and specificities of cytochromes P450 (CYP) in this species. As a first step in characterizing monkey CYPs, a cDNA was cloned by reverse-transcriptase PCR from cynomolgus monkey liver mRNA using oligonucleotide primers based on the human CYP2D6 sequence. The full-length cDNA (called CYP2D17) encoded a 497-amino-acid protein that is 93% identical to human CYP2D6 and 90% identical to marmoset CYP2D19. The CYP2D17 cDNA was cloned into a baculovirus expression vector, and microsomes prepared from CYP2D17-infected insect cells were used to determine the catalytic properties of the recombinant enzyme. The recombinant CYP2D17 results were compared to data generated with monkey liver microsomes, human liver microsomes, and recombinant CYP2D6 and demonstrated catalytic similarity using probe substrates and inhibitors. Recombinant CYP2D17 catalyzed the oxidation of bufuralol to 1'-hydroxybufuralol and dextromethorphan to dextrorphan, reactions shown to be mediated by CYP2D6 in humans; the apparent K(m) values for bufuralol and dextromethorphan were 1 and 0.8 microM, respectively. Moreover, both of these reactions were more strongly inhibited by quinidine than by quinine. A more complete understanding of the substrate specificities and activities of monkey CYPs will be advantageous in delineating species differences in metabolite profiles and metabolic activation of new chemical entities in the pharmaceutical industry.
Amino Acid Sequence↗
Health, valuation of life, and the wish to live.
This research investigated the relationship of an affective-cognitive schema, valuation of life (VOL), to older people's responses to a set of health utility (years of desired life) questions. Six hundred healthy and chronically ill elders aged 70 and older were interviewed to measure quality of life (QOL), mental health, and VOL. Valuation of life was significantly correlated with longer Years of Desired Life under 8 of 10 health conditions when background, health, QOL, and mental health states were controlled. We concluded that VOL is an internal representation of the many positive and negative features of the person and her everyday life that is necessary to comprehend how people may cling to life or welcome its end.
Aged↗
Affect and quality of life: objective and subjective.
OBJECTIVES: The objective of this article is to determine direct and indirect contributions of objective and subjective quality of life (QOL) to positive and negative indicators of mental health. Specifically, the dual-channel hypothesis predicted that objective and subjective social engagement would enhance positive affect (PA) but be unrelated to depression. METHODS: Older people from senior centers and several housing environments volunteered to complete a questionnaire or interview about a number of aspects of their everyday lives (N = 602). Objective and subjective were related to one another. RESULTS: Objective activity participation and subjective time use and friend quality were associated with PA. Only time use was related to depression. DISCUSSION: The importance of assessing both amount of behavior (objective) and its quality (subjective) when measuring QOL was demonstrated. Although external engagement bears a closer relationship to PA than to negative, the dual-channel model relating locus of stimulation differentially to PA and depression requires modification.
Affect↗
Expression and characterization of canine cytochrome P450 2D15.
CYP2D15 is the canine ortholog of human CYP2D6, the human CYP2D isoform involved in the metabolism of drugs such as antiarhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Similar to human, canine CYP2D15 is expressed in the liver, with detectable levels in several other tissues. Three different CYP2D15 cDNA clones were obtained by RT-PCR from dog liver RNA. Two clones corresponded to variant full-length CYP2D15 cDNAs (termed CYP2D15 WT2 and CYP2D15 V1); the third was identified as a splicing variant missing exon 3 (termed CYP2D15 V2). Recombinant baculoviruses were constructed containing full-length cDNAs and used to express CYP2D15 WT2 and CYP2D15 V1 in Spodoptera frugiperda (Sf9) cells with expression levels of up to 0.14 nmol/mg cell protein. As with human CYP2D6, the recombinant CYP2D15 enzymes exhibited bufuralol 1'-hydroxylaseand dextromethorphan O-demethylase activities whencoexpressed with rabbit NADPH:P450 oxidoreductase. For bufuralol 1'-hydroxylase, apparent Km values were 4.9, 3.7, and 2.5 microM and the Vmax values were 0.14, 0.034, and 0.60 nmol/min/mg protein for dog liver microsomes, CYP2D15 WT2, and the variant CYP2D15 V1, respectively. For dextromethorphan O-demethylase, apparent Km values were 0.6, 0.6, and 2.0 microM and the Vmax values were 0.18, 0.034, and 0.057 nmol/min/mg protein for dog liver microsomes, CYP2D15 WT2, and the variant CYP2D15 V1, respectively. The human CYP2D6-specific inhibitor quinidine and the rat CYP2D1-specific inhibitor quinine were both shown to be inhibitors of bufuralol 1'-hydroxylase activity for dog liver microsomes, CYP2D15 WT2, and the CYP2D15 V1 variant with nearly equal potency. Thus, the dog expresses a CYP2D ortholog possessing enzymatic activities similar to human CYP2D6, but is affected by the inhibitors quinine and quinidine in a manner closer to that of rat CYP2D1.
Animals↗
Identification of amino acid residues associated with modulation of flavin-containing monooxygenase (FMO) activity by imipramine: structure/function studies with FMO1 from pig and rabbit.
The activity of the flavin-containing monooxygenase (FMO) can be modulated by a number of nitrogen-containing compounds in a manner that is both isoform and modulator-dependent. We now show that the direction (activation or inhibition) and extent of modulation can also be dependent on substrate concentration. Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at methimazole concentrations greater than 50 or 100 microM, respectively, and inhibits at lower methimazole concentrations. The extent of the activation increases as the substrate concentration increases, and the extent of inhibition increases as the substrate concentration decreases. With either inhibition or activation, the magnitude of the effect shows a similar, direct dependency on imipramine concentration. In contrast, imipramine inhibits the metabolism of methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural basis for this unique ortholog difference between the responses of rabbit and pig FMO1 to imipramine was studied by random chimeragenesis and site-directed mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by imipramine is controlled to a great extent by two areas of the FMO primary structure (residues 381-432 and 433-465). Four amino acids in these regions (positions 381, 400, 420 and 433) and one additional residue (position 186) were identified by site-directed mutagenesis as primary determinants of the imipramine response. When the residues at these positions in rabbit FMO1 are exchanged for the corresponding residues of pig FMO1, a mutant with the functional properties of pig FMO1 is produced. Our results suggest that the response of FMO1 to imipramine involves a distribution between two sites that is regulated by structural features that do not alter the overall binding. The inhibition observed, although it appears to be competitive, likely does not involve competition for a binding site since alteration of imipramine metabolism has no effect on the parameters of methimazole metabolism.
Amino Acid Substitution↗
A stimulation-retreat special care unit for elders with dementing illness.
Two equivalent special care nursing home units for elders with dementing illness were randomly designated as experimental and control units for an intervention called the "stimulation-retreat" model. This model introduced a set of staffing and program changes whose purpose was to diagnose, prescribe, and apply a package of care according to individual needs for additional stimulation or relief from stimulation ("retreat"). A total of 49 experimental and 48 control unit residents completed 12 months of care and were evaluated at baseline, 6 months, and 12 months. It was hypothesized that the intervention would not affect the basic disability (cognitive and activities of daily living functions), would improve negative behaviors and observed affects, and would have maximum impact in increasing positive behaviors and affects. Over time, most functions worsened, including negative attributes and affects. Lesser decline in positive affect and increases in external engagement, however, led to the conclusion that the intervention showed a marginally significant and selective effect on positive behaviors and affect.
Aged↗
The structure of depression among elderly institution residents: affective and somatic correlates of physical frailty.
BACKGROUND: Confounding of depression with somatic illness and anxiety, a problem in any age group, may be especially troublesome in frail older persons. This paper examined this problem in a factor analytic study of the structure of depressive symptomatology, identifying affective and somatic symptom clusters and relating those clusters to health and functional variables cross-sectionally and prospectively over a 1-year interval. METHODS: The factor structure of a DSM-IV symptom checklist was examined among 1,245 elderly long-term care residents. Regression analyses examined the association of resulting factors with cognition, functional disability, self- and physician-rated health, and pain at baseline and a year later. One-year mortality was also examined. RESULTS: Factor analysis revealed three unique symptom clusters: depressed mood, somatic symptoms, and psychic anxiety. Depressed mood and somatic symptoms were associated cross-sectionally with all functional health variables, but psychic anxiety was associated only with pain. Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality; the last effect, however, did not withstand control for baseline health and functioning. Somatic symptoms at baseline predicted decrement in self-rated health a year later. Effects varied as a function of cognitive status. CONCLUSIONS: These data suggest that concerns about the confounding role of somatic symptoms in the association of depression with physical health are unfounded. Although somatic symptoms of depression and anxiety were associated with health and functional status cross-sectionally, depressed mood was by far the stronger predictor of health declines over time.
Aged↗
Psychometric characteristics of the minimum data set I: confirmatory factor analysis.
OBJECTIVE: To determine the structure and statistical reliability of the federally mandated Minimum Data Set (MDS). DESIGN: Confirmatory, hypothesis-testing factor analysis was performed on MDS protocols of 733 nursing home residents. SETTING: All participants were residents of the Philadelphia Geriatric Center. PARTICIPANTS: Participants represented consecutively admitted skilled and intermediate care residents and another pool of residents with probable dementia. MEASUREMENTS: MDS protocols were completed by nurse care coordinators. Item composites hypothesized represented the domains of cognition, activities of daily living, time use, social quality, depression, and problem behaviors. RESULTS: For higher functioning residents (n = 336) and for all residents together, all domain clusters except social quality were confirmed. None of the domain clusters were confirmed within the more impaired (n = 391) group. CONCLUSIONS: The MDS does provide usable indicators of five areas of basic competence of nursing home residents. Lack of reliability in rating many aspects of the behavior and states of cognitively impaired residents is evident, however. Improvement of such measures and rating procedures constitutes a major research priority.
Activities of Daily Living↗
Psychometric characteristics of the minimum data set II: validity.
OBJECTIVE: To determine the validity of the Minimum Data Set (MDS). DESIGN: MDS domain scores were correlated with a variety of independently obtained measures of basic behavioral and mental health functions of 513 nursing home residents. SETTING: All participants were residents of the Philadelphia Geriatric Center. PARTICIPANTS: One group of residents (n = 260) represented consecutive admissions who were able to respond to formal testing. The other group of residents (n = 253) represented presumably cognitively impaired residents whose data did not depend on self-report. MEASUREMENTS: MDS item-composite scores based on a confirmatory factor analysis were derived for the domains of cognition, activities of daily living (ADL), time use, depression, and problem behaviors. Hypotheses stating how these MDS domains should be related to standard measures of cognitive function, ADL, depression, agitation, social behavior, and irritability were tested. CONCLUSIONS: The majority of the hypotheses were upheld, thus suggesting that the MDS is usable as a source of research data. The sizes of the validity coefficients were modest, however. Depression and problem behavior were less well affirmed than cognition, ADL, and Time Use. There is a clear need for improvement in training and probably in the form of MDS measurement in some areas.
Activities of Daily Living↗