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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 91 records · Page 5Linked to original sources
PubMed2000

The use of a simulated environment (easy street) to retrain independent living skills in elderly persons: a randomized controlled trial.

BACKGROUND: Older adults who receive training for functional skills in contextually appropriate environments may show greater functional improvement than persons trained in a traditional environment. Functionally limited older adults receiving training in contextually appropriate environments (simulated home and community settings) may show greater improvement in activities of daily living (ADL) than persons trained in a traditional manner. METHODS: Eighty-eight patients from a day hospital, aged 65 years or older, were randomized to either receive rehabilitation in a simulated environment (Easy Street) or in a gymnasium setting. Rehabilitation focused on retraining functional skills in a contextually appropriate environment (Easy Street) or in a traditional setting (gymnasium) using motor learning principles for a period of 16 weeks. Outcome measures included the Structured Assessment of Instrumental Living Skills (SAILS), a performance measure with criterion and timed components; a self-report health status questionnaire, the Short Form-36 (SF-36); and the patient-orientated goal-directed Canadian Occupational Performance Measure (COPM). RESULTS: There were no group differences on any of the outcome measures: SAILS (p = .3); the SF-36 physical (p = .83) and mental (p = .51); and the COPM performance scale (p = .94) and satisfaction scale (p = .40). CONCLUSIONS: Although we have not excluded benefits of contextually appropriate rehabilitation environments with different intervention approaches, at different stages of rehabilitation or with patients at higher functional levels, our results suggest the appropriateness of a moratorium on these expensive interventions pending demonstration of clear positive effects determined from further study.

Activities of Daily Living↗
PubMed2000

Effectiveness of a bed positioning program for treating older adults with knee contractures who are institutionalized.

BACKGROUND AND PURPOSE: Although contractures in patients in long-term care institutions are an important issue, there have been only a few studies that have evaluated interventions for contractures. The purpose of this study was to determine the effectiveness of a bed positioning program (BPP) for the treatment of patients with knee flexion contractures. SUBJECTS: Sixteen patients with a high level of cognitive and functional impairment (mean age=82 years, SD=6.48, range=71-93) in a chronic care hospital participated in the study. METHODS: The BPP consisted of stretching a patient's knee into extension and then securing and maintaining the position for a period of 40 minutes, 4 times per week. Participants were randomly assigned to 2 groups (n=8 in each group). One group received a BPP for 8 weeks, followed by 8 weeks of no intervention. The other group received the intervention in the reverse order. Once a week, participants were assessed for range of knee extension, knee pain, and skin integrity. RESULTS: Twelve participants completed the study. There was no improvement in participants' range of knee extension during the intervention period. Overall, there was no difference in mean range of knee extension between the intervention period and the no-intervention period. CONCLUSION AND DISCUSSION: The results of this study do not support the use of a BPP for treating patients with knee flexion contractures.

Aged↗
PubMed2000

Improving value measurement in cost-effectiveness analysis.

OBJECTIVE: Before cost-effectiveness analysis (CEA) can fulfill its promise as a tool to guide health care allocation decisions, the method of incorporating societal values into CEA may need to be improved. DESIGN: The study design was a declarative exposition of potential fallacies in the theoretical underpinnings of CEA. Two values held by many people-preferences for giving priority to severely ill patients and preferences to avoid discrimination against people who have limited treatment potential because of disability or chronic illness-that are not currently incorporated into CEA are discussed. CONCLUSIONS: Traditional CEA, through the measurement of quality-adjusted life years (QALYs), is constrained because of a "QALY trap." If, for example, saving the life of a person with paraplegia is equally valuable as saving the life of a person without paraplegia, then current QALY methods force us to conclude that curing paraplegia brings no benefit. Basing cost-effectiveness measurement on societal values rather than QALYs may allow us to better capture public rationing preferences, thereby escaping the QALY trap. CEA can accommodate a wider range of such societal values about fairness in its measurements by amending its methodology.

Attitude to Health↗
PubMed2000

Referral delay and ocular surgical outcome in Terson syndrome.

BACKGROUND: In Terson syndrome, vitreous hemorrhage can result from intracranial hypertension associated with intracranial bleeding. The vitreous hemorrhage can cause a considerable visual handicap. The aim of this study was to determine the outcome of surgery in patients with Terson syndrome and any delay in referral to an ophthalmologist. METHODS: Retrospective case review of 25 eyes of 17 patients undergoing vitrectomy for Terson syndrome. Delay in presentation to an ophthalmologist, intraoperative and postoperative complications, and the final visual acuity were noted. RESULTS: The mean interval between visual symptoms and referral to an ophthalmologist was 5.2 months for the nine unilateral cases and 4.9 months for the eight bilateral cases. Intraoperative complications included retinal break (2) and retinal dialysis (3). Late complications included epiretinal membrane (4), ghost cell glaucoma (1), and cataract (8). Twenty-two of the 25 eyes achieved a final visual acuity of 20/30 or better. CONCLUSION: Vitrectomy for vitreous hemorrhage in Terson syndrome is a safe and effective procedure, offering a rapid and prolonged improvement in vision. There is good reason to consider early vitrectomy, particularly when the hemorrhage is bilateral and dense.

Adult↗
PubMed2000

Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV.

OBJECTIVES: The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. METHODS: Participants with HIV or at risk for HIV infection enrolled in the Women's Interagency HIV Study. Childhood sexual abuse; all physical, sexual, and coercive violence by a partner; HIV serostatus; demographic data; and substance use and sexual habits were assessed. RESULTS: The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection, and exchanging sex for drugs, money, or shelter. CONCLUSIONS: Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence, which may increase the risk of behaviors leading to HIV infection.

Adolescent↗
PubMed1999

Sexual, contraceptive, and drug use behaviors of women with HIV and those at high risk for infection: results from the Women's Interagency HIV Study.

OBJECTIVE: To document the sexual and contraceptive practices of women with HIV infection or who are at risk for infection. DESIGN: Data on the baseline behaviors of 561 HIV-negative and 2040 HIV-positive women were collected as part of the Women's Interagency HIV Study (WIHS). WIHS is a multisite, longitudinal study following the natural history of HIV infection among women in the United States. METHODS: Each participant contributed an interviewer administered, self-report interview including questions on sexual and contraceptive behavior. RESULTS: Women with HIV were less likely to report heterosexual activity in the previous 6 months (65% HIV-positive, 76% HIV-negative). Among sexually active women, there were no differences in the proportion of those reporting vaginal (97% HIV-positive, 98% HIV-negative) or anal sex (12% HIV-positive, 10% HIV-negative), although women with HIV were less likely to report cunnilingus (41% HIV-positive, 70% HIV-negative) and fellatio (48% HIV-positive, 57% HIV-negative). Of women with HIV, 63% always used condoms during vaginal sex (versus 28% HIV-negative), with lower rates reported during other sexual activities. Crack, cocaine, or injecting drug use, reported by 27% of HIV-positive and 35% of HIV-negative women, was associated with inconsistent condom use, independent of serostatus. HIV-positive women who reported using condoms and another contraception method were less consistent condom users (57% consistent versus 67%). CONCLUSIONS: The prevalence of sexual risk behavior in this sample suggests that, although women with HIV exhibit lower levels of sexual risk behavior than uninfected women, many have not been successfully reached with regard to implementing safer behaviors. These findings have implications for more widespread and effective behavioral intervention efforts.

Adolescent↗
PubMed1999

Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase.

The enzyme 6-pyruvoyl tetrahydropterin synthase (PTPS) catalyses the second step in the de novo biosynthesis of tetrahydrobiopterin, the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin. The Zn and Mg-dependent reaction includes a triphosphate elimination, a stereospecific reduction of the N5-C6 double bond and the oxidation of both side-chain hydroxyl groups. The crystal structure of the inactive mutant Cys42Ala of PTPS in complex with its natural substrate dihydroneopterinetriphosphate was determined at 1.9 A resolution. Additionally, the uncomplexed enzyme was refined to 2.0 A resolution. The active site of PTPS consists of the pterin-anchoring Glu A107 neighboured by two catalytic motifs: a Zn(II) binding site and an intersubunit catalytic triad formed by Cys A42, Asp B88 and His B89. In the free enzyme the Zn(II) is in tetravalent co-ordination with three histidine ligands and a water molecule. In the complex the water is replaced by the two substrate side-chain hydroxyl groups yielding a penta-co-ordinated Zn(II) ion. The Zn(II) ion plays a crucial role in catalysis. It activates the protons of the substrate, stabilizes the intermediates and disfavours the breaking of the C1'C2' bond in the pyruvoyl side-chain. Cys A42 is activated by His B89 and Asp B88 for proton abstraction from the two different substrate side-chain atoms C1', and C2'. Replacing Ala A42 in the mutant structure by the wild-type Cys by modelling shows that the C1' and C2' substrate side-chain protons are at equal distances to Cys A42 Sgamma. The basicity of Cys A42 may be increased by a catalytic triad His B89 and Asp B88. The active site of PTPS seems to be optimised to carry out proton abstractions from two different side-chain C1' and C2' atoms, with no obvious preference for one of them. Kinetic studies with dihydroneopterin monophosphate reveal that the triphosphate moiety of the substrate is necessary for enzyme specifity.

Animals↗
PubMed1999

Incorporating societal concerns for fairness in numerical valuations of health programmes.

The paper addresses some limitations of the QALY approach and outlines a valuation procedure that may overcome these limitations. In particular, we focus on the following issues: the distinction between assessing individual utility and assessing societal value of health care; the need to incorporate concerns for severity of illness as an independent factor in a numerical model of societal valuations of health outcomes; similarly, the need to incorporate reluctance to discriminate against patients that happen to have lesser potentials for health than others; and finally, the need to combine measurements of health-related quality of life obtained from actual patients (or former patients) with measurements of distributive preferences in the general population when estimating societal value. We show how equity weights may serve to incorporate concerns for severity and potentials for health in QALY calculations. We also suggest that for chronically ill or disabled people a life year gained should count as one and no less than one as long as the year is considered preferable to being dead by the person concerned. We call our approach 'cost-value analysis'.

Cost-Benefit Analysis↗
PubMed1999

Case and control recruitment, and validation of cases for the MICA case-control study in England, Scotland and Wales.

OBJECTIVES: To describe the processes involved in the selection of cases and controls, and the validation of case diagnosis, in a large case-control study on the association between myocardial infarction (MI) and oral contraceptives. DESIGN: Community case-control study in England, Scotland and Wales. SUBJECTS: Cases were women aged 16-44 with a diagnosis of MI. Controls were age and general practice matched women without a diagnosis of MI. RESULTS: The proportion of interviewed cases per number eligible was 19% (95% CI 12-26%) lower in England and Wales than in Scotland. The kappa score for agreement between three cardiologists on diagnostic categories of the potential cases was 0.52 overall ('moderate' agreement). For the 35 cases resubmitted for categorization, the kappa scores for agreement between the first and second classification for the two national committee cardiologists were 0.32 and 0.23 ('fair' agreement). Age matching of controls was better in Scotland than England and Wales, the proportion of the first choice controls being 14% (95% CI 8-19%) higher in Scotland. The mean time to complete a cluster of interviews (one case and four controls) was 36 days in Scotland and 63 days in England and Wales. CONCLUSIONS: Very close age-matching was achieved overall, although the process was more efficient in Scotland than in England and Wales. Some suggestions for improvement in the case validation process are made.

Journal Article↗
PubMed1999

Production gains from health care: what should be included in cost-effectiveness analyses?

Recent literature has been concerned with the correct measurement of the 'indirect costs and benefits' of health care as well as the issue of including these items in economic evaluations. This article considers the question of which 'indirect benefits' to include in cost effectiveness analysis and cost utility analysis. Within the context of a collectively financed health scheme the relevant issues include not only the size of the net resource costs of providing health care but also which costs and benefits the society is prepared to consider in its assessment of health services. The strong preference for 'equal access for equal need' implies that some production gains may have to be disregarded in the social welfare function. We introduce the notion of socially relevant and socially irrelevant production gains. The analysis suggests that the magnitude of the socially relevant part of the production gains may vary between countries as it depends, first, upon differences in patients' potential contributions to the rest of society (tax rates), and second, the strength of preferences for equity.

Cost of Illness↗
PubMed1999

Long duration electroporation for achieving high level expression of glucocorticoid receptors in mammalian cell lines.

A method is presented that utilizes long duration electroporation (LDE) to more efficiently introduce DNA into mammalian cell lines than standard electroporation techniques. With SV40-based vectors, more than 550,000 glucocorticoid receptors (GRs) per cell could be obtained in COS-7 cells with good cell survival. In experiments with a CMV-driven vector expressing an enhanced Green Fluorescent Protein (EGFP), 54% of the cells were transfected, and 77% of EGFP positive cells expressed EGFP at moderate to high levels. In cell lines not containing the large T antigen, a CMV-driven vector for the GR was superior to the SV40-based vector. In EDR3, DG44, and CV-1 cell lines approximately 220,000, 190,000 and 150,000 GRs/cell were obtained, respectively. Transfection efficiency of the EGFP vector ranged from 44 to 55% for the three cell lines. Cortisol treatment of COS-7 and DG44 cultures cotransfected with vectors expressing the GR and a GRE driven luciferase gene produced 4 to 12 times more enzyme activity per plate with LDE than conventional electroporation protocols. LDE allows transient overexpression of proteins in COS-7 cells at the high levels generally achieved by mammalian overexpression systems only in stable cell lines.

Animals↗
PubMed1999

Crystal structure of 7,8-dihydroneopterin triphosphate epimerase.

BACKGROUND: Dihydroneopterin triphosphate (H2NTP) is the central substrate in the biosynthesis of folate and tetrahydrobiopterin. Folate serves as a cofactor in amino acid and purine biosynthesis and tetrahydrobiopterin is used as a cofactor in amino acid hydroxylation and nitric oxide synthesis. In bacteria, H2NTP enters the folate biosynthetic pathway after nonenzymatic dephosphorylation; in vertebrates, H2NTP is used to synthesize tetrahydrobiopterin. The dihydroneopterin triphosphate epimerase of Escherichia coli catalyzes the inversion of carbon 2' of H2NTP. RESULTS: The crystal structure of the homo-octameric protein has been solved by a combination of multiple isomorphous replacement, Patterson search techniques and cyclic averaging and has been refined to a crystallographic R factor of 18.8% at 2.9 A resolution. The enzyme is a torus-shaped, D4 symmetric homo-octamer with approximate dimensions of 65 x 65 A. Four epimerase monomers form an unusual 16-stranded antiparallel beta barrel by tight association between the N- and C-terminal beta strands of two adjacent subunits. Two tetramers associate in a head-to-head fashion to form the active enzyme complex. CONCLUSIONS: The folding topology, quaternary structure and amino acid sequence of epimerase is similar to that of the dihydroneopterin aldolase involved in the biosynthesis of the vitamin folic acid. The monomer fold of epimerase is also topologically similar to that of GTP cyclohydrolase I (GTP CH-1), 6-pyrovoyl tetrahydropterin synthase (PTPS) and uroate oxidase (UO). Despite a lack of significant sequence homology these proteins share a common subunit fold and oligomerize to form central beta barrel structures employing different cyclic symmetry elements, D4, D5, D3 and D2, respectively. Moreover, these enzymes have a topologically equivalent acceptor site for the 2-amino-4-oxo pyrimidine (2-oxo-4-oxo pyrimidine in uroate oxidase) moiety of their respective substrates.

Amino Acid Sequence↗
PubMed1999

The Assessment of Quality of Life (AQoL) instrument: a psychometric measure of health-related quality of life.

This paper describes constructing the Assessment of Quality of Life (AQoL) instrument; designed to measure health-related quality of life (HRQoL), and to be the descriptive system for a multi-attribute utility instrument. Unlike previous utility instruments' descriptive systems, the AQoL's has been developed using state-of-the-art psychometric procedures. The result is a descriptive system which emphasizes five different facets of HRQoL and which can claim to have construct validity. Based on the WHO's definition of health a model of HRQoL was developed. Items were written by focus groups of doctors and the researchers. These were administered to a construction sample, comprising hospital patients, and community members chosen at random. Final construction was through an iterative process of factor and reliability analyses. The AQoL measures 5 dimensions: illness, independent living, social relationships, physical senses and psychological wellbeing. Each has three items. Exploratory factor analysis showed the dimensions were orthogonal, and each was unidimensional. Internal consistency was alpha = 0.81. Structural equation modeling explored its internal structure; the comparative fit index was 0.90. These preliminary results indicate the AQoL has the prerequisite qualities for a psychometric HRQoL instrument for evaluation; replication with a larger sample is needed to verify these findings. Scaling it for economic evaluation using utilities is being undertaken. Respondents have indicated the AQoL is easy to understand and is quickly completed. Its initial properties suggest it may be widely applicable.

Adult↗
PubMed1999

After-school supervision and adolescent cigarette smoking: contributions of the setting and intensity of after-school self-care.

This paper looks at the independent contributions of the setting and the intensity of after-school self-care to the cigarette smoking behaviors of 2352 ninth graders. We controlled for a variety of correlates of adolescent cigarette smoking that have not been accounted for in existing research. Results indicated that the intensity of the self-care experience was significantly associated with adolescent smoking behavior irrespective of the typical setting of the adolescents' after-school activities. Our findings also indicated that a nonpermissive parenting style, family rule-setting about cigarettes, and especially, in absentia parental monitoring may reduce the likelihood of cigarette smoking among latchkey and nonlatchkey adolescents alike. However, latchkey youth were not any more sensitive to these aspects of parenting than other adolescents. This is consistent with the notion that targeting these aspects of the home lives of all adolescents has the potential to reduce smoking behaviors among latchkey as well as nonlatchkey children.

Adolescent↗
PubMed1999

Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development.

Periconceptional folic acid supplementation reduces the occurrence of several human congenital malformations, including craniofacial, heart and neural tube defects. Although the underlying mechanism is unknown, there may be a maternal-to-fetal folate-transport defect or an inherent fetal biochemical disorder that is neutralized by supplementation. Previous experiments have identified a folate-binding protein (Folbp1) that functions as a membrane receptor to mediate the high-affinity internalization and delivery of folate to the cytoplasm of the cell. In vitro, this receptor facilitates the accumulation of cellular folate a thousand-fold relative to the media, suggesting that it may be essential in cytoplasmic folate delivery in vivo. The importance of an adequate intracellular folate pool for normal embryogenesis has long been recognized in humans and experimental animals. To determine whether Folbp1 is involved in maternal-to-fetal folate transport, we inactivated Folbp1 in mice. We also produced mice lacking Folbp2, another member of the folate receptor family that is GPI anchored but binds folate poorly. Folbp2-/- embryos developed normally, but Folbp1-/- embryos had severe morphogenetic abnormalities and died in utero by embryonic day (E) 10. Supplementing pregnant Folbp1+/- dams with folinic acid reversed this phenotype in nullizygous pups. Our results suggest that Folbp1 has a critical role in folate homeostasis during development, and that functional defects in the human homologue (FOLR1) of Folbp1 may contribute to similar defects in humans.

Animals↗
PubMed1999

A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses.

Both epidural and paravertebral blocks are effective in controlling post-thoracotomy pain, but comparison of preoperative and balanced techniques, measuring pulmonary function and stress responses, has not been undertaken previously. We studied 100 adult patients, premedicated with morphine and diclofenac, allocated randomly to receive thoracic epidural bupivacaine or thoracic paravertebral bupivacaine as preoperative bolus doses followed by continuous infusions. All patients also received diclofenac and patient-controlled morphine. Significantly lower visual analogue pain scores at rest and on coughing were found in the paravertebral group and patient-controlled morphine requirements were less. Pulmonary function was significantly better preserved in the paravertebral group who had higher oxygen saturations and less postoperative respiratory morbidity. There was a significant increase in plasma concentrations of cortisol from baseline in both the epidural and paravertebral groups and in plasma glucose concentrations in the epidural group, but no significant change from baseline in plasma glucose in the paravertebral group. Areas under the plasma concentration vs time curves for cortisol and glucose were significantly lower in the paravertebral groups. Side effects, especially nausea, vomiting and hypotension, were troublesome only in the epidural group. We conclude that with these regimens, paravertebral block was superior to epidural bupivacaine.

Adolescent↗