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Biomedical subjects

L Davies

Publications and source records attributed to L Davies.

At least 19 recordsLinked to original sources

An active covalently linked dimer of human interferon-gamma. Subunit orientation in the native protein.

We have constructed and expressed a covalently linked head to tail dimer of human interferon-gamma (IFN-gamma) in which two monomers are joined head to tail via a rigid peptide hinge using genetic engineering techniques. The hinge was derived from the human immunoglobin IgA1 sequence (Hallewell, R.A., Laria, I., Tabrizi, A., Carlin, G., Getzoff, E.D., Tainer, J.A., Cousens, L.S., and Mullenbach, G.T. (1989) J. Biol. Chem. 264, 5260-5268). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the polypeptide produced by this construction migrates as a 30,000 polypeptide species. The protein elutes as a single species by molecular sieve chromatography under native conditions. The covalently linked dimer exhibits one-half the antiviral activity of native dimeric IFN-gamma; receptor binding assays show the covalently linked dimer binds to the IFN-gamma receptor with one-half the avidity of native IFN-gamma. This difference is not due to conformational differences between the two molecules, as the aromatic region of the NMR spectrum of the purified covalently linked dimer is identical with that of the wild type protein. From these data, we suggest that human IFN-gamma associates in a head to tail dimer in its active configuration. Regions of IFN-gamma are contiguous with the amino and carboxyl termini and are obscured by the hinge peptide in the covalently linked dimer. Our studies demonstrate that these regions may be important for receptor-ligand interaction.

Amino Acid Sequence

Recumbent tic.

A 59-year-old man with a 30-year history of an unusual movement disorder characterised by involuntary axial spasms that occur only in recumbency is described. Clinical and electrophysiological evidence suggest that this disorder is best characterised as a simple tic of unusual form. We have coined the term "recumbent tic" to describe this disorder.

Abdominal Muscles

The economics of femorocrural reconstruction for critical leg ischemia with and without autologous vein.

It is well established that primary arterial reconstruction, even to crural vessels, is cheaper than amputation. Reintervention increases expenditure and may produce mean costs exceeding those of primary amputation. Furthermore, secondary amputation may eventually become necessary. Femorocrural grafts have the highest average "reconstruction policy" cost (i.e., primary procedure and all further operations necessary during follow-up). We must therefore seek support for this potentially expensive form of treatment. In conjunction with health economists we have compared the average policy cost of 130 reconstructions with grafts exceeding 70 cm in length (89 vein grafts, 41 polytetrafluoroethylene grafts with a distal vein collar) with 67 vascular amputations, at mean follow-up of 3 years. One-month mortality rate after reconstruction was less than 1% but was 10% after amputation. At 3 years, however, 20% of both groups were dead. Overall 3-year patency is 65% (72% for vein grafts, 48% for polytetrafluoroethylene grafts). Ninety-seven percent of irreversible graft occlusions resulted in amputation in these patients. After autologous vein grafting reintervention, our follow-up showed increased mean costs from $6898 to $15,024 per patient. After prosthetic grafting, the higher reintervention rate increased from $6898 to $20,416. These mean costs remained less than amputation, reintervention, and additional mobility costs, which amounted to a mean of $21,726 per patient. Important differences in outcome were observed: 70% of patients undergoing amputation were confined to the home compared with only 9% of patients undergoing reconstruction; 30% of patients undergoing amputation were confined to bed or had to use a wheelchair compared with 1% of patients undergoing reconstruction.

Amputation, Surgical

Confidants and companions: choices in later life.

This study examines and compares the correlates of considering each of the following as a confidant or a companion: spouse, children, siblings, other relatives, friends. Using a Canadian sample of 400 respondents aged 65 and over, we found evidence of substitution among the previously married and childless; more extensive ties to children and more intimate ties to friends among women; the importance of geographic proximity to children for confiding and companionship, and to siblings for confiding; the relevance of family size to confiding in siblings; and the precariousness of friendship as one reaches very old age. Predictors of who serve as confidants and as companions are similar, but important differences emerge. We compared our results to those of studies in Australia and the United States and to an earlier analysis of network composition and concluded that the confiding and companionate relations of older persons are best understood by combining the results of relationship-specific and network composition analyses.

Aged

Correlates of using mental health services: implications of using alternative definitions.

BACKGROUND: Studies using varying definitions of mental health visits result in widely divergent estimates. This analysis examines the stability of a predictive model using three varying definitions based on provider type, diagnosis, psychotherapy, and psychotropic medication use. METHODS: Interview and questionnaire data and claims records from the RAND Health Insurance Experiment are used to test these models among 3138 enrollees. RESULTS: Estimates of visits, and factors associated with them, are highly sensitive to definitions. Depression was the only symptom/life situation variable, and education the only sociodemographic measure, predictive across all three models. Risk indicators such as suicide thoughts and drinking problems were only significant for the traditional (mental health specialty) model. While patients within the traditional model definition were significantly younger than other enrollees, those within the model using the most expansive definition were significantly older. Varying the definition also led to different results in respect to experimental manipulations, geographic sites and some specific types of comorbidity. CONCLUSIONS: A reasonable definition, consistent with medical standards, requires, at least, a mental health diagnostic judgment and some form of psychotherapeutic or drug treatment. Studies of the content of mental health care are needed.

Adult

Economic analysis alongside clinical trials. Revisiting the methodological issues.

Controlled clinical trials are recognized as the best source of data on the efficacy of health care interventions and technologies. Because economic evaluation is dependent on the quality of the underlying medical evidence, clinical trials have increasingly been viewed as a natural vehicle for economic analysis. However, the closer integration of economic and clinical research raises many methodological issues. This paper discusses these issues in trial design, collection of resource use data, collection of outcome data, and interpretation and extrapolation of results. Some guidelines are suggested for economic analysts wishing to undertake evaluations alongside clinical trials.

Clinical Trials as Topic

Vasculitic neuropathy. A clinical and pathological study.

The clinical, electrophysiological and pathological features and prognosis of 34 patients with peripheral neuropathy caused by necrotizing vasculitis were evaluated. The causes included polyarteritis nodosa and its Churg-Strauss variant, rheumatoid arthritis, undifferentiated connective tissue disease, Wegener's granulomatosis, primary Sjögren's disease, and chronic lymphocytic leukaemia with cryoglobulinaemia; 2 patients had no evidence of systemic vasculitis. Mononeuritis multiplex was the most common clinical manifestation, followed by asymmetrical polyneuropathy and distal symmetrical polyneuropathy. Pain was a frequent symptom. Nerve conduction studies were abnormal in all cases, and in 3 patients there was conduction block or severe slowing of motor conduction. Necrotizing vasculitis was present in sural nerve biopsies of most cases, and severe active axonal degeneration was a dominant feature. Immunofluorescent staining of blood vessels for immunoglobulin, C3 and fibrinogen was positive in all cases in which it was performed, even when there was no cellular infiltration. All patients were treated with prednisone alone or in combination with other immunosuppressive agents, or with plasmapheresis. Long-term follow-up studies demonstrated that although the peripheral neuropathy usually improved and caused only mild to moderate functional disability, the long-term prognosis of the systemic disease was poor with a 5-yr survival of only 37%.

Adult

HIV prevalence and risk behaviours for HIV transmission in South Australian prisons.

During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.

Adult

Warning signals for malnutrition in the elderly.

Aging and disability are often assumed to coexist in Western society. Nevertheless, most elderly people live in noninstitutional settings. Monitoring and improving the nutritional integrity of the elderly could play a part in helping them remain healthy and independent. A community-based approach to the prevention of malnutrition in elderly people has been developed. This approach teaches warning signals for malnutrition to care providers who are in contact with elderly men and women. Care providers learn to recognize a group of circumstances (warning signals) that could have a negative impact on an elderly person's nutritional status. Examples of risk factors are given, and the interplay between risk factors and warning signals is discussed as well as their combined application. Practical steps for simple intervention are suggested. The dietitian is the nutrition educator and coordinator of this service.

Aged

Risk and selection processes between the general and the specialty mental health sectors.

This paper examines risk, defined as the threat of danger or disruption, as a contextual concept important for understanding patterns of patient selection and referral. We explore the hypothesis that risks associated with mental disorder, as represented by factors such as thoughts about suicide or problems associated with drinking, increase the probability of referral of patients receiving mental health care from general medical practitioners to the specialty mental health sector. Interview and claims data from the RAND Health Insurance Experiment, a large experimental study of coinsurance, are used to examine referral processes over a five-year period. Risk, and especially a measure of suicide thoughts, increase the probability of referral to specialty care. Women and persons with higher education are more likely to use specialty services; older persons are less likely to use such services. Understanding referral requires attention to the behavioral contingencies and illness behavior surrounding the presentation of mental disorder.

Educational Status

Mental effort and elaboration: effects of accessibility and instruction.

The present study examined the effects of accessibility to relevant schematic knowledge for elaboration in the associative learning of noun pairs. Fifth-grade participants performed two simultaneous tasks--associative learning and finger tapping--so that the mental effort demands of elaborating pairs that varied in accessibility could be estimated. The mental effort expended during the creation of sentence elaborations was greater for inaccessible pairs than accessible pairs. This accessibility difference was not observed when subjects were provided with the pair members in sentences. These findings confirm information-processing analyses of the elaboration process and support a knowledge-base interpretation of developmental differences in elaboration effort.

Attention

In vitro embryo culture in the production of identical merino lambs by nuclear transplantation.

This study examined the viability of embryos developed in vitro from 8- to 16-cell stage blastomeres fused with enucleated oocytes. Of 209 blastomeres recovered and subjected to manipulation and electrofusion procedures, 190 (91%) fused successfully, with 86 (45%) of those undergoing cleavage up to the 4- to 16-cell stage when cultured for 66 h in a synthetic oviduct fluid medium. The viability of the embryos was examined by transferring them to recipient ewes and determining the ewes' pregnancy status by ultrasound on Day 45. Of 86 embryos transferred, 14 developed to fetuses in 8 of the 36 recipients, including four sets of identical twins and one set of quads. In contrast, with uncultured and unmanipulated embryos, 15 fetuses developed from 19 embryos transferred at a similar stage of development. The viability of embryos derived from manipulated zygotes cultured in vitro was comparable to that previously reported for studies employing in vivo culture, indicating the potential of in vitro culture systems based on a simple medium for nuclear-transplantation embryos.

Animals

Confidants and companions in later life: the place of family and friends.

Responses from a sample of 400 older persons were used to determine the relative importance of various family members (spouse, children, siblings, other relatives) and friends in the confidant and companion networks of later life. Significant differences exist among older persons (based on gender, marital status, and availability of children) in the salience of these ties as confidants and companions. There are also major differences in the configuration of the confidant vs companion networks. These variations are discussed in the context of the hierarchical-compensation, task specificity, and functional specificity of relationships models of support. The findings demonstrate that a distinction regarding availability of kin must be made among those who never had a particular kin tie (e.g., the childless and single), those who have lost a previous tie (e.g., the widowed), and those whose tie lives far away.

Aged

Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers.

A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups.

Acetaminophen

Species composition and larval habitats of blowfly (Calliphoridae) populations in upland areas in England and Wales.

1. Bait trapping at upland sites in England and Wales, mainly at 400-700 m altitude, showed that Calliphora vomitoria L. usually outnumbered all other blowflies. C.vicina R.-D., C.loewi End. and C.alpina Zett were usually present in much lower numbers, with the last-named occurring at north Pennine sites, but being replaced by C.subalpina Ringd. at a south Pennine (Peak District) and a Welsh site. Catches normally included Cynomya mortuorum L., and Phormia terraenovae R.-D. was present at about half of the sites, usually in low numbers. 2. Lucilia spp. (predominantly L.caesar L.) were often abundant in catches at 300-430 m, but were absent or rare at 500 m and above, except at certain times. 3. Exposure of mouse carcasses at north Pennine upland sites, and rearing of adults from them, showed that they were colonized in a very indeterminate variable way by C.vicina, C.loewi, C.alpina and Cy.mortuorum, with dominant and subsidiary species varying in identity and numbers within periods as short as 3 weeks. 4. Sampling of large carcasses, i.e. hill sheep casualties in Co. Durham, showed that C.vomitoria predominated as the blowfly colonist, with C.vicina and Cy.mortuorum in much smaller numbers.

Animals