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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 181 records · Page 10Linked to original sources
PubMed1994

Reduced platelet cytochrome c oxidase activity in Alzheimer's disease.

We evaluated a simplified method for preparation and analysis of platelet cytochrome c oxidase activity in Alzheimer's disease (AD) and control patients. Mean cytochrome c oxidase activity in controls (n = 17) was 0.233 sec-1/mg whereas mean cytochrome c oxidase activity in Alzheimer patients (n = 19) was 0.193 sec-1/mg, p = 0.033. Complex III (ubiquinol:cytochrome c oxidoreductase), complex II (succinic dehydrogenase), and citrate synthase were all assayed as internal controls and were not significantly different in controls and Alzheimer patients. There is a relatively specific loss of platelet cytochrome c oxidase activity in Alzheimer disease patients.

Aged↗
PubMed1994

Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse.

Macrophages play a pivotal role in the adult inflammatory response to wounding. They are directly responsible for cellular debridement and, by providing a source of growth factors and cytokines, they recruit other inflammatory and fibroblastic cells and influence cell proliferation and tissue remodelling. In this paper we investigate the role of macrophages in clearing areas of programmed cell death in the developing embryo and also their role in embryonic and foetal wound healing. Immunocytochemistry using the monocyte/macrophage-specific monoclonal antibody, F4/80, reveals a close association between areas of programmed cell death in the remodelling interdigital regions of the mouse footplate and of F4/80-positive cells, suggesting that monocyte-derived macrophages, and not locally recruited fibroblastic cells, as previously believed, are responsible for phagocytosing and clearing areas of interdigital apoptosis. Our studies of wound healing reveal that macrophages are not recruited to, and therefore cannot be playing an active role in the healing of, excisional wounds made in the mouse embryo at any stage up until E14.5. Beyond this transition stage we see a significant recruitment of macrophages within 12 hours of wounding. We find that macrophages can be attracted to wounds in earlier embryos if the wound results in significant cell death such as after burning.

Animals↗
PubMed1994

Vowel use of phonologically disordered identical twin boys: a case study.

Very little is known about the vowel systems of phonologically disordered children. This study provides longitudinal data regarding vowel use of identical twin boys between the ages of 3;5 and 4;9. The boys were identified as phonologically disordered; however, their parents chose not to enroll them in therapy. Vowel-use information was taken from spontaneous language samples. It was discovered that initially their phonological disorder also affected their vowel systems, but as their phonological skills increased so did correct use of vowels and their vowel use tended to follow normal developmental trends.

Articulation Disorders↗
PubMed1993

Down by law.

Will legal challenges to health authorities be more successful than before the reforms? Jean McHale and David Hughes report on the case of Rhys Daniels.

Bone Marrow Transplantation↗
PubMed1993

Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor.

Macrophages interact with other cells and components of the extracellular environment by means of adhesion receptors. Adhesion to artificial substrata in vitro facilitates isolation of macrophages, and has been used to generate antibodies that inhibit their migration in vivo. Unlike other cell types, macrophages attach to tissue culture plastic in the absence of divalent cations. Here we use an adhesion assay exploiting this property to isolate a rat monoclonal antibody, 2F8, which totally inhibits divalent cation-independent adhesion of murine macrophages to tissue culture plastic in the presence of fetal calf serum. Immunoprecipitation from macrophages and stably transfected Chinese hamster ovary cells revealed that the antigen recognized by monoclonal 2F8 is identical to murine macrophage scavenger receptor. We propose a novel function for this molecule, previously described as an endocytic receptor, thus providing a mechanism for mononuclear phagocyte recruitment to and retention in ligand-rich tissues such as in atherosclerotic lesions.

Animals↗
PubMed1993

Econometric analyses of national health expenditures: can positive economics help to answer normative questions?

The size of national health care expenditure is an important research and policy issue. This paper reviews theoretical and empirical analyses of an implied optimal size for a health sector. Various economic theories are explicitly or implicitly invoked, but none is fully satisfactory. Theory provides, at best, a loose justification for empirical specifications of health sector behaviour. Nevertheless, this has a large and growing empirical research industry. The complexity of the issues provides an excuse for reliance on empirical analyses using ad hoc models. The paper analyses aggregate time-series data, using the cointegration approach, on health, health care expenditures and national income. Only one national model met both statistical criteria and showed a significant relationship: between potential life years lost and health care expenditure in the UK. The case for any general relationships remains unproven. There is no objective scientific method to determine optimal health expenditure, nor should we expect one. However, positive analyses can help with normative questions. A better understanding of health expenditure determination would arise from better specification of the relationships, perhaps by analysis at a lower level of aggregation.

Bias↗
PubMed1993

Cultural phenomena and the research enterprise: toward a culturally anchored methodology.

Highlights the points at which culture intersects major phases of the research enterprise--problem formulation, population definition, concept and measurement development, research design, methodology, and data analysis--and influences and constrains what researchers deem worthy of investigation and how they interpret what they observe. These ethnocentric biases inhibit the development of a knowledge base for understanding diverse cultural communities. At each step of the research process, the need to carefully examine and expose the underlying cultural assumptions and to generate and develop alternative choices is emphasized. Guidelines are provided to encourage researchers to be aware of and deliberately make choices toward the development of a culturally anchored methodology that balances the demands for rigor and sensitivity.

Culture↗
PubMed1993

General practitioners and the new contract: promoting better health through financial incentives.

In this paper the changes in payment of general practitioners in the UK, introduced in the 1990 contract, are described in detail. The effects of the changes on the structure of general practitioners' incomes is discussed. More emphasis on capitation payments may increase preventive activity in general practice, but, depending on the level at which the capitation fee is set, could lead to shifting of patients to other sectors in the health care economy. Target payments appear to have been successful in increasing the numbers of smears taken. It is clear that doctors respond to financial incentives, but what is not clear is whether their responses will always be in the way intended or lead to more efficient practice.

Capitation Fee↗
PubMed1993

Caring for people efficiently.

The UK government's plans and objectives for community care in the 1990s are examined. The objective of providing care in the community 'wherever possible' is unlikely to be efficient unless the costs and benefits of providing such care are accounted for. Even if it were efficient to provide more care in the community, the mechanisms aimed at ensuring the transfer of funds have been inadequate in terms of encouraging such an objective. These same principles (i.e. the need to assess costs and benefits) should be applied to the design of individual packages of care in the community, when the costs and benefits of carers' time become more important. Case management offers the opportunity to assess individual circumstances which is necessary for the design of efficient packages of care. However, case management is likely to suffer from the problems of fragmentation which makes organisation of flexible packages of care difficult.

Community Health Services↗
PubMed1993

Pain relief for infants undergoing abdominal surgery: comparison of infusions of i.v. morphine and extradural bupivacaine.

We have undertaken a prospective, randomized double-blind study to compare extradural bupivacaine infusions with i.v. morphine infusions for postoperative analgesia in 32 infants younger than 4 yr undergoing abdominal surgery. "Sham" extradural or i.v. catheters were used to maintain the blinded nature of the study. Both techniques provided adequate analgesia for most of the 36-h postoperative period; differences in the pattern or quality of the analgesia were not detected. Patients in the i.v. morphine group were significantly more sedated; this was accompanied by slower ventilatory frequencies (26.7 (SD 1.8) b.p.m.) compared with the extradural group (33.6 (1.3) b.p.m.). Similarly, oxygen saturation was significantly less (P < 0.01) in patients receiving morphine (medians and quartiles of 94.0 (93-96)% compared with 96.0 (93-96)%). Mean systolic arterial pressure was similar in the two groups and there were no life-threatening complications. The lack of sedation was troublesome in three patients in the extradural group.

Abdomen↗
PubMed1993

Idiopathic retroperitoneal fibrosis is a macrophage-rich process. Implications for its pathogenesis and treatment.

Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease of obscure etiology and pathobiology. Using sections of frozen and paraffin-embedded tissue, an immunohistochemical technique, and antibodies to a variety of macrophage- and lymphocyte-associated antigens, we studied six examples of IRF. The results showed a large population of spindle-shaped cells that expressed the immunophenotype of a tissue macrophage, that is, Leu 3a,b (CD4)+, MY7 (CD13)+, Leu M5 (CD11c)+, KP-1 and EBM-11 (CD68)+, human leukocyte antigen (HLA-DR)+, leukocyte common antigen (CD45)+, HAM-56+, and MAC387+. A subpopulation of these cells also reacted with an antibody to the "activation" antigen, interleukin 2R (CD25). A control group of "fibroblastic" lesions including keloids, desmoid tumors, and an aggressive fibromatosis displayed minimal reactivity with this panel of antibodies. The abundance of macrophages suggests that they may play an important role in the pathogenesis of IRF. If, as has been suggested by some studies, IRF is an immune-mediated phenomenon, the macrophages may be triggered to produce cytokines that stimulate fibroblast proliferation and subsequent fibrosis that characterize this disease.

Adult↗
PubMed1993

Suppression of rpsL phenotypes by tuf mutations reveals a unique relationship between translation elongation and growth rate.

We have found a simple relationship between bacterial growth rate and the translation elongation rate. Thus, for a set of defined ribosomal protein S12 mutations which reduce the efficiency of the ternary complex ribosome interaction (and restrict the frequency of translational errors) there is a linear relationship between growth rate and translation elongation rate. When these mutants are combined with defined EF-Tu mutants (which increase the probability of translational errors) both the elongation rate and growth rate reductions are reversed. The reductions and reversals are described by a unique linear relationship. We interpret this to mean that these two types of mutation exert opposing effects on the same molecular interaction. We suggest that this interaction is in the initial selection of the aminoacyl-tRNA on the ribosome. The slope of the relationship between translation elongation rate and growth rate, defined in per cent of the wild-type rates, is close to 1. Interestingly, the reversal of the elongation and growth phenotypes is incomplete, suggesting that the ribosomal mutants have an additional defect which is not compensated for by the ternary complex interaction. Our results show that the efficiency of the ternary complex ribosome interaction limits the translation elongation rate, which in turn correlates with changes in exponential growth rate.

Alleles↗
PubMed1993

Growth and translation elongation rate are sensitive to the concentration of EF-Tu.

We have used quantitative immunoblotting to estimate the amount of EF-Tu in a variety of S. typhimurium strains with wild-type, mutant, insertionally inactivated or plasmid-borne tuf genes. In the same strains we have measured translation elongation rate, exponential growth rate and the level of nonsense codon readthrough. In the wild-type strain, at moderate to fast growth rates, our data show that EF-Tu makes up 8-9% of total cell protein. Strains with either of the tuf genes insertionally inactivated have 65% of the wild-type EF-Tu level, irrespective of which tuf gene remains active, or whether that gene is wild-type or a kirromycin-resistant mutant. Strains with only one active tuf gene have reduced growth and translation elongation rates. From the magnitude of the reduction in elongation rate relative to the level of EF-Tu we calculate that in glucose minimal medium the in vivo saturation level of wild-type ribosomes by ternary complexes is only 63%. Strains with a ribosome mutation causing a poor interaction with ternary complex are non-viable on minimal medium when the level of EF-Tu is reduced.

Cell Division↗
PubMed1993

Low-dose thyrotropin-releasing hormone effects in cognitively impaired alcoholics.

The cognitive effects of a low dose of thyrotropin-releasing hormone (TRH) (2.0 mg, IV) were evaluated in 18 chronic alcoholic patients who exhibited memory dysfunction secondary to chronic alcohol abuse. The study used a double-blind crossover design that compared cognitive functions in patients with 2.0 mg of TRH IV as compared with a placebo. TRH was chosen because of its ability to enhance cholinergic transmission. Only minimal effects were seen with TRH. Patients with a shorter duration of alcohol use (mean of 16 years) performed significantly better with TRH as compared with placebo on a test involving verbal learning and memory. Those with a more chronic history of alcohol abuse (mean of 27 years) did not show such a response. All of the subjects showed cardiovascular response to TRH. Factors that may have contributed to the results of our study are discussed. It is our impression that future studies evaluating the cognitive effects of TRH in chronic alcoholics need to include an evaluation of the functional activity of TRH in the brain.

Adult↗