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Biomedical subjects

D M Edwards

Publications and source records attributed to D M Edwards.

At least 19 recordsLinked to original sources

Polaronic quasiparticles in a strongly correlated electron band.

We show that a strongly renormalized band of polaronic quasiparticle excitations is induced at the Fermi level of an interacting many-electron system on increasing the coupling of the electrons to local phonons. We give results for the local density of states at zero temperature both for the electrons and phonons. The polaronic quasiparticles satisfy Luttinger's theorem for all regimes considered, and their dispersion shows a kink similar to that observed experimentally in copper oxides. Our calculations are based on the dynamical mean field theory and the numerical renormalization group for the hole-doped Holstein-Hubbard model and large on-site repulsion.

Journal Article↗

Disability part 3: improving access to dental practices in Merseyside.

Several Merseyside dental practices took part in disability access audits of practice premises and practice staff took part in disability awareness training. Grants were awarded to part-fund improvements to practice facilities in line with the recommendations in the audit reports. The dental teams reported that the awareness training was very valuable and many common issues arose from the audits. Access for disabled people needs to be considered in all practice developments to ensure that dental practices comply with Part III of the Disability Discrimination Act by 2004.

Architectural Accessibility↗

Disability part 2: access to dental services for disabled people. A questionnaire survey of dental practices in Merseyside.

This article aims to identify how accessible general dental practitioners thought that their services were and to identify the barriers they face in providing care for disabled people. A postal questionnaire survey was undertaken of all general dental practices in the Liverpool, Sefton, St Helens and Knowsley Health Authorities. Only one quarter of practices described themselves as having full physical access for disabled patients. However, despite this, over 90% of practices reported treating disabled patients and most were willing to treat more disabled patients. Dentists identified physical barriers, lack of time and the lack of domiciliary equipment as the main barriers to providing care for disabled people. Although dentists were willing to treat disabled patients few dental practices were accessible at the time of the survey. Further work is needed to ensure that dental practices comply with the Disability Discrimination Act.

Architectural Accessibility↗

Disability part 1: the disability discrimination act (1995)--implications for dentists.

The Disability Discrimination Act (1995) (DDA) aims to end the discrimination which many disabled people face in their day-to-day lives. (1) But how many dentists are aware of their responsibilities under this Act? Dentists are already bound by Parts I and II of the DDA, but Part III, which is due to come into effect in 2004, and which is concerned with physical alterations to premises, has potentially profound implications for many in dental practice. Health Authorities in Merseyside, in the North West of England have been exploring ways in which access to dental care for disabled people can be improved. In this paper, the first of a series of three, we outline the DDA and how it affects dentists in general practice.

Adolescent↗

Incidence of and survival from upper aerodigestive tract cancers in the U.K.: the influence of deprivation.

The aim of the study was to investigate the effect of social deprivation on the incidence of and survival from upper aerodigestive tract (UAT) cancers in the U.K. Incidence was calculated on 25,903 cases of malignant upper aerodigestive tract cancers collected from four cancer registries in the U.K. for the period 1984-1993. A Cox proportional hazard model was used to determine the influence of deprivation, measured in Carstairs quintiles for crude and cause-specific survival on 17,393 of these cases. Patients with UAT cancers who were younger, males or of South Asian origin were more likely to live in a deprived area than in an affluent area. The incidence of UAT cancers in a district was correlated with deprivation score for the district for both men (r = 0.78) and for women (r = 0.60). People who lived in deprived areas had a relative risk of 1.25 (95% confidence interval (CI): 1.15-1.35) of dying from their cancer and of 1.24 (95% CI: 1.13-1.35) of dying from all causes compared with people who lived in affluent areas. People living in deprived areas were more likely to get UAT cancer and were more likely to die from their cancer than people living in affluent areas.

Aged↗

Treatment of upper aerodigestive tract cancers in England and its effect on survival.

The evidence base for head and neck cancers is low with relatively few randomized controlled trials of the two main treatments, surgery and radiotherapy. The aim of the study was to investigate the patterns of surgery and radiotherapy treatment for head and neck cancers in three large areas of England and to investigate their effects on survival. This was a retrospective study of 13510 cases of head and neck cancers (ICD10: C00-C14, C30-C32) diagnosed and treated from 1984 to 1992 in England. We undertook multivariate analyses of survival using a step-wise Cox proportional hazard model and Kaplan-Meier analysis. There were regional variations in the treatments given to patients. Four in ten patients did not receive currently recommended treatments. In multivariate analyses treatment content and timing had an independent effect on survival. Better survival was associated with surgery for mouth cancers, radiotherapy for laryngeal cancers and combined treatment for pharyngeal cancers independent of tumour and demographic factors. Further research is needed to investigate the findings of this study through large randomized controlled trials and multi-centre audits.

Adult↗

Population effects of preventive and therapeutic HIV vaccines in early- and late-stage epidemics.

OBJECTIVE: To evaluate the population effects of potential preventive and therapeutic vaccines in early- and late-stage epidemics in a population of homosexual men. METHODS: An epidemic model was used that simulated the course of the epidemic for a population of homosexual men in San Francisco, California. Vaccine programs were evaluated by the number of cases of HIV averted, the effect on the prevalence of HIV, and by the gain in quality-adjusted life years (QALY) for the total population. RESULTS: In the model, a preventive vaccine prevented 3877 cases of HIV infection during a 20-year period, reduced the projected prevalence of HIV infection from 12 to 7% in a late-stage epidemic, and gained 15,908 QALY. A therapeutic vaccine that did not affect the infectivity of vaccine recipients increased the number of cases of HIV infection by 210, resulted in a slight increase in the prevalence of HIV infection from 12 to 15% in a late-stage epidemic, and gained 8854 QALY. If therapeutic vaccines reduced infectivity, their use could produce net gains of QALY in the population that were similar to gains from the use of preventive vaccines. In an early-stage epidemic, the advantage of a preventive vaccine program relative to a therapeutic vaccine program was markedly enhanced. CONCLUSIONS: Both preventive and therapeutic vaccine programs provided substantial benefit, but their relative merit depended on which outcome measures were assessed. Evaluation of HIV vaccine programs based solely on cases averted or on prevalence of HIV in the population underestimates the benefit associated with therapeutic vaccine programs. The effect of a therapeutic HIV vaccine on the epidemic outcomes depended markedly on whether the therapeutic vaccine reduced the infectivity of the vaccine recipient. The relative merits of preventive and therapeutic vaccines depend on the stage of the epidemic. Field vaccine trials should evaluate correlates of infectivity, such as HIV viral load. HIV vaccine implementation strategies should be tailored to the dynamics of the epidemic in specific populations.

AIDS Vaccines↗

A survey of consultants treating upper aerodigestive tract cancer in the UK.

A study was undertaken to determine the current service provision for the treatment of upper aerodigestive tract (UAT) cancers in the UK. A postal questionnaire was sent to all consultant members of relevant specialist societies, with 1041 (74%) responding. Treatment of UAT cancer is widely dispersed with over 900 consultants from five major disciplines treating, on average, less than 10 cases per year. There were few regional or provider differences in the facilities and services available and in processes used for assessing patients. There is little systematic collection of data for audit or research and some consultants do not record stage. The involvement of other disciplines in the assessment process, use of joint clinics, counselling, specialist nursing and therapy services appears to be low. There is a need for rationalisation of head and neck cancer services; for more systematic collection of data for audit and research and for improvements in the use of joint clinics and support services.

Cancer Care Facilities↗

Oral health care in the lives of Gypsy Travellers in east Hertfordshire.

OBJECTIVE: To explore Gypsy Travellers' perceptions of dental health and dental service use within the context of culture, environment and the use of other services. SETTING: The author was a community dental officer and the study formed part of a MSc dissertation in dental public health. SUBJECTS AND METHODS: Information was obtained from semi-structured interviews with 43 Gypsy Travellers supplemented by a questionnaire and clinical screening of 72 Travellers. MAIN OUTCOME MEASURES: Place of residence, registration with GMP and GDP, school attendance, caries, normative and perceived barriers to care. RESULTS: The Travellers in the study had a high level of unmet need, low dental registration and very little use of preventive services. Travellers have no cultural barriers to dental care. Control of their travelling was the major factor determining access to education and health services. CONCLUSIONS: There is inequity of dental health and dental service use with more disadvantage being experienced by Travellers on unauthorized and transit sites.

Adolescent↗

Diet and hygiene in the lives of Gypsy Travellers in Hertfordshire.

Gypsy Travellers may be regarded as an ethnic group. A study was undertaken to investigate aspects of food and hygiene in the lives of Travellers within the context of their culture and environment. Semi-structured interviews were used to explore these factors. Gypsy Travellers are conscious of having a separate identity and culture. They share particular cultural characteristics in relation to food and hygiene of which dental health professionals should be aware. However, with respect to oral health they have adopted many of the health beliefs and attitudes of the general population. The implications for oral health care and health promotion are discussed.

Adolescent↗

Pharmacokinetics of reboxetine in healthy volunteers. Single against repeated oral doses and lack of enzymatic alterations.

The pharmacokinetics of reboxetine have been investigated in 12 healthy male volunteers after a single 2 mg dose of reboxetine and at steady state, following the last administration of a multiple-dose regimen (2mg twice a day for 5 1/2 d). Reboxetine was analysed in plasma and urine samples collected up to 72 h post-dosing using an HPLC method with UV detection. The urinary excretion rate of 6-beta-hydroxycortisol, used as a marker for cytochrome P450IIIA activity, was also tested, and any possible alteration was correlated to reboxetine plasma levels. The dosing regimen was well tolerated by all subjects. Reboxetine pharmacokinetic parameters, calculated after the single dose using non-compartmental analysis, were in good agreement with those obtained in previous studies. Following the multiple-dosing regimen, no significant deviations from expectation based on linear superposition was observed. The accumulation ratio, based on repeated-dose/single-dose ratios of Cmax, AUC(0-12 h), and C(12 h) was approximately two. A slight rise was recorded for the average excretion rate of 6-beta-hydroxycortisol over 48 h by the end of treatment; however, the difference was not statistically significant and the mean excretion rates were within the normal reference range. Thus a significant induction of P450IIIA was not indicated.

Administration, Oral↗

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding.

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4, and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4 mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax approximately equal to 2 h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F approximately equal to 29 mL min-1; Vz/F approximately equal to 32 L); urinary excretion was approximately 9% of dose, corresponding to a renal clearance of only 3 mL min-1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C-labelled reboxetine, appeared to be dominated by alpha 1-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL-1 (2.8-3.1% unbound with human plasma from three additional volunteers; 1.8-2.0% for 2 gL-1 orosomucoid alpha 1-acid glycoprotein, and 46.4-47.4% for 40 g L-1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL-1 after a 5mg dose).

Adult↗

Pharmacodynamics and relative bioavailability of cabergoline tablets vs solution in healthy volunteers.

The effect of formulation on the urinary pharmacokinetics, pharmacodynamics, and relative bioavailability of cabergoline was investigated. Twelve healthy female volunteers, aged 23-35 years, were treated, according to an open, randomized, crossover design, with cabergoline (1-mg single oral dose) both as tablets and as a solution. The two administrations were separated by a 4-week wash-out period. Cabergoline and prolactin were measured in urine and plasma, respectively, by specific radioimmunoassays. Blood samples were collected before and up to 30 days after dosing. Urine was collected before and up to 8 days after dosing. Cabergoline elimination half-lives calculated from urinary data were 68 and 63 h after administration of the tablets and the solution, respectively. Urinary excretion of unchanged cabergoline accounted, on average, for 1.92% (range, 0.14-3.26) and 1.80% (range, 0.67-3.09) of the dose after administration of the tablets and the aqueous solution, respectively. Relative bioavailability of tablets vs solution was 99% (geometric mean with the 90% confidence intervals of 68-144%). Prolactin levels in 10 out of 12 subjects fell below the detection limit of the assay (1.5 micrograms/L) after both treatments. The mean maximum prolactin decrease (ca. 70%) was achieved by 2 or 3 h after dosing; the effect persisted up to 9 days, being completely exhausted 23-28 days after dosing. The analysis of variance performed on the pharmacodynamic effects of the two cabergoline formulations indicated that the percent decreases of plasma prolactin levels were not significantly different for tablets and solution. These results indicate that the pharmacodynamics and relative bioavailability of cabergoline are not influenced by formulation, as tablets or solution.

Adult↗

Bioavailability of a new oral formulation of medroxyprogesterone acetate compared with the standard formulation: a single dose randomized study.

Twenty-six female patients with breast cancer participated in an open, randomized, cross-over study comparing single dose bioavailability of a recently developed oral medroxyprogesterone acetate (MPA) formulation (200 mg sachet where MPA is loaded in a polyvinylpyrrolidone cross-linked polymer, MPA/PVP) with the standard formulation (500 mg tablet). Blood tests were performed under standardized conditions for 120 h in all patients and MPA plasma concentrations determined by means of HPLC. Dose-normalized AUC(0-tz), AUC (0-infinity) and Cmax were all significantly higher for the MPA/PVP formulation than for the standard formulation. The relative bioavailability of the MPA/PVP formulation was on average three times superior to that of the standard formulation. This new MPA formulation might have important clinical implications for the treatment of hormone-sensitive cancer.

Administration, Oral↗

Determination of the acyl moieties of the antibiotic complex A40926 and their relation with the membrane lipids of the producer strain.

Structures of the fatty acid residues characterizing the various components of A40926 were determined by gas chromatography/mass spectrometry on the methyl esters obtained by methanolysis of the complex. The results confirm the residues previously assigned to Factor A (n-undecanoic acid) and B (10-methyl-undecanoic acid) and establish the residues of Factor A1 (9-methyl-decanoic acid), B1 (n-dodecanoic acid), RS1 (8-methyl-nonanoic acid), RS2 (n-decanoic acid), and RS3 (n-tridecanoic acid). As the Actinomadura species contain in their mycelia large quantities of C15-C17 fatty acid residues as membrane phospholipids, these mycelia were saponified and the fatty acids obtained were analyzed as above. There is a close correlation between the fatty acid content of A40926 complex and that of the longer homologues in the producer mycelia.

Anti-Bacterial Agents↗

The rabbit retina: a long-term model system for aluminum-induced neurofibrillary degeneration.

Aluminum (Al) was injected into the rabbit eye as a potential long-term model system for Al-induced neurofibrillary degeneration (NFD). Neurofibrillary tangles made up of 10 nm phosphorylated neurofilaments were observed in a subpopulation of retinal ganglion cells, located primarily in the peripheral retina. The distribution of affected cells suggested a differential susceptibility of ganglion cells to Al intoxication. Importantly, none of the animals demonstrated any of the central neurological dysfunctions characteristic of previous Al intoxication models. The retinal model should allow for long-term studies of Al intoxication and its potential relationship to neurofibrillary degenerative disorders such as Alzheimer's disease.

Aluminum↗

Folate analogues. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogues of N10-propargyl-5,8-dideazafolic acid.

Structural modifications at the pyrimidine ring and at the C9,N10-bridge region of the thymidylate synthase (TS) inhibitors N10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

Biological Transport↗