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Biomedical subjects

D M Edwards

Publications and source records attributed to D M Edwards.

18 recordsLinked to original sources

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

Short root anomaly.

A case of generalised short root anomaly is described. All permanent teeth had abnormally short roots, associated with microdontia, hypodontia and a dens invaginatus. Members of the patient's family were similarly affected.

Adolescent

Antibiotic SB22484: a novel complex of the aurodox group. I. Taxonomy of the producing organism, isolation of the antibiotics and chemical and biological characterization.

Antibiotic SB22484 is a novel member of the aurodox type antibiotic group produced in submerged-fermentation cultures of Streptomyces sp. NRRL 15496. The antibiotic complex is composed of two pairs of isomers with MW's of 752 and 766. The individual isomers, which were separated by preparative HPLC, equilibrate to a mixture of the isomer pair when left in aqueous solution. In vitro, SB22484 antibiotics strongly inhibited neisseriae and were also active against Streptococci, Ureaplasma urealyticum and Haemophilus influenzae.

Animals

Liquid chromatographic-mass spectrometric studies on rifamycin antibiotics.

The use of a direct liquid introduction type liquid chromatographic-mass spectrometric interface to study highly thermally labile rifamycin antibiotics is described. Using negative ionization, abundant molecular ions were observed, and the spectra, also contained structurally significant fragments. Variation of the high-performance liquid chromatographic parameters did not change the spectra, thus making it easy to change chromatographic conditions. In quantitative studies, a surprising correlation was found, indicating that the mass spectrometric signal was proportional to the square of the sample concentration.

Chemical Phenomena

Congenital epulis of the newborn.

Reported is a case of congenital epulis of the newborn occurring in the mandible and the maxilla. The masses were of such size as to cause respiratory and nursing difficulties. The theories of pathogenesis, the surgical treatment, the histologic appearance, and a 5-year follow-up are described. As with previous cases reported, there has been no recurrence.

Female

Pharmacokinetics of iododoxorubicin in the rat, dog, and monkey.

The pharmacokinetics of iododoxorubicin (I-DOX) have been studied after single dose administration in the rat (iv and po), dog (iv and po), and monkey (iv). Plasma levels and amounts in urine were monitored by HPLC for both I-DOX and its biologically active metabolite, iododoxorubicinol (I-DOXOL). Plasma levels of I-DOX after iv administration could be described by a three-exponential curve with extremely fast initial phase. Terminal elimination half-lives of I-DOX were similar, 6-7 hr, in all three species. Body weight-normalized clearance (CL) and distribution volumes (Vd) of I-DOX were lower in the dog, but were similar in rat and monkey. The pharmacokinetic parameters also implied metabolic differences between species. Mean I-DOXOL/I-DOX AUC ratios were 0.02, 0.47, and 0.58, respectively, in rat, dog, and monkey, values considerably lower than reported in human studies. I-DOXOL remained slightly longer in the body than I-DOX, as seen both from terminal half-lives (9-11 hr) and mean residence times. In all species, renal excretion was virtually negligible: the amount of I-DOX + I-DOXOL in urine was less than 2% of dose. Mean bioavailabilities of I-DOX were 0.23 and 0.46 in rat and dog, respectively, and, in the latter, about half of I-DOXOL formation occurred during or before the first pass.

Animals