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Biomedical subjects

R Davies

Publications and source records attributed to R Davies.

At least 37 records · Page 2Linked to original sources
PubMed2003

Survival in frontotemporal dementia.

OBJECTIVES: To establish survival in patients with pathologically confirmed frontotemporal dementia (FTD) and to determine whether clinical or pathologic subtype affects prognosis. METHODS: The authors reviewed the presenting clinical features of 61 patients with dementia and pathologically confirmed FTD studied in Sydney (n = 31) and Cambridge (n = 30) over a 10-year period. Data were available on time of symptom onset, diagnosis, institutionalization, and death. Cases were classified pathologically as tau-positive and tau-negative. RESULTS: Of the 61 patients with FTD, 26 presented with frontal variant (fvFTD), 9 with semantic dementia, 8 with progressive nonfluent aphasia (PNFA), 9 with associated motor neuron disease (FTD-MND), and 9 with corticobasal degeneration features. There was no difference between the groups in age at symptom onset (overall mean 58.5 +/- 7.8 years), but at diagnosis the PNFA (68.3 +/- 2.7) group was significantly older than the fvFTD (59.9 +/- 7.4) and FTD-MND (57.7 +/- 7.9) groups. The median survival from symptom onset and from diagnosis was 6 +/- 1.1 years (95% CI) for fvFTD and 3 +/- 0.4 years for FTD-MND. Survival across subgroups was equivalent except for the FTD-MND group, which had significantly shorter survival. Cases with tau-positive pathology had an older age at onset and a significantly better prognosis: median survival 9.0 +/- 0.9 years vs 5.0 +/- 1.1 years. CONCLUSIONS: FTD is a malignant disorder with limited life expectancy. FTD-MND has the shortest duration both before and after diagnosis. Tau-positivity is associated with a more slowly progressive form of FTD.

Aged↗
PubMed2003

Observations on Salmonella contamination of commercial laying farms before and after cleaning and disinfection.

Little is known about the effectiveness of the cleaning and disinfection methods in use on commercial laying farms in Great Britain. Samples were taken from poultry house structures and equipment of five cage layer flocks, five barn egg production flocks and two free-range flocks. In the free-range houses there was a decrease in Salmonella after cleaning and disinfection, although the soil in the paddocks remained contaminated. In the barn and especially the cage layer houses, significant residual contamination remained on the surfaces of buildings and equipment. Wildlife pests were also found to be carrying Salmonella in the disinfected houses and free-range paddocks.

Animals↗
PubMed2003

The formulation and evaluation of a CFC-free budesonide pressurised metered dose inhaler.

Although dry powder inhalers are well established for the delivery of corticosteroids, the pressurised metered dose inhaler remains the preferred and most cost effective presentation. To design an HFA solution formulation which matched marketed CFC products (Pulmicort and Desonac DA) two elements of the Chiesi Modulite system, the addition of a non-volatile component and the actuator orifice diameter, were varied. These variables, which were shown by in vitro tests to influence the fine particle dose and its mean particle size in different ways, could be permuted to give an aerosol cloud with size characteristics very close to the comparator products. The likelihood that this would confer clinical equivalence is reinforced by a pharmacokinetic analysis which showed that the chosen HFA solution formula gave similar systemic absorption from the lung as Pulmicort. The equivalence in aerosol characteristics was sustained when the pressurised metered dose inhalers (pMDIs) were used with spacers. The Chiesi Jet and the AstraZeneca Nebuhaler, when used with their respective pMDIs, reduced likely oropharyngeal deposition to the same extent and gave a similar increase in the fine particle dose.

Administration, Inhalation↗
PubMed2003

Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation.

OBJECTIVES: To evaluate the cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease in England and Wales. METHODS: A discrete event simulation model used parameter estimates, derived from peer-reviewed literature, routine data and statistical modelling. Population screening was compared with no screening but with opportunistic eradication in patients presenting with dyspepsia. Costs included screening, eradication and costs averted to provide costs per life years saved (cost/LYS) for preventing gastric cancer and peptic ulcer disease. Sensitivity analyses were undertaken. RESULTS: The cost/LYS from screening at age 40 years was Uk pounds 5860 at discount rates of 6%. The outcomes were sensitive to H. pylori prevalence, the degree of opportunistic eradication, the discount rate, the efficacy of eradication on gastric cancer risk, the risk of complicated peptic ulcer disease and gastric cancer associated with H. pylori infection, and the duration of follow-up. In sensitivity analyses, the cost/LYS rarely exceeded UK pounds 20000 over an 80-year follow-up, but did for shorter periods. CONCLUSIONS: H. pylori screening may be cost-effective in the long term. However, before screening can be recommended further evidence is needed to resolve some of the uncertainties, particularly over the efficacy of eradication on risk of gastric cancer, the risk associated with complicated peptic ulcers, and the effect of more widespread opportunistic testing of patients with dyspepsia.

Adult↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

Modulite: a means of designing the aerosols generated by pressurized metered dose inhalers.

Although popular, the pressurized metered dose inhaler generates coarse, fast moving clouds so that the fraction reaching the lung is small. These shortcomings can be redressed by Modulite which permutes the following variables: the non-volatile components of a solution formula, the actuator orifice geometry, the volume of the metered solution and the vapour pressure of the propellants. This permits the design of aerosols with chosen particle size and plume speed. This facilitates co-ordination of dose generation with inspiration, reduces oropharyngeal deposition and provides a mechanism for targeting drug delivery to different parts of the lung. These principles are exemplified by designing an HFA-propelled beclometasone dipropionate product which closely matches existing products which use chlorofluorocarbons.

Aerosol Propellants↗
PubMed2002

The evaluation of screening policies for diabetic retinopathy using simulation.

AIMS: To develop a model for evaluating screening strategies and to use it to determine the cost effectiveness of varying the screening method and the screening interval. METHODS: A discrete event simulation was designed, validated and run for a population of 500000. Most parameters were derived from peer-reviewed publications. RESULTS: Standard methods of screening save up to 50% of the potential sight years lost. They give up to 85% of the sight years saved by an idealized gold standard programme using mydriatic seven-field photography reported by an ophthalmologist. The mobile camera, used for annual screening and 6-month follow-up after the detection of background retinopathy, had an estimated cost of pound 449200 per year with pound 2842 per sight year saved. It is less efficient to screen Type 2, rather than Type 1 diabetes mellitus patients, but they contributed to almost three-quarters of the sight years saved. CONCLUSIONS: The model can evaluate screening intervals and methods on a national or health authority basis. Results indicate that it appears more cost effective to continue to screen outside an ophthalmology clinic, until treatment is needed. Programmes with annual screening, and more frequent screening for those with background retinopathy, are robust to realistic fluctuations in compliance and screening sensitivity.

Computer Simulation↗
PubMed2001

Environmental contamination and detection of Salmonella enterica serovar enteritidis in laying flocks.

Faecal, dust and other environmental samples were collected from the floors, droppings belts, egg-collection systems and other areas of 14 cage-layer flocks, 10 barn egg production flocks and seven free-range flocks, and cultured for Salmonella species. The distribution of the organism varied with its prevalence and with the vaccination status of the birds. No one sample type was found to be suitable for identifying all contaminated houses. Salmonella was also frequently found on egg-packing equipment and in samples from rodents and wild birds.

Animals↗
PubMed2001

Delayed effects of tamoxifen in hepatocarcinogenesis-resistant Fischer 344 rats as compared with susceptible strains.

The anti-oestrogenic drug tamoxifen has been under investigation as a breast cancer chemopreventive agent for at least a decade. However, its use for this purpose is still debatable since it is able to induce liver tumours in rats via a mechanism involving metabolic activation to a DNA adduct-forming electrophilic intermediate. The metabolic activation and adduct-forming properties of tamoxifen are now well characterized but less is known about its ability to induce hepatic cell proliferation, which is also essential for the carcinogenic process. The effects of tamoxifen on liver weight and cell proliferation were compared in female Fischer 344 (F344), Wistar and Lewis rats given the drug in the diet for up to 26 weeks. The onset and duration of hepatic cell proliferation varied between the strains of rat. In Wistar and Lewis but not F344 rats there was a marked increase in hepatocellular proliferation during the first 4 weeks of tamoxifen administration. In the Wistar strain this was associated with an increase in DNA adduct levels; no such increase was observed in the F344 strain. The onset of the proliferative response was delayed until the 13 week time point in the F344 strain. By the 13 and 26 week time points, cell proliferation in tamoxifen-treated Wistar and Lewis rat liver had returned to normal, but the amount of apoptotic activity in these livers was elevated. This suggests that excess cells generated during the proliferative phase of tamoxifen treatment were being eliminated by apoptosis. In the F344 strain, however, increased proliferative activity was associated with relatively low apoptotic activity at the 26 week time point, suggesting that the delayed proliferative response had yet to be balanced by apoptotic deletion. This is consistent with the fact that tamoxifen-induced hepatocellular tumours develop very late, towards the end of the lifespan, in this strain. The cell proliferative activity of tamoxifen in the Wistar rat liver was compared with that of a non-mutagenic analogue, toremifene. Tamoxifen induced increased cell cycle activity in the livers of rats following gavage dosing at all sampling times (1-12 weeks), whereas toremifene had no effect on the incidence of cycling in hepatic cells, demonstrating that the hepatic cell proliferation is not a general response to anti-oestrogen treatment. These observations suggest that the rate of promotion of liver tumours by tamoxifen is a function of the rate, time of onset and duration of increased cell replication. The susceptibility of rat strains to the hepatocarcinogenic effects of tamoxifen appears to depend upon the balance between initiation via DNA adduct formation, promotion via increased cell proliferation and cell deletion via apoptosis. Our findings suggest that an early proliferative response to tamoxifen is important in this process.

Animals↗
PubMed2001

Observations on the distribution and control of Salmonella species in two integrated broiler companies.

The effectiveness of cleaning and disinfecting broiler farms and the persistence of Salmonella species in two integrated broiler companies was investigated for two years. Both companies used a cleaning and disinfection regime which included the application of a spray of phenolic disinfectant followed by fogging with formaldehyde solution, and this was highly effective in preventing carry-over of infection in the broiler houses. The disinfection of service areas and areas outside the houses was less effective but it had no influence on the Salmonella status of later flocks. Both companies had persistent problems with the contamination of pellet cooling systems in their feedmills with Salmonella 4, 12:d:- in company A, and with Salmonella binza and Salmonella ohio in company B. The hatcher incubators of both companies were also persistently contaminated with Salmonella livingstone and Salmonella thomasville in company A and with Salmonella senftenberg in company B. At both companies sites Salmonella enteritidis and Salmonella typhimurium Tr104 were also isolated occasionally from various locations.

Animals↗
PubMed2001

Genetics of human complement component C4 and evolution the central MHC.

The two classes of human complement component C4 proteins C4A and C4B manifest differential chemical reactivities and binding affinities towards target surfaces and complement receptor CR1. There are multiple, polymorphic allotypes of C4A and C4B proteins. A complex multiplication pattern of C4A and C4B genes with variations in gene size, gene dosage and flanking genes exists in the population. This is probably driven by the selection pressure to respond to a great variety of parasites efficiently and effectively, which the bony fish achieved through the multiplication and diversification of the related complement C3 proteins. Complement C4, C3 and C5 belong to the alpha2 macroglobulin protein family but acquired specific features that include an anaphylatoxin domain, a netrin (NTR) domain, and stretches of basic residues for proteolytic processings to form multiple chain structures. Complement C3 and C4 are important in the innate immune response as they opsonize parasites for phagocytosis. The emergence of complement C3 predates proteins involved in the adaptive immune response as C3 is present in deuterostome invertebrates such as echinoderms. The human C4 genes are located in the central MHC at chromosome 6p21.3. C3 and C5 are located at chromosome 19 and 9, respectively, with representatives of the other groups of genes paralogous to the MHC at 19p13.1-p13.3, 1q21-25, and 9q33-34. The central MHC also contains genes for complement components C2 and Bf. These genes appear to have similar evolutionary histories to C3/C4/C5 and are used here to illustrate stepwise processes resulting in co-location of diverse domains, chromosomal duplication, local segmental duplication and divergence of sequence and function. This model of evolution is useful in the investigation of innate and acquired immunity and in seeking explanations for diseases associated with MHC ancestral haplotypes.

Amino Acid Sequence↗