PubMed Health⌕ Search

Biomedical subjects

P Rogers

Publications and source records attributed to P Rogers.

At least 19 recordsLinked to original sources
PubMed2006

Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice.

Min mice provide a good model of human familial adenomatous polyposis. Recently, we have reported on two recombinant inbred lines (I and V) and the location of a modifier (Mom3) close to Apc, which altered polyp numbers in our mice possibly by modifying the frequency of wild-type (WT) allele loss at Apc; mice with severe disease (line V) showed elevated rates of loss. We now show that in line I only, a single pregnancy caused a significant increase in adenoma multiplicity compared with virgin controls (P<0.001) and that an additional pregnancy conferred a similar risk. Pregnancy was linked to both adenoma initiation and enhanced tumour growth in line I mice, and interline crosses indicated that susceptibility to pregnancy-associated adenomas was under genetic control. We found no evidence for the involvement of oestrodial metabolizing genes or the oestrogen receptors (Esr1 and 2) in tumour multiplicity. Importantly, a significantly elevated frequency of WT allele loss at Apc was observed in adenomas from parous mice (line and backcrossed) carrying the line I Min allele relative to equivalent virgin controls (P=0.015). Our results provide the first experimental evidence for genetic determinants controlling pregnancy-associated tumourigenesis; analogous genetic factors may exist in humans.

Adenomatous Polyposis Coli↗
PubMed2006

Clinical performance with the Levitronix Centrimag short-term ventricular assist device.

BACKGROUND: The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. METHODS: Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 +/- 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). RESULTS: Mean support time was 14.2 +/- 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. CONCLUSIONS: The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.

Adolescent↗
PubMed2006

Judgement of the quality of bowel preparation at screening flexible sigmoidoscopy is associated with variability in adenoma detection rates.

BACKGROUND AND STUDY AIMS: Adenoma detection rates (ADRs) at screening flexible sigmoidoscopy are known to vary between endoscopists. Variability in the technique used and in the quality of bowel preparation may explain this. The aim of this study was to establish whether there is a relationship between the grading of bowel preparation and the ADR. MATERIALS AND METHODS: The relationship between the ADR and assessment of bowel preparation was examined using the full United Kingdom Flexible Sigmoidoscopy Screening Trial data set (n = 38 601). The consistency of the bowel preparation classification was then investigated by six experienced endoscopists (video scorers), who examined 260 flexible sigmoidoscopy cases - 20 from each of the 13 trial endoscopists. RESULTS: Overall, the ADR was significantly higher in flexible sigmoidoscopy examinations with excellent or good bowel preparation ( P = 0.02). However, endoscopists with a higher ADR coded a smaller proportion of their examinations as having excellent/good preparation ( P = 0.002). Video scorers agreed with the trial endoscopists' definition of bowel preparation in 48.9 % of the readings, but they scored the quality of preparation as poorer than the trial endoscopists in 36.4 % and 40.6 %, respectively, in the intermediate-performance group (10 % < ADR < 14 %) and lower-performance group (ADR </= 10 %) in comparison with only 12.9 % in the high-performance group (ADR > or =14 %). There was a significant linear trend between the proportion scored as having poor bowel preparation and the ADR ( P < 0.001), varying from 2.7 % in the higher-performance ADR group to 13.4 % in the lower-performance group. CONCLUSIONS: Endoscopists with a higher ADR are more likely to be critical of the quality of bowel preparation. Training in judgement processes such as non-acceptance of suboptimal bowel preparation is required in order to ensure universally high standards in screening procedures.

Adenoma↗
PubMed2006

Sensitization following LVAD implantation using leucodepleted blood is not due to HLA antibodies.

Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.

Adult↗
PubMed2005

A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: the WEST study.

OBJECTIVE: To determine the effectiveness and predictors of response to lumbar epidural corticosteroid injections (ESI) in patients with sciatica. We performed a 12-month, multicentre, double-blind, randomized, placebo-controlled, parallel-group trial in four secondary pain-care clinics in the Wessex Region. METHODS: Two hundred and twenty-eight patients with a clinical diagnosis of unilateral sciatica of 1-18 months' duration were randomized to either three lumbar ESIs of triamcinolone acetonide or interligamentous saline injections at intervals of 3 weeks. The main outcome measure was the Oswestry low back pain disability questionnaire (ODQ). RESULTS: At 3 weeks, the ESI group demonstrated a transient benefit over the placebo group (patients achieving a 75% improvement in ODQ, 12.5 vs 3.7%; number needed to treat, 11.4). No benefit was demonstrated from 6 to 52 weeks. ESIs did not improve physical function, hasten return to work or reduce the need for surgery. There was no benefit of repeated ESIs over single injection. No clinical predictors of response were found. At the end of the study the majority of patients still had significant pain and disability regardless of intervention. CONCLUSIONS: In this pragmatic study, ESIs offered transient benefit in symptoms at 3 weeks in patients with sciatica, but no sustained benefits in terms of pain, function or need for surgery. Sciatica is a chronic condition requiring a multidisciplinary approach. To fully investigate the value of ESIs, they need to be evaluated as part of a multidisciplinary approach.

Adolescent↗
PubMed2005

Cost-effectiveness and safety of epidural steroids in the management of sciatica.

OBJECTIVES: To investigate the clinical effectiveness of epidural steroid injections (ESIs) in the treatment of sciatica with an adequately powered study and to identify potential predictors of response to ESIs. Also, to investigate the safety and cost-effectiveness of lumbar ESIs in patients with sciatica. DESIGN: A pragmatic, prospective, multicentre, double-blind, randomised, placebo-controlled trial with 12-month follow-up was performed. Patients were stratified according to acute (<4 months since onset) versus chronic (4-18 months) presentation. All analyses were performed on an intention-to-treat basis with last observation carried forward used to impute missing data. SETTING: Rheumatology, orthopaedic and pain clinics in four participating centres: three district hospitals and one teaching hospital in the south of England. PARTICIPANTS: Total of 228 patients listed for ESI with clinically diagnosed unilateral sciatica, aged between 18 and 70 years, who had a duration of symptoms between 4 weeks and 18 months. INTERVENTIONS: Patients received up to three injections of epidural steroid and local anaesthetic (active), or an injection of normal saline into the interspinous ligament (placebo). MAIN OUTCOME MEASURES: The primary outcome measure was the Oswestry Disability Questionnaire (ODQ); measures of pain relief and psychological and physical function were collected. Health economic data on return to work, analgesia use and other interventions were also measured. Quality-adjusted life-years (QALYs) were calculated using the SF-6D, calculated from the Short Form (SF-36). Costs per patient were derived from figures supplied by the centres' finance departments and a costings exercise performed as part of the study. A cost-utility analysis was performed using the SF-36 to calculate costs per QALY. RESULTS: ESI led to a transient benefit in ODQ and pain relief, compared with placebo at 3 weeks (p = 0.017, number needed to treat = 11.4). There was no benefit over placebo between weeks 6 and 52. Using incremental QALYs, this equates to and additional 2.2 days of full health. Acute sciatica seemed to respond no differently to chronic sciatica. There were no significant differences in any other indices, including objective tests of function, return to work or need for surgery at any time-points. There were no clinical predictors of response, although the trial lacked sufficient power to be confident of this. Adverse events were uncommon, with no difference between groups. Costs per QALY to providers under the trial protocol were 44,701 pounds sterling. Costs to the purchaser per QALY were 354,171 pounds sterling. If only one ESI was provided then costs per QALY fell to 25,745 pounds sterling to the provider and 167,145 pounds sterling to the purchaser. ESIs thus failed the QALY threshold recommended by the National Institute for Health and Clinical Excellence (NICE). CONCLUSIONS: Although ESIs appear relatively safe, it was found that they confer only transient benefit in symptoms and self-reported function in a small group of patients with sciatica at substantial costs. ESIs do not provide good value for money if NICE recommendations are followed. Additional research is suggested into the epidemiology of radicular pain, producing a register of all ESIs, possible subgroups who may benefit from ESIs, the use of radiological imaging, optimal early interventions, analgesic agents and nerve root injections, the use of cognitive behavioural therapy in rehabilitation, improved methods of assessment, a comparative cost-utility analysis between various treatment strategies, and methods to reduce the effect of scarring and inflammation.

Acute Disease↗
PubMed2004

Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND).

AIMS: To identify any UK children with variant Creutzfeldt-Jakob disease (vCJD) and obtain information about the causes of progressive intellectual and neurological deterioration (PIND) and the geographical distribution of cases. METHODS: The PIND Study uses the monthly surveillance card that is sent to all UK paediatricians by the British Paediatric Surveillance Unit. Case details are obtained from the reporting paediatricians by telephone interview, site visit, or self completion of a questionnaire. A paediatric neurology expert group then classifies the anonymised cases. The Communicable Disease Surveillance Centre (CDSC) provides mapping support. RESULTS: After five years and five months of surveillance, 1400 children had been reported. In the UK the majority of PIND cases had a confirmed diagnosis (comprising 99 different conditions); 505 "no cases" and 97 "outstanding" cases were excluded. A total of 798 PIND cases were included as follows: 577 with a confirmed underlying diagnosis; six with definite or probable vCJD, 51 who had undiagnosed PIND but were not thought to have vCJD, and 164 cases who were still under investigation. In some districts there were unexpectedly high numbers of PIND cases with a heterogeneous mixture of underlying diagnoses. In the five districts with the largest numbers of resident cases the majority not only came from a particular ethnic group but also had high reported rates of consanguinity. CONCLUSIONS: In districts with large numbers of PIND cases there are major resource implications. These children and their families have complex problems and they need access to diagnostic facilities and appropriate service provision.

Adolescent↗
PubMed2004

Virtual water flows and trade liberalization.

The linkages between agricultural trade and water resources need to be identified and analyzed to better understand the potential impacts that a full liberalization, or lack thereof, will have on water resources. This paper examines trade of virtual water embodied in agricultural products for most countries of the world. The main purpose of the paper, however, is to examine the impact of trade liberalization on virtual-water trade in the future. Based on a simulation of global agricultural trade, a scenario of full liberalization of agriculture was used to assess the net effect of virtual water flows from the relocation of meat and cereals' trade. The paper also identifies the main reasons behind the changes in the magnitude and direction of the net virtual water trade over time, and shows that virtual water trade flows are independent of water resource endowments, contrary to what the Heckscher-Ohlin Theorem states. Finally, based on a formal model, some input demand functions at the country level are estimated. The estimates of the income and agricultural support elasticities of demand for import of virtual water have the expected sign, and are statistically significant. Variables found to have some explanatory power of the variance of virtual water imports are average income; population; agriculture as value added; irrigated area, and exports of goods and services.

Agriculture↗
PubMed2003

Immunohistochemical and ultrastructural characterization of the initial post-hatching development of bovine embryos.

The problems of sustaining placenta formation in embryos produced by nuclear transfer have emphasized the need for basic knowledge about epiblast formation and gastrulation in bovine embryos. The aims of this study were to define stages of bovine post-hatching embryonic development and to analyse functional mechanisms of germ-layer formation. Embryos developed in vivo were collected after slaughter from superovulated cows on days 9, 11, 14 and 21 after insemination and processed for transmission electron microscopy (n = 26) or immunohistochemistry (n = 27) for potential germ-layer characterization (cytokeratin 8 for potential ectoderm; alpha-1-fetoprotein for potential endoderm; and vimentin for potential mesoderm). On day 9, the embryos were devoid of zona pellucida and presented a well-defined inner cell mass (ICM), which was covered by a thin layer of trophoblast cells (the Rauber's layer). Formation of the hypoblast from the inside of the ICM was ongoing. On day 11, the Rauber's layer was focally interrupted and adjacent underlying ICM cells formed tight junctions. The hypoblast, which formed a thin confluent cell layer, was separated from the ICM and the tropho-blast by intercellular matrix. The embryos were ovoid to tubular and displayed a confluent hypoblast on day 14. The epiblast was inserted into the trophoblast epithelium and tight junctions and desmosomes were present between adjacent epiblast cells as well as between peripheral epiblast and trophoblast cells. In some embryos, the epiblast was more or less covered by foldings of trophoblast in the process of forming the amniotic cavity. Cytokeratin 8 was localized to the trophoblast and the hypoblast underlying the epiblast; alpha-1-fetoprotein was localized to most hypoblast cells underlying the trophoblast; and vimentin was localized to most epiblast cells. On day 21, the smallest embryos displayed a primitive streak and formation of the neural groove, whereas the largest embryos presented a neural tube, up to 14 somites and allantois development. These embryos depicted the gradual formation of the endoderm, mesoderm and ectoderm as well as differentiation of paraxial, intermediate and lateral plate mesoderm. Cytokeratin 8 was localized to the trophoblast, the hypoblast and the surface and neural ectoderm; and alpha-1-fetoprotein was localized to the hypoblast, but not the definitive endoderm, the intensity increasing with development. Vimentin was initially localized to some, but not all, cells positioned particularly in the ventral region of the primitive streak, to presumptive definitive endoderm cells inserted into the hypoblast, and to mesoderm. In conclusion, within 2 weeks of hatching, bovine embryos complete formation of the hypoblast and the epiblast, establishment of the amniotic cavity, ingression of epiblast cells for primitive streak formation, involution of cells through the node and the streak for endoderm and mesoderm fomation, neurulation and differentiation of the mesoderm. The recruitment of cells from the epiblast to form the primitive streak as well as the endoderm and mesoderm is associated with expression of the intermediate filament vimentin.

Animals↗
PubMed2002

Enzymatic (R)-phenylacetylcarbinol production in benzaldehyde emulsions.

(R)-Phenylacetylcarbinol [(R)-PAC)] is the chiral precursor for the production of the pharmaceuticals ephedrine and pseudoephedrine. Reaction conditions were improved to achieve increased (R)-PAC levels in a simple batch biotransformation of benzaldehyde emulsions and pyruvate, using partially purified pyruvate decarboxylase (PDC) from the filamentous fungus Rhizopus javanicus NRRL 13161 as the catalyst. Lowering the temperature from 23 degrees C to 6 degrees C decreased initial rates but increased final (R)-PAC concentrations. Addition of ethanol, which increases benzaldehyde solubility, was not beneficial for (R)-PAC production. It was established that proton uptake during biotransformation increases the pH above 7 thereby limiting (R)-PAC production. For small-scale studies, biotransformations were buffered with 2-2.5 M MOPS (initial pH 6.5). High concentrations of MOPS as well as some alcohols and KCl stabilised PDC. A balance between PDC and substrate concentrations was determined with regards to ( R)-PAC production and yields on enzyme and substrates. R. javanicus PDC (7.4 U/ml) produced 50.6 g/l (337 mM) ( R)-PAC in 29 h at 6 degrees C with initial 400 mM benzaldehyde and 600 mM pyruvate. Molar yields on consumed benzaldehyde and pyruvate were 97% and 59%, respectively, with 17% pyruvate degraded and 24% converted into acetaldehyde and acetoin; 43% PDC activity remained, indicating reasonable enzyme stability at high substrate and product concentrations.

Acetone↗
PubMed2002

Sequence-dependent synergism between the new generation platinum agent ZD0473 and paclitaxel in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines.

ZD0473 is a new generation hindered platinum agent currently undergoing worldwide Phase II clinical studies. The in vitro cytotoxicity of ZD0473 either alone or in combination with the anticancer drugs paclitaxel, gemcitabine, vinorelbine, topotecan and doxorubicin was determined using four human ovarian carcinoma cell lines and by the sulphorhodamine B assay (SRB). The lines included one model of acquired cisplatin resistance and one isogenic pair differing only in their p53 status. Notably, the simultaneous exposure to ZD0473 and paclitaxel for 96 h resulted in synergy (as defined by a median effect analysis) in all four cell lines (i.e. independent of cisplatin resistance and p53 status). In addition, synergy was observed in 3/4 lines and 2/4 lines following concomitant exposure to topotecan or gemcitabine, respectively. Sequencing studies with ZD0473 and paclitaxel revealed that, for three of the four cell lines, the combination of ZD0473 administered for 24 h prior to paclitaxel for 24 h conferred a greater growth inhibitory effect than the reverse sequential combination. This scheduling effect was particularly marked for the acquired cisplatin-resistant A2780CisR cell line; synergy being observed with ZD0473/paclitaxel, but antagonism with paclitaxel/ZD0473. This effect did not appear to be correlated with changes in drug-induced cell cycle checkpoints. These data suggest that ZD0473 may be usefully combined with various cytotoxics in the clinic, including paclitaxel, topotecan and gemcitabine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Retention of activity by the new generation platinum agent AMD0473 in four human tumour cell lines possessing acquired resistance to oxaliplatin.

Four models of acquired resistance to the clinically-used platinum drug, oxaliplatin, have been established using human tumour cell lines in vitro; two colon (HCT116 and HT29) and two ovarian (A2780 and CH1). Levels of acquired resistance ranged from 3.0- to 15.8-fold with levels of resistance higher in the colon relative to the ovarian carcinoma cell lines. Notably, the platinum analogue, AMD0473, currently undergoing clinical evaluation, exhibited superior circumvention of acquired oxaliplatin resistance in comparison to either cisplatin or the trinuclear platinum BBR3464. Resistance in the two colon cell lines was unique to oxaliplatin itself among the platinum drugs studied. Acquired oxaliplatin resistance was not due to either reduced drug membrane transport or increased levels of glutathione in any of the four resistant lines. Following exposure to oxaliplatin, a lower level of platinum-DNA adducts was present in acquired oxaliplatin-resistant HT29 cells. In the remaining resistant lines, there was no change in the levels of platinum-DNA adducts relative to the parent lines. There was no change in hMLH1 DNA mismatch repair gene status in any of the four cell line pairs. However, in an A2780 subline where loss of hMLH1 and a p53phe172 mutation occurred, 5-fold resistance to cisplatin was observed, but only 1.7-fold resistance to oxaliplatin and no resistance to AMD0473 were observed. Re-introduction of hMLH1 into these cells caused no significant change in the sensitivity to cisplatin, oxaliplatin or AMD0473. These data show that acquired resistance to oxaliplatin may occur in cell lines (and therefore probably in the clinic) and in the four independent cell lines studied this was circumvented by AMD0473. Alongside previously described models of acquired resistance to cisplatin, these oxaliplatin-resistant cell line models may be useful in the evaluation of further novel platinum agents.

Antineoplastic Agents↗
PubMed2002

Localization of indoleamine 2,3-dioxygenase and 4-hydroxynonenal in normal and pre-eclamptic placentae.

This study was undertaken to compare placental levels of 2,3-Dioxygenase (IDO), a free radical scavenger, and 4-Hydroxynonenal (4-HNE), a major by-product of lipid peroxidation, in normal and pre-eclamptic pregnancies. Placentae were collected at caesarean section from women with a term, normal singleton pregnancy (37-40 weeks' gestation, n=10) and women with a term singleton pregnancy complicated by pre-eclampsia (n=10). IDO and 4-HNE localization and intensity was studied by semi-quantitative immunohistochemistry and differences between groups were analysed using the Mann-Whitney U test. Immunostaining for IDO was located primarily in endothelial cell nuclei, with a reduced level of staining in the cytoplasm, in most capillaries from all placentae examined. A significantly higher level of IDO immunostaining was observed in normal placentae compared to pre-eclamptic placentae (P=0.008). 4-HNE was located mainly in the cytoplasm of syncytiotrophoblast cells of all placentae examined. There were no significant differences in the pattern or intensity of 4-HNE immunostaining levels between normal and pre-eclamptic pregnancies (P=0.684). Our IDO results support the hypothesis of decreased anti-oxidative capability in the placenta and the possibility of an ineffective compensatory mechanism against increased oxidative stress in the fetus.

Adult↗
PubMed2002

Retroperitoneal haematoma associated with low molecular weight heparin.

Enoxaparin (a low molecular weight heparin) has been used extensively for its antithrombotic properties. Complications of its haemorrhagic side-effects have previously been described. We report two cases of extensive retroperitoneal haematoma requiring blood transfusion and inotropic support. One patient developed acute renal failure and did not respond to intensive resuscitative efforts.

Aged↗
PubMed2001

Biotransformation of benzaldehyde into (R)-phenylacetylcarbinol by filamentous fungi or their extracts.

Extracts of 14 filamentous fungi were examined regarding their potential for production of (R)-phenylacetylcarbinol [(R)-PAC], which is the chiral precursor in the manufacture of the pharmaceuticals ephedrine and pseudoephedrine. Benzaldehyde and pyruvate were transformed at a scale of 1.2 ml into PAC by cell-free extracts of all selected strains, covering the broad taxonomic spectrum of Ascomycota, Zygomycota and Basidiomycota. Highest final PAC concentrations were obtained with the extracts of Rhizopus javanicus and Fusarium sp. [78-84 mM (11.7-12.6 g/l) PAC within 20 h from initial substrate concentrations of 100 mM benzaldehyde and 150 mM pyruvate]. (R)-PAC was in about 90-93% enantiomeric excess. Rhizopus javanicus had the advantage of faster growth than Fusarium sp. Rhizopus javanicus mycelia were used as an example in a biotransformation process based on whole cells and benzaldehyde and glucose as substrates. The substrate pyruvate was generated through the fungal fermentation of glucose. Only 19 mM PAC (2.9 g/l) were produced within 8 h from 80 mM benzaldehyde. with evidence of significant benzyl alcohol production.

Acetone↗