Biomedical subjects

A Rogers

Publications and source records attributed to A Rogers.

At least 19 recordsLinked to original sources

PubMed2006

Different effects of raloxifene and estrogen on interleukin-1beta and interleukin-1 receptor antagonist production using in vitro and ex vivo studies.

The increase in lumbar spine BMD in response to Raloxifene (RLX), a selective estrogen receptor modulator, is smaller in magnitude compared to the response to treatment with estradiol (E2). The reasons for this observation are unclear. Estrogen has a potent effect on the production of proinflammatory cytokines which support osteoclastogenic and bone resorption. Therefore the different response to RLX may relate, at least in part, to a difference in the ability of RLX to modulate the production of proinflammatory cytokines which are abundant in the red marrow of the vertebrae. The aim of this study was to determine the effect of RLX and E2 both in vitro and ex vivo on the production of the pro-resorptive cytokine interleukin-1beta (IL-1beta) and its antagonist, interleukin-1 receptor antagonist (IL-1ra). We obtained samples of peripheral blood from (a) 10 untreated postmenopausal women with osteopenia (ages 53 to 72 years, mean 61 years), (b) 15 postmenopausal women (ages 52 to 72 years, mean 63 years) at baseline and after 6 months of RLX therapy (60 mg/day) and (c) 10 postmenopausal women (ages 60 to 75 years, mean 64 years) at baseline and 6 months after a single E2 implant (25 mg). Cultures of whole blood from the untreated women were incubated with RLX or 17beta-E2 at 1 pM, 100 pM, 10 nM and 1 microM concentrations. LPS-stimulated whole blood cultures from the raloxifene- and estradiol-treated women were prepared at baseline and at 6 months. IL-1beta and IL-1ra were measured by ELISA in the conditioned media. In vitro there was a significant dose-dependent decrease in IL-1beta and IL-1ra in response to 17beta-E2 (both P<0.0001) which was not apparent in response to RLX (both P>0.05). In ex vivo cultures from women receiving 6 months treatment with E2 implants, there was a significant decrease in IL-1beta (-36+/-8%, P=0.01) but no significant change in IL-1ra (+29+/-20%, P=0.3). There was no significant change in either IL-1beta or IL-1ra after 6 months RLX therapy (+20+/-14% and +12+/-10%, both P>0.05). We conclude that treatment with RLX, unlike estradiol does not modulate the production of the proinflammatory cytokines IL-1beta and IL-1ra using in vitro or ex vivo whole blood culture methods. This may account, at least in part for the reduced efficacy of RLX therapy compared to estrogen which has been observed in vivo on bone mineral density, bone turnover and reduction in fracture risk.

Aged↗

PubMed2006

Ultrastructure of the reticular basement membrane in asthmatic adults, children and infants.

Reticular basement membrane (RBM) thickening in asthma is considered to be the result of subepithelial fibrosis. Thus, the RBM in asthma should contain an excess of fibrils identified as interstitial collagen and the ratio of fibril to matrix should be increased above normal levels. Electron micrographs of the RBM were compared with those of interstitial collagen deeper in the bronchial wall using endobronchial biopsy specimens from adult asthmatics (aged 18-41 yrs (n = 10)), children with difficult asthma (aged 6-16 yrs (n = 10)), wheezy infants with reversible airflow limitation (aged 0.3-2 yrs (n = 10)) and age-matched nonasthmatic controls: 10 adults, nine children and nine symptomatic infants with normal lung function. Fibrils in the RBM were significantly thinner (median (range) width 39 (30-52) nm versus 59 (48-73) nm), and fewer fibrils were banded than in the interstitial collagen (ratio of banded to non-banded fibrils 0.08 (0-0.17) versus 0.22 (0-1.3)). The ratio of fibrils to matrix in the thickened RBM of asthmatics did not differ from that of their respective controls (1.34 (0.63-2.49) versus 1.18 (0.31-2.6)). The ratio of fibril to matrix in the thickened reticular basement membrane of asthmatics is normal, and, contrary to what is expected in fibrosis, the fibrils do not resemble those of interstitial collagen.

Adolescent↗

PubMed2005

A randomised controlled trial of self-help interventions in patients with a primary care diagnosis of irritable bowel syndrome.

INTRODUCTION: Functional abdominal symptoms are very common and account for nearly two million primary care consultations in Britain every year and produce significant morbidity. The aims of this study were to evaluate the impact of two self-help interventions on consultation rates and symptom severity in patients with a primary care diagnosis of irritable bowel syndrome. METHODS: A total of 420 patients from 54 primary care centres were randomised either to receive self-help information in the form of a guidebook or the guidebook plus a "self-help" group meeting or to be in a control group receiving neither intervention. Data were collected using questionnaires and primary care records. RESULTS: At one year, patients in the guidebook group had a 60% reduction in primary care consultations (p < 0.001) and a reduction in perceived symptom severity (p < 0.001) compared with controls. Allocation to the self-help group conferred no additional benefit. Actual symptom scores did not change significantly in any group. Costs per patient were reduced by Pounds 73 (confidence interval Pounds 43, Pounds 103) or 40% per year. CONCLUSION: Introduction of a self-help guidebook results in a reduction in primary care consultations, a perceived reduction in symptoms, and significant health service savings. This suggests that patients attending their primary care physician with functional abdominal symptoms should be offered self-help information as part of their management.

Adult↗

PubMed2004

c-fos mRNA expression in rat cortical neurons during glutamate-mediated excitotoxicity.

We have previously reported that exposure of mouse cerebellar granule cells (mCGCs) to excitotoxic concentrations of glutamate (Glu) induced a delayed, elevated, and sustained expression of c-fos mRNA, which was N-methyl-D-aspartic acid (NMDA) receptor mediated. In this study, the overstimulation of Glu receptors in primary rat cortical neurons by excitotoxins was used to study the cellular events triggering excitotoxic neuronal cell death, as the rat is the preferred species in regulatory and nonregulatory toxicological investigations. Exposure of rat cortical neurons to excitotoxins at high, toxic concentrations showed a change in the c-fos mRNA expression profile from a transient expression to one of sustained elevated levels. The excitotoxins induced much higher levels of c-fos mRNA in rat cortical neurons than in the mouse CGC system. Glu-induced c-fos mRNA expression, under excitotoxic conditions, was inhibited by D-2-amino-5-phosphonopentanoate (AP5) but not 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), indicating an event mediated by the NMDA subtype of Glu receptors. Using 12 compounds, which covered a range of nontoxic, toxic, and excitotoxic effects on rat cortical neurons, excitotoxicity was paralleled by a sustained, elevated c-fos mRNA expression. Furthermore, on account of the high expression levels of c-fos mRNA under excitotoxic conditions, it is suggested that an unambiguous elevation in c-fos mRNA expression at a single time point of 60 min can be used to predict the excitotoxic properties of a range of functionally different chemical compounds. In view of the high levels of expression of c-fos mRNA, the rat cortical cell system may also be used as a more sensitive model than mCGCs for investigations into early markers of excitotoxicity.

Animals↗

PubMed2004

Contacting controls: are we working harder for similar response rates, and does it make a difference?

Although obtaining high response rates is critical to epidemiologic studies, effort to achieve response rates is undocumented. The authors used three population-based case-control studies conducted in Utah between October 1991 and February 2003 to examine effort required for both initial contact and determination of final status. Differences in lifestyle characteristics between easy- or more-difficult-to-interview female controls were evaluated. Letter, phone, and in-person contacts were recorded to determine contact effort. Regarding effort required to achieve a final outcome, the number of contacts increased from eight to 14 over the 12-year study period. Compared with those in study A (conducted in 1991-1994), controls in studies B and C were twice as likely to require seven or more phone calls and controls in study B were twice as likely to require one or more in-person visit. Hispanic controls in study C were more likely than non-Hispanic White controls to receive an in-person visit and a noncontact letter. Compared with those more difficult to contact, those easy to contact were more likely to be overweight and less likely to have a family history of cancer. The amount of effort required to achieve similar or slightly lower response rates increased over time. This finding may in part depend on demographic characteristics of the population studied.

Adult↗

PubMed2004

Patients' experiences of an open access follow up arrangement in managing inflammatory bowel disease.

BACKGROUND: Improving access is a key policy issue in improving quality of care and extending patient choice and participation. People's experience of changing from fixed outpatient appointments to more flexible direct access arrangements for chronic disease has been underexplored. OBJECTIVES: To examine patients' views on using an open system of access compared with fixed outpatient appointments as part of a guided self-management intervention for inflammatory bowel disease (IBD). DESIGN: Embedded qualitative study undertaken alongside a randomised controlled trial. Semi-structured interviews were undertaken to obtain an in depth understanding of patients' experience of the change in access arrangements. PARTICIPANTS: A purposive sample (n = 30) was drawn from the intervention group (n = 700) according to a range of responses to the trial baseline and follow up quantitative measures. RESULTS: 28 interviews were included in the analysis. Compared with the previous system of fixed appointments, preference for the new open access system was based on enhanced personal control in contacting services and the view that it fitted better with everyday routine management and the requirement for urgent medical contact when symptoms fail to respond to medication. Preference for retaining fixed appointments was based on a sense of security from gaining access which did not require the individual to initiate the request for medical help. CONCLUSIONS: Open access may fit better with patients' self-management of their condition and everyday routines, roles and responsibilities. Ensuring that outpatient organisational arrangements and personnel are responsive to patient initiated requests for appointments is likely to impact on the acceptability of this type of access arrangement. Some people may continue to prefer the fixed appointment system which should be retained if patient choice is to be respected.

Adaptation, Psychological↗

PubMed2004

How do stakeholder groups vary in a Delphi technique about primary mental health care and what factors influence their ratings?

BACKGROUND: While mental health is a core part of primary care, there are few validated quality measures and little relevant internationally published research. Consensus panel methods are a useful means of developing quality measures where evidence is sparse and/or opinions are diverse. However, little is known about the dynamics of consensus techniques and the factors that influence the judgements and ratings of panels and individual panelists. OBJECTIVES: (1) To describe differences in panel ratings on the quality of primary mental health care services by patient, carer, professional and managerial panels within a Delphi procedure; and (2) to explore why different panels and panelists rate quality indicators of primary mental health care differently. DESIGN: Two round postal Delphi technique and exploratory semi-structured interviews. PARTICIPANTS: 115 panelists across 11 panels. Eleven panelists were subsequently interviewed. RESULTS: 87 of 334 indicators (26%) were rated face valid by all 11 panels. There was little disagreement within panel ratings but significant differences between panels. The GP panel rated the least number of indicators valid (n = 138, 41%) and carers the most (n = 304, 91%). The way in which panelists interpreted and conceptualised the indicators and their definition of quality of mental health care affected the way in which participants made their ratings. CONCLUSIONS: Stakeholders in primary mental health care have diverse views of quality of care and these differences translate into how they rate quality indicators. Exploratory interviews suggest that ratings are influenced by past experience, expectations, definitions of quality of care, and perceived power relationships between stakeholders.

Attitude of Health Personnel↗

PubMed2003

Phase transitions in sexual populations subject to stabilizing selection.

We show that a simple model of an evolving sexual population, which dates back to some of the earliest work in theoretical population genetics, exhibits an unexpected and previously unobserved phase transition between ordered and disordered states. This behavior is not present in populations evolving asexually without recombination and is thus important in any comparison of sexual and asexual populations. In order to calculate the details of the phase transition, we use techniques from statistical physics. We introduce the correlation of the population as the order parameter of the system and use maximum entropy inference to find the state of the population at any time.

Biological Evolution↗

PubMed2003

The ABG hydroxyapatite-coated hip prosthesis: one hundred consecutive operations with average 6-year follow-up.

One hundred consecutive ABG (Anatomique Benoist Giraud, Howmedica) hydroxyapatite-coated hip arthroplasties in 97 patients were evaluated prospectively with a follow-up time of 4 to 10 years (mean, 6 years). Clinical results were excellent with an improvement in the Merle d'Aubigne score from 9 preoperatively to 17.4 at 5 years. Thigh pain was persistent in only 3%; it was mild in nature and controlled with simple analgesics. Kaplan-Meyer survivorship analysis was 100% for the femoral stem and 95% for the acetabular cup at 6 years. Of concern was the high polyethylene wear measured with an average of 0.24 mm/y (range, 0.05-0.76 mm/y).

Adult↗

PubMed2003

The perceived expressed emotion in staff scale.

Recent research has highlighted the role of expressed emotion by ward staff in determining the well-being of psychiatric inpatients. Existing methods of assessing staff expressed emotion involve standardized interviews and are expensive and time-consuming. We report the development of a questionnaire measure of expressed emotion in staff as perceived by patients. In study 1, factor analysis of items administered to patients in a variety of settings led to the development of a questionnaire with three subscales: supportiveness, criticism and intrusiveness. In study 2, the test-retest reliability of the questionnaire was found to be adequate, and some evidence of concurrent validity for the scale was obtained against expressed emotion rated from staff speech samples. In study 3, the scale was shown to have good concurrent validity against the ward atmosphere scale, and scores were found to be independent of insight or experience of admission to hospital. The perceived expressed emotion in staff scale is a convenient measure, which may have utility for both research and clinical purposes.

Adult↗

PubMed2003

Developing a departmental culture for reporting adverse incidents.

A simple, reproducible model for reporting adverse events was developed in order to promote cultural awareness and acceptance of risk management within the authors' department. A departmental proforma was created and prospective reporting of adverse events was encouraged. In the six months prior to commencing this study only four adverse incidents were reported. Following the introduction of the proforma 64 critical incidents and near-misses were reported in the one-year period. In conclusion a simple model for reporting critical incidents and near-misses has been established. This has fostered a cultural change within the department and all members of staff feel more comfortable with reporting such incidents. The process is seen as educational and an important part of continuing professional and departmental development. Protocols and changes in organisational practice have been developed to reduce and prevent the occurrence of adverse events and offer patients continuous improvement in care.

Forms and Records Control↗

PubMed2003

A subtle governance: 'soft' medical leadership in English primary care.

In many countries governments are recruiting the medical profession into a more active, transparent regulation of clinical practice. Consequently the medical profession adapts the ways it regulates itself and its relationship to health system managers changes. This paper uses empirical research in English Primary Care Groups (PCGs) and Primary Care Trusts (PCTs) to assess the value of Courpasson's concept of soft bureaucracy as a conceptualisation of these changes. Clinical governance in PCGs and PCTs displays important parallels with governance in soft bureaucracies, but the concept of soft bureaucracy requires modification to make it more applicable to general practice. In English primary care, governance over rank-and-file doctors is exercised by local professional leaders rather than general managers, harnessing their colleagues' perception of threats to professional autonomy and self-regulation rather than fears of competition as the means of 'soft coercion'.

Attitude of Health Personnel↗

PubMed2003

Quality indicators for primary care mental health services.

OBJECTIVES: To identify a generic set of face valid quality indicators for primary care mental health services which reflect a multi-stakeholder perspective and can be used for facilitating quality improvement. DESIGN: Modified two-round postal Delphi questionnaire. SETTING: Geographical spread across Great Britain. PARTICIPANTS: One hundred and fifteen panellists representing 11 different stakeholder groups within primary care mental health services (clinical psychologist, health and social care commissioner, community psychiatric nurse, counsellor, general practitioner, practice nurse/district nurse/health visitor, psychiatrist, social worker, carer, patient and voluntary organisations). MAIN OUTCOME MEASURES: Face validity (median rating of 8 or 9 on a nine point scale with agreement by all panels) for assessing quality of care. RESULTS: A maximum of 334 indicators were rated by panels in the second round; 26% were rated valid by all panels. These indicators were categorised into 21 aspects of care, 11 relating to general practices and 10 relating to health authorities or primary care groups/trusts. There was variation in the total number of indicators rated valid across the different panels. Overall, GPs rated the lowest number of indicators as valid (41%, n=138) and carers rated the highest number valid (91%, n=304). CONCLUSIONS: The quality indicators represent consensus among key stakeholder groups in defining quality of care within primary care mental health services. These indicators could provide a guide for primary care organisations embarking on quality improvement initiatives in mental health care when addressing national targets and standards relating to primary care set out in the National Service Framework for Mental Health for England. Although many of the indicators relate to parochial issues in UK service delivery, the methodology used in the development of the indicators could be applied in other settings to produce locally relevant indicators.

Attitude of Health Personnel↗

PubMed2003

Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

Adult↗

PubMed2003

A randomised controlled trial to assess the impact of a package comprising a patient-orientated, evidence-based self-help guidebook and patient-centred consultations on disease management and satisfaction in inflammatory bowel disease.

OBJECTIVES: To determine if a whole systems approach to self-management improves clinical outcomes and leads to cost-effective use of NHS services. DESIGN: Nineteen hospitals were randomised to 10 control sites and nine intervention sites. Consultants from intervention sites received training in patient-centred care before recruitment and introduced the intervention to eligible patients. Patients at the control sites were recruited and went on to have an ordinary consultation. Qualitative interviews were undertaken to obtain an in-depth understanding of patients' and consultants' experience of the intervention. SETTING: Follow-up outpatient clinics at 19 hospitals in the north-west of England. PARTICIPANTS: Seven hundred patients (297 at intervention sites and 403 at control sites) with established ulcerative colitis or Crohn's disease, aged 16 years and over, and able to write in English. INTERVENTIONS: Consultants were trained to provide a patient-centred approach to care. Guidebooks on ulcerative colitis and Crohn's disease were developed with patients prior to the study. Patients prepared a written self-management plan and self-referred to services based on a self-evaluation of their need for advice. MAIN OUTCOME MEASURES: Rates of hospital outpatient consultation, quality of life (QoL) and acceptability to patients. Health service resource use and assessed cost effectiveness using the EQ-5D. RESULTS: After 1 year, the intervention resulted in fewer hospital visits, without change in the number of primary care visits. Patients felt more able to cope with their condition. The intervention produced no reduction in QoL and did not raise anxiety. The intervention group reported fewer symptom relapses; 74% of patients in the intervention group indicated a preference to continue the system. Qualitative results showed the guidebook was effective but organisational limitations constrained patient-centred aspects of the intervention for some. Cost-effectiveness analyses favoured self-management over standard care. CONCLUSIONS: Further use of this method in chronic disease management seems likely to improve overall patient satisfaction and reduce health expenditure without evidence of adverse effect on disease control. Further attention needs to be given to self-referral and access arrangements and a re-distribution of control to patients through increased adherence to patient-centred norms on the part of consultants. Future research is recommended to evaluate the operating systems within secondary and primary care that would allow self-managers to self-refer and to keep them informed of new treatments, also to explore models for training health professionals in self-care methods, to study long-term effects of self-management in chronic disease and to transfer this approach to other chronic conditions.

Adolescent↗

PubMed2002

Activation of bovine peripheral blood gammadelta T cells for cell division and IFN-gamma production.

Bovine peripheral blood gammadelta T cells have been evaluated for effector function (IFN-gamma production) and clonal expansion in a variety of systems including following activation by mitogens, IL-12, and stimulation, through the T cell receptor (TCR) with anti-CD3 monoclonal antibody (mAb), a cell-bound molecule and a soluble antigenic extract. To evaluate cell division, carboxyfluorescein succinimidyl ester (CFSE) loading of cells and flow cytometric analysis were used, while IFN-gamma production was evaluated by intracytoplasmic staining. It was found that bovine gammadelta T cells produced IFN-gamma and clonally expanded when stimulated through the TCR/CD3 complex by a cell-associated autologous molecule on monocyte, by bacterial components following in vivo sensitization of gammadelta T cells with a leptospira vaccine or by anti-CD3 mAb. In addition, gammadelta T cells were activated efficiently for effector function but not clonal expansion by culturing with IL-12. In contrast, stimulation by Con A or PMA/ionomycin induced efficient replication but only low level IFN-gamma production which was not enhanced by the presence of IL-12. In several systems the amount of IFN-gamma produced per cell by gammadelta T cells was less than that produced by CD4 T cells in the same cultures.

Animals↗

PubMed2002

Evaluation of the 3D BacT/ALERT automated culture system for the detection of microbial contamination of platelet concentrates.

Bacterial transmission remains the major component of morbidity and mortality associated with transfusion-transmitted infections. Platelet concentrates are the most common cause of bacterial transmission. The BacT/ALERT 3D automated blood culture system has the potential to screen platelet concentrates for the presence of bacteria. Evaluation of this system was performed by spiking day 2 apheresis platelet units with individual bacterial isolates at final concentrations of 10 and 100 colony-forming units (cfu) mL-1. Fifteen organisms were used which had been cited in platelet transmission and monitoring studies. BacT/ALERT times to detection were compared with thioglycollate broth cultures, and the performance of five types of BacT/ALERT culture bottles was evaluated. Sampling was performed immediately after the inoculation of the units, and 10 replicates were performed per organism concentration for each of the five types of BacT/ALERT bottles. The mean times for the detection of these 15 organisms by BacT/ALERT, with the exception of Propionibacterium acnes, ranged from 9.1 to 48.1 h (all 10 replicates were positive). In comparison, the time range found using thioglycollate was 12.0-32.3 h (all 10 replicates were positive). P. acnes' BacT/ALERT mean detection times ranged from 89.0 to 177.6 h compared with 75.6-86.4 h for the thioglycollate broth. BacT/ALERT, with the exception of P. acnes, which has dubious clinical significance, gave equivalent or shorter detection times when compared with the thioglycollate broth system. The BacT/ALERT system detected a range of organisms at levels of 10 and 100 cfu mL-1. This study validates the BacT/ALERT microbial detection system for screening platelets. Currently, the system is the only practically viable option available for routinely screening platelet concentrates to prevent bacterial transmission.

Aerobiosis↗

PubMed2002

Helicobacter cetorum sp. nov., a urease-positive Helicobacter species isolated from dolphins and whales.

A novel helicobacter with the proposed name Helicobacter cetorum, sp. nov. (type strain MIT 99-5656; GenBank accession number AF 292378), was cultured from the main stomach of two wild, stranded Atlantic white-sided dolphins (Lagenorhynchus acutus) and from the feces of three captive cetaceans (a Pacific white-sided dolphin [Lagenorhynchus obliquidens]; an Atlantic bottlenose dolphin [Tursiops truncatus]; and a beluga whale [Delphinapterus leucas]). The infected captive cetaceans were either subclinical, or clinical signs included intermittent regurgitation, inappetance, weight loss, and lethargy. Ulcers were observed in the esophagus and forestomach during endoscopic examination in two of the three captive animals. In the third animal, esophageal linear erosions were visualized endoscopically, and histopathological evaluation of the main stomach revealed multifocal lymphoplasmacytic gastritis with silver-stained spiral-shaped bacteria. Helicobacter cetorum is a fusiform gram-negative bacterium with a single bipolar flagellum. The isolates grow under microaerobic conditions at 37 and 42 degrees C but not at 25 degrees C. H. cetorum is urease, catalase, and oxidase positive, and it is sensitive to cephalothin. The isolates from the wild, stranded dolphins were sensitive to nalidixic acid, whereas the isolates from the collection animals were resistant. By 16S rRNA sequencing it was determined that H. cetorum represented a distinct taxon that clusters most closely with H. pylori. Further studies are necessary to determine the role of H. cetorum in the development of gastric ulcers and gastritis of cetaceans. This is the first description and formal naming of a novel Helicobacter species from a marine mammal.

Animals↗