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Biomedical subjects

M Campbell

Publications and source records attributed to M Campbell.

At least 73 records · Page 4Linked to original sources

Endostatin modulates VEGF-mediated barrier dysfunction in the retinal microvascular endothelium.

Recent evidence indicates that the anti-angiogenic peptide endostatin may modulate some of the vasomodulatory effects of vascular endothelial growth factor (VEGF) in the retina, including reduction of blood retinal barrier function although it remains uncertain how endostatin promotes endothelial barrier properties. The current study has sought to examine how physiological levels of endostatin alters VEGF-induced inner BRB function using an in vitro model system and evaluation of occludin and ZO-1 regulatory responses. In addition, the ability of exogenous endostatin to regulate VEGF-mediated retinal vascular permeability in vivo was investigated. Retinal microvascular endothelial cells (RMEC's) were exposed to various concentrations of endostatin. In parallel studies, RMEC monolayers were treated with vascular endothelial growth factor (VEGF165). Vasopermeability of RMEC monolayers and occludin expression were determined. Blood retinal barrier integrity was quantified in mouse retina using Evans Blue assay following intravitreal delivery of VEGF165, endostatin or a VEGF/endostatin combination. Endostatin increased the levels of expression of occludin whilst causing no significant change in FITC-dextran flux across the RMEC monolayer. Endostatin reversed the effects of VEGF165-enhanced permeability between microvascular endothelial cells and induced phosphorylation of occludin. Evans Blue leakage from retinas treated with VEGF was 2.0 fold higher than that of contra-lateral untreated eyes (P<0.05) while leakage of eyes from endostatin treated animals was unchanged. When eyes were injected with a combination of VEGF165 and endostatin there was a significant reduction in retinal vasopermeability when compared to VEGF-injected eyes (P<0.05). We conclude that endostatin can promote integrity of the retinal endothelial barrier, possibly by preventing VEGF-mediated alteration of tight junction integrity. This suggests that endostatin may be of clinical benefit in ocular disorders where significant retinal vasopermeability changes are present.

Animals↗

Controlling postpartum hemorrhage after home births in Tanzania.

OBJECTIVES: Determine safety of household management of postpartum hemorrhage (PPH) with 1000 microg of rectal misoprostol, and assess possible reduction in referrals and the need for additional interventions. METHODS: Traditional birth attendants (TBAs) in Kigoma, Tanzania were trained to recognize PPH (500 ml of blood loss). Blood loss measurement was standardized by using a local garment, the "kanga". TBAs in the intervention area gave 1000 microg of misoprostol rectally when PPH occurred. Those in the non-intervention area referred the women to the nearest facility. RESULTS: 454 women in the intervention and 395 in the non-intervention areas were eligible. 111 in the intervention area and 73 in the non-intervention had PPH. Fewer than 2% of the PPH women in the intervention area were referred, compared with 19% in the non-intervention. CONCLUSION: Misoprostol is a low cost, easy to use technology that can control PPH even without a medically trained attendant.

Administration, Rectal↗

Balance disorder and traumatic brain injury: preliminary findings of a multi-factorial observational study.

The pathophysiology of TBI suggests that balance disorder in this population may be associated with multi-system dysfunction, but this has not been widely explored in the literature. This study was undertaken to begin to describe the nature of balance disorder across the TBI population. A clinically-based observational design was employed and data gathered by a standardized process of structured observation. Twenty-seven subjects were recruited across a range of injury severities. The sample was skewed towards mild/moderate injury with a mean summated GCS score of 9.6. Deficits were observed across a wide range of domains at both individual and group level and the overall level of balance dysfunction was high. Summary results are reported here and a more detailed analysis of individual cases is underway. Additional cross-disciplinary research is required to further develop understanding of the nature of balance disorder in this population and to develop appropriate methods of clinical assessment.

Adult↗

Cost-effectiveness of formoterol and salbutamol as asthma reliever medication in Sweden and in Spain.

This study aimed to evaluate the cost-effectiveness of formoterol (Oxis) Turbuhaler 4.5 microg and salbutamol 200 microg as reliever medications in Sweden and Spain. The study used data on effectiveness (exacerbations and symptom-free days) and resource utilisation from an open, 6-month, parallel-group, multicentre randomised trial with 18,124 asthma patients in 24 countries. Country-specific unit costs for Sweden and for Spain were used to transform resource utilisation data into costs. Total healthcare costs were not significantly different between formoterol and salbutamol dry powder inhalers in Sweden, whereas in Spain, the healthcare costs were 20% higher for formoterol vs. salbutamol pressurised metered dose inhalers. Total healthcare costs increased with disease severity, defined according to the Global Initiative for Asthma guidelines. Compared with salbutamol, formoterol produced statistically significant improvements in effectiveness, less reliever and maintenance medication usage, reduced healthcare resource utilisation, with no increase or a limited increase in healthcare cost.

Administration, Inhalation↗

Involvement in treatment decisions: what do adults with asthma want and what do they get? Results of a cross sectional survey.

BACKGROUND: Current healthcare policy advocates patient participation in treatment decision making. However, in asthma there is little evidence regarding patients' views on such involvement. This study explored the preferred and perceived level of involvement in treatment decisions, rationales for role preference, perceived facilitators of/barriers to involvement, and the interrelationship of role preference and demographic variables in a sample of patients with asthma. METHODS: A cross sectional survey was performed of 230 adults with clinician diagnosed asthma from 10 primary care sites and one specialist respiratory centre in north-west England. Preferred role in treatment decisions was assessed using the Control Preferences Scale. RESULTS: Fifty five (23.9%) preferred an active role, 82 (35.7%) a collaborative role, and 93 (40.4%) a passive role; 19 (8.2%) perceived their role as active compared with 45 (19.6%) collaborative and 166 (72.2%) passive. Only 33.5% (n = 77) of respondents attained their most preferred role; 55.2% (n = 127) were less involved than they preferred. Patient related, professional related, and organisational factors, especially quality and duration of consultations, facilitated or hampered involvement. Role preferences were not strongly associated with demographic variables or asthma severity. CONCLUSIONS: This study in patients with asthma highlights the fact that there is a need for professional and patient education regarding partnership working, skilful communication, and innovative approaches to service delivery.

Adult↗

A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.

OBJECTIVE: To determine the relative cost-effectiveness of three classes of antidepressants: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the modified TCA lofepramine, as first choice treatments for depression in primary care. DESIGN: Open, pragmatic, controlled trial with three randomised arms and one preference arm. Patients were followed up for 12 months. SETTING: UK primary care: 73 practices in urban and rural areas in England. PARTICIPANTS: Patients with a new episode of depressive illness according to GP diagnosis. INTERVENTIONS: Patients were randomised to receive a TCA (amitriptyline, dothiepin or imipramine), an SSRI (fluoxetine, sertraline or paroxetine) or lofepramine. Patients or GPs were able to choose an alternative treatment if preferred. MAIN OUTCOME MEASURES: At baseline the Clinical Interview Schedule, Revised (CIS-R PROQSY computerised version) was administered to establish symptom profiles. Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression (HAD-D), CIS-R, EuroQol (EQ-5D) for quality of life, Short Form (SF-36) for generic health status, and patient and practice records of use of health and social services. The primary effectiveness outcome was the number of depression-free weeks (HAD-D less than 8, with interpolation of intervening values) and the primary cost outcome total direct NHS costs. Quality-adjusted life-years (QALYs) were used as the outcome measure in a secondary analysis. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed. Estimates were bootstrapped with 5000 replications. RESULTS: In total, 327 patients were randomised. Follow-up rates were 68% at 3 months and 52% at 1 year. Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients randomised to TCAs entered the preference arm than those allocated to the other choices. Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm. There were no significant differences between arms in mean cost per depression-free week. For values placed on an additional QALY of over 5000 pounds, treatment with SSRIs was likely to be the most cost-effective strategy. TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively, but these differences were relatively modest. CONCLUSIONS: When comparing the different treatment options, no significant differences were found in outcomes or costs within the sample, but when outcomes and costs were analysed together, the resulting cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option, although the probability of this did not rise above 0.6. Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks. Further research is still needed on the management of depressive illness in primary care. This should address areas such as the optimum severity threshold at which medication should be used; the feasibility and effectiveness of adopting structured depression management programmes in the UK context; the importance of factors such as physical co-morbidity and recent life events in GPs' prescribing decisions; alternative ways of collecting data; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early.

Adolescent↗

Longer term clinical and economic benefits of offering acupuncture care to patients with chronic low back pain.

OBJECTIVES: To test whether patients with persistent non-specific low back pain, when offered access to traditional acupuncture care alongside conventional primary care, gained more long-term relief from pain than those offered conventional care only, for equal or less cost. Safety and acceptability of acupuncture care to patients, and the heterogeneity of outcomes were also tested. DESIGN: A pragmatic, two parallel group, randomised controlled trial. Patients in the experimental arm were offered the option of referral to the acupuncture service comprising six acupuncturists. The control group received usual care from their general practitioner (GP). Eligible patients were randomised in a ratio of 2:1 to the offer of acupuncture to allow between-acupuncturist effects to be tested. SETTING: Three non-NHS acupuncture clinics, with referrals from 39 GPs working in 16 practices in York, UK. PARTICIPANTS: Patients aged 18-65 years with non-specific low back pain of 4-52 weeks' duration, assessed as suitable for primary care management by their general practitioner. INTERVENTIONS: The trial protocol allowed up to ten individualised acupuncture treatments per patient. The acupuncturist determined the content and the number of treatments according to patient need. MAIN OUTCOME MEASURES: The Short Form 36 (SF-36) Bodily Pain dimension (range 0-100 points), assessed at baseline, and 3, 12 and 24 months. The study was powered to detect a 10-point difference between groups at 12 months post-randomisation. Cost--utility analysis was conducted at 24 months using the EuroQoL 5 Dimensions (EQ-5D) and a preference-based single index measure derived from the SF-36 (SF-6D). Secondary outcomes included the McGill Present Pain Index (PPI), Oswestry Pain Disability Index (ODI), all other SF-36 dimensions, medication use, pain-free months in the past year, worry about back pain, satisfaction with care received, and safety and acceptability of acupuncture care. RESULTS: A total of 159 patients were in the 'acupuncture offer' arm and 80 in the 'usual care' arm. All 159 patients randomised to the offer of acupuncture care chose to receive acupuncture treatment, and received an average of eight acupuncture treatments within the trial. Analysis of covariance, adjusting for baseline score, found an intervention effect of 5.6 points on the SF-36 Pain dimension [95% confidence interval (CI) -1.3 to 12.5] in favour of the acupuncture group at 12 months, and 8 points (95% CI 0.7 to 15.3) at 24 months. No evidence of heterogeneity of effect was found for the different acupuncturists. Patients receiving acupuncture care did not report any serious or life-threatening events. No significant treatment effect was found for any of the SF-36 dimensions other than Pain, or for the PPI or the ODI. Patients receiving acupuncture care reported a significantly greater reduction in worry about their back pain at 12 and 24 months compared with the usual care group. At 24 months, the acupuncture care group was significantly more likely to report 12 months pain free and less likely to report the use of medication for pain relief. The acupuncture service was found to be cost-effective at 24 months; the estimated cost per quality-adjusted (QALY) was 4241 pounds sterling (95% CI 191 pounds sterling to 28,026 pounds sterling) using the SF-6D scoring algorithm based on responses to the SF-36, and 3598 pounds sterling (95% CI 189 pounds sterling to 22,035 pounds sterling) using the EQ-5D health status instrument. The NHS costs were greater in the acupuncture care group than in the usual care group. However, the additional resource use was less than the costs of the acupuncture treatment itself, suggesting that some usual care resource use was offset. CONCLUSIONS: Traditional acupuncture care delivered in a primary care setting was safe and acceptable to patients with non-specific low back pain. Acupuncture care and usual care were both associated with clinically significant improvement at 12- and 24-month follow-up. Acupuncture care was significantly more effective in reducing bodily pain than usual care at 24-month follow-up. No benefits relating to function or disability were identified. GP referral to a service providing traditional acupuncture care offers a cost-effective intervention for reducing low back pain over a 2-year period. Further research is needed to examine many aspects of this treatment including its impact compared with other possible short-term packages of care (such as massage, chiropractic or physiotherapy), various aspects of cost-effectiveness, value to patients and implementation protocols.

Acupuncture Therapy↗

Search for doubly charged Higgs bosons decaying to dileptons in pp collisions at square root of s=1.96 TeV.

We present the results of a search for doubly charged Higgs bosons (H+/-+/-) decaying to dileptons (ll(')) using approximately 240 pb(-1) of pp collision data collected by the CDF II experiment at the Fermilab Tevatron. In our search region, given by same-sign ll(') mass m(ll('))>80 GeV/c(2) (100 GeV/c(2) for ee channel), we observe no evidence for H+/-+/- production. We set limits on sigma(pp -->H++H---->l(+)l('+)l(-)l('-)) as a function of the mass of the H+/-+/- and the chirality of its couplings. Assuming exclusive same-sign dilepton decays, we derive lower mass limits on H(+/-+/-)(L) of 133, 136, and 115 GeV/c(2) in the ee, mumu, and emu channels, respectively, and a lower mass limit of 113 GeV/c(2) on H(+/-+/-)(R) in the mumu channel, all at the 95% confidence level.

Journal Article↗

Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home haemodialysis for end-stage renal disease in adults.

BACKGROUND: Renal replacement therapy (RRT) with dialysis and transplantation is the only means of sustaining life for patients with end-stage renal disease (ESRD). Although transplantation is the treatment of choice, the number of donor kidneys are limited and transplants may fail. Hence many patients require long-term or even life-long dialysis. Continuous ambulatory peritoneal dialysis (CAPD) is an alternative to hospital or home haemodialysis for patients with ESRD. OBJECTIVES: To assess the benefits and harms of CAPD versus hospital or home haemodialysis for adults with ESRD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), the Cochrane Renal Group's specialised register, MEDLINE (1966 - May 2002), EMBASE (1980 - May 2002), BIOSIS, CINAHL, SIGLE and NRR without language restriction. Reference lists of retrieved articles and conference proceedings were searched and known investigators and biomedical companies were contacted. Date of most recent search January 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing CAPD to hospital or home haemodialysis for adults with ESRD were to be included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assess the methodological quality of studies. Data was abstracted from included studies onto a standard form by one reviewer and checked by another. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: One trial, reported in abstract form only, was located in the most recent search. There was no statistical difference in death or quality adjusted life years score at 2 years between peritoneal dialysis or haemodialysis patients. REVIEWERS' CONCLUSIONS: There is Insufficient data to allow conclusions to be drawn about the relative effectiveness of CAPD compared with hospital or home haemodialysis for adults with ESRD. Efforts should be made to start and complete adequately powered RCTs, which compare the different dialysis modalities.

Adult↗

Inclusive double-pomeron exchange at the fermilab tevatron p p collider.

We report results from a study of events with a double-Pomeron exchange topology produced in p p collisions at sqrt[s]=1800 GeV. The events are characterized by a leading antiproton and a large rapidity gap on the outgoing proton side. We find that the differential production cross section agrees in shape with predictions based on Regge theory and factorization, and that the ratio of double-Pomeron exchange to single diffractive production rates is relatively unsuppressed as compared to the O(10) suppression factor previously measured in single diffractive production.

Journal Article↗

Measurement of the tt production cross section in pp collisions at sqrt[s]=1.96 TeV using dilepton events.

We report a measurement of the tt production cross section using dilepton events with jets and missing transverse energy in pp collisions at a center-of-mass energy of 1.96 TeV. Using a 197+/-12 pb(-1) data sample recorded by the upgraded Collider Detector at Fermilab, we use two complementary techniques to select candidate events. We compare the number of observed events and selected kinematical distributions with the predictions of the standard model and find good agreement. The combined result of the two techniques yields a tt production cross section of 7.0(+2.4)(-2.1)(stat)+1.6-1.1(syst)+/-0.4(lum) pb.

Journal Article↗

Observation of the narrow state X(3872)-->J/psipi+pi- in pp collisions at sqaure root of s=1.96 TeV.

We report the observation of a narrow state decaying into J/psipi+pi- and produced in 220 pb(-1) of p p-bar collisions at =1.96 Tesqaure root of sV in the CDF II experiment. We observe 730+/-90 decays. The mass is measured to be 3871.3+/-0.7(stat)+/-0.4(syst) MeV/c2, with an observed width consistent with the detector resolution. This is in agreement with the recent observation by the Belle Collaboration of the X(3872) meson.

Journal Article↗

Inclusive search for anomalous production of high-pT like-sign lepton pairs in pp collisions at square root s = 1.8 TeV.

We report on a search for anomalous production of events with at least two charged, isolated, like-sign leptons, each with pT > 11 GeV/c using a 107 pb(-1) sample of 1.8 TeV pp collisions collected by the CDF detector. We define a signal region containing low background from standard model processes. To avoid bias, we fix the final cuts before examining the event yield in the signal region using control regions to test the Monte Carlo predictions. We observe no events in the signal region, consistent with an expectation of 0.63(+0.84)(-0.07) events. We present 95% confidence level limits on new physics processes in both a signature-based context as well as within a representative minimal supergravity (tanbeta = 3) model.

Journal Article↗

Predominance and genetic diversity of community- and hospital-acquired CTX-M extended-spectrum beta-lactamases in York, UK.

OBJECTIVES: This study was conducted to detect the presence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae within the faecal flora of both community- and hospital-based patients in York and to characterize the bla(TEM), bla(SHV) and bla(CTX-M) genes present in these isolates. METHODS: One thousand faeces samples were collected and screened at York Hospital during October-December 2003. Ninety-five non-duplicate Enterobacteriaceae isolates resistant to third-generation cephalosporins were recovered; 22 isolates were selected for further study on the basis of a positive double disc diffusion test for ESBL production. Antibiotic susceptibility testing was performed to a range of antibiotics. The TEM, SHV and CTX-M genes were detected by PCR and the DNA sequenced. RESULTS: The distribution of ESBL-positive isolates from the hospital and community was 1.4:1. These included nine Escherichia coli, seven Enterobacter cloacae, four Citrobacter freundii and a single isolate each of Klebsiella spp. and Salmonella spp. A total of 17 isolates contained bla(CTX-M) (five bla(CTX-M-15), three bla(CTX-M-14) and nine bla(CTX-M-9)). ISEcp1 was present in isolates expressing CTX-M-14 and -15, but was absent upstream of In60-associated bla(CTX-M-9). E. coli isolates also contained either a bla(TEM-1) or bla(TEM-2), whereas six of the E. cloacae carried bla(SHV-12) and the Klebsiella spp. bla(SHV-36) in addition to bla(CTX-M-9). The single Salmonella spp. carried bla(SHV-12). CONCLUSIONS: The overall prevalence of ESBL in isolates of Enterobacteriaceae from York was 1.9%. ESBL-producing isolates were found in both the community and hospital, with the CTX-M type most common. This is also the first report of an ESBL-producing Salmonella in the UK.

Community-Acquired Infections↗

Search for B0s-->micro+micro- and B0d-->micro+micro- decays in pp collisions at square root s = 1.96 TeV.

We report on a search for B(0)(s)-->micro(+)micro(-) and B(0)(d)-->micro(+)micro(-) decays in pp collisions at square root of s=1.96 TeV using 171 pb(-1) of data collected by the CDF II experiment at the Fermilab Tevatron Collider. The decay rates of these rare processes are sensitive to contributions from physics beyond the standard model. One event survives all our selection requirements, consistent with the background expectation. We derive branching ratio limits of B(B(0)(s)-->micro(+)micro(-))<5.8x10(-7) and B(B(0)(d)-->micro(+)micro(-))<1.5x10(-7) at 90% confidence level.

Journal Article↗

Search for Kaluza-Klein graviton emission in pp collisions at square root[s] = 1.8 TeV using the missing energy signature.

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 pb(-1) of ppmacr; collisions at sqrt[s]=1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a (3+1+n)-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for n=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.

Journal Article↗