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Biomedical subjects

Ian Harvey

Publications and source records attributed to Ian Harvey.

At least 37 records · Page 2Linked to original sources

A novel copper site in a cyanobacterial metallochaperone.

The thylakoid lumen of the cyanobacterium Synechocystis PCC 6803 is supplied with copper via two copper-transporting ATPases and a metallochaperone intermediary. We show that the copper site of this metallochaperone is unusual and consists of two cysteine residues and a histidine imidazole located on structurally dynamic loops. Substitution of this histidine residue enhances bacterial two-hybrid interaction with the cytosolic copper exporter, but not the copper importer, suggesting that the interacting surfaces are distinct, with implications for metal transfer.

ATP-Binding Cassette Transporters↗

Assessing quality of life in the elderly: a direct comparison of the EQ-5D and AQoL.

As more research is undertaken on the elderly, accurately assessing changes in their quality of life becomes increasingly important. Generic instruments are the most popular method to assess quality of life, and one of the most widely used is the EQ-5D. However, the range of dimensions, sensitivity of scales and completion rates have been raised as concerns when using this measure with the elderly. The AQoL is a newer instrument which offers greater richness in dimensions of health covered, and potentially offers greater sensitivity to changes in quality of life. This paper presents the results of a 'head-to-head' comparison of the EQ-5D and AQoL in terms of practicality, construct validity, agreement (of absolute scores and their change over time) and sensitivity to change, as part of a randomised controlled trial in the elderly. Poor agreement was found between both the absolute scores from each instrument and change in scores over time. Although the AQoL appeared to have more favourable construct validity, the EQ-5D was easier to administer, had a higher completion rate, and appeared more sensitive to change. We conclude that the AQoL is probably less well suited to measuring health status in a very elderly population than the EQ-5D.

Aged↗

An alternative approach to quantifying and addressing inequity in healthcare provision: access to surgery for lung cancer in the east of England.

STUDY OBJECTIVE: Equitable access to healthcare services should be monitored routinely. This study compares provision of surgery for non-small cell lung cancer in the east of England with incidence of non-small cell lung cancer. In addition to conventional comparisons, process control charts are used to identify areas in which access seems to be significantly different from average. DESIGN: Ecological comparison of surgery rates for non-small cell lung cancer between 1998 and 2000 and incidence of non-small cell lung cancer over the same time period. SETTING: Population of Norfolk, Suffolk, Cambridgeshire. PARTICIPANTS: The denominator was the resident population. Numerators were 4092 deaths from non-small cell lung cancer and 387 surgical procedures for lung cancer. MAIN RESULTS: Incidence of non-small cell lung cancer by primary care trust (PCT) does not correlate with surgical procedure rate, in men r = 0.37 (95% confidence intervals -0.14 to 0.72), in women r = 0.07 (95% confidence intervals -0.43 to 0.53). Control charts indicate that the surgery rate is significantly different from average in three PCTs, high in one and low in two others. The optimum surgery rate is unclear but raising it from 9% to a theoretical level of 15% would mean no PCTs have above average rates while six PCTs have rates that are significantly low. CONCLUSIONS: There does not seem to be equity of access to surgery for patients with non-small cell lung cancer in the east of England. Control charts can help both to identify areas where access is particularly high or low, and also to monitor performance against a theoretical optimum surgery rate.

Carcinoma, Non-Small-Cell Lung↗

The effectiveness of topical preparations for the treatment of earwax: a systematic review.

BACKGROUND: Earwax is a common problem in both primary and secondary care. There is uncertainty as to the most effective topical treatment. AIM: To assess the evidence concerning the efficacy of topical preparations used for treating earwax. DESIGN OF STUDY: Systematic review and meta-analysis. METHOD: Searching for randomised controlled trials (RCTs) of relevant studies. Classification of preparations into three groups, enabling pooling of data and meta-analysis. RESULTS: Of the 18 RCTs included in the review, four were judged to be of high quality. Fifteen preparations including saline and plain water were studied. Oil-based and water-based preparations were equally effective at clearing earwax without syringing (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.4 to 2.3) and facilitating successful syringing (OR = 1.0, 95% CI = 0.6 to 1.6). A non-water-, non-oil-based preparation appeared more effective than an oil-based preparation at both clearing earwax without syringing, and facilitating successful syringing. Immediate syringing after application of a preparation may be as effective as using eardrops for several days and delaying syringing. CONCLUSIONS: On current evidence, there is little to choose between water-based and oil-based preparations; non-water-, non-oil-based preparations appear promising at both clearing earwax and facilitating successful syringing, but further large trials are needed. Although immediate ear syringing is effective and convenient for patients, it may be less cost-effective than using eardrops and perhaps avoiding syringing. Most of the evidence regarding such a common and time-consuming problem is not of high quality.

Administration, Topical↗

Warts.

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Bleomycin↗

Time out of mind.

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Health Priorities↗

Meta-analysis of data on costs from trials of counselling in primary care: using individual patient data to overcome sample size limitations in economic analyses.

OBJECTIVE: To assess the feasibility of overcoming sample size limitations in economic analyses of clinical trials through meta-analysis of data on individual patients from multiple trials. DESIGN: Meta-analysis of individual patient data from trials of counselling in primary care compared with usual care by a general practitioner. SETTING: Primary care. PATIENTS: People with mental health problems. MAIN OUTCOME MEASURES: Direct treatment costs, depressive symptoms, and cost effectiveness. RESULTS: Meta-analysis of individual patient data proved feasible. The results showed that the previous analyses of individual trials were underpowered to provide useful conclusions about the cost comparisons. The results are sensitive to assumptions made about the costs of sessions with a counsellor and the management of patients by a general practitioner. CONCLUSIONS: Meta-analysis of individual patient data may assist in overcoming sample size limitations in economic analyses. Although feasible, such analysis has shortcomings that may limit the validity of the results. The relative costs and benefits of this method, as opposed to further collection of primary data, are as yet unclear.

Clinical Trials as Topic↗

Application of stopped flow techniques and energy dispersive EXAFS for investigation of the reactions of transition metal complexes in solution: activation of nickel beta-diketonates to form homogeneous catalysts, electron transfer reactions involving iron(III) and oxidative addition to iridium(I).

Stopped-flow techniques of rapid mixing have been combined with energy dispersive X-ray absorption spectroscopy to monitor the reaction of Ni(dpm)2 [dpm = Bu1C(O)CHC(O)Bu1] by aluminium alkyls (AlEt2X, X = OEt and Et) to form the active species for the catalytic di- and tri-merisation of hex-1-ene. Acquisition times down to ca. 30 ms were achieved on Station 9.3 of the SRS using a photodiode array detector. The EXAFS features of the resulting solution complexes are of the form [Ni(O-O)R)(alkene)]. In the presence of PPh3, [Ni(O-O)(R)(PPh3) appears to be the redominant type of species. The reduction of aqueous Fe(III) by hydroquinone was investigated on ID24 at the ESRF by Fe K-edge energy dispersive EXAFS with a CCD camera as detector, spectra were obtained in 1 ms or longer. No intermediate inner sphere complex was detected prior to the formation of aqueous Fe(II). Finally the oxidative addition of CH3SO3CF3 to [IrI2(CO)2]- was monitored on Station 9.3 with a silicon microstrip detector. A single acquisition of 400 micros was feasible, with spectra recorded in multiples of 1.2 ms. In that time, the first stage of the reaction had been completed, with a slower stage thereafter. The results are consistent with the two-stage ionic oxidative addition mechanism.

Journal Article↗

Does breakfast-club attendance affect schoolchildren's nutrient intake? A study of dietary intake at three schools.

Lack of breakfast has been implicated as a factor contributing to children's poor diets and school performance. Breakfast-club schemes, where children are provided with breakfast in school at the start of the school day, have been initiated by the Department of Health in schools throughout England, UK. The aim of the present study was to compare the energy and nutrient intakes of schoolchildren who attended breakfast clubs (attendee subjects) with those who did not (control subjects). Three different schools were studied, involving a total of 111 children aged between 9 and 15 years. There were fifty-nine attendee and fifty-two control subjects. The two groups were matched for eligibility for school meals. All subjects completed a 3 d weighed food diary for estimation of nutrient intake. Height and weight were measured and BMI calculated. Nutrient intake data were analysed using a general linear model with age as a covariate. The demographic and anthropometric characteristics of the attendee and control subjects were similar. Children who attended breakfast clubs had significantly greater intakes of fat (% energy), saturated fat (% energy) and Na than control subjects. Thus, in these schools breakfast-club participation was not associated with superior nutrient intake or improvements in dietary pattern.

Adolescent↗

Relationship between body mass and gastro-oesophageal reflux symptoms: The Bristol Helicobacter Project.

OBJECTIVE: To examine the relationship between body mass and gastro-oesophageal reflux in a large population-representative sample from the UK. DESIGN AND SETTING: Cross-sectional population-based study, as part of a randomized controlled trial of eradication of Helicobacter pylori infection, in Southwest England. Subjects In all, 10 537 subjects, aged 20-59 years, were recruited from seven general practices. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken. MAIN OUTCOME MEASURE: Relationship between overweight (body mass index [BMI] >/=25 kg/m(2) and </=30 kg/m(2)) or obesity (BMI >30 kg/m(2)) and frequency and severity of heartburn and acid regurgitation. RESULTS: Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux. The adjusted odds ratios (OR) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 (95% CI: 1.33-2.50) and 1.50 (95% CI: 1.13-1.99) respectively. Corresponding OR (95% CI) relating to obese patients were 2.91 (95% CI: 2.07-4.08) and 2.23 (95% CI: 1.44-3.45) respectively. The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance: OR = 1.19; 95% CI: 1.07-1.33. CONCLUSIONS: Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight.

Adult↗

A qualitative investigation of vaccine risk perception amongst parents who immunize their children: a matter of public health concern.

BACKGROUND: Little is known about risk perception amongst parents who have their children immunized, as opposed to those who do not. Our objective was to assess their vaccine risk perception and thereby to identify strategies to prevent further deterioration in uptake. METHODS: An in-depth interview study was conducted with parents in two nurseries, one urban and one rural in Norfolk, together with a pilot study. All their children were fully immunized. Topics related to parents' vaccine risk perceptions. RESULTS: Certain known risk characteristics were attributable to the measles, mumps and rubella vaccine, including feeling of dread, lack of control and doubt in scientific knowledge. Furthermore, this study re-emphasizes that parents lack trust in government agencies and may have doubts in the medical profession as the 'managers' of vaccine risk. CONCLUSIONS: Results highlighted an urgent need to address concerns amongst parents who immunize, to prevent them changing their practice in the face of further vaccine controversies.

Adult↗

Reduced risk of atopic disorders in adults with Helicobacter pylori infection.

BACKGROUND: Childhood infections may be necessary to prime the developing immune system in an appropriate manner. In developed countries, the incidence of childhood infections is decreasing, which might explain the observed rise in the prevalence of asthma and other atopic disorders in recent years. AIM: To determine whether Helicobacter pylori gastritis, a chronic bacterial infection that is usually acquired in early childhood and then persists throughout life, affects the risk of developing asthma and other atopic disorders. STUDY DESIGN: Cross-sectional study of the prevalence of three atopic disorders in 3244 subjects participating in a community-based, prospective, randomized, controlled trial of H. pylori eradication, the Bristol Helicobacter Project. The presence or absence of active H. pylori infection was determined by the 13C-urea breath test. The prevalence of asthma, eczema and allergic rhinitis was measured by assessing the use of appropriate medications as surrogate markers for these conditions. RESULTS: There was a 30% reduction in the prevalence of all three atopic disorders in people who had active H. pylori infection, although for each individual atopic disorder the numbers were not quite large enough to reach statistical significance. CONCLUSIONS: H. pylori infection is associated with a substantially reduced risk of three common atopic disorders. This is further indirect evidence of the importance of childhood infections in influencing the development of a normal immune response. As such infections become progressively less common in developed countries such as the UK, other methods will need to be developed to try to reduce the risk of atopic disorders.

Adult↗

Costs and concentration of cancer care: evidence for pancreatic, oesophageal and gastric cancers in National Health Service hospitals.

OBJECTIVES: To examine relationships between the cost of hospital cancer care and the degree of specialisation of patients' doctors and hospitals as indicated by their annual case-loads. METHODS: Three cohorts comprising 2294 patients with cancers of the pancreas, oesophagus and stomach in 29 acute National Health Service (NHS) hospitals in south-west England and South Wales were followed prospectively for a year. For each patient, prognostic variables, service activity and survival data were recorded, and the hospital cost of cancer care and cost per year survived were estimated. Costs were estimated from quantities of resource units provided and a single set of unit costs. Costs per day survived after presentation to hospital were calculated as estimates of cost-effectiveness. Linear regression analyses examined the effects on total costs, and on costs per day survived of doctors' and hospitals' annual patient volumes, adjusting for prognostic variables and treatments. RESULTS: General ward care rather than specific treatments and investigations accounted for most of total costs. Costs per patient increased significantly with increasing doctor volumes. After adjustment for prognosis and treatments, however, cost-volume relationships were U-shaped, reflecting more active intervention by higher volume doctors, along with little activity and long stays among patients of lower volume doctors. Cost per day survived also had U-shaped relationships with doctor volumes. Regression models using continuous rather than categorical volume terms fitted the data best. CONCLUSIONS: Doctors' specialisation is at least as important for efficiency and effectiveness as hospitals' specialisation. Cost and cost per day survived increased and then decreased with increasing doctor volumes, highlighting the need for critical attention to costs as services become highly specialised. Specialisation occurs along a continuum, with no clear volume threshold effects on survival or costs.

England↗

Warts.

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Bleomycin↗

Synergistic anion and metal binding to the ferric ion-binding protein from Neisseria gonorrhoeae.

The 34-kDa periplasmic iron-transport protein (FBP) from Neisseria gonorrhoeae (nFBP) contains Fe(III) and (hydrogen)phosphate (synergistic anion). It has a characteristic ligand-to-metal charge-transfer absorption band at 481 nm. Phosphate can be displaced by (bi)carbonate to give Fe.CO(3).nFBP (lambda(max) 459 nm). The local structures of native Fe-PO(4)-nFBP and Fe.CO(3).nFBP were determined by EXAFS at the FeK edge using full multiple scattering analysis. The EXAFS analysis reveals that both phosphate and carbonate ligands bind to FBP in monodentate mode in contrast to transferrins, which bind carbonate in bidentate mode. The EXAFS analysis also suggests an alternative to the crystallographically determined position of the Glu ligand, and this in turn suggests that an H-bonding network may help to stabilize monodentate binding of the synergistic anion. The anions oxalate, pyrophosphate, and nitrilotriacetate also appear to serve as synergistic anions but not sulfate or perchlorate. The oxidation of Fe(II) in the presence of nFBP led to a weak Fe(III).nFBP complex (lambda(max) 471 nm). Iron and phosphate can be removed from FBP at low pH (pH 4.5) in the presence of a large excess of citrate. Apo-FBP is less soluble and less stable than Fe.nFBP and binds relatively weakly to Ga(III) and Bi(III) but not to Co(III) ions, all of which bind strongly to apo-human serum transferrin.

Anions↗

Local treatments for cutaneous warts: systematic review.

OBJECTIVE: To assess the evidence for the efficacy of local treatments for cutaneous warts. METHODS: Systematic review of randomised controlled trials. MAIN OUTCOMES MEASURES: Total clearance of warts and adverse effects such as irritation, pain, and blistering. STUDY SELECTION: Randomised controlled trials of any local treatment for uncomplicated cutaneous warts. All published and unpublished material was considered, with no restriction on date or language. RESULTS: 50 included trials provided generally weak evidence because of poor methods and reporting. The best evidence was for topical treatments containing salicylic acid. Data pooled from six placebo controlled trials showed a cure rate of 75% (144 of 191) in cases compared with 48% (89 of 185) in controls (odds ratio 3.91, 95% confidence interval 2.40 to 6.36). Some evidence for the efficacy of contact immunotherapy was provided by two small trials comparing dinitrochlorobenzene with placebo. Evidence for the efficacy of cryotherapy was limited. No consistent evidence was found for the efficacy of intralesional bleomycin, and only limited evidence was found for the efficacy of topical fluorouracil, intralesional interferons, photodynamic therapy, and pulsed dye laser. CONCLUSIONS: Reviewed trials of local treatments for cutaneous warts were highly variable in methods and quality, and there was a paucity of evidence from randomised, placebo controlled trials on which to base the rational use of the treatments. There is good evidence that topical treatments containing salicylic acid have a therapeutic effect and some evidence for the efficacy of dinitrochlorobenzene. Less evidence was found for the efficacy of all the other treatments reviewed, including cryotherapy.

Anti-Bacterial Agents↗