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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 19 recordsLinked to original sources

Patient knowledge and misconceptions of osteoarthritis assessed by a validated self-completed knowledge questionnaire (PKQ-OA).

OBJECTIVES: To design and validate an osteoarthritis (OA) patient knowledge questionnaire (PKQ-OA) and to use it to assess the patients' level of knowledge of their disease, treatments and appropriate management techniques. METHODS: The PKQ-OA comprises 16 multiple choice questions with 30 correct answers. It was developed in two phases and tested for face validity, readability (Flesch Reading Index) and understanding, reliability (Kuder-Richardson Formula 20) and reproducibility (test/retest). The questionnaire was then used to assess knowledge of disease and management of OA in a cohort of 83 patients with established disease. RESULTS: The PKQ was found to be fairly easy to read, reliable (r = 0.75) and reproducible (r = 0.81; P < 0.01). The overall median score for the PKQ-OA was 19 ranging from 8 to 26. There was a highly significant association between the scores obtained and the number of years patients had spent in formal education, higher scores equating with greater length of education (P < 0.005). The majority of patients was knowledgeable about the symptoms of OA and exercise, but confused joint protection and energy conservation. The most worrying finding was the lack of knowledge regarding analgesics and some aspects of non-steroidal anti-inflammatory drug (NSAID) therapy. Less than a third of patients knew that analgesics could be taken prophylactically and 70% did not know that they should be taken when pain starts to build. Among the patients 34% did not know that NSAIDs should be taken with or following food. CONCLUSIONS: The PKQ-OA is a readable, reliable and reproducible questionnaire. It is quick to complete and score and could be used in out patient clinics or GP surgeries to assess knowledge of patients with OA.

Adult↗

Immunogenicity of the rF1+rV vaccine for plague with identification of potential immune correlates.

The rF1+rV candidate sub-unit vaccine for plague, formulated by adsorption to alhydrogel, has been demonstrated to be immunogenic in the cynomolgus macaque in a clinically relevant dose-range (5-40 microg of each sub-unit) and regimen. Following two doses of vaccine, a specific IgG titre developed in a dose-related manner with predominance of the IgG1/IgG2 isotypes. Groups of macaques receiving only a single dose of vaccine at the 40 microg dose-level had a significantly reduced peak IgG response and faster decline to baseline. Serum collected at week 5 from 19 immunised animals competed with and displaced murine Mab7.3 from binding to the V antigen in vitro. By week 53 of the schedule, although absolute IgG titres had declined, 17/19 macaque sera tested contained competing antibody, indicating the durability of a functional immune response to rF1+rV in this species. Thirteen of these week 53 sera were passively transferred into groups of naive mice, and all conferred full or partial protection against subsequent challenge of the mice with plague. Generally, those sera which were most competitive with Mab 7.3 for binding to V antigen were fully protective by passive transfer, although one week-53 serum sample was fully protective by passive transfer but not active by competitive ELISA. The early development of protective immunity in macaques was also indicated from the protection conferred on naive mice by the passive transfer of immune macaque serum collected at 2-10 weeks of the immunisation schedule. Serum samples from representative macaques within this time period also inhibited the Yersinia-mediated cytotoxicity of J774 macrophages in a qualitative in vitro assay of type three secretion.

Animals↗

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗

Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates.

BACKGROUND: Many different embryo selection criteria have been used in assisted reproductive technologies (ART), but there are no published prospective studies to ascertain their usefulness in predicting implantation. METHODS: In a prospective trial, 20 early scoring parameters previously reported to influence clinical outcome were collected, but embryos were selected for transfer by current laboratory protocols; day 1 pronuclear (PN) (Z) score combined with day 3 or 5 morphology. Data points for each oocyte/embryo were scored independently and tracked individually. Data were analysed retrospectively for parameters most likely to result in a positive pregnancy test, fetal heartbeat (FHB) and delivery. RESULTS: Results indicated that day 1 PN morphology and nucleolar precursor body (NPB) ratio, day 2 cell number, blastomere symmetry and nucleation and the ability to cleave from day 2 to day 3 were the six most significant factors in fetal development. This outcome was then applied prospectively over 8 months. The implantation rate (IR) and clinical pregnancy rate (CPR) increased in each age group, and the number of embryos used decreased. CONCLUSION: In conclusion, early parameters that include PN morphology, number and ratio of NPBs per nucleus and the day 2 morphology of cleaving embryos are stronger positive predictors of implantation than day 3 morphology or the ability to achieve the blastocyst stage of development. Parameters that were most consistently correlated with no delivery were lack of PN symmetry, day 2 multinucleation and uneven cell size. Day 3 and day 5 parameters were not significant compared with the combination of early parameters.

Adult↗

The disposal of radioactive ferric floc.

An iron hydroxide floc is used as treatment for adsorbing low amounts of actinides during nuclear fuel re-processing. This waste is cemented only after pre-treatment with Ca(OH)(2). Characterisation of all simulant material has been undertaken using XRD, TGA and SEM/EDS. The floc is a moderately alkaline colloidal slurry containing approximately 15wt% solids, with the main particulate being an amorphous hydrated iron oxide. The main phase formed during pre-treatment appears to be an X-ray amorphous hydrated calcium-ferrate phase. Embedded within this are small amounts of crystalline Ca(OH)(2), calcite, Fe(6)(OH)(12)(CO(3)), Ca(6)Fe(2)(SO(4))(3)(OH)(12).26H(2)O and Ca(3)B(2)O(6), and can form depending on concentrations of Ca(OH)(2) and time. Apart from Ca(OH)(2) and calcite, none of the crystalline phases detected during pre-treatment are detected when the floc is encapsulated in an OPC/PFA composite cement hydrated for 90 days. The main crystalline phase detected in the hardened wasteform is a solid solution hydrogarnet, Ca(3)AlFe(SiO(4))(OH)(8), known as C(3)(A,F)SH(4) in cement chemistry nomenclature.

Construction Materials↗

The effect of sodium chloride on the dissolution of calcium silicate hydrate gels.

The use of cement based materials will be widespread in the long-term management of radioactive materials in the United Kingdom. One of the applications could be the Nirex reference vault backfill (NRVB) as an engineered barrier within a deep geological repository. NRVB confers alkaline conditions, which would provide a robust chemical barrier through the control of the solubility of some key radionuclides, enhanced sorption and minimised corrosion of steel containers. An understanding of the dissolution of C-S-H gels in cement under the appropriate conditions (e.g., saline groundwaters) is necessary to demonstrate the expected evolution of the chemistry over time and to provide sufficient cement to buffer the porewater conditions for the required time. A programme of experimental work has been undertaken to investigate C-S-H gel dissolution behaviour in sodium chloride solutions and the effect of calcium/silicon ratio (C/S), temperature and cation type on this behaviour. Reductions in calcium concentration and pH values were observed with samples equilibrated at 45 degrees C compared to those prepared at 25 degrees C. The effect of salt cation type on salt-concentration dependence of the dissolution of C-S-H gels was investigated by the addition of lithium or potassium chloride in place of sodium chloride for gels with a C/S of 1.0 and 1.8. With a C/S of 1.0, similar increases in dissolved calcium concentration with increasing ionic strength were recorded for the different salts. However, at a C/S of 1.8, anomalously high calcium concentrations were observed in the presence of lithium.

Calcium Compounds↗

Treatment of chronic transfusion-dependent gastric antral vascular ectasia (watermelon stomach) with thalidomide.

Gastric antral vascular ectasia (GAVE) is a rare condition causing chronic GI blood loss that often proves difficult to treat. Many patients require repeated transfusions despite best efforts made with endoscopic and pharmacological therapies. We attempted to manage a patient with endoscopic resistant GAVE with Thalidomide. Within 3 months the patient became transfusion independent and has maintained an adequate haemoglobin for 9 months on the Thalidomide therapy.

Anemia, Refractory↗

Inherited association of breast and colorectal cancer: limited role of CHEK2 compared with high-penetrance genes.

We assessed the association between breast cancer (BC) and colorectal cancer (CRC) from referral pattern to the Regional Genetics Service including molecular analysis. Hospital computer records and/or department referral books were used to identify cases referred to the Regional Genetic Service during a 16-year period (1990-2005 inclusive). All files were reviewed along with associated demographic data, risk assessments, referral details and results from mutation testing. Families were assessed for hereditary breast and colorectal cancer (HBCC) criteria, and all families with eligible individuals were tested for the 1100delC mutation in CHEK2. A total of 8,612 families were identified. One hundred and sixteen of 1,631 (7.5%) families with a primary referral for CRC fulfilled the criteria for HBCC, whereas only 68/6981 (1%) BC referrals fulfilled these criteria. Blood samples were obtained from 113 individuals from 83/184 families. Only 1/113 (1%) has screened positive for the CHEK2 mutation, whereas 14 (17%) families segregate BRCA1/2 mutations and at least 7 (8.5%) carry MLH1/MSH2 mutations. HBCC syndrome, if it exists as a separate entity, is not likely to be due to CHEK2 mutations. Many families are explicable by existing high-penetrance genes, and further work is necessary to elucidate whether the remainder is due to chance or as yet undiscovered genes.

Base Sequence↗

Search for coherent charged pion production in neutrino-carbon interactions.

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.

Journal Article↗

Cardiovascular responses of three salmonid species affected with amoebic gill disease (AGD).

The cardiovascular effects of amoebic gill disease (AGD) were investigated immediately following surgery in three salmonid species; Atlantic salmon (Salmo salar L.), brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss Walbaum). Fish, both naïve (control) and infected (AGD-affected) of each species, were fitted with dorsal aorta catheters and cardiac flow probes. Cardiac output and dorsal aortic pressures were then continuously measured over a 6-h period following surgery. Results showed that Atlantic salmon, brown trout and rainbow trout displayed similar dorsal aortic pressure, cardiac output, and systemic vascular resistance (mean dorsal aotic pressure divided by cardiac output) values. However, the only significant differences relating to disease status i.e. infected or control, were found in Atlantic salmon. Although no significant differences were seen in dorsal aortic pressure values, AGD-affected salmon displayed significantly elevated systemic vascular resistance at 4 and 6 h post surgery. Cardiac output was also approximately 35% lower in AGD-affected salmon compared to the non-affected control counterparts. These results comparatively examine cardiac function in response to AGD across three salmonid species and highlight species-specific cardiovascular responses that occur in association with disease. It is suggested that the apparent cardiac dysfunction seen in AGD-affected Atlantic salmon could, under stressful conditions, become exacerbated. Cardiac failure is therefore suggested to be a possible physiological mechanism by which AGD causes or contributes to mortality in Atlantic salmon.

Amebiasis↗

Evidence for muon neutrino oscillation in an accelerator-based experiment.

We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).

Journal Article↗

PVN galanin increases fat storage and promotes obesity by causing muscle to utilize carbohydrate more than fat.

To understand the function of the feeding-stimulatory peptide, galanin (GAL), in eating and body weight regulation, the present experiments tested the effects of both acute and chronic injections of this peptide into the paraventricular nucleus (PVN) of rats. With food absent during the test, acute injection of GAL (300 pmol/0.3 microl) significantly increased phosphofructokinase activity in muscle, suggesting enhanced capacity to metabolize carbohydrate, and reduced circulating glucose levels. It also decreased beta-hydroxyacyl-CoA dehydrogenase activity in muscle, indicating reduced fat oxidation, while increasing circulating non-esterified fatty acids (NEFA) and lipoprotein lipase activity in adipose tissue (aLPL). Chronic PVN injections of GAL (300 pmol/0.3 microl/injection) versus saline over 7-10 days significantly stimulated daily caloric intake and increased the weight of four dissected fat depots by 30-40%. These effects, accompanied by elevated levels of leptin, triglycerides, NEFA and aLPL activity, were evident only in rats on a diet with at least 35% fat. Thus, by favoring carbohydrate over fat metabolism in muscle and reversing hyperglycemia, PVN GAL may have a function in counteracting the metabolic disturbances induced by a high-fat diet. As a consequence of these actions, GAL can promote the partitioning of lipids away from oxidation in muscle towards storage in adipose tissue.

3-Hydroxyacyl CoA Dehydrogenases↗

Cerebrospinal fluid and serum concentrations of beta-trace protein during pregnancy.

We conducted a prospective observational study among a cohort of 40 term parturients undergoing spinal anaesthesia for elective Caesarean section, to determine the concentration of beta-trace protein in cerebrospinal fluid (CSF) and serum. Serum and CSF samples, taken at the time of dural puncture, were assayed by nephelometry. The mean serum beta-trace protein concentration was 0.39 mg.l(-1) and the mean CSF concentration was 27.9 mg.l(-1), giving a mean ratio of CSF to serum concentration of 76. This ratio is higher than that published for non-pregnant females and for males because of both a higher mean CSF and a lower mean serum beta-trace protein concentration. The concentration correlated positively with both serum creatinine and gestational age. If these concentrations are used to estimate the normal range, we propose that the nephelometric measurement of beta-trace protein might prove a useful diagnostic test for cerebrospinal fluid-cutaneous fistula in parturients.

Adult↗

Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.

AIMS: Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks' treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes. METHODS: A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication. RESULTS: Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference. CONCLUSIONS: In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

Adolescent↗

Effect of season of application on the adhesion, retention and recontamination of herbage by potentially toxic metals and sewage sludge.

Grassland in the United Kingdom can accept sewage sludge when, as a result of cropping restrictions, arable land cannot. However, one of the uncertainties associated with the application of sewage sludge to grassland is the potential exposure of the grazing ruminant to sewage sludge particulates adhered to the grass or deposited on the soil surface. The implications of elevated levels of sludge particulates and associated potentially toxic metals (PTMs) are the potential accumulation of PTMs into edible tissues of the grazing animal. Two experiments were performed to investigate the effect of season of application on the adhesion, retention and recontamination of herbage by sewage sludge and PTMs. In each experiment, three treatments were installed, an untreated control, application of sludge in the autumn and application of sludge in the spring. Sewage sludge particulates and PTMs were eluted sequentially 21 days after the application of sludge using water and detergent and the residual (tissue) concentrations were monitored. Total concentrations in each fraction and adhesion indices were calculated. Soil samples taken from the sward treatments after each application showed no elevated concentrations of PTMs or concentrations that approached the maximum concentrations allowed for soils amended with sewage sludge. The amounts of sludge adhered to herbage ranged from 114 to 360 g sludge DM/kg herbage DM. There was evidence of preferential retention of PTMs to herbage. However, during the 21-day no grazing period there was a general decline in concentration of all PTMs. Copper was retained on the herbage for greater periods of time compared to Zn, CD, Pb and Fe (P < 0.01). The proportion of Pb recovered from the water phase increased during the 21-day no grazing period in comparison to Cu, Zn and Fe (P < 0.001). It is concluded that the concentrations of PTMs adhered and integral to herbage as a result of surface application of sewage sludge are likely to fall to acceptable levels in well-managed permanent grassland.

Adsorption↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗