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Biomedical subjects

E Ward

Publications and source records attributed to E Ward.

At least 19 recordsLinked to original sources
PubMed2006

In vitro study of foot kinematics using a dynamic walking cadaver model.

There is a dearth of information on navicular, cuboid, cuneiform and metatarsal kinematics during walking and our objective was to study the kinematic contributions these bones might make to foot function. A dynamic cadaver model of walking was used to apply forces to cadaver feet and mobilise them in a manner similar to in vivo. Kinematic data were recorded from 13 cadaver feet. Given limitations to the simulation, the data describe what the cadaver feet were capable of in response to the forces applied, rather than exactly how they performed in vivo. The talonavicular joint was more mobile than the calcaneocuboid joint. The range of motion between cuneiforms and navicular was similar to that between talus and navicular. Metatarsals four and five were more mobile relative to the cuboid than metatarsals one, two and three relative to the cuneiforms. This work has confirmed the complexity of rear, mid and forefoot kinematics. The data demonstrate the potential for often-ignored foot joints to contribute significantly to the overall kinematic function of the foot. Previous emphasis on the ankle and sub talar joints as the principal articulating components of the foot has neglected more distal articulations. The results also demonstrate the extent to which the rigid segment assumptions of previous foot kinematics research have over simplified the foot.

Biomechanical Phenomena↗
PubMed2005

High risk health behaviours among adult Jamaicans.

The purpose of this study was to assess the prevalence of high risk health behaviours among adult Jamaicans aged 15-49 years in 2000, and to compare the results with the 1993 survey. A nationally representative sample of 2013 persons aged 15-74 years was surveyed in 2000 using cluster sampling in the Jamaica Healthy Lifestyle Survey (Wilks et al, unpublished). Interviewer administered questionnaires and anthropometrical measurements were done. Data for a sub-sample of adults aged 15-49 years were analyzed The sub-sample included 1401 persons (473 men and 928 women). Significantly more men (18.6%) than women (4.3%) reported never having had a blood pressure check (p = 0.0001). Approximately one-third of the women reported that they had never had a Pap smear (36.0%) or a breast examination (31.2%). Current cigarette smoking was reported in 28.6% of men and 7.7% of women (OR 3.73 CI 2.71, 5.15), while 49.0% of men and 15.0% of women ever smoked marijuana (OR 3.28 CI 2.56, 4.20). Significantly more men (28.0%) than women (11.7%) reported ever having a sexually transmitted disease (OR 2.93 CI 2.16, 3.97); having more than one sexual partner in the past year (49.1% vs 11.4%, OR 4.31 CI 3.22, 5.76) and usually using a condom during sexual intercourse (55.3% vs 40.5%, OR 1.3 CI 1.11, 1.68). Between 1993 and 2000, significant trends include: more persons reported having a blood pressure check, a reduction in multiple sexual partners, increased condom use at last sex (women), reduced crack/cocaine use (males) and increased marijuana smoking. Although there were some significant positive lifestyle trends between 1993 and 2000, high risk behaviours remain common among Jamaican adults. Comprehensive health promotion programmes are needed to address these risk behaviours.

Adolescent↗
PubMed2003

Patient-practitioner agreement: does it matter?

BACKGROUND: Good communication is a crucial clinical skill. Previous research demonstrated better clinical outcomes when practitioners and patients agree about the nature of patients' core presenting complaints. We investigated the nature of this agreement and its impact on outcome among depressed primary care patients. METHOD: We compared presenting problem formulations completed by patients, GPs and therapists in a primary care randomized controlled trial of cognitive-behavioural therapy and non-directive counselling for depression. Participants compiled formulations from a list of 13 potential problems of self-completed questionnaires. Subjects scored at least 14 on the Beck Depression Inventory (BDI) at baseline. Outcome measure for this study included BDI at 4 and 12 months, failure to attend for therapy when referred, dropout from therapy and patient satisfaction. RESULTS: Among 464 trial patients, 395 received therapy. Patient baseline problem formulations included significantly more items than GPs, who identified significantly more items than therapists. Agreement levels varied according to a range of patient and professional variables. While patients in complete agreement with their therapists about their main problem after assessment had lower average BDI scores at 12 months (9.7 v. 12.8, P=0.03); we found no other significant associations between the extent of agreement and clinical outcome. There were significant (but relatively weak) associations between agreement and aspects of patient satisfaction. CONCLUSION: Our results suggest that detailed mutual understanding of the presenting complaints may be less important than agreement that the core problem is psychological, and that referral for psychological therapy is appropriate.

Adolescent↗
PubMed2003

Oral glutamine in paediatric oncology patients: a dose finding study.

OBJECTIVE: The purpose of this study was to determine the most appropriate dose of oral glutamine to use in a further clinical study in paediatric oncology patients. DESIGN: This was a phase I, pharmokinetic study. SETTING: The study was carried out at The Yorkshire Regional Centre for Paediatric Oncology and Haematology, St James's University Hospital, Leeds, UK. SUBJECTS: Thirteen patients undergoing treatment for paediatric malignancy participated in this study. All 13 completed the study. INTERVENTIONS: The most appropriate dose was determined by patient acceptability and by plasma glutamine and ammonia levels measured at timed intervals after ingestion of a single glutamine dose. RESULTS: Doses of 0.35, 0.5 and 0.65 g/kg were well tolerated with no untoward plasma glutamine and ammonia levels. One patient was recruited to a higher dose of 0.75 g/kg, but the plasma glutamine and ammonia levels peaked at 2601 and 155 micro mol/l, respectively. The ammonia level was greater than the acceptable upper limit. It was difficult to disperse the glutamine adequately at this dose, resulting in the suspension being found to be unpalatable and therefore no further patients were recruited at this dose. CONCLUSION: It was concluded that 0.65 g/kg is a safe dose of glutamine to use in a clinical study in paediatric oncology patients.

Administration, Oral↗
PubMed2001

Intolerance to an extensively hydrolysed formula mistaken for postoperative diarrhoea in a child with neuroblastoma.

BACKGROUND: Persistent diarrhoea has recently been reported as a common problem following surgical resection for advanced abdominal neuroblastoma. CASE STUDY: A 10-month-old child, who had previously had no nutritional problems whilst undergoing chemotherapy treatment for a stage IV neuroblastoma, developed severe diarrhoea following tumour resection. He required nutritional support and was commenced on a continuous overnight nasogastric feed of a non-milk protein hydrolysate feed (MCT Pepdite 0-2, S.H.S. International Ltd, UK) His diarrhoea persisted and it was assumed that this was a postoperative problem which in time would regress. Two months later the child was admitted with a rectal prolapse, and a colonoscopy and biopsy suggested allergic protocolitis. The diarrhoea resolved rapidly on stopping the feed. CONCLUSION: Although he was never re-challenged with the non-milk protein hydrolysate, it appears that he had a rare intolerance to an extensively hydrolysed protein formula which was masked by the assumption that his diarrhoea was a postoperative problem.

Abdominal Neoplasms↗
PubMed2001

Gene targeting in Arabidopsis.

Precise modification by gene targeting (GT) provides an important tool for studies of gene function in vivo. Although routine with many organisms, only isolated examples of GT events have been reported for flowering plants. These were at low frequencies precluding reliable estimation of targeting efficiency and evaluation of GT mechanisms. Here we present an unambiguous and straightforward system for detection of GT events in Arabidopsis using an endogenous nuclear gene encoding protoporphyrinogen oxidase (PPO), involved in chlorophyll and heme syntheses. Inhibition of PPO by the herbicide Butafenacil results in rapid plant death. However, the combination of two particular mutations renders PPO highly resistant to Butafenacil. We exploited this feature for selection of GT events by introducing the mutations into the PPO gene by homologous recombination. We have estimated the basal GT frequency to be 2.4 x 10(-3). Approximately one-third of events were true GT (TGT) leading to the anticipated modification of the chromosomal PPO copy. The remaining events could be classified as ectopic GT (EGT) arising by modification of vector DNA by the chromosomal template and its random integration into the Arabidopsis genome. Thus the TGT frequency in our experimental setup is 0.72 x 10(-3). In view of the high efficiency of Arabidopsis transformation, GT experiments of a reasonable size followed by a PCR screen for GT events should also allow for modification of non-selectable targets. Moreover, the system presented here should contribute significantly to future improvement of GT technology in plants.

Arabidopsis↗
PubMed2001

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Carcinogens↗
PubMed2001

Methods for integrated air sampling and dna analysis for detection of airborne fungal spores.

Integrated air sampling and PCR-based methods for detecting airborne fungal spores, using Penicillium roqueforti as a model fungus, are described. P. roqueforti spores were collected directly into Eppendorf tubes using a miniature cyclone-type air sampler. They were then suspended in 0.1% Nonidet P-40, and counted using microscopy. Serial dilutions of the spores were made. Three methods were used to produce DNA for PCR tests: adding untreated spores to PCRs, disrupting spores (fracturing of spore walls to release the contents) using Ballotini beads, and disrupting spores followed by DNA purification. Three P. roqueforti-specific assays were tested: single-step PCR, nested PCR, and PCR followed by Southern blotting and probing. Disrupting the spores was found to be essential for achieving maximum sensitivity of the assay. Adding untreated spores to the PCR did allow the detection of P. roqueforti, but this was never achieved when fewer than 1,000 spores were added to the PCR. By disrupting the spores, with or without subsequent DNA purification, it was possible to detect DNA from a single spore. When known quantities of P. roqueforti spores were added to air samples consisting of high concentrations of unidentified fungal spores, pollen, and dust, detection sensitivity was reduced. P. roqueforti DNA could not be detected using untreated or disrupted spore suspensions added to the PCRs. However, using purified DNA, it was possible to detect 10 P. roqueforti spores in a background of 4,500 other spores. For all DNA extraction methods, nested PCR was more sensitive than single-step PCR or PCR followed by Southern blotting.

Air Microbiology↗
PubMed2001

Pharmacokinetic/pharmacodynamic study of ZD9331, a nonpolyglutamatable inhibitor of thymidylate synthase, in a murine model following two curative administration schedules.

ZD9331 is a nonpolyglutamatable antifolate inhibitor of thymidylate synthase currently in clinical development. This enzyme is crucial for DNA synthesis and catalyzes the reductive methylation of dUMP to form thymidylate, which is subsequently converted to dTTP. The pharmacokinetics of two curative antitumor doses of ZD9331 administered by either a single i.p. bolus injection (50 mg/kg) or by 24-h s.c. infusion (3 mg/kg) have been measured in a thymidine salvage-incompetent murine lymphoma model (L5178Y) using a sensitive and specific ELISA. To gain an understanding of the relationship between the pharmacokinetics of ZD9331 and antitumor activity perturbations in tumor, dTTP and dUMP concentrations were also determined. After bolus administration, ZD9331 was eliminated from plasma and tissues relatively rapidly, with terminal elimination (lambda(z) 0-24 h) of 4-6 h. Liver concentrations were 8-fold higher than those measured in the plasma. Kidney and lymphoma drug concentrations were similar to those of plasma, although there was evidence of a slower overall elimination of drug at later time points. Steady-state concentrations of ZD9331 were obtained 4-5 h after the start of the 24 h s.c. infusion. At the end of infusion, elimination rates were similar for plasma and tissues (approximately 3.5 h) but appeared to be slower in the tumor at later time points. Liver concentrations were approximately 4-fold higher, and kidney and tumor concentrations were similar to those in the circulation. Depletion of dTTP and elevation in dUMP in the tumor were consistent with inhibition of thymidylate synthase after both administration schedules, although the time for which dTTP was decreased was longer (approximately 24 h) for the infusional route than for the bolus injection (<16 h). The results suggest that antitumor activity is dependent on attaining adequate drug concentrations to affect dTTP pools as well as on the duration of effective drug levels.

Animals↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I: clinical effectiveness.

OBJECTIVE: To compare the clinical effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients. DESIGN: Prospective, controlled trial with randomised and patient preference allocation arms. SETTING: General practices in London and greater Manchester. PARTICIPANTS: 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion. INTERVENTIONS: Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists. MAIN OUTCOME MEASURES: Beck depression inventory scores, other psychiatric symptoms, social functioning, and satisfaction with treatment measured at baseline and at 4 and 12 months. RESULTS: 197 patients were randomly assigned to treatment, 137 chose their treatment, and 130 were randomised only between the two psychological therapies. All groups improved significantly over time. At four months, patients randomised to non-directive counselling or cognitive-behaviour therapy improved more in terms of the Beck depression inventory (mean (SD) scores 12.9 (9.3) and 14.3 (10.8) respectively) than those randomised to usual general practitioner care (18.3 (12.4)). However, there was no significant difference between the two therapies. There were no significant differences between the three treatment groups at 12 months (Beck depression scores 11.8 (9.6), 11.4 (10.8), and 12.1 (10.3) for non-directive counselling, cognitive-behaviour therapy, and general practitioner care). CONCLUSIONS: Psychological therapy was a more effective treatment for depression than usual general practitioner care in the short term, but after one year there was no difference in outcome.

Adult↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. II: cost effectiveness.

OBJECTIVE: To compare the cost effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients. DESIGN: Prospective, controlled trial with randomised and patient preference allocation arms. SETTING: General practices in London and greater Manchester. PARTICIPANTS: 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion. INTERVENTIONS: Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists. MAIN OUTCOME MEASURES: Beck depression inventory scores, EuroQol measure of health related quality of life, direct treatment and non-treatment costs, and cost of lost production. RESULTS: 197 patients were randomly assigned to treatment, 137 chose their treatment, and 130 were randomised only between the two psychological therapies. At four months, both non-directive counselling and cognitive-behaviour therapy reduced depressive symptoms to a significantly greater extent than usual general practitioner care. There was no significant difference in outcome between treatments at 12 months. There were no significant differences in direct costs, production losses, or societal costs between the three treatments at either four or 12 months. Sensitivity analyses did not suggest that the results depended on particular assumptions in the statistical analysis. CONCLUSIONS: Within the constraints of available power, the data suggest that both brief psychological therapies may be significantly more cost effective than usual care in the short term, as benefit was gained with no significant difference in cost. There are no significant differences between treatments in either outcomes or costs at 12 months.

Adult↗
PubMed2000

Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana.

Catalyzing the first step in the de novo synthesis of adenylmonophosphate, adenylosuccinate synthetase (AdSS) is a known target for herbicides and antibiotics. We have purified and crystallized recombinant AdSS from Arabidopsis thaliana and Tritium aestivum, expressed in Escherichia coli. The structures of A. thaliana and T. aestivum AdSS in complex with GDP were solved at 2.9 A and 3.0 A resolution, respectively. Comparison with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein. The longer N terminus in the plant sequences is at the same place as the longer C terminus of the E. coli sequence in the 3D structure. The GDP-binding sites have one additional hydrogen-bonding partner, which is a plausible explanation for the lower K(m) value. Due to its special position, this partner may also enable GTP to initiate a conformational change, which was, in E. coli AdSS, exclusively activated by ligands at the IMP-binding site. The dimer interfaces show up to six hydrogen bonds and six salt-bridges more than in the E. coli structure, although the contact areas have approximately the same size.

Adenylosuccinate Synthase↗
PubMed2000

Binding of porcine sperm plasma membrane proteins to sheep, hamster and mouse oocyte plasma membrane.

Four porcine sperm plasma membrane proteins were previously identified as putative ligands for the oocyte plasma membrane. The present study examined the binding of these proteins and two additional porcine sperm membrane proteins to oocytes from sheep, mice and hamsters as a first step in assessing potential conservation of these putative sperm ligands across species and across mammalian orders. Plasma membrane vesicles were isolated from porcine sperm, solubilised, and the proteins separated by one-dimensional gel electrophoresis. The 7, 27, 39 and 62 kDa porcine sperm protein bands demonstrating predominant binding of the porcine oocyte plasma membrane on ligand blots, a 90 kDa protein band demonstrating minor binding, and a 97 kDa protein band that did not bind the oocyte plasma membrane probe were electroeluted. Proteins were biotinylated, and incubated with zona-free oocytes. Bound biotinylated protein was labelled with fluorescent avidin and the oocytes examined with a confocal microscope. The 7 kDa, 27 kDa and the 39 kDa proteins bound to the sheep oocytes but not to a majority of the hamster or mouse oocytes. The 62 kDa protein bound to sheep oocytes and mouse oocytes but not to a majority of the hamster oocytes. The 90 kDa protein bound to oocytes from all three species. The 97 kDa protein, which did not recognise the porcine oocyte probe on a Western ligand blot, did not bind to oocytes from any species and served as a negative control. These observations are consistent with significant conservation of molecule and function among species within the same mammalian order. Hence, one species may be a good model for other species from the same order. Only limited conservation of binding activity of porcine sperm plasma membrane proteins to rodent oocytes was observed, suggesting a greater divergence either in molecular structure or in function among species from different orders.

Animals↗
PubMed2000

Safety and immunogenicity of a paediatric presentation of an influenza vaccine.

BACKGROUND: Flu vaccination in otherwise healthy infants and young children is important to prevent severe disease, as well as to control epidemic spread of influenza infection. AIMS: To examine the safety and immunogenicity of a paediatric presentation of a purified, inactivated, triton split influenza vaccine. METHODS: Two doses of the vaccine, provided in prefilled syringes of 0.25 ml, were administered, one month apart, to 67 children under 3 years of age. RESULTS: Nine cases of immediate reaction to vaccination (macules/papules) were observed after the second injection only. During the study period, 9% of children experienced at least one delayed local reaction, and 28% of children presented at least one systemic reaction. Almost all reactions were mild and transient. Immunogenicity results surpassed the European Community recommendations for a 0.50 ml dose of vaccine in adults. CONCLUSION: This paediatric formulation of inactivated flu vaccine appears safe and immunogenic in children from 6 months to 3 years of age; the convenient presentation in a prefilled syringe of 0.25 ml volume will facilitate administration of the dose recommended for young children.

Antibodies, Viral↗
PubMed2000

Monoclonal antibodies.

Monoclonal antibodies are essential tools for many molecular immunology investigations. In particular, when used in combination with techniques such as epitope mapping and molecular modelling, monoclonal antibodies enable the antigenic profiling and visualisation of macromolecular surfaces. In addition, monoclonal antibodies have become key components in a vast array of clinical laboratory diagnostic tests. Their wide application in detecting and identifying serum analytes, cell markers, and pathogenic agents has largely arisen through the exquisite specificity of these unique reagents. Furthermore, the continuous culture of hybridoma cells that produce these antibodies offers the potential of an unlimited supply of reagent. In essence, when compared with the rather limited supply of polyclonal antibody reagents, the feature of a continuous supply enables the standardisation of both the reagent and the assay technique. Clearly, polyclonal and monoclonal antibodies have their advantages and disadvantages in terms of generation, cost, and overall applications. Ultimately, monoclonal antibodies are only produced when necessary because their production is time consuming and frustrating, although greatly rewarding (at least most of the time!). This is especially apparent when a monoclonal antibody can be applied successfully in a routine pathology laboratory or can aid in the clinical diagnosis and treatment of patients. In this article, the generation and application of monoclonal antibodies are demystified to enable greater understanding and hopefully formulate novel ideas for clinicians and scientists alike.

Antibodies, Monoclonal↗