Biomedical subjects

G Lewis

Publications and source records attributed to G Lewis.

At least 91 records · Page 5Linked to original sources

PubMed2000

Relative influence of composition and viscosity of acrylic bone cement on its apparent fracture toughness.

The composition and viscosity of an acrylic bone cement have both been identified in the literature as being parameters that affect the mechanical properties of the material and, by extension, the in vivo longevity of cemented arthroplasties. The objective of the present study was to determine the relative influence of these parameters on a key cement mechanical property; namely, its fracture toughness. Two sets of cements were selected purposefully to allow the study objective to be achieved. Thus, one set comprised two cements with very similar compositions but very different viscosities (Cemex RX, a medium-viscosity brand, and Cemex Isoplastic, a high-viscosity brand) while the other set comprised two cements with similar viscosities but with many differences in composition (Cemex Isoplastic and CMW 1). Values of the fracture toughness (as determined using chevron-notched short rod specimens) [K(ISR)] obtained for Cemex RX and Cemex Isoplastic were 1.83 +/- 0.12 and 1.85 +/- 0.12 MPa square root(m), respectively, with the difference not being statistically significant. The K(ISR) values obtained for Cemex Isoplastic and CMW 1 were 1.85 +/- 0.12 and 1.64 +/- 0.18 MPa square root(m), respectively, with the difference being statistically significant. Thus, the influence of cement composition on its K(ISR) is more marked relative to the influence of cement viscosity. Explanations of this finding are offered, together with comments on the implications of the results for the in vivo longevity of cemented arthroplasties.

Acrylic Resins↗

PubMed2000

Hydroxyapatite-coated bioalloy surfaces: current status and future challenges.

The present review contains salient features of the most widely used methods for depositing hydroxyapatite (HA) coatings on bioalloy substrates. These methods range from the ubiquitous plasma spraying in air to the recently introduced ion beam enhanced deposition technique. Special attention is paid to the residual stress in the coating that arises from various sources and whose magnitude impacts the adhesion of the coating to the substrate and, hence, the efficacy of the coated part (see, for example, the in vivo performance of HA-coated orthopaedic and dental implants). Thus, the plethora of methods for estimating residual stresses in HA-coated systems are critically examined. The review concludes with a detailed presentation of ten areas for future research work.

Alloys↗

PubMed1999

Aftercare and clinical characteristics of people with mental illness who commit suicide: a case-control study.

BACKGROUND: Suicide prevention is now a health priority in many countries. In the UK, there are specific targets for reducing the suicide rate in the general population and in people with mental illness. However, there is almost no evidence for the effectiveness of health services in reducing suicide, and little evidence linking suicide to any aspect of health-service care. METHOD: We conducted a case-control study of people who committed suicide after discharge from psychiatric inpatient care. Cases were a 30-month sample of 149 people who had received an inquest verdict of suicide or open verdict in Greater Manchester, and who had a history of psychiatric admission in the 5 years before death. Controls were surviving psychiatric patients individually matched for age, sex, diagnosis, and date of last admission. Cases and controls were compared on aspects of psychiatric care, and on clinical and social variables, information being obtained from case notes. FINDINGS: Those who took their own lives were more likely to have had their care reduced (odds ratio 3.7 [95% CI 1.8-7.6]) at the final appointment in the community before death. Suicide was also associated with a history of self-harm (3.1 [1.7-5.7]), suicidal thoughts during aftercare (1.9 [1.0-3.5]) and the most recent admission as the first illness (2.0 [1.1-3.6]). The associations reported above took account of a number of confounding factors, including the predictable risk of suicide judged from case notes. Only 34% of suicides had an identifiable key worker, the essence of the Care Programme Approach. This frequency was no higher than that for controls, reflecting the difficulty of identifying those likely to commit suicide. INTERPRETATION: Reductions in care are strongly associated with suicide by people with mental illness, and may be contributory. The implication is that maintaining care beyond the point of clinical recovery is important in protecting high-risk individuals. Several clinical variables indicate high risk but greater risk is not generally addressed in health service provisions.

Adolescent↗

PubMed1999

X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution.

5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to form the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a homo-octameric structure with 422 symmetry in which each subunit adopts the TIM barrel fold with a 30-residue N-terminal arm. Pairs of monomers associate with their arms wrapped around each other. Four of these dimers interact, principally via their arm regions, to form octamers in which each active site is located on the surface. The active site contains two lysine residues (195 and 247), one of which (Lys 247) forms a Schiff base link with the bound substrate analogue, levulinic acid. Of the two substrate binding sites (referred to as A and P), our analysis defines the residues forming the P-site, which is where the first ALA molecule to associate with the enzyme binds. The carboxyl group of the levulinic acid moiety forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In proximity to the levulinic acid is a zinc binding site formed by three cysteines (Cys 120, 122, and 130) and a solvent molecule. We infer that the second substrate binding site (or A-site) is located between the triple-cysteine zinc site and the bound levulinic acid moiety. Two invariant arginine residues in a loop covering the active site (Arg 205 and Arg 216) appear to be appropriately placed to bind the carboxylate of the A-site substrate. Another metal binding site, close to the active site flap, in which a putative zinc ion is coordinated by a carboxyl and five solvent molecules may account for the activating properties of magnesium ions.

Binding Sites↗

PubMed1999

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers.

Previous studies have demonstrated a synergistic interaction between rhuMAb HER2 and the cytotoxic drug cisplatin in human breast and ovarian cancer cells. To define the nature of the interaction between rhuMAb HER2 and other classes of cytotoxic drugs, we applied multiple drug effect/combination index (CI) isobologram analysis to a variety of chemotherapeutic drug/rhuMAb HER2 combinations in vitro. Synergistic interactions at clinically relevant drug concentrations were observed for rhuMAb HER2 in combination with cisplatin (CI=0.48, P=0.003), thiotepa (CI=0.67, P=0.0008), and etoposide (CI=0.54, P=0.0003). Additive cytotoxic effects were observed with rhuMAb HER2 plus doxorubicin (CI=1.16, P=0.13), paclitaxel (CI=0.91, P=0.21), methotrexate (CI=1.15, P=0.28), and vinblastine (CI=1.09, P=0.26). One drug, 5-fluorouracil, was found to be antagonistic with rhuMAb HER2 in vitro (CI=2.87, P=0.0001). In vivo drug/rhuMAb HER2 studies were conducted with HER-2/neu-transfected, MCF7 human breast cancer xenografts in athymic mice. Combinations of rhuMAb HER2 plus cyclophosphamide, doxorubicin, paclitaxel, methotrexate, etoposide, and vinblastine in vivo resulted in a significant reduction in xenograft volume compared to chemotherapy alone (P<0.05). Xenografts treated with rhuMAb HER2 plus 5-fluorouracil were not significantly different from 5-fluorouracil alone controls consistent with the subadditive effects observed with this combination in vitro. The synergistic interaction of rhuMAb HER2 with alkylating agents, platinum analogs and topoisomerase II inhibitors, as well as the additive interaction with taxanes, anthracyclines and some antimetabolites in HER-2/neu-overexpressing breast cancer cells demonstrates that these are rational combinations to test in human clinical trials.

Adenocarcinoma↗

PubMed1999

Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care.

OBJECTIVES: To examine the effect of patients' causal attributions of common somatic symptoms on recognition by general practitioners of cases of depression and anxiety and to test the hypothesis that normalising attributions make recognition less likely. DESIGN: Cross sectional survey. SETTING: One general practice of eight doctors in Bristol. SUBJECTS: 305 general practice attenders. MAIN OUTCOME MEASURE: The rate of detection by general practitioners of cases of depression and anxiety as defined by the general health questionnaire. RESULTS: Consecutive attenders completed the general health questionnaire and the symptom interpretation questionnaire, which scores style of symptom attribution along the dimensions of psychologising, somatising, and normalising. General practitioners detected depression or anxiety in 56 (36%; 95% confidence interval 28% to 44%) of the 157 patients who scored highly on the general health questionnaire. Subjects with a normalising attributional style were less likely to be detected as cases; doctors did not make any psychological diagnosis in 46 (85%; 73% to 93%) of 54 patients who had high questionnaire and high normalising scores. Those with a psychologising style were more likely to be detected; doctors did not detect 21 (38%; 25% to 52%) of 55 patients who had high questionnaire and high psychologising scores. The somatisation scale was not associated with low detection rates. This pattern of results persisted after adjustment for age, sex, general health questionnaire score, and general practitioner. CONCLUSIONS: Normalising attributions minimise symptoms and are non-pathological in character. The normalising attributional style is predominant in general practice attenders and is an important cause of low rates of detection of depression and anxiety.

Adolescent↗

PubMed1999

Effect of mixing method and storage temperature of cement constituents on the fatigue and porosity of acrylic bone cement.

The influence of the storage temperature of the cement constituents prior to mixing (21 vs. 4 degrees C) and the mixing method (hand mixing vs. vacuum mixing) on the uniaxial tension-compression fatigue performance and porosity of Palacos R acrylic bone cement was studied. The fatigue results were analyzed using the three-parameter Weibull equation. The fatigue performance was expressed as an index I, which was defined as the product of the Weibull characteristic fatigue life and the square root of the Weibull slope. Statistical analyses of these results show that although the mixing method (for a given storage temperature) exerts a significant influence on the fatigue performance and areal porosity, the effect of storage temperature (for a given mixing method) on either of these parameters is not significant.

Biocompatible Materials↗

PubMed1999

"You don't give me flowers anymore": an analysis of gift-giving to medical and psychiatric inpatients.

BACKGROUND: If someone is admitted to hospital, it is customary for them to receive gifts from their friends and relatives. To assess the degree to which the mentally ill receive this type of support, this study set out to assess the level of gift-giving to the mentally ill compared with the physically ill during hospital admissions. METHOD: Subjects were 33 psychiatric and 23 medical female inpatients. Assessment was with a short interview on the subject of gifts received. Confounders were controlled for, in particular the number of family members who knew of the admission. RESULTS: Medical patients received significantly more flowers: odds ratio 8.8 (95% confidence interval 1.6-64.2, P = 0.004); get-well-soon cards: OR 5.7 (95% CI 1.4-25.3, P = 0.006) and other gifts: OR 5.7 (95% CI 1.4-23.6, P = 0.004). Adjustment for the potential confounders did not significantly affect the associations. CONCLUSIONS: The results suggested that during hospital admissions, the behaviour of relatives and friends of mentally ill patients is rejecting. The authors suggest that more education for relatives may help to improve this picture.

Adult↗

PubMed1999

Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: the value of oxygen supplementation.

PURPOSE: To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions. METHODS: Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase. RESULTS: Results from the two animals kept in normoxia after retinal detachment confirmed previous reports that detachment caused the proliferation of Muller cells, the hypertrophy of Muller cell processes, and the disruption of glutamate recycling by Muller cells. Oxygen supplementation during detachment reduced Muller cell proliferation and hypertrophy and reduced the abnormalities in the distributions of glutamate, GluR-2, and glutamine synthetase. CONCLUSIONS: Oxygen supplementation reduced the reaction of retinal Muller cells to retinal detachment, limiting their proliferation and helping to maintain their normal structure and function. In the clinical setting, oxygen supplementation between diagnosis and reattachment surgery may reduce the incidence and severity of glial-based complications, such as proliferative vitreoretinopathy.

Animals↗

PubMed1999

Limiting photoreceptor death and deconstruction during experimental retinal detachment: the value of oxygen supplementation.

PURPOSE: To assess the role of hypoxia in causing the death and deconstruction of photoreceptors in detached retinas and the effectiveness of supplemental oxygen in limiting such damage. METHODS: Retinal detachment was induced surgically in the right eye of each of 10 cats. The cats were allowed to survive surgery for 3 days. Two were kept for these 3 days in normoxia (room air, 21% oxygen) and eight in hyperoxia (70% oxygen). The retinas were examined for cell death by use of labels for normal and fragmenting DNA, with antibodies and a cone sheath-specific lectin to demonstrate the status of their inner and outer segments, the synaptic structures of the outer plexiform layer, and the distribution of basic fibroblast growth factor (bFGF) and with in situ hybridization to demonstrate bFGF mRNA. RESULTS: Retinal detachment without oxygen supplementation caused the death of some photoreceptors; the loss of cytochrome oxidase from the inner segments and the collapse of the outer segments of surviving photoreceptors; the loss of synaptophysin profiles from the outer plexiform layer; and the loss of bFGF protein from retinal neurons and neuroglia but not from retinal vessels. Oxygen supplementation (hyperoxia) during detachment mitigated all these changes, reducing photoreceptor death, maintaining the specialized structures of surviving photoreceptors, and stabilizing the bFGF within the retina. CONCLUSIONS: In experimental retinal detachment, hypoxia caused by the separation of outer retina from its normal source of nutrients is a factor in inducing the death and deconstruction of photoreceptors as well as in the loss of bFGF from the detached retina. Hyperoxia offered to human patients between diagnosis of retinal detachment and surgery may enhance the function of the reattached retina.

Animals↗

PubMed1999

Apparent fracture toughness of acrylic bone cement: effect of test specimen configuration and sterilization method.

The plane strain fracture toughness of Palacos R bone cement was determined using linear elastic fracture mechanics (LEFM) principles and three different test specimen configurations: single edge notched three-point (SENB), rectangular compact tension (RCT), and chevron notched short rod (CNSR). Another aspect of the study was an investigation of the effect of three methods used to sterilize the powder constituents of the cement-none, gamma irradiation and ethylene oxide--on the fracture toughness of the fully polymerized material. A detailed justification is provided for using LEFM. The fracture toughness results obtained using the CNSR specimens were, on average, 14 and 16% higher than those obtained using the SENB and RCT types, respectively. These differences are accounted for in terms of differences in four aspects of these specimen configuration (namely, residual stress effects, loading rate, material inhomogeneity, and the nature of the test). For a given specimen configuration, gamma irradiation produced a statistically significant decrease in fracture toughness which, it is suggested, is due to the concomitant depreciation in molecular weight. For a given cement type, there is no statistically significant difference in fracture toughness results obtained using SENB and RCT specimens. It is thus suggested that either of these configurations can be used to determine the fracture toughness of acrylic bone cement.

Bone Cements↗

PubMed1999

Harmonising and competing for medicines regulation: how healthy are the European Union's systems of drug approval?

Europeanised procedures of marketing authorisation for medicines are becoming increasingly important within EU Member States relative to national licensing systems. Since 1 January 1998 parallel national applications for drug approvals in EU Member States have disappeared and it is only possible to market a new drug in more than one Member State via Europeanised procedures. Yet the implications of these Euro-procedures for public health remain little researched or debated. This paper discusses the health and safety implications of three key features of such Europeanisation, namely, the harmonisation of drug safety standards, the competition between the national regulatory agencies of Member States for application fees from industry and the industrial capture of regulators within the regulatory process. Drawing on 42 interviews in Brussels, Germany, Sweden, the Netherlands and the UK, the perspectives of European regulators, industrial scientists and regulatory affairs managers on these matters are analysed. While most industry sources believe that the new Euro-procedures will not harm public health, at least half of the regulators were concerned that European harmonisation of safety standards and competition between national agencies to accelerate approval times in order to attract industry fees pose a threat to public health and safety. National regulatory agencies find themselves in an internal EU market competing for regulatory fees from industry. This marketisation of regulation puts pressure on regulators to 'sell themselves' as the fastest in reviewing and approving drugs. Swedish regulators displayed the greatest anxieties about these matters. Unfortunately, we found it impossible to verify these regulators' worries or industry's optimism because of the secrecy that attends these Euro-procedures. Thus, a situation obtains in which a significant number of regulators are warning that the EU medicines licensing systems, which are being put in place, might well compromise safety, yet these systems are deficient in their capacity to accommodate independent scrutiny, upon which informed policy changes could be based.

Consumer Product Safety↗

PubMed1999

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Age Factors↗

PubMed1999

Suicide, religion, and socioeconomic conditions. An ecological study in 26 countries, 1990.

STUDY OBJECTIVE: Relative risks are frequently assumed to be stable across populations but this may not apply in psychiatric epidemiology where sociocultural context may modify them. Such ecological effect modification will give curved associations between aggregated risk factor and outcome. This was examined in connection with the ecological association between suicide rates and an aggregate index of religiosity. DESIGN: Ecological study of associations between suicide rates and an index of religiosity, adjusted for socioeconomic variation. The effect of stratification of the study sample according to levels of religiosity, was examined. SETTING: 26 European and American countries. SUBJECTS: Interview data from 37,688 people aggregated by country. OUTCOME MEASURES: Age and sex specific (1986-1990) suicide rates. MAIN RESULT: Adjusted for socioeconomic variation, negative associations of male suicide rates with religiosity were apparent in the 13 least religious countries only (test for interaction F (1, 25) = 5.6; p = 0.026). Associations between religiosity and female suicide rates did not vary across countries. CONCLUSION: The bent ecological association was apparent only after adjustment for socioeconomic variation suggesting that, rather than confounding, ecological modification of individual level links between religion and male (but not female) suicide risk is the responsible mechanism. This concurs with micro-level findings suggesting that suicide acceptance depends not only on personal but also on contextual levels of religious belief, and that men are more sensitive to this phenomenon than women. In psychiatric epidemiology, relative risks vary with the exposure's prevalence. This has important implications for research and prevention.

Adolescent↗

PubMed1999

Pragmatic randomised controlled trials in psychiatry.

BACKGROUND: Randomised controlled trials (RCTs) are the most important method of evaluating new treatments and treatment policies. Despite this, there are relatively few large pragmatic RCTs in psychiatry. AIMS: To explore the main advantages of large pragmatic RCTs and the obstacles to performing them in psychiatry. METHOD: A narrative review of literature on pragmatic RCTs with examples drawn from psychiatry and other medical specialities. RESULTS: Obstacles to performing pragmatic RCTs in psychiatry include the complexity of psychiatric interventions, the complexity of outcomes used in psychiatry and the difficulties of blinding subjects and investigators to some psychiatric interventions. CONCLUSIONS: Researchers need to frame questions in a form that is relevant to clinicians and to convince clinicians to cooperate in simple large pragmatic trials.

Cluster Analysis↗

PubMed1999

Heritability of social cognitive skills in children and adolescents.

BACKGROUND: Social cognitive skills are those which enable understanding of social situations; they are relevant to a variety of psychiatric disorders including autism, schizophrenia and externalizing behaviour problems in children. AIMS: To examine the heritability of social cognitive skills. METHOD: Using a population-based sample of twins aged 5-17, the genetic and environmental influences on social cognitive skills were examined. RESULTS: Male scores were higher than female scores (P < 0.001), indicating poorer social cognition among males. A heritability of 0.68 (95% CI 0.43-0.78) was found, with shared environmental influences accounting for only 0.05 of the variance (95% CI 0.00-0.28). This could be removed from the model without worsening the fit. There were no significant differences in genetic effects between the genders, but age-related changes were found, with younger twins showing greater genetic influence on social cognition. CONCLUSIONS: Social cognition appears to be under considerable genetic influence in the population and shows significant male-female differences. No gender differences in genetic influences on the variance of scores were found, but the effects of age were significant.

Adolescent↗

PubMed1999

Biomechanics as a basis for management of intra-articular fractures of the calcaneus.

This article presents a critical examination of biomechanics studies in the literature that could shed light on or contribute to the development of methods of managing intra-articular calcaneal fractures. An appreciation and understanding of such studies is predicated on a sound knowledge of a number of germane topics: the anatomy of the normal calcaneus, the pathomechanics of the calcaneus, fracture-classification schemes, and fracture-management methods. The first part of this review presents overviews of these topics. The biomechanics studies are then reviewed in detail. The article concludes with a description of research areas that might close the gaps identified in these studies.

Biomechanical Phenomena↗

PubMed1999

Effect of two variables on the fatigue performance of acrylic bone cement: mixing method and viscosity.

The goal of the present work was to establish the relative influence of one exogenous variable versus one endogenous variable on the fully-reversed tension-compression fatigue performance of bone cement. The method used to mix the cement constituents was the exogenous variable, while the viscosity of the mixed cement dough was the endogenous variable. Two commercial cement formulations (Palacos R and Osteopal) and two cement mixing methods (hand mixing and vacuum mixing) were used. It was found that for a given mixing method, cement viscosity exerts a marginal influence on fatigue performance. On the other hand, for a given cement formulation, vacuum mixing led to a statistically significant improvement in fatigue performance. The present results demonstrate the superior influence of mixing method over cement viscosity.

Acrylates↗