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Biomedical subjects

D J Wood

Publications and source records attributed to D J Wood.

At least 19 recordsLinked to original sources

Polio vaccine: the first 50 years and beyond. Summary of the meeting and next steps.

A conference on "Polio vaccine: the first 50 years and beyond" was held in Toronto, Canada, June 2005. The purpose of the conference was to bring together regulators, manufacturers, academics and public health authorities to celebrate the accomplishments of the past 50 years, to consider the challenges of achieving and sustaining polio eradication and to review standardization and regulatory issues around existing and new polio vaccines. In the final session of the conference the following summary of the meeting was presented.

Disease Outbreaks↗

Indirect selective laser sintering of an apatite-mullite glass-ceramic for potential use in bone replacement applications.

The feasibility of using indirect selective laser sintering (SLS) to produce parts from glass-ceramic materials for bone replacement applications has been investigated. A castable glass based on the system SiO2 x Al2O3 x P2O5 x CaO x CaF2 that crystallizes to a glass-ceramic with apatite and mullite phases was produced, blended with an acrylic binder, and processed by SLS. Green parts with good structural integrity were produced using a wide range of processing conditions, allowing both monolayer and multilayer components to be constructed. Following SLS the parts were post-processed to remove the binder and to crystallize fully the material, evolving the apatite and mullite phases. The parts were heated to 1200 degrees C using a number of different time-temperature profiles, following which the processed material was analysed by differential thermal analysis, X-ray diffraction, and scanning electron microscopy, and tested for flexural strength. An increase in strength was achieved by infiltrating the brown parts with a resorbable phosphate glass, although this altered the crystal phases present in the material.

Aluminum Silicates↗

Iontophoresed segmental allografts in revision arthroplasty for infection.

Revision arthroplasty after infection can often be complicated by both extensive bone loss and a relatively high rate of re-infection. Using allograft to address the bone loss in such patients is controversial because of the perceived risk of bacterial infection from the use of avascular graft material. We describe 12 two-stage revisions for infection in which segmental allografts were loaded with antibiotics using iontophoresis, a technique using an electrical potential to drive ionised antibiotics into cortical bone. Iontophoresis produced high levels of antibiotic in the allograft, which eluted into the surrounding tissues. We postulate that this offers protection from infection in the high-risk peri-operative period. None of the 12 patients who had two-stage revision with iontophoresed allografts had further infection after a mean period of 47 months (14 to 78).

Aged↗

Iontophoresis of antibiotics into segmental allografts.

Iontophoresis is a novel technique which may be used to facilitate the movement of antibiotics into the substance of bone using an electrical potential applied externally. We have examined the rate of early infection in allografts following application of this technique in clinical practice. A total of 31 patients undergoing revision arthroplasty or surgery for limb salvage received 34 iontophoresed sequential allografts, of which 26 survived for a minimum of two years. The mean serum antibiotic levels after operation were low (gentamicin 0.37 mg/l (0.2 to 0.5); flucloxacillin 1 mg/l (0 to 1) and the levels in the drains were high (gentamicin 40 mg/l (2.5 to 131); flucloxacillin 17 mg/l (1 to 43). There were no early deep infections. Two late infections were presumed to be haemotogenous; 28 of the 34 allografts were retained. In 12 patients with pre-existing proven infection further infection has not occurred at a mean follow-up of 51 months (24 to 82).

Adolescent↗

Bone allograft non-union is related to excessive osteoclastic bone resorption: a sheep model study.

Using a sheep femoral allograft model we have investigated the cellular and molecular mechanisms associated with non-union of bone allografts. Histomorphometric analysis revealed that allograft non-unions featured both marked increases in osteoclast (OC) numbers and total eroded bone surface as compared to allografts which had undergone direct union. Three distinct cellular layers lying adjacent to the allograft bone surface were identified in all non-union cases. The outer or fibroblastic layer contained an abundance of fibroblasts and connective tissue. Circumscribing this layer was a band of synovial-like cells consisting mainly of large spindle-shaped mononuclear cells mixed with scattered round-shaped mononuclear cells. The third layer, which was directly juxtaposed to the allograft bone surface, consisted predominantly of multinuclear OCs which were positively identified by calcitonin receptor immunohistochemistry. Interestingly, in-situ hybridisation revealed that surrounding synovial-like cells in non-union allografts, expressed abundant gene transcripts for receptor activator NF-kappaB ligand (RANKL), a membrane bound factor critical for both the induction of OC activity and osteoclastogenesis. We propose that excessive bone resorption by host OCs contributes, at least partially, to the failure of bone allografts. The production of RANKL by synovial-like fibroblasts may be the driving force responsible for the elevated generation and activation of OCs. Based on such evidence novel therapeutic strategies for the treatment of non-union bone allografts using anti-bone resorbing agents may be devised.

Animals↗

Processing of an apatite-mullite glass-ceramic and an hydroxyapatite/phosphate glass composite by selective laser sintering.

The work presented details the results of an investigation into the feasibility of using Selective Laser Sintering (SLS) to directly produce customised bioceramic implants. The materials used were bioactive in nature and included a glass-ceramic and a combination of hydroxyapatite and phosphate glass. The glass-ceramic was selected from the range of apatite-mullite materials in the SiO2.Al2O3.CaO.CaF2.P2O5 series, due to their potentially suitable biological and mechanical properties. The hydroxyapatite and phosphate glass combination was chosen to allow an alternative production approach to be investigated. The viability of using both these materials with the SLS process was assessed and the process route and resulting material properties characterised using a variety of techniques including Differential Thermal Analysis (DTA), X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The results obtained indicate that it was possible to produce multiple layer components from both materials using the SLS process. The glass-ceramic materials could only be processed at very low scan speeds and powers, yielding relatively brittle components. It was though possible to produce parts from the hydroxyapatite and phosphate glass combination across a much wider range of parameters, producing parts which had a greater potential for possible implant production.

Aluminum Silicates↗

Fluorapatite-mullite glass sputter coated Ti6Al4V for biomedical applications.

A number of bioactive ceramics have been researched since the development of Bioglass in the 1970's. Fluorapatite mullite has been developed from the dental glass-ceramics used for more general hard tissue replacement. Being brittle in nature, glass-ceramics are currently used mainly as coatings. This paper shows that fluorapatite glass LG112 can be used as a sputtered glass coating on roughened surfaces of Ti6Al4V for possible future use for medical implants. An AFM was used to measure the roughness of the surface before and after coating to determine the change in the topography due to the coating process as this greatly affects cell attachment. The sputter coating partially filled in the artificially roughened surface, changing the prepared topography. Osteoblasts have been successfully grown on the surface of these coatings, showing biocompatibility with bone tissue and therefore potential use in hard tissue repair.

Alloys↗

Microleakage of glass-ionomer cement placed in association with non-setting calcium hydroxide.

The purpose of this investigation was to determine whether non-setting calcium hydroxide [Ca (OH)2] cement placed in the root canal system of premolar teeth would affect the subsequent microleakage of a glass-ionomer restoration (GIC). Following selection, 62 human premolar teeth extracted for orthodontic reasons were accessed and root canals prepared according to a standardized procedure. The specimens were then allocated randomly into two major groups each of 30 teeth. Two other teeth were used as a positive and a negative control. The control group was restored with glass-ionomer cement following drying of the canal and placement of a cotton wool pledget. The test group had all canals dressed with non-setting Ca(OH)2 and then was subdivided, one set (n = 22) being restored following conditioning of the access cavity margins, the other (n = 8) having the margins cleaned with a hand excavator. Samples were assessed for microleakage using a two-point scoring system (leakage or no leakage) in conjunction with a clearing technique using AgNO3. Using Fisher's exact test, a statistically significant difference was found between the control and test groups (P < 0.05) but there was no significant difference between the excavated and conditioned cavities (P=0.55). It is concluded that contamination of access cavity margins with Ca(OH)2 during medication of a root canal interferes with the bond of GIC, resulting in increased microleakage in vitro.

Algorithms↗

Pre-surgery knee joint loading patterns during walking predict the presence and severity of anterior knee pain after total knee arthroplasty.

This study tested if abnormal sagittal knee joint loading patterns after total knee arthroplasty (TKA) were present pre-surgery, and if patterns with higher external knee flexion moments were related to the presence and severity of post-surgery anterior knee pain. Gait analysis and clinical evaluation were performed on 34 patients (41 arthroplasties) both before and 12-18 months after TKA, and on 20 healthy age-matched controls at matched velocities. The majority of knees with abnormal flexor or extensor sagittal knee joint loading patterns post-surgery (18 of 26, 69%) also displayed these patterns pre-surgery. Knee joint loading in the early mid-stance phase of walking prior to surgery was identified by stepwise regression as a significant predictor of the presence (exp(beta)=2.9, CI: 1.2-6.8, p=0.017) and severity of post-surgery anterior knee pain (R2=0.314, p=0.019). Therefore, the frequency and severity of anterior knee pain after TKA can be partially explained by retained pre-surgery gait patterns that had higher external flexion moments in the early mid-stance phase, which place higher forces on the patellofemoral joint.

Arthroplasty, Replacement, Knee↗

A clinical report of 85 fractured metallic post-retained crowns.

AIM: To determine any patient, technique or material factors that were significantly associated with post fracture in metallic post systems. SUMMARY: Eighty-five fractured metal posts were retrieved over a 5-year period from a total of 84 patients who attended a dental hospital for treatment. A record was kept of the patient's dentition to identify the tooth with the fractured post, the number of teeth present, the excursive guidance scheme and the likely post design and material. Radiographs of 67 of these teeth were available. The presence or absence of a periapical lesion was noted as was the quality of the root filling. Maxillary lateral incisors, followed by maxillary centrals were associated with most of the fractured posts. The median survival to fracture was 36 months. The number of teeth in the dentition had a mode of 28. The most commonly fractured post design was a serrated and parallel design with an average diameter of 1.2 mm at the site of fracture. Apical lesions were found in 67% of the teeth with radiographs. Only 12% of teeth with a 'good' apical filling as opposed to 55% with a 'poor' apical filling had apical lesions. KEY LEARNING POINTS: . Maxillary lateral incisors, followed by maxillary central incisors are at greatest risk of having a fractured metallic post. . Having a large number of teeth in the dentition or an adequate length of post was not protective against metallic post fracture. . Teeth with fractured post-retained crowns had a high incidence of apical lesions.

Crowns↗

Equity of access to adult hospice inpatient care within north-west England.

There is a growing debate about the question of equity of access to hospice and palliative care services. Even countries with relatively well developed palliative care systems are considered to have problems of access and inequity of provision. Despite these concerns, we still lack a relevant evidence base to serve as a guide to action. We present an analysis of access to adult hospice inpatient provision in the north-west region of England that employs Geographical Information Systems (GIS). Measures of the possible demand for, and supply of, hospice inpatient services are used to determine the potential accessibility of cancer patients, assessed at the level of small areas (electoral wards). Further, the use of deprivation scores permits an analysis of the equity of access to adult inpatient hospice care, leading to the identification of areas where additional service provision may be warranted. Our research is subject to a number of caveats--it is limited to inpatient hospice provision and does not include other kinds of inpatient and community-based palliative care services. Likewise, we recognise that not everyone with cancer will require palliative care and also that palliative care needs exist among those with nonmalignant conditions. Nevertheless, our methodology is one that can also be applied more generally.

Adult↗

Molecular characterisation of chondrocytes in autologous chondrocyte implantation.

Autologous chondrocyte implantation (ACI) relies on the use of cultured cells. However, the biosynthetic profile of cultured chondrocytes is shown to be altered during in vitro expansion. The purpose of this study therefore, was to examine the cellular phenotype of chondrocytes cultured for ACI and to determine the apoptotic index of cells implanted into patients. Using electron microscopy, immunohistochemistry, RT-PCR and flow cytometry analyses, we have investigated protein and gene expression of several chondrocyte-specific, or associated markers in cultured cells used for implantation in patients. They included S-100, type I and II collagen, aggrecan, transforming growth factor beta, glucocorticoid receptor alpha and beta and vitamin D3 receptor. We have also examined the apoptotic index of chondrocytes. Our results demonstrated that cultured cells for ACI display the characteristics of chondrocytes. These cells are round in shape, contain numerous small surface processes of cytoplasmic membrane and have an accumulation of glycogen within the cytoplasm. They express S-100, aggrecan TGF-beta, glucocorticoid receptor alpha and vitamin D3 receptor as evidenced by either immunohistochemistry or RT-PCR, however, there is variation in the expression of type I, type II collagen glucocorticoid receptor beta between cases. Chondrocyte used for implantation has relatively low level of apoptosis (<11%). In conclusion, although there was variation in the level of expression of these genetic markers, our data indicate that cultured cells used for ACI were of chondrocytic lineage cells and have low level of apoptotic cells.

Adult↗

The determination of freeway space using two different methods.

The aim of this study was to determine the average freeway space of dentate subjects and relate this to recommended ranges for edentulous patients, also to see if any differences were observed between two different methods of measuring freeway space. The freeway space of 72 dentate subjects was measured, first using a Willis gauge, and secondly using a pair of sprung dividers. The intra- and interoperator variability was evaluated as was the reproducibility of the accuracy of both techniques. The mean freeway space using the Willis gauge was 3.3 mm, for both intra and inter operator variability, and with the sprung dividers 3.1 and 2.9 mm, respectively, with no significant difference being seen between any combination of results (P > 0.05). Individual measurements within the two measuring methods being assessed showed significant differences (P < 0.05). The mean measurements of freeway space in dentate subjects found in this study were within the recommended 2-4 mm range, however, 15% of the subjects in the study had freeway space measurements outside this range. This study would suggest that the range for freeway space measurement could more realistically be 2-7 mm.

Adult↗

New vaccine technologies.

New vaccine development for potential use in human medicine is buoyant. New science (genomics and proteomics) is presenting major new opportunities. New approaches (DNA vaccines, new combination vaccines, new formulations, novel delivery routes, new adjuvants) are being vigorously explored. New needs (defence vaccines) are being identified. One common element in all these varied areas is that pre-clinical evaluation of a candidate new vaccine is a pre-requisite before initiation of clinical trials in humans. Laboratory evaluation also usually continues during the clinical phase of vaccine development. Pre-clinical and laboratory evaluations often involve animals. Data from these studies are used to support an application for marketing authorisation. Regulatory Authorities use precedent to help assess these applications. Where no precedent exists the Regulatory Authorities apply risk-benefit analyses based on the perceived risks of a new product or process. These perceived risks are constantly reviewed as experience is gained. The World Health Organisation facilitates the development of scientific consensus on issues that have an impact on the quality and safety of biological medicines, including vaccines. New vaccine technologies often present new challenges for the safety and efficacy evaluation of candidate preparations. Animal models are usually very important in this process. The number of new vaccine candidates seems set to increase in the short-term.

Animals↗

The effect of luting media on the fracture resistance of a flame sprayed all-ceramic crown.

OBJECTIVES: This in vitro study investigated the effect of selected luting media on the fracture resistance of a flame-sprayed all-ceramic crown. METHODS: Three groups of 10 human upper premolar teeth were prepared for crowning using a standardised technique. Flame sprayed crowns were fabricated and cemented onto the preparations using zinc phosphate (ZPC), glass polyalkenoate (GPC) or composite luting cement (CLC). During crown seating, a pressure perfusion system simulated pulpal fluid outflow equivalent to 300mm of H2O. Compressive fracture resistance was determined for each group using a Universal Testing Machine with a crosshead speed of 1mm min(-1). A group of unrestored teeth acted as a control. RESULTS: The fracture resistance of the groups ranked as follows: ZPC>CLC>>GPC=unrestored teeth. The difference between the fracture resistance of ZPC and CLC groups and the control group was statistically significant. The mode of fracture between the luted crowns and natural crowns was markedly different. CONCLUSIONS: When tested in compression, a new, flame-sprayed all-ceramic crown, when luted in place using ZPC, GPC or CLC, could produce strengths comparable to or greater than natural unrestored teeth. The luting agent used significantly affected the recorded fracture loads.

Analysis of Variance↗

Ultraviolet disinfection with a novel microwave-powered device.

AIMS: To evaluate the antimicrobial efficacy of a novel u.v. beaker, powered in a domestic microwave oven. METHODS AND RESULTS: Three beakers were compared, with most rapid killing obtained in the Neutra Plasma 50. Ultraviolet light generated within the beakers efficiently killed planktonic and surface-associated Streptococcus mutans, Pseudomonas aeruginosa, vegetative Bacillus stearothermophilus, herpes simplex and polio viruses. Candida albicans and Mycobacterium phleii were less rapidly killed, and only 70% inactivation of B. stearothermophilus endospores was achieved. Irradiation for 45 s reduced viable bacterial counts in saliva by > 99%. CONCLUSIONS: The u.v.-generating beakers efficiently reduced viable counts of bacteria, yeast and viruses. Kinetics of killing varied, reflecting the fact that lethal mechanisms are complex, and probably depend on interplay between u.v. and heat. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel method of generating u.v., using a cheap and widely available power source, provides a rapid, inexpensive and non-toxic method of disinfection with a wide range of applications in hospitals, clinics and the home.

Bacteria↗

The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts.

Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, uniformly distributed amongst which are large multinucleated osteoclast-like giant cells. Although the term "Giant Cell Tumour" (and the erroneous historical term 'osteoclastoma') may imply that it is the multinucleated giant cells which are responsible for the proliferative capacity of the tumour, there is evidence that the stromal-like cells, the major component of the mononuclear cell population, represent the true neoplastic component of the neoplasm. The diagnosis and management of conventional GCT are often challenging and there is considerable current interest in its pathobiology. The precise histogenesis of GCT and the nature of its varying cellular constituents have remained a matter of some controversy. Factors influencing the clinical course and biological aggression of GCT are also unclear. In this selective review, the clinicopathological characteristics of GCT are summarised and current areas of interest in the study of the neoplasm are presented and discussed. Lastly, a hypothetical model of the mechanism of histogenesis and the biological behaviour of GCT is presented.

Animals↗