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David Wood

Publications and source records attributed to David Wood.

At least 37 records · Page 2Linked to original sources

Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004.

The World Health Organization (WHO) is undertaking consultations on immunological responses as parameters for evaluation and licensure of new Japanese encephalitis (JE) vaccines. Immunological markers could be used by vaccine developers and regulatory authorities to assess vaccine efficacy in absence of clinical efficacy data. The consultation which is reported here reviewed current data on mechanisms of protective immunity gathered from animal experimentation, clinical data from licensed vaccines and from vaccine candidates still in clinical development. Immunological assays and readouts for use in evaluation of candidate vaccines were also discussed. The consultation made a series of recommendations for specifications on immunological criteria to assess JE vaccine efficacy. More detailed recommendations will be drafted following further consultations to serve as WHO guidelines for evaluation and licensure for new JE vaccines.

Antibodies, Viral↗

Mitochondrial DNA and retroviral RNA analyses of archival oral polio vaccine (OPV CHAT) materials: evidence of macaque nuclear sequences confirms substrate identity.

Inoculation of live experimental oral poliovirus vaccines (OPV CHAT) during the 1950s in central Africa has been proposed to account for the introduction of HIV into human populations. For this to have occurred, it would have been necessary for chimpanzee rather than macaque kidney epithelial cells to have been included in the preparation of early OPV materials. Theoretically, this could have led to contamination with a progenitor of HIV-1 derived from a related simian immunodeficiency virus of chimpanzees (SIVCPZ). In this article we present further detailed analyses of two samples of OPV, CHAT 10A-11 and CHAT 6039/Yugo, which were used in early human trials of poliovirus vaccination. Recovery of poliovirus by culture techniques confirmed the biological viability of the vaccines and sequence analysis of poliovirus RNA specifically identified the presence of the CHAT strain. Independent nested sets of oligonucleotide primers specific for HIV-1/SIVCPZ and HIV-2/SIVMAC/SIVSM phylogenetic lineages, respectively, indicated no evidence of HIV/SIV RNA in either vaccine preparation, at a sensitivity of 100 RNA equivalents/ml. Analysis of cellular substrate by the amplification of two distinct regions of mitochondrial DNA (D-loop control region and 12S ribosomal sequences) revealed no evidence of chimpanzee cellular sequences. However, this approach positively identified rhesus and cynomolgus macaque DNA for the CHAT 10A-11 and CHAT 6039/Yugo vaccine preparations, respectively. Analysis of multiple clones of mtDNA 12S rDNA indicated a relatively high number of nuclear mitochondrial DNA sequences (numts) in the CHAT 10A-11 material, but confirmed the macaque origin of cellular substrate used in vaccine preparation. These data reinforce earlier findings on this topic providing no evidence to support the contention that poliovirus vaccination was responsible for the introduction of HIV into humans and sparking the AIDS pandemic.

Animals↗

Microcomputerised tomography evaluation of 10% carbamide peroxide applied to enamel.

OBJECTIVES: There is still some controversy in the dental literature whether carbamide peroxide bleaching causes demineralization of teeth. One of the reasons for this controversy is that there is as yet no reliable, non-destructive in vitro method for assessing mineral loss in bleached teeth. The objective of this study was to investigate the possible demineralization effect of 10% carbamide peroxide bleaching agent on enamel and dentine non-destructively. METHODS: microCT images were obtained of 12 human molar tooth sections. These sections had 10% carbamide peroxide applied for eight hours a day over a period of 15 days. Further tomographic images were obtained and the mineral content prior to and post bleaching assessed. RESULTS: A total of 144 regions were evaluated using the image processing language available in the work station. The application of 10% carbamide peroxide was found to cause demineralization of the enamel extended to a depth of 50 microm below the enamel surface (Paired t-test, p<0.05). CONCLUSIONS: This study confirmed that microCT was indeed a highly suitable method for assessing mineral content of dental enamel after bleach application. It is recommended that application of bleaching agents should be carefully considered in patients susceptible to caries and tooth wear.

Carbamide Peroxide↗

Evaluation of a signal intensity mask in the interpretation of functional MR imaging activation maps.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence of susceptibility artifacts on functional MR imaging (fMRI) studies and their effect on fMRI readings. We hypothesized that the availability of the signal intensity maps (SIMs) changes the interpretation of fMRI studies in which susceptibility artifacts affected eloquent brain regions. METHODS: We reviewed 152 consecutive clinical fMRI studies performed with a SIM. The SIM consisted of the initial echo-planar images (EPI) in each section thresholded to eliminate signal intensity from outside the brain and then overlaid on anatomic images. The cause of the artifact was then determined by examining the images. Cases with a susceptibility artifact in eloquent brain were included in a blinded study read by four readers, first without and then with the SIM. For each reader, the number of times the interpretation changed on viewing the SIM was counted. RESULTS: Of 152 patients, 44% had signal intensity loss involving cerebral cortex and 18% involving an eloquent brain region. Causes of the artifacts were: surgical site artifact, blood products, dental devices, calcium, basal ganglia calcifications, ICP monitors, embolization materials, and air. When provided with the SIM, readers changed interpretations in 8-38% of patient cases, depending on reader experience and size and location of susceptibility artifact. CONCLUSION: Patients referred for clinical fMRI have a high incidence of susceptibility artifacts, whose presence and size can be determined by inspection of the SIM but not anatomic images. The availability of the SIM may affect interpretation of the fMRI.

Artifacts↗

The characteristics of Chinese healthcare facilities.

The Chinese healthcare system has been the focus of a great deal of attention from international companies who are interested in entering the world's largest healthcare marketplace. It is generally acknowledged that Chinese healthcare facilities, on the whole, do not conform to international standards; however, the specific areas in which there are differences are not well known or appreciated. An understanding of these differences is a critical aspect of the investment analysis and market assessment associated with a healthcare-based business in China. This article will delineate the major differences between the international model for the provision of healthcare and that found in mainland China. These differences include the physical characteristics, organizational structure issues, operational issues and financial management issues of Chinese hospitals, clinics and medical care providers.

China↗

A longitudinal, microgenetic study of the emergence of false belief understanding and inhibition skills.

Two theories that attempt to explain the relationship between false belief understanding and inhibition skills were investigated: (1) theory of mind development improves self-control, and (2) executive control is necessary for developing a theory of mind. A microgenetic approach was adopted, with a group of 21 children completing a battery of inhibition and false belief understanding tasks every four weeks for six phases of testing. The results showed that the majority of children were able to perform well on a test of executive inhibition before having a good understanding of false beliefs, thus supporting theory (2). The results also illustrated that while the children's inhibition skills developed relatively gradually, their understanding of false beliefs progressed from a consistent lack of understanding through a period of unstable performance, during which some children failed tests that they had previously passed.

Child, Preschool↗

The health of children in immigration detention: how does Australia compare?

We live in an age when the number of refugees worldwide is increasing. All of them have suffered physically or emotionally to a varying degree in their country of origin. The transit to a country of resettlement is fraught with further difficulties or the risk of death. This article explores the different approach taken to the management of this issue by Denmark and Iceland, in comparison to that of Australia. In particular, the different approaches to health care for children and their families are identified. The management of these issues by Denmark and Iceland would appear to be a model to follow. Outcomes of the different managements have not been assessed.

Adolescent↗

Expression and localization of extracellular matrix metalloproteinase inducer in giant cell tumor of bone.

Matrix metalloproteinases (MMPs) are regarded as a significant regulator in tumor invasion and metastasis. Previous studies have shown that extracellular matrix metalloproteinase inducer (EMMPRIN) in tumor cells induces the synthesis of MMPs. EMMPRIN is abundantly present on the surface of tumor cells and stimulate adjacent stromal cells to synthesize MMPs to induce tumor progression. Giant cell tumor (GCT) of bone is a benign but locally aggressive primary neoplasm of bone. The spindle-shaped mononuclear stromal cells are considered to be the tumor components of GCT, which are capable of inducing osteoclast formation by recruiting the circulating monocyte and macrophage. In this study, we proposed that EMMPRIN is associated with the biological progression and aggressiveness of GCT. We have conducted semi-quantitative RT-PCR to determine the correlation of EMMPRIN expression with the clinical stage of GCT. We have also examined the cellular localization of EMMPRIN in GCT using in-situ hybridization (ISH) and Immunohistochemistry (IH). The results showed that EMMPRIN was present in GCT and its mRNA levels were associated with the clinical stage of GCT. Higher expression level of EMMPRIN was observed in GCT with advanced stage (stage III). There was a great significance (P < 0.05) of EMMPRIN expression between stage I & II and stage III GCTs. Both ISH and IH demonstrated that EMMPRIN is present at the multinuclear osteoclast-like giant cells of GCT, with strong immunostaining on the cell membrane. The stromal-like tumor cells were also positively stained but the intensity was weaker. Interestingly, the production of EMMPRIN in osteoclast-like cells of GCT seems to be regulated by stromal-like tumor cells. Receptor activator of NF-kappaB ligand (RANKL), which has been previously shown to be produced by the stromal-like tumor cells for the recruitment of osteoclast-like giant cells in GCT, enhanced the expression of EMMPRIN mRNA during the differentiation of macrophage-like RAW(264.7) cells into osteoclasts. In short, our studies suggest that EMMPRIN may be an important regulatory factor involved in the biological behaviors of GCT.

Animals↗

Effects of Bafilomycin A1: an inhibitor of vacuolar H (+)-ATPases on endocytosis and apoptosis in RAW cells and RAW cell-derived osteoclasts.

Bafilomycin A1, a specific inhibitor of V-ATPases, is a potent inhibitor of bone resorption, but the underlying mechanisms of its action remain unclear. In this study, we investigated the effect of Bafilomycin A1 on endocytosis and apoptosis in RAW cells and RAW cell-derived osteoclasts. Quantitative analysis by flow cytometry showed that Bafilomycin A1 increased total transferrin levels when RAW cells were exposed to labeled transferrin and decreased the total uptake of Dextran-rhodamine B, both in a dose- and time-dependent fashion, indicating that Bafilomycin influences receptor-mediated and fluid phase endocytosis in these cells. Furthermore, Bafilomycin A1 induced apoptosis of RAW cells in a dose dependent manner as evidenced by Annexin V flow cytometry. The action of Bafilomycin A1 on endocytotic events appeared to be more sensitive and occurred earlier than on its apoptosis inducing effects, suggesting that interrupting of endocytosis might be an early sign of Bafilomycin-mediated osteoclast inhibition. Semi-quantitative RT-PCR analysis showed that the gene transcripts of putative Bafilomycin A1 binding subunit, V-ATPase-subunit a3, were expressed in the preosteoclastic RAW cell line, and up-regulated during RANKL-induced osteoclastogenesis. Osteoclasts treated with Bafilomycin A1 exhibited apoptosis as well as altered cellular localization of Transferrin Alexa 647. Given that endocytosis and apoptosis are important processes during osteoclastic bone resorption, the potent effect of Bafilomycin A1 on endocytosis and apoptosis of osteoclasts and their precursor cells may in part account for Bafilomycin A1 inhibited bone resorption.

Apoptosis↗

Six-year-olds' difficulties handling intensional contexts.

Previous research shows that children have difficulties handling intensional contexts even when they can pass a test of false belief (e.g. Cognition 67 (1998) 287; Cognition 25 (1987) 289). Some authors (Perner, J. (1991). Understanding the representational mind. Cambridge, MA: MIT Press; Cognition 25 (1987) 289) place these difficulties in the linguistic and not the mental representational domain. The experiments reported here examined whether 6-year-old children could answer questions in an intensional context that did not require the explicit verbal characterization of a belief. We replicated previous findings and found that children answered according to their own knowledge in an intensional context. This occurred even though they responded by choosing a picture to insert into a protagonist's thought bubble rather than report the belief verbally. Children could correctly answer questions about the knowledge state of the protagonist and pass a test of false belief. Further experiments ruled out methodological explanations. Experiment 2 showed that the difference in answering according to own knowledge between the false belief and intensional stories is not accounted for by procedural factors in the two types of test. Experiment 3 revealed that children did not answer according to their own knowledge by default. Experiment 4 suggested that answering according to own knowledge was not a result of pictorial salience. Results are discussed in relation to the simulation-theory debate.

Child↗

Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer.

OBJECTIVES: To evaluate the efficacy and safety of neoadjuvant docetaxel and estramustine in patients with high-risk, newly diagnosed, prostate cancer. METHODS: Eligible patients had prostate cancer with one or more of the following criteria: clinical Stage T2b or greater, prostate-specific antigen (PSA) of 15 ng/mL or greater, and/or Gleason score of 8 to 10. Chemotherapy consisted of docetaxel (70 mg/m(2)) on day 1 and estramustine (280 mg three times daily) on days 1 to 3 every 21 days for three to six courses. This was followed by local therapy, as deemed appropriate. RESULTS: Twenty-one patients with a median age of 60 years, median PSA level of 16.1 ng/mL (range 2.4 to 175), and median baseline testosterone of 3.4 ng/mL were enrolled. Seven patients met one of the inclusion criteria, 10 met two, and 4 met three. The Gleason score was 8 or greater in 14 patients. A median of five cycles of chemotherapy was delivered. The most frequent high-grade toxicities were grade 3 (8 patients) and 4 (1 patient) neutropenia and deep venous thrombosis (grade 3 in 2 patients) before institution of low-dose warfarin. All patients responded as determined by protocol-defined criteria. Ten patients underwent radical prostatectomy, with negative surgical margins in 7 patients, and 11 received radiotherapy with negative preradiotherapy biopsies in 2. CONCLUSIONS: Induction docetaxel and estramustine is well tolerated and feasible in patients with newly diagnosed, high-risk prostate cancer. This combination is active; however, its efficacy relative to hormonal therapy will require a controlled randomized trial.

Aged↗

Immunization safety priority project at the World Health Organization.

In 1999, the World Health Organization's (WHO) Department of Vaccines and Biologicals launched the Immunization Safety Priority Project with the aim of establishing a comprehensive system to ensure the safety of all immunizations given in national immunization programs. Countries are the primary focus of the project. WHO has a role, not only because of its technical and normative role, but also because of its privileged relationship with country authorities and other partners, and its global vision and mandate. The four major areas of focus in the project are to (1) promote and coordinate research and development of safer and simpler delivery systems; (2) ensure vaccine safety, from vaccine development all the way through clinical trials and vaccine distribution until use; (3) broaden access to safer and more efficient systems for vaccine delivery and management of sharps waste; and (4) establish efficient mechanisms to detect serious or potentially serious adverse events following immunization, and enable prompt and effective response. The project emphasizes the importance of advocating safety and building capacity at national levels.

Advisory Committees↗

Blood pressure is insufficiently controlled in European patients with established coronary heart disease.

BACKGROUND: Elevated blood pressure is associated with an impaired prognosis in patients with established coronary heart disease. Adequate blood pressure control is therefore of utmost importance. We report on two successive European surveys that evaluated whether the goals given in recommendations on secondary prevention are achieved. METHODS: The first European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE I) survey was conducted during 1995-1996 in 21 hospitals in nine European countries. The second survey (EUROASPIRE II) was conducted during 1999-2000 in 47 hospitals (including 20 hospitals that participated in EUROASPIRE I) in 15 Europeans countries. Consecutive patients (aged < 71 years) were identified from hospital records after coronary artery bypass grafting, percutaneous coronary intervention, myocardial infarction, or myocardial ischaemia. Patients were invited for an interview and examination at least 6 months after hospitalization. During the interview, blood pressure was measured in a standardized fashion. Systolic blood pressure >/= 140 mmHg and/or a diastolic blood pressure >/= 90 mmHg were considered as elevated blood pressure. EUROASPIRE II provides a more comprehensive view on the actual management of patients with established coronary disease. Therefore, we decided to concentrate mainly on the EUROASPIRE II data, and to use EUROASPIRE I for the evaluation of time trends. RESULTS: In EUROASPIRE II, 5556 patients were interviewed, and 51% were diagnosed with elevated blood pressure. Large regional variations in the prevalence of elevated blood pressure were observed, with values ranging from 37 to 64%. Twenty-five per cent (1401) of patients were on a diet to reduce blood pressure, and among these 61% had elevated blood pressure. The prevalence of elevated blood pressure among the 4827 (87%) patients taking blood pressure-lowering medication (which was not necessarily taken as an antihypertensive treatment) was 51%. Patients with elevated blood pressure were more likely to be diabetic, hypercholesterolemic, and obese than normotensive patients. The proportion of patients who reported being aware of their hypertensive status was somewhat higher in EUROASPIRE II than in EUROASPIRE I (71 versus 67%), and the use of blood pressure-lowering medication was intensified (91 versus 85%). However, these changes were not accompanied by a decrease in the prevalence of elevated blood pressure (54 versus 55% in centres that participated in both surveys). CONCLUSION: During 1995-2000 the prevalence of elevated blood pressure in patients with established coronary heart disease remained at an unacceptably high level. Throughout Europe, still about half of coronary patients require more intensive blood pressure management.

Aged↗

European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts).

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organisations--European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific task force. The ESC Committee for practice guidelines (CPG) supervises and coordinates the preparation of new guidelines and expert consensus documents produced by task forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements.

Adult↗