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Biomedical subjects

D Webb

Publications and source records attributed to D Webb.

At least 19 recordsLinked to original sources
PubMed2006

Weight gain is associated with improved glycaemic control but with adverse changes in plasma lipids and blood pressure isn Type 1 diabetes.

AIMS: To assess the effects of weight gain on metabolic control, plasma lipids and blood pressure in patients with Type 1 diabetes. METHODS: Patients in the EURODIAB Prospective Complications Study (n = 3250) were examined at baseline and 1800 (55%) were re-examined a mean of 7.3 years later. Patients had Type 1 diabetes, defined as a diagnosis made before age 36 years and with a need for continuous insulin therapy within a year of diagnosis. Patients were aged 15-60 years at baseline and were stratified for age, sex and duration of diabetes. RESULTS: The change in HbA(1c) from baseline to follow-up examination was significantly more favourable in those who gained 5 kg or more during follow-up ('marked weight gain') than in patients who gained less or no weight or lost weight ('less or no weight gain'). In those with marked weight gain, there was a significantly greater rise in plasma triglycerides and total cholesterol and significantly less favourable changes in low-density lipoprotein and high-density lipoprotein cholesterol compared with those with less or no weight gain, with or without adjustment for HbA(1c). Systolic and diastolic blood pressure also rose significantly more in the group with marked weight gain. CONCLUSION: Weight gain in patients with Type 1 diabetes has adverse effects on plasma lipids and blood pressure, despite a small improvement in glycaemic control.

Adolescent↗
PubMed2005

Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy.

Acute Disease↗
PubMed2005

Is pregnancy a risk factor for microvascular complications? The EURODIAB Prospective Complications Study.

AIMS: To examine the long-term influence of pregnancy on the development and progression of microvascular complications in Type 1 diabetes. METHODS: In the EURODIAB Prospective Complications Study (PCS), 793 women potentially child bearing at baseline completed the follow-up (7.3 years) and 163 (21%) gave birth during the follow-up period. We compared risk factors [mean levels of age, duration of diabetes, HbA(1c), systolic blood pressure (SBP) and proportion giving birth] between those that did or did not develop microvascular complications during the follow-up period. RESULTS: For the 425 childless women at baseline, 102 gave birth during follow-up. HbA(1c) was a significant risk factor for progression to microalbuminuria but age, duration of diabetes, systolic blood pressure or giving birth were not. Duration of diabetes and high HbA(1c) were significant risk factors for progression to proliferative retinopathy, whereas giving birth was not. Similar results were obtained for progression to any form of retinopathy. Giving birth was not significantly related to the incidence of neuropathy. Similar results were obtained for women with children at baseline giving birth during follow-up (n = 61/368). CONCLUSIONS: In this European study, having a first or another pregnancy did not seem to be a risk factor for long-term progression of any microvascular complication. This is in accordance with the findings of the Diabetes Control and Complications Trial (DCCT).

Adult↗
PubMed2004

Tumorigenesis by adenovirus type 12 in newborn Syrian hamsters.

Ad12 oncogenesis in hamsters has been studied in detail to provide the following new data in this tumor model. Cells in the Ad12-induced tumors, often thought to be of neuronal origin, actually exhibit mesenchymal and neuronal characteristics and are probably of an undifferentiated derivation. Their intraperitoneal spread upon intramuscular injection of Ad12 adds another important new aspect. Differences in the integration patterns among the tumors suggest clonal origins from individual transformation events. Ad12 gene expression in the tumors is determined, at least in part, by the patterns of DNA methylation imprinted de novo upon the integrated Ad12 genomes. Differential Ad12 gene expression patterns, which have previously not been described in tumors, are an important parameter in Ad12 oncogenesis. The availability of cellular DNA arrays has opened up unprecedented possibilities to document changes in cellular transcription patterns, particularly of cancer-specific genes. These patterns exhibit differences and similarities among the different Ad12-induced tumors. Among the cellular genes, which are expressed in the Ad12-induced tumors, many are cancer-specific. We pursue the hypothesis that these alterations in cellular transcription patterns as a consequence of viral DNA integration and expression play an essential role in Ad12 oncogenesis.

Adenoviruses, Human↗
PubMed2004

Improving the quality of mental health services in Personal Medical Services pilots: a longitudinal qualitative study.

BACKGROUND: A series of government initiatives in the UK have included strategies to improve the quality of services received by patients, including fundholding, the development of National Service Frameworks, clinical governance, and Personal Medical Services (PMS). PMS represents a new contractual arrangement between government and general practitioners (GPs) which provides new investment in return for more detailed specification of processes and outcomes of care. OBJECTIVES: To evaluate the effects of PMS on the quality of primary mental health care between 1998 and 2001. DESIGN: Multiple longitudinal case studies. Semi-structured interviews with key staff within practices (GPs, nurses, practice managers) and outside (health authority and primary care group/trust managers). SAMPLE: Six first wave PMS sites which had specifically planned to improve their mental health care. RESULTS: Improvements in mental health care were found in some PMS practices and not in others. Five mechanisms associated with successful quality improvement in mental health were identified: clear goals, effective teamwork within the practice, routine use of protocols and audits, additional resources, and effective collaboration with community and secondary care. Sites where these factors were not present struggled to meet their objectives. CONCLUSION: The five mechanisms which resulted in improved mental health care were facilitated by the new contractual arrangements in PMS. The new contracts were not a necessary part of these changes, but they enabled sites with an identified interest and motivation to make the changes. The contractual changes were not in themselves sufficient to improve care.

Humans↗
PubMed2004

Childhood stroke following varicella infection.

Stroke in childhood remains unexplained in a significant proportion of those affected. We present a 4 year-old boy who presented with a stroke following a recent uncomplicated chickenpox infection. Varicella is increasingly recognized as a cause of acute ischaemic events in childhood and a recent history of chickenpox should be sought in children who present with a stroke.

Chickenpox↗
PubMed2003

Biofiltration eliminates nuisance chemical odors from industrial air streams.

This paper focuses on recent developments of biofiltration technology used in treating nuisance chemical odors from industrial and municipal air streams. In the biofiltration process, odorous chemical constituents in the air are first transported to biofilms by diffusion, solubilization and adsorption processes. Bacteria within the biofilms oxidize odor constituents into harmless and odorless products. Through successful laboratory and pilot research on biofiltration of odorous air-stream constituents, numerous commercial biofilters have been designed and installed across North America. In this paper, case studies related to biofiltration of air emissions from meat rendering plants, municipal wastewater treatment applications, and printed circuit board production are discussed to demonstrate the robustness of this technology in eliminating a wide variety of compounds.

Air Pollution↗
PubMed2003

Nasal bone length throughout gestation: normal ranges based on 3537 fetal ultrasound measurements.

OBJECTIVE: To establish normal ranges for nasal bone length measurements throughout gestation and to compare measurements in two subsets of patients of different race (African-American vs. Caucasian) to determine whether a different normal range should be used in these populations. METHOD: Normal nasal bone length reference ranges were generated using prenatal measurements by a standardized technique in 3537 fetuses. RESULTS: The nasal bone lengths were found to correlate positively with advancing gestation (R(2) = 0.77, second-order polynomial). No statistical difference was found between African-American and Caucasian subjects. CONCLUSION: These reference ranges may prove to be useful in prenatal screening and diagnosis of syndromes known to be associated with nasal hypoplasia. Different normal ranges for African-American and Caucasian women are not required.

Embryonic and Fetal Development↗
PubMed2003

The abortive infection of Syrian hamster cells with human adenovirus type 12.

Human adenovirus type 12 (Ad12) induces undifferentiated tumors in newborn Syrian hamsters, and this tumor model has been investigated in detail in our laboratory. One of the characteristics of the Ad12-hamster cell system is a strictly abortive infection cycle. In this chapter, we summarize previous and more recent results of studies on the interaction of Ad12 with the nonpermissive BHK21 hamster cell line. The block of Ad12 replication lies before viral DNA replication and late gene transcription which cannot be detected with the most sensitive techniques. Ad12 adsorption, cellular uptake and transport of the viral DNA to the nucleus are less efficient in the nonpermissive hamster cells than in permissive human cells. However, most of the early functions of the Ad12 genome are expressed in BHK21 cells, though at a low level. In the downstream region, the first exon, of the major late promoter (MLP) of Ad12 DNA, a mitigator element of 33 nucleotide pairs in length has been identified which contributes to the inactivity of the MLP in hamster cells and its markedly decreased activity in human cells. The E1 functions of Ad2 or Ad5 are capable of partly complementing the Ad12 deficiencies in hamster cells in that Ad12 viral DNA replication and late gene transcription can proceed, e.g. in a BHK hamster cell line, BHK297-C131,which carries in an integrated form and constitutively expresses the E1 region of Ad5 DNA. Nevertheless, the late Ad12 mRNAs, which are synthesized in this system with the authentic nucleotide sequence, fail to be translated to structural viral proteins. Hence, infectious virions are not produced in the partly complementing system. Probably there is also a translational block for late Ad12 mRNAs in hamster cells. We have recently shown that the overexpression of the Ad12 preterminal protein (pTP) gene or of the E1A gene facilitates the synthesis of full-length, authentic Ad12 DNA in BHK21 cells infected with Ad12. Apparently the pTP has a hitherto unknown function in eliciting full cycles of Ad12 DNA replication even in nonpermissive BHK21 cells when sufficient levels of Ad12 pTP are produced. We pursue the possibility that the completely abortive infection cycle of Ad12 in hamster cells ensures the survival of Ad12-induced hamster tumor cells which all carry, integrated in their genomes, multiple copies of Ad12 DNA. In this way, the viral genomes are immortalized and expanded in a huge number of tumor cells.

Adenoviruses, Human↗
PubMed2003

Assessing technician effects when extracting quantities from microscope images.

Consider an experiment where the response is based on an image; e.g., an image captured to a computer file by a digital camera mounted on a microscope. Suppose relevant quantitative measures are extracted from the images so that results can be analyzed by conventional statistical methods. The steps involved in extracting the measures may require that the technicians, who are processing the images, perform some subjective manipulations. In this case, it is important to determine the bias and variability, if any, attributable to the technicians' decisions. This paper describes the experimental design and statistical analyses that are useful for those determinations. The design and analysis are illustrated by application to two biofilm research projects that involved quantitative image analysis. In one investigation, the technician was required to choose a threshold level, then the image analysis program automatically extracted relevant measures from the resulting black and white image. In the other investigation, the technician was required to choose fiducial points in each of two images collected on different microscopes; then the image analysis program registered the images by stretching, rotating, and overlaying them, so that their quantitative features could be correlated. These investigations elucidated the effects of the technicians' decisions, thereby helping us to assess properly the statistical uncertainties in the conclusions for the primary experiments.

Analysis of Variance↗
PubMed2002

MFO induction potential of fish species native to the Swan-Canning Estuary, Western Australia.

The use of mixed function oxygenase (MFO) enzymes as a potential biomarker of pollution in the Swan-Canning Estuary was investigated in four indigenous fish species, Perth herring (Nematalosa vlaminghi), sea mullet (Mugil cephalus), yellowtail trumpeter (Amniataba caudavittata), and black bream (Acanthopagrus butcheri). Each experimental fish was intraperitoneally injected with 10 micrograms/kg of 3,3',4,4',5-pentachlorobiphenyl per kilogram of fish using corn oil as a carrier. Controls were injected with 1 mL corn oil per kilo. Induction of the hepatic ethoxyresorufin-O-deethylase (EROD) activity was measured 10 days post injection. Perth herring did not survive the experimental period due to the poor ability of this fish to endure captivity and handling. Yellowtail trumpeter demonstrated a low EROD induction response (2-fold relative to controls), while sea mullet displayed a moderate EROD induction potential (3.5-fold relative to controls). Because of their lower EROD induction potential, yellowtail trumpeter and sea mullet were not considered the most suitable bioindicator species for Western Australian estuarine waters. Black bream has desirable population traits and had a relatively high MFO induction potential response (9-fold relative to controls). From the results it was concluded that, when using EROD induction as a biomarker, black bream is a suitable fish to use as a bioindicator species for investigations into the health of the Swan-Canning Estuary.

Animals↗
PubMed2002

Non-myeloablative stem cell transplantation for congenital immunodeficiencies.

Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital immunodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality. We have therefore used a low-intensity conditioning regime for transplantation in this group of immunodeficiency patients. Twenty-one patients with a variety of different immunodeficiencies were treated using the following conditioning regimes: (1) fludarabine/melphalan/ATG or Campath 1H (n=16), (2) fludarabine/cyclophosphamide/Campath 1H (n=1), (3) TBI/CyA/MMF (n=1), (4) fludarabine/melphalan/busulphan/ATG (n=3). In 13 cases matched (n=9) and 1 Ag mismatched (n=4) unrelated donors were used and in eight cases transplants from matched siblings (n=4), 1 Ag mismatched sibling (n=1), matched parent (n=1) and haploidentical parents (n=3) were performed. At a median follow-up of 13 months, 19 of 21 (90%) patients were still alive following the transplant procedure. Despite a T cell replete graft and the use of unrelated donor grafts in the majority of patients studied there was no evidence of significant organ disease. Immune reconstitution in terms of CD3+ and CD4+ T cell recovery and function was equivalent in comparison with a historical cohort. We believe that this low-intensity approach has significant implications for transplantation of individuals with immunodeficiency states with established organ disease.

Adolescent↗
PubMed2001

Cellular and early viral factors in the interaction of adenovirus type 12 with hamster cells: the abortive response.

The interaction of human adenovirus type 12 (Ad12) with Syrian hamster cells is remarkable in that there is a block of viral DNA replication and late gene transcription. We have screened several cellular factors known to play a role in adenovirus replication for their possible contributions to the interactions of Ad12 in the abortive BHK21 hamster cell system. (1) Western blot analyses of total protein extracts from Ad12- or Ad2-infected BHK21 cells do not reveal a significant difference in the accumulation of NFIII protein at different times after infection. Transcriptional levels of the NFIII gene in BHK21 cells are not altered upon the abortive infection with Ad12 or the productive infection with Ad2. The amount of NFIII protein is markedly reduced in nuclear extracts from BHK21 cells as compared with extracts from C131 hamster cells or human HeLa cells. A presumptive defect in NFIII transport to the nuclei rather than overall reduced NFIII gene transcription might explain the low abundance of NFIII in the nuclei of uninfected or Ad12-infected BHK21 cells. The productive infection of BHK21 or C131 cells with Ad2 leads to an increase in the NFIII concentration in the nuclei of infected cells, late after infection to a decrease; (2) NFI levels in the nuclei of mock-infected or Ad2- or Ad12-infected BHK21 cells are comparable with those in HeLa or in C131 cells. Thus, deficiencies in NFI may not play a role in the abortive system; (3) The absence of morphological alterations in PML protein domains from globular to track-like structures in the nuclei of Ad12-infected hamster cells correlates with the inability of Ad12 DNA to replicate in BHK21 cells. In BHK21 cells, the E4-ORF3 of Ad12 DNA is only weakly transcribed and only small amounts of the gene product are synthesized. In Ad12-infected C131 cells, which allow the replication of Ad12 DNA, the E4-ORF3 of Ad12 DNA is expressed, and track-like PML protein structures are observed. Transfection of the 12-E4-ORF3-EGFP construct leads to the expression of both the green fluorescent protein (GFP) and of the 12-E4-ORF3 gene product in 20-30% of the transfected BHK21 cells and elicits the morphological reorganization of the PML protein structures in the successfully transfected BHK21 cells. Similar results are obtained upon transfection of the 2-E4-ORF3 construct. Untransfected cells or cells transfected with the empty pIRES2-pEGFP vector carry the globular PML protein phenotype; (4) The expression of the 12-E4-ORF3-EGFP and/or of the NFIII-EGFP constructs upon transfection following Ad12-infection of BHK21 cells fails to promote Ad12 DNA replication. Hence, the formation of track-like PML protein structures in BHK21 cells by itself is not a sufficient precondition for Ad12 DNA replication in this abortive system. The data demonstrate that the expression of NFI, NFIII, and/or the conversion of the PML domains do not suffice to elicit Ad12 DNA replication in the abortive hamster cell system.

Adenovirus E4 Proteins↗
PubMed2001

Regaining chondrocyte phenotype in thermosensitive gel culture.

Chondrocyte tissue engineering continues to be a challenging problem. When chondrocytes are duplicated in vitro, it is imperative to obtain an adequate number of cells of optimal phenotype. A temperature-sensitive polymer gel, a copolymer of poly(N-isopropylacrylamide) and acrylic acid (PNiPAAm-co-Aac), has the ability of gelling at 37 degrees C (the lower critical solution temperature, LCST) or above and liquefying below that temperature (Vernon and Gutowska, Macromol. Symp. 1996;109:155-167). The hypothesis of this study was that chondrocytes could (1) duplicate in the copolymer gel; (2) regain their chondrocyte phenotype; and (3) be easily recovered from the gel by simply lowering the temperature below 37 degrees C. Chondrocytes from adult rabbit scapular cartilage were harvested and cultured in a monolayer culture until confluency (approximately 2 weeks). Next, the cells were harvested and seeded into the copolymer gel and cultured for 2-4 weeks. The phenotype of the cultured cells was then characterized. Two groups of control cultures, monolayer and agarose gel, were used to compare their ability to maintain chondrocyte phenotype. The results showed that chondrocytes isolated from rabbit scapula can re-express chondrocyte phenotype in agarose culture and polymer gel culture but not in monolayer culture. Also, cultured chondrocytes can be easily recovered from polymer gel culture by simply lowering the temperature. This new in vitro method of chondrocyte culture is recommended for chondrocyte propagation and regaining chondrocyte phenotype before cell seeding or transplantation.

Acrylamide↗
PubMed2001

Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia.

The hazards associated with invasive candidiasis and aspergillosis in oncology patients are well recognised. These conditions typically present late in treatment, often after prolonged or recurrent episodes of neutropenia. We report the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis in two children with acute lymphoblastic leukaemia, early in the induction phase of treatment and within a 3-month interval, in the same oncology unit. The initial presentation of facial pain was rapidly followed by the development of cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures and death within 9 days of symptom onset, despite aggressive management with high-dose liposomal amphotericin (Ambisome), surgical debridement and local instillation of amphotericin solution. These cases highlight the need for awareness of zygomycosis as a potentially lethal fungal infection that can present even with short duration exposure to the usual risk factors. Their occurrence within a limited time period raises questions as to the relative importance of environmental exposure. The failure of medical and surgical intervention to impact on the course illustrates the need to develop appropriate preventative strategies which may have to incorporate measures to reduce the environmental exposure of susceptible patients.

Absidia↗
PubMed2001

Gastrin-releasing peptide is a potent vasodilator in humans.

OBJECTIVES: Our objective was to characterize the local vascular effects of gastrin-releasing peptide in forearm resistance vessels as a biomarker to aid the clinical development of broad-spectrum neuropeptide antagonists as anticancer agents. METHODS: On different occasions, 7 healthy male volunteers received brachial artery infusions of gastrin-releasing peptide, and forearm blood flow was measured by venous occlusion plethysmography. Dose-finding studies identified a range of pharmacologically active doses of gastrin-releasing peptide (3 to 450 pmol/min) for use in dose response and tachyphylaxis studies. The nitric oxide clamp method was used for the assessment of the contribution of nitric oxide to the vasodilatory effect shown. RESULTS AND CONCLUSIONS: Gastrin-releasing peptide proved to be a potent, dose-dependent arteriolar vasodilator. The time to onset and offset of effect was rapid, within minutes, and marked tachyphylaxis was shown, with recovery by approximately 20 minutes. The contribution of nitric oxide to this vasodilatation was minimal. Forearm blood flow studies with the use of gastrin-releasing peptide may be usefully incorporated into the further clinical development of broad-spectrum neuropeptide growth factor antagonists.

Adult↗