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Biomedical subjects

Ian Taylor

Publications and source records attributed to Ian Taylor.

11 recordsLinked to original sources
PubMed2006

A unique service in UK delivering Plastibell circumcision: review of 9-year results.

Muslim infants undergo circumcision for religious reasons and Bradford has a high Muslim population. The National Health Service in UK does not provide religious circumcision, so in 1996 a nurse-delivered circumcision service led by consultant urologists was set up at a no-profit and cost-only basis. Plastibell circumcision was offered to all infants between 6 and 14 weeks old and performed under local anaesthesia. Information leaflets and videotapes about the procedure were available to parents prior to the procedure. A three monthly audit of the service was undertaken. Between July 1996 and June 2005 (9 years) 1,129 circumcisions were performed. The common complications were problems with the ring (3.6%) and bleeding (3%). Overall, there was 96% satisfaction rate among the service users. The Plastibell technique for circumcision is a simple method and can be safely performed by trained nurses with acceptable complication rates.

Circumcision, Male↗
PubMed2006

Phase II study of sorafenib in patients with advanced hepatocellular carcinoma.

PURPOSE: This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients. METHODS: Patients with inoperable HCC, no prior systemic treatment, and Child-Pugh (CP) A or B, received continuous, oral sorafenib 400 mg bid in 4-week cycles. Tumor response was assessed every two cycles using modified WHO criteria. Sorafenib pharmacokinetics were measured in plasma samples. Biomarker analysis included phosphorylated extracellular signal regulated kinase (pERK) in pretreatment biopsies (immunohistochemistry) and blood-cell RNA expression patterns in selected patients. RESULTS: Of 137 patients treated (male, 71%; median age, 69 years), 72% had CP A, and 28% had CP B. On the basis of independent assessment, three (2.2%) patients achieved a partial response, eight (5.8%) had a minor response, and 46 (33.6%) had stable disease for at least 16 weeks. Investigator-assessed median time to progression (TTP) was 4.2 months, and median overall survival was 9.2 months. Grade 3/4 drug-related toxicities included fatigue (9.5%), diarrhea (8.0%), and hand-foot skin reaction (5.1%). There were no significant pharmacokinetic differences between CP A and B patients. Pretreatment tumor pERK levels correlated with TTP. A panel of 18 expressed genes was identified that distinguished "nonprogressors" from "progressors" with an estimated 100% accuracy. CONCLUSION: Although single-agent sorafenib has modest efficacy in HCC, the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents.

Adult↗
PubMed2006

Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.

Activating mutations in Ras and B-RAF were identified in several human cancers. In addition, several receptor tyrosine kinases, acting upstream of Ras, were found either mutated or overexpressed in human tumors. Because oncogenic activation of the Ras/RAF pathway may lead to a sustained proliferative signal resulting in tumor growth and progression, inhibition of this pathway represents an attractive approach for cancer drug discovery. A novel class of biaryl urea that inhibits C-RAF kinase was discovered using a combination of medicinal and combinatorial chemistry approaches. This effort culminated in the identification of the clinical candidate BAY 43-9006 (Sorafenib, Nexavar), which has recently been approved by the FDA for advanced renal cell carcinoma in phase III clinical trials. Sorafenib inhibited the kinase activity of both C-RAF and B-RAF (wild type and V600E mutant). It inhibited MEK and ERK phosphorylation in various cancer cell lines and tumor xenografts and exhibited potent oral antitumor activity in a broad spectrum of human tumor xenograft models. Further characterization of sorafenib revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis. Thus, sorafenib may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling). In phase I and phase II clinical trials, sorafenib showed limited side effects and, more importantly, disease stabilization. This agent is currently being evaluated in phase III clinical trials in renal cell and hepatocellular carcinomas.

Benzenesulfonates↗
PubMed2006

Mobile peer-to-grid architecture for paramedical emergency operations.

In this paper we describe a distributed architecture that could be used to link emergency medical centres, hospitals, telephone operators, and ambulances into a hybrid Peer-to-Peer (P2P) and Grid system for the sharing of information and transport of data. Distributed computing techniques can be used to connect static and mobile systems, bringing the different tools, expertise and databases together to aggregate patient data "on-the-fly" and then integrate it into a situation and context-specific patient-centred virtual environment. The scenario presented in this paper encapsulates connecting mobile tools and medical devices from ambulances, enabling data transfer to medical centres, and aggregating patient data from numerous sources. The proposed P2G (Peer-to-Grid) framework consolidates Peer-to-Peer and Grid computing research by addressing the mobility of transiently connected devices while supporting interactive configurability of components for dynamic data-driven distributed paramedical scenarios.

Allied Health Personnel↗
PubMed2004

BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis.

The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional characterization showed that BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrated significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor beta, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrated inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non-small-cell lung cancer cell lines expressing mutant KRAS were insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor beta, and VEGFR-3 cellular receptor autophosphorylation was also observed for BAY 43-9006. Once daily oral dosing of BAY 43-9006 demonstrated broad-spectrum antitumor activity in colon, breast, and non-small-cell lung cancer xenograft models. Immunohistochemistry demonstrated a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrated significant inhibition of neovascularization in all three of the xenograft models. These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.

Administration, Oral↗
PubMed2003

High-content proteomics: fluorescence multiplexing using an integrated, high-sensitivity, multiwavelength charge-coupled device imaging system.

The detection of proteins in 2-D gels and their subsequent identification by MS is still the "gold standard" in proteomics. Fluorescent detection has increasingly replaced colorimetric and radiometric detection on gels and blots. The reasons for this are multiple and varied and include higher sensitivity, better quantitation, increased dynamic range, speed, safety and ease of use. Unlike other methods, fluorescent protein detection is also typically very consistent in response from protein to protein and in many cases is compatible with MS methods for protein identification. The superior sensitivity and benefits achieved by fluorescent techniques have spurred the development of instrumentation capable of delivering precise, sensitive, high-resolution image acquisition over a wide variety of excitation and emission wavelengths. This report focuses on applications using the highly sensitive, charge-coupled device based ProXPRESS multilabel imager, readily configurable for image acquisition over a wide variety of wavelengths (380-700 nm and ultraviolet (UV)) using xenon lamp or UV excitation. The ability to simultaneously detect enzyme activities or protein modifications with different color fluorescent probes in addition to total protein amounts (multiplexing) allows the further mining of proteomic data content from a single set of protein samples. To this end, the development of instrumentation that enables a multiplexing strategy will become central to in-depth proteomic studies. The ProXPRESS maximizes the efficiency of experimental strategies that require flexibility and multicolor fluorescence detection.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2002

Diabetic gustatory sweating.

Gustatory sweating is a potential manifestation of autonomic dysfunction in diabetes. This syndrome is seen in long-standing diabetes and is associated with nephropathy, peripheral neuropathy, and other signs of dysautonomia. Symptoms of profuse head and neck diaphoresis with eating may suggest this clinical diagnosis. We present a patient who had complicated diabetes with symptoms of gustatory sweating and other evidence of dysautonomia. Diagnosis and treatment possibilities are discussed, with a review of the literature and an emphasis on bedside testing.

Diabetes Mellitus, Type 2↗
PubMed2000

New Labour and the enabling state.

The notion of the 'enabling state' gained currency in the UK during the 1990s as an alternative to the 'providing' or the welfare state. It reflected the process of contracting out in the NHS and compulsory competitive tendering (CCT) in local government during the 1980s, but was also associated with developments during the 1990s in health, social care and education in particular. The creation of an internal market in the NHS and the associated purchaser-provider split appeared to transfer 'ownership' of services increasingly to the providers - hospitals, General Practitioners (GPs) and schools. The mixed economy of care that was stimulated by the 1990 NHS and Community Care Act appeared to offer local authorities the opportunity to enable non state providers to offer care services in the community. The new service charters were part of the enablement process because they offered users more opportunity to influence provision. This article examines how far service providers were enabled and assesses the extent to which new Labour's policies enhance or reject the 'enabling state' in favour of more direct provision.

Journal Article↗
PubMed2000

Landmarks in the early duplication cycles of Aspergillus fumigatus and Aspergillus nidulans: polarity, germ tube emergence and septation.

When the spores of filamentous fungi break dormancy, nuclear division is accompanied by a series of ordered morphological events including the switch from isotropic to polar growth, the emergence of a second germ tube from the conidium and septation. Correlation of these morphological events with nuclear number allows them to serve as duplication cycle landmarks. Early duplication cycle landmarks have been characterized in Aspergillus nidulans, but not in other filamentous fungi. To learn more about duplication cycle control in filamentous fungi, a study was undertaken to compare the timing of landmarks in Aspergillus fumigatus and A. nidulans. Nuclear duplication took approximately 45 min in A. fumigatus, with mitosis occupying roughly 5% of this period. Under the same conditions, nuclear duplication in A. nidulans took approximately 60 min, with mitosis occupying roughly 4% of this period. In A. fumigatus the isotropic to polar switch preceded the first mitosis in 22% of cells, while in A. nidulans the isotropic to polar switch did not occur until after the first mitosis. In both A. fumigatus and A. nidulans the earliest emergence of a second germ tube from the conidium occurred after the third mitotic division. However, by the fifth mitosis only 19% of A. fumigatus conidia had a second germ tube, compared to 98% of A. nidulans conidia. In both A. fumigatus and A. nidulans, formation of the first septum occurred after the fourth mitotic division. In all experiments a few cells lagged behind the others in nuclear number. In this delayed group, it was common to see landmark events at an earlier mitotic division. Differences in nuclear number when identical landmarks occur in A. fumigatus versus A. nidulans, and uncoupling of mitotic division and landmarks in delayed cells suggest that nuclear division and morphogenesis lie in parallel pathways, perhaps coordinated by checkpoints.

Aspergillus fumigatus↗