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Stephen Thompson

Publications and source records attributed to Stephen Thompson.

10 recordsLinked to original sources
PubMed2006

Estimation of the optimal brachytherapy utilization rate in the treatment of carcinoma of the uterine cervix: review of clinical practice guidelines and primary evidence.

BACKGROUND: Brachytherapy (BT) is an integral part of cervical carcinoma treatment. There have been no attempts to estimate the optimal proportion of new cervical carcinoma cases that should be treated with BT, that is, the optimal rate of brachytherapy utilization (BTU). METHODS: Evidence-based guidelines and primary evidence were used to construct a BTU tree for carcinoma of the uterine cervix. Searches were performed of the epidemiological literature to ascertain the proportion of patients who fulfilled criteria for BT. The robustness of the model was tested by sensitivity analyses and by peer review. A patterns of care study of BT in New South Wales for 2003 was conducted, and actual BTU for cervical carcinoma determined. The differences between optimal and actual rates of BTU were assessed. RESULTS: The optimal cervical carcinoma BTU was 49% (range, 42% to 50%). In New South Wales in 2003, actual BTU was only 30% of 256 cervical carcinoma patients. The major discrepancy was for FIGO stage IB-IIA disease, where there was an underutilization of BT, estimated to be 15% actual use compared with 47% optimal use. In Surveillance, Epidemiology, and End Results (SEER) areas, there was underutilization for stage IB-IIA (22% actual BTU versus 47% optimal BTU) and for stage IIB-IVA (54% actual BTU versus 100% optimal BTU). CONCLUSIONS: BT for cervical carcinoma is underutilized in New South Wales and in SEER areas. The authors' model of optimal BTU can be used as a quality assurance tool to provide an evidence-based benchmark against which actual patterns of practice can be measured. The model can also be used to help determine adequacy of BT resource allocation.

Benchmarking↗
PubMed2006

A simple procedure for the photoregulation of chymotrypsin activity.

A convenient and rapid method for the photo-regulation of the proteolytic enzyme alpha-chymotrypsin is described. When alpha-chymotrypsin is coated with photolytic 1-(2-nitrophenyl)ethanol residues this not only markedly reduces the capability of the enzyme to digest both of the small substrates N-benzoyl-L-tyrosine ethyl ester and N-succinyl-L-phenylalanine p-nitroanilide, but also completely inhibits the enzyme's proteolytic activity. The inactivated alpha-chymotrypsin can then be reactivated under physiological conditions, when and where it is required, by exposure to UV-A light. These results further demonstrate that 1-(2-nitrophenyl)ethanol coated proteins can often be used as light sensitive biological switches as a simple alternative to site directed procedures.

Animals↗
PubMed2006

A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group.

The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent studies did not show similar favorable contribution of chemotherapy to the outcome of these children. Further efforts to identify active chemotherapy agents in children include use of agents that have shown efficacy in adult patients with high-grade glioma and agents that have shown promise in mice bearing human xenografts of brain tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of two such agents, procarbazine and topotecan in newly diagnosed patients with high-grade glioma who had measurable disease after diagnostic surgery. Neither agent showed efficacy within the confines of the statistical design of the study. This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT). Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.

BACKGROUND: This is a "proof of concept study" to test the hypothesis that pulsed radiofrequency, PRF, produces cell stress at the primary afferent level without signs of overt thermal damage. We assumed that cell stress would result in impairment of normal function, and used the expression of activating transcription factor 3, ATF3, as an indicator of cellular "stress". METHODS: PRF (20 ms of 500-kHz RF pulses, delivered at a rate of 2 Hz; maximum temperature 42 degrees C) was delivered either to the sciatic nerve of adult rats in mid thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen. Controls were sham-operated or L4 axotomised. All tissues were examined 14 days after surgery. The percentage of CGRP- or ATF3-positive DRG neuronal somata was calculated using image analysis software (SigmaScan Pro 4). RESULTS: ATF3 expression was upregulated in L4 DRG neuronal cell bodies, irrespective of their size, after axotomy. It was also upregulated significantly (p<0.002) and selectively, in small and medium calibre L4 DRG neurons, when PRF was applied close to the DRG just distal to the intervertebral foramen. PRF did not produce any obvious cellular changes in the nerve or L4 DRG neurons when applied to the sciatic nerve in mid-thigh. CONCLUSION: PRF has a biological effect, unlikely to be related to overt thermal damage. It appears to be selective in that it targets the group of neurons whose axons are the small diameter C and Adelta nociceptive fibres.

Activating Transcription Factor 3↗
PubMed2005

Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection.

Drug Design↗
PubMed2005

Understanding mass school shootings: links between personhood and power in the competitive school environment.

This paper explores perspectives about certain individual and social characteristics that may contribute to school shootings by students. It begins with perspectives on individual/environment fit, arguing first that persons marginalized by their caregivers during their upbringing, and by their peers, are lacking in the social interactions that help develop ethical behavior. Our argument contends that lacking such interactions may result in the failure to develop a sound moral philosophy. Further, we argue that when such persons enter the highly competitive environment found in some suburban and rural schools, some will be continually and consistently marginalized, finding their means of self-expression and sense of significance subdued. Their need for self-expression and a sense of significance as persons will surface, but without the benefit of a moral philosophy to guide that expression, this may result in deviant means of expression, such as violence--even extraordinary violence. We do not attempt to identify a list of specific traits of school shooters, which might lead to the development of a profile of school shooters. Rather, we are concerned with the characteristics of the environment in which shootings might occur, and how students not fully prepared for that environment might react. Thus, this paper is an overview of how seeds of the neglect of the basic needs of personhood, when sown early in life, and nurtured by peers, might come to fruition in the fertile field of the competitive school environment.

Adolescent↗
PubMed2004

Small-molecule-protein conjugation procedures.

Small-molecule-protein conjugates are often required to act as immunogeneic complexes in the production of both monoclonal and polyclonal antibodies against small antigens. When antibodies have been obtained, they (and/or the small antigens) need to be labeled to facilitate their use in diagnostic assays. It is often impossible or extremely expensive to obtain the required conjugates. This chapter therefore discusses the common procedures used to couple small molecules to proteins and the analysis of the resulting conjugates. Practical guidance is given on the coupling of small molecule carboxyl, hydroxyl, and amine residues to amine and sulfhydryl residues on proteins using linkage techniques in which the author has extensive experience. Although a comprehensive list and analysis of every available linker is not given, the practical advice should enable the reader to use any commercially available linker productively to its optimum potential.

Animals↗
PubMed2004

Immunoprecipitation and blotting: the visualization of small amounts of antigens using antibodies and lectins.

The practical problems encountered when purifying and visualizing small amounts of antigens from complex cellular and protein mixtures are explored. Practical aspects and the relative advantages and disadvantages of immunoprecipitation and blotting, the two most commonly used antibody techniques, are discussed. As glycosylation of antigens is becoming recognized as an important factor in the progress of many diseases, a short section on the use of lectins in precipitation and blotting techniques is also included. It is highly likely that a combination of precipitation followed by blotting, using either lectin followed by antibodies or antibody followed by lectins, will become a valuable tool in characterizing cellular antigens and the progression of disease.

Animals↗
PubMed2003

Software for automatic calibration of synchrotron powder diffractometers.

An automatic procedure to calibrate angular-dispersive monochromatic diffraction instruments has been developed at the Daresbury Synchrotron Radiation Source. The procedure uses a macro Language to control the powder diffraction instruments to locate Bragg reflections and perform peak-centre refinement from a standard reference material. The information obtained is used to refine the wavelength of the radiation used and the angular offset of the detector arm. The concept and implementation of the new software are described with applications to demonstrate its viability. The results of a reliability and accuracy study are also presented.

Journal Article↗