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Biomedical subjects

B Evans

Publications and source records attributed to B Evans.

At least 19 recordsLinked to original sources
PubMed2006

The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: potential steroid-sparing role for DHEA.

Osteoporosis and associated fractures are the most common and debilitating complication of glucocorticoid use. The use of alternative anti-inflammatory agents without the deleterious skeletal effects of glucocorticoids is needed. Dehydroepiandrosterone (DHEA) may have immunomodulatory as well as positive effects on bone. For our further understanding of the mechanisms of action of DHEA, as a steroid-sparing agent, we investigated and compared the effects of dexamethasone (DEX) and DHEA on the regulation of the downstream effector pathway of osteoclastogenesis; RANKL/OPG and a range of inflammatory/pro-resorbing cytokines and receptors using a human clonal osteoblastic cell line. The cells were treated with DEX, DHEA, and androstenedione (ANDI). The mRNA expression of RANKL and OPG was determined by real-time PCR after overnight incubation. The regulation of a broad spectrum of cytokines by DEX and DHEA was also investigated using a human cytokine/growth factor and receptor gene array consisting of 268 cytokine-related cDNAs. To confirm some of the gene expression changes, protein production was measured by ELISA. RANKL expression and RANKL/OPG ratio were increased by DEX. This effect was reversed by co-treatment with both DHEA or ANDI. Several pro-inflammatory/resorptive cytokines including IL-6, IL-4, IFN-gamma, macrophage inhibitory factor (MIF) were down-regulated not only by DEX but also by DHEA. In contrast to DEX, DHEA did not lead to suppression of growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor-5 (FGF-5), insulin-like growth factor-binding protein3 (IGF-BP3). Several new target genes previously documented to influence bone formation were up-regulated by DHEA such as Notch 2, insulin receptor, thrombin receptor (PAR1). The data suggest that DHEA has immunomodulatory properties without the catabolic effects on bone remodeling, observed with glucocorticoid use. DHEA may thus prove useful as a steroid-sparing agent in the management of inflammatory disorders such as SLE or rheumatoid arthritis. Further in vivo studies are indicated.

Androstenedione↗
PubMed2006

Salvage prostate cryoablation after primary interstitial brachytherapy failure: a feasible approach.

Salvage treatment for recurrent prostate cancer remains a very difficult and challenging field in urologic oncology. The introduction of minimally invasive surgical procedures such a targeted cryoablation brings some hope with its feasibility and efficacy to become a potentially curable treatment. We present the case of a 75-year-old male with prostate cancer treated primarily by brachytherapy, who developed late locally recurrent disease that was successfully treated with targeted salvage cryoablation.

Aged↗
PubMed2005

Effect of epidural volume extension on dose requirement of intrathecal hyperbaric bupivacaine at Caesarean section.

BACKGROUND: The technique of epidural volume extension (EVE) involves the injection of saline into the extradural space immediately following the intrathecal injection, as part of a combined spinal-epidural (CSE) anaesthetic. One of the suggested benefits of EVE is a reduction in local anaesthetic required. The aim of this study was to test this hypothesis by comparing the median effective doses (ED50) of hyperbaric bupivacaine with fentanyl 25 microg with and without EVE for Caesarean section. METHODS: Sixty women were randomized to receive either CSE anaesthesia with EVE (EVE group) or no EVE (NEVE group). Using a double-blinded, up-down sequential technique, varying doses of bupivacaine with fentanyl 25 microg were administered. ED50 was estimated from up-down reversals and probit regression. RESULTS: The ED50 for bupivacaine was similar and not significantly different in the two groups (5.1 mg in the EVE and 6.1 mg in the NEVE group; difference 1.0 mg, 95% CI -0.12 to 2.2, P=0.08). CONCLUSIONS: This study illustrates that whilst low doses of intrathecal bupivacaine can be effectively used for Caesarean section, at such doses EVE does not appear to offer reliable or clinically relevant reductions in dosing with intrathecal bupivacaine.

Adjuvants, Anesthesia↗
PubMed2005

Severe uncontrolled pain in buttock in a patient on naltrexone: a diagnostic challenge.

A 26-year-old woman with a history of intravenous drug use was admitted to hospital with worsening pain in the right buttock radiating to the lateral part of the thigh and to the calf with no suspicion of cauda equina compression. Eventually, a diagnosis of sacroiliitis was made and appropriate antibiotics were administered. Provision of analgesia for this patient was difficult. On admission her medications included naltrexone, venlafaxine and tramadol. Initially naltrexone was continued and analgesia provided by epidural local anaesthetic and clonidine, intravenous ketamine and oral agents. After several days, naltrexone was ceased and opioids were used in addition to the other analgesics. The epidural analgesia was only partially effective, perhaps because of inadequate blockade of the L4-S1 nerve roots, which carry sensation from the sacroiliac joint. Naltrexone is a long-acting opioid antagonist. If opioid analgesia is planned, it is necessary to cease naltrexone for 24 to 72 hours. In an emergency, if non-opioid techniques prove ineffective, short-acting opioids can be titrated to effect in a monitored environment.

Adult↗
PubMed2004

Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream.

Pyoderma gangrenosum is potentially a devastating and destructive disorder. There is no uniformly effective or specific therapy for pyoderma gangrenosum. Previous reports of nicotine therapy for pyoderma gangrenosum have suggested it to be efficacious. Unfortunately, previous reports were restricted by the use of commercially available preparations of nicotine, either as a gum or patch formulation. We have used topical nicotine 0.5% w/w cetamacrogol formula A cream that enables direct application onto the lesion, as well as dose and concentration variation. Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.

Administration, Cutaneous↗
PubMed2003

Visual function following neurosurgical optic nerve decompression for compressive optic neuropathy.

AIMS: To assess the course of visual function after neurosurgical decompression of the optic nerve during resection of intracranial tumours. To obtain information that may be used to counsel patients. METHODS: A retrospective review of the acuity and visual fields of 27 patients undergoing neurosurgical decompression of 36 optic nerves in a regional neurosurgical centre. Two groups were considered, those undergoing craniotomy for sphenoid wing meningioma en plaque, and those undergoing an extended transbasal approach to intracranial tumours. RESULTS: At the last follow-up (1-97 months), improvement in acuity was seen in 47% of eyes with decompressed nerves. One-third of these showed late improvement, and two-thirds showed immediate improvement. In total, 20% of eyes had worse acuity at the last follow-up compared with preoperative values, just under one-third of these showed late deterioration, and the remainder showed immediate deterioration. In total, 33% of eyes achieved acuities equal to those recorded preoperatively, 6% improving to this level postoperatively. CONCLUSIONS: The majority of eyes in this study maintained or improved acuity after decompression. A proportion of eyes continue to improve after surgery, and a proportion deteriorate. There is no relation between duration of preoperative symptoms or the level of preoperative acuity and the change in acuity achieved.

Adult↗
PubMed2002

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay.

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for > 15 weeks in dry conditions up to 45 degrees C and in humid conditions up to 37 degrees C. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Animals↗
PubMed2002

Behavioural surveillance: the value of national coordination.

Behavioural surveillance programmes have enabled the description of population patterns of risk behaviours for STI and HIV transmission and aid in the understanding of how epidemics of STI are generated. They have been instrumental in helping to refine public health interventions and inform the targeting of sexual health promotion and disease control strategies. The formalization and coordination of behavioural surveillance in England and Wales could optimise our ability to measure the impact of interventions and health promotion strategies on behaviour. This will be particularly useful for monitoring the progress towards specific disease control targets set in the Department of Health's new Sexual Health and HIV Strategy.

Communicable Disease Control↗
PubMed2002

A novel mutation in human PAX9 causes molar oligodontia.

Experimental and animal studies, as well as genetic mutations in man, have indicated that the development of dentition is under the control of several genes. So far, mutations in MSX1 and PAX9 have been associated with dominantly inherited forms of human tooth agenesis that mainly involve posterior teeth. We identified a large kindred with several individuals affected with molar oligodontia that was transmitted as an isolated autosomal-dominant trait. Two-point linkage analysis using DNA from the family and polymorphic marker D14S288 in chromosome 14q12 produced a maximum lod score of 2.29 at theta = 0.1. Direct sequencing of exons 2 to 4 of PAX9 revealed a cytosine insertion mutation at nucleotide 793, leading to a premature termination of translation at aa 315. Our results support the conclusion that molar oligodontia is due to allelic heterogeneity in PAX9, and these data further corroborate the role of PAX9 as an important regulator of molar development.

Adult↗
PubMed2001

Time-lapse 3-D seismic imaging of shallow subsurface contaminant flow.

This paper presents a physical modelling study outlining a technique whereby buoyant contaminant flow within water-saturated unconsolidated sand was remotely monitored utilizing the time-lapse 3-D (TL3-D) seismic response. The controlled temperature and pressure conditions, along with the high level of acquisition repeatability attainable using sandbox physical models, allow the TL3-D seismic response to pore fluid movement to be distinguished from all other effects. TL3-D seismic techniques are currently being developed to monitor hydrocarbon reserves within producing reservoirs in an endeavour to improve overall recovery. However, in many ways, sandbox models under atmospheric conditions more accurately simulate the shallow subsurface than petroleum reservoirs. For this reason, perhaps the greatest application for analogue sandbox modelling is to improve our understanding of shallow groundwater and environmental flow mechanisms. Two fluid flow simulations were conducted whereby air and kerosene were injected into separate water-saturated unconsolidated sand models. In both experiments, a base 3-D seismic volume was recorded and compared with six later monitor surveys recorded while the injection program was conducted. Normal incidence amplitude and P-wave velocity information were extracted from the TL3-D seismic data to provide visualization of contaminant migration. Reflection amplitudes displayed qualitative areal distribution of fluids when a suitable impedance contrast existed between pore fluids. TL3-D seismic reflection tomography can potentially monitor the change in areal distribution of fluid contaminants over time, indicating flow patterns. However, other research and this current work have not established a quantifiable relationship between either normal reflection amplitudes and attenuation and fluid saturation. Generally, different pore fluids will have unique seismic velocities due to differences in compressibility and density. The predictable relationships that exist between P-wave velocity and fluid saturation can allow a quantitative assessment of contaminant migration.

Forecasting↗
PubMed2001

Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library.

A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.

Animals↗
PubMed2001

Formulation and process optimization to eliminate picking from market image tablets.

A tablet formulation when compressed using market image tooling may cause picking of powder. A D-optimal statistical experiment was designed to optimize the direct compression formulation and the process to alleviate picking of powder. The effects of levels of magnesium stearate, colloidal silicon dioxide (CSD), and lubrication time on picking were investigated using original compression tooling. These optimization results provided a small robust manufacturing region, hence a change in the cut angles of embossed letters and numbers from 70 degrees to 90 degrees in the modified compression tooling was evaluated. A statistical analysis of the data identified a robust manufacturing region that included formulations containing magnesium stearate 1-1.25% w/w, CSD 0.1-0.3% w/w, with a lubrication time of 5-10 min when compressed using modified compression tooling. The results indicate a significant reduction in picking by increasing the cut angles of embossed letters and numbers in the modified compression tooling. By evaluating interactions between various variables, we demonstrate a concentration dependent effect of CSD on the lubrication efficiency of magnesium stearate and compactability of microcrystalline cellulose containing formulation. In addition, the lubrication efficiency of magnesium stearate is maintained by blending CSD with powder blend prior to lubrication with magnesium stearate.

Drug Compounding↗