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Biomedical subjects

M Shelley

Publications and source records attributed to M Shelley.

At least 19 recordsLinked to original sources
PubMed2006

Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer.

BACKGROUND: Hormone therapy for early prostate cancer has demonstrated an improvement in clinical and pathological variables, but not always an improvement in overall survival. We performed a systematic review of both adjuvant and neo-adjuvant hormone therapy combined with surgery or radiotherapy in localised or locally advanced prostate cancer. OBJECTIVES: The objective of this review was to undertake a systematic review and, if possible, a meta-analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer. SEARCH STRATEGY: We searched MEDLINE (1966-2006), EMBASE, The Cochrane Library, Science Citation Index, LILACS, and SIGLE for relevant randomised trials. Handsearching of appropriate publications was also undertaken. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1-T4, any N, M0, comparing neo-adjuvant or adjuvant hormonal deprivation in combination with primary therapy (radical radiotherapy or radical prostatectomy) versus primary therapy alone were included in this review. DATA COLLECTION AND ANALYSIS: Data were extracted from eligible studies and assessed for quality, and included information on study design, participants, interventions, and outcomes. Comparable data were pooled together for meta-analysis with intention-to treat principle. MAIN RESULTS: Men with prostate cancer have different clinical outcomes based on their risk (T1-T2, T3-T4, PSA levels and Gleason score). However, the majority of studies included in this review did not report results by risk groups; therefore, it was not possible to perform sub-group analysis. Neo-adjuvant hormonal therapy prior to prostatectomy did not improve overall survival (OR 1.11, 95% CI 0.67 to 1.85, P = 0.69). However, there was a significant reduction in the positive surgical margin rate (OR 0.34, 95% CI 0.27 to 0.42, P < 0.00001) and a significant improvement in other pathological variables such as lymph node involvement, pathological staging and organ confined rates. There was a borderline significant reduction of disease recurrence rates (OR 0.74, 95% CI 0.55 to 1.0, P = 0.05), in favour of treatment. The use of longer duration of neo-adjuvant hormones, that is either 6 or 8 months prior to prostatectomy, was associated with a significant reduction in positive surgical margins (OR 0.56, 95% CI 0.39 to 0.80, P = 0.002). In one study, neo-adjuvant hormones prior to radiotherapy significantly improved overall survival for Gleason 2 to 6 patients; although, in two studies, there was no improvement in disease-specific survival (OR 0.99, 95% CI 0.75 to 1.32, P = 0.97). However, there was a significant improvement in both clinical disease-free survival (OR 1.86, 95% CI 1.93 to 2.40, P < 0.00001) and biochemical disease-free survival (OR 1.93, 95% CI 1.45 to 2.56, P < 0.00001). Adjuvant androgen deprivation following prostatectomy did not significantly improve overall survival at 5 years (OR 1.50, 95% CI 0.79 to 2.85, P = 0.2); although one study reported a significant disease-specific survival advantage with adjuvant therapy (P = 0.001). In addition, there was a significant improvement in disease-free survival at both 5 years (OR 3.73, 95%CI 2.30 to 6.03, P < 0.00001) and 10 years (OR 2.06, 95% CI 1.34 to 3.15, P = 0.0009). Adjuvant therapy following radiotherapy resulted in a significant overall survival gain apparent at 5 (OR 1.46, 95% CI 1.17 to 1.83, P = 0.0009) and 10 years (OR 1.44, 95% CI 1.13 to 1.84, P = 0.003); although there was significant heterogeneity (P = 0.09 and P = 0.07, respectively). There was also a significant improvement in disease-specific survival (OR 2.10, 95% CI 1.53 to 2.88, P = 0.00001) and disease-free survival (OR 2.53, 95% CI 2.05 to 3.12, P < 0.00001) at 5 years. AUTHORS' CONCLUSIONS: Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.

Androgen Antagonists↗
PubMed2006

Bisphosphonates for advanced prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer in men in many western countries. It is characterized by its propensity for bone metastases which occur in more than 80% of patients with advanced disease. Patients are at risk of complications including pain, hypercalcaemia, bone fracture and spinal cord compression. Hormonal treatment is the mainstay of treatment for these patients but most of them will then become hormone refractory. Bisphosphonates act by inhibiting osteoclast activities and are a potential therapeutic option for metastatic prostate cancer. In addition, they have been shown to reduce pain in patients with bone metastases as a consequence of multiple myeloma. Early uncontrolled studies of bisphosphonates in metastatic prostate cancer patients have shown encouraging results. OBJECTIVES: The objective of this review was to determine the effectiveness of bisphosphonates in relieving pain in patients with bone metastases from prostate cancer. SEARCH STRATEGY: Studies were identified by electronic search of bibliographic databases including MEDLINE, EMBASE, CancerLit and the Cochrane Controlled Trials Register. Handsearching included Proceedings of American Society of Clinical Oncology and reference lists of all eligible trials identified. SELECTION CRITERIA: Randomised controlled studies comparing the effectiveness of bisphosphonates with placebo or open control for pain relief in patients with bone metastases from prostate cancer. DATA COLLECTION AND ANALYSIS: Data were extracted from eligible studies and included study design, participants, interventions and outcomes. Comparable data were pooled together for meta-analysis with intention-to-treat principle. Outcomes included pain response, analgesic consumption, skeletal events (including pathological fractures, spinal cord compression, bone radiotherapy, bone surgery), prostate cancer death, disease progression, radiological response, PSA response, adverse events, performance status, quality of life and comparisons between different routes, doses and types of bisphosphonates. MAIN RESULTS: One thousand nine hundred and fifty-five patients from ten studies were included in this review. The pain response rates were 27.9% and 21.1% for the treatment group and the control group, respectively, with an absolute risk difference of 6.8%. The OR for pain response was 1.54 (95% CI 0.97 to 2.44, P = 0.07), showing a trend of improved pain relief in the bisphosphonate group, although this was not statistically significant. The rates for skeletal events were 37.8% and 43.0% for the treatment group and the control group, respectively, with an absolute risk difference of 5.2%. The OR for skeletal events was 0.79 (95% CI 0.62 to 1.00, P = 0.05). A significant increase in nausea was observed in patients who received bisphosphonates compared to placebo. No increase in other adverse events was observed. There was no statistically significant difference between the bisphosphonate group and the control group in terms of prostate cancer death, disease progression, radiological response and PSA response. There are insufficient data to guide the choice of bisphosphonates or the dose and the route of administration . AUTHORS' CONCLUSIONS: Bisphosphonates should be considered for patients with metastatic prostate cancer for the treatment of refractory bone pain and prevention of skeletal events. More research is needed to guide the choice of bisphosphonates, optimal treatment schedule as well as cost-benefit comparisons. Combining results from different studies is difficult because different tools were used to assess pain, and also, bisphosphonates vary considerably in potency. This review highlights the need for standardisation and co-ordination among researchers in cancer pain studies.

Bone Density Conservation Agents↗
PubMed2006

Periodic sedimentation in a Stokesian fluid.

We study the sedimentation of two identical but nonspherical particles sedimenting in a Stokesian fluid. Experiments and numerical simulations reveal periodic orbits wherein the bodies mutually induce an in-phase rotational motion accompanied by periodic modulations of sedimentation speed and separation distance. We term these "tumbling orbits" and find that they appear over a broad range of body shapes.

Journal Article↗
PubMed2005

Cotton liners to mediate glove comfort for greenhouse applicators.

Greenhouse applicators' acceptance of cotton knit gloves worn as liners under nitrile chemical-resistant gloves (CRG) for pesticide application was investigated through a wear study in Iowa and New York. Comfort was assessed by questionnaires and interviews with 10 applicators. Contamination levels of four pesticides on CRG and liners at thumb, forefinger, palm, and cuff locations were determined by chemical analysis using high-performance liquid chromatography or gas chromatography. Applicators reported feeling more comfortable with cotton liners under their CRG than without and that cotton liners were easy to manage. Contamination was significantly greater on nitrile CRG than on cotton liners underneath, but a few liner specimens had measurable contamination. No significant contamination differences were found between right- and left-hand gloves. Contamination varied significantly by hand location, with cuffs least, and by pesticide, with chlorpyrifos most. These results support the Environmental Protection Agency's recommendation that liners should be disposable, but further work on liners and their laundering feasibility seems indicated.

Agriculture↗
PubMed2005

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma.

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Administration, Inhalation↗
PubMed2002

Cleanup of gloves contaminated with granular terbufos and tefluthrin.

Chemical-resistant gloves are used for protection from pesticides in farming operations. Cleanup of gloves after pesticide contamination was the focus of this research. Nitrile, neoprene, and barrier laminate glove specimens were exposed to 300 mg terbufos or tefluthrin granules for 3 or 30 min in petri dishes in a laboratory. Specimens were cleaned by flush with running water or LaunderOmeter washing with detergent. Following the cleanup treatments, specimens were dried and placed in test tubes with solvents to extract pesticide residue. Levels of contamination remaining were determined by gas chromatography. The residue remaining varied with exposure time, material type, cleanup method, and pesticide. Flush was more effective with the shorter exposure time. Tefluthrin was more effectively removed than terbufos. Barrier laminate was confirmed as a single-use material. Cleanup procedures reduced contamination in nitrile and neoprene, but findings show that these materials retained residue after cleanup.

Agriculture↗
PubMed2001

How simple cells are made in a nonlinear network model of the visual cortex.

Simple cells in the striate cortex respond to visual stimuli in an approximately linear manner, although the LGN input to the striate cortex, and the cortical network itself, are highly nonlinear. Although simple cells are vital for visual perception, there has been no satisfactory explanation of how they are produced in the cortex. To examine this question, we have developed a large-scale neuronal network model of layer 4Calpha in V1 of the macaque cortex that is based on, and constrained by, realistic cortical anatomy and physiology. This paper has two aims: (1) to show that neurons in the model respond like simple cells. (2) To identify how the model generates this linearized response in a nonlinear network. Each neuron in the model receives nonlinear excitation from the lateral geniculate nucleus (LGN). The cells of the model receive strong (nonlinear) lateral inhibition from other neurons in the model cortex. Mathematical analysis of the dependence of membrane potential on synaptic conductances, and computer simulations, reveal that the nonlinearity of corticocortical inhibition cancels the nonlinear excitatory input from the LGN. This interaction produces linearized responses that agree with both extracellular and intracellular measurements. The model correctly accounts for experimental results about the time course of simple cell responses and also generates testable predictions about variation in linearity with position in the cortex, and the effect on the linearity of signal summation, caused by unbalancing the relative strengths of excitation and inhibition pharmacologically or with extrinsic current.

Action Potentials↗
PubMed2001

Effects of exposure time, material type, and granular pesticide on glove contamination.

Chemical-resistant gloves are recommended for pesticide applicators to reduce their exposure to agricultural chemicals. In this research, three chemical-resistant glove materials-nitrile, neoprene, and barrier laminate-were studied in relation to contamination with granular terbufos and tefluthrin. Surfaces of specimens backed with alpha cellulose were contaminated with 300 mg of either granular terbufos or tefluthrin for 1-, 2-, 4-, 8-, 16-, and 24-h time periods in petri dishes in the laboratory. Residues were extracted using ethyl acetate for terbufos and iso-octane for tefluthrin in test tubes for 24 h. Analysis of extracts by gas chromatograph and statistical analysis of the data showed that contamination levels varied with the time of exposure, material type, and pesticide used. Pesticide was not detected in the alpha cellulose even after 24 h contamination time. A linear relationship was found between contamination level and exposure time for terbufos in the three materials, with longer exposure times causing higher contamination levels. Contamination of nitrile was significantly less than neoprene or barrier laminate. Exposed glove materials contained higher levels of contamination of terbufos than tefluthrin.

Chromatography, Gas↗
PubMed2000

Flexible filaments in a flowing soap film as a model for one-dimensional flags in a two-dimensional wind.

The dynamics of swimming fish and flapping flags involves a complicated interaction of their deformable shapes with the surrounding fluid flow. Even in the passive case of a flag, the flag exerts forces on the fluid through its own inertia and elastic responses, and is likewise acted on by hydrodynamic pressure and drag. But such couplings are not well understood. Here we study these interactions experimentally, using an analogous system of flexible filaments in flowing soap films. We find that, for a single filament (or 'flag') held at its upstream end and otherwise unconstrained, there are two distinct, stable dynamical states. The first is a stretched-straight state: the filament is immobile and aligned in the flow direction. The existence of this state seems to refute the common belief that a flag is always unstable and will flap. The second is a flapping state: the filament executes a sinuous motion in a manner akin to the flapping of a flag in the wind. We study further the hydrodynamically coupled interaction between two such filaments, and demonstrate the existence of four different dynamical states.

Journal Article↗
PubMed2000

A neuronal network model of macaque primary visual cortex (V1): orientation selectivity and dynamics in the input layer 4Calpha.

In this paper, we offer an explanation for how selectivity for orientation could be produced by a model with circuitry that is based on the anatomy of V1 cortex. It is a network model of layer 4Calpha in macaque primary visual cortex (area V1). The model consists of a large number of integrate-and-fire conductance-based point neurons, both excitatory and inhibitory, which represent dynamics in a small patch of 4Calpha-1 mm(2) in lateral area-which contains four orientation hypercolumns. The physiological properties and coupling architectures of the model are derived from experimental data for layer 4Calpha of macaque. Convergent feed-forward input from many neurons of the lateral geniculate nucleus sets up an orientation preference, in a pinwheel pattern with an orientation preference singularity in the center of the pattern. Recurrent cortical connections cause the network to sharpen its selectivity. The pattern of local lateral connections is taken as isotropic, with the spatial range of monosynaptic excitation exceeding that of inhibition. The model (i) obtains sharpening, diversity in selectivity, and dynamics of orientation selectivity, each in qualitative agreement with experiment; and (ii) predicts more sharpening near orientation preference singularities.

Animals↗
PubMed2000

Is the quality of asthma prescribing, as measured by the general practice ratio of corticosteroid to bronchodilator, associated with asthma morbidity?

The objective of this study was to determine whether the quality of asthma prescribing in general practice is associated with the severity of asthma patients' symptoms. Cross-sectional survey of asthma-like symptoms in patients prescribed antiasthma therapy was used. The setting was two general practices with contrasting ratios of corticosteroid to bronchodilator (high vs. low). The main outcome measures were: patient symptoms score and patient characteristics (age, gender, diagnosis, smoking, social class, and deprivation status). Patients on antiasthma therapy from the practice with the low corticosteroid to bronchodilator ratio had a higher mean symptom score (20.1, 95% CI 18.6, 21.7) than patients on antiasthma therapy from the practice with the high corticosteroid to bronchodilator ratio (13.2, 95% CI 11.8, 14.5). The mean difference in patient symptom score between the two practices was 7.0 (95% CI 4.9, 9.0); this changed little after adjustment for potential confounders. The quality of prescribing, as measured by the practice ratio of corticosteroid to bronchodilator, appears to be an important factor in the outcome of asthma care. The ratio of corticosteroid to bronchodilator in a general practice is one indicator of the quality of prescribing for asthma.

Adolescent↗
PubMed1996

Is the ratio of inhaled corticosteroid to bronchodilator a good indicator of the quality of asthma prescribing? Cross sectional study linking prescribing data to data on admissions.

OBJECTIVE: To investigate the ratio of inhaled corticosteroid to bronchodilator as a measure of the quality of asthma prescribing by general practitioners. DESIGN: Ecological cross sectional study linking general practitioner asthma prescribing with hospital admission data and a measure of deprivation. SUBJECTS: 11 family health services authorities in the West Midlands region and 99 general practices in North Staffordshire. MAIN OUTCOME MEASURES: Hospital admission rates for asthma; the ratio of inhaled corticosteroid to bronchodilator; and Townsend deprivation scores. RESULTS: No overall significant correlation was found between admission rates for asthma and corticosteroid:bronchodilator ratios for family health services authorities (Spearman's rs = -0.109, P = 0.750) or general practices (rs = -0.084, P = 0.407). In deprived family health services authority areas and general practices an inverse non-significant correlation existed between admission rates for asthma and corticosteroid:bronchodilator ratios (rs = -0.300, P = 0.624; rs = -0.218, P = 0.136). In contrast, in more affluent areas and general practices a positive non-significant correlation existed between admission rates and corticosteroid:bronchodilator ratios (rs = 0.371, P = 0.468; rs = 0.038, P = 0.792). CONCLUSION: Although the corticosteroid:bronchodilator ratio may be a valid indicator of the quality of prescribing for individual patients with asthma, caution should be applied in interpreting aggregated ratios. Differences in the severity of asthma or the prevalence of chronic obstructive pulmonary disease may explain inconsistent associations between admission rates for asthma and corticosteroid:bronchodilator ratios in family health services authorities and general practices with different deprivation scores.

Administration, Inhalation↗
PubMed1996

Reduction of urinary basic fibroblast growth factor using pentosan polysulphate sodium.

OBJECTIVE: To evaluate the use of pentosan polysulphate sodium (PPS) to reduce the level of urinary basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: Forty-one patients with a clam enterocystoplasty were randomized to receive either 200 mg three times daily of oral PPS (n = 21) or placebo (n = 20) for 6 weeks. Three patients acted as a cross-over study. Urinary bFGF was measured before and after treatment and the degree of symptomatic benefit assessed using a questionnaire. RESULTS: There was no reduction in bFGF in the patients receiving placebo (P = 0.235) but there was a statistically significant reduction in bFGF (P = 0.0251) in the patients receiving PPS, most of whom were symptomatically improved, especially with regard to mucus production. CONCLUSION: PPS may have a role in reducing urinary bFGF in patients with bladder tumours or following an enterocystoplasty and also in improving the quality of life of patients with a clam enterocystoplasty.

Adolescent↗
PubMed1996

Elevated levels of basic fibroblast growth factor in the urine of clam enterocystoplasty patients.

PURPOSE: We determined whether basic fibroblast growth factor is elevated in the urine of patients who have undergone clam ileocystoplasty. MATERIALS AND METHODS: An immunoassay technique was used to measure urinary basic fibroblast growth factor in 50 patients equally divided between those with and without neuropathy who had undergone clam enterocystoplasty. The results were compared with urinary basic fibroblast growth factor concentrations from 25 healthy age and sex matched volunteers. RESULTS: There is a highly significant elevation of urinary basic fibroblast growth factor in clam enterocystoplasty patients compared to controls, which is not related to the presence or absence of infection. There is no difference between those with and without neuropathy. CONCLUSIONS: Elevated levels of basic fibroblast growth factor are an important consideration in the malignant potential of the clam procedure.

Adolescent↗