Characterization of the renal pharmacology of HP-522, a loop diuretic with uricosuric activity.
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Biomedical subjects
Publications and source records attributed to S J Wilson.
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Photoplethysmography (PPG) is a common optical technique used to monitor peripheral pulsation. Studies have shown that minimal variability in phase characteristics is critical to attain accurate estimation of timing-related measurements, such as heart rate and pulse transit time. Observed abrupt changes from baseline of these measurements have shown to identify abnormalities in clinical studies. This study investigates nominal fluctuations when different detection settings were used on the PPG signals. The results indicate that there can be differences in variations observed, and an appropriate detection setting can minimize phase-induced errors in clinical interpretation of timing-related physiologic measurements.
Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.
Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in obese patients are limited. Some manufacturers have recommended a maximum daily dose of LMWH not to be exceeded. The purpose of this study was to determine if body weight influenced the anticoagulant response to a weight-based dose of LMWH for the treatment of venous thromboembolism. Patients with serum creatinine levels < 150 micromol/l receiving the LMWH, dalteparin 200 anti-Xa IU/kg based on actual body weight subcutaneously once daily for the treatment of deep vein thrombosis or pulmonary embolism, were eligible for the study. Patients received a minimum of 5 days LMWH treatment. Patients had peak anti-Xa levels (IL Test Chromogenic assay) measured 3-4 h following their day 3 injection and trough anti-Xa levels measured immediately prior to injections on day 3 and 5. No dose adjustments were made on the basis of the anti-Xa levels. Patients were a priori stratified into three weight classes: (A) within 20% of ideal body weight (IBW) (n = 13); (B) 20-40% of IBW (n = 14), and (C) greater than 40% of IBW (n = 10). The largest patient weighed 190 kg and had a body mass index of 58. Mean daily LMWH doses were 14,030, 17,646 and 23, 565 IU for groups A, B and C, respectively. Mean (SD) trough anti-Xa levels on day 3 were 0.12 (0.05) anti-Xa IU/ml for group A, 0.11 (0.03) anti-Xa IU/ml for group B and 0.11 (0.03) anti-Xa IU/ml for group C (p > 0.2). Similar trough anti-Xa levels were observed on day 5. Mean (SD) peak anti-Xa levels on day 3 were 1.01 (0.20) anti-Xa IU/ml, 0.97 (0.21) anti-Xa IU/ml and 1.12 (0.22) anti-Xa IU/ml for groups A, B and C, respectively (p > 0.2). No thromboembolic or bleeding complications occurred during LMWH therapy in any patients. These findings suggest that body mass does not appear to have an important effect on the response to LMWH up to a weight of 190 kg in patients with normal or near normal renal function.
BACKGROUND: A recent NIH Workshop and an ERS Task Force concluded that more work was needed to understand mechanisms of severe and chronic asthma. This report describes a series of studies that identify aberrant epithelial mesenchymal signalling in the airways as an important event in maintaining inflammation and driving remodelling in response to environmental injury. METHODS: Immunohistochemistry, genotyping and functional studies conducted on cultured asthmatic cells and mucosal biopsies were used to identify biochemical pathways involved in epithelial injury and repair in asthma and their relationship to disease severity. RESULTS: Our findings suggest that the asthmatic state results from an interaction between a susceptible epithelium and Th-2-mediated inflammation to alter the communication between the epithelium and the underlying mesenchyme - the epithelial mesenchymal trophic unit - leading to disease persistence, airway remodelling and refractoriness to corticosteroid treatment. CONCLUSIONS: Asthma is more than an inflammatory disorder, but requires engagement of important signalling pathways involved in epithelial repair and tissue remodelling. These pathways involving EGFRs and TGF-betaRs provide targets against which to develop novel therapies for chronic asthma.
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