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Biomedical subjects

Timothy P Murphy

Publications and source records attributed to Timothy P Murphy.

22 records · Page 2Linked to original sources

Chronic renal ischemia: pathophysiologic mechanisms of cardiovascular and renal disease.

Chronic renal ischemia caused by renal artery stenosis (RAS) elicits a complex biologic response. Although the traditional pathophysiologic pathways underlying renal ischemia have been well studied, there is emerging evidence that additional mechanisms may be responsible for producing many of the hemodynamic alterations and end-organ injury seen in patients with RAS, including persistent hypertension, renal insufficiency, and cardiac disturbance syndromes. A better understanding of these mechanisms may allow earlier identification of RAS, provide markers to predict the response to revascularization, or allow unique therapeutic targets for drug development. This and a subsequent article will explore the pathophysiologic and clinical implications of chronic renal ischemia.

Cardiovascular Diseases↗

Chronic renal ischemia: implications for cardiovascular disease risk.

Chronic renal ischemia caused by atherosclerotic renal artery stenosis (RAS) is gaining recognition as a potentially important risk factor for cardiovascular (CV) morbidity and mortality. The etiology of increased risk of CV events is multifaceted and includes direct physiologic changes that increase risk as well as intermediate clinical effects that are associated with worse outcome. Physiologic changes associated with increased CV risk in patients with RAS include increased production of fibrogenic and vasoactive peptides such as renin, angiotensin, endothelin, and catecholamines, as well as endothelial cell dysfunction. Clinical intermediate conditions associated with higher incidences of CV events seen in patients with renal ischemia include hypertension, systemic atherosclerosis, chronic renal failure, and left ventricular hypertrophy and dysfunction. More thorough understanding of the myriad physiologic changes seen in patients with RAS will likely improve patient selection for renal artery revascularization. Clinical trials should examine a full range of CV and renal outcomes, not just blood pressure, to adequately assess the merits of revascularization.

Chronic Disease↗

Pharmacokinetics and excretion of gamma-hydroxybutyrate (GHB) in healthy subjects.

In Europe and the United States, the recreational use of gamma-hydroxy butyric acid (GHB) at dance clubs and "rave" parties has increased substantially. In addition, GHB is used to assist in the commission of sexual assaults. The aim of this controlled clinical study was to acquire pharmacokinetic profiles, detection times, and excretion rates in human subjects. Eight GHB-naïve volunteers were administered a single 25-mg/kg body weight oral dose of GHB, and plasma, urine, and oral fluid specimens were analyzed by using gas chromatography-mass spectrometry (GC-MS). Liquid-liquid extraction was performed after acid conversion of GHB to gamma-butyrolactone. Limits of quantitation of 0.1 (oral fluid), 0.2 (urine), and 0.5 microg/mL (plasma) could be achieved in the selected ion monitoring mode. GHB plasma peaks of 39.4 +/- 25.2 microg/mL (mean +/- SEM) occurred 20-45 min after administration. The terminal plasma elimination half-life was 30.4 +/- 2.45 min, the distribution volume 52.7 +/- 15.0 L, and the total clearance 1228 +/- 233 microL/min. In oral fluid, GHB could be detected up to 360 min, with peak concentrations of 203 +/- 92.4 microg/mL in the 10-min samples. In urine, 200 +/- 71.8 and 230 +/- 86.3 microg/mL, were the highest GHB levels measured at 30 and 60 min, respectively. Only 1.2 +/- 0.2% of the dose was excreted, resulting in a detection window of 720 min. Common side-effects were confusion, sleepiness, and dizziness; euphoria and change of vital functions were not observed. GHB is extensively metabolized and rapidly eliminated in urine and oral fluid. Consequently, samples should be collected as soon as possible after ingestion.

Adjuvants, Anesthesia↗