Low sensitivity of current clinical markers (serum creatinine, blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.
Patients with locally advanced oropharyngeal cancer are at risk for poor outcomes due to the multi-modal nature of treatment and the potential for treatment-related toxicity. Although treatment with concurrent chemotherapy and radiotherapy has drastically reduced the need for a debilitating and disfiguring surgery, treatment related toxicities are often difficult to control. Acute toxicities include mucositis, skin desquamation, depression, cachexia, fatigue and nausea and vomiting. Failure to control these symptoms can adversely affect the patient's ability to complete their treatment regimen. Although there are many promising new treatments in the area of symptom management for this patient population, a review of the literature reflects the need for more research.
The purpose of this investigation was to compare the variability of vancomycin concentrations in the serum and CNS when administered continuously or as intermittent intravenous infusions in the rat. The hypothesis for this investigation was that the magnitude of change in serum vancomycin concentrations directly relates to the extent of vancomycin concentration fluctuations in the CNS. Microdialysis and serum sampling techniques were employed and biologic samples were analysed for vancomycin using HPLC. Over the dosing interval, the mean changes in concentrations were 71.8 +/- 9.8% and 13.6 +/- 9.3% for serum and 61.7 +/- 7.8% and 6.8 +/- 3.5% for brain extracellular fluid in the intermittent and continuously infused groups, respectively. Accordingly, the relative changes in vancomycin concentrations in brain extracellular fluid were closely associated with corresponding changes in serum concentrations (R2=0.94). Thus, continuous intravenous administration of vancomycin results in minimal serum and CNS tissue concentration changes as compared to traditional intermittent dosing methods and allows for more consistent vancomycin concentrations in the CNS.
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