A convenient LC-MS method for assessment of glucose kinetics in vivo with D-[13C6]glucose as a tracer.

BACKGROUND: The isotope-labeled intravenous glucose tolerance test (IVGTT) combined with computer modeling is widely used to derive parameters related to glucose metabolism in vivo. Most of these methods involve use of either (2)H(2)-labeled or (13)C(1)-labeled D-glucose as a tracer with GC-MS to measure the isotope enrichment. These methods are challenging, both technologically and economically. We have developed a novel approach that is suitable for labeled-IVGTT studies involving a large cohort of individuals. METHODS: The tracer, D-[(13)C(6)]glucose, is a low-cost alternative with the significant advantage that the sixth isotope of natural glucose has virtually zero natural abundance, which facilitates isotopomer analysis with <1% labeled glucose in the infusate. After deproteinization of plasma samples collected at various times, glucose is converted to a stable derivative, purified by solid-phase extraction (SPE), and analyzed by HPLC-electrospray ionization mass spectrometry to accumulate the isotope-abundance data for the A+2, A+3, and A+6 ions of the glucose derivative. A 2-pool modeling program was used to derive standard kinetic parameters. RESULTS: With labeled-IVGTT data from 10 healthy male individuals, the values for insulin sensitivity, glucose effectiveness, and the plasma clearance rate estimated with the 2-pool minimal model compared well with values obtained via traditional methods. CONCLUSIONS: The relative simplicity and robustness of the new method permit the preparation and analysis of up to 48 samples/day, a throughput equivalent to 2 complete IVGTT experiments, and this method is readily adaptable to existing 96 well-format purification and analytical systems.

Assessment of a point-of-care lactate monitor in emergency admissions of adult horses to a referral hospital.

BACKGROUND: Blood lactate concentration [LAC] is considered a useful indicator of disease severity in horses. Agreement of point-of-care (POC) lactate monitors with laboratory standards has not been established for clinically abnormal horses. HYPOTHESIS: It was hypothesized that results from a POC lactate monitor would be in agreement with a laboratory-based measurement of [LAC]. ANIMALS: The study included adult horses presented for emergency evaluation. METHODS: A prospective observational study was performed. [LAC] was measured with whole blood (AWB) and plasma (APL) by means of a POC monitor (Accutrend) and compared with results from whole blood measured by a laboratory blood gas analyzer (NOVA). RESULTS: Samples from 221 horses were used to compare the 2 lactate measurement techniques. Agreement (p +/- SE) was closest between APL and NOVA (0.97 +/- 0.01); an average observed difference of 0.15 +/- 0.89 (mean +/- SD) and 95% limits of agreement (LOA) -1.89, 1.59 also were found. Agreement was preserved and 95% LOA further decreased in horses with NOVA [LAC] of <5 mM and PCV <40%. Agreement was modest when testing whole blood samples on the POC monitor with increased 95% LOA. CONCLUSIONS AND CLINICAL IMPORTANCE: Results indicate close agreement between NOVA and the POC monitor when [LAC] was measured with plasma. Results were less consistent at higher [LAC] but sufficiently reliable to follow trends. Although whole blood may be used with the POC monitor to identify clinically important hyperlactatemia, results may be insufficiently reliable to monitor trends.

Surgical and nonsurgical management of sagittal slab fractures of the third carpal bone in racehorses: 32 cases (1991-2001).

OBJECTIVE: To compare results (ie, return to racing and earnings per race start) of surgical versus nonsurgical management of sagittal slab fractures of the third carpal bone in racehorses. DESIGN: Retrospective study. ANIMALS: 32 racehorses (19 Thoroughbreds, 11 Standardbreds, and 2 Arabians). PROCEDURE: Medical records and radiographs were reviewed to obtain information regarding signalment and treatment. Follow-up information was obtained from race records. Robust regression analysis was performed to evaluate earnings per start in horses that raced at least once before and after injury. RESULTS: 22 (69%) horses raced at least once after treatment of the fracture. All 7 horses treated by means of interfragmentary compression raced after treatment, and horses that underwent interfragmentary compression had significantly higher earnings per start after the injury than did horses treated without surgery. Eight of 9 horses treated by means of arthroscopic debridement of the damaged cartilage and bone raced after treatment, but only 7 of 16 horses treated without surgery (ie, stall rest) were able to return to racing after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that racehorses with sagittal slab fractures of the third carpal bone have a favorable prognosis for return to racing after treatment. Horses treated surgically were more likely to race after treatment than were horses treated without surgery.

Statistical characteristics of area under the receiver operating characteristic curve for a simple prognostic model using traditional and bootstrapped approaches.

Prognostic models are increasingly common in the biomedical literature. These models are frequently evaluated with respect to their ability to discriminate between those with and without an outcome. The area under the receiver-operating curve (AROC) is often used to assess discrimination. In this study, we introduce a bootstrap method, and, using Monte Carlo simulation, we compare three different bootstrap approaches with four commonly used methods in their ability to accurately estimate 95% confidence intervals (CIs) around the AROC for a simple prognostic model. We also evaluated the power of a bootstrap method and the commonly used trapezoid rule to compare different prognostic models. We show that several good methods exist for calculating 95% CIs of AROC, but the maximum likelihood estimation method should not be used with small sample sizes. We further show that for our simple prognostic model a bootstrap z-statistic approach is preferred over the trapezoidal method when comparing the AROCs of two related models.