Use of Iatrogenic Lipid Emulsion and Subsequent Plasmapheresis for the Treatment of Amitriptyline Overdose.

Plasmapheresis for the treatment of hypertriglyceridemia is relatively uncommon and mostly reported either in patients experiencing hypertriglyceridemia-induced acute pancreatitis or patients with therapy-resistant familial hypercholesterolemia. Standard therapies for hypertriglyceridemia include dietary modification and lipid-lowering medication. For severe hypertriglyceridemia, the risk of pancreatitis increases significantly as triglyceride levels increase above 1000 mg/dL, and current therapies are unable to reduce triglyceride levels rapidly enough. Here, we report a case of a 48-year-old male patient who presented to the emergency department due to an amitriptyline overdose. In addition to being started on IV sodium bicarbonate therapy, an intravenous 20% fat emulsion bolus at 1.5 mL/kg was administered followed by 0.25 mL/kg/min infusion for 4 hours as a strategy to absorb lipophilic amitriptyline. Two days posttreatment, he was noted to have substantial hypertriglyceridemia (serum triglycerides: 6,475 mg/dL). His amylase was within the normal range at 37 U/L (reference range: 20-100 U/L), his lipase was low at 40 U/L (reference range: 75-390 U/L), and he was without evidence of any clinical sequelae secondary to hypertriglyceridemia (e.g., pancreatitis). Due to the severity of his hypertriglyceridemia, plasmapheresis was initiated urgently for rapid reduction in serum triglyceride levels to prevent pancreatitis and end-organ damage. He underwent a 1-plasma volume exchange with 5% albumin as the replacement fluid. This reduced his triglyceride levels to 185 mg/dL (reference range: 3-149 mg/dL). His symptoms secondary to his amitriptyline overdose were also resolved. Here, we report a 2-step process of intravenous lipid emulsion followed by plasmapheresis for amitriptyline overdose.

Impact of Triazole Therapeutic Drug Monitoring Availability and Timing.

Therapeutic drug monitoring (TDM) is an established strategy to optimize antifungal therapy with certain triazoles. While established relationships exist between concentration and safety or efficacy, the impact of TDM timing on outcomes is unknown. We report clinical outcomes, including antifungal exposure and mortality, in patients receiving institutional versus reference laboratory TDM. The availability of in-house triazole assays reduced the time to drug concentration result (12 versus 68 h; P < 0.001) and time to achieve therapeutic serum concentrations (10 versus 31 days; P < 0.001). Subtherapeutic concentrations were associated with higher patient mortality (32% versus 13.3%; P = 0.036).

Development of a sensitive LC/MS/MS method for vitamin D metabolites: 1,25 Dihydroxyvitamin D2&3 measurement using a novel derivatization agent.

Active vitamin D metabolites 1,25-dihydroxyvitamin D2 [1,25-(OH)2-D2; derived from ergocalciferol] and D3 [1,25-(OH)2-D3; derived from cholecalciferol] are found in low levels in the circulation and require a very sensitive method for measurement. Radioimmunoassay (RIA) has been the method of choice, but it lacks the specificity needed to distinguish between 1,25-(OH)2-D2 and -D3, whereas liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods have the advantage of high specificity and sensitivity. Here, we compare a new derivative for ionizing 1,25-(OH)2-D to enhance the signal and provide the most sensitive assay for measuring vitamin D. We used the Amplifex diene method of derivatizing prior to LC/MS/MS and compared it to the standard RIA method and the 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) method of derivatizing prior to LC/MS/MS. In the evaluation of 20 human serum samples, all methods correlated strongly across the upper levels of the standard 1,25-(OH)2-D2 and -D3 ranges (Amplifex and RIA, pc=0.97; Amplifex and PTAD, pc=0.96) but less strongly on the lower levels of the standard range (Amplifex and RIA, pc=0.81; Amplifex and PTAD, pc=0.65) suggesting differences in the sensitivities between the assays. The Amplifex method was determined to be more sensitive than the PTAD method, as peak areas were significantly higher for the Amplifex method and provided for a 10 fold higher signal-to-noise ratio than PTAD. Therefore, the Amplifex LC/MS/MS method is the most sensitive and specific method available for measuring 1,25-(OH)2-D2 and -D3 while using the smallest sample volume.

Health perceptions in patients who undergo screening and workup for prostate cancer.

OBJECTIVES: False-positive screening tests may induce persistent psychological distress. This study was designed to determine whether a positive screening test with negative biopsy findings for prostate cancer is associated with worsened mental health during short-term follow-up. METHODS: We conducted a cross-sectional telephone survey of two groups of men approximately 2 months after testing: group 1, 109 men with an abnormal prostate-specific antigen level or digital rectal examination findings but with negative biopsy findings for prostate cancer; and group 2, 101 age-matched primary care patients with PSA screening levels in the reference range (less than 4 ng/mL). Primary outcomes included state anxiety and prostate cancer-related worry. Secondary outcomes included Medical Outcomes Study Short Form 36-item Health Survey subscales and sexual function items. Multivariate regression techniques were used to adjust for differences in baseline covariates. RESULTS: Group 1 patients were more worried than group 2 patients about getting prostate cancer (mean worry 3.9 versus 4.5, P = 0.0001, using a 5-point scale, with 1 indicating extreme worry and 5 no worry). Group 1 patients also perceived their risk of prostate cancer to be significantly greater than that of controls (P = 0.001). No significant differences were found across state anxiety or Medical Outcomes Study Short Form 36-item Health Survey subscales. Sexual bother was greater for group 1 patients, with 19% reporting that sexual function was a moderate to big problem compared with 10% of group 2 patients (P = 0.0001). CONCLUSIONS: Men with abnormal prostate cancer screening tests report increased cancer-related worry and more problems with sexual function, despite having a negative biopsy result. Effective counseling interventions are needed before prostate cancer screening and during follow-up.

HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary assays.

BACKGROUND: The concentration of 25-hydroxyvitamin D [25(OH)D] in serum has been designated the functional indicator of vitamin D (VitD) nutritional status. Unfortunately, variability among 25(OH)D assays limits clinician ability to monitor VitD status, supplementation, and toxicity. METHODS: We developed an HPLC method that selectively measures 25-hydroxyvitamin D2 [25(OH)D2] and D3 [25(OH)D3] and compared this assay with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, a competitive protein-binding assay (CPBA) on the Nichols Advantage platform, and an RIA from Diasorin. RESULTS: For the new HPLC assay, between-run CVs were 2.6%-4.9% for 25(OH)D3 and 3.2%-13% for 25(OH)D2; recoveries were 95%-102%; and the assay was linear from 5 microg/L to at least 200 microg/L. Comparison data were as follows: for HPLC vs LC-MS/MS, y = 1.01x - 4.82 microg/L (Sy/x = 4.93 microg/L; r = 0.996) for 25(OH)D3, and y = 0.902x - 0.566 microg/L (Sy/x = 2.56 microg/L; r = 0.9965 for 25(OH)D2; for HPLC vs Diasorin RIA, y = 0.709x - 5.86 microg/L (Sy/x = 7.35 microg/L; r = 0.7509); and for HPLC vs Nichols Advantage CPBA, y = 1.00x - 3.60 microg/L (Sy/x = 32.7 microg/L; r = 0.6823). CONCLUSIONS: The new HPLC method is reliable, robust, and has advantages compared with the Nichols Advantage CPBA and the Diasorin RIA. The Nichols Advantage CPBA overestimated or underestimated 25(OH)D concentrations predicated on the prevailing metabolite present in patients' sera.

Postprandial lipoprotein changes in patients taking antiretroviral therapy for HIV infection.

OBJECTIVE: Dyslipidemia is common among patients receiving antiretroviral therapy for HIV infection. The purpose of this study was to determine whether postprandial lipemia contributes to the dyslipidemia observed in HIV-positive patients taking antiretroviral therapy. METHODS AND RESULTS: A standardized fat load was administered to 65 subjects (group 1 35 HIV-positive subjects receiving protease inhibitors [PIs]; group 2 20 HIV-positive subjects not receiving PIs; group 3 10 HIV-negative controls). Serum triglycerides, retinyl palmitate, and lipoproteins were measured using enzymatic and nuclear magnetic resonance spectroscopic techniques. Compared with HIV-negative controls, peak postprandial retinyl palmitate and large very low-density lipoprotein (VLDL) levels occurred later in both HIV-positive groups, and a delayed decrease in serum triglycerides was observed. However, postprandial areas under the curve (AUCs) for triglycerides, retinyl palmitate, chylomicrons, and large VLDL were similar. Postprandial AUCs for intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs) were higher in group 1 than groups 2 and 3 (all P<0.035). CONCLUSIONS: Postprandial clearance of triglyceride-rich lipoproteins is delayed in HIV-positive individuals receiving antiretroviral therapy. Compared with HIV-positive individuals not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial IDLs and LDLs. An oral fat load was administered to 55 HIV-positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride-rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV-positive subjects not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial intermediate-density and low-density lipoproteins.

Inaccuracy of lipid measurements with the portable Cholestech L.D.X analyzer in patients with hypercholesterolemia.

BACKGROUND: Although total cholesterol concentrations measured by portable lipid analyzers have acceptable bias and precision in young and middle-aged adults, clinically relevant differences in HDL-cholesterol (HDL-C) and triglyceride values have been described. Furthermore, the accuracy of portable lipid analyzers in older hyperlipidemic individuals, who have a high incidence of coronary heart disease, has not been validated. This study determined the biases and variability in portable lipid measurements in older patients with hypercholesterolemia and related them to National Cholesterol Education Program Adult Treatment Panel III guidelines. METHODS: Participants were > or =70 years of age with fasting serum LDL-cholesterol (LDL-C) concentrations > 1.40 g/L. Fasting fingerstick samples were analyzed on a Cholestech L.D.X desktop analyzer. Antecubital venous samples were analyzed in a proficiency-certified clinical laboratory. RESULTS: Portable measurements systematically overestimated triglycerides (0.296 g/L; P <0.001) and HDL-C (0.015 g/L; P = 0.026). LDL-C concentrations were underestimated (0.043 g/L; P = 0.046). Total and non-HDL cholesterol calculations based on the portable lipid device provided unbiased estimates, but wide variability was present. Significant variability in lipid determinations limited their clinical usefulness in individual patients, especially because 2 SD of the mean bias between the laboratory and the portable determinations of LDL-C and non-HDL cholesterol exceeded the 0.30 g/L cutoff that defines treatment targets in the current lipid guidelines. CONCLUSIONS: Lipid values obtained from portable lipid analyzers may be useful for screening, but they should not be used to make clinical decisions regarding the diagnosis and management of dyslipidemia in individual patients.