A call for snakebite research.
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Animals↗
Biomedical subjects
R L Norris
Publications and source records attributed to R L Norris.
Snakes as an overlooked natural vector control resource.
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Animals↗
High-performance liquid chromatography-tandem mass spectrometry as a reference for analysis of tacrolimus to assess two immunoassays in patients with liver and renal transplants.
The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (< 10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation < 10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD > 13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD > 23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some patients in whom effective therapeutic concentrations can be less than 5.0 microg/l.
Chromatography, High Pressure Liquid↗
Sensitive, specific quantitative analysis of tacrolimus (FK506) in blood by liquid chromatography-electrospray tandem mass spectrometry.
The capacity of liquid chromatography-tandem mass spectrometry (LC-MS2) to detect and define individual components in a complex mixture has been utilized to develop a quantitative assay of the potent immunosuppressant drug, tacrolimus. Trough blood concentrations were measured in 175 samples obtained over several weeks after liver transplantation from seven patients. The assay was linear over the range of 0.2 to 100 micrograms/L. Imprecision was <8%, and accuracy was 99-101%. The turnaround time for a batch of 20 samples was 2.5 h. No interference from any of the other drugs being administered to the patients was evident. An ELISA also performed on the same samples overestimated the concentrations substantially, as indicated by a plot of the difference between the results for the two methods vs their mean. The favorable characteristics of the LC-MS2 assay, especially its sensitivity and specificity, will facilitate detailed pharmacokinetic studies of tacrolimus, particularly under circumstances in which metabolism is perturbed by either hepatic dysfunction or drug interactions.
Animals↗
Delayed use of widow spider antivenin.
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Adult↗
Evaluation and comparison of the TDxII, Stratus, and OPUS digoxin assays.
Three automated immunoassays for digoxin in serum were evaluated--Abbott TDxII, Baxter Stratus, and Behring OPUS. The accuracy and precision of the assays were assessed by weighed-in controls and an external quality control program. Coefficients of variation of all methods in serum were < or = 10% at weighed-in concentrations of digoxin of 1 and 2.5 micrograms/L. Accuracy relative to weighed-in concentrations of 1 and 2.5 micrograms/L ranged from 98 to 126% for all methods. Comparative results from patient samples showed little difference between the TDxII and Stratus and a greater difference observed between the TDxII and OPUS assays. The detection of digoxin-free samples containing digoxin-like immunoreactive substances (DLIS) in neonatal cord blood, pregnant patients, and liver and renal recipients by each assay was then assessed. The TDxII exhibited the highest incidence of DLIS. This is evident in neonatal cord blood in which 40.4% of samples tested positive. In comparison, the extent of DLIS detected by Stratus was less and OPUS exhibited no DLIS in any of the groups studied. A case study of a patient treated with anti-digoxin Fab fragments (Digibind) also was included for analysis by each method. Fourteen hours after Digibind administration, the TDxII registered a digoxin concentration of 49.5 micrograms/L compared with 3.73, 1.80, and 2.49 micrograms/L for Stratus, OPUS, and ultrafiltered TDxII methods, respectively. The results indicate that to determine the concentration of digoxin after the administration of Digiband, the OPUS or fluorescence polarization immunoassay (FPIA)-ultrafiltered samples by TDxII are the assays of choice.
Adult↗
Sensitive high-performance liquid chromatographic assay with ultraviolet detection of methadone enantiomers in plasma.
Methadone is being prescribed increasingly as an analgesic in palliative medicine. R-Methadone has been shown to be responsible for most of the pharmacological activity of this drug. Despite that in most countries it is administered as the racemate. Few assay methods for the enantiomers are available; e en fewer can determine accurately the low concentrations of enantiomers required to undertake pharmacokinetic studies in patients taking the drug in analgesic doses. We present here an HPLC method used to determine concentrations of the specific enantiomers of methadone as low as 5.0 ng/ml with adequate precision and accuracy. The mean R/S ratio of the plasma concentrations was 0.80 +/- 0.05 (n = 3 samples) in one patient taking 25-27.5 mg daily and 1.21 +/- 0.12 (n = 6 samples) in another taking 10-20 mg daily. In the second patient, concentrations of the enantiomers ranged between 5.8 and 25.9 ng/ml. Tricyclic antidepressants did not interfere with the assay but dextropropoxyphene did. Its presence could be detected by dual wavelength monitoring.
Adult↗
Comparison of high-performance liquid chromatography and monoclonal fluorescence polarization immunoassay for the determination of whole-blood cyclosporin A in liver and heart transplant patients.
Conflicting conclusions have been drawn from comparisons of high-performance liquid chromatography (HPLC) and the Abbott Diagnostics monoclonal fluorescence polarization immunoassay (mFPIA) for cyclosporin. The aim of this study was to compare whole blood cyclosporin A (CsA) concentrations measured by both mFPIA and HPLC in liver and heart transplant patients. One hundred and twenty-four liver and 62 heart transplant patient samples were assayed by both methods. Assay imprecision for both methods during the studies was < 7% over the range 150-800 micrograms/L. At an HPLC-determined concentration of 100 micrograms/L, mFPIA overestimated CsA by 60% (liver) and 77% (heart). At 300 micrograms/L, the overestimation was 40% (liver) and 45% (heart). On this basis, the mFPIA is not interchangeable with HPLC.
Antibodies, Monoclonal↗
A reliable high-performance liquid chromatography assay for high-throughput routine cyclosporin A monitoring in whole blood.
We report here a reliable high-performance liquid chromatography-ultraviolet assay for routine assay of cyclosporin A (CsA) in whole blood using solid-phase extraction. This assay is linear, between 20 and 2,000 micrograms/L, with correlation coefficients > 0.998 for five consecutive standard curves. All coefficients of variation (CV) were < 8% at CsA concentrations of 45, 480, and 1,800 micrograms/L, with the exception of the between-day CV at 45 micrograms/L, which was < 15%. The relative accuracy of the method is > 94% at 45, 480, and 1,800 micrograms/L. The mean recoveries for CsA and cyclosporin D (internal standard) were 38.2 +/- 4.8% (n = 45) and 40.1 +/- 6.7% (n = 45), respectively. This method has proven to be reliable and robust in a high-throughput therapeutic drug monitoring laboratory.
Chemistry, Clinical↗
The influence of vancomycin concentration and the pH of plasma on vancomycin protein binding.
A review of numerous studies of the protein binding of vancomycin suggests major discrepancies among their results. The reported percent protein binding of vancomycin varies from 0% to 98%. The influence of pH and concentration on the protein binding of vancomycin was investigated in this study. There was a significant difference (p < 0.001) in percent protein binding in vancomycin-spiked plasma samples across the pH range of 7.0-8.0. There was no significant difference (p > 0.05) in percent protein binding in vancomycin-spiked plasma samples across the concentration range of 2-80 mg/L. It is likely that some of the variation reported to date may be due to a lack of control of pH during the measurement of protein binding of vancomycin.
Blood Proteins↗
Ketorolac for sickle cell vaso-occlusive crisis pain in the emergency department: lack of a narcotic-sparing effect.
STUDY OBJECTIVE: To determine if a single dose of intramuscular ketorolac given on presentation to the emergency department has a narcotic-sparing effect in adult patients with sickle cell vaso-occlusive crisis pain. DESIGN: A prospective, randomized, single-dose, double-blind study. SETTING: ED of a university hospital and an affiliated county hospital. TYPE OF PARTICIPANTS: Eighteen adult patients who presented to the ED with sickle cell crisis pain a total of 24 times. INTERVENTIONS: Patients were randomized to receive either ketorolac 60 mg IM or placebo on presentation to the ED. Subjects were administered meperidine on presentation and then received a standardized dose of meperidine every 30 minutes during the four-hour observation period based on the severity of pain. MEASUREMENTS AND MAIN RESULTS: The 12 subjects in the ketorolac group received an average of 231 +/- 92 mg meperidine, whereas the 12 subjects in the placebo group received an average meperidine dose of 250 +/- 85 mg (P = .61). CONCLUSION: The use of intramuscular ketorolac did not lead to a clinically significant reduction in the requirement for narcotics during the four-hour ED treatment period.
Acute Disease↗
Local anesthetics.
Emergency physicians often rely on the use of local anesthetic agents to relieve patient discomfort, and research continues in an effort to develop new agents with improved anesthetic qualities. Eventually, a nontoxic, rapidly acting agent may become available that could provide profound anesthesia of long duration when applied topically to intact skin or wounds. Until the "perfect" agent is developed, physicians can help the patient by making knowledgeable choices regarding local anesthetic techniques. By choosing topical agents when appropriate and buffering agents to be infiltrated, using courteous techniques of injection, and being cognizant of potential adverse reactions, the physician can turn a potentially unpleasant and frightening situation for the patient into a positive experience that promotes satisfaction and cooperation.
Anesthetics, Local↗
Apparent coral snake envenomation in a patient without visible fang marks.
Envenomation by the North American coral snake is an uncommon entity in the United States. In most cases fang marks will be present, although they may be quite small and difficult to see. The case of a young man who demonstrated evidence of envenomation following the bite of a Texas coral snake (Micrurus fulvius tenere), despite the absence of any apparent fang marks on close examination, is reported. The problems associated with coral snake envenomation in terms of diagnosis and management are reviewed.
Adult↗
Preliminary observations on the effects of hyperbaric oxygen therapy on western diamondback rattlesnake (Crotalus atrox) venom poisoning in the rabbit model.
Intermittent hyperbaric oxygen therapy has been shown to reduce skeletal muscle necrosis in a compartment syndrome animal model. To study whether intermittent exposure to hyperbaric oxygen augments antivenin therapy in reducing muscle necrosis, we injected sublethal doses of Western Diamondback rattlesnake (Crotalus atrox) venom intramuscularly into the hind legs of New Zealand White rabbits. In this pilot study, the animals were divided into three treatment groups. The first group received one vial of antivenin intravenously, the second group received one vial of antivenin intravenously plus three hyperbaric oxygen treatments, and the third group received no treatments. There were no statistically significant differences among the groups. These preliminary observations suggest that muscle necrosis secondary to Crotalus atrox venom poisoning is not significantly altered either by Antivenin [Crotalidae] Polyvalent at the dose level we used or in combination with intermittent hyperbaric oxygen treatments in this rabbit model.
Animals↗
Deep vein thrombosis in an adolescent.
We report an unusual case of deep vein thrombosis following minor trauma in an adolescent who presented with a swollen, tender, lower extremity. Work-up consisted of a venogram which demonstrated occlusion of the deep venous system in the proximal leg. The patient was hospitalized for intravenous heparin followed by oral anticoagulation therapy. The problem of deep venous thrombosis in adolescents and the approach to diagnosis are discussed.
Adolescent↗
A modified assay for cyclosporin in blood using solid-phase extraction with high-performance liquid chromatography.
A modified procedure for measuring cyclosporin in whole blood by high-performance liquid chromatography is described and evaluated for clinical use. Sample preparation uses solid-phase extraction cartridges that can be reused. Life of the reverse-phase analytical column exceeds 1,000 injections at 70 degrees C. Cyclosporins A and D (internal standard) elute after 5.6 and 7.6 min, respectively. Calibration plots are linear from 50 ng/ml to at least 2,000 ng/ml. Within-day and between-day imprecision is less than 9% (coefficient of variation). Minimum measurable concentration is 50 ng/ml.
Chromatography, High Pressure Liquid↗
Temelastine does not affect theophylline pharmacokinetics in normal subjects.
The pharmacokinetics of theophylline (i.v. aminophylline 250 mg) were studied in a balanced, double-blind crossover following the administration of oral temelastine (100 mg) or placebo, twice daily for 7 days, to 10 normal volunteers. Comparison of volumes of distribution, elimination rate constants, elimination half-lives and areas under the plasma concentration-time curve indicated that temelastine had no significant effect on theophylline pharmacokinetics.
Adult↗