Evaluation of an automated method for measuring von Willebrand factor activity in clinical samples without ristocetin.

INTRODUCTION: The development of an automated, von Willebrand factor (VWF) activity assay, Innovance(®) VWF Ac (VWF:Ac), which measures VWF binding to the platelet receptor glycoprotein Ibα without ristocetin, led us to evaluate the assay for diagnosing von Willebrand disease (VWD) and monitoring therapy. METHODS: After validating that the assay could be performed on an instrument from a different manufacturer, we compared VWF:Ac to VWF ristocetin cofactor activity (VWF:RCo) findings, including ratios of activity/antigen, for 100 healthy controls and 262 consecutive clinical samples from 217 patients (197 adults, 64 children, n = 1 age unknown) referred for VWF testing. RESULTS: There was excellent correlation (R(2) = 0.96) between VWF:Ac results run at two different sites on two different instruments. VWF:Ac had greater precision and sensitivity to low levels of VWF than the VWF:RCo method. Although there was good correlation between VWF:Ac and VWF:RCo results among healthy controls and patient subjects, VWF:Ac results were undetectable and/or significantly lower than VWF:RCo among patients who had types 2A, 2B, or 2M VWD. Additionally, a higher proportion of patient samples were classified as showing qualitative defects using the VWF:Ac compared with VWF:RCo method. While most samples drawn on VWD therapy had similar VWF levels by VWF:Ac and VWF:RCo, a type 2B VWD subject on replacement had much lower activity estimated by VWF:Ac. CONCLUSION: We conclude that Innovance(®) VWF Ac is suitable for the diagnosis, classification, and monitoring of VWD, and that it has a number of advantages over VWF:RCo method.

Simultaneous measurement of adenosine triphosphate release and aggregation potentiates human platelet aggregation responses for some subjects, including persons with Quebec platelet disorder.

Platelet aggregometry and dense granule adenosine triphosphate (ATP) release assays are helpful to diagnose platelet disorders. Some laboratories simultaneously measure aggregation and ATP release using Chronolume® a commercial reagent containing D-luciferin, firefly luciferase and magnesium. Chronolume® can potentiate sub-maximal aggregation responses, normalising canine platelet disorder findings. We investigated if Chronolume® potentiates human platelet aggregation responses after observing discrepancies suspicious of potentiation. Among patients simultaneously tested by light transmission aggregometry (LTA) on two instruments, 18/43 (42%), including 14/24 (58%) with platelet disorders, showed full secondary aggregation with one or more agonists only in tests with Chronolume®. As subjects with Quebec platelet disorder (QPD) did not show the expected absent secondary aggregation responses to epinephrine in tests with Chronolume®, the reason for the discrepancy was investigated using samples from 10 QPD subjects. Like sub-threshold ADP (0.75 µM), Chronolume® significantly increased QPD LTA responses to epinephrine (p<0.0001) and it increased both initial and secondary aggregation responses, leading to dense granule release. This potentiation was not restricted to QPD and it was mimicked adding 1-2 mM magnesium, but not D-luciferin or firefly luciferase, to LTA assays. Chronolume® potentiated the ADP aggregation responses of QPD subjects with a reduced response. Furthermore, it increased whole blood aggregation responses of healthy control samples to multiple agonists, tested at concentrations used for the diagnosis of platelet disorders (p values <0.05). Laboratories should be aware that measuring ATP release with Chronolume® can potentiate LTA and whole blood aggregation responses, which alters findings for some human platelet disorders, including QPD.

Biodistribution of liposome-associated bupivacaine after extradural administration to rabbits.

After one extradural injection of 0.25% bupivacaine 0.3 ml and 3H-bupivacaine 0.005 mCi in multilamellar liposomes, no systemic radioactivity (plasma, liver, heart muscle) was obtained for 1 h, and the labelling was less than that of systemic distribution of plain bupivacaine for the following 3 h. In contrast, radioactivity in the lumbar spinal nerves peaked in the first hour and remained higher than that of plain bupivacaine for 4 h. No radioactivity was measured in cerebrospinal fluid. Small unilamellar vesicles incorporating 3H-cholesterol did not significantly label spinal nerves and central nervous structures indicating that the mode of action of liposomal bupivacaine did not involve uptake by nerve structures. Rapid uptake of radioactivity by spinal nerves suggested exchange of bupivacaine between liposomes and nerve sheaths.

Pharmacokinetics and tissue distribution of ofloxacin in human subjects during a multiple dose regimen.

The pharmacokinetics of ofloxacin was studied in normal male volunteers selected from a student population. The aim of this study was to ascertain whether ofloxacin accumulated in plasma after administering six oral doses of the drug. The drug was administered in 300 mg tablets at intervals of 12 h for a total period of 72 h. The results clearly demonstrated that a modest accumulation of ofloxacin was observed between the first and second oral intake of the drug (R = 1.4); thereafter a steady-state plasma concentration was maintained at all time periods tested during the study. Furthermore, there was a broad fluctuation of approximately 80% between the Cmax and Cmin in the plasma levels of the drug during a 12-hour dosing interval. Hence demonstrating that a constant dose, repeatedly administered at a constant time interval of 12 h, ensured a broad range of concentrations of ofloxacin plasma, bile and other tissues which should favour the therapeutic success of the drug. There was agreement between the results of these studies and those in hospitalized patients suffering from severe infections. Analysis of ofloxacin after multiple dosing regimens in these patients showed measurable concentrations of the drug in the various tissues examined; hence suggesting a relative good bioavailability of the drug, which presumably reflected the high degree of success rates in these patients.

Enfermería y epilepsia / Nursing and epilepsy

La epilepsia, enfermedad rodeada de estigmas, espectacularidad y mitos, constituye un desafío para enfermería en cuanto ella puede contribuir a su prevención así como a asegurar el menor grado de daño y la pronta recuperación de quienes la padecen. Este artículo presenta suscintamente un panorama general de las responsabilidades de la enfermera al respecto (AU)

Enfermería y epilepsia / Nursing and epilepsy

La epilepsia, enfermedad rodeada de estigmas, espectacularidad y mitos, constituye un desafío para enfermería en cuanto ella puede contribuir a su prevención así como a asegurar el menor grado de daño y la pronta recuperación de quienes la padecen. Este artículo presenta suscintamente un panorama general de las responsabilidades de la enfermera al respecto