Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease.

OBJECTIVE: Laboratory tests including optical platelet aggregometry (OPA), platelet function analyser (PFA-100), and thromboxane B2 (TXB2) metabolite levels have been used to define aspirin resistance. This study characterised the prevalence of aspirin resistance in patients with ischaemic heart disease (IHD) and investigated the concordance and repeatability of these tests. DESIGN, SETTING AND PATIENTS: Consecutive outpatients with stable IHD were enrolled. They were commenced on 150 mg aspirin daily (day 0) and had platelet function assessment (OPA and PFA-100) and quantitative analysis of serum/urine TXB2 at day > or =7 and then at a second visit approximately 2 weeks later. MAIN OUTCOME MEASURES: We assessed the prevalence of aspirin resistance by each method, concordance between methods of measuring response to aspirin and association between time points to assess the predictability of response over time. RESULTS: 172 patients (62.7 (SD 8.7) years, 83.1% male) were recruited. At visits 1 and 2, respectively, 1.7% and 4.7% were aspirin resistant by OPA, whereas 22.1% and 20.3% were aspirin resistant by PFA-100. There were poor associations between PFA-100 and OPA, and between TXB2 metabolites and platelet function tests. OPA and PFA-100 results were poorly associated between visits (kappa = 0.16 and kappa = 0.42, respectively) as were TXB2 metabolites, suggesting that aspirin resistance is not predictable over time. CONCLUSIONS: The prevalence of aspirin resistance is dependent on the method of testing. Response varies on a temporal basis, indicating that testing on a single occasion is inadequate to diagnose resistance or guide therapy in a clinical setting.

Bioavailability of two selegiline hydrochloride tablet products.

The bioavailability of two selegiline HCl (CAS 14611-52-0) tablet products was compared in a single-blind, single-dose, randomised, two-way, cross-over study with 25 healthy volunteers. A test preparation of selegiline HCl (4 x 5 mg tablets) was compared to a reference preparation of selegiline HCl (4 x 5 mg tablets). The volunteers were randomised receiving each treatment once. Two clinic days were separated by a wash-out period of between 6 and 14 days. The variable AUC(0-infinity) was the primary characteristic of the extent of formation (bioavailability) of the selegiline metabolites, desmethylselegiline and methamphetamine. For desmethylselegiline the point estimate (90% confidence interval) of the "test/reference" mean ratio for the variable Cmax is 98.4% (91.2% to 106%), for AUC(0-infinity) 103% (97.6% to 109%), and for Cmax/ AUC(0-infinity) 95.6% (89.4% to 102%). For methamphetamine the point estimate (90% confidence interval) of the "test/reference" mean ratio for the variable Cmax is 101% (96.8% to 105%), for AUC(0-infinity) 102% (95.3% to 109%), and for Cmax/AUC(0-infinity) 99.0% (91.5% to 107%). The results of this study indicate that the test preparation is bioequivalent to the reference preparation with respect to both the rate and extent of formation of desmethylselegiline and methamphetamine.

The structure and function of a slowly adapting touch corpuscle in hairy skin.

1. Slowly adapting cutaneous mechanoreceptors, in the cat and primates, have been studied by histological and neurophysiological methods.2. Each touch corpuscle is a dome-shaped elevation of the epidermis, whose deepest layer contains up to fifty specialized tactile cells.3. Nerve plates, enclosed by the tactile cell (Merkel cells), are connected to a single myelinated axon in the dense collagenous core of the corpuscle.4. The corpuscle generated > 1000 impulses/sec when excited by vertical surface pressure. The response was highly localized and showed a low mechanical threshold, the frequency being dependent upon the velocity and amplitude of the displacement. There was a period of rapid adaptation before a sustained response which might continue for > 30 min.5. A quantitative analysis of the responses to excitation by displacements of differing amplitude, velocity and duration is included.6. The discharge of touch corpuscle units evoked by a mechanical stimulus was temperature-sensitive, and was enhanced by a fall in skin temperature.