An inhibitory effect of veratridine during tetanic stimulation of the rat diaphragm

The membrane ‘labilizer’ veratridine (3.7 ± 10^-6 m) which potentiates the contractions at twitch (0.1 Hz) stimulation due to multiple discharges, inhibited the tetanic contractions (50 Hz in 10 s) and the simultaneously recorded electromyogram in a use-dependent way, leading to fading of tetanic tension. The effect was equal during indirect and direct stimulation, and could therefore be localized to the excitable sarcolemma. This was confirmed by intracellular recording of action potentials, showing a marked veratridine-induced fallout of action potentials during continuous 50 Hz stimulation, whereas endplate potentials were unaffected. Accordingly, veratridine probably caused a use-dependent inhibition of the Na⁺ channels of the excitable sarcolemma. The tetanic fade was unaffected by K⁺ depolarization, increased by hyperpolarization in K⁺-free solution, and decreased by high Ca²⁺. All these changes of the ionic concentrations inhibited the twitch potentiating effect of veratridine. Since hyperpolarization and increasing the electric field in the membrane with high Ca^,+ had opposite effects on the tetanic fade, the field change was probably not the cause of the antagonism in high Ca²⁺. Instead, a membrane stabilizing effect of high Ca²⁺ is suggested, since the neutral local anaesthetic benzocaine (1.5 ± 10^-4 m), which is also a membrane stabilizing drug, had the same effects as high Ca²⁺ on the veratridine-induced tetanic fade. The effect of veratrine during tetanic stimulation was partly reversible upon washing. The reversibility was enhanced by high Ca²⁺ or benzocaine.     

IMPROVED TOLERABILITY OF FELODIPINE COMPARED WITH AMLODIPINE IN ELDERLY HYPERTENSIVES: A RANDOMISED,DOUBLE-BLIND STUDY IN 535 PATIENTS,FOCUSING ON VASODILATORY ADVERSE EVENTS

SUMMARY The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was >160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p=0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.     

Reconciling scientific and religious discourse about madness during the age of reason: lessons for today?

Reconciling scientific and religious discourse about madness during the age of reason: lessons for today? This paper argues that the secularization of madness, during the seventeenth and eighteenth centuries, occurred as a consequence of cultural change that accompanied the social upheavals of the age. In examining the reconciliation of competing explanations for madness, from theological and empirical viewpoints, it is suggested that these paradigms were never totally separated and argued that developments during this period were a consequence of continual interaction and dialogue between these contrasting views. Furthermore, it is suggested that an understanding of these changing times can illuminate present debates surrounding mental illness.     

Magnetic resonance imaging of cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis is a rare familial sterol storage disease with accumulation of cholestanol and cholesterol particularly in xanthomas, bile and brain. Magnetic resonance imaging is a useful modality for imaging the affected tissues. It contributes to the evaluation and management of the disease.     

Clinical Evaluation of Atrial Synchronous Ventricular Inhibited Pacemakers

The technical specifications and the operation of two atrial synchronous ventricular inhibited (ASVIP) pacemaker designs are described along with the results of clinical evaluation of these pacemakers in 30 patients. Clinical advantages of such pacemakers are contrasted with the performance of A-V sequential (DVI) and atrial synchronous (VAT) systems.