A self-scored medical history teaching technique.

A technique to teach second-year medical students to make diagnostic assessments from information gained in a medical interview is presented. This method involves having students read transcripts of actual interviews, write medical histories, and make medical assessments of the patient's problem without benefit of physical examination or laboratory data. Four lectures were given which discussed the relationships between symptoms and physical illness. Students wrote medical histories and made diagnostic assessments based on transcribed medical histories. They then discussed the medical and psychosocial aspects of the patient's problem with family physicians in small group discussions. A new self-scoring technique is described which gives students rapid feedback on their written medical histories.

Benzodiazepine-opiate antagonism--a problem in intensive-care therapy.

A 14-year-old previously fit schoolboy was admitted with staphylococcal pneumonia secondary to influenza A infection. His condition deteriorated as he developed adult respiratory distress syndrome (ARDS); during a stormy recovery exceptionally high doses of benzodiazepines and opiates were given in order to suppress voluntary breathing during a successful period of assisted ventilation. It is possible that benzodiazepine-opiate antagonism developed. Subsequent studies in laboratory mice indicate that the respiratory depressant effects of morphine can be antagonized by prior treatment with lorazepam.

The use of neurally released agonist in the measurement of antagonism at alpha-adrenoceptors.

Graded contractile responses of the rat vas deferens were obtained to trains containing varying numbers of pulses delivered transmurally at 500 Hz, allowing construction of pulse-response curves. In the presence of postjunctional adrenoceptor blocking drugs, these curves were displaced to the right in a parallel manner, allowing the estimation of pA2 values for the drugs. Activity of drugs at prejunctional adrenoceptors was estimated from the reduction of inhibition of the response to a second pulse delivered 3 s after trains containing different numbers of pulses. It is suggested that the technique is more physiological than others used to determine the antagonistic activity of drugs at adrenoceptors.

Separation of adrenergic and non-adrenergic contractions to field stimulation in the rat vas deferens.

Adrenergic and 'non-adrenergic' nerve-induced contractions in rat vas deferens were separated pharmacologically. Responses to single stimuli comprised two components, an alpha-noradrenergic component (IIs), dominant in the epididymal portion, and a 'non-adrenergic' component (Is), dominant in the prostatic portion. Is but not IIs was blocked by nifedipine. A combination of adrenergic blockade and nifedipine virtually abolished all components. After cocaine, a third component (IIIs) emerged which was abolished by either adrenergic blockade or nifedipine. The response to trains of stimuli consisted of 'twitch' and 'secondary' components. This biphasic time course was modified by adrenergic blockade or nifedipine to reveal the time course of the 'non-adrenergic' and adrenergic components, respectively: these did not correspond to the 'twitch' and 'secondary' components. A combination of adrenergic blockade and nifedipine virtually abolished the whole response. Prejunctional alpha 2-adrenoceptor-mediated inhibition of the contractile responses could be blocked by selective alpha 2-adrenoceptor antagonists. The adrenergic contractile response demonstrated this 'feed-back' even on the second pulse at 0.5 Hz. Endogenous inhibition of the 'non-adrenergic' contraction required higher frequencies or enhancement of the extracellular concentration of noradrenaline by blockade of its neuronal uptake. Contractile responses to exogenous noradrenaline were abolished by nifedipine, at a concentration that did not affect the adrenergic (IIs) neurotransmission. These results reinforce the view that part of the motor transmission in rat vas deferens is non-adrenergic and allow the disentanglement of the various postjunctional and prejunctional elements contributing to the complex response to a train of stimuli.

Evidence to support the hypothesis that ATP is a co-transmitter in rat vas deferens.

Application of exogenous ATP or of noradrenaline (NA) produced responses in bisected rat vas deferens which mimicked the biphasic responses to nerve stimulation, and these actions were modified by nifedipine and verapamil in a manner similar to the modification of the 2 phases of the responses of the vas to nerve stimulation. It is proposed that sufficient evidence now exists to support the hypothesis that in this tissue, ATP is released along with NA from the motor nerves and that ATP may indeed be a co-transmitter.

A comparison of the effects of nifedipine and verapamil on rat vas deferens.

Nifedipine preferentially blocks contractions of the prostatic end of the rat vas deferens to single pulse field stimulation, leaving the epididymal end largely unaffected. This action is not due entirely to antagonism of calcium influx. Verapamil unexpectedly potentiated the responses of the prostatic portion, and antagonized those of the epididymal end. The use of nifedipine may, therefore, allow investigations of adrenergic mechanisms on this tissue to be studied without the complications of non-adrenergic transmission.

The effect of a benzotriazinium salt on in vitro and in vivo arrhythmias in guinea-pigs and mice.

In guinea-pig Langendorff hearts, a benzotriazinium derivative, 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI), increased the ventricular refractory period, increased the ventricular fibrillation threshold to electrical stimulation and converted persistent ventricular fibrillation to sinus rhythm. TnPBI also converted aconitine-induced tachyarrhythmias to sinus rhythm in the same preparation. In mice pretreated with TnPBI, both acutely and chronically, the amount of intravenous aconitine necessary to produce cardiac arrhythmias was increased. In guinea-pigs anaesthetised with halothane. TnPBI converted adrenaline-induced arrhythmias to sinus rhythm.

Comparison of the effects of a benzotriazinium iodide and quinidine on guinea-pig heart.

1 The actions of 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI) and quinidine were compared on guinea-pig heart preparations. 2 Quinidine had negative inotropic and chronotropic effects on guinea-pig isolated atria and on Langendorff hearts: TnPBI had negative inotropic and chronotropic effects on Langendorff hearts, but showed a positive inotropic effect on isolated atria at low dose levels. 3 Both quinidine and TnPBI increased the effective refractory period of guinea-pig atrial preparations. 4 The effects of TnPBI on transmembrane action potentials indicated a mixed class I and class III action according to the classification of Vaughan Williams (1970). 5 These effects are discussed in relation to the antiarrhythmic actions of TnPBI.

The local anaesthetic activity of a benzotriazinium salt.

1 The local anaesthetic properties of 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI) were compared with those of lignocaine hydrochloride on intact and desheathed sciatic nerves of the frog, on the phrenic nerve-hemidiaphragm preparation of the rat, and by the intradermal wheal test in the guinea-pig. 2 Both TnPBI and lignocaine were more potent on desheathed than on intact sciatic nerves. The potency of TnPBI was affected more than that of lignocaine by the presence of the sheath in intact nerves. 3 Both drugs inhibited conduction in the rat phrenic nerve, as shown by the reduction in twitch tension of the diaphragm elicited by nerve stimulation. TnPBI also caused an initial augmentation of the twitch tension of the diaphragm when applied directly to the muscle. 4 TnPBI was shown to be approximately twice as potent as lignocaine by the guinea-pig intradermal wheal test. 5 These results are discussed in view of the known effects of TnPBI on intracellular calcium storage.

Comparison of the effects of caffeine and a 2-alkyl-1,2,3-benzotriazinium iodide on frog rectus abdominis.

1 The mode of action of 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI), which induced contractures of frog rectus abdominis muscle, was investigated. 2 TnPBI caused contractures of frog rectus abdominis when the muscle had been depolarized with potassium chloride. 3 Experiments with TnPBI and caffeine in calcium-free Ringer suggested that both compounds produce contractures by releasing intracellular bound calcium. 4 It is suggested that at least two calcium stores are involved, one of which is sensitive to caffeine while both are sensitive to TnPBI.