Calculations of temperature rise produced in body tissue by a spherical electrode

Two estimates of temperature rise produced in body tissue when a spherical electrode passes current have been calculated. The estimates bracket the expected temperature rise. Time-transient and steady-state results have been obtained. The effects of heat transfer through the highly conductive metal electrode and irreversible. Faradaic reactions have been considered. The calculations indicate that electrodes smaller than about 2 μm in radius produce a peak temperature rise of about 1°C when driven by typical square current pulses of 25 μA intensity and 200 μs duration. The results are presented in a graphic form allowing for quick estimation of the expected peak temperature rise around electrodes of a specific radius, which are driven with a pulse of known current density and duration.     

A case of acute ventricular capture threshold rise associated with flecainide acetate

Antiarrhythmic agents may increase capture threshold, but this is rarely of clinical significance. Flecainide acetate, a class IC agent, is reported to have a significant effect on the myocardial capture threshold. In this presentation, we report the case of a 72-year-old male, with a previously implanted VVI pacemaker due to sick sinus syndrome, who was treated with flecainide acetate for paroxysmal atrial arrhythmia control. During the fifteenth day of treatment, an abrupt rise in the ventricular capture threshold with ventricular pacing failure was noted. The capture threshold decreased two days after discontinuation of flecainide acetate.     

The nature of molecular recognition by T cells

Considerable progress has been made in characterizing four key sets of interactions controlling antigen responsiveness in T cells, involving the following: the T cell antigen receptor, its coreceptors CD4 and CD8, the costimulatory receptors CD28 and CTLA-4, and the accessory molecule CD2. Complementary work has defined the general biophysical properties of interactions between cell surface molecules. Among the major conclusions are that these interactions are structurally heterogeneous, often reflecting clear-cut functional constraints, and that, although they all interact relatively weakly, hierarchical differences in the stabilities of the signaling complexes formed by these molecules may influence the sequence of steps leading to T cell activation. Here we review these developments and highlight the major challenges remaining as the field moves toward formulating quantitative models of T cell recognition.     

Intracortical origin of the short latency facilitation produced by pairs of threshold magnetic stimuli applied to human motor cortex

Under certain conditions, EMG responses evoked by pairs of transcranial magnetic stimuli over the motor cortex are larger than the sum of the responses to each stimulus given alone. This occurs with interstimulus intervals of around 1.3, 2.5 and 4.3 ms and could be due to interaction between the responses to each stimulus at either the cortex or spinal cord. We recorded the descending volleys set up by such pairs of stimuli from the cervical epidural space of five patients implanted with chronic stimulators for pain control. Interstimulus intervals of 1, 1.2, 1.4 and 2 ms were used to investigate the first peak of facilitation. Enhanced EMG responses occurred after pairs of stimuli at 1, 1.2 and 1.4 ms, and these were accompanied by larger and more numerous descending volleys than expected from the sum of each stimulus alone. We conclude that facilitatory interaction between the stimuli can occur within the cerebral cortex. This may involve elements that produce repetitive I-wave activity in response to a single stimulus.     

The error threshold

Basic principles underlying the population dynamics of bacteria and viruses are presented, with emphasis on RNA viruses. Concepts reviewed here include fitness, mutant generation, competition, selection, sequence space and the theoretical origins of quasispecies. A "wild-type" virus is no longer viewed as the fittest type, but as the center of gravity of a population landscape. A consequence of quasispecies is the existence of an error threshold for selective competence. The error threshold has a justification in quasispecies theory and lends itself to exploration of strategies to drive viral populations over the error threshold, the central theme of this volume.     

The inevitable rise of mediocrity in academic medicine

The present analysis addresses the question of how it has been possible for academic medicine to grow and lose its creative productivity at the same time. A mathematical model is developed to simulate the mechanisms that govern growth of medical systems over time. Time-dependent growth of system size increases the occurrence of statistical deviations of all system parameters. Deviations are correlated with costs and creative output. As deviation-induced costs start to strain the system's tolerance, means become implemented to restrict deviation, which ultimately also reduces its creative output. To maintain growth combined with high levels of creative output, an academic medical system would need to continuously branch off and nurture smaller subsystems, which pursue their own set of goals relatively independently of the overall academic structure.     

The role of mesolimbic dopamine in conditioned locomotion produced by amphetamine

Daily administration of psychomotor stimulants in a distinctive environment can impart on the environment stimulantlike properties. Rats injected with amphetamine (0.75 mg/kg, sc) daily for 5 days exhibited a robust unconditioned locomotor response, measured in photocell cages, and showed a conditioned locomotor response when treated with saline on the 6th day. This conditioned locomotor response was found to be significantly attenuated by 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens when the lesion was made either pre- or postconditioning. Similarly, although rats with 6-OHDA lesions of the nucleus accumbens exhibited a robust supersensitive unconditioned locomotor hyperactivity in response to apomorphine (0.1 mg/kg, sc), they did not show a conditioned response on the test day. These results suggest that the mesolimbic dopamine system may be responsible for both the unconditioned and conditioned locomotor responses to psychomotor stimulant drugs. Further, conditioned locomotion depends on a critical interaction between the physiological release of presynaptic dopamine and occupation of postsynaptic receptors.