Sudden Death Late After Doxorubicin Administration: Use of Electrophysiological Study and Treatment by Automatic Implantable Cardioverter Defibrillator

Two patients who survived cardiac arrest late after doxorubicin administration are described. Both patients had nonischemic, dilated cardiomyopathies and underwent electrophysiological studies during which no ventricular arrhythmias were induced. Their negative electrophysiological studies despite well documented cardiac arrests and subsequent clinical courses suggest that patients with cardiomyopathies after doxorubicin administra tion and dilated cardiomyopathies of other etiologies have similar natural histories. Treatment with an automatic implantable cardioverter defibrillator appears to be a reasonable therapeutic option for patients with anthracyline associated cardiac disease who have survived their malignancy but at the price of developing life-threatening arrhythmias.     

A digest of memory phenomena for addiction research

The implications for addiction research of recent knowledge about human memory are described. It is important that research using self-reported data understands the limits of suck data. The nature of human memory and the selective, constructive processes of remembering provide one set of limits. Abandoning retrospective data entirely is not feasible in addiction research, for it would require the abandonment of current and prospective self-reported data as well, as they are also subject to memory biases. Because of memory distortions, self-reports, even by rigorous questionnaire, are biased narratives rather than incomplete but otherwise accurate evocations of past events. These limits necessitate caution and humility in the interpretation of findings, and cannot be eliminated by any particular set of research methods. There will never be a philosophers’stone which will convert self-reported data into absolutely accurate figures of quantity, frequency and timing. Nor is it straightforward to infer social and psychological causality from the organization and timing of events as remembered.     

Synthesis of a cyclic analogue of the C-loop region of epidermal growth factor,containing 1-aminocyclopropane-1-carboxylic acid

We report the synthesis of a cyclic analogue of epidermal growth factor sequence 33–42 with substitution of 1-aminocyclopropane-1-carboxylic acid for glycine at position 39 (N-acetyl-Cys-Val-Ile-Gly-Tyr-Ser-ACPCA-Asp-Arg-Cys-NH₂). The analogue was synthesised by solid-phase methods, using t-Boc chemistry and acid-labile side-chain protecting groups. The use of the 4-methoxybenzyl protecting group for C- and N-terminal cysteine residues resulted in the spontaneous formation of the desired intramolecular disulfide bond after HF deprotection.     

Bilateral hypoglossal nerve palsies following head injury

Bilateral hypoglossal nerve palsies following head injury are very rare, with only two cases previously being reported. We present the case of an 11 year old boy who developed this disorder after being struck by a car and discuss the mechanism of injury which is most likely traction on the hypoglossal nerve.     

The Effect of Magnetic Resonance Imagers on Implanted Neurostimulators

This in-vitro study was designed to investigate the safety of various implanted neurostimulators in magnetic resonance (MR) imagers. The effects of the static and changing magnetic fields and the radio frequency (RF) electromagnetic field generated by 0.35 and 1.5 T MR imagers on the voltage output of four models of implantable passive neurostimulators and two models of implantable self-powered neurostimulators was studied. The neurostimulators were mounted on a support and placed in the imagers. An oscilloscope monitored the voltages at the outputs of the neurostimulators. For an Avery single-channel stimulator, located at the isocenter, the amplitude of the output pulses induced by the 0.35 T imager was 6V; from a 1.5 T imager, it was 12 V. These amplitudes can cause discomfort and possible harm to a patient if the typical therapeutic value is 1-5 V. The amplitude of the stimulator receiver's output decreased to relatively safe values beyond 40 cm from the isocenter. By contrast, there was no significant voltage output from the Medtronic SE-4 receiver. For two models of self-powered neurostimulators, the Medtronic Itrel and the Cordis MK II, the programmed stimulus parameters were not affected by the pulsed magnetic fields of the MR imagers. However, the RF fields at the isocenter heated the metal case of the stimulators. The rotational and linear forces produced by the fixed magnet on the Cordis MK II were judged to be too strong for a patient with this implant to be scanned. The study showed that patients with certain types of implanted neurostimulators can be scanned safely under certain conditions.     

Opioids in Pain and Cardiovascular Responses: Overview of Common Features

Common Opioid Actions in Pain and Cardiovascular Stress Responses. This overview describes three parallel aspects of the architecture and function of opioid action in nociceptive and cardiovascular spheres. First, in both circumstances, opioid secretion and receptor activation are essentially dormant during basal conditions and assume physiological importance only during stress. Second, in either context, opioids produce their responses by activating complementary mechanisms centrally and in the periphery. Third, endorphins act as "neuromodulators" of either type of response through a typical cellular architecture in which they diminish underlying excitatory neurotransmission.     

Predicting initiation to and cessation of buprenorphine and temazepam use amongst adolescents

Two interviews separated by 12 months (mean) were conducted with a purposive sample of Glaswegian adolescent drug misusers. Across that interval, beginning to use buprenorphine and temazepam were predictable by prior extent of other substance use, especially cannabis and tobacco, and by the Drug Misuse Scale, using selected MMPI items. About 50% of those who had been using either drug prior to first interview did not use at all between first and second interview. For temazepam, this cessation was not predictable, but ceasing to use buprenorphine was more likely the less time subjects had used this drug and if they had never injected. It is concluded that personality and frequent substance use predispose to drug misuse, but that additional factors must lead to dependence.     

Mechanism of Lethal Proarrhythmia Observed in the Cardiac Arrhythmia Suppression Trial: Role of Adrenergic Modulation of Drug Binding

A variety of recent in vivo studies have sought to clarify the mechanism underlying the proarrhythmic response to flecainide in the Cardiac Arrhythmia Suppression Trial (CAST). Increased inducibility of relatively stable ventricular arrhythmias in subacute and chronic postinfarction models has been universally observed. The arrhythmogenesis has been explained in part by drug induced modulation of anisotropic conduction in persistently ischemic tissue, increased durations of vulnerable windows, enhanced generation of unidirectional block with the introduction of extrastimuli, variability of repolarization within the ventricular wall, and the creation of stable reentrant circuits with narrow central zones of propagation. While these data explain arrhythmo-genesis in general, malignant ventricular arrhythmia capable of producing the excess sudden or arrhythmic death mortality in the CAST trial have not been universally observed, nor have the proported beneficial effects of β-blockade seen in the CAST trial and other studies been explained. Additional studies examining the adrenergic modulation of flecainide binding have shown reversal of flecainide effects in normal tissue, but paradoxical amplification of flecainide induced conduction slowing in depolarized tissue. This variable effect in normal versus abnormal tissue produces significant dispersions of conduction with an expected increased propensity for conduction failure in response to ectopy, increased liminal length for impulse propagation, enhanced vulnerability to premature extrastimuli, and completed reentrant circuits in regions of depressed membrane potentials. This, along with the decrease in action potential duration and accompanying refractoriness in the setting of adrenergic modulation may favor more malignant double wavelet or unstable ventricular arrhythmias.