Endocrine Modulation of Reproduction

The ability of foreign compounds to affect the functioning ofvarious endocrine systems is currently thought responsible fora wide variety of effects. The presentations in this Symposiumreviewed the evidence for and against the involvement of endocrinesystems in several different aspects of reproduction. The mechanismbehind the ability of a triazine herbicide to cause enhancedappearance of mammary tumors in one strain of female rats isreviewed by Stevens. The data suggest that enhanced aging, notdirect mammary modulation, is responsible. Dietary phytoestrogens,the mediators of their actions, their effects in various biologicalsystems, and the relationships between phytoestrogen producersand consumers are all provocatively and succinctly reviewedby Hughes. Kelce presents the strategy used to dissect the modeand mechanisms of action of a fungicide that opened a new awarenessin reproductive toxicology: the possibility of xenobiotics beingantiandrogens. Finally, to heighten our understanding of theinterplay among hormonal systems in vivo, Hess reviews the datathat show that androgens are not the only hormones importantin the development of the male reproductive system: the pituitaryis shown to play a critical role at specific stages of development.The breadth of these presentations, and the implications oftheir findings, should make us pause and realize how much thereis still to discover about the interaction between the reproductivesystem and anthropogenic compounds.     

In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis -induced spleen T cell proliferative responses as well as IFN-γ and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 μg of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-γ production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis .     

Improved Short-Term Outcomes of Primary Coronary Stenting Compared to Primary Balloon Angioplasty in Acute Myocardial Infarction at Experienced Centers: The PAMI Study Group Experience

To study the additive benefits of routine stent implantation in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) at experienced centers, we compared the outcomes of the 982 patients undergoing PTCA for acute myocardial infarction (AMI) in the Primary Angioplasty in Myocardial Infarction-2 (PAMI-2) trial (only 1% of whom were stented) to the 312 patients in the PAMI Stent Pilot Trial (236 [76%] of whom were stented). The inclusion and exclusion criteria, PTCA methodology, and definitions used were prespecified to be identical between the two trials. Compared to the primary PTCA approach in PAMI-2, the strategy of stenting all eligible lesions in the PAMI Stent Pilot Trial was associated with reduced rates of in-hospital death (0.6% vs 2.7%, P = 0.03), reinfarction (1.3% vs 4.6%, P = 0.008), recurrent ischemia (3.5% vs 11.6%, P < 0.0001), target vessel revascularization (7.3% vs 11.4%, P = 0.04), and a shorter hospital stay (6.4 ± 4.4 vs 7.1 ± 6.2 days, P = 0.01). By multiple logistic regression analysis in 1,294 patients, stent implantation versus PTCA only was the strongest predictor of freedom from the composite in-hospital end point of death, reinfarction, or target vessel revascularization (TVR) (8.3% vs 15.0%, multivariate odds ratio = 0.4, P < 0.0001). These data strongly suggest that despite the excellent results achieved when primary PTCA is performed by experienced operators, the short-term outcomes of mechanical reperfusion can be further improved by a primary stent strategy.     

From the brain to bad behaviour and back again: Neurocognitive and psychobiological mechanisms of driving while impaired by alcohol

Issues. Driving while impaired by alcohol (DWI) is responsible for substantial mortality and injury. Significant gaps in our understanding of DWI re‐offending, or recidivism, reduce our ability to practically assess recidivism probability and to match interventions to individual risk profiles. These shortcomings reflect the baffling heterogeneity in the DWI population and the limited focus of much existing DWI recidivism research to psychosocial, psychological and substance use correlates. Approach. This narrative review summarises the evidence for the contribution of neurocognitive and psychobiological mechanisms to DWI behaviour and recidivism. Given the nascent nature of this literature, insight into the putative contribution of these mechanisms to DWI is also drawn from other experimental literatures, particularly those on alcohol use disorders and cognitive and behavioural neuroscience. Key Findings. Alcohol‐related neurotoxicity and dysregulation of hypothalamic–pituitary–adrenal axis and serotonergic systems may underlie certain offender characteristics consistently correlated with heightened DWI risk, persistence and intervention resistance. Their markers are less vulnerable to sources of bias than subjective psychosocial indices and are more far‐reaching than alcohol abuse in explaining DWI behaviour and recidivism. Implications. The investigation of neurocognitive and psychobiological mechanisms in DWI research is a promising avenue for discerning clinically meaningful subgroups within the DWI population. This can lead to research and development in alternative assessment and more targeted intervention technologies. Conclusion. Multidimensional research in DWI and recidivism offers novel avenues for increasing road safety.[Brown TG, Ouimet MC, Nadeau L, Gianoulakis C, Lepage M, Tremblay J, Dongier M. From the brain to bad behaviour and back again: Neurocognitive and psychobiological mechanisms of driving while impaired by alcohol. Drug Alcohol Rev 2009;28:406–418]     

Atrial Refractory Periods after Atrial Premature Beats in Patients with Paroxysmal Atrial Fibrillation

To study the effects of an atrial premature beat on atrial refractory periods, we investigated 11 patients (group A) who were the control group, 12 patients suffering from paroxysmal atrial fibrillation (group B), and 10 patients (group C) without arrhythmias but with cardiopathy or cardiomyopathy. At every eighth complex of a constant atrial electrostimulated rhythm a fixed premature extrastimulus was introduced, and effective and functional refractory periods (ERP and FRP) were measured in three different sites of the right atrium, before and after introduction of this extrastimulus. Average ERP and FRP shortened respectively in group A, from 220.28 ± 25.68 msec and 281.17 ± 28.15 msec before extrastimulation, to 190.58 ± 22.74 msec and 245.88 ± 19.86 msec after; in group B, from 219.44 ± 27.38 msec and 284 ± 30.06 msec to 191.66 ± 28.72 msec and 253.23 ± 34.01 msec; and in group C from 229.03 ± 29.65 msec and 289.67 ± 51.62 msec to 194.19 ± 24.6 msec and 237.74 ± 39.59 msec. The average dispersions of ERP and FRP in group A were, respectively: 41.81 ± 21.36 msec and 36.36 ± 18.04 msec before extrastimulation, 28.18 ± 18.14 msec and 35.45 ± 15.72 msec after. In group B: 26.66 ± 19.46 msec and 41.66 ± 16.96 msec versus 45.83 ± 23.91 msec and 45 ± 34.77 msec and in group C: 27 ±11.59 msec and 45 ± 29.15 msec versus 29 ± 18.52 and 27 ± 18.88. It is concluded that an atrial premature beat tends to shorten the dispersion of atrial refractory periods when patients are free of arrhythmias, and to lengthen them when paroxysmal atrial fibrillation are documented.     

Sino-Atrial Dissociation: Evidence by Intracardiac Recordings in Man and by Microelectrode Studies on Isolated Rabbit Atrium

The electrophysiologic mechanisms of sinus dysfunction have recently been determined by direct recordings of the sinus node electrogram. The association of various degrees of abnormalities in the formation of the impulse within the sinus node and of sinoatrial conduction block, represents the pathophysiological substrate of the mechanism of sinus node dysfunction. The purpose of this work is to present clinical and experimental data supporting the concept of sinus node isolation. In our clinical case, the sinus node was probably intact despite aspects of sinus node dysfunction on the surface ECG. Sinus node electrograms were recorded with a sinoatrial conduction time of 100 ms (normal values in our laboratory: 83 ms +/- 38 ms). Atrial mapping demonstrated that the area depolarized by the sinus node involved a 2 cm2 zone surrounding it. This perisinusal activity could not be recorded on the surface ECG. Both exit and entry blocks in the sinus node were demonstrated. Our experimental data showed a total desynchronization between the electrical activity of the sinus node and that of the atrium under hypoxic conditions. Both types of cases demonstrated that an atrial dysrhythmia was coexisting with regular sinus activity. From these data we concluded that a sinus node free from any pathological involvement could be associated with severe symptoms of sinus node dysfunction on the surface ECG.     

Cardiac Resynchronization Therapy is an Important Advance in the Management of Congestive Heart Failure

Cardiac resynchronization therapy (CRT) is an emerging therapy that improves symptoms and exercise tolerance in patients with advanced heart failure, left ventricular systolic dysfunction, and intraventricular conduction delay. By correcting the AV, interventricular, and intraventricular dyssynchrony induced by conduction disorders, controlled studies have shown that CRT improved functional status, decreased heart failure hospitalization rate, and might have a positive effect on left ventricular remodeling. Recent and preliminary data from the COMPANION trial suggest that CRT alone or in association with defibrillator capacity significantly reduced total mortality and hospitalization and that total mortality was significantly reduced only in the CRT plus implantable cardioverter defibrillator (ICD) group. Many questions remain unanswered, particularly the selection of responder patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. S27-S29, September 2003, Suppl.)