Heroin self-administration in dependent Wistar rats: increased sensitivity to naloxone

  Rationale: Non-dependent and dependent opiate users appear to be driven by two distinct motivational factors: the primary reinforcing properties of the drug, and the negative reinforcing effects associated with relieving the negative affective component of opiate withdrawal in the dependent state. Objective: To investigate the motivational significance of opioid dependence on heroin self-administration (HSA) in rodents. Methods: Rats were trained to self-administer heroin intravenously (0.06 mg/kg per infusion; FR1), and opiate dependence was induced by subcutaneous implantation of two morphine (75 mg base) pellets.Rats in a non-dependent control group received placebo pellets. Three days after pellet implantation, HSA was resumed in daily 3-h sessions until baseline criteria were met and testing was conducted with subcutaneous injections of vehicle or naloxone (0, 0.003, 0.01, 0.03 mg/kg) 115 min into the session. Results: Morphine-dependent rats significantly increased HSA upon 0.01 mg/kg naloxone treatment, but decreased response rates at 0.03 mg/kg. Placebo pellet-implanted rats increased heroin intake at the 0.01 and 0.03 mg/kg doses. In a second experiment, the HSA session was shortened to 1 h and the training dose reduced to 0.03 mg/kg per infusion in new groups of animals. HSA in placebo pellet-implanted rats was increased only following the highest dose of the antagonist, while dependent rats were still affected by naloxone doses of 0.003–0.03 mg/kg. When subjected to a progressive-ratio schedule (experiment 3), breaking point values in dependent animals were 198% above baseline. Conclusions: The present study supports the hypothesis that dependence-induction by morphine-pellet implant in rats resulted in increased sensitivity to very small naloxone doses, as measured by changes in HSA. Taken together, these data suggest that opiate dependence, as measured by changes in sensitivity to naloxone, is a continuum which can contribute to the motivational state of drug-seeking. Received: 5 June 1998 / Final version: 21 December 1998     

Cancer : saison 1 et saison 2

A 42 years patient with breast cancer relates the announcement of her disease, four years ago, associated with a denial of the disease. The recurrence of the disease under the form of bone metastasis, a year ago, erases the initial selfdenial strategy. The patient’s life and rythm are therefore shattered; the patient’s paintings reveal this evolution. The psychotherapy engaged at the beginning of the disease allows a return to a repressed past and the search of the “father’s name”.     

Neonatal status epilepticus due to lamination disorder without significant cell death

Background: Malformations of the cerebral cortex may be associated with severe epilepsy and status epilepticus. It has been shown that status epilepticus models induce excitotoxic cell death. In humans, very few data are available. Case and results: We report a case of a multifocal disorder of the lamination diagnosed in a neonate, borne at 30 weeks’ gestation, who died from a refractory status epilepticus at two months and half. This abnormality was not detected by repeated MRI studies. Only microscopic investigations permitted to identify this disorder of the lamination. We found also little cell death or cell loss. Discussion: Our report highlights the possible false negative results of MRI in a newborn. We can also discuss that immature human brain maybe less sensitive to neuronal injury than mature as described in animal models.     

The rationale and design of the SMART CRT trial

Aims

The SMART CRT study will assess the efficacy of an atrioventricular optimization algorithm to improve reverse remodeling among patients undergoing cardiac resynchronization therapy (CRT) in the presence of interventricular electrical delay.

Methods and results

The SMART CRT study is a global, multicenter, prospective, randomized study of patients undergoing CRT implantation. The primary endpoint of this trial is response rate to CRT, defined as decrease in left ventricular end‐systolic volume (LVESV) ≥15% at 6 months compared to preimplant baseline. Additional prespecified analyses are: (1) clinical composite endpoint combining all‐cause mortality, heart failure events, New York Heart Association class, and Quality of Life (using a patient global assessment instrument); (2) the individual components of the clinical composite endpoint; (3) 6‐minute walk distance; (4) Kansas City Cardiomyopathy Questionnaire; (5) LVESV as a continuous variable; and (6) absolute left‐ventricular ejection fraction. Subjects with intraventricular delay ≥ 70 ms measured between the right ventricular and left ventricular pacing leads will be randomized in a 1:1 ratio to have either an AV Delay and pacing chamber determined by SmartDelay? or a Fixed AV Delay of 120 ms with biventricular pacing. Enrollment of an estimated 726 of subjects from up to 100 centers worldwide is planned to achieve 436 randomized subjects and 370 complete data sets required to power the primary endpoint.

Conclusions

This trial will provide important data regarding the importance of AV Delay programming in patients with prolonged interventricular delay at the pacing sites.