Decreasing the toxic potential of intravenous regional anaesthesia

In an attempt to reduce the dose of local anaesthetic agent during intravenous regional anaesthesia (IVRA) of the upper limb, we have used a forearm tourniquet in 12 adult volunteers. The volume of the forearm venous system was predetermined angiographically. We performed IVRA with three solutions of lidocaine (0.25, 0.375, 0.5 per cent) administered in a volume equal to the forearm venous system. Angiographic results indicate that: a forearm tourniquet provides adequate vascular isolation; the volume of the forearm venous system can be correlated with body weight; the progression of the fluid in the venous system follows a pattern that is similar for all patients with the small veins of the distal forearm and proximal hand being filled last. With this technique, lidocaine 0.5 per cent resulted in a dose of 1.5 mg.kg-1 and provided excellent analgesia. Lower concentrations were unsatisfactory. We conclude that the use of a forearm tourniquet allows reduction of the local anaesthetic dose to a non-toxic level and thus increases the safety of IVRA.     

L’acte et son énigme. Entre l’indicible et l’innommable

Contiguous with social spaces, the prison is invested with a degree of secrecy. However, those who are incarcerated tolerate the space, which imprisons them with difficulty, insofar as this place, which punishes them, does not allow them to approach an act where the significance escapes. The act, which led them to this place, identifies them, more than it interrogates the “acting out of the act”, which is profoundly enigmatic and rarely questioned. The legal procedures fix behaviors by a ruling, which is hardly suitable for clarifying acts, which inhibit the significance. Based on clinical situations, we have attempted to conduct investigations concerning the act, defining the role, which the psychologist, orientated by psychoanalysis, must have in the individual work that he maintains with the prisoners. Far from numbing the significance, the aim is to articulate the statements with the contradictions, which compose them, to let an aborted word appear under appropriate discourse; the one which touches on the unspeakable. Taken literally, the significant point of the act is revealed to be less expressible than it had seemed and allows a glimpse of unsuspected areas.     

Dose-response and comparative efficacy and tolerability of quetiapine across psychiatric disorders: a systematic review of the placebo-controlled monotherapy and add-on trials

The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.     

HLA polymorphisms and cervical human Papillomavirus infection in a cohort of Montreal University students

BACKGROUND: Only a minority of women with human papillomavirus (HPV) infection eventually develop cervical cancer, which suggests that host immune mechanisms play a role in the disease. HLA polymorphisms have been linked to the risk of cervical cancer, but very little is known about the role that they play in the acquisition and persistence of HPV infection. METHODS: A cohort study of cervical HPV infections was used to examine the role that 5 HLA alleles (B*07, DQB1*03, DQB1*0602, DRB1*13, and DRB1*1501) play in determining the risk of HPV positivity and persistence in 524 female university students in Montreal. HPV positivity was determined by use of the MY09/11 polymerase-chain-reaction protocol. HLA alleles from purified DNA from cervical specimens were typed by use of a polymerase-chain-reaction technique using sequence-specific primers. RESULTS: HLA DRB1*13 was associated with cumulative risk of HPV infections (odds ratio [OR], 1.7 [95% confidence interval {CI}, 1.0-2.8]), for oncogenic HPV (OR, 1.6 [95% CI, 0.9-2.8]), and for HPV-16 (OR, 2.0 [95% CI, 0.9-4.4]). DQB1*03 was consistently associated with a lower cumulative risk of HPV infections, but this association was not statistically significant. None of the alleles affected the risk of HPV persistence. CONCLUSIONS: The results of this study support the hypothesis that certain HLA class II polymorphisms mediate genetic susceptibility to the acquisition of HPV infection.     

Effects of granisetron, a 5-HT3 receptor antagonist, on morphine-induced potentiation of brain stimulation reward

Using the curve-shift method, we studied the effects of four doses (0.003, 0.03, 0.3 and 3 mg/kg, s.c.) of granisetron (endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methyl-1H-indazole-3-carboxamide hydrochloride), a selective 5-hydroxytryptamine₃ (5-HT₃) receptor antagonist, on the potentiation of brain stimulation reward by microinjection of 2.5 μg/0.25 μl of morphine sulphate (7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol sulphate) into the ventral tegmental area. As previously reported, morphine produced a significant reduction in reward threshold without altering maximal rates of responding. Granisetron attenuated the potentiating effect of morphine at the highest dose and failed to alter reward threshold or maximal rates of responding when given alone, except at the lowest dose where a small and statistically significant increase in threshold was found. These results provide additional evidence that 5-HT₃ receptor antagonists may reduce the rewarding effect of opiates and do not impair the ability to produce operant responses. The weak attenuation observed with granisetron alone suggests that 5-HT₃ receptors are unlikely to constitute an important influence on the directly stimulated reward-relevant pathway(s).     

Saccular stimulation of the human cortex: A functional magnetic resonance imaging study

Recent imaging studies have reported the projection of semicircular canal signals onto wide regions of the cerebral cortex but little is known about otolith projections onto the cerebral cortex. We used functional magnetic resonance imaging (fMRI) to investigate the activation of the cortex by loud clicks that selectively stimulate the sacculus. Twelve normal volunteers were presented with auditory stimuli via an earphone containing a piezo electric element. High-intensity [maximum volume of 120 dB (SPL)] or low-intensity [maximum volume of 110 dB (SPL)] clicks were delivered at a frequency of 1 Hz and lasted 1 ms. We first checked that the high-intensity, but not low-intensity, clicks stimulated the sacculus by determining the vestibular evoked myogenic potentials. We then analyzed two task conditions (high- and low-intensity clicks) in a boxcar paradigm. We obtained gradient echo echo-planar images by using a 1.5 T MRI system. We analyzed the fMRI time series data with SPM2. High-intensity clicks activated wide areas of the cortex, namely, the frontal lobe (prefrontal cortex, premotor cortex, and frontal eye fields), parietal lobe (the region around the intraparietal sulcus, temporo-parietal junction, and paracentral lobule), and cingulate cortex. These areas are similar to those reported in previous imaging studies that analyzed the cortical responses to the activation of the semicircular canals. Thus, semicircular canal and otolith/saccular signals may be processed in similar regions of the human cortex.     

A comparison of the excitability cycles of the hypothalamic fibers involved in self-stimulation and exploration

The excitability cycles of hypothalamic neurons stimulated by a single electrode which induced exploration and self-stimulation were determined behaviorally using a double pulse technique. The data show that the neurons subserving these behaviors have similar recovery properties. A tentative hypothesis concerning neural relationships between these behaviors is proposed.     

Localization of reward-relevant neurons in the pontine tegmentum: a moveable electrode mapping study

Monopolar moveable stimulation electrodes were implanted in male adult rats in order to map the reward substrate in the pontine tegmentum. Electrodes were implanted 6 mm below the surface of the skull and subsequently lowered by steps of 0.16 or 0.32 mm. Each bar press in a Skinner box delivered a train (0.4 s in duration) of cathodal rectangular pulses of fixed intensity (200 microA) and width (0.1 ms). Self-stimulation was recorded from zero to maximum performance by varying the number of pulses per train. The rewarding effectiveness of the stimulation at each positive site was inferred by determining the frequency threshold. Out of 476 sites that were sampled, 137 supported self-stimulation. Eighty-one percent of the positive sites (111 out of 137) were located within 1 mm of the midline. Of the 181 sites that were sampled in the region posterior to the caudal end of the dorsal raphe, only 9 sites (less than 5%) supported self-stimulation. These results suggest that the majority of neurons that constitute the brainstem reward substrate either originate from and/or terminate in the rostral pons.