New insights into the interaction of emodin with lipid membranes.

Emodin is a natural anthraquinone derivative found in nature, widely known as an herbal medicine. Here, the partition, location, and interaction of emodin with lipid membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are experimentally investigated with different techniques. Our studies have considered the neutral form of emodin (EMH) and its anionic/deprotonated form (EM-), and their interaction with a more and less packed lipid membrane, DMPC at the gel and fluid phases, respectively. Though DSC results indicate that the two species, EMH and EM-, similarly disrupt the packing of DMPC bilayers, spin labels clearly show that EMH causes a stronger bilayer disruption, both in gel and fluid DMPC. Fluorescence spectroscopy shows that both EMH and EM- have a high affinity for DMPC: the binding of EM- to both gel and fluid DMPC bilayers was found to be quite similar, and similar to that of EMH to gel DMPC, Kp = (1.4 ± 0.3)x103. However, EMH was found to bind twice more strongly to fluid DMPC bilayers, Kp = (3.2 ± 0.3)x103. Spin labels and optical absorption spectroscopy indicate that emodin is located close to the lipid bilayer surface, and suggest that EM- is closer to the lipid/water interface than EMH, as expected. The present studies present a relevant contribution to the current understanding of the effect the two species of emodin, EMH and EM-, present on different microregions of an organism, as local pH values can vary significantly, can cause in a neutral lipid membrane, either more or less packed, liked gel and fluid DMPC, respectively, and could be extended to lipid domains of biological membranes.

Functional MRI of sustained attention in bipolar mania.

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.

Thermal phase behavior of DMPG bilayers in aqueous dispersions as revealed by 2H- and 31P-NMR.

The synthetic lipid 1,2-dimyristoyl-sn-3-phosphoglycerol (DMPG), when dispersed in water/NaCl exhibits a complex phase behavior caused by its almost unlimited swelling in excess water. Using deuterium ((2)H)- and phosphorus ((31)P)-NMR we have studied the molecular properties of DMPG/water/NaCl dispersions as a function of lipid and NaCl concentration. We have measured the order profile of the hydrophobic part of the lipid bilayer with deuterated DMPG while the orientation of the phosphoglycerol headgroup was deduced from the (31)P NMR chemical shielding anisotropy. At temperatures >30 °C we observe well-resolved (2)H- and (31)P NMR spectra not much different from other liquid crystalline bilayers. From the order profiles it is possible to deduce the average length of the flexible fatty acyl chain. Unusual spectra are obtained in the temperature interval of 20-25 °C, indicating one or several phase transitions. The most dramatic changes are seen at low lipid concentration and low ionic strength. Under these conditions and at 25 °C, the phosphoglycerol headgroup rotates into the hydrocarbon layer and the hydrocarbon chains show larger flexing motions than at higher temperatures. The orientation of the phosphoglycerol headgroup depends on the bilayer surface charge and correlates with the degree of dissociation of DMPG-Na(+). The larger the negative surface charge, the more the headgroup rotates toward the nonpolar region.

Evaluation of dental pulp temperature rise during photo-activated decontamination (PAD) of caries: an in vitro study.

Photo-activated decontamination (PAD) has been reported in caries treatment as an aid in dentine decontamination. The aim of this study is to verify the harmlessness for pulp vitality of photo-activated decontamination (PAD) in caries treatment. Twenty freshly extracted single-rooted teeth were used. Deep class I cavities with a

Pulp temperature increase during photo-activated disinfection (PAD) of periodontal pockets: an in vitro study.

The capacity of photo-sensitizers, used in combination with laser light to kill micro-organisms has been demonstrated in different studies. Photo-activated disinfection (PAD) has been introduced in periodontology as an aid for disinfection of periodontal pockets. The aim of this study is to verify the harm for dental vitality of the use of PAD in periodontal pockets. Root canals of 24 freshly extracted human teeth where prepared using profiles up to a size of ISO #50 and filled with thermo-conductor paste. A silicon-based false gum was made in which a periodontal pocket was created and filled with photo-sensitizer phenothiazine chloride (phenothiazine-5-ium, 3.7-bis (dimethylamino)-, chloride). The external root surface was irradiated during 60 s with a 660-nm diode laser (output power: 20 mW; power density: 0.090 W/cm(2); Energy density: 5.46 J/cm(2)) using a periodontal tip with a diameter of 1 mm and a length of 7 mm. Temperatures were recorded inside the root canal using a thermocouple. Measurements were recorded every second, starting at 10 s before lasering, during the irradiation and were continued for 150 s after the end of irradiation, and six measurements were done per tooth. An average temperature increase of 0.48 +/- 0.11 degrees C was recorded. Our results demonstrated that pulp temperature increase was lower than 3 degrees C, which is considered to be harmless for pulp injury. Regarding pulp temperature increase, the use of PAD for disinfection of periodontal pockets can be considered as a safe procedure for dental vitality.

Pain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation.

[Hypnosis and pain perception]. / Hypnose et perception de la douleur.

Improvement in functional neuroimaging allows researchers to disentangle the brain mechanisms involved in the pain modulation encountered during hypnosis. It has been shown that the anterior cingulate and prefrontal cortices are important in the modulation of incoming sensory and noxious input. Moreover, clinical studies in certain types of surgery (eg thyroidectomy, mastectomy and plastic surgery) have demonstrated that hypnosis may avoid general anesthesia.

[Analgesia for wound dressing by continuous peripheral nerve block]. / Analgésie par blocs nerveux périphériques continus dans le cadre des soins de plaies cutanées.

We present the case of a patient with a circumferential venous ulcer at the level of the calf. She is hospitalized for surgical treatment by continuous aspiration dressing and coverage with skin graft. This patient presents a history of chronic pain, on which classical medications have few effects and are accompanied by side effects. After discussion with the patient, a double continuous peripheral nervous block (femoral and sciatic nerve) is set up to improve the tolerance to wound dressing. This technique presents favorable antalgic results. The indications and the different techniques of block performance (by electrostimulation or echo-guided) are described. The infectious risks related to the presence of catheter near cutaneous wounds are clarified according to recent data of literature. The relevance of these techniques in correlation with the development of chronic pain and on the trophicity of the wounds are also discussed.

Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics.

The rapid awakening without residual analgesic effect seen with the new "fast-in-fast-out" anesthetic agents forces us to anticipate post-operative pain management. More then ever, "balanced analgesia" appears the key for successful transition between anesthesia and post-operative analgesia. This review focuses on practical aspects seeking to answer the following questions: which analgesics should be used?; how should they be given?; at what stage of the anesthetic time should they be injected? In the absence of a loco-regional technique, analgesics must be given before the end of surgery to obtain a quiet awakening. The transition in this delicate period may be facilitated by the intra-operative use of various adjuvant therapies such as ketamine, lidocaine infusion, clonidine, and magnesium, that reduce the needs for opioid and/or post-operative pain severity. All non-opioid analgesics (propacetamol, NSAIDs, tramadol) must be given according to their pharmacokinetic characteristics, indications and contraindications to ensure the required analgesic effect is effective at the time of awakening. If tramadol is not used, an initial dose of a long-acting opioid should be given 20-30 minutes before the end of surgery. Insufficient analgesia must be corrected by titrating an opioid intravenously before allowing the patient to control his/her analgesia using a PCA pump.

[The Hemovigilance Commission of the University Hospital Center]. / La commission d'hémovigilance du CHU.

As suggested by the National Blood Council, a Hemovigilance Committee was set up in the University Hospital of Liège in 1995. A multidisciplinary discussion takes place on any action aiming at the improvement of transfusion safety, and the follow-up of its implementation. The first issue to be discussed was the set up of a detailed documentation of all blood transfusions. The data are now recorded on a single document allowing proper identification of people and products involved, and of the eventual incidents. This document has lead to a better transfusion safety and to an improved administrative management of blood transfusion. The Commission has been coordinating two multi-centric studies analyzing the consumption of fresh blood products and the incidence of transfusion reactions. Among blood-saving policies, autologous transfusion and volume reduction of samples drawn for laboratory purposes have been discussed. Other measures were taken to improve the labeling of samples for cross-mach and to actively follow-up transfusion reactions. By its actions and advises, the Commission aims to direct strategies towards a safe and rational use of blood products.

Sedation, analgesia and anesthesia for interventional radiological procedures in adults. Part II. Recommendations for interventional radiologists.

Benzodiazepines are given orally as a premedication before an interventional radiological procedure. Local analgesia is achieved by drugs such as lidocaine, bupivacaine or ropivacaine. General analgesia is obtained by non opioid analgesics and opioid narcotics. For intravenous sedation, benzodiazepines such as ketamine or propofol should be administered under the supervision of an anesthesiologist. A preprocedure consultation with the anesthesiologist is recommended. Monitoring equipments, drugs and nursing staff assistance should be provided in the interventional suite. Vital signs should be monitored for several hours until patient's discharge. Close collaboration between anesthesiologists and interventional radiologists is a prerequisite for achieving high standard sedation and analgesia.

Auditory processing in the vegetative state.

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness.

Restoration of thalamocortical connectivity after recovery from persistent vegetative state.

By use of H2(15)O positron emission tomography we have shown that functional connectivity between intralaminar thalamic nuclei and prefrontal and anterior cingulate cortices was altered during vegetative state but not after recovery of consciousness.

Neural mechanisms of antinociceptive effects of hypnosis.

BACKGROUND: The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus. METHODS: The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation). RESULTS: Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations. CONCLUSIONS: Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex.

Evaluation of acute normovolemic hemodilution for surgical repair of craniosynostosis.

This clinical report investigated the potential benefit of acute normovolemic hemodilution (ANH) as a blood-saving technique in the surgical repair of craniosynostosis. Over a 4-year period, 34 healthy children undergoing surgical repair of scaphocephaly or pachycephaly were randomly assigned to two groups of 17 patients each. Patients of the first group (ANH group) were submitted to ANH (target Ht: 25%) immediately before surgery and patients of the second group (Control group) were not. During surgery, estimated blood loss was compensated with a 5% albumin solution and no autologous or homologous blood was transfused. At the end of surgery, intraoperative blood loss (mean +/- SD) calculated on the basis of the Ht value and the children weight was 21.3+/-8% of the estimated blood volume (EBV) in the ANH group and 24+/-6.6% in the Control group. Children of the ANH group received their autologous blood (18.9+/-3.3% of EBV) systematically at the end of surgery. In the postoperative period, homologous blood was transfused when the Ht value was equal or less than 21%. Both groups were comparable regarding age, weight, type of craniosynostosis, duration of surgery, EBV, and preoperative Ht value. No difference was observed between ANH and Control groups in the number of patients who received homologous blood (15/17 and 14/17, respectively), in the amount of homologous blood transfused (17+/-4.7% and 19.6+/-6.3% of the EBV, respectively), and in the Ht value before hospital discharge (29.4+/-5.0% and 30.7+/-4.9%, respectively). In conclusion, this report suggests that ANH reduces neither the incidence of homologous transfusion nor the amount of homologous blood transfused in this series of children undergoing surgical repair of craniosynostosis.

Functional neuroanatomy of hypnotic state.

BACKGROUND: The aim of the present study was to describe the distribution of regional cerebral blood flow during the hypnotic state (HS) in humans, using positron-emission tomography (PET) and statistical parametric mapping. METHODS: The hypnotic state relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness." A group of 9 subjects under polygraphic monitoring received six H215O infusions and was scanned in the following order: alert-HS-HS-HS with color hallucination-HS with color hallucination-alert. PET data were analyzed using statistical parametric mapping (SPM95). RESULTS: The group analysis showed that hypnotic state is related to the activation of a widespread, mainly left-sided, set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal cortices and a few right-sided regions: occipital and anterior cingulate cortices. CONCLUSIONS: The pattern of activation during hypnotic state differs from those induced in normal subjects by the simple evocation of autobiographical memories. It shares many similarities with mental imagery, from which it differs by the relative deactivation of precuneus.

Psychological approaches during conscious sedation. Hypnosis versus stress reducing strategies: a prospective randomized study.

Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological approaches for reducing perioperative discomfort during conscious sedation for plastic surgery. Sixty patients scheduled for elective plastic surgery under local anesthesia and intravenous sedation (midazolam and alfentanil upon request) were included in the study after providing informed consent. They were randomly allocated to either stress reducing strategies (control: CONT) or hypnosis (HYP) during the entire surgical procedure. Both techniques were performed by the same anesthesiologist (MEF). Patient behavior was noted during surgery by a psychologist, the patient noted anxiety, pain, perceived control before, during and after surgery, and postoperative nausea and vomiting (PONV). Patient satisfaction and surgical conditions were also recorded. Peri- and postoperative anxiety and pain were significantly lower in the HYP group. This reduction in anxiety and pain were achieved despite a significant reduction in intraoperative requirements for midazolam and alfentanil in the HYP group (alfentanil: 8.7 +/- 0.9 microg kg(-1)/h(-1) vs. 19.4 +/- 2 microg kg(-1)/h(-1), P < 0.001; midazolam: 0.04 +/- 0.003 mg kg(-1)/h(-1) vs. 0.09 +/- 0.01 mg kg(-1)/h(-1), P < 0.001). Patients in the HYP group reported an impression of more intraoperative control than those in the CONT group (P < 0.01). PONV were significantly reduced in the HYP group (6.5% vs. 30.8%, P < 0.001). Surgical conditions were better in the HYP group. Less signs of patient discomfort and pain were observed by the psychologist in the HYP group (P < 0.001). Vital signs were significantly more stable in the HYP group. Patient satisfaction score was significantly higher in the HYP group (P < 0.004). This study suggests that hypnosis provides better perioperative pain and anxiety relief, allows for significant reductions in alfentanil and midazolam requirements, and improves patient satisfaction and surgical conditions as compared with conventional stress reducing strategies support in patients receiving conscious sedation for plastic surgery.

Pain after laparoscopic cholecystectomy: characteristics and effect of intraperitoneal bupivacaine.

Although pain after laparoscopic cholecystectomy is less intense than after open cholecystectomy, some patients still experience considerable discomfort. Furthermore, the characteristics of postlaparoscopy pain differ considerably from those seen after laparotomy. Therefore, we investigated the time course of different pain components after laparoscopic cholecystectomy and the effects of intraperitoneal bupivacaine on these different components. Forty ASA physical status grade I-II patients were randomly assigned to receive either 80 mL of bupivacaine 0.125% with epinephrine 1/200,000 (n = 20) or the same volume of saline (n = 20) instilled under the right hemidiaphragm at the end of surgery. Intensity of total pain, visceral pain, parietal pain, and shoulder pain was assessed 1, 2, 4, 6, 8, 24, and 48 h after surgery. Analgesic consumption was also recorded. Patient data were similar in the two groups. In the saline group, visceral pain was significantly more intense than parietal pain at each time point; visceral and parietal pain were greater than shoulder pain during the first 8 h postoperatively. Intraperitoneal bupivacaine did not significantly affect any of the different components of postoperative pain. Analgesic consumption was similar in the two groups. This study demonstrates that visceral pain accounts for most of the pain experienced after laparoscopic cholecystectomy. Intraperitoneal bupivacaine is not effective for treating any type of pain after laparoscopic cholecystectomy.

Hypnosis as adjunct therapy in conscious sedation for plastic surgery.

BACKGROUND AND OBJECTIVES: Sedation is often requested during local and regional anesthesia. However, some surgical procedures, such as plastic surgery, require conscious sedation, which may be difficult to achieve. Hypnosis, used routinely to provide conscious sedation in the authors' Department of Plastic Surgery, results in high patient and surgeon satisfaction. The authors conducted a retrospective study to investigate the benefits of hypnosis in supplementing local anesthesia. METHODS: The study included 337 patients undergoing minor and major plastic surgical procedures under local anesthesia and conscious intravenous sedation. Patients were divided into three groups depending on the sedation technique: intravenous sedation (n = 137) using only midazolam and alfentanil; hypnosis (n = 172), during which patients achieved a hypnotic trance level with age regression; and relaxation (n = 28), comprising patients in whom hypnosis was induced without attaining a trance level. In all three groups, midazolam and alfentanil were titrated to achieve patient immobility, in response to patient complaints, and to maintain hemodynamic stability. Midazolam and alfentanil requirements; intra- and postoperative pain scores; as well as pre-, intra-, and postoperative anxiety score, reported on a 10-cm visual analog scale, were recorded and compared in the three groups. RESULTS: Intraoperative anxiety reported by patients in the hypnosis group (0.7 +/- 0.11) and in the relaxation group (2.08 +/- 0.4) was significantly (P < .001) less than in the intravenous sedation group (5.6 +/- 1.6). Pain scores during surgery were significantly greater in the intravenous sedation group (4.9 +/- 0.6) than in the hypnosis group (1.36 +/- 0.12; P < .001) and the relaxation group (1.82 +/- 0.6; P < .01). Furthermore, midazolam requirements were significantly lower in the hypnosis group (P < .001) and in the relaxation group (P < .01) as compared with the intravenous sedation group: respectively, 0.04 +/- 0.002, 0.07 +/- 0.005, and 0.11 +/- 0.01 mg/kg/h. Alfentanil requirements were significantly decreased in the hypnosis group, as compared with the intravenous sedation group: 10.2 +/- 0.6 microgram/kg/h versus 15.5 +/- 2.07 micrograms/kg/h; P < .002. In the relaxation group, alfentanil requirements were 14.3 +/- 1.5 micrograms/kg/h (ns). Postoperative nausea and vomiting were reported by 1.2% of patients in the hypnosis group, 12.8% in the relaxation group and 26.7% in the intravenous sedation group. Greater patient satisfaction with the anesthetic procedure and greater surgical comfort were also reported in the hypnosis group. CONCLUSIONS: Successful hypnosis as an adjunct sedation procedure to conscious intravenous sedation provided better pain and anxiety relief than conventional intravenous sedation and allowed for a significant reduction in midazolam and alfentanil requirements. Patient satisfaction was significantly improved.