[PAL-PRAT study: Healthcare workers' knowledge and perception of palliative practices in a Cancer Center]. / Quelle connaissance et quelle perception ont les professionnels de santé d'un Centre de lutte contre le cancer à propos des pratiques palliatives encadrées par la loi Claeys-Leonetti : étude PAL PRAT.

INTRODUCTION: The issue of end-of-life care is the subject of a sensitive debate in French society, particularly regarding the possibility for certain patients to have access to medical assistance in dying. The aim of this study was to assess the knowledge and opinion of healthcare providers on the care practices for patients at the end of life, as well as to highlight any specificities in their discourse. METHOD: A survey of healthcare providers' opinions, composed of closed and open questions, that were analyzed using a lexicometric approach, was distributed in a cancer center. RESULTS: The results of the study reveal a good knowledge of the different procedures. Professionals considered that advance directives should be systematically collected; a majority of them differentiated euthanasia from deep continuous sedation and perceived the latter as a means of relieving patients' suffering without inducing death. The different procedures related to the active assistance in dying were known by a majority of professionals and the survey did not identify a dominant trend concerning the will to practice euthanasia if the legal framework allowed it. Half of the participants considered their training insufficient, indicating the need to fill this gap. DISCUSSION: This survey underlines the importance of training and support for the professionals caring for patients in palliative situation and their relatives in France.

Innovative ceramic-matrix composite substrates with tunable electrical conductivity for high-power applications.

A wide band gap semiconductor power module can operate at higher voltages as compared with its traditional silicon counterpart. However, its insulating system undergoes stronger electric fields at the triple point between the ceramic substrate, the metallic tracks and the encapsulating polymer, which can dramatically reduce its lifespan. Here we report an original concept based on the local modification of the substrate properties to mitigate such electrical stress. Numerical simulations revealed its potential to reduce this constraint by up to 50%. This concept was realized by developing, through a practical approach, a novel substrate made of an AlN-based ceramic (material A) integrating a nanocomposite volume endowed with controlled properties and geometry. This approach implies first the spark plasma sintering of the AlN powder with additives (Y2O3, CaF2) to endow the material A with a very low electrical conductivity (σ) and high thermal conductivity (k). Graphene nanoplatelets (GNP) were incorporated within this material to fabricate a nanocomposite with a controlled σ anisotropy that otherwise reached a striking ratio of 106 at 20°C for 1.25 vol% GNP. Our approach secondly aimed at developing an effective process allowing to integrate this nanocomposite into the material A with a very high degree of reproducibility. It finally consisted in establishing the electrical contacts on the achieved substrate and encapsulating it for breakdown testing. The novel substrate enabled a mitigation of the electrical constraint by diminishing its intensity and shifting it from the triple point to a less constrained area. It already brought an improvement in breakdown voltage (VB) by 15% as compared to the traditional substrate, and revealed the potential for achieving higher VB as well. This work lays the foundation for the development of novel multifunctional ceramic-matrix composite substrates sought for power electronics as well as for other potential applications.

Maternal pain during pregnancy dose-dependently predicts postpartum depression: The Japan Environment and Children's Study.

BACKGROUND: Postpartum depression (PPD) affects women during the first year after delivery. This study investigated the association between prenatal pain (maternal pain during pregnancy) and PPD. METHODS: Data were analyzed from the Japan Environment and Children's Study (JECS), a nationwide prospective birth cohort study. Information on prenatal pain was collected twice during pregnancy through self-administered questionnaires. PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale at one month postpartum. Poisson regression analyses were performed to investigate the association between prenatal pain and PPD, with other putative risk factors adjusted in the model. RESULTS: Among 84,801 study subjects, 11,535 (13.6%) were screened as positive for PPD. In the present study, the occurrence of prenatal pain was 69.6 and 84.0% at the first trimester and the second/third trimester, respectively. A positive relationship between any degree of pain and PPD in both the first and the second/third trimester was observed. A significant linear dose-dependent association was also found (Ptrend < 0.001) when the subjects were divided by the severity of pain. Using participants without any pain at either point as a reference, those with persistent pain both at the first and the second/third trimesters showed the highest risk for PPD: aRR = 1.95 (95%CI: 1.76-2.15; p < 0.001). LIMITATIONS: No detailed information regarding the type or site of prenatal pain was available in the JECS questionnaires, neither did data concerning delivery and postpartum pain. CONCLUSIONS: The study results suggest that prenatal pain is a dose-dependent risk factor for the development of PPD.

Temperature Influence on PI/Si3N4 Nanocomposite Dielectric Properties: A Multiscale Approach.

The interphase area appears to have a great impact on nanocomposite (NC) dielectric properties. However, the underlying mechanisms are still poorly understood, mainly because the interphase properties remain unknown. This is even more true if the temperature increases. In this study, a multiscale characterization of polyimide/silicon nitride (PI/Si3N4) NC dielectric properties is performed at various temperatures. Using a nanomechanical characterization approach, the interphase width was estimated to be 30 ± 2 nm and 42 ± 3 nm for untreated and silane-treated nanoparticles, respectively. At room temperature, the interphase dielectric permittivity is lower than that of the matrix. It increases with the temperature, and at 150 °C, the interphase and matrix permittivities reach the same value. At the macroscale, an improvement of the dielectric breakdown is observed at high temperature (by a factor of 2 at 300 °C) for NC compared to neat PI. The comparison between nano- and macro-scale measurements leads to the understanding of a strong correlation between interphase properties and NC ones. Indeed, the NC macroscopic dielectric permittivity is well reproduced from nanoscale permittivity results using mixing laws. Finally, a strong correlation between the interphase dielectric permittivity and NC breakdown strength is observed.

Acute and long-term effects of haloperidol on surgery-induced neuroinflammation and cognitive deficits in aged rats.

PURPOSE: Neuroinflammation may contribute to the pathogenesis of the cognitive symptoms of postoperative delirium (POD) and its subsequent long-term cognitive impairment. Haloperidol (HAL), a dopamine receptor antagonist, is widely used to treat POD, whereas the effects of HAL on postoperative neuroinflammation and related cognitive deficits have been underdetermined. METHODS: Aged rats underwent sham or abdominal surgery and were subcutaneously treated with either vehicle, low-dose (0.5 mg/kg bolus, then 0.5 mg/kg/day infusion), or high-dose (2.0 mg/kg bolus, then 2.0 mg/kg/day infusion) HAL. All treatments were initiated immediately after surgery and continued for 48 h. On either postoperative day 2 (early) or 7 (late), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Following the cognitive testing, the levels of pro-inflammatory cytokines, as well as dopamine and its metabolite, in hippocampus and medial prefrontal cortex (mPFC) were measured. RESULTS: In the early postoperative period, surgery induced acute neuroinflammation along with related trace and context memory dysfunction. Dopamine turnover was increased in both hippocampus and mPFC, whereas no relationship with memory functions was observed. However, HAL even at high-dose failed to restore the surgery-induced neuroinflammation and related cognitive deficits. In the late postoperative period, chronic neuroinflammation was detected only in hippocampus, which was associated with context, but not trace memory dysfunction. Neither low- nor high-dose HAL could prevent the development of these late-phase neurocognitive deficits. CONCLUSION: Our findings indicate that perioperative administration with HAL may have no effects on postoperative neuroinflammation and related cognitive impairment.

Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats.

The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6 h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.

Therapeutic experience with tramadol for opioid dependence in a patient with chronic low back pain: a case report.

BACKGROUND: Long-term opioid treatment for chronic non-cancer pain has become controversial, given the increasing prevalence of opioid dependence. However, there is little information on therapeutic strategies for this condition in Japanese patients. Here, we present a case of successful management of iatrogenic opioid dependence with tramadol in a patient with chronic low back pain. CASE PRESENTATION: A 68-year-old male suffering from intractable low back pain was referred to our pain clinic. He was previously treated in another hospital with transdermal fentanyl patches 6 mg/day and fentanyl sublingual tablets (100 µg as required) for this condition. On the basis of medical examination, including a review of the patient's medical history, physical examination, X-ray, and his family statement, we diagnosed him with iatrogenic opioid dependence due to inadequate fentanyl use. Then, we developed a treatment plan consisting in fentanyl detoxification with a weak opioid, tramadol. At first, the use of fentanyl sublingual tablets was interrupted after obtaining informed consent. Then, we reduced the dose of transdermal fentanyl 1 mg per 4-5 days replacing with oral sustained-release tramadol. The patient developed mild to moderate withdrawal symptoms during this period, which could be effectively managed by supportive treatments. The hospital psychiatry liaison team continuously provided the patient and his wife with information, counseling, and education regarding the treatment of opioid dependence. Throughout the detoxification process, his reported pain did not exacerbate, even slightly improved over time. The final prescription was sustained-release tramadol 300 mg/day without fentanyl, and his activities of daily living drastically improved. However, unfortunately, he died due to an aortic dissection of stent-graft edge 65 days after surgery. CONCLUSIONS: Our case highlighted that sustained-release tramadol could be effectively applied as a detoxification agent for iatrogenic opioid dependence in patients with chronic non-cancer pain.

Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats.

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels.

Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats.

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway.

Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats.

PURPOSE: The purpose of this study was to investigate the age-, time-, and brain region-dependent postoperative neuroinflammatory trajectory, and its association with neurocognitive outcomes in rats. METHODS: Adult and aged rats were randomly assigned to one of three groups: control, isoflurane anesthesia alone, and isoflurane anesthesia with abdominal surgery. On either postoperative day 2 (early phase) or 7 (late phase), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Freezing behavior was used as an index of fear memory. Following the cognitive testing, the levels of pro-inflammatory cytokines in several brain regions were measured using enzyme-linked immunosorbent assay (n = 8 in each group). RESULTS: In the early postoperative period, surgery under isoflurane anesthesia induced acute neuroinflammation along with related trace and context memory dysfunction. Such acute neuroinflammatory responses were comparably observed in both adult and aged animals, whereas the aged rats were more likely to exhibit behavioral changes. On the other hand, in the late postoperative period, neither neuroinflammation in all tested brain regions nor concomitant memory decline were found in adult animals. Significant neuroinflammation was detected only in the hippocampus of aged rats, which was associated with context, but not trace memory dysfunction. CONCLUSION: Our findings indicate that surgery-induced acute, transient, brain-wide neuroinflammation may be involved in the pathogenesis of the postoperative delirium-like cognitive deficits in rats. Furthermore, neuroinflammation may convert from acute to chronic in an age- and hippocampal-specific manner, likely resulting in the development of sustained cognitive dysfunction.

The role of hippocampal brain-derived neurotrophic factor in age-related differences in neuropathic pain behavior in rats.

AIMS: This study was aimed to explore the contribution of central brain-derived neurotrophic factor (BDNF) in the neuropathic pain pathogenesis using an aged rodent model. MAIN METHODS: Adult and aged rats were randomly assigned to either a sciatic nerve ligation (SNL) group or a control skin sham surgery group. Sensory behavioral testing were performed on the day before surgery and on the 3rd, 7th, 14th, and 21st days after surgery, followed by measurement of BDNF protein levels in different brain regions. In another experiment, the hippocampal BDNF gene expression after SNL surgery was assessed at different time-points. Furthermore, the analgesic effects of intranasal BDNF administration were tested in SNL animals. KEY FINDINGS: Our behavioral results demonstrated that the hyperalgesia-like behavior after painful nerve injury has a higher incidence in aged rats compared with in adult animals. In particular, the hippocampal BDNF levels were inversely correlated with the probability of hyperalgesia-type behavior, in both brain-region specific and age-dependent manner. Time-course analysis showed that the hippocampal levels of BDNF mRNA in aged and adult rats started to decrease 7 and 14 days after surgery, respectively. However, the decrease was more pronounced in aged animals. Moreover, the repeated intranasal BDNF treatment could restore the central BDNF signaling, counteracting the age-related exacerbation of hyperalgesic behavior. SIGNIFICANCE: Our findings imply that hippocampal BDNF may be related with the pathogenesis of elderly neuropathic pain. Pharmacological data further suggest that brain BDNF may be modifiable in aged neuropathic animals, and therefore, represent a promising target for intervention.

Effects of epigallocatechin-3-gallate on systemic inflammation-induced cognitive dysfunction in aged rats.

PURPOSE: In this study, we examined the effects of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on sepsis-induced neurocognitive abnormity in aged rats. METHODS: Aged rats received an intraperitoneal (i.p.) injection of 5.0 mg/kg lipopolysaccharide (LPS) or saline. Animals were further divided into three groups: control, low-dose EGCG (4.0 mg/kg), and high-dose EGCG (20 mg/kg). EGCG was i.p. injected at the same time, 24 and 48 h after LPS administration. Survival rate was recorded for 1 week. All surviving animals were assessed for cognitive function using the novel object recognition test, followed by measurement of hippocampal cytokine levels. In an additional set of experiments, the liver function test was performed. Furthermore, the effects of EGCG on cytokine release from microglia isolated from young and aged rats were assessed. RESULTS: The survival rate in LPS-treated control rats was 77.8%, which was decreased to 72.2 and 33.3% in the low and high EGCG groups, respectively. In the surviving animals, the LPS-treated control rats exhibited impaired cognitive performance and increased pro-inflammatory cytokine levels compared with untreated animals. None of these neurocognitive alterations were affected by low or high EGCG treatment. Blood chemical analysis showed co-administration of EGCG with LPS resulted in a marked increase in both aspartate aminotransferase and alanine aminotransferase levels. In addition, EGCG inhibited LPS-induced cytokine release, whereas the suppressive ability of EGCG was lower in aged microglia compared with in young microglia. CONCLUSIONS: Our findings demonstrated that EGCG cannot prevent hippocampal neuroinflammation and related memory deficits in aged rats surviving sepsis.

The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats.

PURPOSE: Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model. METHODS: The surgical and sham-surgical animals were randomly divided into saline-treated control, 5.0 mg/kg LPS-treated, 10 µg/kg DEX-treated, and 5.0 mg/kg LPS + 10 µg/kg DEX-treated groups. In the surgical animals, a 1-cm-long plantar incision was made through the skin and fascia under isoflurane anesthesia. The sham-surgical rats were only anesthetized. All treatments were administered by a single intraperitoneal (i.p.) injection 60 min before surgery. Acute postoperative pain was assessed using the Rat Grimace Scale (RGS) one day before surgery (baseline) and at 2 h post incision. In another experiment, the involvement of the α2-adrenergic receptor was tested using atipamezole, an α2-adrenergic receptor antagonist. RESULTS: In the sham-surgical animals, the RGS did not increase at 2 h after sham surgery compared with the corresponding baseline values in all groups. In the surgical rats, however, the postoperative RGS value of the LPS group was significantly higher than the control group, indicating LPS-induced postoperative hyperalgesia. Administration of intraoperative DEX could prevent the development of such LPS-induced exacerbated post-incisional pain. In addition, the preventive effects of intraoperative DEX were inhibited by pretreatment with atipamezole. CONCLUSION: Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α2-adrenergic receptor signaling pathway.

General anesthesia in a patient with asymptomatic second-degree two-to-one atrioventricular block.

BACKGROUND: The major perioperative concern in patients with second-degree atrioventricular (AV) block is the progression to complete AV block. Therefore, the prophylactic implantation of a temporary pacemaker prior to surgery is recommended, especially in symptomatic patients. However, as no quantitative preoperative risk assessment from progression to complete AV block is available, there is currently no established indication for preoperative prophylactic pacemaker implantation. Here, we present a case of progression from asymptomatic second-degree two-to-one (2:1) AV block to complete AV block following the induction of general anesthesia. CASE PRESENTATION: A 69-year-old female with degenerative spinal stenosis was scheduled for transforaminal lumbar interbody fusion surgery under general anesthesia. She had no cardiac symptoms, but routine preoperative resting 12-lead electrocardiogram revealed second-degree 2:1 AV block. After discussion with the surgeon and referring cardiologist, we scheduled the surgery without implantation of a temporary pacemaker before surgery for the following reasons: (1) asymptomatic, (2) no evidence of underlying cardiac disease, and (3) a narrow QRS complex. On the day of surgery, general anesthesia was induced with 150 mg of intravenous thiamylal and 25 µg of fentanyl, followed by intravenous administration of 50 mg of rocuronium to facilitate endotracheal intubation. Sevoflurane (1.0-2.0%) was used to maintain anesthesia. A few minutes after induction, the 2:1 AV block progressively converted to complete AV block, and the surgery was postponed. During emergence from anesthesia, the third-degree AV block recovered to 2:1 AV block, similar with the preoperative pattern. The patient was monitored in the intensive care unit for 2 days and then transferred to the normal orthopedic ward uneventfully. One month later, the surgery was rescheduled with preoperative implantation of a temporary pacemaker. A slow mask induction using sevoflurane with oxygen was started. Upon loss of consciousness during the inhalation of initial sevoflurane, complete AV block developed and temporary pacing was immediately initiated. Subsequent anesthesia and surgery were uneventful. The patient made an uncomplicated recovery from surgery with stable hemodynamics. The temporary pacemaker was not required after surgery, and the pacemaker catheter was removed 1 day after surgery. CONCLUSIONS: The present case indicates that a prophylactic pacemaker should be implanted preoperatively in patients who have 2:1 AV block even without symptoms.

Does preoperative patient's estimated acceptable pain affect the satisfaction with postoperative pain management?

BACKGROUND: Patient satisfaction with postoperative pain management is an important quality indicator in patient health care, but its determinants are poorly understood. Here, we examined the contribution of the discrepancy between an individual's estimated acceptable and actual postoperative pain scores to the overall satisfaction with pain treatment. FINDINGS: A total of 93 surgical patients were included in this study. Preoperatively, the subjects were asked to rate their estimated acceptable postoperative pain using a numerical rating scale (NRS). One day after the surgery, the patients were again asked to give NRS ratings of the overall actual pain intensity they had experienced, as well as their satisfaction with the provided pain treatment. The median estimated acceptable and actual NRS values for postoperative pain were 4.0 (3.0-5.0) and 4.0 (2.0-5.0), respectively. Although there was no correlation between the degree of patient satisfaction and preoperative estimated acceptable pain intensity, there was a significant negative correlation between the degree of patient satisfaction and postoperative actual pain intensity. When the preoperative estimated acceptable NRS value was compared with the postoperative actual value for each individual, postoperative NRS was greater in 34 cases (36.6%), less in 43 cases (46.2%), and equal in 16 cases (17.2%). The degree of patient satisfaction was not significantly correlated with the magnitude of difference between preoperative estimated acceptable NRS and postoperative actual NRS. CONCLUSIONS: Our findings suggest that inquiring about the estimated acceptable pain before surgery may not help anesthesiologists to understand the patient's goal of pain management for improving patient satisfaction.

Preventive effects of dexmedetomidine on the development of cognitive dysfunction following systemic inflammation in aged rats.

PURPOSE: In the present study, we examined whether and by what mechanisms dexmedetomidine (DMED) prevents the development of systemic inflammation (SI)-induced cognitive dysfunction in aged rats. METHODS: Animals received a single intraperitoneal (i.p.) injection of either 5.0 mg/kg lipopolysaccharide (LPS) or vehicle. LPS-treated rats were further divided into three groups: early DMED, late DMED, or midazolam (MDZ) treatment (n = 12 each). Seven days after LPS injection, cognitive function was evaluated using a novel object recognition task, followed by measurement of hippocampal levels of proinflammatory cytokines and Toll-like receptor 4 (TLR-4) expression. For ex vivo experiments, microglia were isolated from the hippocampus for assessment of cytokine response to LPS. RESULTS: LPS-treated rats showed memory deficits, hippocampal neuroinflammation, and TLR-4 upregulation as compared to saline-treated animals. However, early DMED treatment was able to attenuate these SI-induced neurocognitive changes, whereas no benefits were observed in the MDZ and late DMED treatment groups. In ex vivo experiments, early DMED treatment prevented the development of SI-induced excessive microglial hyperactivation, which was blocked by the nonspecific α2-adrenergic receptor (AR) antagonist atipamezole or the specific α2A-AR antagonist BRL-44408, but not by the specific α2B/C-AR antagonist ARC-239. On the other hand, neither DMED nor MDZ had a direct effect on LPS-induced release of pro-inflammatory cytokines from hippocampal microglia at clinically relevant concentrations. CONCLUSION: Our findings highlight that treatment with DMED during, but not after, peripheral SI can prevent subsequent hippocampal neuroinflammation, overexpression of TLR-4 in microglia, and cognitive dysfunction, as mediated by the α2A-AR signaling pathway.

Peripheral nerve block with a high concentration of tetracaine dissolved in bupivacaine for intractable post-herpetic itch: a case report.

BACKGROUND: Post-herpetic itch (PHI) is a neuropathic itch syndrome following herpes zoster. It has been reported that PHI is occasionally sufficiently severe to compromise patients' quality of life and frequently refractory to treatment. Here, we present a case of severe chronic PHI successfully treated with supraorbital nerve block using a high concentration of tetracaine dissolved in bupivacaine. CASE PRESENTATION: An 82-year-old man presented with severe chronic itching in the ophthalmic branch of the left trigeminal nerve dermatome, following acute herpes zoster. The patient's itching was unresponsive to usual medical treatments for PHI including antiepileptic drugs, topical capsaicin cream, and supraorbital nerve radiofrequency thermo-coagulation. Topical lidocaine cream could relieve the itching, but could not provide long-term relief of itching and thus failed to achieve a satisfactory result. After these conventional treatments, left supraorbital nerve block using 4% tetracaine dissolved with 0.5% bupivacaine was conducted. Afterwards, the patient experienced long-lasting resolution of the itching with improvement of sleep disturbance. A transient, mild edema of the eyelids occurred, but there were no other complications. CONCLUSIONS: Peripheral nerve block using 4% tetracaine dissolved with 0.5% bupivacaine was beneficial in relieving PHI in the ophthalmic division of the trigeminal nerve.

Failure of lumbar puncture in a patient with spinal epidural lipomatosis: a case report.

We report a case of difficult lumbar puncture due to the inability to obtain adequate cerebrospinal fluid (CSF) in a patient later diagnosed with spinal epidural lipomatosis (SEL). A 76-year-old man with a body mass index (BMI) of 24.1 kg/m2 was scheduled for transurethral resection of a bladder tumor for superficial bladder cancer under spinal anesthesia. The patient had a 3-year history of inhaled steroid use for the management of chronic obstructive pulmonary disease. After placing the patient in the right lateral position, a lumbar puncture was performed via the median approach. However, CSF could not be tapped adequately despite repeated attempts at lumbar puncture, so general anesthetic was administered instead. Subsequently, both anesthesia and surgery proceeded uneventfully. On the first postoperative day, the patient developed mild postdural puncture headache (PDPH), which was treated conservatively. No postoperative neurological complications related to spinal anesthesia were observed. Approximately 2 months after discharge, the patient reported progressive lower back pain and was diagnosed with SEL by magnetic resonance imaging (MRI). A lumbar laminectomy and removal of excessive adipose tissue was performed. After surgery, the patient's symptoms resolved. The pathogenesis of SEL involves excess fat tissue deposition in the spinal canal, which can lead to obliteration of the spinal subarachnoid space. Therefore, in this patient, the SEL was thought to have caused the inability to obtain adequate CSF during lumbar puncture, and was associated with difficult spinal anesthesia.

A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common cause of inherited peripheral neuropathy, with an estimated frequency of 1/2500. We studied a large family with 17 patients affected by the axonal form of CMT (CMT2). Analysis of the 15 genes or loci known to date was negative. Genome-wide genotyping identified a CMT2 locus in 16q21-q23 between D16S3050 and D16S3106. The maximum two-point LOD score was 4.77 at theta = 0 for marker D16S3050. Sequencing of candidate genes identified a unique mutation, c.986G>A (p.Arg329His), affecting a totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA synthetase (AlaRS). A second family with the same mutation and a different founder was then identified in a cohort of 91 CMT2 families. Although mislocation of mutant Arg329His-AlaRS in axons remains to be evaluated, experimental data point mostly to a quantitative reduction in tRNA(Ala) aminoacylation. Aminoacylation and editing functions closely cooperate in AlaRS, and Arg329His mutation could also lead to qualitative errors participating in neurodegeneration. Our report documents in 18 patients the deleterious impact of a mutation in human cytoplasmic AlaRS and broadens the spectrum of defects found in tRNA synthetases. Patients present with sensory-motor distal degeneration secondary to predominant axonal neuropathy, slight demyelination, and no atypical or additional CNS features.