Robust unfolding of MeV x-ray spectra from filter stack spectrometer data.

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.

Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good.

In this review, we will describe the immunopathogies of immune reconstitution inflammatory syndrome, IRIS. IRIS occurs in a small subset of HIV patient, initiating combination antiretroviral therapy (ART), where immune reconstitution becomes dysregulated, resulting in an overly robust antigen-specific inflammatory reaction. We will discuss IRIS in terms of the associated coinfections: mycobacteria, cryptococci, and viruses.

An unusual case of focal segmental glomerulosclerosis presenting with retropharyngeal edema.

INTRODUCTION: Acute neck swelling with pharyngeal signs often triggers emergency consultation. Treatment and diagnosis are usually multidisciplinary. Failing to find a possible etiology may lead to misdiagnosis. CASE PRESENTATION: A young man presented to the emergency room with a 4-day history of cough, neck swelling and sore throat. Laboratory testing showed a leukocyte count of 9200 without left shift. Mild elevated CRP with 1.7 was noted and computed tomography (CT) showed fluid accumulation in the retropharyngeal space and neck edema down to thyroid region. Antibiotic was prescribed and admitted to infection ward under the impression of deep neck infection. During hospitalization, needle aspiration was performed where water fluid was collected without pus. Investigations showed massive proteinuria, hypoalbuminemia and hypercholesterolemia. The early focal segmental glomerulosclerosis was found by renal biopsy. After prednisolone 60mg daily and albumin supplement, the neck swelling, swallowing pain and general edema had completely resolved. DISCUSSION: The purpose of this case is to raise awareness of nephrotic syndrome as an unusual but possibly cause of retropharyngeal edema. We highlight the diagnostic features that will allow the physicians to make the correct diagnosis, avoid unnecessary incision and drainage, and commence effective treatment early in the disease course.

Melatonin ameliorates brain injury induced by systemic lipopolysaccharide in neonatal rats.

Our previous study showed that lipopolysaccharide (LPS)-induced brain injury in the neonatal rat is associated with nitrosative and oxidative stress. The present study was conducted to examine whether melatonin, an endogenous molecule with antioxidant properties, reduces systemic LPS-induced nitrosative and oxidative damage in the neonatal rat brain. Intraperitoneal (i.p.) injection of LPS (2mg/kg) was administered to Sprague-Dawley rat pups on postnatal day 5 (P5), and i.p. administration of melatonin (20mg/kg) or vehicle was performed 5min after LPS injection. Sensorimotor behavioral tests were performed 24h after LPS exposure, and brain injury was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, and acute brain injury, as indicated by the loss of oligodendrocyte immunoreactivity and a decrease in mitochondrial activity in the neonatal rat brain. Melatonin treatment significantly reduced LPS-induced neurobehavioral disturbances and brain damage in neonatal rats. The neuroprotective effect of melatonin was associated with attenuation of LPS-induced nitrosative and oxidative stress, as indicated by the decreased nitrotyrosine- and 4-hydroxynonenal-positive staining in the brain following melatonin and LPS exposure in neonatal rats. Further, melatonin significantly attenuated LPS-induced increases in the number of activated microglia in the neonatal rat brain. The protection provided by melatonin was also associated with a reduced number of inducible nitric oxide synthase (iNOS)+ cells, which were double-labeled with ED1 (microglia). Our results show that melatonin prevents the brain injury and neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on nitrosative and oxidative stress.

Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.

OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and increased risk of cardiovascular disease events. However, the prevalence and extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and carotid atherosclerosis were compared in 70 patients with psoriasis (46 ± 9 years, 71% male) without known cardiovascular disease or joint involvement and 51 age- and gender-matched healthy control subjects (45 ± 7 years, 71% male). Systemic inflammation was assessed by the level of high-sensitivity C-reactive protein (hs-CRP). Coronary atherosclerosis was determined by the coronary calcification score (CCS) measured by multi-detector computed tomography. Carotid atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima-media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher degree of coronary atherosclerosis estimated by the mean CCS (67.4 ± 349.2 vs. 0.5 ± 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly greater in patients with psoriasis than in control subjects (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was independently associated with increased cIMT. Amongst participants with no traditional cardiovascular disease risk factors, hs-CRP level was higher in patients with psoriasis than in controls. CONCLUSION: The present results demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid arteries in patients with psoriasis, but not in age- and gender-matched control subjects. Low-grade inflammation could explain the presence of premature atherosclerosis in patients with psoriasis.

The implementation of an end-of-life integrated care pathway in a Chinese population.

The integrated care pathway is used in end-of-life care to improve quality of care; the Liverpool Care Pathway (LCP) has been used in Europe and North America. Tuen Mun Hospital is a regional hospital in Hong Kong, China. The End-of-life Care Pathway (ECP) based on the concepts used in the Liverpool Care Pathway, was developed, with modification to suit the local condition. Criteria for entry onto the ECP were that the multidisciplinary team agreed the patient was dying, and was at least two of the following: bedbound; semi-comatose; only able to take sips of fluid; no longer able to take tablets. The ECP template replaced all other inpatient documents. The ECP was implemented in the palliative care unit for terminal cancer patients. An audit was performed to review the result. Fifty-one Chinese patients were included in the audit with mean age 64. The median duration of ECP use was 24 hours. All patients had current medication assessed and non-essential drugs were discontinued. The audit result suggested integrated care pathway in end-of-life care could be implemented successfully in an Oriental culture. The acceptance of using the ECP as a standard clinical practice takes time and education. Appropriate template design and supervision are the keys to success.

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats by reversing the coupling of mu-opioid receptors from Gs-protein to coupling to Gi-protein.

Pertussis toxin (PTX) treatment results in ADP-ribosylation of Gi-protein and thus in disruption of mu-opioid receptor signal transduction and loss of the antinociceptive effect of morphine. We have previously demonstrated that pretreatment with ultra-low dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The present study further examined the effect of ultra-low dose naloxone on mu-opioid receptor signaling in PTX-treated rats and the underlying mechanism. Male Wistar rats implanted with an intrathecal catheter received an intrathecal injection of saline or PTX (1 microg in 5 microl of saline), then, 4 days later, were pretreated by intrathecal injection with either saline or ultra-low dose naloxone (15 ng in 5 microl of saline), followed, 30 min later, by saline or morphine (10 microg in 5 microl of saline). Four days after PTX injection, thermal hyperalgesia was observed, together with increased coupling of excitatory Gs-protein to mu-opioid receptors in the spinal cord. Ultra-low dose naloxone pretreatment preserved the antinociceptive effect of morphine, and this effect was completely blocked by the mu-opioid receptor antagonist CTOP, but not by the kappa-opioid receptor antagonist nor-BNI or the delta-opioid receptor antagonist naltrindole. Moreover, a co-immunoprecipitation study showed that ultra-low dose naloxone restored mu-opioid receptor/Gi-protein coupling and inhibited the PTX-induced mu-opioid receptor/Gs-protein coupling. In addition to the anti-neuroinflammatory effect and glutamate transporter modulation previously observed in PTX-treated rats, the re-establishment of mu-opioid receptor Gi/Go-protein coupling is involved in the restoration of the antinociceptive effect of morphine by ultra-low dose naloxone pretreatment by normalizing the balance between the excitatory and inhibitory signaling pathways. These results show that ultra-low dose naloxone preserves the antinociceptive effect of morphine, suppresses spinal neuroinflammation, and reduces PTX-elevated excitatory Gs-coupled opioid receptors in PTX-treated rats. We suggest that ultra-low dose naloxone might be clinically valuable in pain management.

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway.

We previously demonstrated that ultra-low dose naloxone restores the antinociceptive effect of morphine in rats with pertussis toxin (PTX)-induced thermal hyperalgesia by reversing the downregulation of glutamate transporter (GT) expression and suppressing spinal neuroinflammation. In the present study, we examined the underlying mechanisms of this anti-inflammatory effect in PTX-treated rats, particularly on the expression of GTs. Male Wistar rats were implanted with an intrathecal catheter and, in some cases, with a microdialysis probe. All rats were injected intrathecally with saline (5 microl) or PTX (1 microg), then, 4 days later, were randomly assigned to receive a single injection of saline, ultra-low dose naloxone (15 ng), or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 microg), followed by morphine injection (10 microg) 30 min later. Our results showed that PTX injection induced activation of microglia and a significant increase in P-p38 MAPK expression in the spinal cord. Ultra-low dose naloxone plus morphine significantly inhibited the effect of PTX on P-p38 MAPK expression in the spinal cord, while the p38 MAPK inhibitor SB203580 attenuated the PTX-induced mechanical allodynia, thermal hyperalgesia, increase in spinal cerebrospinal fluid excitatory amino acids, and downregulation of GTs. These results show that the restoration of the antinociceptive effect of morphine and GT expression in PTX-treated rats by ultra-low dose naloxone involves suppression of the p38 MAPK signal transduction cascade.

Relative reliability of the auditory evoked potential and Bispectral Index for monitoring sedation level in surgical intensive care patients.

Sedation is an important adjunct therapy for patients in the intensive care unit. The objective of the present study was to observe correlation between an established subjective measure, the Ramsay Sedation Scale, and two objective tools for monitoring critically ill patients: the Bispectral Index (BIS) and auditory evoked potential. Ninety patients undergoing major surgery scheduled for postoperative mechanical ventilation and continuous sedation with propofol and fentanyl were selected. Electrodes for determining BIS and auditory evoked potential were placed on the foreheads of all patients according to manufacturer's specifications at least six hours after patients' arrival at the intensive care unit. Ramsay Sedation Scale, BIS, signal quality index, composite A-line autoregressive index (AAI) and electromyographic activities were recorded every five minutes for 30 minutes. BIS and AAI showed good correlation amongst readings (r(s)=0.697, P <0.01). Both were significantly influenced by electromyographic activities (BIS, r(s)=0.735, P <0.01; AAI, r(s)=0.856, P <0.01). Comparison of BIS and AAI revealed an acceptable correlation between electroencephalogram variables and the Ramsay Sedation Scale (BIS, tau=-0.689; AAI, tau=-0.621; P <0.01). In conclusion, the auditory evoked potential and BIS monitors revealed an acceptable correlation with the Ramsay Sedation Scale. However, the BIS and auditory evoked potential monitors do not perform adequately as a substitute in the assessment of sedated intensive care unit patients. These monitors could be used as part of an integrated approach for the evaluation of those patients especially when the subjective scales do not work well in the setting of neuromuscular blockade or may not be sufficiently sensitive to evaluate very deep sedation.

Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits.

OBJECTIVE: The present study aimed to determine the role of excitatory amino acids (EAAs) and EAA transporters (EAATs) in an osteoarthritis (OA) model of rabbit knees. METHODS: OA was induced in New Zealand white male rabbits by anterior cruciate ligament transection (ACLT) in one knee of one hind limb; the other knee left unoperated. Rabbits that received ACLT of knee were assigned to the ACLT group (n=6), while a sham-operated group (n=6) underwent arthrotomy with no ACLT. Six naïve rabbits that received no surgery were used as normal control. The width of the knee joint was measured to determine the severity of joint inflammation. Before operation and at 10, 20, and 30 weeks after operation, knee joint dialysates were collected by microdialysis and assayed for EAAs by high-performance liquid chromatography. Gross morphology and histopathology and EAATs glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) expression in the articular cartilage of the knees were evaluated by immunohistochemistry and western blot analysis. RESULTS: In the ACLT knees, a significant increase in the joint width was observed (5.3+/-0.9 mm, P<0.05) at 30 weeks after operation, while the sham-operated and naïve knees showed no difference as compared with the basal values. The concentrations (microM) of aspartate and glutamate in knee dialysates at 30 weeks after ACLT in naïve, sham, and ACLT were 0.36+/-0.07 and 4.5+/-1.10; 0.38+/-0.09 and 4.61+/-1.11; 0.67+/-0.18 and 9.71+/-2.89, respectively. Levels of glutamate and aspartate in the dialysates obtained from the ACLT knees increased by 213.3+/-29.6% and 187.5+/-33.8% (P<0.05) when compared to those in the sham-operated knees. Both naïve and ACLT chondrocytes were positively stained by antibodies against GLAST and GLT-1. GLAST and GLT-1 protein expressions were significantly increased in the ACLT knees (P<0.05). CONCLUSION: Our findings indicate an involvement of EAAs and EAATs in the pathogenesis of OA in ACLT rabbits.

Amitriptyline induces nuclear transcription factor-kappaB-dependent glutamate transporter upregulation in chronic morphine-infused rats.

We previously showed that intrathecal co-administration of amitriptyline with morphine upregulates the expression of the glial glutamate transporters glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) and restores neuronal glutamate transporter excitatory amino acid carrier 1 (EAAC1) expression in chronically morphine-infused rats. The present study examined the role of nuclear transcription factor-kappaB (NF-kappaB) in the regulation of the expression of GLAST, GLT-1, and EAAC1 following long-term amitriptyline/morphine co-infusion. Male Wistar rats were implanted with two intrathecal catheters with or without a microdialysis probe; one of the catheters was used for continuous infusion of saline (control), morphine (15 microg/h), or morphine plus amitriptyline (both 15 microg/h) for 5 days, while the other was used for a single daily intrathecal injection of the NF-kappaB inhibitor Ro106-9920 (10 microl of 10 microM) for 5 days. We found that amitriptyline co-infusion restored the antinociceptive effect of morphine (4.5-fold right-shift in the morphine dose-response curve compared with a 65-fold right-shift in its absence) and this effect was inhibited by Ro106-9920 administration (48-fold right-shift). Moreover, amitriptyline/morphine co-infusion increased IkappaBalpha phosphorylation and the translocation of NF-kappaB p65 from the cytosol to the nucleus. Daily intrathecal injection of Ro106-9920 prevented the amitriptyline/morphine-induced NF-kappaB p65 translocation and reversed the amitriptyline/morphine-induced GLAST and GLT-1 upregulation and inhibited the restoration of EAAC1 expression. The Ro106-9920 injections abolished the inhibitory effect of amitriptyline on the morphine-evoked release of excitatory amino acids into the spinal cerebrospinal fluid (CSF) dialysates. In conclusion, amitriptyline/morphine co-infusion restores the antinociceptive effect of morphine and upregulates GLAST and GLT-1 expression and restores EAAC1 expression to baseline levels, thus reducing excitatory amino acid levels in the spinal CSF dialysates. The mechanism involves activation of the NF-kappaB pathway, but may also involve other pathways.

N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and associated glial fibrillary acid protein up-regulation: a proteomic approach.

BACKGROUND: It is well known that long-term morphine administration results in tolerance, which limits the clinical use of this drug in pain management. METHODS: Male Wistar rats were randomly assigned to receive one of four different infusions: morphine [15 microg/h, intrathecal (i.t.)], saline, MK-801 (5 microg/h, i.t.) plus morphine (15 microg/h, i.t.), or MK-801 (5 microg/h, i.t.) alone. RESULTS: Morphine infusion induced a maximal antinociceptive effect on day 1 and tolerance on day 3, and the maximal anti-receptive tolerance was observed on day 5. Co-infusing MK-801 with morphine attenuated morphine's anti-receptive tolerance. Two-dimensional gel electrophoretic analysis of spinal proteins revealed that eight protein spots were up-regulated in morphine-tolerant rats, and that they were significantly inhibited by MK-801 co-infusion. Among the up-regulated proteins, glial fibrillary acid protein (GFAP), a glial-specific maker, was identified by mass spectrometry. This finding was also confirmed by Western blot analysis. CONCLUSION: Using proteomic analysis, we identified eight GFAP protein spots that were up-regulated in the dorsal horn of morphine-tolerant rat spinal cords. This up-regulation was partly inhibited by N-methyl-D-aspartate receptor antagonist MK-801 co-infusion, which suggests that GFAP protein can be considered to be a pathogenesis marker of morphine tolerance.

Pre-medication with intravenous clonidine suppresses fentanyl-induced cough.

BACKGROUND: A reflex cough is often observed after an intravenous bolus of fentanyl. This study was conducted to determine whether pre-treatment with intravenous clonidine could effectively attenuate fentanyl-induced cough. METHODS: Three hundred ASA I-II patients, aged between 18 and 80 years, undergoing various elective surgeries, were enrolled in this study. All patients were randomly assigned to one of two groups treated with intravenous clonidine 2 microg/kg (clonidine group) or the same volume of normal saline (control group). Intravenous fentanyl (2 microg/kg in 2 s) was injected 2 min after the clonidine or normal saline injection. Changes in the hemodynamics, auditory evoked potentials (AEPs) and Observer Assessment of Alertness/Sedation (OAA/S) rating scale were recorded before and 2 min after the clonidine or normal saline injection and 1 min after the fentanyl injection. The number of coughs 1 min after the fentanyl injection was also recorded. RESULTS: Patients in the clonidine group showed a significantly lower incidence of cough than those in the control group (17.3% vs. 38.7%, respectively; P < 0.01). The blood pressure was lower in the clonidine group than in the control group. There were no significant differences in AEP or OAA/S rating scale. CONCLUSIONS: Pre-treatment with intravenous clonidine (2 microg/kg) suppressed the reflex cough induced by fentanyl, with mild hemodynamic changes. Therefore, intravenous clonidine may be a clinically useful method of suppressing fentanyl-induced cough.

Protective effect of intrathecal ketorolac in spinal cord ischemia in rats: a microdialysis study.

BACKGROUND: The prevention of ischemic paraplegia after thoracoabdominal aortic surgery is challenging for both anesthesiologists and surgeons. In a previous study, we showed that intrathecal ketorolac pre-treatment protects rats against ischemic spinal cord injury. In the present study, using a microdialysis method, we investigated whether this neuroprotective effect was related to changes in the spinal cord release of nitric oxide (NO) or the excitatory amino acids (EAAs) aspartate and glutamate. METHODS: Rats were randomized to receive either intrathecal saline or ketorolac 60 microg (10 rats per group), 1 h before spinal cord ischemic injury induced by balloon inflation of a 2F Fogarty catheter in the thoracic aorta with maintenance of the proximal arterial blood pressure at 40 mmHg for 11 min, followed by reperfusion. Another 10 animals were used as the sham-operated control group. Ischemic injury was assessed by hind limb motor function. Cerebrospinal fluid dialysates were collected at baseline (before ischemia) and at 1, 2, 3, 4, 6, 12 and 24 h after the start of reperfusion, and were analyzed for EAAs using high-performance liquid chromatography and for NO metabolites using an NO analyzer. RESULTS: The results showed that intrathecal ketorolac attenuated spinal cord ischemic injury. Dialysate concentrations of NO and EAAs were increased after spinal cord ischemia, and this effect was inhibited by intrathecal administration of ketorolac. CONCLUSIONS: The results of this study suggest that the neuroprotective effect of intrathecal ketorolac in spinal cord ischemia in rats may be caused by a decrease in the spinal cord release of NO and EAAs.

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids.

OBJECTIVE: Our present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100 microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Naïve (Naïve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia. RESULTS: Parecoxib alone had no effect on cartilage and synovium of normal knees in Naïve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12, P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs 189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively). CONCLUSION: This study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression.

Combined general-epidural anesthesia decreases the desflurane requirement for equivalent A-line ARX index in colorectal surgery.

BACKGROUND: The present study used the A-line ARX index, derived from auditory evoked potential measurements, to examine the effect of epidural lidocaine on the end-tidal concentration of desflurane during general anesthesia. METHODS: Thirty ASA I-II patients scheduled for elective colorectal surgery were included and randomized, in a double-blinded fashion, to receive general anesthesia, and 15 ml of either 2% lidocaine (group GE, n=15) or normal saline (group GS, n=15) was administered epidurally with a maintenance infusion rate of 6 ml h-1. After a 10-min high-flow oxygen wash-in period, desflurane was titrated to a target A-line ARX index (AAI) of 20+/-5. RESULTS: Epidural lidocaine reduced the end-tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P<0.001). The initial mean value of AAI was 87.8 (range 78-99) in group GE and 88.13 (79-99) in group GS before general anesthesia induction, the AAI values were approximately 19.7 (15-25) in group GE and 20.2 (16-25) in group GS during anesthesia maintenance, and returned to 84.53 (77-98) in group GE and 86.87 (79-98) in group GS when the patients regained consciousness in the recovery room. No statistical difference in the AAI values was observed either before, during, or after emergence of anesthesia. No patient reported intraoperative awareness. CONCLUSIONS: Lower-than-expected concentrations of volatile anesthetics are sufficient to maintain appropriate a clinical anesthesia effect during combined general-epidural anesthesia under auditory-evoked potential monitoring.

Dexamethasone modulates the development of morphine tolerance and expression of glutamate transporters in rats.

We recently demonstrated an increase in spinal cerebrospinal fluid (CSF) excitatory amino acids (EAAs) in morphine-tolerant rats after morphine challenge. The present study examined whether co-infusion of the glucocorticoid dexamethasone (DEX) co-infusion inhibited morphine tolerance and the morphine challenge-induced EAAs increase after long-term morphine infusion. Intrathecal (i.t.) catheters and one microdialysis probe were implanted to male Wistar rats. Rats were divided into four groups: i.t. morphine (15 microg/h), saline (1 microl/h), DEX (2 microg/h), or DEX (2 microg/h) plus morphine (15 microg/h) infusion for 5 days. Tail-flick responses were examined before drug infusion and daily after the start of infusion for 5 days. Moreover, on day 5 after morphine challenge (50 microg, i.t.), CSF EAAs was also measured. Rat spinal cords were removed on day 5, and prepared for Western blot analysis of different glutamate transporters (GTs). The AD50 (analgesic dose) on day 5 was 1.33 microg in saline-infused rats, 83.84 microg in morphine-tolerant rats, and 10.15 microg in DEX plus morphine co-infused rats. Single DEX (2 microg, i.t.) injection did not enhance morphine's antinociceptive effect in either naïve or morphine-tolerant rats. No difference in CSF EAA level was observed in all groups between baseline (before drug infusion) and on day 5 after tolerance developed. Surprisingly, on day 5, after morphine challenge, an increase in glutamate and aspartate (284+/-47% and 201+/-18% of basal) concentration was observed, and morphine lost its antinociceptive effect (maximum percent effect, MPE = 41+/-12%), whereas DEX/morphine co-infusion inhibited morphine-evoked EAA increase with a MPE = 97+/-2%. DEX co-infusion prevented the downregulation of glial glutamate transporters (GLAST (Glu-Asp transporter) and GLT-1 (Glu transporter-1)), but not the neuronal GT EAAC1 (excitatory amino acid carrier). Upregulation of GLT-1 was also observed (204+/-20% of basal). DEX co-infusion inhibits the morphine-challenge induced EAA increase and prevents the loss of morphine's antinociceptive effect after long-term morphine infusion.