Significant Delay In Recovery Research Articles

Principal component analysis on the effect of early morning awakening in major depressive disorder

Sleep disturbance is one of the most prevalent symptoms associated with Major Depressive Disorder (MDD). A recent article (Wu et al., 2022, Journal of Multiscale Neuroscience 1, 133-139) explored the significant relationship between early morning awakening (EMA), a type of sleep disturbance, and recovery in MDD patients. In the paper, the authors examined the relationship between EMA and the treatment of MDD with twelve neuropsychological parameters. The authors employed two univariate statistical techniques, students’ t-test and ANOVA, to analyze their data. While their analysis derived a meaningful conclusion that EMA may result in a statistically and clinically significant delay in recovery, we found that a multivariate statistical technique, principal component analysis (PCA), extracted additional quantitative information from their study. In this paper, we present quantitative features in the interaction between EMA and the treatment of MDD obtained from PCA.

Effect of early morning awakening in major depressive disorder

Patients with the major depressive disorder usually manifest with sleep disturbance. Early morning awakening is more closely related to major depressive disorder than other sleep disturbances. This study aimed to assess the effect of early morning awakening in treating patients with major depressive disorder. The eligible patients were divided into two groups according to whether they woke up at 2-4 a.m: early morning awakening and non-early morning awakening group. All patients were assessed using the Hamilton Depression Scale, Hamilton Anxiety Scale, and Repeatable Battery for the Assessment of Neuropsychological Status scores at baseline and the fourth week. Twenty-one men and 31 women (mean age 25.13 ±10.67 years) were enrolled. There was a significant main effect of early morning awakening in the Hamilton Depression Scale (P = 0.04) and Hamilton Anxiety Scale (P = 0.01) at the fourth week after treatment. But there was no significant difference in cognitive changes between the two groups. In conclusion, a major depressive disorder with early morning awakening may result in statistically and clinically significant delay in recovery.

The CGRP/macrophage axis signal facilitates inflammation recovery in the intestine

The mechanism of the recovery of immune inflammation in the intestine remains to be investigated. The calcitonin-related protein (CGRP; neuropeptide) has immune regulatory capacity. We observed that lower levels of CGRP were found in the colon biopsies of UC patients. CGRP were negatively correlated to TNF-α, IL-1β and IFN-γ in biopsy samples. The levels of TGF-β were lower in the UC group than that of the normal control (NC) group, which were positively correlated with the CGRP levels. Blocking CGRP significantly delayed recovery from colitis inflammation. CGRP induced the TGF-β-expressing CD4+ Tim4+ macrophages in the intestine. CD4+ Tim4+ macrophages demonstrated immune regulatory function in suppressing proliferation of isolated T cells of colitis and induced apoptosis of T cells. Ablation of the Tgfb1 expression in macrophages resulted in a significant delay in recovery of inflammation in colitis, which was rescued by reconstitution of the CD4+ Tim4+ macrophages in mice.

Chemically-induced colitis is more severe in mice expressing TLR4 SNPs: a novel model for studying human Inflammatory Bowel Disease

Abstract Innate immune cells sense “danger” encountered in the environment using pattern recognition receptors (PRRs). The Toll-Like Receptors (TLRs) are a large family of PRRs, among which TLR4 is unique in the complexity of its downstream signaling. Single nucleotide polymorphisms (SNPs) expressed in the ectodomain of human TLR4 (D299G/T399I), have been shown to affect the functionality of this receptor. Population genetics studies have shown that these SNP frequencies vary geographically and among different ethnic backgrounds, with both SNPs co-segregating in ~10% of Caucasians. Humans expressing these TLR4 SNPs are LPS-hyporesponsive and exhibit increased susceptibility to certain bacterial infections and severe colitis. Our laboratory engineered a knock-in mouse strain that homozygously expresses homologous TLR4 SNPs (D298G/N397I). TLR4-SNP mice and their macrophages are LPS-hyporesponsive and exhibit altered susceptibility to bacterial and viral infections. To evaluate the mechanisms by which TLR4 SNPs contribute to Inflammatory Bowel Disease (IBD), we utilized a chemically-induced colonic inflammation and repair model to compare the responses of wild-type (WT) vs. TLR4-SNP mice. After 7 days of 3% dextran sodium sulfate (DSS) in the drinking water, followed by an additional 7 days of recovery, TLR4-SNP mice were found to be significantly more sensitive than WT mice to DSS-induced colitis (e.g., weight loss, fecal blood, colon length, histopathology, and a significant delay in recovery after DSS removal). Ongoing studies to determine if differences in the microbiota of TLR4-SNP mice vs. WT mice contribute to this phenotype are expected to provide insights into mechanisms underlying human IBD. Supported by NIH T32 AI095190.

Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease

Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith, PLoS One 8, e73204 (2013); S. Kozar et al., Cell Stem Cell 13, 626-633 (2013)], how they are impacted by enteric infections remains poorly defined. Here, we investigate infection-mediated damage to the colonic stem cell compartment and how this affects epithelial repair and recovery from infection. Using the pathogen Clostridioides difficile, we show that infection disrupts murine intestinal cellular organization and integrity deep into the epithelium, to expose the otherwise protected stem cell compartment, in a TcdB-mediated process. Exposure and susceptibility of colonic stem cells to intoxication compromises their function during infection, which diminishes their ability to repair the injured epithelium, shown by altered stem cell signaling and a reduction in the growth of colonic organoids from stem cells isolated from infected mice. We also show, using both mouse and human colonic organoids, that TcdB from epidemic ribotype 027 strains does not require Frizzled 1/2/7 binding to elicit this dysfunctional stem cell state. This stem cell dysfunction induces a significant delay in recovery and repair of the intestinal epithelium of up to 2 wk post the infection peak. Our results uncover a mechanism by which an enteric pathogen subverts repair processes by targeting stem cells during infection and preventing epithelial regeneration, which prolongs epithelial barrier impairment and creates an environment in which disease recurrence is likely.

An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy.

Background and Aims:Anticonvulsants are used routinely for seizure prophylaxis in patients with supratentorial tumour who present with/without seizures. Excessive use of prophylactic anticonvulsant may delay the recovery from anaesthesia. We have studied the recovery profiles of patients who received an additional dose of anticonvulsant in comparison with those who received only the regular dose.Methods:In this prospective observational study, patients were anaesthetised using standard anaesthesia protocol. An additional dose of anticonvulsant was administered in one group, while the other group received only the regular dose. Time taken for extubation, eye opening, obeying commands and orientation were compared between the two groups. Haemodynamics, depth of anaesthesia, the plasma anticonvulsant levels and the incidence of seizures were compared between the two groups.Results:A total of 36 patients were studied, of which 19 received regular dose and 17 received an additional dose. There was no significant difference in recovery time between the two groups. Subgroup analysis was performed for phenytoin and sodium valproate. There was a clinically significant delay in recovery in patients who received an additional phenytoin compared to those who received regular dose (time to obey commands >15 min and orientation time >1hour) but, it was not statistically significant. Administration of an additional dose of valproate did not prolong the recovery time.Conclusion:An additional dose of sodium valproate did not cause a delay in recovery both, clinically and statistically. However, the administration of an additional dose of phenytoin caused a clinically significant delay in recovery but was not statistically significant.

Comparison of Functional Outcome after Extended versus Super-Extended Pelvic Lymph Node Dissection during Radical Prostatectomy in High-Risk Localized Prostate Cancer.

Urinary continence and erectile function (EF) are best preserved when meticulous dissection of prostate and nerve sparing technique are used during radical prostatectomy (RP). However, extent of lymph node dissection (LND) may also adversely affect functional results. To determine whether performing a super-extended LND (seLND) has a significant effect on recovery of urinary continence and EF after RP. All patients who underwent RP from January 2007 until December 2013 were handed questionnaires assessing continence and EF. All patients in whom at least an extended LND (eLND) was performed were selected. This search yielded 526 patients. 172 of these patients had filed out 2 or more questionnaires and were included in our analysis. All questionnaires were reviewed. We used Kaplan-Meier analyses and multivariate Cox analysis to assess the difference in recovery of continence and EF over time for eLND/seLND. Primary endpoints were full recovery of continence (no loss of urine) and full recovery of EF (successful intercourse possible). Patients who did not reach the endpoint when the last questionnaire was filled out were censored at that time. Median follow-up was 12.43 months for continence, and 18.97 months for EF. Patients undergoing seLND have a lower chance of regaining both urinary continence [hazard ratio (HR) 0.59, 95% CI 0.39-0.90, p = 0.026] and EF (HR 0.28, 95% CI 0.13-0.57, p = 0.009). Age at surgery had a significant influence on both continence and EF in multivariate analysis. Major limitation of the study was that no formal preoperative assessment of continence and potency was done. Extending the LND template beyond the eLND template may cause at least a significant delay in recovery of urinary continence and leads to less recovery of EF.

“No donor”? Consider a haploidentical transplant

Haploidentical stem cell transplantation (HaploSCT) is an attractive option for patients requiring a hematopoietic stem cell transplant who do not have an HLA-matched donor, because it is cheaper, can be performed faster, and may extend transplantation to virtually all patients in need. Significant advances have been made in the recent decade with dramatic improvement in treatment outcomes. Historically, overcoming the HLA-incompatibility barrier has been a significant limitation to the expansion of this form of transplant. While ex vivo T-cell depletion effectively prevented the development of acute GVHD, it was associated with a higher treatment-related mortality, in excess of 40% in some series, due to a significant delay in recovery of the adaptive immune system. Newer methods have successfully maintained the memory T cells in the graft and/or selectively depleted alloreactive T cells, and are associated with improved treatment outcomes. Post-transplant cyclophosphamide for GVHD prevention has proven very effective in controlling GVHD with lower incidence of infectious complications and treatment-related mortality—as low as 7% at 1 year—and has become the new standard in how this transplant is performed. Here, we reviewed the current experience with this approach and various other strategies employed to control alloreactivity in this setting, including selective depletion of T cells from the graft, as well as we discuss post-transplantation therapy to prevent disease relapse and improve immunologic reconstitution.

Loss of Notch1 Disrupts the Barrier Repair in the Corneal Epithelium

The corneal epithelium is the outermost layer of the cornea that directly faces the outside environment, hence it plays a critical barrier function. Previously, conditional loss of Notch1 on the ocular surface was found to cause inflammation and keratinization of the corneal epithelium. This was in part attributed to impaired vitamin A metabolism, loss of the meibomian glands and recurrent eyelid trauma. We hypothesized that Notch1 plays an essential role in the corneal epithelial barrier function and is a contributing factor in the pathologic changes in these mice. Notch1 was conditionally deleted in adult Notch1flox/flox, K14-Cre-ERT+/- mice using hydroxy-tamoxifen. The results indicated that conditional deletion of Notch1 on the ocular surface leads to progressive impairment of the epithelial barrier function before the onset of corneal opacification and keratinization. Loss of the barrier was demonstrated both by an increase in in vivo corneal fluorescein staining and by enhanced penetration of a small molecule through the epithelium. Corneal epithelial wounding resulted in significant delay in recovery of the barrier function in conditional Notch1-/- mice compared to wild type. Mice with conditional deletion of Notch1 did not demonstrate any evidence of dry eyes based on aqueous tear production and had normal conjunctival goblet cells. In a calcium switch experiment in vitro, Notch1-/- cells demonstrated delayed membrane localization of the tight junction protein ZO-1 consistent with a defect in the epithelial tight junction formation. These findings highlight the role of Notch1 in epithelial differentiation and suggest that intrinsic defects in the corneal epithelial barrier recovery after wounding is an important contributing factor to the development of inflammatory keratinization in Notch1-/- mice.

Moderate Intermittent Hypoxia: Effect on Two-Choice Reaction Time Followed by a Significant Delay in Recovery

Moderate Intermittent Hypoxia: Effect on Two-Choice Reaction Time Followed by a Significant Delay in Recovery

Moderate Intermittent Hypoxia: Effect on Two-Choice Reaction Time Followed by a Significant Delay in Recovery

Hypoxia continues to be a significant source of peril in military aviation. Over three dozen hypoxia-related incidents were reported in the past decade with three resulting in fatalities (Clark & Megown, 2005; Ostrander, 2008). Previous work has addressed loss of consciousness resulting from extreme levels of hypoxia (Carlyle, 1963); however, most mishaps are related to moderate hypoxia exposure. More work is required to establish the cognitive effects of moderate hypoxia and the time required, post-exposure, to fully recover. The present study examined the effect of a ten minute exposure to an air mixture equivalent to 20,000 ft on two-choice reaction time. Carryover effects were assessed over a ten minute recovery period. Hypoxia exposure resulted in significant delays in two-choice reaction time. Significant carry-over effects continued to be detected throughout the recovery period. This information is essential to military aviation, where high levels of cognitive performance are required after moderate hypoxia exposure.

In Vitro and in Vivo Inhibition of JAK2 Signaling by Potent and Selective JAK2 Inhibitor

Recent advances in understanding the role of JAK2 V617F mutation in Bcr-Abl negative myeloproliferative (MPD) diseases pathogenesis opened up a possibility to develop highly targeted therapies against these debilitating ailments. We used a Ba/F3 cell line expressing the V617F mutant of JAK2 to screen a focused small molecule library for potential inhibitors of JAK2 V617F-dependent proliferation. Further extensive SAR of initial hits resulted in identification of R723, a potent and selective JAK2 inhibitor. This molecule is strongly antiproliferative (IC50 130–200 nM) against mouse BaF3 cells used for initial screening as well as against human UKE1 and SET2 cell lines harboring the same mutation. On the other hand, R723 has only weak activity in IL2-dependent (i.e. JAK1/JAK3-dependent) proliferation assays performed with human primary T (IC50 1300 nM) and mouse T-cell leukaemia CTLL2 cells (IC50 600 nM). A 10 to 20 fold cell-based selectivity of R723 was further confirmed by measuring inhibition of constitutive STAT5 phosphorylation in SET2 and BaF3 cells versus inhibition of IL-2 inducible STAT5 phosphorylation in human primary T and mouse CTLL2 cells using FACS-based approach. Compound R723 has low nonspecific antiproliferative activity against JAK2-independent MOLT4, A549 and H1299 cell lines with an IC50 ranging from 4 to 6 uM. The molecule has been also proven to be potent (IC50 of 2 nM against JAK2 in biochemical assay) and highly selective (window of more than 500 fold over JAK1 and 10 fold over JAK3) inhibitor of JAK2 kinase in vitro. Moreover, when tested in biochemical assay against a panel of more than 200 kinases at a concentration of 20 nM (IC90 for JAK2), R723 inhibited none of them. The selectivity of R723 was further confirmed using a variety of cell-based assays probing T-, B- and mast cell activation. Compound R723 was further evaluated in a stress-induced erythropoiesis mouse model, where kinetics of EPO-dependent hematocrit recovery from phenylhydrazine-induced anemia was assessed. Significant delay in recovery was observed at doses of 75 and 100 mg/kg bid indicating strong compound effect on EPOR signaling in vivo. The result could not be attributed to general toxicity effects as 14 day toxicology study did not identify any abnormalities at doses tested. As a result, R723 could become the basis for next generation of potent and selective compounds targeting JAK2-dependent myeloproliferative diseases.

Toll-like receptor signaling is critical for Wallerian degeneration and functional recovery after peripheral nerve injury.

Toll-like receptors (TLRs) bind specific components conserved among microorganisms as well as endogenous ligands produced by necrotic cells, injured axons, and the extracellular matrix. Here, we investigated whether TLRs are involved in regulating the immune response, Wallerian degeneration (WD), and nerve regeneration after sciatic nerve lesion. Early expression of interleukin-1beta and monocyte chemoattractant protein-1 was compromised in the sciatic nerve distal stump of mice deficient in TLR signaling. In addition, significantly fewer macrophages were recruited and/or activated in the sciatic nerve distal stump of TLR2-, TLR4-, and MyD88-deficient mice compared with wild-type littermates, whereas WD, axonal regeneration, and recovery of locomotor function were impaired. In contrast, animals that received a single microinjection of TLR2 and TLR4 ligands at the site of sciatic nerve lesion had faster clearance of the degenerating myelin and recovered earlier than saline-injected control rats. Finally, rats that had altered innate immune response through dexamethasone treatment exhibited three times more myelin debris in their sciatic nerve distal stump and a significant delay in recovery of locomotor function. Our results provide strong evidence that TLR signaling plays a critical role in orchestrating the innate immune response leading to efficient and rapid clearance of inhibitory myelin debris and nerve regeneration.

Energy Status, Lipid-Soluble Vitamins, and Acute Phase Proteins in Periparturient Holstein and Jersey Dairy Cows With or Without Subclinical Mastitis

In a retrospective, case-controlled, observational study, associations among indices of negative energy balance, plasma lipid and lipid-soluble vitamin concentrations, plasma acute phase protein status, and occurrence of a new subclinical intramammary infection (IMI) during the periparturient period were determined. Cows were paired based on breed and expected parturition date (EPD) and monitored from the cessation of lactation through wk 8 of the subsequent lactation. A cow was identified as developing a new IMI if the intramammary pathogen isolated postpartum differed from that isolated in wk −9 (relative to EPD). Mean body condition score (BCS) of cows at wk −9 was 3.71±0.12. Fifteen Holstein and 15 Jersey dairy cows met the study selection criteria. Cows with a new IMI had greater body condition score, body weight, and body weight loss compared with cows that did not develop a new IMI. Prepartum plasma concentrations of β-carotene were greater for Jersey cows with a new IMI compared with Jersey cows without a new IMI and Holstein cows, regardless of IMI status. However, there was a significant delay in recovery of plasma concentrations of β-carotene postpartum for Jersey cows with a new IMI compared with Jersey cows without a new IMI. Plasma α-tocopherol, albumin, and retinol binding protein concentrations were greater during the periparturient period for cows without a new IMI. Plasma haptoglobin was increased at wk 1 postpartum for cows without a new IMI. Milk protein and lactose percentages and milk urea N were decreased and somatic cell counts were increased in cows identified with a new IMI compared with cows that did not develop a new IMI. Dairy cows with greater tissue energy stores prepartum and reduced plasma proteins, β-carotene, and α-tocopherol had a greater risk for developing a new IMI during the periparturient period.

Magnesium as an adjuvant during general anaesthesia

We read with interest the study by Gupta et al. on the use of magnesium as an adjuvant during general anaesthesia [1]. We would like to share some observations on the study. Magnesium efficacy and usefulness in different clinical settings has recently been extensively reviewed [2]. However, clinical use of a drug warrants examination of its safety profile and cost effectiveness. Currently, the use of magnesium in clinical practice is limited to emergency and life-threatening conditions [3] because its safety profile has not yet been extensively studied. In their study, Gupta and colleagues used 30 mg.kg−1 of magnesium sulphate prior to induction and 10 mg.kg−1.h−1 by continuous infusion during surgery, but they didn't explain the rationale for this dose regimen. Most previous studies have used doses between 40 and 60 mg.kg−1 at induction, followed by 8–15 mg.kg−1.h−1 intra-operatively [4-7]. They compared time to recovery of the twitch height to 25% (T3) and time to reach a BIS value of 80 following discontinuation of rocuronium (30 min before end of surgery) and propofol (at skin closure) infusions, respectively. However, they did not describe when the magnesium sulphate infusion was stopped. They concluded that there was a significant delay in recovery of T3 and recovery of the BIS to 80 in the magnesium group. A rise in serum magnesium from 1.99 to 2.17 mg.dl−1 was observed postoperatively, but this did not exceed the normal physiological range. Serum magnesium concentration was not measured intra-operatively. We believe that for an accurate interpretation of the results such intra-operative concentrations are important. As the serum magnesium concentration did not exceed the physiological range, and we don't know the intra-operative concentration, it is difficult to explain the reason for the delay in recovery of T3 and BIS. The context-sensitive half-life of magnesium has not, to our knowledge, been studied. Although the therapeutic and toxic serum magnesium concentrations are known, the clinical severity of the effects is not always correlated with the degree of hypermagnesaemia [8] and it is important to observe for early clinical signs of magnesium toxicity. In the anaesthetised patient, signs such as flushing, nausea, vomiting, somnolence, deep coma will clearly be missed. Cardiovascular monitoring in anaesthetised patients can only detect late signs of cardiac toxicity and the influence of other confounding factors is difficult to rule out. Finally, the authors have not elaborated on the cost effectiveness of the proposed regimen. We have made a calculation based on the data given in the study and the pricing given in the British National Formulary [3]. We estimated a total saving of only £0.80 over 5 h. The total cost of propofol, rocuronium and fentanyl used over the 5-h period for a patient with mean weight of 70 kg in their control group (group B) is £35.51. In the magnesium group (group A) with a mean weight of 65 kg the cost of the same drugs is £19.11, but there is an additional cost of £15.60 for the magnesium. We suggest that the use of this regimen will not be cost effective and would not be free from the risk of toxicity.

The fibroblast growth factor-2 antisense gene inhibits nuclear accumulation of FGF-2 and delays cell cycle progression in C6 glioma cells

Fibroblast growth factor-2 (FGF-2) is a potent heparin-binding protein with growth-promoting and anti-apoptotic activity. Transcription of the GFG/NUDT6 gene on the opposite DNA strand generates an overlapping antisense RNA (FGF-AS) implicated in the post-transcriptional regulation of FGF-2. C6 glioma cells coordinately express FGF-2 and FGF-AS mRNA in a cell cycle-dependent manner. Cellular FGF-2 immunoreactivity was also cell cycle-dependent, with marked nuclear accumulation during S-phase. Stable transfection and overexpression of the FGF-AS RNA resulted in suppression of total cellular FGF-2, and a reduction in nuclear accumulation of FGF-2 isoforms. Serum stimulation of growth-arrested wild-type cells evoked a rapid nuclear translocation of FGF-2, and cell cycle re-entry. FGF-AS transfectants, in contrast, showed a significant delay in recovery of both nuclear FGF-2 staining and S-phase re-entry. Similar results were observed when cells were released from aphidicolin-induced G1 arrest or subjected to heat shock. These findings indicate that FGF-AS RNA inhibits expression and cell cycle-dependent nuclear accumulation of FGF-2, and this is associated with a marked delay in S-phase progression. The results suggest that the endogenous FGF antisense RNA may play a significant functional role in the regulation of FGF-2 dependent cell proliferation in FGF-2 expressing cells.

Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction.

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine (n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion (n = 12), LAD deendothelization (n = 11), or a sham operation (n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin (n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 +/- 4.6 to 1.9 +/- 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 +/- 7.0 to 3.4 +/- 3.9 ml/min), with a significant delay in recovery (P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.

THE CHANGE OF INTRATYMPANIC PRESSURE DURING GENERAL ANESTHESIA WITH LARYNGEAL MASK

S230 It is known that nitrous oxide(N2 O) causes either a volume or a pressure increase, due to diffusion, inclosed body spaces. In the intratympanic cavity both pressure(ITP) and volume increase because of its semicompliant boundaries, the tympanic membrane and the eustachian tube. This results in bulging of the intact drum which may be important during operations such as tympanoplasty. This problem is avoided if N2 O is discontinued 30min before the anticipated placement of the graft. [1] Our purpose is to examine the effects of N2 O on ITP during general anesthesia with LM compared to tracheal intubation. METHODS: Eleven patients with normal healthy ears were divided into two groups either use of LM(n=6) or intubation(n=5). All patients were induced with propofol /vecuronium intravenously. We measured MEP by using tympanometer and the time which take ITP reached beyond 200 dePa level after inspiration of N2 O. Anesthesia was maintained with sevoflurane 2% and N2 O 66% in oxygen. Moreover, ITP were measured in oxygen 100% after elimination of N2 O and after extubation in both groups. Patients were maintained ETCO2 between 30mmHg and 35mmHg. RESULTS: With inspiration of N2 O, ITP increased progressively in both groups. It took 16 +/- 5 min in the intubation group and 42 +/- 18 min in LM group that ITP reached to peak level (>or=to200dePa) from after inspiration of N (2) O. After cessation of inhalation of N2 O, ITP decreased progressively. It took 68 +/- 24 min in LM group that ITP recovered to about 100 dePa(125 +/- 17 dePa), which never recovered to normal level and was much longer than that in intubation group (33 +/- 14 min, p<0.05).After removal of LM, ITP recovered to normal level. DISCUSSION: An increase in ITP depends on the following factors: a) duration of N2 O; b) Concentration of N2 O or another gas used; c) Presence of a blocked or narrow eustachian tube; d) control ventilation (swallowing reflexes). [2] Consequently, it is suggested that as the one of the reasons of significant delay in recovery of ITP is due to compression to the eustachian tube by using LM.

Response to the Valsalva manoeuvre after spinal anaesthesia.

The waveform from a Criticare 504 pulse oximeter was recorded during the performance of a standard Valsalva manoeuvre in 20 patients before and after spinal anaesthesia. The pulse oximeter waveform showed changes typical of the expected heart rate and pulse volume changes seen in each phase of the Valsalva manoeuvre. There were no significant changes in the typical pulse volume changes of the Valsalva manoeuvre after spinal anaesthesia, which achieved a sensory block ranging in upper extent from T3-T12. There was, however, a significant delay in recovery of the pulse volume in phase 4 of the Valsalva manoeuvre after spinal anaesthesia from a mean (SD) of 3.1 (0.9) s to 6.2 (3.1) s (p less than 0.05). There was also a significant reduction in reflex bradycardia seen in phase 4. However, this was found only at 5, 10 and 15 min after spinal anaesthesia and was not associated with a significant change in Valsalva ratio or maximum-to-minimum rate ratio. The study confirms that the normal response to a standard Valsalva manoeuvre is suppressed only mildly during spinal anaesthesia in normovolaemic fit patients.

Hypothermia following acute carbon monoxide poisoning increases mortality

The effect of body temperature during recovery from acute severe carbon monoxide (CO) poisoning on morbidity and mortality was investigated using an unanesthetized animal model. Levine prepared female rats were exposed to 2700 ppm CO for 90 min, displaying the usual hypothermia, hypotension and bradycardia. Body temperature in survivors was either maintained at the terminal CO exposure value for 4 h (‘cooled’), rapidly raised to the pre-CO exposure value for 4 h (‘heated’) or allowed to return to normal naturally (‘unheated’). Following this period of recovery, the ‘heated’ rats sustained the lowest mortality rate (22%), the ‘unheated’ rats a greater mortality rate (44%), and the ‘cooled’ rats the highest mortality rate (50%). Inclusive of the surviving rats, there were no significant differences in neurologic deficit between the three groups, after 4, 24 or 48 h of recovery. Aside from a significant delay in recovery of blood pressure in the ‘heated’ rats relative to the other two treatment groups post-CO, there were no differences in blood pressure, heart rate or plasma glucose. The results suggest that rapid return to euthermia improves survival following acute severe CO poisoning, contrasting with an earlier study showing the detrimental effect of euthermia during CO poisoning.