Temporal Genetic Modifications after Controlled Cortical Impact--Understanding Traumatic Brain Injury through a Systematic Network Approach.

Traumatic brain injury (TBI) is a primary injury caused by external physical force and also a secondary injury caused by biological processes such as metabolic, cellular, and other molecular events that eventually lead to brain cell death, tissue and nerve damage, and atrophy. It is a common disease process (as opposed to an event) that causes disabilities and high death rates. In order to treat all the repercussions of this injury, treatment becomes increasingly complex and difficult throughout the evolution of a TBI. Using high-throughput microarray data, we developed a systems biology approach to explore potential molecular mechanisms at four time points post-TBI (4, 8, 24, and 72 h), using a controlled cortical impact (CCI) model. We identified 27, 50, 48, and 59 significant proteins as network biomarkers at these four time points, respectively. We present their network structures to illustrate the protein-protein interactions (PPIs). We also identified UBC (Ubiquitin C), SUMO1, CDKN1A (cyclindependent kinase inhibitor 1A), and MYC as the core network biomarkers at the four time points, respectively. Using the functional analytical tool MetaCore™, we explored regulatory mechanisms and biological processes and conducted a statistical analysis of the four networks. The analytical results support some recent findings regarding TBI and provide additional guidance and directions for future research.

Comparison of 3 video laryngoscopes with the Macintosh in a manikin with easy and difficult simulated airways.

OBJECTIVES: Tracheal intubation is used to maintain a patent airway and can occasionally be difficult in a potentially difficult airway, especially for novice managers. In this study, we evaluated the time required, extent of the difficulty, and number of dental clicks in the tracheal intubation for novice medical students between the Macintosh (Truphatek International Ltd, Netanya, Israel) and 3 video laryngoscopes in normal and difficult simulated intubation positions on manikins on both the table and floor. METHODS: We recruited 20 medical students as novice airway managers. They used the Macintosh, Truview (Truphatek International Ltd, Netanya, Israel), Glidescope (Verathon Inc., Bothell, WA), and Airway Scope (AWS) (Pentax Corporation, Tokyo, Japan) laryngoscopes in normal and difficult simulated airways on manikins on both the table and floor. The time to intubate, modified Cormack-Lehane score, intubation difficulty score, and dental click number were estimated and compared. RESULTS: All 20 medical students completed the study. The AWS required the shortest intubation time, provided the best glottic view and easiest intubation, and resulted in less dental clicks compared with the other 3 laryngoscopes; these phenomena were particularly prominent in the cervical-spine immobilization position on the floor. Although all video laryngoscopes provided better glottic views than the Macintosh laryngoscopy in terms of time to intubate, intubation difficulty score, and the number of dental clicks, the outcomes from the Macintosh laryngoscope were better than those of the Truview and Glidescope. CONCLUSIONS: The AWS may have the potential for quicker, easier, and safer tracheal intubation in scenarios involving difficult airways for a novice airway manager.

Comparison of dexamethasone with ondansetron or haloperidol for prevention of patient-controlled analgesia-related postoperative nausea and vomiting: a randomized clinical trial.

BACKGROUND: Patient-controlled analgesia (PCA) with parenteral opioids is associated with a high incidence of postoperative nausea and vomiting (PONV). The aim of the present study was to compare the efficacy of dexamethasone plus haloperidol with dexamethasone plus ondansetron for the prevention of PCA-related PONV. Patients who received dexamethasone alone were used as controls. METHODS: A total of 135 female patients (n = 45 in each of three groups) were eligible to participate in this randomized trial. A total of 135 female patients (n = 45 in each of three groups) were eligible to participate in this randomized trial. Dexamethasone 5 mg IV was administered after the induction of anesthesia in dexamethasone group (group D) patients. Patients in the dexamethasone plus haloperidol group (group DH) and in the dexamethasone plus ondansetron (group DO) further received haloperidol 2 mg IM or ondansetron 4 mg IV, respectively, 30 min before the end of surgery. The complete response rates, incidence of PONV, need for rescue medication, average pain and sedation scores, recovery times, and adverse events were observed postoperatively. RESULTS: The incidences of total PONV in the first 24 h in groups DH (35%) and DO (30%) were significantly lower than those of group D (57%) (p < 0.05 for each comparison). The differences between groups DH and DO were insignificant. The incidence of PONV was significantly smaller in the DH and DO groups than predicted by the patients' underlying risks. Pain scores, sedation scores, and recovery times were similar among the three study groups, and no clinically relevant prolongation of the electrocardiographic QTc interval was observed in any patient. conclusions: Dexamethasone 5 mg with either haloperidol 2 mg or ondansetron 4 mg provides a better antiemetic effect than dexamethasone 5 mg alone in patients receiving postoperative morphine PCA.

Dynamic effects of respiration on aortic blood flow and its autonomic control in rats.

1. Respiratory related arterial pressure variability may reflect body fluid status and/or cardiac sympathetic function. The underlying mechanism is not clear. 2. In the present study, we used an electromagnetic blood flow meter to measure ascending aortic blood flow, from which stroke volume was integrated, to study respiration-stroke volume coupling and its underlying neural regulation. Experiments were performed on male Sprague-Dawley rats that were anaesthetized with pentobarbital sodium, paralysed with pancuronium and under mechanical ventilation. 3. Programmed irregular ventilation evoked significant variability in arterial pressure, aortic flow and stroke volume signals. Good coupling was noted between lung volume and aortic flow, as well as between lung volume and stroke volume; this coupling persisted under all experimental conditions. The aortic flow power and stroke volume variability and the transfer magnitude of the lung volume-aortic flow and lung volume-stroke volume couplings were suppressed by 1 mg/kg propranolol, but not by 0.3 mg/kg atropine or a combination of 0.3 mg/kg atropine and 2.5 mg/kg phentolamine. 4. These results suggest that respiratory related variability in aortic flow and stroke volume, which ultimately contributes to arterial pressure variability, is primarily under cardiac sympathetic control via beta-adrenoceptors in anaesthetized and mechanically ventilated rats.

Sympathetic and parasympathetic activities evaluated by heart-rate variability in head injury of various severities.

OBJECTIVE: To investigate the autonomic function in patients with brain damage of various extents. The purposes were to correlate the parameters derived from spectral analysis of the heart-rate variability (HRV) with the classic Glasgow coma scale (GCS), and to evaluate the possible clinical application of HRV in the autonomic functions in patients with various severities of brain-stem injury. METHODS: A total of 90 patients was divided into 5 groups based on the GCS: I: 15, II: 9-14, III: 4-8, no pupil dilatation, IV: 4-8, pupil dilatation, and V: 3, brain death. Electrocardiogram was recorded for frequency-domain analysis of RR intervals. HRV were categorized into the low-frequency (LF, 0.04-0.15Hz) and high-frequency power (HF, 0.15-0.40Hz), LF to HF power ratio (LF/HF), normalized powers (LF and HF%). These HRV parameters were correlated with the severity of brain damage. RESULTS: The LF, HF, LF%, and LF/HF in Group I were essentially similar to those in the normal subjects. LF and HF decreased from Group I to IV. All parameters were nearly absent in Group V. CONCLUSIONS: The increases in LF% and LF/HF with the decrease in HF indicate augmented sympathetic and attenuated parasympathetic drive. These changes were related to the severity of brain-stem damage. Both LF and HF were nearly abolished in brain death. SIGNIFICANCE: Our analysis indicates that HRV may be an useful tool for evaluating the autonomic functions in patients with brain damage of various degrees.

Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data.

BACKGROUND: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. RESULTS: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. CONCLUSIONS: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans.

To explore whether depth of sleep is related to changes in autonomic control, continuous power-spectral analysis of the electroencephalogram (EEG) and heart rate variability (HRV) was performed in ten normal subjects during nocturnal sleep. Quiet sleep (QS) was associated with an increase in high-frequency power (HF) of HRV (0.15-0.4 Hz) but a decrease in low-frequency power (LF) (0.04-0.15 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. We conclude that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not. Our methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.

The use of the GlideScope® for tracheal intubation in patients with halo vest.

OBJECTIVE: GlideScope® provides better laryngoscopic view and is advantageous in tracheal intubation in ankylosing spondylitis patients with difficult airway. METHODS: This study was performed to investigate the use of the GlideScope® for tracheal intubation in 15 patients wearing halo vests scheduled for elective surgery under general anesthesia. Preoperative airway assessments were evaluated to predict the difficulty of tracheal intubation. Before intubation, all patients were given a modified Cormack and Lehane (MCLS) grade and percentage of glottic opening (POGO) score by the intubating anesthesiologist having resorted to direct laryngoscopy (DL) with a Macintosh Size 3 blade depiction. Then intubation with the GlideScope® was performed, during which the larynx was inspected and given another MCLS grade and POGO score. RESULTS: Fourteen of the 15 patients had MCLS Grade III or IV by direct Macintosh laryngoscopy and were considered to have a difficult laryngoscopy. Nasal tracheal intubation by the GlideScope® was successful on all occasions. The GlideScope® improved the MCLS grade and POGO score in all patients who had put on a halo vest as compared with those on DL (p<0.01). The GlideScope® also provided a better laryngoscopic view than that by a DL. All of the patients who wore halo vests and presented with suspected difficult airways could be intubated successfully with the GlideScope®. CONCLUSION: The use of the GlideScope® for tracheal intubation could be an alternative option in patients with a difficult airway, whose surgery was circumscribed under general anesthesia with tracheal intubation.

Trachway intubating stylet for tracheal intubation in an ankylosing spondylitis patient undergoing total hip replacement under general anesthesia.

The Trachway is a new device which provides better glottic view than conventional direct laryngoscopy during tracheal intubation. This intubating stylet consists of a camera on the distal tip of the style, with a monitor attached to the rechargeable handle, so that it can overcome the difficulty of limited neck motion and mouth opening in tracheal intubation. We present here a 54-year-old man with ankylosing spondylitis, scheduled to undergo total hip replacement. Pre-operative airway assessment revealed a recognized difficult airway. The Trachway was successfully used for oral tracheal intubation at the first attempt. The Trachway can be an alternative choice for intubation in ankylosing spondylitis patients.

Accidental pulmonary emboli noted by TEE during aortic valve replacement: a case report.

Pulmonary embolism (PE) is difficult to diagnose clinically. In a patient who was scheduled for elective aortic valve replacement, several fresh emboli were recognized in the right atrium on transesophageal echocardiography (TEE). The PEs then disappeared on the echocardiographic image, with significant immediate hemodynamic changes noted by real-time monitors, such as tachycardia and increased pulmonary artery (PA) pressure. Pulmonary embolism was highly suspected. After cardiopulmonary bypass and aortic valve replacement, PA thromboembolectomy was performed successfully. The patient survived and was discharged from the hospital 17 days later without sequelae.

Pentax-airway scope for tracheal intubation breaks through the limitation of neck motion in an ankylosing spondylitis patient wearing halo vest--a case report.

The Airway Scope (AWS) provides better glottic view than the conventional direct laryngoscopy in tracheal intubation. With it, the endotracheal tube can be more easily inserted into the tracheal lumen easily. We hereby presented a 24-year-old ankylosing spondylitis (AS) patient wearing a halo vest who was successfully intubated for undergoing cervical spine surgery involving C1 and C2 under general anesthesia. Pre-operative airway assessment revealed that he was a case of difficult intubation. An AWS was used for oral tracheal intubation which was achieved smoothly in the first attempt. AWS can be an alternative device for airway management in a patient wearing halo vest.

Emergency tracheal intubation in an ankylosing spondylitis patient in the lateral position using the GlideScope.

Anesthesia for ankylosing spondylitis (AS) patients with difficult airway is of great stress to anesthesiologists. If tracheal intubation is not mandatory for general anesthesia, laryngeal mask airway (LMA) may suffice for adequate ventilation. Yet, in certain circumstances, no one can guarantee that LMA will reliably serve the purpose in surgical AS patients, especially in operations performed in the lateral decubitus position. We present here an AS patient with difficult airway scheduled for hip surgery. General anesthesia with sevoflurane conveyed by an LMA through spontaneous ventilation in the lateral decubitus position was planned, and the induction was smoothly done. Unfortunately, laryngospasm and oxygen desaturation occurred during the operation; the patient was successfully rescued by nasal intubation with a GlideScope in the lateral decubitus position without interrupting the operation.

Dexamethasone prevents postoperative nausea and vomiting more effectively in women with motion sickness.

PURPOSE: To evaluate the antiemetic effect of iv dexamethasone for preventing postoperative nausea and vomiting (PONV) in women with and without a history of motion sickness. METHODS: This randomized, double-blinded, placebo-controlled study was carried out in 168 female patients with (n = 84) and without (n = 84) a history of motion sickness undergoing gynecological laparoscopy. Patients received 8 mg dexamethasone or saline immediately before induction of anesthesia. Postoperatively patients were assessed for 24 hr for nausea, vomiting, and complete response (no vomiting, no need for rescue antiemetics). RESULTS: The complete response for patients with a history of motion sickness was 80.5% and 37.5% for recipients of dexamethasone and saline, respectively [P < 0.001; number needed-to-treat (NNT) = 2.3]; with corresponding incidences of 83.3% and 53.7% when there was no such history (P = 0.009; NNT = 3.4). Calculation of the efficacy of dexamethasone for the different subgroups shows that dexamethasone was 45.3% more effective in patients with motion sickness than in those without it. CONCLUSIONS: Prophylactic administration of dexamethasone is effective in reducing PONV in patients with and without a history of motion sickness. The results of this study were more favourable in patients with a history of motion sickness, demonstrating a higher effectiveness of dexamethasone for preventing PONV in this subgroup of patients.

Respiratory-related arterial pressure variability as an indicator of graded blood loss: involvement of the autonomic nervous system.

During positive pressure mechanical ventilation, percentile systolic pressure variation (%SPV) or respiratory-related arterial pressure variability (RAPV) have both been used in assessment of graded haemorrhage. We aimed to investigate whether changes in %SPV and RAPV are correlated during graded haemorrhage (by 5, 10 or 20% of the estimated blood volume) in anaesthetized positive pressure ventilated rats and to investigate the involvement of autonomic regulation. Saline vehicle or atropine produced no discernible effect on baseline %SPV or RAPV but, thereafter, %SPV and RAPV increased progressively with graded haemorrhage. Propranolol significantly decreased baseline %SPV and RAPV and changes induced in %SPV and RAPV by graded haemorrhage. Phentolamine significantly enhanced baseline %SPV and RAPV, and further enhancement of %SPV and RAPV by graded haemorrhage did not occur until 20% of the estimated blood volume was removed. RAPV was significantly correlated with %SPV in all experimental groups. We conclude that RAPV is comparable with%SPV as an indicator of graded haemorrhage and that, in anaesthetized and positive pressure ventilated rats, both are dependent on autonomic function, especially beta-adrenoceptors.

Effect of esmolol on positive-pressure ventilation-induced variations of arterial pressure in anaesthetized humans.

Positive-pressure ventilation-induced variations in arterial pressure have been related to cardiac sympathetic activity in animals. However, the effect of beta-adrenoceptor blockade on these variations in anaesthetized humans under positive-pressure ventilation has not yet been investigated. In the present study, RAPV (respiratory-related arterial pressure variability) and %SPV (percentile systolic pressure variation) were determined before and after esmolol treatment in ten mechanically ventilated patients. RAPV and %SPV decreased significantly after intravenous esmolol (1 mg/kg of body weight) treatment (maximal decrease of RAPV, 50% and %SPV, 35%). Linear regression analysis of RAPV and %SPV before and after esmolol treatment both revealed high correlation (r = 0.93 and 0.91 respectively). The amplitudes of RAPV and %SPV also significantly increased in a graded way with higher tidal volumes. Thus we propose that esmolol suppresses the variations in arterial pressure induced by positive-pressure mechanical ventilation, and we suggest that RAPV and %SPV may be alternative choices for monitoring cardiac sympathetic regulation in anaesthetized patients under positive-pressure ventilation.