Current Ventilator and Oxygen Management during General Anesthesia: A Multicenter, Cross-sectional Observational Study.

BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

Differences in stroke phases, arm-leg coordination and velocity fluctuation due to event, gender and performance level in breaststroke.

The purpose of this study was to analyse stroke phases, arm-leg coordination and trunk motion fluctuation during breaststroke in elite male and female 50, 100 and 200 m events at the 9th FINA World Swimming Championships, Fukuoka 2001. Four phases of the arm stroke and three phases of the leg kick as well as phases of simultaneous arm and leg propulsion and recovery were identified from video of swimmers' motions below the surface. The duration of each phase was expressed as a proportion of the whole stroke cycle. Three measures of the arm-leg coordination, percent simultaneous arm-leg recovery time (%SRT), percent arm lag time (%ALT) and percent simultaneous arm-leg propulsion time (%SPT) were calculated. Mean mid-pool swimming hip velocity (V), stroke rate (SR) and stroke length (SL) were also calculated. In addition, the intra-cycle hip velocity of the swimmers was obtained by cinematographic analysis. The SR decreased and SL increased significantly as the event distance increased. For the arm-leg coordination the %ALT, %SPT and %SRT indicated significant differences between event, gender and performance level. In particular, for increasing event distance and for the higher performing swimmer the lower the %SPT and the higher the %SRT. In addition, the range of the intra-cycle hip velocity fluctuation in the lower performing group was greater than the higher performing group. The non-propulsive phase seems to be a key factor for better performance. The breaststroke swimmers must avoid rapid deceleration during the non-propulsive phase by adopting a low resistance posture and stroking technique.

Matrix metalloproteinase-7 facilitates insulin-like growth factor bioavailability through its proteinase activity on insulin-like growth factor binding protein 3.

Matrix metalloproteinase-7 (MMP-7) secreted by cancer cells has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Recent epidemiologic studies have established a correlation between high levels of circulating insulin-like growth factor (IGF) and low levels of IGF binding protein 3 (IGFBP-3), and relative risk of developing colon, breast, prostate, and lung cancer, which are known to produce MMP-7. In this study, IGFBP-3 was assessed as a candidate for the physiologic substrate of MMP-7. MMP-7 proteolysis generated four major fragments (26 kDa, 17 kDa, 15.5 kDa, and 15.5 kDa), and two cleavage sites were identified: one at the site of hydrolysis of the K(144)-I(145) peptide bond and one at the R(95)-L(96) peptide bond. The former site is different from the previously reported site of cleavage of IGFBP-3 by other proteases. Addition of IGFBP-3 inhibited IGF-I-mediated IGF type 1 receptor (IGF-IR) phosphorylation and activation of the downstream molecule Akt in BALB/c 3T3 fibroblasts overexpressing human IGF-IR (3T3-IGF-IR) and in two human colon cancer cell lines (COLO201 and HT29). Coincubation of the IGF-I/IGFBP-3 complex with MMP-7 restored IGF-I-mediated IGF-IR phosphorylation and activation of Akt in these cell lines. The IGF-I signal recovered by MMP-7 protected against apoptosis induced by anoikis in 3T3-IGF-IR cells. These results indicate that MMP-7 proteolysis of IGFBP-3 plays a crucial role in regulating IGF-I bioavailability, thereby promoting cell survival. This mechanism may contribute to the tumorigenesis of MMP-7-producing IGF-IR-expressing tumors in the primary site and to organ-specific metastasis in a paracrine manner.

Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.

The multisubunit transcription elongation factor NELF (for negative elongation factor) acts together with DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, A to E. NELF-A has sequence similarity to hepatitis delta antigen (HDAg), the viral protein that binds to and activates RNAPII, whereas NELF-E is an RNA-binding protein whose RNA-binding activity is critical for NELF function. To understand the interactions of DSIF, NELF, and RNAPII at a molecular level, we identified the B, C, and D proteins of human NELF. NELF-B is identical to COBRA1, recently reported to associate with the product of breast cancer susceptibility gene BRCA1. NELF-C and NELF-D are highly related or identical to the protein called TH1, of unknown function. NELF-B and NELF-C or NELF-D are integral subunits that bring NELF-A and NELF-E together, and coexpression of these four proteins in insect cells resulted in the reconstitution of functionally active NELF. Detailed analyses using mutated recombinant complexes indicated that the small region of NELF-A with similarity to HDAg is critical for RNAPII binding and for transcriptional pausing. This study defines several important protein-protein interactions and opens the way for understanding the mechanism of DSIF- and NELF-induced transcriptional pausing.

Identification of Hsp90 as a stimulatory host factor involved in influenza virus RNA synthesis.

Efficient transcription and replication of the influenza virus genome are dependent upon host-derived factors. Using an in vitro RNA synthesis system, we have purified and identified Hsp90 as one of the host factors that stimulate viral RNA polymerase activity. Hsp90 interacted with the PB2 subunit of the viral RNA polymerase through the amino-terminal chaperone domain and the middle region containing a highly acidic domain. The acidic middle region was also responsible for its stimulatory activity. We found that a portion of Hsp90 is re-localized to the cell nucleus after viral infection. A PB2 fragment containing a Hsp90 binding domain inhibited viral gene expression in a dominant-negative manner. These results suggest that Hsp90 is a host factor for the influenza virus RNA polymerase.

Endo-beta-N-acetylglucosaminidase, an enzyme involved in processing of free oligosaccharides in the cytosol.

Formation of oligosaccharides occurs both in the cytosol and in the lumen of the endoplasmic reticulum (ER). Luminal oligosaccharides are transported into the cytosol to ensure that they do not interfere with proper functioning of the glycan-dependent quality control machinery in the lumen of the ER for newly synthesized glycoproteins. Once in the cytosol, free oligosaccharides are catabolized, possibly to maximize the reutilization of the component sugars. An endo-beta-N-acetylglucosaminidase (ENGase) is a key enzyme involved in the processing of free oligosaccharides in the cytosol. This enzyme activity has been widely described in animal cells, but the gene encoding this enzyme activity has not been reported. Here, we report the identification of the gene encoding human cytosolic ENGase. After 11 steps, the enzyme was purified 150,000-fold to homogeneity from hen oviduct, and several internal amino acid sequences were analyzed. Based on the internal sequence and examination of expressed sequence tag (EST) databases, we identified the human orthologue of the purified protein. The human protein consists of 743 aa and has no apparent signal sequence, supporting the idea that this enzyme is localized in the cytosol. By expressing the cDNA of the putative human ENGase in COS-7 cells, the enzyme activity in the soluble fraction was enhanced 100-fold over the basal level, confirming that the human gene identified indeed encodes for ENGase. Careful gene database surveys revealed the occurrence of ENGase homologues in Drosophila melanogaster, Caenorhabditis elegans, and Arabidopsis thaliana, indicating the broad occurrence of ENGase in higher eukaryotes. This gene was expressed in a variety of human tissues, suggesting that this enzyme is involved in basic biological processes in eukaryotic cells.

[A case of multiple organ dysfunction following postoperative epididymitis].

We report a case of multiple organ dysfunction following epididymitis. A 53-year-old male patient was admitted to our emergency room with bilateral clavicular fractures, multiple costal fractures and left hemopneumothorax due to a traffic accident. Open reduction of the right clavicular fracture was performed under general anesthesia on the sixth hospital day. A bladder balloon catheter was inserted after induction of anesthesia. The clinical course in the perioperative period was satisfactory and the bladder balloon catheter was removed on the seventh hospital day. However, spontaneous left scrotal pain with tenderness, intense heat with swelling developing on the tenth hospital day, and hypotension, dyspnea and oliguria were noted on the eleventh hospital day. Blood chemistry data showed severe inflammatory findings. Chest X-ray showed acute respiratory distress syndrome. Blood coagulation data showed pre-disseminated intravascular coagulation. The patient's condition continued to deteriorate and we suspected septic shock due to left epididymitis. Emergent left orchiectomy was performed under local anesthesia on the twelfth hospital day. Postoperatively he recovered rapidly. We consider that multiple organ dysfunction following postoperative epididymitis was caused by cytokines released due to systemic inflammatory response syndrome (SIRS) after the trauma, operation, and placement of the bladder catheter. In conclusion, it is important to note that patients with SIRS should undergo further examinations of septic shock immediately and resection of the causative tissue should be performed as soon as possible.

[Efficacy of propofol in controlling myoclonus during rewarming in a brain hypothermia patient].

Propofol is an intravenous anaesthetic agent having anticonvulsant property. We report here a case in which propofol was effective in controlling myoclonus during rewarming in brain hypothermia patient. A 35-year-old male patient was admitted in a comatose state with right-sided hemiparesis, anisocoria and absence of bilateral light reflex. On admission, a head CT showed traumatic subarachnoid hemorrhage, left subdural hematoma, 10 mm midline shift and tentorial herniation with massive brain swelling together with extensive hypodensity in the frontal, temporal and occipital lobes bilaterally. Left decompressive hemicraniectomy, removal of hematoma and brain hypothermia therapy were started immediately. Postoperative head CT showed 15 mm midline shift. The temperature of the jugular bulb was maintained at 34 degrees C for 2 days together with sedation using midazolam under artificial ventilation. The patient was gradually rewarmed at a rate of 0.5 degree C per day from the third hospital day. Myoclonus of sudden onset developed on the patient's head and upper extremities on the third hospital day. An intravenous bolus injection of 10 mg midazolam and continued intravenous infusion of midazolam were given but they did not completely stop myoclonus. A bolus of propofol 60 mg was given intravenously and continuous intravenous infusion of propofol 2 mg.kg-1.hr-1 was started after which the progression of myoclonus disappeared. Myoclonus was kept controlled until the continuous intravenous infusion of midazolam and propofol was discontinued on the sixth hospital day, after which myoclonus occurred again after extubation on the seventh hospital day. The clinical course of this case suggests that propofol might be an alternative effective agent to suppress refractory myoclonus.