Driving-pressure-independent protective effects of open lung approach against experimental acute respiratory distress syndrome.

BACKGROUND: The open lung approach (OLA) reportedly has lung-protective effects against acute respiratory distress syndrome (ARDS). Recently, lowering of the driving pressure (ΔP), rather than improvement in lung aeration per se, has come to be considered as the primary lung-protective mechanism of OLA. However, the driving pressure-independent protective effects of OLA have never been evaluated in experimental studies. We here evaluated whether OLA shows protective effects against experimental ARDS even when the ΔP is not lowered. METHODS: Lipopolysaccharide was intratracheally administered to rats to establish experimental ARDS. After 24 h, rats were mechanically ventilated and randomly allocated to the OLA or control group. In the OLA group, 5 cmH2O positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) were applied. Neither PEEP nor RM was applied to the rats in the control group. Dynamic ΔP was kept at 15 cmH2O in both groups. After 6 h of mechanical ventilation, rats in both groups received RM to inflate reversible atelectasis of the lungs. Arterial blood gas analysis, lung computed tomography, histological evaluation, and comprehensive biochemical analysis were performed. RESULTS: OLA significantly improved lung aeration, arterial oxygenation, and gas exchange. Even after RM in both groups, the differences in these parameters between the two groups persisted, indicating that the atelectasis-induced respiratory dysfunction observed in the control group is not an easily reversible functional problem. Lung histological damage was severe in the dorsal dependent area in both groups, but was attenuated by OLA. White blood cell counts, protein concentrations, and tissue injury markers in the broncho-alveolar lavage fluid (BALF) were higher in the control than in the OLA group. Furthermore, levels of CXCL-7, a platelet-derived chemokine, were higher in the BALF from the control group, indicating that OLA protects the lungs by suppressing platelet activation. CONCLUSIONS: OLA shows protective effects against experimental ARDS, even when the ΔP is not decreased. In addition to reducing ΔP, maintaining lung aeration seems to be important for lung protection in ARDS.

Hyperleukocytosis Complicated by Intracerebral Hemorrhage and Spurious Hypoxemia: A Case Report and Literature Review.

We present the management of a 15-year-old girl with acute myeloid leukemia who presented with massive hyperleukocytosis and neurological deficit due to intracerebral hemorrhage. Surgical intervention was considered but ultimately not undertaken because of the presence of massive hyperleukocytosis, thrombocytopenia, hypokalemia, and considerable discrepancy between the oxygen saturation values determined mechanically and by peripheral oximetry. Aggressive treatment of the hyperleukocytosis was immediately started, which improved the patient's overall condition and rendered surgical intervention unnecessary. This report shows that immediate treatment of massive hyperleukocytosis and critical interpretation of laboratory results in patients with hyperleukocytosis are warranted.

Deep Breathing Improves End-Tidal Carbon Dioxide Monitoring of an Oxygen Nasal Cannula-Based Capnometry Device in Subjects Extubated After Abdominal Surgery.

BACKGROUND: Capnometry detects hypoventilation earlier than pulse oximetry while supplemental oxygen is being administered. We compared the end-tidal CO2 (PETCO2 ) measured using a newly developed oxygen nasal cannula with a CO2-sampling port and the PaCO2 in extubated subjects after abdominal surgery. We also investigated whether the difference between PaCO2 and PETCO2 is affected by resting, by spontaneous breathing with the mouth consciously closed, and by deep breathing with the mouth closed. METHODS: Adult post-abdominal surgery subjects admitted to the ICU were enrolled. After extubation, oxygen was supplied at 4 L/min using a capnometry-type oxygen cannula. The breathing frequency, PETCO2 , and PaCO2 were measured after 30 min of oxygen supplementation. PETCO2 was continuously measured during rest, during breathing with the mouth consciously closed, and during deep breathing with the mouth closed. The difference between PETCO2 and PaCO2 during various breathing patterns was analyzed using the Bland-Altman method. RESULTS: Twenty subjects were included. The bias ± SD (limits of agreement) for breathing frequency measured by capnometry compared with those obtained by direct measurement was 0.4 ± 3.6 (-6.7 to 7.4). In PETCO2 compared with PaCO2 , the biases (limits of agreement) were 14.8 ± 8.2 (-1.3 to 30.9) at rest, 10.2 ± 6.4 (-2.3 to 22.7) with the mouth closed, and 7.7 ± 5.6 (-3.2 to 18.6) for deep breathing with the mouth closed. PETCO2 determined using the capnometry device yielded unreliable and widely ranging values under various breathing patterns. However, deep breathing with the mouth closed decreased the difference between PETCO2 and PaCO2 , as compared with other breathing patterns. CONCLUSIONS: PETCO2 measurements under deep breathing with mouth closed with a capnometry-type oxygen cannula improved the prediction of the absolute value of PaCO2 in extubated post-abdominal surgical subjects without respiratory dysfunction.

[Epidural Anesthesia with Non-invasive Positive Pressure Ventilation for Laparotomy in a Patient with Amyotrophic Lateral Sclerosis].

In patients with amyotrophic lateral sclerosis (ALS), general anesthesia carries a significant risk of respiratory complications and may result in prolonged intubation. Epidural anesthesia may be a feasible alternative in selected cases but may impair respiratory function by producing intercostal muscle weakness. Here, we present a case of ALS who underwent emergency laparotomy that was successfully managed with epidural anesthesia and non-invasive positive pressure ventilation.

Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.

Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor alpha (ERalpha) through phosphorylation of Ser-118 within the ERalpha N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERalpha (hERalpha) activation function-1 that physically associated with ERalpha dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERalpha-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.

p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor.

The androgen receptor (AR) has two transactivation functions that have been mapped to the N- and C-terminal domains and designated as activation function-1 (AF-1) and AF-2, respectively. While the molecular basis for AF-2 function has been well studied, little is known about AF-1 coregulators. Therefore, we attempted to identify AF-1-interacting proteins from HEK293 cells by biochemical purification followed by mass fingerprinting by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Purified AF-1 region-interacting proteins were found to contain nuclear RNA-binding protein p54(nrb), polypyrimidine tract-binding protein-associated splicing factor (PSF), paraspeckle protein 1 (PSP1), and PSP2, which are assumed to be involved in pre-mRNA processing. p54(nrb) interacted with AR via the A/B domain in a ligand-dependent manner. Reflecting the physical interaction between p54(nrb) and the AR A/B domain, AR AF-1 function was potentiated by p54(nrb). Our results suggest that p54(nrb) functions as a coactivator of AR that potentiates transcription, and presumably splicing as well.