守谷 俊

【背景】本邦における異物による気道閉塞患者に対する現場処置の実態は不明である。本研究では、当院に搬送された目撃のある気道異物患者に対する初期対応の実態から、転帰改善になにが必要かを明らかにする。【方法】2003年1月から2006年12月までに当救命救急センターに搬送された、目撃のある気道異物による窒息症例50例を対象にした。患者搬送時に目撃者および救急隊から異物内容と現場での処置を聴取し、1)年齢、2)性別、3)反応消失後の異物除去行為の有無、4)bystander cardiopulmonary resuscitation(CPR)の有無、5)覚知から救急隊現場到着までの時間、6)覚知から患者の病院到着までの時間、7)気道閉塞の原因が大きな一塊の異物片か否か、8)普段の食事介助が必要か否かと転帰との関連について検索した。【結果】全症例、救急隊到着時には傷病者の反応は消失していた。反応消失までに、目撃者によるHeimlich法などの異物除去が施行された症例は存在しなかった。反応消失後は、気道異物の除去のみを施行している症例が50%であり、38%が119番通報のみであった。反応消失後にCPRを行った症例は12%であった。最終転帰(退院もしくは転院時)は、死亡34例(死亡群)、生存16例(生存群)であった。両群間で生存退院に対して、統計学的有意であったのは、119番通報から患者の病院到着までの時間だけであった。【結論】気道異物による反応消失前にHeimlich法などの異物除去の処置が施行された症例は存在しなかった。反応消失後にCPRを行った症例はわずか12%であった。一次救命処置に関する講習会が各地で頻回に行われているが、生命を脅かす病態に対する対処法が一般救助者や介護施設のヘルスケアプロバイダーに普及していない可能性がある。今後、一次救命処置における気道閉塞患者など生命を脅かす病態に対する救急処置法の講習が普及しているかどうかの実態調査と更なる救急処置法の普及活動が必要である。(著者抄録)

【背景】本邦における異物による気道閉塞患者に対する現場処置の実態は不明である。本研究では，当院に搬送された目撃のある気道異物患者に対する初期対応の実態から，転帰改善になにが必要かを明らかにする。【方法】2003年 1 月から2006年12月までに当救命救急センターに搬送された，目撃のある気道異物による窒息症例50例を対象にした。患者搬送時に目撃者および救急隊から異物内容と現場での処置を聴取し，1）年齢，2）性別，3）反応消失後の異物除去行為の有無，4）bystander cardiopulmonary resuscitation（CPR）の有無，5）覚知から救急隊現場到着までの時間，6）覚知から患者の病院到着までの時間，7）気道閉塞の原因が大きな一塊の異物片か否か，8）普段の食事介助が必要か否かと転帰との関連について検索した。【結果】全症例，救急隊到着時には傷病者の反応は消失していた。反応消失までに，目撃者によるHeimlich法などの異物除去が施行された症例は存在しなかった。反応消失後は，気道異物の除去のみを施行している症例が50%であり，38%が119番通報のみであった。反応消失後にCPRを行った症例は12%であった。最終転帰（退院もしくは転院時）は，死亡34例（死亡群），生存16例（生存群）であった。両群間で生存退院に対して，統計学的有意であったのは，119番通報から患者の病院到着までの時間だけであった。【結論】気道異物による反応消失前にHeimlich法などの異物除去の処置が施行された症例は存在しなかった。反応消失後にCPRを行った症例はわずか12%であった。一次救命処置に関する講習会が各地で頻回に行われているが，生命を脅かす病態に対する対処法が一般救助者や介護施設のヘルスケアプロバイダーに普及していない可能性がある。今後，一次救命処置における気道閉塞患者など生命を脅かす病態に対する救急処置法の講習が普及しているかどうかの実態調査と更なる救急処置法の普及活動が必要である。

To ensure a continuing pipeline in pharmaceutical research, lead candidates must possess appropriate metabolic stability in the drug discovery process. In vitro ADMET (absorption, distribution, metabolism, elimination, and toxicity) screening provides us with useful information regarding the metabolic stability of compounds. However, before the synthesis stage, an efficient process is required in order to deal with the vast quantity of data from large compound libraries and high-throughput screening. Here we have derived a relationship between the chemical structure and its metabolic stability for a data set of in-house compounds by means of various in silico machine learning such as random forest, support vector machine (SVM), logistic regression, and recursive partitioning. For model building, 1952 proprietary compounds comprising two classes (stable/unstable) were used with 193 descriptors calculated by Molecular Operating Environment. The results using test compounds have demonstrated that all classifiers yielded satisfactory results (accuracy > 0.8, sensitivity > 0.9, specificity > 0.6, and precision > 0.8). Above all, classification by random forest as well as SVM yielded kappa values of approximately 0.7 in an independent validation set, slightly higher than other classification tools. These results suggest that nonlinear/ensemble-based classification methods might prove useful in the area of in silico ADME modeling.

BACKGROUND: This study evaluated the changes in chemokine interleukin (IL)-8 production from endothelial cells under various hyperglycemic conditions and investigated whether the hyperglycemia associated with the acute inflammatory response could enhance the IL-8 production from the endothelial cells. MATERIALS AND METHODS: Human umbilical endothelial cells (HUVECs) were seeded at a concentration of 1 x 10(5) cells/well and cultured. The culture medium was replaced with Medium 199 containing various concentrations of glucose (final glucose concentration of culture medium was 100, 200, 300, 400, 500 mg/dL; n = 7 each) with or without 100 ng of tumor necrosis factor-alpha (TNF-alpha). After 12 or 24 h at 37 degrees C, the supernatants were collected from the cultures and stored at -80 degrees C until cytokine assay. IL-8 levels of the samples from the supernatants were quantified using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: The IL-8 production by the HUVECs was significantly higher in the high glucose culture than in the control culture (glucose concentration of 100 mg/dL) (P < 0.05). Moreover, the hyperglycemia associated with elevated TNF-alpha was found to enhance the level of IL-8 production by the HUVECs cultured at all glucose concentrations and over both time courses, compared to the control (P < 0.05). CONCLUSIONS: In this study we observed a significant augmentation of IL-8 production by endothelial cells during short-term hyperglycemia, and a similar but significantly stronger augmentation was obtained through TNF treatment. These findings suggest that the hyperglycemia associated with acute inflammatory response after trauma may put the patients at high risk for secondary tissue damage.

BACKGROUND/AIMS: Although there have been numerous studies that nitric oxide (NO) is produced in monocytes and macrophages in animal models, it still remains controversial whether NO is produced by human monocytes and macrophages. To clarify whether NO is produced by human monocytes in patients with systemic inflammatory response syndrome (SIRS), we examined the expression of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) and constitutive nitric oxide synthase (cNOS) mRNA in cultured monocytes derived from severe acute pancreatitis patients complicated with SIRS. METHODOLOGY: Monocytes were harvested from peripheral blood of nine severe acute pancreatitis patients with SIRS (group S) and five mild acute pancreatitis patients with no SIRS (group M). Then we examined the expression of iNOS mRNA and cNOS mRNA in cultured monocytes using the reverse transcription PCR (RT-PCR) method. RESULTS: iNOS mRNA was expressed in the cultured monocytes derived from eight of the nine patients in group S, but not in any of the five patients in group M, while cNOS mRNA was not found in cultured monocytes derived from any patient in either group. CONCLUSIONS: Although it is still not clear whether NO is produced in human monocytes or not, these findings indicate that iNOS is induced in monocytes in severe acute pancreatitis patients with SIRS, but not in mild pancreatitis patients.

AIMS: Therapeutic hypothermia appears to improve the outcome of pre-hospital cardio-pulmonary arrest (CPA) in patients with an initial cardiac rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia (VF/VT). Notwithstanding, the outcome of this procedure is certainly difficult to predict based solely on the initial rhythm. The aim of the present study was to predict the outcome using auditory brainstem responses (ABRs) in CPA patients treated with therapeutic hypothermia. DESIGN AND SETTING: A prospective observational study in the intensive care unit of a university hospital. PATIENTS: The study included 26 patients resuscitated from out-of-hospital CPA. INTERVENTIONS: Basic and advanced cardiac life support, intensive care and post-resuscitative hypothermia. MEASUREMENT AND RESULTS: ABRs were recorded immediately after the return of spontaneous circulation (ROSC). An ABR wave V was recorded in 16 patients. Among 8 patients with a favourable outcome, the initial rhythms were VF/VT in 6 patients and other rhythms in 2. All 10 patients without a detectable ABR wave V had an unfavourable outcome. The VF/VT as the initial arrest rhythm and the presence of wave V were significantly (p = 0.0095) correlated with a favourable outcome. The presence of wave V had a 100% sensitivity to a favourable outcome. CONCLUSION: The absence of the ABR wave V in the early phase after ROSC wave indicated a reduced effect of therapeutic hypothermia, even in cases that underwent hypothermia promptly after out-of-hospital CPA. Measurement of ABRs appears to be useful as a predictor of effectiveness and as a criterion for determining the indication for therapeutic hypothermia.

気管挿管下の重症頭部外傷患者に対して，プロポフォール使用中に洞停止を来した症例を経験した。症例は17歳，男性。家屋の2階から転落し，重度の意識障害（JCS Ⅲ-200）のため救命救急センターに搬送された。頭部単純CT検査において，外傷性くも膜下出血と脳室内出血の所見を認めた。来院時心電図では心拍数88/分，洞調律，P-P間隔が0.68秒と異常を認めなかったが，第7病日に脈拍38/分，P‐P間隔不整でP-P間隔が2.86秒と延長した洞停止が出現したため，lCU入室時から脳低温療法実施のため使用していたプロポフォールの持続投与を中止した。投与中止後，徐脈性不整脈を認めることはなかった。集中治療における持続的なプロポフォール使用は，年齢，心電図所見，投与用量にかかわらず徐脈性不整脈が生じる可能性がある。そのため徐脈性不整脈が生じた場合，プロポフォール投与の中止を考慮する必要がある。

17歳男.家屋2階から転落し,重度意識障害が認められたため,救急救命センターに搬送された.頭部単純CTで,外傷性くも膜下出血と脳室内出血の所見を得た.ICU入室直後から鎮静の目的でプロポフォールの持続投与を開始し,脳低温療法を施行した.来院時心電図では異常を認めなかったが,第7病日,脈拍38/分,P-P間隔不整でP-P間隔が延長した.洞停止と診断し,プロポフォールの投与を中止した.その後徐脈性不整脈は認められなかった.患者は意識改善を認め,運動機能も独歩まで改善して第34病日に退院した.重症頭部外傷に対する集中治療でのプロポフォールの使用は,徐脈性不整脈が生じる可能性があり,徐脈性不整脈が生じた場合,その投与の中止を考慮する必要がある

Patients suffering from traumatic intracranial hemorrhage (TICH) may experience an episode of catastrophic intraoperative hypotension (IHT), after decompression of the brain. The aim of this study was to investigate the risk factors for IHT during emergency craniotomy A total of 67 patients, who underwent emergency craniotomy due to TICH, were divided into two groups: IHT ( n=31 ) or without IHT ( n=36 ). Data concerning (1) age; (2) gender; (3) mechanism of injury; (4) Glasgow Coma Scale (GCS) on admission; (5) abnormality of the pupils (anisocoria or mydriasis); (6) mean arterial blood pressure; (7) heart rate; (8) time elapsed before craniotomy from injury; (9) initial brain CT scans; (10) duration of craniotomy; and (11) total infusion or urine volume until craniotomy were collected prospectively as IHT risk factors. Low GCS score (<5), tachycardia (heart rate >112min(-1)) and hypertension (mean blood pressure >131mmHg) before emergency craniotomy were strongly ( P<0.05 ) associated with IHT. Delayed surgery (>173min until craniotomy) also had a significant ( P<0.005 ) effect on IHT. The risk factors for IHT were considered as a low GCS score on admission, tachycardia, hypertension before emergency craniotomy and delayed surgery. These results suggested the patients with IHT had a high sympathetic tone before emergency craniotomy A sudden reduction in sympathetic tone after surgical decompression of the brain might cause IHT. We concluded that an important factor in the occurrence of IHT was not only the injury severity, but also the balance between sympathetic and parasympathetic activity before decompression surgery.

目的:脳動脈瘤破裂によるクモ膜下出血(SAH)患者に脳動脈瘤からのminor leakによるwarning headache(警告頭痛)を認めることがある。本研究の目的は,warning headache後に再出血を起こした患者の臨床経過の特徴と早期に治療を開始するための必要条件を明らかにすることである。対象と方法:過去5年間に当院に搬送された脳動脈瘤破裂によるSAH患者194例で検討した。入院までの経緯は,来院時に家族や親類,友人および救急隊などから得た現病歴を参考にした。本研究では,「最近のこれまで経験したことのない突然発症型の頭痛」をwarning headache (first SAH)と定義し,warning headacheを経験した群(WH+群)とwarning headacheを経験しなかった群(WH-群)の2群に分類しWH+群の特徴を検索した。結果:WH+群は49例(25.3%)で,すべて来院時WFNS分類grade IV, Vであった。そのうち34例(69.4%)がwarning headache後も医療機関を受診せず自宅や職場で安静にし経過観察をしていた。直ちに医療機関を受診したのは15例(30.6%)で,このうち4例でSAHの診断がなされず帰宅している。warning headacheから再出血までの時間は,2時間以内:65.3% (32/49例)が多く,24時間から1週間以内の症例は全体の20.4%であった。WH+群の死亡率は81.6%で,WH-群のうちWFNS分類grade I-III群(9.1%; p<0.001)もしくはgrade IV, V群(56.1%; p<0.01)の死亡率と比較して有意に高率であった。考察:warning headache後の受診率は低く,再出血を起こした患者の死亡率は高率であった。SAHに認められるwarning headacheの正確な診断だけではなく,専門医への受診率を向上させることが必要である。転帰の改善には,患者とその家族や初期診察医がSAHの頭痛であるとの早期認識が必要である。

心肺蘇生後に脳低温療法を行った症例の聴性脳幹反応, 脳波と予後を検討した。蘇生後平均3時間の聴性脳幹反応でV波が同定できない群は7例中6例が死亡し, 同定可能群 (生存/死亡=10/3) に比し有意に死亡率が高かった。聴性脳幹反応のV波の同定は蘇生後脳低温療法を行うにあたり生命予後の予測に有用と考えられた。一方, 心肺蘇生後24時間以内の脳波が平坦でもその後に脳波活動が記録され予後良好例が存在した。24時間以内に脳波でBurst suppressionを示した症例は全例が予後不良であった。心肺蘇生後に脳波での脳機能評価による予後予測は有効であるが, 蘇生後24時間以内の平坦脳波においては解釈に注意を要する。

To evaluate the significance of an electrophysiologic monitoring system during brain hypothermia, we measured the brainstem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and topographic electroencephalography (EEG) in 29 critically ill patients (15 with severe head injury and 14 with encephalopathy following cardiopulmonary resuscitation). When the temperature measured in the internal jugular vein fell from 36 degrees C to 33 degrees C, the prolongation of latency in BAEPs was 0.1 +/-: 0.06 ms in wave I, 0.5 +/- 0.23 ms in wave III, and 0.92 +/- 0.86 ms in wave V. In addition, the prolongation of latency in SEPs was 1.2 +/- 0.2 ms in N13 and 2.1 +/- 0.4 ms in N20. The bifrontal fast wave responses, except for those of primary injured lesions, in the topographic EEG were recognized in 9 of 13 patients within 30 min after the injection of midazolam which was used as a sedative. When the temperature fell from 36 degrees C to 33 degrees C, the ratio of the delta and theta waves to the alpha waves recorded from 12 scalp electrodes increased. An electrophysiologic evaluation in critically ill patients should thus be considered an effective real-time monitoring system in patients experiencing brain hypothermia.

We have analyzed and evaluated what is the best metabolic monitoring system to determine the prognosis for maintenance of neurological function in severe head injured patients. Acute subdural hematoma (ASDH) was recognized in fifteen of 22 patients and cerebral contusion in seven in this series. Intracranial pressure (ICP), jugular venous pH and jugular bulb venous oxygen saturation (SjO2) were continuously monitored as soon as possible following stabilization. The measurement of cerebral blood flow (CBF) was carried out using a stable Xenon-computerized tomography (Xe-CT). After measuring CBF, 3% carbon dioxide (CO2) loading was conducted to determine CO2 responses (ΔCBF/ΔCO2). In patients who died (D), jugular venous pH showed evidence of acidosis (6.3-7.2) with ΔCBF/ΔCO2z &lt I and cerebral metabolic rate of oxygen (CMRO2) &lt 1.21 within several hours of the trauma. On the other hand, arterial pH was shown to be within the normal range. In vegetative state (VS) and severe disability (SD) patients, jugular venous pH was shown to be within normal range, with ΔCBF/ΔCO2 &lt I and 1.44 &lt CMRO2 &lt 1.79. In all of moderate disability (MD) and good recovery (GR) patients, jugular venous pH was shown to be within the normal range, with ΔCBF/ACO2 &gt I and 1.65 &lt CMRO2 &lt 1.85. These results suggest that jugular venous pH, CO2 response and CMRO2, were useful as early prognostic indicators in the maintenance of neurological function.

The role of Ca2+ in cellular injury has received particular attention in studies of acute spinal cord trauma. In this context, the spatial and temporal distribution of extracellular Ca2+ ([Ca2+](e)) may have an important bearing on the development of secondary tissue injury. We therefore studied the spatial-temporal distribution of [Ca2+](e) following moderate (25 g-cm) contusive injury to the rat thoracic (T9-T11) spinal cord. Double-barreled, Ca2+-selective microelectrodes were used to measure the magnitude and time course of [Ca2+](e) at increasing depths from the dorsal spinal cord surface. After 2 h, the tissue was frozen and later analyzed for total Ca concentration using atomic absorption spectroscopy. [Ca2+](e) fell at all depths, but the decrease was maximal at 250 and 500 mu m from the dorsal surface, where, at 0-10 min after injury, [Ca2+](e) averaged 0.09 +/- 0.03 and 0.06 +/- 0.03 mM respectively. By 2 h postinjury, [Ca2+](e) recovered to nearly 1 mM across all depths. Over this time, total tissue calcium concentration ([Ca](t)) was 4.54 +/- 0.16 mu mol/g in injured cords vs 2.75 +/- 0.1 mu mol/g in sham-operated controls. These data place emphasis on the dorsal gray matter as a principal site of ionic derangement in acute spinal cord injury. The implications of these findings are discussed with reference to secondary injury processes.