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BACKGROUND Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. METHODS We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. RESULTS The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p

Nanoparticle albumin-bound paclitaxel(nab-PTX)is effective as second-line chemotherapy for advanced gastric cancer. Long-term administration is generally impossible because of peripheral sensory neuropathy. However, we report 2 cases that were treated with35 cycles of nab-PTX with dose reduction to control disease progression, which appears to be the highest number cycles so far reported. Case 1 was a male patient in his 70s, with distant lymph node metastases and an advanced primary lesion(tub2). He received 6 cycles S-1/CDDP and achieved a partial response; however, the treatment was changed to second-line chemotherapy with nab-PTX because of adverse effects; the dose of nab-PTX was reduced by 60% every 3 weeks. At the time of writing, 36 cycles have been administered and disease control has been maintained, with Grade 2 peripheral sensory neuropathy. Case 2 was another male patient in his 70s, who underwent total gastrectomy for gastric cancer(mucinous adenocarcinoma). Virchow metastasis was detected 6months after surgery. He received 1 cycle S-1/CDDP and achieved a partial response; however, treatment was changed to second-line chemotherapy with nab-PTX because of adverse effects; the dose of nab-PTX was reduced by 60% every 3 weeks. At the time of writing, 41 cycles have been administered and disease control has been maintained, with Grade 2 peripheral sensory neuropathy.

The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission. We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3–4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0–2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07–0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93–0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.

Brain death (BD) is a physiological state defined as complete and irreversible loss of brain function. Organ transplantation from a patient with BD is controversial in Japan because there are two classifications of BD: legal BD in which the organs can be donated and general BD in which the organs cannot be donated. The significance of BD in the terminal phase remains in the realm of scientific debate. As indicated by the increasing number of organ transplants from brain-dead donors, certain clinical diagnosis for determining BD in adults is becoming established. However, regardless of whether or not organ transplantation is involved, there are many unresolved issues regarding BD in children. Here, we will discuss the historical background of BD determination in children, pediatric emergencies and BD, and unresolved issues related to pediatric BD.

Microwave technology has been widely used in numerous applications; however, excessive microwave exposure causes adverse effects, particularly in the brain. The present study aimed to evaluate the change in the number of neural cells and presence of apoptotic cells in rats for one month after exposure to excessive microwave radiation. The rats were exposed to 3.0 kW of microwaves for 0.1 sec and were sacrificed after 24 h (n=3), or 3 (n=3), 7 (n=3), 14 (n=3) or 28 days (n=4) of exposure. The neural cells were counted in the motor cortex and hippocampus [cornu ammonis 1 (CA1) and CA2] and the percentage of positive cells stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) were also measured, which detected apoptotic cell death in the choroid plexus in the lateral ventricle, motor cortex and hippocampus. In the CA1, the number of neural cells decreased significantly by day 28 compared with that in the control (60.7 vs. 50.6, P=0.0358), but did not decrease before day 28. There were no significant differences on any day in the CA2 and the motor cortex. The number of cells showed a significant increase on day 7 compared to the control in the choroid plexus (2.1±1.1 vs. 21.8±19.1%, P=0.0318). There were no significant differences from the controls in the percentage of TUNEL-positive cells in the motor cortex and hippocampus. The effects of microwave exposure on the brain remain unclear; however, microwave-induced neurotrauma shows the same pathological changes as blast traumatic brain injury.

Nestin, a class VI intermediate filament protein, is expressed by neuronal progenitor cells in the subventricular zone (SVZ). In the present study, we analyzed the nestin expression and phosphorylation levels in nerve cells in a mouse model of cerebral ischemia and reperfusion. C57BL/6 mice were subjected to three-vessel occlusion for 14 min, and were killed either 1 or 4 days after the procedure. The percentages of cells in the SVZ that were positive for nestin, Thr(1495)-phosphorylated nestin or Ki67 did not significantly differ between the ischemic reperfusion and sham groups. Conversely, in the striatum and cornu ammonis 2 (CA2) regions, the mice at 4 days after ischemic reperfusion showed significantly higher numbers and percentages of nerve cells that were positive for nestin, Thr(1495)-phosphorylated nestin and Ki67 compared to results from the other groups. To our knowledge, this is the first description of phosphorylated nestin expression in neural progenitor cells in the SVZ of adult mice. In this cerebral ischemia and reperfusion mouse model, cells positive for Thr(1495)-phosphorylated nestin were increased in the striatum and CA2 field of the hippocampus; suggesting that nestin phosphorylation may play an important role in mitotically active neuronal progenitor cells.

Japan has experienced numerous incidents of chemical disasters and terrorist attacks. Here we review the history of changes in countermeasures against such incidents. Since 2004, the Civil Protection Law, more formally known as the "Law Concerning the Measures for Protection of the People in Armed Attack Situations etc" was enacted to fully prepare the nation for chemical terrorism. According to this law, the Japanese government must carry out Civil Protection Exercises on an annual basis to gauge response. Problem areas that remain are chosen and addressed one by one until they are judged to be resolved in subsequent exercises.

Traumatic cerebrovascular injury (TCVI) is a serious complication of severe head injury, with a high mortality rate. To establish a proper treatment strategy for TCVI, we investigated patients with a high risk of TCVI according to the Guidelines for the Management of Severe Head Injury (hereafter "the Guidelines") to elucidate the validity of the criteria for TCVI in the Guidelines and the appropriate screening timing and methods. Of those transported to our facility between December 2008 and June 2012, 67 individuals with a high risk of TCVI were evaluated to reveal the proper timing and methods of vascular evaluation. Of the 67 patients, 21 had a diagnosis of TCVI based on cerebral angiography, three-dimensional computed tomography angiography (3DCTA), or magnetic resonance imaging (MRI), accounting for 6.4% of all patients with severe head injury and as high as 31.3% of patients with a high risk of TCVI according to the Guidelines. In addition, according to the Glasgow Outcome Scale (GOS), outcomes were three deaths due to primary brain injury, six cases of persistent vegetative state, five cases of severe disability, three cases of moderate disability, and four cases of good recovery. Although 3DCTA is a simple and convenient diagnostic method, cerebral angiography is necessary to evaluate dissecting lesions. If patients have any signs or symptoms of TCVI, as described in the Guidelines, cerebral angiography or 3DCTA should be performed as an initial screening method within 72 hours of admission, followed by cerebral angiography on postadmission Day 14 ± 2 to prevent failed diagnosis.

Predictive variables of delayed cerebral ischemia (DCI) and pulmonary edema following subarachnoid hemorrhage (SAH) remain unknown. We aimed to determine associations between transpulmonary thermodilution-derived variables and DCI and pulmonary edema occurrence after SAH. We reviewed 34 consecutive SAH patients monitored by the PiCCO system. Six patients developed DCI at 7 days after SAH on average; 28 did not (non-DCI). We compared the variable measures for 1 day before DCI occurred (DCI day -1) in the DCI group and 6 days after SAH (non-DCI day -1) in the non-DCI group for control. The mean value of the global end-diastolic volume index (GEDI) for DCI day -1 was lower than that for non-DCI day -1 (676 ± 65 vs. 872 ± 85 mL/m, P = 0.04). Central venous pressure (CVP) was not significantly different (7.8 ± 3.1 vs. 9.4 ± 1.9 cm H2O, P = 0.45). At day -1 for both DCI and non-DCI, 11 patients (32%) had pulmonary edema. Global end-diastolic volume index was significantly higher in patients with pulmonary edema than in those without this condition (947 ± 126 vs. 766 ± 81 mL/m, P = 0.02); CVP was not significantly different (8.7 ± 2.8 vs. 9.2 ± 2.1 cm H2O, P = 0.78). Although significant correlation was found between extravascular lung water (EVLW) measures and GEDI (r = 0.58, P = 0.001), EVLW and CVP were not correlated (r = 0.03, P = 0.88). Thus, GEDI might be associated with DCI occurrence and EVLW accumulation after SAH.

Inflammation and the coagulation system may influence the genesis of chronic subdural hematoma (CSDH). The appearance of CSDH on computed tomography (CT) varies with the stage of the hematoma. This study investigated the pathogenesis and the recurrence of CSDH by comparing cytokine levels with the CT features of CSDH in 26 patients with 34 CSDHs who underwent single burr-hole surgery at our hospital between October 2004 and November 2006. The hematoma components removed during the procedure were examined, and the hematoma serum levels of cytokines measured such as thrombomodulin (TM), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and interleukin-10 (IL-10). Using CT, mixed density hematomas were distinguished from other homogeneous hematomas, and found that the TM level was significantly higher in mixed density hematomas than in homogeneous hematomas (p = 0.043). Mixed density hematomas were classified into three subtypes (laminar, separated, and trabecular hematomas). The TM level was significantly higher in laminar and separated hematomas than in other hematomas (p = 0.01). The levels of IL-6, TNFα, and IL-10 were extremely high, but showed no significant differences in relation to the CT features. Mixed density hematomas had high recurrence rate, as reported previously, and TM level was high in mixed density hematomas such as laminar and separated mixed density hematomas. The present findings suggest that the types of CSDH associated with high TM levels tend to have higher recurrence rate.

On March 11, 2011, an earthquake occurred off the coast of Honshu, Japan. The quake was followed by a powerful tsunami that caused extensive damage to the east coast of the Tohoku and Kanto regions. This disaster destroyed the medical system in place and thus drastically reduced the ability of the healthcare system to handle the large number of casualties. During the initial response to this disaster, we participated in several types of outreach medical relief teams dispatched to the affected area from the day of the earthquake onwards. The ratio of persons injured to persons missing or dead for the 2011 Japan disaster (0.31: 5,994 to 19,371) was much lower than for the Indian Ocean Tsunami of 2004 in Thailand (1.01; 8,457 to 8,393) and for the Great Hanshin-Awaji Earthquake of 1995 in Japan (6.80; 43,792 to 6,437). The different ratios for the different types of disasters indicate that medical relief efforts in response to natural disasters should be tailored to the type of disaster to optimize the effectiveness of the response and prevent further deaths. From a medical viewpoint, unnecessary deaths must be prevented following natural disasters. Doing so requires appropriate information transmission and an understanding of the mission's overall and specific objectives: 1) rapid search and rescue; 2) early care in the field, evacuation centers, and primary clinics; 3) definitive evaluation at disaster base hospitals; and 4) proper evacuation to unaffected areas. We propose a descriptive device that can guide headquarters in dealing with the commonalities of a disaster.

This report describes our onsite medical rounds and fact-finding activities conducted in the acute phase and medical relief work conducted in the subacute phase in Miyagi prefecture following the Great East Japan Earthquake and subsequent tsunami that occurred off northeastern Honshu on March 11, 2011. As part of the All-Japan Hospital Association medical team deployed to the disaster area, a Nippon Medical School team conducted fact-finding and onsite medical rounds and evaluated basic life and medical needs in the affected areas of Shiogama and Tagajo. We performed triage for more than 2,000 casualties, but in our medical rounds of hospitals, clinics, and nursing homes, we found no severely injured person but did find 1 case of hyperglycemia. We conducted medical rounds at evacuation shelters in Kesennuma City during the subacute phase of the disaster, from March 17 through June 1, as part of the Tokyo Medical Association medical teams deployed. Sixty-seven staff members (17 teams), including 46 physicians, 11 nurses, 3 pharmacists, and 1 clinical psychotherapist, joined this mission. Most patients complained of a worsening of symptoms of preexisting conditions, such as hypertension, respiratory problems, and diabetes, rather than of medical problems specifically related to the tsunami. In the acute phase of the disaster, the information infrastructure was decimated and we could not obtain enough information about conditions in the affected areas, such as how many persons were severely injured, how severely lifeline services had been damaged, and what was lacking. To start obtaining this information, we conducted medical rounds. This proved to be a good decision, as we found many injured persons in evacuation shelters without medication, communication devices, or transportation. Also, basic necessities for life, such as water and food, were lacking. We were able to evaluate these basic needs and inform local disaster headquarters of them. In Kesennuma City, we found that some evacuation shelters could not contact others even after 1 week after the earthquake. We realized from our experiences that, unlike our activities following more localized earthquake disasters, the first task following such large-scale disasters is to acquire information on basic life needs, including medication needs, and the number of persons requiring assistance. We must provide medical relief according to the unique characteristics of the disaster-affected areas as well as the specific nature of the disaster, in this case, a tsunami.

Patients with degenerative diseases of the cervical spine, such as ossification of the posterior longitudinal ligament, spondylosis, and canal stenosis, sometimes present with acute spinal cord injury caused by minor trauma. However, the relative risk of cervical cord injury with these diseases is unknown. The clinical and radiological features of 94 elderly patients with head injury, 57 men and 37 women aged from 65 to 98 years (mean 76.6 years), were retrospectively analyzed to assess the association of spinal cord injury with degenerative cervical diseases. Degenerative cervical diseases were present in 25 patients, and spinal cord injury was more common in the patients with degenerative diseases (11/25 patients) than in the patients without such diseases (3/69 patients; relative risk = 10.2). The incidence of degenerative cervical diseases seems to be increasing in Japan because life expectancy has increased and the elderly are a rapidly growing part of the population. A fall while walking or cycling is a common mechanism of head injury and/or cervical cord injury in the elderly. To decrease the occurrence of cervical myelopathy, prevention by increasing social awareness and avoiding traffic accidents and falls is important.

Thrombopoietin is the cytokine involved in megakaryopoiesis and its receptor (c-Mpl) is considered to regulate development of megakaryocyte. In this research, to elucidate the underlying mechanisms of c-mpl gene expression in megakaryoblastic cells, we investigated the effect of a protein kinase C (PKC) on c-mpl promoter activity in a time-dependent manner. PKC is a member of a family of serine/threonine protein kinases in the cytosol involved in cell growth and differentiation. Phorbol 12-myristate 13-acetate (PMA) is known as PKC activator, significantly enhanced the c-mpl promoter activity and PKC inhibitor, 2-methylpiperazine dihydrochloride (H-7) suppressed the up-regulation of PMA-induced promoter activity and this effect decreased in a time-dependent manner. These results clearly suggest that in megakaryoblastic cells, PKC plays the crucial role in the initiation of up-regulation of PMA-induced c-mpl promoter activity.

Lessons learned from the Great Hanshin-Awaji earthquake of 1995 underscored the necessity of establishing Disaster Medical Assistance Teams (DMATs) in Japan, and in 2005, the Japanese government's Central Disaster Prevention Council revised its Basic Disaster Management Plan to include full deployment of DMATs in disaster areas. Defining a DMAT as a trained, mobile, self-contained medical team that can act in the acute phase of a disaster (48 to 72 hours after its occurrence) to provide medical treatment in the devastated area, the revised plan called for the training of DMAT personnel for rapid deployment to any area of the country hit by a disaster. This paper presents descriptive data on the number and types of missions carried out by Japan DMAT (J-DMAT) in its first 5 years, and clarifies how J-DMAT differs from its counterpart in the United States (US-DMAT). The DMAT that the present authors belong to has been deployed for 2 natural disasters and 1 man-made disaster, and the operations carried out during these deployments are analyzed. Reports on J-DMAT activities published from 2004 through 2009 by the Japanese Association for Disaster Medicine are also included in the analysis. After training courses for J-DMAT personnel started in fiscal 2004, J-DMATs were deployed for 8 disasters in a period of 4 years. Five of these were natural disasters, and 3 man-made. Of the 5 natural disasters, 3 were earthquakes, and of the 3 man-made disasters, 2 were derailment accidents. Unlike in the United States, where hurricanes and floods account for the greatest number of DMAT deployments, earthquakes cause the largest number of disasters in Japan. Because Japan is small in comparison with the US (Japan has about 1/25 the land area of the US), most J-DMATs head for devastated areas by car from their respective hospitals. This is one reason why J-DMATs are smaller and more agile than US-DMATs. Another difference is that J-DMATs' activities following earthquakes involve providing treatment in confined spaces, triage, and stabilization of injuries: these services are required in the acute phase of a disaster, but the critical period is over in a much shorter time than in the case of water-related disasters. In response the kind of man-made disasters that occur in Japan-mainly transportation accidents, and occasional cases of random street violence-J-DMATs need to be deployed as soon as possible to provide medical services at the scene at the critical stage of the disaster. This means that J-DMATs have to be compact. The fact that J-DMATs are smaller and more agile than US-DMATs is a result of the types of disaster that hit Japan and the relatively small size of the country.

A 33-year-old female presented with a rare case of severe vasospasm following the rupture of an arteriovenous malformation (AVM) without subarachnoid hemorrhage. Initial computed tomography (CT) revealed a subcutaneous hematoma and cast formation of intraventricular clots without the deposition of subarachnoid blood in any basal cistern. Cerebral angiography revealed a small AVM located in the right parietal lobe without aneurysmal formations. Repeat CT demonstrated no evidence of subarachnoid clots expected with the presence of intraventricular clots and she was transferred to a general ward. She suffered sudden onset of motor aphasia and disturbance of consciousness on Day 17 after the hemorrhage. Magnetic resonance imaging indicated diffuse cortical infarction and subsequent magnetic resonance angiography revealed severe narrowing of the bilateral internal carotid arteries. Three-dimensional CT angiography on the same day indicated similar findings. She was transferred back to the intensive care unit for critical treatment. However, she suffered persistent mild right hemiparesis and motor aphasia. The characteristic features of vasospasm after intraventricular hemorrhage from AVMs are delayed onset, acute deterioration of consciousness, female predominance, and localization to the bilateral internal carotid arteries. Treatment of patients with AVM rupture should consider the risk of severe vasospasm, even if there is no subarachnoid clot.

Phorbol-12-myristate-13-acetate (PMA) significantly elevated c-mpl promoter activity and the protein kinase C (PKC) inhibitors GF 109203, H7 and calphostin C conspicuously reduced the steady level of the activity. Destruction of the -107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in decrease of the promoter activity by 49.6% and 48.2%, respectively, and destruction of -69Ets and -28Ets elements dramatically decreased the activity by 93.4% and 82.6%, respectively, while mutation of -77GATA moderately reduced the activity by 28.6%. We conclude that the expression of the c-mpl gene is modulated by transcription through a PKC-dependent pathway and that Ets elements at -69 and -28 nucleotides in front of the transcription start site are critical that Sp1(-107) and Sp1(-57) are also important and that GATA(-77) is less involved as a positive regulatory element in c-mpl gene expression induced by PMA in CMK cells.

直腸癌, 腎癌後術に発生した胃腺扁平上皮癌の1例を経験した. 症例は71歳の男性. スクリーニングの上部消化管内視鏡で胃体上部小彎から胃角部にかけて3型の腫瘍を認め, 術前の生検では低分化腺癌, 印環細胞癌が認められた. 胃全摘を施行した. 切除標本では体上部から前庭部にかけて60×55mm大の3型腫瘍を認めた. 組織学的検索では扁平上皮癌と中分化から低分化の腺癌の部分が混在し, 腺扁平上皮癌と診断した. 進行度はStage IIIB (T3 N2 P0 H0 M0 CY0) であった. 膀胱癌の治療後に術後補助化学療法を行ったものの術後6カ月で再発を認め, 術後8カ月で癌死し, 予後不良であった. 本症例は胃腺扁平上皮癌に直腸癌, 腎癌, 膀胱癌を合併しており, 比較的稀と考えられた.

Elevated serum levels of thrombomodulin (TM) and von Willebrand factor (vWf) are good indicators of injury and activation of cerebral endothelium in patients with severe simple head injury. The present study evaluated cerebral endothelial injury or activation as the serum levels of TM and vWf in elderly and younger patients with similar brain trauma, to evaluate the primary parenchymal injury of the brain. Patients with head injury were classified into the young group (16-30 years), the middle-aged group (31-65 years), and the elderly group (over 66 years). There was no difference in Glasgow Coma Scale on admission between the three groups. The serum levels of TM and vWf at 2 hours after injury were significantly higher in the elderly group than in the other groups. However, the serum levels of TM and vWf were not significantly different at 3 and 7 days after injury. Cerebral endothelial activation and injury were significantly higher in elderly patients just after head injury than in younger patients, which suggests that greater sensitivity to endothelial injury and activation may be important in the worse outcome after head injury in elderly patients compared with younger patients.

Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals play an important role in global cerebral I/R. Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, have been reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. The recently introduced XOR inhibitor febuxostat, which is a more potent inhibitor than allopurinol, is expected to decrease free radical production more effectively. Here, we analyzed the effects of allopurinol and febuxostat in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Pathological examinations, which were performed in each group in the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, revealed that there was a decrease in the number of neuronal cells in the 14-min occlusion model in both regions and that drugs that were administered to prevent this damage were not effective. The enzymatic activity was extremely low in the mouse brain, and XOR could not be detected in the nonischemic and ischemic mice brains with western blot analyses. Thus, one of the reasons for the decreased effectiveness of XOR inhibitors in controlling severe whole-brain ischemia in a mouse model was the low levels of expression of XOR in the mouse brain.

The Appleby procedure has been used in the surgical treatment of advanced gastric cancer. This procedure consists of a combined resection of the whole of the stomach, the body and tail of the pancreas, and the spleen, as well as resection of the celiac artery. This procedure can also be used for operative resection of cancer of the body of the pancreas. The hepatic arterial flow is supplied from the arcade of the supramesenteric artery. In the past, the extent of hepatic arterial flow after the celiac artery had been clamped was evaluated by finger palpation. However, this is not an objective method. Here, we describe two patients with pancreatic body cancer, in one of whom the Appleby procedure was followed. However, in the other, this operation could not be performed because the residual blood supply to the liver would have been inadequate. The hepatic arterial flow was assessed using intraoperative Doppler ultrasonography (US) of the intrahepatic artery (arterial flow of segment 3). In case 1 (a 45-year-old man), the hepatic arterial flow prior to clamping of the celiac artery was 68.4 cm/s, and this flow was reduced to 22.1 cm/s after the clamping. The color and consistency of the liver surface remained good. Because there was adequate hepatic arterial flow after the celiac artery was clamped, the Appleby procedure was performed. However, in case 2 (a 65-year-old man), the hepatic arterial flow after the celiac artery had been clamped was reduced from 47.9 cm/s to 14.3 cm/s. The liver surface became dark and the liver shrank. In addition, there were various preoperative medical conditions in this patient. We decided not to proceed with the Appleby procedure. Intraoperative Doppler US measurement of the hepatic arterial flow is a useful technique, particularly in combination with the assessment of the color and tension of the liver, the age of the patient, and the extent of preoperative comorbidity, in determining whether an Appleby procedure is feasible.

症例は63歳の女性で2002年3月, 前医で直腸癌に対し低位前方切除術を施行されたが, 術後早期より膣からの便汁の排泄があり直腸膣瘻と診断された. 2回の瘻孔切除縫合術, 4回の内視鏡的クリッピング術, 人工肛門造設を行うも治癒しえず, 2002年11月, 当科に紹介となった. 2003年月, 手術を施行した. 瘻孔部の切除を行い, 右薄筋の筋皮弁を用い膣後壁, 直腸瘻孔部を充填形成した. 術後経過は良好で問題となるような機能障害も出現しなかった. 2003年6月人工肛門を閉鎖. 現在, 術後約1年を経過したが瘻孔再発の徴候はない. 直腸術後の難治性直腸膣瘻に対する, 薄筋筋皮弁による外陰部形成術は機能障害の出現もなく患者のQOL向上に非常に貢献しうる術式と考えられた.

内膀胱上窩ヘルニアは極めて稀であり,いまだ術前正診例の報告はない.今回われわれが経験した症例は,術前CTをretrospectiveに検討した結果,正診にいたる特徴的な所見を呈していた.この経験を踏まえ,若干の文献的考察を加えて報告する.症例は腹部手術歴のない78歳,男性.腹痛,腹部膨満,嘔気が出現し,近医受診したところ,イレウスを認めたため,当院を紹介され受診した.腹部CT検査で拡張した小腸を認め鼠径ヘルニア嵌頓と診断したが,その後用手的に還納したと判断し,保存的に経過観察した.しかし,次の日のCT検査でも状態は変わらず腸管の嵌頓は改善されていないと判断し,緊急手術を施行した.開腹所見で回腸末端から約70cm口側の小腸の内膀胱上窩ヘルニア嵌頓による絞扼性イレウスと診断した.手術は回腸部分切除術,ヘルニア門の縫合閉鎖を行った.術後経過順調で第11病日に退院となった.原因不明のイレウスで発症した症例に対しては,内膀胱上窩ヘルニアも念頭において腹部CT検査を施行することが肝要であり,本症例のような特徴的な所見を呈していれば,術前に診断することが可能であると考えられた.

We describe an alpha-fetoprotein (AFP)-producing pancreatic cancer irradiated intra- and postoperatively. A 64-year-old man with a hypoechic lesion in the pancreatic head and body was referred to us. On admission, his serum AFP level was markedly elevated (441 ng/ml). Computed tomography showed a 65 x 35 mm diameter tumor in the pancreatic head and body. The tumor periphery was enhanced with contrast medium. Angiography revealed faint tumor staining. After laparotomy, curative resection was impossible, because several arteries were embedded in the metastatic lymph nodes. Core needle biopsy was performed. The tumor was irradiated intraoperatively (25 Gy; area, 8 cm(2)). The diagnosis was moderately to poorly differentiated pancreatic adenocarcinoma. Immunohistochemical staining revealed AFP-positive cytoplasm in some cancer cells. The tumor shrunk significantly (longest axis, from 65 to 30 mm) after postoperative external beam radiation therapy (total, 40 Gy). The serum AFP level fell dramatically (from 441 to 2.5 ng/ml). However, distal gastrectomy for postradiation gastric ulceration was required. The patient did well without tumor regrowth or signs of liver or lymph node metastases 1 year 10 months after his first operation. In conclusion, we treated a rare AFP-producing pancreatic cancer with radiotherapy, which was effective. However, care is needed to avoid external beam radiation-induced gastrointestinal ulceration.

Background. Preoperative portal embolization (PE) is used to stimulate liver hypertrophy in the nonembolized lobe. We studied liver volume and function with computed tomography and technetium-99m-galactosyl human serum albumin (99mTc-GSA) scintigraphy before PE and at 1 or 2 weeks after PE. Methods. Right PE was performed in 30 patients. Morphologic and functional hypertrophy in the left lobe after PE was determined and related to the presence or absence of cholestasis, biliary drainage of the embolized lobe, and postoperative liver failure. Results. The volume of the left lobe and 99mTc-GSA uptake increased rapidly for the first week after PE, but no significant increase was seen during the second week. Morphologic hypertrophy was less pronounced in patients with jaundice (P =.03). When PE was performed at a total bilirubin level above 2 mg/dL, the interval between PE and surgery was prolonged because of cholangitis and liver abscess formation. The net morphologic hypertrophy ratio was significantly higher in livers that had undergone left lobe drainage only (9.1% ± 0.9%) compared with those in which there was drainage of the embolized lobes (5.7% ± 0.9%; P =.03). The volume and 99mTc-GSA uptake of the left lobe in the second week after PE was significantly smaller in patients with postoperative liver failure (33.7% ± 2.4% and 18.0% ± 2.1%, respectively) than in patients without liver failure (46.2% ± 1.4% and 38.4% ± 2.3%; P =.003 and P =.01, respectively). Conclusion. In the nonembolized lobe, the functional increase in 99mTc-GSA uptake is more pronounced than suggested by the degree of morphologic hypertrophy. Whenever possible, biliary drainage should not be performed in the lobe undergoing hepatectomy. 99mTc-GSA SPECT scintigraphy is useful for the evaluation of postoperative liver failure. (Surgery 2003;133:495-506.)

患者は29歳,女性.腹部腫瘤を自覚し近医より当科紹介となった.左上腹部に小児頭大の腫瘤を触知し,入院中に腫瘤は下腹部に移動した. CT検査では左上腹部から骨盤にいたる巨大な多房性嚢胞性腫瘍を認め,一部に充実性成分を伴っていた.可動性からは大網や腸間膜からの発生,形態からは膵粘液性嚢胞腫瘍も疑われたが,腫瘍上縁が胃の腹側に位置し膵原発は否定された.血管造影検査では肝動脈外側区域枝が栄養血管として腫瘍に向かう所見が得られた.以上より肝嚢胞腺腫または腺癌と診断し手術を施行した.腫瘍は著明に肝外性に発育しており,外側区域部分切除にて腫瘍を摘出した. 22・18×14cm, 1,955gの嚢胞性腫瘍で病理組織検査では肝嚢胞腺腫と診断された.本疾患は比較的稀であると同時に,本症例では著明な肝外発育を示した点で診断がやや困難であったが, CTおよび血管造影検査にて肝原発との診断が可能であった.

1977年から2001年7月までに当科で経験した直腸脱20例(11例に他施設での手術既往あり.再発による再手術例3例を含むと23手術例となる)を対象とし,病悩期間,各術式の成績を検討した.検討項目は再発率・合併症および長期経過後の症状の改善度・満足度とした.追跡調査は電話を使用した.術式の内訳は会陰式が6例でGant-三輪法4例,粘膜縫縮法2例であった.腹式は17例で直腸剥離仙骨前固定術13例,腹腔鏡下直腸固定術2例,人工肛門造設術2例であった. Thiersch法は21例に併用した.再発率は会陰式33%(2/6),腹式(人工肛門造設術を除く)6.7%(1/15)であった.合併症はThiersch法固定糸の感染2例,弛み5例,イレウスが1例に認められた.追跡可能であった13例は全て腹式手術の症例であり,全例で満足しているとの結果であった.腹腔鏡下手術の2例も経過良好であった.直腸固定術の長期経過後の満足度は高く,再発率も低かった.

Background and Purpose: Few studies have described the risk factors associated with the development of neurological pulmonary edema (NPE after subarachnoid hemorrhage (SAH. We have hypothesized that acute‑phase increases in serum lactate levels are associated with the early development of NPE following SAH. The aim of this study was to clarify the association between lactic acidosis and NPE in patients with nontraumati cS AH. Methods: We retrospectively evaluated 140 patients with nontraumatic SAH who were directly transported to the Nippon Medical School Hospital emergency roo mb y the emergency medical services. We compared patients in whom NPE developed (NPE group and those in whom it did not (non‑NPE group. Results: The median (quartiles 1―3 arrival time at the hospital was 32 minutes (28―38 minutes after the emergency call was received. Although the characteristics of the NPE and non‑NPE groups including mean arterial pressure (121.3 [109.0―144.5] and 124.6 [108.7―142.6] mm Hg respectively; P=0.96 were similar the median pH and the bicarbonate ion (HCO3 ­ concentrations were significantly lower in the NPE group than in the non‑NPE group (pH 7.33 [7.28―7.37] vs. 7.39 [7.35―7.43]; P=0.002; HCO3 ­ 20.8 [18.6―22.6] vs. 22.8 [20.9―24.7] mmol L; P= 0.01. The lactate concentration was significantly higher in the NPE group (54.0 [40.3―61.0] mg dL than in the non‑NPE group (28.0 [17.0―37.5] mg dL; P

In recent years, 193nm immersion lithography has been extended instead of adopting EUV lithography. And multi-patterning technology is now widely applied, which requires tighter specification as the pattern size gets smaller on advanced semiconductor devices. Regarding the mask registration metrology, it is necessary to consider some difficult challenges like tight repeatability and complex In-Die pattern measurement. In this study, the registration measurement capability was investigated on new registration metrology tool IPRO5+, and new measurement method called Model-Based measurement was evaluated. And the performance and the prospect for advanced technology masks of the IPRO5+ were discussed based on the evaluation results.

Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to examine participating possibility of GATA promoter element in TPO- induced c-mpl gene expression through a PKC-independent pathway, the promoter activity of site-directed mutagenesis and the effect of potein kinase C modulator were measured by a transient transfection assay system. Together with our previous results on the TPO-induced c-mpl promoter, this study indicates destruction of -77GATA in c-mpl promoter decreased the activity by 47.3% under existence of GF109203. These results suggest that GATA promoter element plays significant role in TPO-induced c-mpl gene expression through a PKC-independent pathway.

Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by chronic inflammatory fibrosis of the extra- and intrahepatic bile ducts. Although the prognosis of patients with PSC was believed to be poor, some patients have not experienced the expected rapid clinical progression. A 51-year-old man with PSC was initially hospitalized for jaundice. Laboratory data showed low levels of the complement components C3, C4, and CH50. Percutaneous transhepatic biliary drainage was performed. Cholangiography revealed complete obstruction of the common bile duct below the confluence of the cystic duct. The confluence of the hepatic duct was resected and it was reconstructed by hepaticojejunostomy for palliation of the obstructive jaundice. Increased thickness of the walls of the common bile duct, right hepatic bile duct, and gallbladder was observed. Histopathological examination of the resected specimen revealed periductal fibrosis, with an onion-skin-like appearance. The patient is currently doing well, approximately 7 years after the surgery, without any signs of PSC recurrence. In this extraordinary patient, the laboratory data for C3, C4, and CH50 showed a complete return to normal levels. The positive results in this patient suggest that resection of the confluence of the hepatic duct may be an effective surgical treatment for noncirrhotic PSC patients who have dominant extrahepatic strictures.