Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture.

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II-III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II-III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II-III NSCLC in the real-world setting.

Cognitive and behavioral status in Japanese ALS patients: a multicenter study.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression. METHODS: Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests. Caregivers were asked to complete the ALS-FTD-Questionnaire (ALS-FTD-Q), a behavioral screen. We defined severe cognitive impairment (MoCA < 21 or FAB < 11), mild impairment (11 ≤ MoCA ≤ 25 or 11 ≤ FAB ≤ 15), and normal cognition (MoCA > 25 or FAB > 15). Severe and mild behavioral impairments and normal behavior were defined by the ALS-FTD-Q scores. RESULTS: In 145 ALS patients, better cognitive scores were correlated with earlier age at onset, whereas a worse behavioral score was associated with a longer disease duration and higher level of anxiety and depression. Around seventy percent of all ALS patients showed mild (40-45%) or severe cognitive impairment with cognitive impairment outnumbering behavioral impairment fivefold. Cognitive functions were more impaired in patients with age of onset over 65 years, while behavioral scores were not related to age. CONCLUSIONS: Considering the high prevalence of in particular cognitive impairment, and the diversity of impairments, the cognitive and behavioral aspects of Japanese ALS patients should be given more attention clinically.

[Solitary lymph node metastasis from early-stage hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation: a case report and review of the Japanese literature].

A 77-year-old man with chronic hepatitis C underwent transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC) in segment 8 of the liver. Necrosis was confirmed radiologically. After 19 months, recurrent HCC in segment 6 was treated with TACE and RFA. There was no recurrence. Direct-acting antiviral (DAA) therapy 24 months after the initial procedure led to a sustained virologic response. AFP-L3 markedly increased 11 months after DAA therapy, and MRI 6 months after that showed a solitary lymph node near the common bile duct. Because no intrahepatic recurrence or other lymph nodes were seen, the solitary node was excised. Histopathology showed metastatic HCC. There has been no subsequent recurrence over 13 months of follow-up.

Spontaneous Celiac and Splenic Artery Dissection.

Dissection of the splanchnic artery unrelated to an aortic lesion is extremely rare. We describe a patient with dissection of the celiac and splenic arteries causing splenic circulatory impairment. A 55-year-old Japanese man was referred to our hospital for left back pain that suddenly occurred 3 days previously and spread to the left flank. He had complicated sleep apnea syndrome well controlled with continuous positive airway pressure, and had been prophylactically taking aspirin (100 mg/day) because of asymptomatic cerebral lacunar infarcts. Contrast-enhanced computed tomography (CT) in the arterial phase revealed dissection from the celiac root extending to the entire splenic artery, the caliber of which was irregularly narrowed, causing malperfusion in the spleen. Because of hemodynamic stability and lack of impending sequelae, the patient was carefully observed with rest, strict blood pressure control, and aspirin administration. One month later, CT revealed restoration of the caliber of the dissected arteries and regression of the organizing false lumen, which confirmed the patient's recovery. Despite the extreme rarity or nonspecific symptoms, splanchnic artery dissection should be considered a potentially life-threatening emergency. This case supports the possible benefit of starting antithrombotic treatment early to prevent thrombotic sequelae such as organ infarction and aneurysmal formation.

Putting "sticky notes" on the electronic medical record to promote intra-hospital referral of hepatitis B and C virus-positive patients to hepatology specialists: an exploratory study.

BACKGROUND: Currently, no system for appropriate intra-hospital collaboration regarding hepatitis virus positive individuals exists, even in medical institutions with hepatologists among their staff. The main objective of this study was to explore a simple alert system to promote the referral of patients with hepatitis B surface antigen (HBsAg)- or anti-hepatitis C virus (HCV) antibodies positivity to hepatologists through electronic medical records. METHODS: Since April 2014 at Osaka City Juso Hospital, "sticky notes" have been put on the electronic medical records of patients newly diagnosed with HBsAg- or anti-HCV- antibodies positivity to recommend intra-hospital referral of those patients to specialists. In this study, we investigated the number of referrals to hepatologists before vs. after the introduction of this system (that is, in fiscal years 2013 [Period 1] and 2014 [Period 2], respectively), and the subsequent clinical courses of the patients. RESULTS: The proportions of patients with HBsAg and anti-HCV antibody positivity did not show statistically significant differences between Period 1 and Period 2 (1.6 % [43/2,757] vs. 1.3 % [39/2,891], p = 0.58; and 5.8 % [156/2,674] vs. 5.3 % [147/2,790], p = 0.39, respectively). However, the referral proportions for patients with HBsAg- and anti-HCV antibody positivity were significantly higher in Period 2 (73 % [11/15] and 65 % [41/63], respectively) than in Period 1 (28 % [5/18] and 17 % [9/54]) (p = 0.009 and p < 0.001, respectively). Among patients who were referred to hepatologists, 2 HBsAg-positive and 4 anti-HCV antibody positive patients initiated antiviral treatment. CONCLUSION: Our simple electronic medical record based alert system effectively promoted intra-hospital referral of hepatitis virus-positive patients, who have been detected by screening tests, to hepatologists.

Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients.

The Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) is more useful than pre-existing laboratory tests for predicting hazardous drinking: a cross-sectional study.

BACKGROUND: It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking. METHODS: A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. RESULTS: Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant. CONCLUSIONS: This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking.

The Alcohol Use Disorders. Identification Test (AUDIT) score is useful for predicting alcohol consumption.

It is important to screen for alcohol consumption and drinking customs by using a stan- dardized method. The aim of this study was to investigate whether standardized questionnaire was useful for predicting alcohol consumption. A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted the Internal Medicine Department of Osaka City Juso Hospital. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. Forty (23%) male patients reported daily alcohol consumption 40 g, and 16 (10%) female patients reported consumption 20 g. The optimal cutoff values of hazardous drinking (all patients)/ drinker (male)/ drinker (female) were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2/ 7.2/ 6.1, with sensitivity of 95.5%/ 96.3%/ 88.9%, specificity of 87.0%/ 96.3%/ 88.9%, false positive rate of 13.0%/ 9.4%/6.6%, false negative rate of 4.5%/ 3.'%/ 11.1%, and area under the receiver operating characteristic curve of 0.97/ 0.98/ 0.99. In conclusion, this study showed that the AUDIT score was useful for predicting alcohol consumption.

The management of tumor motions in the stereotactic irradiation to lung cancer under the use of Abches to control active breathing.

PURPOSE: Breathing control is crucial to ensuring the accuracy of stereotactic irradiation for lung cancer. This study monitored respiration in patients with inoperable nonsmall-cell lung cancer using a respiration-monitoring apparatus, Abches, and investigated the reproducibility of tumor position in these patients. METHODS: Subjects comprised 32 patients with nonsmall-cell lung cancer who were administered stereotactic radiotherapy under breath-holding conditions monitored by Abches. Computed tomography (CT) was performed under breath-holding conditions using Abches (Abches scan) for treatment planning. A free-breathing scan was performed to determine the range of tumor motions in a given position. After the free-breathing scan, Abches scan was repeated and the tumor position thus defined was taken as the intrafraction tumor position. Abches scan was also performed just before treatment, and the tumor position thus defined was taken as the interfraction tumor position. To calculate the errors, tumor positions were compared based on Abches scan for the initial treatment plan. The error in tumor position was measured using the BrainSCAN treatment-planning device, then compared for each lung lobe. RESULTS: Displacements in tumor position were calculated in three dimensions (i.e., superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) dimensions) and recorded as absolute values. For the whole lung, average intrafraction tumor displacement was 1.1 mm (L-R), 1.9 mm (A-P), and 2.0 mm (S-I); the average interfraction tumor displacement was 1.1 mm (L-R), 2.1 mm (A-P), and 2.0 mm (S-I); and the average free-breathing tumor displacement was 2.3 mm (L-R), 3.5 mm (A-P), and 7.9 mm (S-I). The difference between using Abches and free breathing could be reduced from approximately 20 mm at the maximum to approximately 3 mm in the S-I direction for both intrafraction and interfraction positions in the lower lobe. In addition, maximum intrafraction tumor displacement with the use of Abches was 4.5 mm (S-I) in the lingular segment. These results suggest that use of the Abches system can reduce deviations in tumor position to levels below those achieved under free breathing, irrespective of the tumor location. CONCLUSIONS: Respiratory control with high accuracy and reproducibility is required for high-precision radiotherapy of inoperable nonsmall-cell lung cancer and was achieved using Abches in this study.

Onset of adult-onset Still's disease following influenza vaccination.

We describe that case of a 61-year-old woman who developed high spiking fever, sore throat, polyarthralgia, and salmon pink evanescent rash following influenza vaccination. A diagnosis of adult-onset Still's disease (AOSD) was made based on clinical and laboratory findings. Methylprednisolone pulse therapy followed by oral prednisolone resulted in a favorable outcome. This is the second published case in which a causal relationship between vaccination and onset of AOSD is suggested. Bystander activation would appear to play an important role in inducing the immune reaction.

Meta-analysis of laparoscopy-assisted and open distal gastrectomy for gastric cancer.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is a minimally invasive technique. We performed a meta-analysis of five randomized clinical trials (RCTs) to evaluate and compare the benefits of LADG with those of open distal gastrectomy (ODG). METHODS: The present meta-analysis was based on the comparison of LADG with ODG for gastric cancer. The following factors were examined: operative time, estimated blood loss, number of harvested lymph nodes, time to resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. RESULTS: We selected five RCTs to compare LADG with ODG for gastric cancer. A total of 326 patients with gastric cancer were included in this meta-analysis of whom 164 underwent LADG and 162 underwent ODG. There was a significant difference in the volume of intraoperative blood loss, period of hospital stay, frequency of analgesic administration, and rate of complications between LADG and ODG. There was no difference in the resumption of oral intake, rate of tumor recurrence, and mortality. The operative time was significantly longer and the number of harvested lymph nodes was significantly smaller in LADG than in ODG. CONCLUSION: LADG is significantly superior to ODG regarding the volume of blood loss, duration of hospital stay, level of pain, and risk of complications. There was no difference in the resumption of oral intake, rate of tumor recurrence, and mortality. However, LADG was significantly inferior to ODG regarding operative time and also had a smaller number of harvested lymph nodes.

A meta-analysis of randomized controlled trials that compared laparoscopy-assisted and open distal gastrectomy for early gastric cancer.

BACKGROUND: We conducted a meta-analysis to evaluate and compare the advantages of laparoscopy-assisted distal gastrectomy (LADG) over open distal gastrectomy (ODG) for treating early gastric cancer (EGC). METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and January 2010 by using the following search terms: laparoscopy-assisted gastrectomy, laparoscopic gastrectomy, and early gastric cancer. The following data were analyzed: operative time, estimated blood loss, number of harvested lymph nodes, time required for resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. RESULTS: We selected four papers reporting randomized control studies (RCTs) that compared LADG with ODG for EGC. Our meta-analysis included 267 patients with EGC; of these, 134 and 133 had undergone LADG and ODG, respectively. The volume of intraoperative blood loss, frequency of analgesic administration, and rate of complications were significantly lesser for LADG than for ODG. However, the time required for resumption of oral intake and duration of hospital stay did not significantly differ between LADG and ODG. The operative time for LADG was significantly longer than that for ODG; further, the number of harvested lymph nodes was significantly lesser in the LADG group than in the ODG group. CONCLUSION: LADG is advantageous over ODG because it results in lesser blood loss, is less painful, and is associated with a low risk of complications. Additional RCTs that compare LADG and ODG and investigate the long-term oncological outcomes of LADG are required to determine the advantages of LADG over ODG.

Urinary trypsin inhibitor suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

OBJECTIVES: To investigate the effects of ulinastatin, a urinary trypsin inhibitor (UTI), on jugular venous superoxide radical (O2⁻·) generation, oxidative stress, early inflammation, and endothelial activation in forebrain ischemia/reperfusion (FBI/R) rats. METHODS: Fourteen Wistar rats were allocated to a control group (n = 7) and a UTI group (n = 7). Throughout the experiments, O2⁻· in the jugular vein was measured by the produced current using a novel electrochemical O2⁻· sensor. Forebrain ischemia was induced by occlusion of the bilateral common caroti darteries with hemorrhagic hypotension for 20 min, followed by reperfusion. In the UTI group, UTI (5 U/g) was administered intravenously immediately after reperfusion. At 60 min after reperfusion, plasma and brain were harvested, and malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: O2⁻· current increased gradually during forebrain ischemia in both groups. The current increased markedly in the control group immediately after reperfusion but was significantly attenuated in the UTI group after reperfusion. Brain and plasma malondialdehyde, HMGB1, and ICAM-1 were significantly attenuated in the UTI group compared with those in the control group, except for brain HMGB1, which was associated with the amount of O2⁻· generated during FBI/R. DISCUSSION: UTI suppressed jugular venous O2⁻· generation, oxidative stress, early inflammation, and endothelial activation in FBI/R rats. Therefore, UTI might be a useful agent for the therapy of the cerebral ischemia/reperfusion pathophysiology.

Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats.

OBJECTIVE AND DESIGN: The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats. MATERIALS AND TREATMENT: Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 microg/g) was administered intravenously to the control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of saline to the sham group. METHODS: The O(2)(-*) generated was measured as the current in the right atrium using an electrochemical O(2)(-*) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration. RESULTS: The O(2)(-*) current increased in the control group and was significantly attenuated in the UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in the UTI group. CONCLUSIONS: UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.

Moderate hypothermia suppresses jugular venous superoxide anion radical, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

The aim of this study was to assess the effect of moderate hypothermia (MH) on generation of jugular venous superoxide radical (O2-.), oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion (FBI/R) rats. Twenty-one Wistar rats were allocated to a control group (n=7, 37 degrees C), a pre-MH group (n=7, 32 degrees C before ischemia), and a post-MH group (n=7, 32 degrees C after reperfusion). MH was induced before induction of ischemia in the pre-MH group and just after reperfusion in the post-MH group. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries with hemorrhagic hypotension for 10 min, followed by reperfusion. O(2)(-)(.) in the jugular vein was measured from the produced current using a novel O2-. sensor. The O2-. current showed a gradual increase during forebrain ischemia in the control and post-MH groups but was attenuated in the pre-MH group. Following reperfusion, the current showed a marked increase in the control group but was strongly attenuated in the pre- and post-MH groups. Concentrations of malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma 120 min after reperfusion in the pre- and post-MH groups were significantly lower than those in the control group, except for plasma HMGB1 in the post-MH group. In conclusion, MH suppressed O2-. measured in the jugular vein, oxidative stress, early inflammation, and endothelial injury in FBI/R rats.

Hyperoxia suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats: laboratory study.

This study used an electrochemical O2. sensor to investigate the effects of hyperoxia on generation of the superoxide radical (O2.) in the jugular vein during forebrain I/R in rats. Twenty-eight male Wistar rats were allocated to a sham group (n = 7; sham-treated rats with inspired oxygen fraction [FiO2] of 0.4), a hemorrhagic shock and reperfusion (HS/R) group (n = 7; HS without carotid artery occlusion and reperfusion with FiO2 of 0.4), a normoxia group (n = 7; forebrain ischemia produced by bilateral carotid arteries occlusion with HS and reperfusion with FiO2 of 0.4), and a hyperoxia group (n = 7; forebrain ischemia with FiO2 of 0.4 and reperfusion with FiO2 of 1.0). The jugular venous O2. current was measured for 10 min during forebrain ischemia and for 120 min after reperfusion. The O2. current increased gradually during forebrain ischemia in the three groups other than the sham group. Immediately after reperfusion, the current showed a marked increase in the normoxia group and a pronounced decrease in the hyperoxia group. Levels of brain and plasma malondialdehyde, high-mobility group box 1 protein, and intercellular adhesion molecule 1 were significantly attenuated in the hyperoxia group relative to those in the normoxia group. In conclusion, hyperoxia suppressed jugular venous O2. generation and malondialdehyde, high-mobility group box 1, and intercellular adhesion molecule 1 in the brain and plasma in the acute phase of cerebral I/R. Thus, the administration of 100% oxygen immediately after reperfusion suppresses oxidative stress and early inflammation in cerebral I/R.

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion.

We recently reported that excessive superoxide anion radical (O(2)(-)) was generated in the jugular vein during reperfusion in rats with forebrain ischemia/reperfusion using a novel electrochemical sensor and excessive O(2)(-) generation was associated with oxidative stress, early inflammation, and endothelial injury. However, the source of O(2)(-) was still unclear. Therefore, we used allopurinol, a potent inhibitor of xanthine oxidase (XO), to clarify the source of O(2)(-) generated in rats with forebrain ischemia/reperfusion. The increased O(2)(-) current and the quantified partial value of electricity (Q), which was calculated by the integration of the current, were significantly attenuated after reperfusion by pretreatment with allopurinol. Malondialdehyde (MDA) in the brain and plasma, high-mobility group box 1 (HMGB1) in plasma, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma were significantly attenuated in rats pretreated with allopurinol with dose-dependency in comparison to those in control rats. There were significant correlations between total Q and MDA, HMGB, or ICAM-1 in the brain and plasma. Allopurinol pretreatment suppressed O(2)(-) generation in the brain-perfused blood in the jugular vein, and oxidative stress, early inflammation, and endothelial injury in the acute phase of forebrain ischemia/reperfusion. Thus, XO is one of the major sources of O(2)(-)- in blood after reperfusion in rats with forebrain ischemia/reperfusion.