The first report of acute respiratory distress syndrome (ARDS) was published in 1967, and even now acute lung injury (ALI) and ARDS are severe forms of diffuse lung disease that impose a substantial health burden all over the world. Recent estimates indicate approximately 190,000 cases per year of ALI in the United States each year, with an associated 74,500 deaths per year. Common causes of ALI/ARDS are sepsis, pneumonia, trauma, aspiration pneumonia, pancreatitis, and so on. Several pathologic stages of ALI/ARDS have been described: acute inflammation with neutrophil infiltration, fibroproliferative phase with hyaline membranes, with varying degrees of interstitial fibrosis, and resolution phase. There has been intense investigation into the pathophysiologic events relevant to each stage of ALI/ARDS, and much has been learned in the alveolar epithelial, endobronchial homeostasis, and alveolar cell immune responses, especially neutrophils and alveolar macrophages in an animal model. However, these effective results in the animal models are not equally adoptive to those in randomized, controlled trials. The clinical course of ALI/ARDS is variable with the likely pathophysiologic complexity of human ALI/ARDS. In 1994, the definition was recommended by the American-European Consensus Conference Committee, which facilitated easy nomination of patients with ALI/ARDS for a randomized, clinical trial. Here, we review the recent randomized, clinical trials of ALI/ARDS.

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Objective The aim of this study was to analyze the effects of anti-thrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) on gastroduodenal bleeding.
Patients and Methods The study subjects were 544 patients (421 males and 123 females, mean age, 64.2 years) who were treated endoscopically for bleeding gastroduodenal ulcers from January 1995 to August 2008. Of the 544 patients, 276 (50.7%) had a history of treatment for ≥1 month with an antithrombotic agent or NSAIDs, including low-dose aspirin (n=94), other NSAIDs (n=91), warfarin (n=43), or any combination of the three (combination treatment group; n=48). On the other hand, 268 patients had not previously received any of these drugs (control group). Clinical features and endoscopic therapeutic results were assessed and compared.
Results Helicobacter pylori infection was detected in 187 of the 241 (77.6%) patients examined. Of the 544 patients, 199 (36.6%) attended the Department of Cardiology or Cardiovascular Surgery, and 170 (31.3%) patients were already being treated with antiulcer medication, including proton pump inhibitors (n=18 [3.3%]). Forty (7.4%) patients suffered from rebleeding after intervention; the incidence of ulcer rebleeding was not significantly different between patients being treated with any such drugs (4.7% [13/276]) and those that had not previously received any antithrombotic agent or NSAIDs (10.1% [27/268]).
Conclusion Antithrombotic therapy and NSAIDs use contributed to bleeding in 50.7% of patients with gastroduodenal ulcers. These drugs are a major cause of ulcer bleeding, but are not necessarily considered a risk factor for rebleeding after endoscopic hemostasis.

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Objective To evaluate the relationship of the presenting features of acute coronary syndrome (ACS) to in-hospital adverse events (total and cardiac deaths, heart failure and serious dysrhythmia) and the effects of coronary intervention.
Background Patients with ACS may present with dyspnea, shock and/or cardiac arrest with or without accompanying chest pain.
Methods We evaluated 9,373 patients (age 65±12 years and 60% males) enrolled in the Thai ACS Registry. Cardiac dyspnea included shortness of breath on exertion, and/or at rest, orthopnea, or paroxysmal nocturnal dyspnea presumed from cardiac sources. Shock was present if systolic blood pressure was <90 mmHg for >30 min with symptoms of end-organ hypoperfusion. Post cardiac arrest was identified if cardiopulmonary resuscitation was required. We calculated the frequencies of these presenting features and assessed their contribution toward in-hospital adverse events (total and cardiac deaths, heart failure and serious arrhythmias) for the whole ACS and each entity of ACS and the effects of in-hospital interventions, both coronary and medicinal.
Results Cardiac dyspnea, shock and post cardiac arrest were seen in 32.7%, 9.3%, and 4.2% of patients, respectively. In-hospital adverse events occurred more frequently in patients with these presenting features than those without (p<0.05). Cardiac dyspnea and shock were independent predictors of heart failure and death, respectively, while post cardiac arrest independently identified patients at risk of arrhythmia, total and cardiac death, regardless of the subgroup of ACS. Coronary revascularization significantly reduced the risk of total and cardiac death.
Conclusion These 3 presenting features of ACS portend a poor prognosis, regardless of the subgroup of ACS and should be considered as important early indicators for early intervention.

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Objective Metabolic syndrome is associated with a high risk of cardiovascular morbidity and mortality. The predominant cause of metabolic syndrome is an unhealthy lifestyle. Healthy habits are represented by Breslow's 7 healthy practices, Morimoto's 8 items and Ikeda's 6 healthy habits. This study was done to determine which set of healthy habits was most likely to result in a reduced risk of developing the metabolic syndrome.
Methods From April 1, 2000 through March 31, 2007, 6,765 males and 2,789 females underwent a medical check-up at Jikei University Hospital in Japan. They completed a simple, self-administered lifestyle questionnaire based on the 3 classifications of healthy habits. The responses were divided into 3 groups (poor, moderate and favorable) according to each of the healthy habit criteria. The incidence of metabolic syndrome was defined in participants who were newly diagnosed during the follow-up using Japanese-specific diagnostic criteria. The Kaplan-Meier cumulative 7-year incidence was calculated. Kaplan-Meier curves were compared using the long-rank test adjusted for age.
Results In females, Breslow's, Morimoto's and Ikeda's healthy habits showed significant differences in the incidence between poor and moderate groups, and between poor and favorable groups. In males, a significant difference was observed among the poor, moderate and favorable groups for Ikeda's healthy habits. However, no significant difference was observed for Breslow's healthy practices. Morimoto's items only showed a significant difference between the poor and moderate groups.
Conclusion Among the 3 models tested, Ikeda's healthy habits were the most useful for decreasing the risk of metabolic syndrome in Japanese.

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Objective The significance of estimated glomerular filtration rate (e-GFR) in diabetic nephropathy has yet to be clearly determined. We therefore compared albuminuria and e-GFR for usefulness in predicting progressive decline in renal function.
Methods A total of 1,303 subjects with type 2 diabetes mellitus whose e-GFR was more than 30 mL/min/1.73 m² were followed for three years. Associations of clinical staging based on AER and that based on e-GFR with progression of renal insufficiency (e-GFR <30 mL/min/1.73 m²) were evaluated.
Results On univariate analysis, both clinical stages based on e-GFR and AER were significant variables (p<0.05). On multiple logistic regression analysis, the odds ratio for macroalbuminuria was 132.3, and that for microalbuminuria was 10.3 while that for e-GFR less than 60 mL/min/1.73 m² was 9.0 for further deterioration of renal function. On the other hand, subjects without albuminuria exhibited a rate of disease progression of less than 1% irrespective of e-GFR level.
Conclusions Both albuminuria and reduced e-GFR are significant and independent risk factors for further deterioration of diabetic nephropathy, though albuminuria had a greater odds ratio than reduced e-GFR for deterioration of renal function over a three-year period. e-GFR exhibited additive risk for deterioration of diabetic nephropathy within three years only when albuminuria was present.

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Objective and Methods Idiopathic interstitial pneumonias (IIPs) frequently occur in association with lung cancer. However, there is no consensus on the best treatment of acute exacerbation of IIP in lung cancer patients (LC with IIP), including those with iatrogenic acute lung injury resulting from cancer treatments. We aimed to identify an appropriate strategy for treatment of this condition. We analyzed clinical features of 120 LC with IIP, retrospectively.
Results The incidence of acute exacerbation related to anticancer treatment was 22.7%; when the incidence was examined separately for patients receiving chemotherapy or the best supportive care, the incidence was 20.0% and 31.3%, respectively. Additional investigations should be directed to finding suitable regimens for treatment of LC with IIP and the selection of appropriate patients with LC with IIP for chemotherapy. The incidence of acute exacerbation caused by combination regimens of carboplatin + paclitaxel or a platinum agent + etoposide was significantly lower than that of other regimens (0% vs. 18%, respectively; p=0.025, Fisher's Exact Test). Patients with high levels of C-reactive protein before chemotherapy had a significantly higher risk of developing acute exacerbation (odds ratio 5.60, p=0.028).
Conclusion There was no evidence that anticancer treatment, including chemotherapy, should be avoided in LC with IIP. To establish an appropriate cancer treatment for LC with IIP, a prospective clinical study should be performed to evaluate various treatment modalities in a larger patient population.

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Objective To study the incidence and clinical features of acute juvenile female non-herpetic encephalitis (AJFNHE) in Japan.
Methods A nationwide questionnaire on patients with severe non-herpetic encephalitis of unknown etiology with a prolonged clinical course or death was sent to the departments of Internal Medicine, Neurology, Pediatrics, and Emergency and Critical Care at all hospitals with 200 beds or more in Japan.
Results The recovery rate was 25% (1,279 out of 5,030 departments) and 90 patients were enrolled in this study. The annual incidence was 0.33/10⁶ population. 85% of patients were female. The means and standard deviations of age at onset and hospital stay were 26±10 years and 180±228 days. As first symptoms, fever and psychosis were presented in 90%. Among the neurological symptoms, disturbance of consciousness was presented in 92%, convulsions in 65%, and involuntary movements in 55%. Respiratory failure during hospitalization was observed in 71% and required care with mechanical ventilation. The detection rate of anti-GluR ε2 and/or δ1 antibodies was 67% of patients. Anti-N-methyl-D-aspartate receptor NR1/NR2 antibody was detected in all four examined patients with anti-GluR ε2 antibody, and also detected in both of the two examined patients without anti-GluR ε2 antibody. As for outcome, 46% returned to work and 37% returned home, but 7% died. Associated tumors were demonstrated in 39%. All reported patients had ovarian tumors, among which teratoma was the most frequent.
Conclusion A nationwide survey provided data for the annual incidence and clinical features of AJFNHE in Japan.

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Objective Scopolamine butylbromide (SB), a muscarinic receptor antagonist, is used commonly in gastric X-ray examination in the physical check-up in Japan. This study describes clinical features of SB-induced headache.
Patients and Methods SB-induced headache was defined as headache that started within 20 minutes after intramuscular administration of SB (20 mg/body). The Primary and the secondary headaches were diagnosed according to the ICHD-II criteria. SB-induced headache was classified as headache induced by acute substance use or that due to exposure (ICHD-II code 8.1). Clinical features and background of subjects with SB-induced headache were analyzed. We also estimated the frequency of SB-related headache between migraineurs and non-migraineurs.
Results A total of 54 subjects (39 women and 15 men) experienced SB-induced headache. All subjects had the present history of migraine. Nine subjects had ≥2 times of the headache. Mean age (SD) was 46.2 (9.7) years [46.2 (9.7) for women and 46.3 (10.0) for men]. Clinical hallmarks of headache showed that pulsating / throbbing pain occurred in diffuse or bilateral head sites. Headache worsened at 20-30 minutes from the onset and persisted for 6-18 hours, and ameliorated gradually 8 hours later. All subjects had repeated nausea and vomiting. Severity of headache revealed severe degree requiring complete bed rest in 50 subjects (92.6%). SB-induced headache had similar characteristics as migraine without aura (MO) attacks. Liver and renal functions were normal in all SB-related migraineurs. They had no allergic history of medication and food. In 1,865 non-migraine controls, one healthy subject had a mild degree of migraine like headache triggered by SB injection.
Conclusion SB triggers a severe degree MO like headache or worsens pre-existing migraine in some migraineurs. SB-induced headache could contribute to disequilibrium between acetylcholine and other neuropeptides. We should use SB more carefully as it can be an aggravating drug of migraine.

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Herein, we encountered an 89-year-old woman with pancreatic cancer who presented with fever without infective focus, leukocytosis of 45,860 /μL, and elevation of serum granulocyte-colony stimulating factor (G-CSF). The patient could not receive any curative therapy due to an extremely aggressive clinical course. Specimens taken at necropsy revealed an adenosquamous carcinoma positive for G-CSF by immunohistochemistry; it was only the second reported case to date. She was finally diagnosed with G-CSF-producing pancreatic cancer. In light of the above, clinicians should consider the presence of G-CSF-producing tumors, including pancreatic cancer, when presented with patients showing leukocytosis of unknown origin and fever without infective focus.

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A 15-year-old, woman, Crohn's disease patient, who carried the TPMT *3C heterozygous mutant, complained of alopecia 3 days after starting 6-mercaptopurine (6-MP) and then developed severe myelosuppression 6 weeks after starting 6-MP. The alopecia involved scalp hair only (body hair preserved) and was dominant in the temporal region. Following these side effects, transient remission of Crohn's disease occurred. Myelosuppression due to 6-MP is a rare but life-threatening side effect that is difficult to predict despite continuous monitoring of complete blood cell counts. In the present case, 6-MP-induced alopecia preceded myelosuppression and progressed rapidly as the myelosuppression worsened.

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A 59-year-old man was admitted because of congestive heart failure. He was suspected to have acromegaly, and magnetic resonance imaging revealed a pituitary macroadenoma. Endocrine examination revealed elevated plasma levels of growth hormone (GH) and insulin-like growth factor (IGF)-1, and an oral glucose tolerance test failed to suppress plasma GH levels, consistent with the diagnosis of GH-producing pituitary tumor. Treatment with octreotide, followed by transsphenoidal surgery resulted in normalization of plasma GH/IGF-1 levels, accompanied by the improvement of cardiac function. Thus, it is suggested that excess GH/IGF-1 axis is involved in the development of acromegaly-related cardiomyopathy in the present case.

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A 59-year-old woman was diagnosed as having Graves' disease and type 1 diabetes. DNA molecular HLA typing detected DRB1^*0405 and DQB1^*0401, as well as the haplotypes of DRB1^*0901-DQB1^*0303. We also performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to identify allele variations of other loci. The patient's son also manifested Graves' disease and type 1 diabetes, with both cases having strikingly homologous clinical features. Familial clustering of Graves' disease and type 1 diabetes, and their tendency to occur together along with a similar clinical course suggest that their etiology may involve shared genetic factors.

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We report two Japanese women with androgen excess symptoms. Analyses of 21-hydroxylase gene demonstrated that a 24-year-old Japanese woman had a homozygous mutation of IVS2-13 A/C>G, while a 25-year-old Japanese woman had a compound heterozygous mutation of I172N and E245del1nt, a novel mutation which would result in completely nonfunctional enzyme due to a frame shift. As IVS2-13 A/C>G and I172N have been classified as mutations leading to severe impairment in enzyme activity, this study not only clarified a novel mutation causing 21-hydroxylase deficiency, but also demonstrated that genotype and phenotype do not correlate well in these cases.

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Chromic acid is a strong metal acid and acute poisoning is very rare, but very serious with severe skin injury, renal and liver failure. The majority of published cases were suicide attempts with lethal outcomes. We describe the case of a 55-year-old man who had accidentally taken a sip of 20% chromic acid (estimated chromium intake: 2.3 g). Renal and liver failure were not present at presentation, but appeared later in the course of disease. He was treated with hemodialysis, no chelating agents or other methods for enhancing elimination were used. Liver and renal function improved over the next 30 days and the patient was discharged after 45 days of hospitalization with no need for dialysis. In the follow-up period of eight months his renal function remained depressed, but stable.

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A 17-year-old-man developed left-sided pneumothorax in 1995. Chest computed tomography (CT) showed a thick-walled cavity in the left lower lobe. Video-assisted thoracic surgery was performed, and pathologic findings of the resected lung showed a cavity, organizing hematoma, and a fibrous nodule. Fragility of connective tissue was suspected, and biochemical and molecular analysis showed reduction of type III collagen production and point mutation of the COL3A1 gene. The patient was diagnosed as having vascular-type Ehlers-Danlos syndrome (EDS). From 2002, the patient developed hemoptysis and bloody sputum once a year. Chest CT detected several nodules and cavities, which were regarded as hematomas with or without excretion. Several vascular changes including aneurysmal formations have been found since 2002, and an aneurysm of the left ulnar artery was resected. The patient continues to be followed regularly on an outpatient basis. We report a rare case of vascular-type EDS who developed pulmonary symptoms as an initial complication.

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Cerebral venous thrombosis (CVT) may present with a variety of symptoms and findings consisting of either only persistent headache, or slowly progressive stroke over several days, or even coma. CVT may develop in relation to hypercoagulable states. However, even after extensive investigation, a predisposing factor could not be identified in some cases. We report a case of CVT associated with heterozygous V Leiden mutation and sarcoidosis. Since most factor V gene heterozygous individuals do not exhibit clinical thrombotic events, the venous thrombosis of our patient suggests convergence of an inherited predisposition (heterozygous factor V Leiden mutation) with an acquired thrombogenic stimulus (sarcoidosis). Early diagnosis and treatment with anticoagulation is pivotal for a favorable outcome.

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A 56-year-old woman suffered from hepatic and bone metastases of breast cancer. Two months after starting combination chemotherapy with trastuzumab and docetaxel, air-space consolidation was observed in the right lower lung lobe on a chest computed tomography (CT) and a high serum KL-6 level was detected. Drug-induced pneumonitis with organizing pneumonia type was suspected, however, a transbronchial lung biopsy and cytological examination of the bronchoalveolar lavage fluid provided evidence of metastatic breast cancer. While the lung is a frequently affected site from metastasis of breast cancer, we report a rare case presenting as air-space consolidation on a chest CT.

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