Objective The aim of this study was to evaluate the efficacy and safety of combination therapy of natural human interferon-beta and ribavirin for patients for whom prior interferon therapy was discontinued due to depression induced by interferon-alpha. Methods Inclusion criteria were as follows; 1) HCV-genotype 1b, 2) serum HCV RNA level of ≥100 KIU/mL, 3) stopping the prior interferon-alpha monotherapy or combination therapy of interferon-alpha and ribavirin due to the appearance of depression. A total of 14 were enrolled in this prospective cohort study. The treatment period of combination therapy was 48 weeks. Depression states, reflected by Beck depression inventories and Hamilton depression rating scale, were assessed during combination therapy. Nonparametric procedures were employed for the analysis of background features of the patients with sustained virological response (SVR) and without SVR. A p value of <0.05 was considered to indicate a significant difference. Results Five of 14 patients (37.5%) had SVR by the intention to treat analysis. The SVR rate in patients who showed negative HCV RNA at 12 and 24 weeks after the initiation of combination therapy was 100% (4/4) and 83.3% (5/6), respectively. All of the patients continued the combination therapy owing to disappearance of severely adverse events contained the exacerbation of depression. Combination therapy did not yield a statistical difference in Beck depression inventories and Hamilton depression rating scale. Conclusion The combination therapy of IFN-beta and ribavirin is a possible therapy selection for the patients for whom interferon therapy was discontinued due to depression induced by interferon-alpha.
Background Although reports on endosonography-guided biliary drainage (ESBD) have been increasing, only a few discuss deployment of a self-expandable metal stent (SEMS) in the first session. Objective To evaluate the safety and efficacy of ESBD with the one-step placement of a newly designed fully-covered SEMS. Patient and Methods Five patients with malignant biliary obstruction in whom one-step placement of an anti-migration designed SEMS in the first session of ESBD had been attempted between January 2007 and October 2009 were included in this study. Main outcome measurements were technical and clinical successes, early complications, and short-term results. Results ESBD was attempted to bridge the extrahepatic bile duct and the duodenum and one-step SEMS placement was successful in all cases. There were no early complications related to ESBD and excellent biliary decompression was obtained in all cases. SEMS dysfunction such as stent migration and occlusion was not seen during the follow-up period (mean follow-up 138 days, range 102-184 days). Conclusion One-step placement of a fully-covered SEMS in ESBD is possibly a safe and effective treatment for biliary obstruction.
Background and Purpose Fever is a common symptom of acute aortic dissection. The beginning time and duration of fever after percutaneous endovascular stent-graft in patients with aortic dissection is not well known. The present study was undertaken to investigate the characteristics of fever after percutaneous endovascular stent-graft in patients with type B aortic dissection. Methods and Results In this retrospective study the data of a total of 64 patients with type B acute aortic dissection undergoing percutaneous endovascular stent-graft were collected and analyzed. In total, 55 patients (85.9%) had fever after stent-graft. The time of fever onset was during the initial 2 days after interventional procedure (92.7%), and the duration of fever of most patients was not beyond 7 days after stent implantation. The fever before stent implantation was associated with the beginning time of fever after stent implantation, but not with the duration of fever. Conclusion The results of this study could provide important reference information for the evaluation of fever before and after interventional treatment in patients with acute aortic dissection.
Background The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism has been suggested to be linked to the risk of essential hypertension (EH), however the results are still debatable. Objective and Methods To assess the association between eNOS G894T gene polymorphism and EH, such electronic databases as Pubmed, Embase, Web of Science, China Biological Medicine Database (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The selection criteria were as follows: a) Evaluation of the association of eNOS G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis criteria of the World Health Organization (WHO) in 1999. c) The study results were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was analyzed by current meta-analysis. Random effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). Results In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese population, the distribution of T allele frequency was 0.154 for EH group and 0.128 for the control group. A significant association was found between G894T gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency of T allele was 1.33 (95% CI:1.13-1.56, Pheterogeneity <0.00001). In the stratified analysis by ethnicity, there was a significant association in Han subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was 1.31 (95% CI:1.09-1.59, Pheterogeneity <0.00001). No significant increased risk for EH was found in the non-Han subgroup (p=0.08). Conclusion In the current meta-analysis, T allele of eNOS G894T gene was suggested to be related to the increased risk of EH in the Chinese population, particularly in those of Han ethnicity.
Objective Lifestyle modification as well as combination antihypertensive therapy is necessary to achieve strict blood pressure (BP) control as advocated by the guidelines for the treatment of hypertension. The aim of this study was to investigate the status of adherence to lifestyle modifications and BP control status in hypertensive outpatients. Methods and Patients Subjects are 661 hypertensive outpatients who had been followed at National Kyushu Medical Center. We assessed BP control status based on the average clinic BP on two occasions. In addition, we investigated the adherence to the individual items of lifestyle modification by a questionnaire. Results Average BP was 129 ± 10/71 ± 11 mmHg and overall rate of achieving goal BP was 60.1%. Achieving rate of each target BP category was 83.3% in the elderly patients (<140/90 mmHg), 56.7% in the young/middle patients (<130/85 mmHg) and 45.5% in the patients with diabetes mellitus/chronic kidney disease/myocardial infarction (<130/80 mmHg). Adherance to each item of lifestyle modification was as follows: Patients who answered to be conscious about salt restriction was 80.9%, those with increased intake of fruits/vegetables was 79.0%, reduced intake of cholesterol/saturated fatty acids was 67.9%, presence of obesity was 37.7%, daily exercise for ≥30 min was 31.9%, habitual alcohol intake was 38.0%, habitual smoking was 9.8%. Only 22.5% of the patients had no lifestyle items to be modified. On the other hand, 19.6% of patients had more than 3 items to be modified. Subjects with more than 3 lifestyle items to be modified are more frequently found in young, male, and obese groups. Conclusion We conclude that about 60% of the patients achieved goal BP by the intensive combination therapy. The lifestyle modification seems to be important especially for the young, male and obese patients.
Objective The objective was to clarify the significance of high high-density lipoprotein cholesterol (HDL-C) levels in the metabolic syndrome (MetS). The evaluation focused on insulin resistance as an indicator of early-stage MetS. Methods and Subjects Of 2705 men who first underwent an annual health check-up at Tokai University Hachioji Hospital, 2129 men were included in this study, after exclusion of those on medication for hypertension, diabetes or dyslipidemia, and those with a prior history of ischemic heart disease, cerebrovascular disease or chronic renal failure. MetS risk factors include the following five parameters: waist circumference, blood pressure, plasma glucose, triglycerides and HDL-C. The correlations between HDL-C and number of MetS risks with homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed. HOMA-IR, number of risks, habits of smoking, exercise and drinking alcohol, stratified by HDL-C levels, were compared in MetS subjects. Results In cases with ≤2 risk factors, the higher the HDL-C, the lower the HOMA-IR. However, with ≥3 risk factors for MetS, the HOMA-IR increased when HDL-C was ≥90 mg/dL. In MetS subjects, the rate of alcohol intake ≥75 g/day was high when HDL-C was ≥90 mg/dL. Conclusion In MetS subjects with high HDL-C levels, insulin resistance was increased. Therefore, in persons with high HDL-C levels, it is important to monitor the amount of alcohol consumption and reduce alcohol consumption to <75 g/day.
Background and Objective Physical activity (PA) is considered an important approach to prevent and treat obesity and hyperuricemia. The purpose of the present study was to examine the influence of PA intensity and aerobic fitness on anthropometric indices and serum uric acid in obese individuals. Methods PA was examined using a single-axial accelerometer and aerobic fitness was assessed by electric cycle ergometry in obese middle-aged men (n=71, 47.2 ± 4.4 years). PA was defined as light (<3 metabolic equivalents [METs]), moderate (3.0-6.0 METs) or vigorous (>6.0 METs) intensity from the corresponding METs multiplied by time spent at the corresponding intensity levels. Serum uric acid was measured by the uricase peroxidase method. Results The association between aerobic fitness index (lactate threshold) and serum uric acid did not reach statistical significance after adjustment for potential confounding factors (age, body mass index [BMI], and alcohol consumption) (β=-0.110, p=0.138). Light intensity PA was inversely associated with BMI and waist circumference, even after adjustment for age and alcohol consumption (BMI: β=-0.543, p=0.023; waist circumference: β=-1.333, p=0.016). Moderate intensity PA, but not light or vigorous intensity PA, was inversely correlated with the uric acid level and this remained significant after adjustment for age, BMI, and alcohol consumption (β=-0.222, p=0.036). Conclusion Our results suggest that light intensity PA may have an important role in weight control while moderate intensity PA may be associated with the lower uric acid concentrations in obese individuals.
Aim An adequate β cell number is important to prevent the onset and development of type 2 diabetes. The aim of this study was to determine if phytoestrogen gesintein has protective effects against high glucose-induced cell apoptosis in human pancreas cells, and to try to determine the possible mechanism for this protection. Methods Human pancreatic β cells were subjected to normal (5 mM) or high glucose (25 mM) with and without the presence of 100nM genistein, and also in the presence and absence of the pure anti-estrogen ICI-182780 (100 nM). Bcl-2 siRNA transfection was performed to investigate if the effect of genistein was also Bcl-2 dependent. Cell proliferation and apoptosis were determined by Tritiated Thymidine Incorporation Assay and Cell Apoptosis Detection ELISA. Estrogen receptor and Bcl-2 mRNA expression was measured by Real-time Quantitative PCR. Results High glucose concentration caused cell proliferation inhibition and apoptosis in cultured human pancreatic β cells, and these effects were significantly reversed by genistein (P<0.01). Estrogen receptor beta was expressed in the cultured cells, and genistein protection was blocked by ICI-182780 administration as well as Bcl-2 siRNA transfection. Conclusion Phytoestrogen gave protection against high glucose-induced pancreatic cell damage through estrogen receptor beta and Bcl-2 dependent pathways.
Objective Early diagnosis is a key factor in the management of chronic obstructive pulmonary disease (COPD). Although mass screening is widely used, little is known about its accuracy and efficacy. This study investigated whether using spirometry during mass screening to detect COPD among community residents might be ineffective because of variability in the training and experience of examiners. Participants and Methods Both spirometry and a self-written questionnaire-based survey, including questions designed to detect respiratory symptoms, were conducted on community residents. Two separate studies were conducted on islanders living in similar environments. Study I was performed from 2004 to 2007 on Hachijyo Island residents, while study II, with a similar study design, was performed in 2003 on Inno Island residents. Results In study I, 3,592 subjects underwent examination over the 4-year study period; of these, 378 subjects underwent repeated examinations. Approximately 25% of the subjects had respiratory symptoms. Acceptable spirometry recordings were obtained for 62.0% (2004) to 84.1% (2006) of the subjects. In study II, 167 of the 254 subjects (65.7%) had respiratory symptoms. Acceptable assessment recordings were achieved in 254 subjects (95.5%). The suitability of the recordings was influenced by the extent/level of training of the examiners and the accompanying thoracic specialists. Conclusion We concluded that the effectiveness of health check-ups for COPD evaluation using spirometry was greatly influenced by the quality of the examiners, even when the subjects had respiratory symptoms. Thus, we recommend caution when screening for early signs of COPD during health check-ups.
Background The diagnostic sensitivity of current bronchoscopy for peripheral lung cancer is inadequate because the bronchoscope insertion range is limited and confirmation of the position of the biopsy apparatus at the lesion under X-ray fluoroscopy is inaccurate. The combination of ultrathin bronchoscopy and computed tomography (CT) is effective for solving these problems. Objective This study was a retrospective study analyzing prospectively collected data to identify factors contributing to the diagnosis and the appropriate biopsy method in CT-guided ultrathin bronchoscopy for peripheral lung cancer. Methods The subjects comprised 86 patients (88 lesions) who underwent CT-guided ultrathin bronchoscopy and were finally diagnosed with peripheral lung cancer. We evaluated the diagnostic yield according to specific factors and also according to the sample collection method. Results Sixty-nine lesions were diagnosed as lung cancer, and the diagnostic yield was 78.4% (80.3% in lesions ≤2 cm in diameter). Multivariate analysis showed that the factors contributing to the diagnosis were the observation range by ultrathin bronchoscopy and the presence/absence of the involved bronchus or pulmonary artery. Pathological evaluation facilitated histological diagnoses in 53 (65.4%) of 81 lesions. In 16 lesions, only the cytological diagnosis was positive. Conclusion CT-guided ultrathin bronchoscopy may be particularly useful for lesions for which the involved bronchus or pulmonary artery can be confirmed, and observation of bronchi of the 6th generation or more is possible. Since the specimen preparation rate is low, the combination of histopathological diagnosis with cytological diagnosis particularly that of the discharge attached to the forceps, is optimal.
Objective Procalcitonin (PCT) has been increasingly used as a biomarker of infection. The purpose of this study was to evaluate its diagnostic value after hematopoietic stem cell transplantation (HSCT), where non-infectious febrile complications such as graft-versus-host disease frequently develop. Methods We retrospectively analyzed 144 febrile episodes (infections: 82, and noninfections: 62) in adult patients with hematological disorders, including 57 and 87 episodes in HSCT and non-HSCT patients, respectively. Results Of 57 febrile episodes in HSCT patients, 46 (86%) and 25 (44%) revealed positivity for C-reactive protein (CRP) and PCT, respectively. Among 87 febrile episodes in non-HSCT patients, 81 (93%) and 22 (25%) events showed positive results of CRP and PCT. Both of these biomarkers were associated with infectious episodes in univariate analysis. Multivariate analysis showed that a high cut-off level (>9.5 mg/dL) of CRP was a better indicator for infections than PCT in HSCT patients, while PCT positivity was more diagnostic for infections than any cutoff CRP level in non-HSCT patients. Conclusion It may be necessary to interpret the results of these biomarkers with different orders of priority in transplant versus nontransplant patients.
Objective Carpal tunnel syndrome (CTS) severity increases with age. Ultrasonographic measurement of the median nerve cross-sectional area (CSA) is an additional or complementary method for CTS diagnosis. The present study was aimed to investigate the diagnostic significance of median nerve CSA in various age groups of CTS patients. Methods The subjects were patients with electrophysiologically confirmed CTS and age-matched controls. Sonographic measurements of the median nerve CSA were performed. Results A total of 279 hands of 175 patients with CTS and 50 normal hands were examined. CSA was correlated with distal motor and sensory latencies of the median nerve and severity of CTS. CTS severity increased with age, particularly in patients over 80; however, their median nerve CSA was not enlarged regardless of their high severity of CTS. Conclusion Although the median nerve CSA is a useful diagnostic measurement for CTS, it should be emphasized that its diagnostic significance might be limited in aged patients. In particular, in very elderly patients, careful evaluation of CTS severity is necessary.
Objective The aim of this multicenter cross-sectional study was to assess the relation between fatigue in a large number of Japanese patients with Parkinson's disease (PD) and drugs taken to treat PD. Method We used the 16-item Parkinson Fatigue Scale (PFS-16), which was designed to assess fatigue exclusively associated with PD. Multiple logistic regression analyses were used to assess the relation between antiparkinson drugs and fatigue in PD. Results A total of 350 non-demented PD patients were enrolled. Fatigue (PFS score of ≥4) was revealed in 319 patients (91%). Pramipexole was administered to 24% of PD patients. Multiple logistic regression analysis revealed that the administration of Pramipexole was significantly related to low rates of fatigue in PD patients with Hoehn and Yahr stage <3 (p=0.011, odds ratio=5.23, 95% confidence interval; 1.47-18.63). Conclusion The reduced fatigue in PD patients was observed in taking Pramipexole.
Hyponatremia is a common clinical problem that results from various causes. Hypothyroidism is known to be one of the causes of this disorder. We report a case of metastatic thyroid cancer presenting with severe hyponatremia in association with hypothyroidism induced by pretreatment of I131 therapy, such as a low-iodine diet and withdrawal of thyroid hormone. Serum arginine vasopressin (AVP) was elevated and urine osmolality was higher than that of serum. Saline infusion and thyroid hormone replacement normalized serum sodium and AVP. Inappropriate secretion of AVP in hypothyroid state was thought to be one of the causes of this hyponatremia.
Thrombo-embolism is one of the serious complications of takotsubo syndrome (TS). It typically occurs in the classical mid-apical left ventricular ballooning form of TS. This complication has not been reported in cases of left mid-ventricular ballooning type of TS. We describe a 67-year-old woman who presented with 2-3 days of increasing signs and symptoms of heart failure. Echocardiography showed marked hypokinesia/akinesia in the mid-anterior, mid-anterolateral, and mid-inferior wall of the left ventricle and mild hypokinesia in the apical region. There was also hypokinesia of the mid and apical parts of the right ventricle. One day after admission, she developed acute left-sided renal infarction. Left ventriculography and coronary angiography 3 days after admission showed typical left mid-ventricular ballooning with no identifiable coronary lesion. Follow-up echocardiography showed complete resolution of left and right ventricular dysfunction. Takotsubo syndrome with right ventricular involvement complicated with heart failure and left renal embolic infarction was diagnosed. The mechanism of left renal embolic infarction is discussed.
A 49-year-old otherwise healthy man was admitted to our hospital because of repeated generalized convulsions after influenza A virus infection. His family history was notable for consanguinity of parents. Initial laboratory tests revealed metabolic alkalosis with hypomagnesemia, as well as an elevated high density lipoprotein cholesterol level. He was diagnosed with Gitelman's syndrome and cholesteryl ester transfer protein deficiency by identifying homozygous mutations of causative genes, SLC12A3 and CETP, respectively. These two genes are located in the vicinity on chromosome 16, suggesting the possibility of autozygosity. This is the first case report highlighting the co-existence of these genetic disorders.
Polycystic ovary syndrome (PCOS) and Graves' disease are the common causes of menstrual irregularity leading to infertility in women of child-bearing age. A 21-year-old female patient visited us with complaints of oligomenorrhea and hand tremor. She was diagnosed as having PCOS and hyperthyroid Graves' disease, simultaneously. She had low body weight (BMI: 16.4 kg/m2), mild hirsutism, and thyrotoxicosis. The patient was treated with anti-thyroid drug and beta-blocker for about two years, and then recovered to normal thyroid function. Although some studies have suggested a connection between PCOS and autoimmune thyroiditis, no study indicated that PCOS is associated with Graves' disease until now. Here, we describe the first case report of a lean woman with normal insulin sensitivity presenting PCOS and Graves' disease simultaneously.
A 66-year-old woman rheumatoid arthritis was treated with methotrexate and tocilizumab. Chest radiography revealed bilateral consolidation of an upper lesion in the lung. Laboratory data indicated a hepatic disorder and increased eosinophils. Transbronchial lung biopsy specimens showed organizing pneumonia. Infection was unfavorable based on culture and PCR. Drug lymphocyte stimulation test showed positive results both for methotrexate and tocilizumab. We were concerned that her pneumonitis was drug-induced. And the symptoms appeared after the infusion of tocilizumab. Here, we report a case of tocilizumab-induced organizing pneumonia.
A 60-year-old man was admitted to our hospital complaining of general malaise. Examination of arterial blood gases on room air revealed hypoxia. Pulmonary function test showed restrictive abnormality. Chest high-resolution CT showed diffuse mosaic attenuation without evident pulmonary artery abnormality on contrast chest CT. Based on these findings, interstitial pneumonia or chronic pulmonary thromboembolism was suspected. The findings of bronchoalveolar lavage revealed 4.4×105 cells/mL, including 89.6% macrophages, 9.4% lymphocytes, and 1.0% neutrophils. TBLB showed marked alveolitis. Moreover video-assisted thoracoscopic surgical biopsy was performed. Biopsies of the lung specimen showed focal infarct with surrounding mild mononuclear cell infiltrates (homogenous cellular alveolitis). 99mTc pulmonary perfusion and 81mKr ventilation scintigraphy showed V/Q mismatch. Furthermore, pulmonary angiography also revealed inadequate artery flow corresponding to the mismatch area of scintigraphy. Collagen vascular diseases and abnormality of coagulation factors were not detected. Multiple perfusion defects persisted for more than 6 months. Thus, finally the patient was diagnosed with chronic pulmonary thromboembolism, pathologically showing homogenous cellular alveolitis.
A 64-year-old woman was referred to our center presenting with thirst, malaise, and pain in both legs which occurred one week before admission. She was revealed to have hyperglycemia and diabetic ketoacidosis (DKA). After therapy for diabetic ketoacidosis was started, her blood glucose levels were improved, but urinary ketone body excretion persisted. Laboratory examination indicated a significant impairment of insulin secretion, although anti-GAD and anti-IA-2 antibody were not detected. After admission, she complained about weakness of lower extremities, which spread to her upper extremities. The diagnosis of Guillain-Barré syndrome (GBS) was made based on the nerve conduction study and cerebrospinal fluid analysis. The intravenous immunoglobulin therapy was started, and her muscle weakness showed gradual improvement. Although the possibility that GBS was casually accompanied with DKA could not be completely excluded, we considered that DKA triggered the development of GBS in this case. Although GBS is a rare condition, the present case suggests that GBS should be included in the differential diagnosis of DKA with its atypical course.
Pachydermoperiostosis (PDP) is a rare disorder of bone and connective tissue growth. A 21-year-old man was referred to our hospital with anemia. He showed characteristics of PDP. Bone marrow biopsy showed myelofibrosis. Chromosomal abnormalities or JAK2 mutation were not found. Anemia gradually progressed, and he became transfusion-dependent. Oral prednisolone was initiated; it gradually improved his anemia and rendered the patient free of transfusion. However, other clinical symptoms such as clubbed fingers and skin hypertrophy remained unimproved. In this case, the serum concentration of vascular endothelial growth factor and transforming growth factor-β levels were increased. Further investigation will be necessary to establish appropriate treatment strategies for this disease.
We report a 47-year-old man with acute leukemia who survived a severe case of necrotizing fasciitis caused by Clostridium perfringens involving his right upper extremity. On day 5 after stem cell transplantation, progressive local tissue necrosis led to septicemia and disseminated intravascular coagulation. Early diagnosis and prompt initiation of appropriate therapy, including surgical debridement and broad-spectrum antibiotics, were crucial. A recombinant thrombomodulin might have not only resolved the coagulation problem but also prevented multiple organ failure associated with the systemic inflammatory response.
We report a patient with rheumatoid arthritis (RA) who developed leukoencephalopathy while being treated with low-dose methotrexate (MTX). She suddenly developed loss of recent memory and left homonymous hemianopsia ascribable to the bilateral but right-predominant occipitotemporal lesions. Intravenous administration of dexamethasone and cessation of MTX quickly relieved her clinical symptoms. Low-dose MTX-induced leukoencephalopathy is a rare complication in RA, but is important with regard to the possibility of serious neurological sequellae.
The present report describes two patients with leprous neuropathy diagnosed in Japan and manifesting with different clinical features. A 78-year-old Japanese man presented with a 3-year history of numbness and weakness affecting the upper and lower extremities. Although he did not have skin eruptions, nerve biopsy revealed acid-fast bacilli. Another patient, a 41-year-old Japanese-Brazilian man, presented with a 1-month history of numbness in the right fourth and fifth fingers and whole-body erythema. These cases highlight the fact that, as a result of worldwide travel and immigration, leprosy should still be considered in the differential diagnosis of neuropathy in developed countries.
Nontuberculous mycobacterium (NTM) is an infrequent cause of prosthetic knee joint infections. Simultaneous infection with different NTM species in a prosthetic knee joint has not been previously reported. A case of prosthetic knee joint infection caused by Mycobacterium abscessus and M. fortuitum is described in this report. The patient was successfully treated with adequate antibiotics and surgery. The clinical features of sixteen previously reported cases of prosthetic knee joint infection caused by NTM are reviewed.
Pulmonary infection after a tsunami is often polymicrobial and tends to form chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a combined pulmonary infection of Legionella and multiple antibiotic-resistant Escherichia coli in a previously well 75-year-old woman following immersion in tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region Pacific Coast Earthquake of 2011. She needed drainage several times and the long-term use of multiple antibiotics according to the type of bacteria found and antibiotic susceptibility. We should be mindful of infections caused by multiple pathogens in the environment in Japan as a consequence of a tsunami disaster.