From human neuroblastoma-derived SILA cells we have established a -0 cell line that is deficient in both respiration and mitochondrial DNA. Lactate dehydrogenase activity, lactate production, and growth in the medium without glucose indicate that these cells shift from aerobic to anaerobic metabolism. Electron microscopic observations revealed abnormal mitochondria with unique cristae structures. Staining with MitoTracker dye showed that the mitochondrial transmembrane potential was reduced by 30 -40% from the parent cell levels. These cells were markedly susceptible to H 2 O 2 and died apparently by a necrotic mechanism, a process blocked by deferoxamine in the parent cells but not -0 cells. Analysis by inductively coupled plasmamass spectrometry revealed an approximately 3-fold accumulation of iron in the -0 cells at confluence (n ‫؍‬ 4 -6, three clones, *p < 0.05). Iron and four other metals were all elevated in the cells of one of the -0 clones and were similar to control levels in the control cybrid cells, which were replenished with normal mitochondrial DNA. Their sensitivity to H 2 O 2 was also similar to that of the parent cells. These results indicate that a newly established neuronal related -0 cell line is highly susceptible to active oxygen species and that these toxicity effects appear to be related to an accumulation of transition metals, which probably occurs through the respiratory impairment.Iron and other transition metals exacerbate and in some cases initiate the degeneration of neurons (e.g. 1-3) through the Fenton reaction (4). In the brain of patients with Alzheimer's disease (AD), 1 an increase in the content of iron (5-9) and aluminum (4, 7) has been reported, and treatment of AD patients with iron chelators has been discussed (10). In the brain of patients with Parkinson's disease and Huntington's disease, iron and other metals also appear to accumulate (8,11). It is important to note that all of these diseases show mitochondrial abnormalities to some extent (12-19), suggesting a coupling of metal accumulation with mitochondrial deficiency. More direct evidence of mitochondrial and iron association in neurodegenerative disorders comes from an increase in mitochondrial iron in the fibroblasts of patients with Friedreich's ataxia, whose responsible gene is the mitochondrial frataxin (3,20,21). It would also be intriguing to uncover an association of mitochondrial respiratory deficiency and cell death with an accumulation of metals because a new, pivotal, regulatory role for mitochondria in cell survival and death has emerged from a growing body of evidence (for a review, see Ref. 22).We considered mtDNA-depleted (rho)-0 cells (23) to be a useful cellular model in an analysis of the consequences of chronic mitochondrial impairment and decreased respiration. These cells have served as a recipient for diseased mtDNAs (13,24,25) and are a valuable cellular tool for analyzing the coupling between cellular phenotypes and chronic respiratory deficiency (26 -28) and for searching for genes couple...

A 66-year-old man with a several year history of thrombocytopenia, pleural effusion and ascites, anasarca, and organomegaly presented with general fatigue, appetite loss, dyspnea with type II respiratory failure. The precise history of the patient and the re-evaluation of lymph node and bone marrow biopsies conducted by the previous physician indicated TAFRO syndrome. The patient's laboratory data improved for a year with tocilizumab, but then worsened to the point that the patient required artificial ventilation due to the deterioration of type II respiratory failure. The replacement of tocilizumab with rituximab yielded a steady improvement, but it was necessary to address the patient's persistent respiratory failure. Peripheral nerve disorder might have been involved with the patient's respiratory failure.

Objective This study aimed to evaluate the effects of establishing a Department of General Internal Medicine (DGIM) on the length of hospitalization. We evaluated the length of hospitalization associated with diseases for which full-time specialists were not available and were instead treated by physicians of the DGIM after its establishment. Methods A retrospective cohort study was conducted with a review of the subjects' medical records. The subjects included patients ! 16 years of age who were hospitalized with pneumonia or cerebral infarction and treated by a physician with a specialty in internal medicine as the disease outside their specialty prior to DGIM establishment (October 1, 2006 to September 30, 2008 or by a physician of the DGIM after its establishment (October 1, 2009 to September 30, 2011). The primary outcome was the change in the length of hospitalization. The length of hospitalization for heart failure, which was treated by specialists (cardiologists) in both study periods, was also examined for comparison. Results We evaluated 322 and 423 cases of pneumonia treated before and after the establishment of the DGIM, as well as 223 and 229 cases of cerebral infarction and 132 and 206 cases of heart failure, respectively. The length of hospitalization before and after establishment of the DGIM was 21.6 and 16.0 days for the pneumonia patients (p<0.001) and 24.2 and 19.9 days for the cerebral infarction patients (p<0.001), respectively. On the other hand, the change in the length of hospitalization for the heart failure patients was not statistically significant (19.9 vs. 17.6 days; p=0.281). Conclusion The establishment of the DGIM reduced the length of hospitalization associated with diseases for which full-time specialists were not available by over 17%.

BackgroundVarious types of medical institutions perform treatments for lower respiratory tract infections. However, few studies have assessed and compared practice patterns across different medical institutions in Japan. To assess practice patterns for community-acquired lower respiratory tract infections among patients who needed hospitalization, we examined the use of injection antibiotics and the implementation of bacteriological examinations, and compared these across medical institutions. We then evaluated whether bacteriological examinations were being adequately implemented.MethodsA cross-sectional study was conducted using a database of health insurance claims. Subjects were patients (≥16 years old) who received injection antibiotics to treat lower respiratory tract infections, and who were listed among 2004–2007 insurance claims data. For each type of antibiotic, we obtained the dose prescribed, the number of patients treated, and the frequency of bacteriological examinations.ResultsA total of 1649 patients were evaluated. The implementation rate of Gram stain and sputum culture was 14% at clinics (<20 beds), approximately 30% at small hospitals (20–99 beds), and 40%–45% at medium-sized (100–499 beds) and large hospitals (≥500 beds). As a whole, beta-lactams were most frequently used, accounting for 80% of all antibiotics used. Among beta-lactams, penicillins comprised 25% of the total amount of drugs used at hospitals with ≥300 beds, but approximately 13% at clinics and small hospitals.ConclusionPractice patterns varied depending on the size of the medical institution. The implementation rate of bacteriological examinations was not high enough, especially at clinics and small hospitals.

Background Few studies have investigated the relationship between lower‐jaw mobility and oral ingestible food texture choices in elderly patients. This study aimed to evaluate whether lower‐jaw mobility affects levels of food texture modification. Methods This prospective cohort study targeted inpatients aged ≥65 years with pneumonia or urinary tract infection from August 2014 through July 2015. We defined “lower‐jaw mobility” as movement of the lower jaw (more than about 1 cm) when gently supported from both sides of the mandibular angle with index fingers. The primary outcome was food texture at discharge, which was evaluated using “Japanese Dysphagia Diet 2013”: non per os, codes 0‐4 (in the order of increasing swallowing difficulty), and normal meal. Results We evaluated 38 patients in the mobility group (mean age: 86.5 years) and 251 patients in the nonmobility group (mean age: 83.2 years). Percentages of patients capable of ingesting each food texture were as follows (mobility vs nonmobility): normal meal, 5.3% vs 50.1%; code 4, 39.5% vs 31.9%; code 3, 5.3% vs 8.8%; code 2, 10.5% vs 4.4%; code 1, 2.6% vs 0.8%; code 0, 0.0% vs 0.4%; and non per os, 36.8% vs 2.8%. Food texture codes were lower in the mobility group ( P < 0.001). These relationships remained significant even after adjusting for potential confounding factors in multivariate analysis ( P < 0.001). Conclusion Elderly patients with lower‐jaw mobility were restricted to texture‐modified foods. Lower‐jaw mobility can be assessed easily even by nonmedical personnel, and regular assessment could help identify elderly patients requiring dietary adjustment.

Objectives Since patients with stroke frequently develop bladder dysfunction, a careful approach is required to reduce unnecessary indwelling urinary catheter (IUC) for preventing catheter‐associated urinary tract infection (CAUTI). This study aimed to assess the effectiveness and safety of a program to promote appropriate IUC use in stroke care. Methods We conducted a prospective interrupted time series study in three tertiary care hospitals in Japan. Adult patients with acute stroke were eligible. The study consisted of three phases: baseline, education and implementation. Our program included an assessment of IUC indications, educational meetings among healthcare professionals, reminders for removal of inappropriate IUC and a urinary retention protocol. The primary outcome was the proportion of inappropriate IUC use to assess effectiveness. The device utilization ratio and incidence of CAUTI were examined to assess effectiveness, and incidences of urinary retention and all symptomatic urinary tract infection (UTI) were examined to assess safety. Results Among 976 patients who met the inclusion criteria, 738 were analysed. Inappropriate IUC use decreased from 50.1% in the baseline phase to 22.5% in the implementation phase (absolute risk reduction in interrupted time series analysis 42.4% [95% confidence interval, 19.2%–65.6%]). The device utilization ratio decreased from 0.302 to 0.194 (p < 0.001), whereas CAUTI did not change significantly (from 8.81 to 8.28 per 1000 catheter‐days; incidence rate ratio 0.95 [0.44–1.94]). All symptomatic UTI decreased from 9.5% to 4.9% (p = 0.015), with no increase in urinary retention. Conclusions Our program improved the appropriateness of IUC use in stroke care while ensuring safety.

A 21-year-old man twice developed sudden dyspnea during running examinations for promotion. Chest computed tomography (CT) revealed lobular ground-glass opacity and centrilobular shadows bilaterally. The bronchoscopy findings were consistent with alveolar hemorrhage, and echocardiography showed severe hypokinesia a few hours later. A mass was subsequently identified along the abdominal aorta on enhanced CT and iodine-131 metaiodobenzylguanidine scintigraphy. Catecholamine oversecretion, which was later confirmed, may have increased the pulmonary vein pressure, thus resulting in the development of an alveolar hemorrhage, and damaged the cardiac muscles as manifested by hypokinesia. Since the patient had not previously developed alveolar hemorrhage during usual exercise, emotional stress superimposed on the physical activity may have triggered the paraganglioma to secrete excessive catecholamines, thus resulting in the observed symptoms.

Introduction: Few studies have evaluated serum phosphate levels in patients with Legionella pneumonia admitted to hospitals in Japan. This study aimed to assess serum phosphate levels among inpatients with Legionella pneumonia on admission and compare them to those of inpatients with non-Legionella community-acquired pneumonia. Methods: This case-control study included patients aged ≥16 years who were treated for Legionella pneumonia from April 2011 through March 2017 and those aged ≥16 years who were treated for non-Legionella community-acquired pneumonia from August 2014 through July 2015. Legionella pneumonia was diagnosed based on a positive result on the urinary antigen test, as well as radiographic examinations. Serum phosphate levels on admission were compared between Legionella and non-Legionella patients. In addition, serum phosphate levels on admission and on hospital day 5–7 were compared in Legionella patients. Results: We evaluated 8 Legionella patients and 61 non-Legionella patients. Median serum phosphate levels on admission were 1.90 and 2.80 mg/dL in Legionella and non-Legionella patients, respectively ( P = 0.008). By hospital day 5–7, serum phosphate levels in Legionella patients had increased to 2.61 mg/dL ( P = 0.029, relative to admission), which did not significantly differ from those of non-Legionella patients on admission ( P = 0.372). Conclusion: Serum phosphate levels on admission were approximately 32% lower in Legionella pneumonia patients compared to non-Legionella pneumonia patients, but both were comparable by hospital day 7.