Association between number of institutions with coronary computed tomography angiography and regional mortality ratio of acute myocardial infarction: a nationwide ecological study using a spatial Bayesian model.

BACKGROUND: Coronary computed tomography angiography (CTA) has demonstrated high diagnostic accuracy for detection of coronary artery stenosis, and healthcare providers can detect coronary artery disease in earlier stages before it develops into more serious clinical conditions such as acute myocardial infarction (AMI). We hypothesized that the mortality ratio of AMI in regions with a higher density of coronary CTA is lower than that in regions with a lower density of coronary CTA. METHODS: This ecological and cross-sectional study using secondary data targeted all secondary medical service areas (SMSAs) in Japan (n = 349). We obtained the numbers of cardiologists, institutions with coronary CTA, and institutions with a cardiac catheterization laboratory (CCL) as medical resources, socioeconomic factors, lifestyle factors, exercise habit factors, and AMI mortality data from a Japanese national database. We evaluated the association between the number of these medical resources and the standardized mortality ratio (SMR) of AMI in each SMSA using a hierarchical Bayesian model accounting for spatial autocorrelation (i.e., a conditional autoregressive model). We assumed a Poisson distribution for the observed number of AMI-related deaths and set the expected number of AMI-related deaths as the offset variable. RESULTS: The number of institutions with coronary CTA was negatively and significantly associated with the SMR of AMI (relative risk [RR] 0.900; 95% credible interval [CI] 0.848-0.953), while the SMR in each SMSA was not significantly associated with the number of either cardiologists (RR 0.997; 95% CI 0.988-1.004) or institutions with a CCL (RR 1.026; 95% CI 0.963-1.096). CONCLUSIONS: We observed a significant association between the number of institutions with coronary CTA and the SMR of AMI. Effective allocation of coronary CTA in each region is recommended, and it would be important to clarify the standing position of coronary CTA in regional networking for AMI treatment in the future.

Board certification and urban-rural migration of physicians in Japan.

BACKGROUND: The board certification system serves as a quality assurance system for physicians, and its design and operation are important health policy issues. In Japan, board certification was established and operated independently by academic societies and has not been directly linked to reimbursement systems. The phenomenon of younger physicians seeking specialist careers has raised concerns about acceleration of the tendency of fewer physicians working in rural areas and the maldistribution of physicians. Little is known about the associations between physicians' geographical migration patterns and board certification status changes or between the continuation of urban/rural practice and the maintenance of board certification. This study aimed to identify these associations and to discuss their policy implications. METHODS: We analyzed 2012 and 2014 data from the Survey of Physicians, Dentists, and Pharmacists, a national census survey. To analyze geographical migration patterns, transitions in practice location (rural, intermediate, and urban) were analyzed by board certification status change (new, lost, consistently certified, and consistently uncertified). Logistic regression analysis was conducted to assess whether the odds of migrating to more urban/rural municipalities were associated with board certification status changes, adjusting for covariates, and whether practicing in a rural area was associated with maintaining board certification. RESULTS: Among 18,726 newly board-certified physicians, 94.9% (13,435/14,150) of those working in urban areas before certification remained in urban areas, whereas 64.6% (393/608) of those working in rural areas stayed in rural areas. Those who were newly certified had higher odds of moving to more urban areas, adjusting for covariates. Those who stayed in rural areas showed lower odds of maintaining board certification, adjusting for covariates. CONCLUSIONS: Newly board-certified physicians are more likely to migrate to other types of areas, particularly more urban areas, than other physicians. Allocating more training quotas to rural areas could be one option for leveling the distribution of specialists. It also appeared that those practicing in rural areas have difficulty maintaining their certification, so the need to establish a support system for already-certified physicians in rural areas should be emphasized.

Internal medicine board certification and career pathways in Japan.

BACKGROUND: Establishing and managing a board certification system is a common concern for many countries. In Japan, the board certification system is under revision. The purpose of this study was to describe present status of internal medicine specialist board certification, to identify factors associated with maintenance of board certification and to investigate changes in area of practice when physicians move from hospital to clinic practice. METHODS: We analyzed 2010 and 2012 data from the Survey of Physicians, Dentists and Pharmacists. We conducted logistic regression analysis to identify factors associated with the maintenance of board certification between 2010 and 2012. We also analyzed data on career transition from hospitals to clinics for hospital physicians with board certification. RESULTS: It was common for physicians seeking board certification to do so in their early career. The odds of maintaining board certification were lower in women and those working in locations other than academic hospitals, and higher in physicians with subspecialty practice areas. Among hospital physicians with board certification who moved to clinics between 2010 and 2012, 95.8% remained in internal medicine or its subspecialty areas and 87.7% maintained board certification but changed their practice from a subspecialty area to more general internal medicine. CONCLUSION: Revisions of the internal medicine board certification system must consider different physician career pathways including mid-career moves while maintaining certification quality. This will help to secure an adequate number and distribution of specialists. To meet the increasing demand for generalist physicians, it is important to design programs to train specialists in general practice.

Application of quantum computing to a linear non-Gaussian acyclic model for novel medical knowledge discovery.

Recently, the utilization of real-world medical data collected from clinical sites has been attracting attention. Especially as the number of variables in real-world medical data increases, causal discovery becomes more and more effective. On the other hand, it is necessary to develop new causal discovery algorithms suitable for small data sets for situations where sample sizes are insufficient to detect reasonable causal relationships, such as rare diseases and emerging infectious diseases. This study aims to develop a new causal discovery algorithm suitable for a small number of real-world medical data using quantum computing, one of the emerging information technologies attracting attention for its application in machine learning. In this study, a new algorithm that applies the quantum kernel to a linear non-Gaussian acyclic model, one of the causal discovery algorithms, is developed. Experiments on several artificial data sets showed that the new algorithm proposed in this study was more accurate than existing methods with the Gaussian kernel under various conditions in the low-data regime. When the new algorithm was applied to real-world medical data, a case was confirmed in which the causal structure could be correctly estimated even when the amount of data was small, which was not possible with existing methods. Furthermore, the possibility of implementing the new algorithm on real quantum hardware was discussed. This study suggests that the new proposed algorithm using quantum computing might be a good choice among the causal discovery algorithms in the low-data regime for novel medical knowledge discovery.

Impact of a Clinical Text-Based Fall Prediction Model on Preventing Extended Hospital Stays for Elderly Inpatients: Model Development and Performance Evaluation.

BACKGROUND: Falls may cause elderly people to be bedridden, requiring professional intervention; thus, fall prevention is crucial. The use of electronic health records (EHRs) is expected to provide highly accurate risk assessment and length-of-stay data related to falls, which may be used to estimate the costs and benefits of prevention. However, no studies to date have investigated the extent to which hospital stays could be shortened through fall avoidance resulting from the use of prediction tools. OBJECTIVE: We first estimated the extended length of hospital stay caused by falls among elderly inpatients. Next, we developed a model that predicts falls using clinical text as input and evaluated its accuracy. Finally, we estimated the potentially shortened hospital stay that would be made possible by appropriate interventions based on the prediction model. METHODS: Patients aged 65 years or older were selected as subjects, and the EHRs of 1728 falls and 70,586 nonfalls were subjected to analysis. The extended-stay lengths were estimated using propensity score matching of 49 associated variables. Bidirectional encoder representations from transformers and bidirectional long short-term memory methods were used to predict falls from clinical text. The estimated length of stay and the outputs of the prediction model were used to determine stay reductions. RESULTS: The extended length of hospital stay due to falls was estimated to be 17.8 days (95% CI 16.6-19.0), which dropped to 8.6 days when there were unobserved covariates at an odds ratio of 2.0. The accuracy of the prediction model was as follows: area under the receiver operating characteristic curve, 0.851; F-value, 0.165; recall, 0.737; precision, 0.093; and specificity, 0.839. When assuming interventions with 25% or 100% effectiveness against cases where the model predicted a fall, the stay reduction was estimated at 0.022 and 0.099 days/day, respectively. CONCLUSIONS: The accuracy of the prediction model using clinical text is considered to be higher than the prediction accuracy of conventional assessments. However, our model's precision remained low at 9.3%. This may be due, in part, to the inclusion of cases in which falls did not occur because of preventative interventions during hospitalization. Nonetheless, it is estimated that interventions for cases when falls were predicted will reduce medical costs by 886 Yen/day (~US $6.50/day) of intervention, even if the preventative effect is 25%. Limitations include the fact that these results cannot be extrapolated to short- or long-term hospitalization cases, and that this was a single-center study.

Increased motility and invasiveness in tumor cells that survive 10 Gy irradiation.

Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin beta1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.

Transcription factor 8 activates R-Ras to regulate angiogenesis.

We have recently reported that transcription factor 8 (TCF8) negatively regulates pathological angiogenesis by regulating endothelial invasiveness by acting as a transcriptional attenuator of matrix metalloproteinase 1. TCF8 also modulates cell-matrix and cell-cell adhesion; however molecular mechanism of this TCF8 function remains obscure. Here, we provide evidence that TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator. Tube formation by human umbilical vein endothelial cells (HUVECs) facilitated by TCF8 suppression was significantly inhibited by the expression of constitutive active mutant of R-Ras. When we examined the mRNA expression levels of R-Ras regulators, no significant changes were observed to explain the R-Ras activation by TCF8. Interestingly, we found that TCF8 bound to CalDAG-GEFIII, an R-Ras activator, in the cytosol, indicating that TCF8 emanates signaling for R-Ras activation from cytosol to regulate angiogenesis negatively.

Facility and Regional Factors Associated With the New Adoption of Electronic Medical Records in Japan: Nationwide Longitudinal Observational Study.

BACKGROUND: The rate of adoption of electronic medical record (EMR) systems has increased internationally, and new EMR adoption is currently a major topic in Japan. However, no study has performed a detailed analysis of longitudinal data to evaluate the changes in the EMR adoption status over time. OBJECTIVE: This study aimed to evaluate the changes in the EMR adoption status over time in hospitals and clinics in Japan and to examine the facility and regional factors associated with these changes. METHODS: Secondary longitudinal data were created by matching data in fiscal year (FY) 2011 and FY 2014 using reference numbers. EMR adoption status was defined as "EMR adoption," "specified adoption schedule," or "no adoption schedule." Data were obtained for hospitals (n=4410) and clinics (n=67,329) that had no adoption schedule in FY 2011 and for hospitals (n=1068) and clinics (n=3132) with a specified adoption schedule in FY 2011. The EMR adoption statuses of medical institutions in FY 2014 were also examined. A multinomial logistic model was used to investigate the associations between EMR adoption status in FY 2014 and facility and regional factors in FY 2011. Considering the regional variations of these models, multilevel analyses with second levels were conducted. These models were constructed separately for hospitals and clinics, resulting in four multinomial logistic models. The odds ratio (OR) and 95% Bayesian credible interval (CI) were estimated for each variable. RESULTS: A total of 6.9% of hospitals and 14.82% of clinics with no EMR adoption schedules in FY 2011 had adopted EMR by FY 2014, while 10.49% of hospitals and 33.65% of clinics with specified adoption schedules in FY 2011 had cancelled the scheduled adoption by FY 2014. For hospitals with no adoption schedules in FY 2011, EMR adoption/scheduled adoption was associated with practice size characteristics, such as number of outpatients (from quantile 4 to quantile 1: OR 1.67, 95% CI 1.005-2.84 and OR 2.40, 95% CI 1.80-3.21, respectively), and number of doctors (from quantile 4 to quantile 1: OR 4.20, 95% CI 2.39-7.31 and OR 2.02, 95% CI 1.52-2.64, respectively). For clinics with specified EMR adoption schedules in FY 2011, the factors negatively associated with EMR adoption/cancellation of scheduled EMR adoption were the presence of beds (quantile 4 to quantile 1: OR 0.57, 95% CI 0.45-0.72 and OR 0.74, 95% CI 0.58-0.96, respectively) and having a private establisher (quantile 4 to quantile 1: OR 0.27, 95% CI 0.13-0.55 and OR 0.43, 95% CI 0.19-0.91, respectively). No regional factors were significantly associated with the EMR adoption status of hospitals with no EMR adoption schedules; population density was positively associated with EMR adoption in clinics with no EMR adoption schedule (quantile 4 to quantile 1: OR 1.49, 95% CI 1.32-1.69). CONCLUSIONS: Different approaches are needed to promote new adoption of EMR systems in hospitals as compared to clinics. It is important to induce decision making in small- and medium-sized hospitals, and regional postdecision technical support is important to avoid cancellation of scheduled EMR adoption in clinics.

PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling.

Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer.

Regional differences in electronic medical record adoption in Japan: A nationwide longitudinal ecological study.

PURPOSE: Regional differences in the adoption of electronic medical records (EMR) are a major problem, yet little is known about these differences internationally. We analyzed regional differences in EMR adoption in Japan and evaluated factors associated with these differences. METHODS: This nationwide ecological study used secondary data from all secondary medical service areas (SMSAs) in fiscal years 2008 (n = 348) and 2014 (n = 344). For each SMSA we collected the following information from a Japanese national database: the number of medical facilities that had adopted EMR, the population density, the average per capita income, the number of working doctors per 1000 people, and the proportion of interns to all working doctors. To adjust for medical facility characteristics in each SMSA, such as number of beds, public versus private hospital, and hospital type (psychiatric or other), we estimated the standardized adoption ratio (SAR) for EMR adoption, modeled on the standardized mortality ratio. We calculated Moran's I for the SAR and investigated whether the SAR had spatial autocorrelations. We evaluated the association between the SAR and regional factors with a conditional autoregressive model. We compared these results in 2008 and 2014, for both hospitals and clinics. RESULTS: While the EMR adoption rate in SMSAs increased, Moran's I of the SAR in hospitals was close to 1 in both 2008 and 2014, and Moran's I of the SAR in clinics increased from 2008 to 2014. For hospitals, there was a significant association between the proportion of interns to all working doctors and the SAR only in 2008. For clinics, average income in the SMSA was positively associated with the SAR, whereas the number of working doctors was negatively associated with the SAR in both 2008 and 2014. Population density was positively associated with the SAR only in 2014. CONCLUSION: From 2008 to 2014, EMR adoption in Japan generally increased, but geographical differences did not improve. Regional factors associated with the SAR were different for hospitals than for clinics. Therefore, the government should take different approaches for clinics and hospitals to improve regional differences in EMR adoption, especially in providing financial and technical support.

Evaluation of cognitive and social functioning in patients requiring long-term inpatient psychiatric care using the International Classification of Functioning, Disability, and Health: a large-scale, multi-institutional observational study.

PURPOSE: We comprehensively evaluated cognitive and social functioning in patients requiring long-term inpatient psychiatric care using the International Classification of Functioning, Disability, and Health. METHOD: We surveyed 1967 patients receiving long-term inpatient psychiatric care. Patients were further categorized into an old long-stay group (n = 892, >5 years in hospitals) and a new long-stay group (n = 1075, 1-5 years in hospitals). We obtained responses for all the International Classification of Functioning, Disability, and Health items in domain b (Body Functions) and domain d (Activities and Participation). We estimated weighted means for each item using the propensity score to adjust for confounding factors. RESULTS: Responses were received from 307 hospitals (response rate of hospitals: 25.5%). Cognitive and social functioning in the old long-stay group was more severely impaired than in the new long-stay group. No statistically significant differences were observed regarding the International Classification of Functioning, Disability, and Health items associated with basic activities of daily living between the two groups. CONCLUSION: Combined therapy consisting of cognitive remediation and rehabilitation on social functioning for this patient population should be started from the early stage of hospitalization. Non-restrictive, independent environments may also be optimal for this patient population. Implications for rehabilitation Rehabilitation of cognitive and social functioning for patients requiring long-term inpatient psychiatric care should be started in the early stages of hospitalization. In psychiatric fields, the International Classification of Functioning, Disability, and Health checklist could facilitate individualized rehabilitation planning by allowing healthcare professionals to visually assess the comprehensive functioning of each patient using graphics such as radar charts.

A stable pulsed power supply for multi-beamline XFEL operations.

Since an X-ray Free Electron Laser (XFEL) facility is a linac-based single-user machine, a multi-beamline mode of operation, which improves the efficiency of user experiments, is critical for accommodating users' rapidly increasing demand for beamtime. A key supporting technology is a highly stable pulsed power supply (PS), which enables stable XFEL operations by precisely switching the beam route. We developed a high-power pulsed PS to drive a kicker magnet installed in a SACLA's beam switching system. SiC MOSFETs were adapted as switching elements to reduce the required size and to increase the electric power efficiency. The PS we developed provides two key capabilities: (i) a high current stability of 20 ppm (peak-to-peak) at a peak power of 0.24 MW and (ii) generation of controllable, bipolar, and trapezoidal current waveforms at 60 Hz. This paper describes the overall concept, the detailed design, the performance achieved, and the initial beam test results.

Association between the Density of Physicians and Suicide Rates in Japan: Nationwide Ecological Study Using a Spatial Bayesian Model.

BACKGROUND: Regional disparity in suicide rates is a serious problem worldwide. One possible cause is unequal distribution of the health workforce, especially psychiatrists. Research about the association between regional physician numbers and suicide rates is therefore important but studies are rare. The objective of this study was to evaluate the association between physician numbers and suicide rates in Japan, by municipality. METHODS: The study included all the municipalities in Japan (n = 1,896). We estimated smoothed standardized mortality ratios of suicide rates for each municipality and evaluated the association between health workforce and suicide rates using a hierarchical Bayesian model accounting for spatially correlated random effects, a conditional autoregressive model. We assumed a Poisson distribution for the observed number of suicides and set the expected number of suicides as the offset variable. The explanatory variables were numbers of physicians, a binary variable for the presence of psychiatrists, and social covariates. RESULTS: After adjustment for socioeconomic factors, suicide rates in municipalities that had at least one psychiatrist were lower than those in the other municipalities. There was, however, a positive and statistically significant association between the number of physicians and suicide rates. CONCLUSIONS: Suicide rates in municipalities that had at least one psychiatrist were lower than those in other municipalities, but the number of physicians was positively and significantly related with suicide rates. To improve the regional disparity in suicide rates, the government should encourage psychiatrists to participate in community-based suicide prevention programs and to settle in municipalities that currently have no psychiatrists. The government and other stakeholders should also construct better networks between psychiatrists and non-psychiatrists to support sharing of information for suicide prevention.

Can exercise training with weight loss lower serum C-reactive protein levels?

OBJECTIVE: C-reactive protein (CRP), an obesity-related inflammatory marker, is a promising predictor for cardiovascular disease and may be a mediator for atherogenesis. It has been reported that diet-induced weight loss lowered CRP levels. However, the effect of exercise training, another therapy that can reduce weight, on CRP is still unclear. We examined effects of exercise training with weight loss on CRP levels and conventional cardiovascular risks. METHODS AND RESULTS: A total of 227 apparently healthy women were recruited, and 199 subjects (average age 52 years) completed a 2-month weight reduction program consisting of supervised aerobic exercises. After the program, weight was reduced from 65.8 to 62.8 kg (P<0.0001), and all conventional variables were remarkably improved. Similarly, CRP levels were significantly decreased, from 0.63 (0.28 to 1.19) to 0.41 (0.18 to 0.80) mg/L (P<0.0001). However, in contrast to other variables, the changes in CRP levels were not proportionally associated with the extent of weight reduction. In the quartile analysis of % weight reduction, the largest weight reduction quartile did not show significant decreases in CRP levels, whereas moderate quartile showed remarkable CRP decreases. CONCLUSIONS: Exercise training with weight reduction disproportionately lowered CRP levels. Considering inflammatory status, there might be an optimal pace of exercise with weight loss.

Evidence for the involvement of the cyclooxygenase-metabolic pathway in diclofenac-induced inhibition of spontaneous contraction of rat portal vein smooth muscle cells.

The effects of diclofenac, a cyclooxygenase (COX) inhibitor, were investigated on spontaneous phasic contractions of longitudinal preparations of the rat portal vein. Diclofenac produced a concentration-dependent decrease in the amplitude of these spontaneous phasic contractions. Diclofenac (30 microM) decreased the amplitude of the spontaneous phasic increase in the F340/F380 ratio of Fura PE3, an indicator of intracellular Ca2+ concentration. It also reduced the number of action potentials in each burst discharge without changing the resting membrane potential of longitudinal smooth muscle cells. The extent of the distribution of Lucifer Yellow injected into a smooth muscle cell was decreased in the presence of diclofenac (30 microM). Both AH6809, a prostanoid EP receptor antagonist, and SQ22536, an adenylate cyclase inhibitor, decreased the amplitude of the spontaneous contractions. On the other hand, neither ozagrel, a thromboxane synthase inhibitor, nor SQ29548, a prostanoid TP receptor antagonist, significantly affected spontaneous contractions. These results indicate that diclofenac inhibits the amplitude of spontaneous contractions of the rat portal vein through inhibition of electrical activity, which may be related to an inhibition of the cyclooxygenase pathway.

[In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002].

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

Gradual recovery from dyslexia and related serial magnetoencephalographic changes in the lexicosemantic centers after resection of a mesial temporal astrocytoma. Case report.

Letter-perception centers are not held in as high regard as motor- and language-related cortices during planning of neurosurgical procedures, and there have been no reports suggesting cortical reorganization of reading ability. The authors describe a patient with a left mesial temporal glioma in whom two letter-perception centers (the anterior portion of the left superior temporal gyrus and the left fusiform gyrus) were successfully localized before surgery by performing magnetoencephalography (MEG) during reading tasks. Control MEG examinations of 15 healthy volunteers were also performed to assist in a careful interpretation of patient results. Although a radical resection of the mesial temporal glioma, which involved the left fusiform gyrus, caused severe dyslexia, the patient's impaired reading skills improved gradually during a 1-year postoperative period. In the meantime, the spared left superior temporal gyrus displayed an overshot recovery of MEG responses. During the postoperative period there was no obvious recovery in MEG signals and no compensatory activity in the contralateral fusiform gyrus. This case demonstrates that lexicosemantic centers involved in the reading process can be noninvasively localized using MEG and that the results obtained are highly reliable for surgical planning. The results of the repeated MEG reflected sequentially the patient's recovery from dyslexia. This is the first report in which MEG studies have been shown to predict preoperatively the risk of dyslexia and demonstrate its serial physiological recovery.

Visualization of the eloquent motor system by integration of MEG, functional, and anisotropic diffusion-weighted MRI in functional neuronavigation.

BACKGROUND: In this study, we visualized the eloquent motor system including the somatosensory-motor cortex and corticospinal tract on a neuronavigation system, integrating magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and anisotropic diffusion-weighted MRI (ADWI). METHODS: Four patients with brain lesions adjacent to the eloquent motor system were studied. Motor-evoked responses (MER) by finger-tapping paradigm were acquired with a 1.5-Tesla MR scanner, and somatosensory-evoked magnetic fields (SEF) by median nerve stimulation were measured with a 204-channel MEG system. In the same fMRI examination, ADWI and anatomic three-dimensional T1-weighted imaging (3-D MRI) were obtained. Activated areas of MER, estimated SEF dipoles, and the corticospinal tract on ADWI were coregistered to 3-D MRI, and the combined MR data were transferred to a neuronavigation system (functional neuronavigation). Intraoperative recording of cortical somatosensory-evoked potentials was performed for confirmation of the central sulcus. RESULTS: Combination of fMRI and MEG enabled firm identification of the central sulcus. Functional neuronavigation facilitated extensive tumor resection, having the advantage of sparing the motor cortex and corticospinal tract in all cases. CONCLUSIONS: The proposed functional neuronavigation allows neurosurgeons to perform effective and maximal resection of brain lesions, identifying and sparing eloquent cortical components and their subcortical connections. Potential clinical application of this technique is discussed.

[Activities of antimicrobial agents against 8,474 clinical isolates obtained from 37 medical institutions during 2000 in Japan].

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.

Angiotensin-converting enzyme and angiotensinogen gene polymorphism in hypertrophic cardiomyopathy.

To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), the authors studied 96 patients with HCM (mean age 50 years, 55% male), 105 of their unaffected siblings and offspring, and 160 healthy subjects without known hypertension and left ventricular hypertrophy who were frequency matched by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected family members. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% versus 78%, chi(2)=4.6, P<0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% versus 12%, chi(2)=4.6, P<0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% versus 78%). The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk. The authors also determined angiotensin-converting enzyme gene insertion/deletion polymorphism. The D allele frequency was higher in SHCM than in FHCM. The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. These results also suggest that angiotensin-converting enzyme and angiotensinogen gene polymorphism are genetic contributing factors associated with cardiac hypertrophy in HCM.