The Changes in Broad-spectrum Antimicrobial Consumption during the COVID-19 Pandemic in a Japanese Acute Tertiary-care Hospital: An Interrupted Time-series Analysis.

Objective The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and hospitals in Japan have been forced to respond to the situation. This study evaluated the broad-spectrum antimicrobial use before and during the COVID-19 pandemic in an acute tertiary-care hospital. Methods This single-center, retrospective study was conducted between January 2019 and June 2021. Patients We reviewed patients treated with three broad-spectrum antipseudomonal agents: carbapenems, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1,000 patient-days, and the monthly incidences of Clostridioides difficile infection (CDI), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenemase-producing Enterobacteriaceae (CPE) were recorded. Results The median monthly carbapenem-DOTs during the pre-pandemic and pandemic era were 8.4 and 8.2 per 1,000 patient-days, respectively. A time-series analysis showed non-significant changes in the level between periods (coefficients: 2.08; 95% confidence interval [CI]: -2.9 to 7.0; p=0.44). No change in the trend of monthly carbapenem-DOTs was observed after intervention. No post-intervention changes in the incidence of MRPA or CPE were observed; however, the trend in the incidence of CDI per 1,000 patient-days significantly differed between the two periods (coefficient: -0.04; 95% CI: -0.07, 0.00; p=0.01), and a downward trend was observed in the monthly CDI incidence during the COVID-19 period. Conclusion The consumption of broad intravenous antimicrobial agents has not changed significantly during the pandemic. We need to maintain the quality of medical care, including antimicrobial stewardship, even in specialized resource-limited facilities during a pandemic.

The importance of infectious disease specialists consulting on a weekly basis in a Japanese tertiary care hospital: A retrospective observational study.

Limited data are available regarding part-time infectious disease consultations (IDCs) and their importance in tertiary care teaching hospitals in Japan. This is a retrospective review of IDCs from June 2016 to March 2021 and describes IDC services provided by part-time infectious disease specialists once a week for 4 hours, and their impact on the quality of medical care, including antimicrobial stewardship. Data, such as the requesting department, requesting reasons, and final diagnoses, were analyzed. In April 2018, part-time infectious disease specialists launched consultation services and attended an antimicrobial stewardship team conference. Meropenem, tazobactam/piperacillin, and cefepime monthly days of therapy (DOT) were calculated to assess the effect of each intervention; a pre-post analysis was conducted using the Kruskal-Wallis test. Additional quality improvement (QI) projects related to infectious diseases were implemented. There were 237 IDCs during the study period. Consultations were mostly requested by the General Internal Medicine, Emergency Medicine, and Cardiology departments. The most common diagnoses were bone/joint, respiratory, and genitourinary infections. Infectious disease services, even on a part-time basis, achieve good outcomes in patient management, antimicrobial stewardship, and QI projects. DOT/1000 patient-days were reduced for meropenem and cefepime, while it increased for tazobactam/piperacillin. The DOT/1000 patient-days for the 3-antipseudomonal agents significantly decreased during this period. After implementing the QI tetanus vaccination project in the Emergency Room, the number of tetanus toxoid vaccinations per month increased.

Impact of the antimicrobial stewardship program on hospital-acquired candidemia.

Antibiotic stewardship programs reduce antibiotic use without negative clinical outcomes. However, epidemiological data describing the relationship between implementing antimicrobial stewardship and candidemia incidence are scarce. This study aimed to evaluate the effect of antibiotic stewardship on the incidence of hospital acquired candidemia. We conducted a retrospective study from April 2017 to September 2020. We reviewed patients that were treated with three broad-spectrum antipseudomonal agents: carbapenem, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1000 patient-days, and the monthly incidence of hospital acquired candidemia was recorded. The median monthly carbapenem-DOTs during pre-intervention and intervention were 28.4 and 10.0, respectively. Time-series analysis showed significant level changes after intervention: - 10.0 DOTs (p = 0.02). There was a downward trend in the monthly carbapenem-DOTs after intervention. The median hospital-acquired candidemia incidence was 0.17 and 0.08 per 1000 patient-days during pre-intervention and intervention periods, respectively. Time-series analysis showed a significant level change after intervention (- 0.16 per 1000 patient-days; p = 0.048). The trend in the incidence of hospital-acquired candidemia did not significantly change between pre-intervention and intervention. Decreased broad-spectrum antibiotic use (particularly carbapenem) by our antimicrobial stewardship term may reduce hospital-acquired candidemia incidences.

Muscle strength is a stronger prognostic factor than muscle mass in patients with gastrointestinal and hepatobiliary pancreatic cancers.

OBJECTIVES: Sarcopenia has been reported as a prognostic risk factor in patients with gastrointestinal (GI) and hepatobiliary pancreatic (HBP) cancers. This study aimed to investigate whether the loss of muscle mass or strength is a stronger prognostic factor, and explore the cutoff values of skeletal muscle mass index (SMI) and handgrip strength (HGS) based on the survival outcome in patients with GI and HBP cancers. METHODS: A total of 480 elderly patients with primary GI and HBP cancers who underwent their first resection surgery were analyzed retrospectively. Patients were divided into four groups: Appropriate SMI and HGS, low SMI alone, low HGS alone, and low SMI and HGS. Low SMI was derived from a bioelectrical impedance analysis, and low HGS was defined according to the Asian Working Group for Sarcopenia 2019 criteria. RESULTS: The multivariate analysis showed that low SMI was a significant risk factor for mortality in men only, but low HGS was significant in both sexes. From the multivariate analysis of the four groups, low HGS alone and low SMI and HGS showed a significantly higher hazard ratio than appropriate SMI and HGS in both sexes. An SMI of 7.21 kg/m2 and HGS of 28 kg were obtained as cutoff values based on the 3-y survival outcomes in men. CONCLUSIONS: Low muscle strength was a stronger prognostic factor than low muscle mass. Therefore, measuring muscle strength in all patients is essential.

Accuracy of an Artificial Intelligence-Based Model for Estimating Leftover Liquid Food in Hospitals: Validation Study.

BACKGROUND: An accurate evaluation of the nutritional status of malnourished hospitalized patients at a higher risk of complications, such as frailty or disability, is crucial. Visual methods of estimating food intake are popular for evaluating the nutritional status in clinical environments. However, from the perspective of accurate measurement, such methods are unreliable. OBJECTIVE: The accuracy of estimating leftover liquid food in hospitals using an artificial intelligence (AI)-based model was compared to that of visual estimation. METHODS: The accuracy of the AI-based model (AI estimation) was compared to that of the visual estimation method for thin rice gruel as staple food and fermented milk and peach juice as side dishes. A total of 576 images of liquid food (432 images of thin rice gruel, 72 of fermented milk, and 72 of peach juice) were used. The mean absolute error, root mean squared error, and coefficient of determination (R2) were used as metrics for determining the accuracy of the evaluation process. Welch t test and the confusion matrix were used to examine the difference of mean absolute error between AI and visual estimation. RESULTS: The mean absolute errors obtained through the AI estimation approach were 0.63 for fermented milk, 0.25 for peach juice, and 0.85 for the total. These were significantly smaller than those obtained using the visual estimation approach, which were 1.40 (P<.001) for fermented milk, 0.90 (P<.001) for peach juice, and 1.03 (P=.009) for the total. By contrast, the mean absolute error for thin rice gruel obtained using the AI estimation method (0.99) did not differ significantly from that obtained using visual estimation (0.99). The confusion matrix for thin rice gruel showed variation in the distribution of errors, indicating that the errors in the AI estimation were biased toward the case of many leftovers. The mean squared error for all liquid foods tended to be smaller for the AI estimation than for the visual estimation. Additionally, the coefficient of determination (R2) for fermented milk and peach juice tended to be larger for the AI estimation than for the visual estimation, and the R2 value for the total was equal in terms of accuracy between the AI and visual estimations. CONCLUSIONS: The AI estimation approach achieved a smaller mean absolute error and root mean squared error and a larger coefficient of determination (R2) than the visual estimation approach for the side dishes. Additionally, the AI estimation approach achieved a smaller mean absolute error and root mean squared error compared to the visual estimation method, and the coefficient of determination (R2) was similar to that of the visual estimation method for the total. AI estimation measures liquid food intake in hospitals more precisely than visual estimation, but its accuracy in estimating staple food leftovers requires improvement.

Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and Hepatobiliary-Pancreatic Cancers.

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m2 for men and 15 kg/m2 for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival.

Hyponatremia is a Prognostic Factor in Patients Receiving Nutrition Support.

BACKGROUND: Hyponatremia, the most common electrolyte disorder, has been reported to be related to increased mortality. However, the association between hyponatremia and prognoses remains unclear in patients with nutrition support team (NST) intervention. This study aimed to determine the prevalence of abnormal serum sodium levels, its relation to patient data, and the impact of hyponatremia on prognosis. METHODS: Patients who received nutrition support at Tokushima University Hospital for the first time and whose serum sodium levels were measured at the start of NST intervention were enrolled. Patients were classified into three groups according to their serum Na levels at the start of NST intervention: hyponatremia group, normonatremia group, and hypernatremia group. RESULTS: In the hyponatremia group compared to the normonatremia group, body weight and body mass index were significantly lower. C-reactive protein levels and urea nitrogen/creatinine ratios were significantly higher. Meanwhile, there was no significant difference in the estimated glomerular filtration rate among the groups. The prevalence of malnutrition and anemia were the highest in the hyponatremia group. The 3-year survival rate was approximately 45% in the hyponatremia group, which was the lowest of all three groups. The mortality risk ratio of the hyponatremia group to the normonatremia group was 2.29. CONCLUSIONS: Hyponatremia in NST intervention patients is an independent prognostic predictor. Therefore, adding an assessment of serum sodium at the beginning of NST intervention can identify patients at high risk at an early stage and may improve the quality of NST activity.

Effects of Palonosetron on Nausea and Vomiting Induced by Multiple-Day Chemotherapy: A Retrospective Study.

Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT3 RAs) and second-generation 5-HT3 RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT3 RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT3 RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.

Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. METHODS: A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. RESULTS: The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08-2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m2 was an independent poor prognostic factor. CONCLUSIONS: EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m2 is most associated with prognosis in patients with preoperative GI and HBP cancers.

Possible Dissemination of a Panton-Valentine Leukocidin-Positive Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398 Clone in Tokyo, Japan.

In the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has been identified in livestock animals, such as swine, poultry, and veal calves, and has been termed livestock-associated MRSA (LA-MRSA). LA-MRSA sequence type (ST) 398 strains can effectively infect and colonize humans, with subsequent human-to-human transmission in both community and hospital settings. Unlike other countries, LA-MRSA had not been reported in Japanese patients until 2019. However, we recently reported a case of intractable arthritis caused by an LA-MRSA CC398 (ST1232) clone, which is a single-locus variant of ST398, in a patient in Tokyo, Japan, with no animal contact (Nakaminami H, et al. Emerg Infect Dis. 2020; 26: 795-7.). Uniquely, the strain was positive for Panton-Valentine leukocidin. Here, we report the second such case in Japan. To prevent the dissemination of LA-MRSA in the Japanese community, the prevalence of the CC398 MRSA clone should be closely monitored in the future.

Impact of phase angle on postoperative prognosis in patients with gastrointestinal and hepatobiliary-pancreatic cancer.

OBJECTIVE: Phase angle (PhA), by bioelectrical impedance analysis, has been used in patients with several diseases; however, its prognostic value in patients with gastrointestinal (GI) and hepatobiliary-pancreatic (HBP) cancer is unclear. The aim of the present study was to investigate the effects of PhA on postoperative short- outcomes and long-term survival in these patients. METHODS: This retrospective study reviewed data from 501 patients with GI and HBP cancers who underwent first resection surgery. The data were divided into the following groups according to the preoperative PhA quartile values by sex: high-PhA group with the highest quartile (Q4), normal-PhA group with middle quartiles (Q3 and Q2), and low-PhA group with the lowest quartile (Q1). Preoperative nutritional statuses, postoperative short-term outcomes during hospitalization, and 5-y survival between three groups were compared. Cox proportional hazard models were used to evaluate the prognostic effect of PhA. RESULTS: PhA positively correlated with body weight, skeletal muscle mass, and handgrip strength, and negatively correlated with age and levels of C-reactive protein. The low-PhA group showed a higher prevalence of malnutrition (48%) than normal-PhA (25%), and high-PhA groups (9%; P < 0.001). The incidence of postoperative severe complications was 10% for all patients (14% in low-PhA, 12% in normal-PhA, and 4% in high-PhA; P = 0.018). The incidence of prolonged stays in a postoperative high-care or intensive care unit was 8% in all patients (16% in low-PhA, 8% in normal-PhA, and 2% in high-PhA; P < 0.001). The 5-y survival rate was 74% in all patients (68% in low-PhA, 74% in normal-PhA, and 79% in high-PhA; P < 0.001). The multivariate analysis demonstrated that a low-PhA group was an independent risk factor for mortality (hazard ratio, 1.99; 95% confidence interval, 1.05-3.90; P = 0.034). CONCLUSION: PhA is a useful short-term and long-term postoperative prognostic marker for patients with GI and HBP cancers.

Change during an 8-Year Period in Streptococcus Pyogenes emm Types in Pharyngeal Isolates from Children with Noninvasive Infections.

BACKGROUND: Streptococcus pyogenes, or group A streptococcus (GAS), is one of the most common bacterial pathogens in children. GAS can cause such nonserious and noninvasive diseases as pharyngitis and skin infection, as well as serious, invasive diseases like streptococcal toxic shock syndrome. One factor that makes GAS pathogenic is the type-specific M protein on its cell surface. To identify emm types and their characteristics, we previously examined GAS strains isolated from children with noninvasive infections at our hospital. The present study was conducted 8 years later, for comparison. METHODS: The 23 participants were inpatients and outpatients at Nippon Medical School Tama Nagayama Hospital during 2016 and 2017. A pharyngeal swab specimen was obtained from each child, and genes encoding M proteins were amplified by polymerase chain reaction. RESULTS: emm type analysis identified emm1 in 11 of the 23 strains and emm12 in 4. Three group G streptococcus (GGS) strains carried M-like protein genes. CONCLUSIONS: The predominant emm type was emm12 in our previous report and emm1 in this study. This study also identified 3 GGS strains among the isolates, which carried either the stg245, stg6795, or stg840 M-like protein gene. One GAS strain carried stg485, a gene associated with GGS rather than GAS.

Body fat mass is correlated with serum transthyretin levels in maintenance hemodialysis patients.

Serum transthyretin (TTR), also known as prealbumin, is a reliable nutritional indicator and an independent prognostic factor for maintenance hemodialysis patients. However, we recently reported that serum TTR levels did not affect protein-energy wasting (PEW). In this study, we investigated factors affecting serum TTR levels in 60 maintenance hemodialysis patients. The patients were divided into High-TTR and Low-TTR groups according to the median serum TTR level. Albumin levels were significantly higher and C-reactive protein (CRP) levels were significantly lower in the High-TTR group than in the Low-TTR group. Although body fat mass was significantly higher in the High-TTR group than in the Low-TTR group, no significant difference in body fat ratio were observed. These findings suggest that body fat mass is related to serum TTR levels, apart from factors such as albumin and CRP levels, which showed correlations with serum TTR levels. Because body fat mass is related to better survival in maintenance hemodialysis patients, it may contribute to the prognostic value of serum TTR levels. In addition, in such patients, it may be important to evaluate body fat mass rather than body fat ratio and to maintain the minimum necessary body fat mass. J. Med. Invest. 64: 222-227, August, 2017.

Factors affecting radiation exposure dose in nursing staff during (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVES: We evaluated factors associated with increased radiation exposure dose in nursing staff who assisted patients with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) examinations. METHODS: The Barthel Index and Mini-Mental State Examination (MMSE) score were obtained before PET/CT examinations in 193 patients (mean age ± SD, 77.7 ± 8.0 yr). Three nurses self-measured their radiation exposure dose while assisting patients during each PET examination. Disturbance factors during PET examinations (use of a stretcher or wheelchair, use of lines or tubes connected to the patient, use of diapers or urethral catheterization, patient age), (18)F-FDG injection dose, and previous PET/CT experience in the patients and outpatient or inpatient status were evaluated as factors possibly associated with increased radiation exposure. Principle component analysis, univariate analysis, and multivariate regression analysis were used for assessing associations between radiation exposure dose and factors. RESULTS: The mean radiation exposure dose of the nursing staff was 6.07 ± 5.71 µSv per examination. Statistically significant factors associated with increased radiation exposure (<8 or ≥8 µSv/case) in the univariate analysis were the Barthel Index (<75 or ≥75), MMSE score (<22 or ≥22) of the patients, numbers of lines or tubes to the patient, use of a stretcher or wheelchair, and (18)F-FDG injection dose. Multivariate logistic regression modeling showed that the Barthel Index (<75 or ≥75) and MMSE score (<22 or ≥22) of the patients were significant factors in the final model. CONCLUSIONS: Lower Barthel Indexes (lower ADL) and lower MMSE scores (lower cognitive function) were independent factors associated with increased radiation exposure dose in nursing staff assisting during (18)F-FDG PET/CT.

A conceptual definition of vocational rehabilitation based on the ICF: building a shared global model.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) is a conceptual framework and classification system by the World Health Organization (WHO) to understand functioning. The objective of this discussion paper is to offer a conceptual definition for vocational rehabilitation (VR) based on the ICF. METHOD: We presented the ICF as a model for application in VR and the rationale for the integration of the ICF. We also briefly reviewed other work disability models. RESULTS: Five essential elements of foci were found towards a conceptual definition of VR: an engagement or re-engagement to work, along a work continuum, involved health conditions or events leading to work disability, patient-centered and evidence-based, and is multi-professional or multidisciplinary. CONCLUSIONS: VR refers to a multi-professional approach that is provided to individuals of working age with health-related impairments, limitations, or restrictions with work functioning and whose primary aim is to optimize work participation. We propose that the ICF and VR interface be explored further using empirical and qualitative works and encouraging stakeholders' participation.

Progressive leukoencephalopathy associated with aluminum deposits in myelin sheath.

A 20-year-old woman with progressive leukoencephalopathy developed mental and motor disabilities and fell into a coma after suffering head trauma and febrile episodes from infancy. Brain imaging showed massive abnormal signals in the white matter. The electron spectroscopic imaging of biopsied brain tissue confirmed the electron-dense deposits to be associated with aluminum accumulation in the myelin sheath. Her brain pathology, which showed ferritin- and naphtochrome green-positive deposits, supported the imaging analysis. The clinicopathological features indicate a new form of progressive leukoencephalopathy.

Assessment of vocational opportunities and continuing job placement for persons with mental disabilities: factors indicating levels of necessary support.

We determined primary factors in allocating support for vocational opportunities and continuing job placement for clients with mental disabilities. The study analyzed 29 items regarding work attitudes and vocational skills for 70 clients as assessed by the Tokyo Metropolitan Rehabilitation Center for the Physically and Mentally Disabled. The evaluations were performed using the situational assessment approach with a 3-point support scale system assigned through observation of behavior. The results of these evaluations placed 35 clients in employment groups (A and B) and 35 clients in a sheltered workshop group (C). The data was analyzed by multivariate analysis. Predictions of success and functional differences among the groups were indicated by the data. Differences were found among the three groups in work attitudes and skills such as "self-direction" and "directions for social participation". Out of the 35 clients currently employed, 11 were recognized as needing ongoing assistance from supported employment offices. For the supported employment group (B), the major work attitudes and skills for which they required continuous services for maintaining stable jobs were 'emotional stability' and 'learning of working skills and accomplishment of work.' In a previous study, the major differences between the competitive employment group (A) and the sheltered workshop group (C) were in areas of 'responsibilities,' 'goals for life,' 'motivation for the work and understanding of contents for work,' and 'safety during work.' Our study supports these findings. In addition, transition from the sheltered workshop to supported employment required training to improve skills and support for 'responsibilities,' 'goals for life,' 'participation in leisure activities and community-based activities,' and 'preparation and cleaning for work.'

[Various central nervous system involvements in dystrophinopathy: clinical and genetic considerations].

Duchenne and Becker muscular dystrophies, generically called dystrophinopathy, are caused by mutations of the dystrophin gene. It is not surprising that mutations of the dystrophin gene cause various neurological symptoms, since dystrophin protein is found in the brain tissue as well as in the muscle fiber cell membrane. However, few studies have reported on the frequency of central nervous complications other than mental retardation. Also, the relationship between the types of abnormal dystrophin gene and central nervous symptoms remains to be revealed. Medical records of 200 patients with dystrophinopathy from 167 extended families who had visited our institution during the past 15 years were reviewed to elucidate the frequency of central nervous complications. Fifty-four (27%) had mental retardation (an intelligence quotient less than 70), 15 (7.5%) had autism, 12 (6%) had epilepsy. 8 (4%) had febrile convulsion. 131 of these patients also underwent genetic testing. All patients with central nervous symptoms except one pair of siblings had some form of genetic deficiency or duplication distal to exon 44. Central nervous symptoms other than mental retardation are also common in patients with dystrophinopathy. These central nervous complications may be associated with mutations in the isoforms derived from exon 44 to 79.

[Drug-induced hypersensitivity due to phenytoin].

This study aimed to clarify factors associated with intravenous administered phenytoin-induced hypersensitivity reaction. The incidence of hypersensitivity was significantly more frequent in boys than in girls (P < 0.05). Patients with hypersensitivity were relatively younger than those without hypersensitivity, although the difference was not statistically significant. There was no relation between the initial dose or maximum blood level of phenytoin and the occurrence of hypersensitivity. The initial serum level of phenytoin was significantly lower in patients with hypersensitivity than in those without hypersensitivity (P < 0.05), whereas the total dose of phenytoin was relatively larger in patients with hypersensitivity than those without. Reactivation of human herpes virus-6 was not recognized in all 3 patients in whom virological examination was performed using real-time polymerase chain reaction.

Epidermal growth factor directs sex-specific steroid signaling through Src activation.

Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. We have revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5alpha-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5alpha-dihydrotestosterone may be responsible for the different extent of observed cell growth.