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Exercise is a key intervention for improving older adults’ physical function and life expectancy. Here, we investigated a short-term intervention program designed to improve the physical functioning of elderly adults in a community-dwelling setting. We examined the effect of a 5-week combined exercise and education program on the physical function, social engagement, mobility performance, and fear of falling in 42 subjects older than 65 years. Eleven subjects dropped out. There was significant improvement in the 30-second chair stand test ( p

Bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial repair and angiogenesis. Reduced number of circulating EPCs is associated with future cardiovascular events. We tested whether dysregulated glucose and/or triglyceride (TG) metabolism has an impact on EPC homeostasis. The analysis of metabolic factors associated with circulating EPC number in humans revealed that postprandial hyperglycemia is negatively correlated with circulating EPC number, and this correlation appears to be further enhanced in the presence of postprandial hypertriglyceridemia (hTG). We therefore examined the effect of glucose/TG spikes on bone marrow lineage-sca-1

Although the left coronary artery (LCA) has a flow profile in that most blood flow occurs during diastole rather than systole, the right coronary artery (RCA) has a flow pattern that is less diastolic dominant. This study assessed whether coronary pressure waveforms distal to stenoses with the same fractional flow reserve (FFR) was the same between the LCA and RCA. A total of 347 vessels from 318 patients who underwent FFR measurements were included. Conventional FFR was calculated as the ratio of the mean coronary distal pressure (Pd) to the mean aortic pressure (Pa) at maximal hyperemia. The pressure drop ratios in systole (PDRsystole) and diastole (PDRdiastole) were calculated as the sum of (Pa minus Pd) divided by the sum of Pa at the intracoronary diastolic and systolic pressure phases, respectively. Analysis of covariance of the regression line of correlation between conventional FFR and PDRsystole revealed that the slope was significantly greater in the RCA than in the left anterior descending artery (LAD) and left circumflex artery (LCX) (−0.765, −0.578, and −0.589, p

Objective: To investigate the relationship between changes in nutritional status and the functional outcome of adult post-stroke patients hospitalized for rehabilitation. Design: A cross-sectional study. Subjects: Post-stroke patients (n = 134) who were admitted to a convalescent rehabilitation ward. Methods: On admission and discharge, the nutritional status of each subject was assessed using the “controlling nutritional status” system. Activities of daily living were assessed using the Functional Independence Measure (FIM). Patients were divided into 2 categories: (i) those whose nutritional status improved or remained normal during the rehabilitation; and (ii) all others. Results: The median age of patients was 65.5 years. Although there were no significant differences between the 2 categories in most characteristics, the FIM efficiency was significantly higher (0.230 in the improved category and 0.133 in the other; p

It has been reported that weight gain at discharge compared with admission is associated with improved activities of daily living in convalescent rehabilitation (CR) patients with low body mass index. Here, we investigated whether weight maintenance or gain during the early phase of CR after stroke correlates with a better functional recovery in patients with a wide range of BMI values. We conducted this retrospective cohort study in a CR ward of our hospital and included adult stroke patients admitted to the ward from January 2014 to December 2018. After ~1 month of hospitalization, the patients were classified into weight loss and weight maintenance or gain (WMG) groups based on the Global Leadership Initiative on Malnutrition criteria for weight. We adopted the motor functional independence measure (FIM) gain as the primary outcome. The motor FIM gain tended to be greater in the WMG group but without statistical significance. However, multiple regression analysis showed that WMG was significantly and positively associated with motor FIM gain. In conclusion, weight maintenance or gain in patients during the early phase of CR after stroke may be considered as a predictor of their functional recovery, and nutritional management to prevent weight loss immediately after the start of rehabilitation would contribute to this.

Background/purpose The prognosis of patients with intermediate-risk neuroblastoma is favorable; therefore, a reduction therapy is desired. However, the long-term prognosis of those with residual tumor is unclear. The aim of this study was to clarify the necessity of residual tumor resection. Methods We retrospectively reviewed the records of patients diagnosed with intermediate-risk neuroblastoma who either were treated by chemotherapy only (nonresection group; n=16), or received postchemotherapy tumor resection (resection group; n=9). Results In the nonresection group, tumor size decreased in 14 patients; 5 had no detectable local tumor at the end of the follow-up period. Tumor size increased in 2 patients 1.5–2.5years postchemotherapy. Both patients received additional treatment and survived. All patients survived during the median follow-up time of 127months. In the resection group, 5 patients received complete resections and 4 patients received nearly complete resections. All patients survived during the median follow-up time of 84months. In 8 out of 9 resected tumors, regression or maturation was pathologically induced by chemotherapy-only treatment. Conclusion Patients with intermediate-risk neuroblastoma with or without postchemotherapy residual tumor resection had an excellent long-term outcome. The tumor pathology with intermediate-risk neuroblastoma might be susceptible to change to regression or maturation by chemotherapy. Level of evidence IV

BACKGROUND We previously identified circulating mesoangioblasts (cMABs), a subset of mesenchymal stem cells that express cardiac mesodermal markers, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). We also found that hepatocyte growth factor (HGF) is upregulated during cardiac surgery with CPB in humans, and induces MAB-like cell mobilization in rodents. These results strongly suggest that heparin induced MAB mobilization via HGF upregulation. Here, we tested this hypothesis in patients undergoing cardiac surgery or cardiac catheterization. We also examined whether human cMABs are derived from the heart.Methods and Results:Plasma HGF levels were determined by ELISA. Mononuclear cells isolated from blood samples were cultured on fibronectin-coated dishes, and outgrowing cMAB colonies were counted. We first confirmed that HGF upregulation and cMAB mobilization were observed before the start of CPB, excluding the possibility that CPB is the primary inducer of cMAB mobilization. We then examined patients undergoing cardiac catheterization and found that heparin significantly increased plasma HGF levels and the number of cMAB colonies in a dose-dependent manner. The results of simultaneous blood sampling from the aortic sinus, coronary sinus, and right atrium were consistent with the notion that human cMABs are derived from the heart. CONCLUSIONS Human cMABs are mobilized by heparin injection during cardiac surgery or cardiac catheterization, presumably via HGF upregulation.

A growing number of studies suggest critical tumor suppressor roles of the SWI/SNF chromatin remodeling complex in a variety of human cancers. The recent discovery of SMARCA4-deficient thoracic sarcomas has added to the list of tumor groups with the SMARCA4 inactivating mutation. To better characterize these tumors and establish their nosological status, we undertook a clinicopathological and molecular analysis of 12 SMARCA4-deficient thoracic sarcomas and compared them with three potentially related disease entities. Eleven men and one woman with SMARCA4-deficient thoracic sarcomas (aged 27-82 years, median 39 years) were included in the study. Most of the patients had heavy smoking exposure and pulmonary emphysema/bullae. The primary tumors were large and involved the thoracic region in all cases and simultaneously affected the abdominal cavity in 3 cases. The patients followed a rapid course, with a median survival of 7 months. Histologically, all tumors showed diffuse sheets of mildly dyscohesive, relatively monotonous, and undifferentiated epithelioid cells with prominent nucleoli. Immunohistochemically, all tumors demonstrated a complete absence (8 cases) or diffuse severe reduction (4 cases) of SMARCA4 expression. Cytokeratin, CD34, SOX2, SALL4, and p53 were expressed in 6/12, 10/12, 10/12, 10/12, and 7/10 cases, respectively. SMARCA2 expression was deficient in 11/12 cases, and none (0/8) expressed claudin-4. Targeted sequencing was performed in 5 cases and demonstrated the inactivating SMARCA4 mutation in each case and uncovered alterations in TP53 (5/5), NF1 (2/5), CDKN2A (2/5), KRAS (1/5), and KEAP1 (1/5), among others. Comparative analysis supported the distinctiveness of SMARCA4-deficient thoracic sarcomas as they were distinguishable from 13 malignant rhabdoid tumors, 15 epithelioid sarcomas, and 12 SMARCA4-deficient lung carcinomas based on clinicopathological and immunohistochemical grounds. SMARCA4-deficient thoracic sarcomas constitute a unique, highly lethal entity that requires full recognition and differentiation from other epithelioid malignancies involving the thoracic region.

Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway blockade has become a promising therapeutic target in adult cancers. We evaluated PD-L1 expression and tumor-infiltrating CD8(+) T cells in formalin-fixed, paraffin-embedded tumor specimens from 53 untreated pediatric patients with eight cancer types: neuroblastoma, extracranial malignant germ cell tumor, hepatoblastoma, germinoma, medulloblastoma, renal tumor, rhabdomyosarcoma, and atypical teratoid/rhabdoid tumor. One rhabdomyosarcoma with the shortest survival exhibited membranous PD-L1 expression and germinoma contained abundant tumor-infiltrating CD8(+) T cells and PD-L1-positive macrophages. The PD-1/PD-L1 pathway tended to be inactive in pediatric cancers.

Background Thrombotic microangiopathy (TMA) represents a spectrum of serious disorders characterized by occlusive microvascular thrombosis, thrombocytopenia and end-organ damage. TMA is associated with a broad range of conditions and is also a well-described complication of both cancer and its treatment. Case report A 77-year-old Japanese woman underwent S-1 and cisplatin chemotherapy for treatment of advanced gastric cancer with multiple lymph node and liver metastases. She was found with severe anemia and thrombocytopenia during the third course of chemotherapy. She was diagnosed with TMA based on thrombocytopenia, schistocytosis, hemolytic anemia and renal dysfunction. She underwent treatment with plasmapheresis; however, her response to treatment was poor and died on day 16 of hospitalization. The autopsy performed revealed microthrombi in the glomeruli and tubulonecrosis in the kidneys. Conclusion This is the first case report of TMA in association with the use of S-1 and cisplatin. Therapists have to take account of TMA when using S-1 and cisplatin treatment.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a useful biomarker for adult ulcerative colitis (UC) activity. In the present study, we evaluated whether PGE-MUM can also be a biomarker of pediatric UC activity and compared its efficacy in predicting UC activity with that of C-reactive protein and erythrocyte sedimentation rate.Twenty-nine pediatric patients with UC (8-18 years) and 29 healthy age- and sex-matched subjects were enrolled. UC activity was evaluated using the Pediatric Ulcerative Colitis Activity Index, highest Mayo endoscopic scoring (Mayo), and Matts grading (Matts) for histologic scoring, and the sum of Mayo (total of 6 segments) and Matts in all patients with UC. PGE-MUM levels were measured using a radioimmunoassay.PGE-MUM levels were elevated in endoscopically and histologically active UC patients, but not in patients with endoscopic and histologic remission or controls. PGE-MUM levels positively and significantly correlated with UC activity. PGE-MUM levels were positively correlated with Pediatric Ulcerative Colitis Activity Index (r = 0.594), highest Mayo (r = 0.462), the sum of Mayo (r = 0.694), and the sum of Matts (r = 0.613), but not with highest Matt (r = 0.352). The sum of Mayo and the sum of Matts, which reflect total colon inflammation, showed highest correlation with PGE-MUM. C-reactive protein levels did not correlate with any UC activity scores. Erythrocyte sedimentation rate exhibited correlation (r = 0.490) with the sum of Mayo only.PGE-MUM is a reliable biomarker that reflects both the endoscopic and histologic activity of the entire colon in pediatric UC.

Background Kasabach-Merritt phenomenon (KMP) is a rare condition and optimal treatments have not yet been established, especially for cases that are unresponsive to first-line therapy. We retrospectively reviewed 11 KMP cases treated over the past 13 years in our institute. Observations With the exception of 1 case, steroids were administered as the first-line therapy. Eight cases required second-line or third-line therapy. The effective salvage therapies include interferon (n=1), radiotherapy (n=1), and chemotherapy (n=5). One case continues to depend upon chemotherapy. Three refractory cases were therapy dependent over 1 year of age, whereas 8 were treated effectively by 6 months of age. Conclusions Chemotherapy seems to be the most effective therapy for steroid-resistant KMP cases.

Rhabdoid tumor is characterized by rhabdoid cells and shows complete loss of SMARCB1/INI1 protein expression. In existing classifications, the diagnostic synonyms vary depending on the anatomic site: rhabdoid tumors in the central nervous system or extra-central nervous system are, respectively, classified as atypical teratoid/rhabdoid tumor or malignant rhabdoid tumor. In this study, we analyzed the histological, immunohistochemical, microRNA, and clinicopathological statuses of tumors initially diagnosed as malignant rhabdoid tumor (n=33), atypical teratoid/rhabdoid tumor (n=11), and pediatric undifferentiated/unclassified sarcoma (n=8) with complete loss of SMARCB1/INI1 expression, and considered the possibility of their histological reclassification. Our analysis indicated that the tumors could be histologically reclassified into three groups: conventional-type tumors resembling malignant rhabdoid tumor, atypical teratoid/rhabdoid-type tumors resembling atypical teratoid/rhabdoid tumor, and small cell-type tumors resembling malignant lymphoma. The reclassified conventional type was composed of 27 malignant rhabdoid tumors and 9 atypical teratoid/rhabdoid tumors (36 cases). The atypical teratoid/rhabdoid type consisted of six malignant rhabdoid tumors, two atypical teratoid/rhabdoid tumors, and two undifferentiated/unclassified sarcomas (10 cases). The six cases of small cell type were made up of six undifferentiated/unclassified sarcomas. All of the available tumor specimens were positive for vimentin and epithelial marker (EMA, CAM5.2, or AE1/AE3). MicroRNA profiles were not significantly different between the conventional- and small cell-type tumors (Pearson's correlation coefficient: 0.888300 or 0.891388). There was no significant difference in overall survival between atypical teratoid/rhabdoid tumor and malignant rhabdoid tumor (P=0.16). In addition, there were no significant differences in survival between any of the reclassified combinations. In conclusion, we could classify eight tumors initially diagnosed as undifferentiated/unclassified sarcomas into two cases of atypical teratoid/rhabdoid type and six cases of small cell type. We suggest that reclassification of malignant rhabdoid tumors into three groups according to their histologic features rather than the traditional classification by sites of origin would be favorable for their histopathological diagnosis.

We report the case of a 14-year-old female with acute myeloid leukemia (AML) and myeloid sarcomas (MS) in the anterior mediastinum and around numerous bones. Laboratory tests showed a white blood cell count of 4.0 × 10(9)/l with 7.0 % blasts. Computed tomography revealed a mediastinal mass and pleural effusion; pleural effusion cytology was negative for malignant cells. In addition, disseminated intravascular coagulation (DIC) was present. Following DIC therapy, thoracoscopic and bone marrow biopsies were performed. Immunostaining and surface marker analysis revealed that the blast cells were positive for cytoplasmic myeloperoxidase, CD4, CD7, CD33, CD44, CD117, and HLA-DR, but negative for CD34 and CD56. Karyotype was normal. MS associated with AML was diagnosed. Multidrug chemotherapy for AML was completely ineffective, and MS continued to progress. Immunohistochemistry revealed that the blasts were negative for asparagine synthetase (AS); therefore, chemotherapy including L: -asparaginase was initiated. After the first administration of L: -asparaginase, the patient's condition improved; however, she subsequently developed tumor lysis syndrome and sepsis, which eventually led to death. Aggressive MS in childhood is rare and refractory to existing AML chemotherapy. Chemotherapy including L: -asparaginase may prove to be effective in such cases, especially those in which blast cells show negative AS expression.

Many studies have demonstrated the association between telomere length in mitotic cells and aging, but the relationship between telomere length in post-mitotic cells and aging in human populations has remained largely unclear. In this study, we assessed the dynamics of telomere length (terminal restriction fragment length—TRF) in normal pituitary glands obtained at autopsy from 65 patients aged between 0 and 100 years. The initial length (the value for neonatal pituitary) was 14.2 ± 1.1 kbp (mean of the median TRF value ± SD), being the longest among those for other systemic organs. The annual telomere reduction rates for pituitary (21 bp) were equivalent to or below the lowest values for various cells and tissues. Hence, comparison of TRF lengths among organs revealed that the pituitary gland retained longer telomeres than most other organs throughout life. The median TRF value showed a significant decrease between newborns and the 61–75 age group, but then leveled off or increased slightly in advanced age groups. These data indicate that innate telomere length is highly conserved in the pituitary and suggest that pituitary telomere length provides a good basic indicator for studies of telomere biology. Electronic supplementary material The online version of this article (doi:10.1007/s11357-011-9280-y) contains supplementary material, which is available to authorized users.

Laparoscopic spleen-preserving distal pancreatectomy (LSDP) with conservation of the splenic vessels is gaining acceptance as a reliable treatment for selected patients with low-grade malignant tumors of the pancreas in adults. The operation requires advanced laparoscopic skills to safely divide the fine branches of the splenic vessels. Laparoscopic spleen-preserving distal pancreatectomy with conservation of splenic vessels is rarely reported in children. We describe a 12-year-old girl with solid pseudopapillary tumor in the body of the pancreas that was successfully treated with LSDP, preserving the splenic vessels. The postoperative course was uneventful, and the functional and aesthetic results were satisfactory. Laparoscopic spleen-preserving distal pancreatectomy with conservation of splenic vessels may be a safe and feasible treatment option for children with pancreatic disease.

Ataxia-telangiectasia-like disorder (ATLD) is caused by mutations of the MRE11 gene and is characterized by cerebellar ataxia, increased frequency of chromosomal translocations and hypersensitivity to ionizing radiation. ATLD is a rare genetic disease and the associated pathological changes in the brain are unclear. Here, we report the neuropathological findings in the first cases of genetically confirmed ATLD in a pair of Japanese male siblings. Magnetic resonance imaging studies performed during infancy revealed that both subjects had cerebellar atrophy. They died of pulmonary cancer at 9 and 16 years. The siblings had the same compound heterozygous mutations of the MRE11 gene. Brain autopsy demonstrated mild and severe cerebellar atrophy in the vermis and medial part of the hemispheres, oral to the horizontal fissure, respectively. Nuclear immunoreactivity for MRE11 was absent in neurons of cerebellar cortex, cerebral cortex, basal ganglia and midbrain, whereas being widespread in normal control brains. Immunoreactivity for the DNA oxidative stress marker, 8-hydroxy-2'-deoxyguanosine, was identified in nuclei of granule cells and Bergmann glial cells. The combination of MRE11 deficiency and DNA oxidative injury might have led to selective cerebellar degeneration.

A case of malignant rhabdoid tumor (MRT) of the liver in a 4-month-old boy with hepatomegaly was described with the help of US and CT findings. The boy had multiple liver tumors, and the liver parenchyma showed a diffuse heterogeneous appearance. Lymph node swelling was noted, although the alpha-fetoprotein concentration was not elevated. A diagnosis of MRT was confirmed pathologically. Twenty-seven cases of MRT of the liver with solitary tumors, multiple tumors, or diffuse infiltration have been reported in the English-language literature. Diagnostic imaging plays an important role in detecting metastasis because of the high frequency of distant metastasis in MRT of the liver.

We investigated the telomere lengths of individual cell types in lingual mucosa using an improved tissue quantitative fluorescence in situ hybridization (Q-FISH) method. Our tissue Q-FISH method compensates for partially cut nuclei in a tissue section by using the telomere:centromere ratio (TCR). We normalized our TCR measurements (NTCR) using a section from a block of cultured cells placed on the same slide, thus improving the accuracy and reproducibility of the results. Normal lingual mucosa was obtained from 21 autopsied individuals. Immunohistochemistry showed positivity mainly for p27, p63, and CK19 in basal cells, and for Ki-67 in parabasal cells. Q-FISH revealed that NTCR was significantly highest in basal cells and lowest in prickle cells, and also that telomere length regressed at a certain rate in each cell type, firstly. Significant correlations of NTCR among the three epithelial cell types were demonstrated. The present findings appear to support the theory that stem cells exist in the basal layer of the lingual epithelium. The reduction of telomere length with age and in each cell layer is consistent with the telomere biology theory of cell proliferation and differentiation in oral mucosa.

Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.

Many studies have demonstrated the association between telomere length in mitotic cells and carcinogenesis and mortality, but little attention has been focused on post-mitotic cells and human life expectancy. We assessed the relationship between telomere length in cerebral gray and white matter and longevity in 72 autopsied Japanese patients aged 0–100 years using Southern blot hybridization. The mean telomere lengths in the gray and white matter were 12.3 ± 2.5 kilobase pairs and 11.4 ± 2.1 kilobase pairs, respectively. The mean telomere lengths in 60–69 year decadal group were less than those of neonates, and declined further in the 70–79-year age group, but those in groups of further advanced age were longer than in the 70–79 year group (70–79 < 80–89 < 90–100 years of age). Thus, the 90–100-year age group possessed significantly longer telomeres than the 70s (p = 0.029). Autopsy protocols showed a decrease in the rate of cancer death in individuals in their 80s (p = 0.041) and 90s (p = 0.017) versus those in their 60s, and in their 80s the mean telomere length in the gray matter from cancer death patients was significantly shorter than that of patients who died of other diseases (p = 0.04). These data suggest that innate telomere lengths are maintained very well in the cerebrum, and are associated with longevity. Our study lends indispensable support to the hypothesis that longer telomeres protect the genome from instability (a major cause of carcinogenesis) and are beneficial for longevity.

Gastrinoma is rare in children. We report the case of a 9-year-old boy with weight loss and vomiting. Upper gastrointestinal imaging showed severe stenosis of the duodenum. Although gastrin was very high, imaging did not show a gastrinoma. Selective arterial secretagogue injection (SASI) test indicated a tumor within the gastroduodenal arterial zone. In accordance with the SASI test result, we performed laparoscopic-assisted pancreaticoduodenectomy (LAPD). Postoperative biochemistry confirmed complete resection of the gastrinoma, and the patient was asymptomatic at follow up, 30 months after surgery. Even in patients with negative imaging for gastrinoma, aggressive resection following accurate localization on SASI test is biochemically curative. In such cases, the tumor is probably very small and LAPD may offer a minimally invasive procedure. As far as we know, LAPD in a child has not been previously reported.

Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5'-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies.

Muscle atrophy and weakness impair activity of daily living (ADL). We examined whether chair stand exercise can improve ADL of hemodialysis patients.A randomized controlled trial.A single center study.Outpatients on hemodialysis older than 60 years (61-79 years).Twelve weeks of intervention with chair stand exercise, 3 sessions/week versus the control exercise (stretch, 1 session/week).The primary outcome was the change in functional independence measure (FIM) score from baseline. The secondary outcomes were changes in thigh circumference, muscle strength of quadriceps, 6-minute walking distance, maximum duration of chair stand exercise, health-related quality of life, cognitive function serum albumin, and hemoglobin.Among the 27 patients who were randomized, 17 completed the study. The change in FIM from baseline was greater in the intervention group (1 [1-3] vs. 0 [0-0], median (minimum to maximum), P .001) due to the significant improvement in the FIM subscales related to mobility (bed/chair/wheel chair) and locomotion (stair). Among the secondary outcomes, significant difference was noticed in the changes in thigh circumference and the physical component summary score of health-related quality of life by Medical Outcome Study 36-Item Short-Form Health Survey (SF-36v2).Chair stand exercise improved ADL in the hemodialysis patients aged older than 60 years.

Aims Malignant rhabdoid tumours (MRTs) and epithelioid sarcomas (ESs) are distinctive malignant neoplasms with characteristic clinicopathological features. However, these two tumour types share some phenotypic features, such as epithelioid/rhabdoid cytology, expression of epithelial markers, and immunohistochemical loss of INI1. The distinction can be problematic in atypical clinical settings, and ancillary diagnostic tools are needed. The expression of CD34 is widely cited as favouring the diagnosis of ES, but no formal comparative study has been performed in the post-INI1 era. Here, we evaluated the utility of SALL4 for differentiating MRTs from ESs, and compared its performance with that of CD34. Methods and results Fifteen MRTs and 36 ESs were retrieved. All MRTs and ESs lacked INI1 reactivity, except for one MRT that lacked BRG1. A representative slide from each case was stained using antibodies against SALL4 and CD34. Ten (67%) of the 15 MRTs expressed SALL4. In contrast, only one (3%) of the 36 ESs expressed SALL4. CD34 staining was observed in nine (60%) of the MRTs and 29 (81%) of the ESs. Conclusions Despite moderate sensitivity, SALL4 expression may aid in distinguishing MRTs from ESs. CD34 was found to have questionable utility in making such distinctions.

Background/Purpose: In infants, neuroblastoma has been known to spontaneously differentiate into a benign ganglioneuroma. Although several investigators have compared mass-screened with unscreened, disseminated with localized, and adrenal with retroperitoneal neuroblastoma, there are very few cross-comparisons of the above parameters. Herein, the authors report the maturation of mass-screened, localized adrenal neuroblastoma. Methods: Fifty-one mass-screened adrenal neuroblastomas were divided into 2 groups. In infants less than 1 year of age (Group A), 45 neuroblastomas were resected, whereas 6 neuroblastomas were resected after observation in 1- to 4-year-old children (group B). Histopathology of the tumors in the 2 groups was compared. Data were analyzed by X 2 test, and P Results: According to the International Neuroblastoma Pathological Classification, 41 of 45 tumors of group A were "differentiating neuroblastoma" and 4 of 6 tumors of group B were "maturing ganglioneuroma." Maturation toward ganglioneuroblastoma was observed in 16 neuroblastomas of group A (36%) and 6 neuroblastomas of group B (100%). In group A, 58% had low mitosis karyorrhexis index (MKI); all patients in group B had low MKI. Conclusions: If left untreated, maturation of mass-screened, localized adrenal neuroblastomas is a common phenomenon. These children do not need to undergo early operation. J Pediatr Surg 36:1633-1636. Copyright © 2001 by W.B. Saunders Company.

A novel hepatitis-associated DNA virus, designated as transfusion-transmitted virus (TTV), was identified recently. We investigated the frequency of TTV viremia in hepatitis C virus (HCV) carriers on maintenance hemodialysis to determine whether TTV coinfection has any clinical relevance. The subjects were 50 hemodialysis patients who had been followed over 4 years after diagnosis of HCV infection. Stored serum samples derived from each patient every 12th month after enrollment were subjected to polymerase chain reaction to amplify TTV DNA and HCV RNA. At enrollment, TTV viremia was detected in 24 (48%) HCV-positive patients irrespective of the number of previous blood transfusions and the duration of hemodialysis. The presence of TTV viremia had no relation to serum alanine aminotransferase (ALT) levels, HCV viremic levels or HCV genotypes. After enrollment, HCV infection persisted in all patients over the 4-year follow-up period, whereas spontaneous resolution of TTV infection was observed in 7 (29%) of the 24 TTV viremic cases (annual rate 7.3%, 95% confidence interval [CI] 0.8-25.5%). Evidence for TTV infection was found in 4 (15%) of the 26 TTV nonviremic patients (annual incidence 3.9%, 95% CI 0.1-19. 6%). The relationship between the ALT profile and TTV infection during follow up was not evident. Active TTV coinfection occurs frequently in HCV carriers undergoing hemodialysis but exerts no biochemical or virological influence on the underlying hepatitis C. Lack of disease association and the frequent spontaneous resolution of infection suggest that the clinical significance of TTV infection remains unclear.

Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection.

The prognosis for metastatic malignant rhabdoid tumor (MRT) is poor, and metastatic (stage IV) MRT was resistant to conventional treatment, with less than 20% of cure rate. Moreover, there have been no reports of patients who have survived relapsed stage IV MRT. Here we report a long-term survivor of relapsed MRT with lung metastasis at diagnosis. He was diagnosed as MRT of the kidney at 5-month-old. After resection of the renal tumor, he was treated with ICE (ifosfamide, carboplatin, and etoposide), total abdominal irradiation 10.8 Gy and high-dose chemotherapy using thiotepa and melphalan. Six months after initial treatment, a relapse in the lung was detected, and he received chemotherapy including doxorubicin/pirarubicin for 78 weeks. He is alive at five years of follow up, without any evidence of disease. Our report suggests the important role of anthracycline in treatment of MRT.

Purpose We evaluated the clinicopathological characteristics of pediatric sacrococcygeal germ cell tumors (SGCTs) and yolk sac tumors (YSTs) developing after sacrococcygeal teratoma (SCT) resection, and discussed the pathogenesis of sacrococcygeal YST. Methods We retrospectively analyzed pediatric SGCT patients attending 10 Japanese institutions. Results A total of 289 patients were eligible, of which 74.6% were girls. The mean age at surgery was 7.1 months. There were 194 mature and 47 immature teratomas, and 48 YSTs. YST developed after SCT resection in 13 patients (5.4% of SCTs), and was detected between 5 and 30 months after resection. At initial surgery, 9 of these 13 patients were neonates, 12 underwent gross complete resection with coccygectomy, and 9 had histologically mature teratoma without microscopic YST foci. Postoperative serum alpha-fetoprotein (AFP) levels were regularly examined in 11 patients. Intervals of AFP measurement ≤ 4 months helped to detect subclinical localized YSTs for resection. Conclusions The characteristics of SGCT in Japanese children were similar with those reported in Europe or the United States. YST developed after SCT resection not only in patients with previously reported risk factors. We recommend that patients undergo serum AFP monitoring every 3 months for ≥ 3 years after SCT resection.

We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment.

Recently, it was reported that ependymoblastoma and embryonal tumor with abundant neuropil and true rosettes (ETANTR) show 19q13.42 amplification at a high frequency, suggesting that these tumors may constitute a single entity. As ependymoblastic rosettes are the most prominent features in both subtypes, embryonal tumor with multilayered rosettes (ETMR) was proposed, for which 19q13.42 amplification represents a specific molecular hallmark. However, ependymoblastic rosettes are not specific to ependymoblastoma and ETANTR, and are also found in a few other embryonal tumors as well as immature teratomas, and knowledge on 19q13.42 amplification in these tumors is limited. In this study, we performed fluorescence in situ hybridazation (FISH) analysis and differential polymerase chain reaction (PCR), and detected 19q13.42 amplification in three out of four ETANTR, one ependymoblastoma and one medulloepithelioma with ETANTR components, whereas none of the two atypical teratoid/rhabdoid tumors (AT/RT) with ependymoblastic rosettes nor two immature teratomas with developing neuroectodermal structures showed such amplification, suggesting that medulloepitheliomas would possibly be included in ETMR, and ependymoblastic rosettes in AT/RT do not signify that these tumors constitute ETMR. Also, we found C19MC rather than miR‐371‐373 was amplified in one ETANTR, suggesting that C19MC miRNA cluster seems to be more closely linked to the pathogenesis of ETMR.

Expression of p53 and c-myc was investigated and compared with cell proliferative activity in a series of 40 hepatocellular carcinomas (HCC), by means of enhanced immunohistochemistry. p53 expression was demonstrated in 5 out of 40 HCC (12.5%) with the incidence increasing in 5 out of 40 HCC (12.5%) with the incidence increasing in proportion to the histological grading of malignancy: thus, 0% of well-differentiated, 6.9% of moderately differentiated and 33.3% of poorly differentiated lesions were positive. The proliferating-cell nuclear antigen (PCNA) labeling index also showed a statistically significant increase with this grading. Distribution patterns of PCNA-positive cell were divided into four types: scatter, marginal, mosaic and diffuse. Four HCC cases, predominantly of the poorly differentiated type, exhibited the diffuse pattern. Generally, p53 overexpression corresponded well with PCNA positivity. In contrast, there was no correlation between c-myc overexpression, found in 19 out of 40 HCC (47.5%), and histological grading of HCC or PCNA labeling index. The distribution pattern of c-myc-positive HCC cells was also different from that of PCNA and p53. Our results suggest that p53 overexpression closely relates to proliferation of HCC cells. Furthermore, there may be a consistent difference in regulatory mechanisms between p53 and c-myc expression in multistep hepatocarcinogenesis.

This is a case report of an 82-year-old man with squamous cell lung cancer which produced GCSF. The leukocyte cell count was elevated to 94, 400/mm3. The serum G-CSF concentration was also elevated to 351 pg/ml. This is the first report to demonstrate, by application of immunohistochemical staining techniques directly to tumor tissue obtained at autopsy, squamous carcinoma cells which produce G-CSF. The tumor cells were stained with monoclonal anti-G-CSF antibodies.(Internal Medicine 32: 468-471, 1993)

Sialolipoma is a new variant of salivary gland lipoma that was first proposed by Nagao et al (Histopathology 2001;38:30-36). Three cases of submandibular gland sialolipoma have been previously reported in the English literature, all of which were in adults. We report an unusual case of sialolipoma of the submandibular gland in a 3-year-old boy. This is the first reported case of submandibular gland sialolipoma in a child.

We investigated the impact of glycemic control on the emergence of cardiovascular disease (CVD) in diabetic patients who were on maintenance hemodialysis in a prospective observational study. One hundred and thirty-four diabetic hemodialysis patients (63 +/- 10 years-old, hemodialysis duration of 4.5 +/- 3.9 years) at a single dialysis center were enrolled. The cohort was observed prospectively for 5 years, and the emergence of fatal and non-fatal CVD was recorded. Patients were categorized into two groups; good (mean hemoglobin (Hb) A1C7.0%, N = 65) and poor HbA1C (mean HbA1Cor = 7.0%, N = 69). The relationship between glycemic control and CVD emergence was evaluated by Kaplan-Meier estimation and Cox proportional hazard models. During the follow-up period, 50 CVD events were observed. The cumulative CVD incidence in the poor HbA1C group was significantly higher than that of the good HbA1C group, as determined by Kaplan-Meier estimation (P = 0.0250, log-rank test). After adjustment for gender, age, duration of dialysis, and past history of CVD, a multivariate Cox proportional hazard model showed that poor HbA1C was a significant predictor of CVD events (hazards ratio [HR] 1.828 [95% CI, 1.008-3.314], P = 0.0470). When ischemic heart disease, cerebral infarction, and arteriosclerosis obliterans were determined as an endpoint, both HbA1C levels and the poor HbA1C group were significant predictors for the emergence of CVD (HR 1.269 per 1% HbA1C [95%CI, 1.022-1.574], P = 0.0307,and HR 2.816 [95% CI, 1.377-5.759], P = 0.0046, respectively). In diabetic hemodialysis patients, poor glycemic control is a significant, independent predictor of the emergence of CVD, indicating the importance of careful management of glycemic control in hemodialysis patients.

We have conducted systematic studies to measure telomere length in human tissues of all types. Progressive telomere shortening with aging was studied in specimens of normal pancreas obtained at autopsy from 69 subjects aged 0 to 100 yr, and age-related shortening of telomere length at a rate of 36 base pairs (bp) per year was detected. Mean telomere length (±SD) was 13.9 ± 1.4 kilobase pairs (kbp) in 16 neonates, as opposed to 8.4 kbp in 2 centenarians. Mean telomere length (±SD) in four age groups, 0–24, 25–49, 50–74, and 75–100 yr, was 13.5 ± 1.5, 12.3 ± 0.7, 11.3 ± 2.5, and 10.7 ± 1.8, respectively.

The aim of this study was to evaluate the advantages and complications of endosurgical procedures for benign and malignant pediatric solid tumors. Endosurgical techniques of biopsy and excision were used for diagnosis and treatment of solid tumors, respectively. Since July 1997, a total of 24 biopsies and 24 excisions have been performed laparoscopically for neuroblastoma ( n=24), ovarian solid tumors ( n=10) and other tumors. Seventeen biopsies and six excisions were performed for abdominal neuroblastoma, while ten excisions were performed for ovarian tumor. In these patients, the length of the operation, blood loss, time to start postoperative feeding, time to start postoperative chemotherapy and length of hospital stay were evaluated and compared to the those of the open surgery group. Furthermore, intra- and postoperative complications were analyzed in all patients of both groups. The length of the hospital stay and time to start postoperative feeding were significantly shorter in the group of patients who underwent endosurgical procedures for either abdominal neuroblastoma or ovarian tumor when compared to the open procedure group. The time to start postoperative chemotherapy was shorter only in the abdominal neuroblastoma group. The procedure for two patients undergoing endosurgical tumor excision had to be converted to open surgery due to large tumor size. Two weeks after thoracoscopic excision of a dumb bell-type neurofibroma, one patient underwent open repair of the dura mater because of leakage of cerebrospinal fluid. There were no port-site recurrences in any tumor types. Endosurgical procedures for solid tumors are effective and minimally invasive. However, better indicators are needed for their implementation in order to prevent complications and subsequent conversions to open procedures.

A fatality from a tracheoesophageal fistula (TEF) in two extremely low birth weight infants is presented. The sudden onset of intractable respiratory failure accompanied by the absence of chest movement and breathing sounds was observed. The typical clinical symptoms were concealed because the infants required mechanical ventilation and nasogastric feedings. When ventilated infants with these symptoms are suspected of the diagnosis of TEF, prompt reintubation under the guidance of a flexible bronchoscopy may be life saving because the endotracheal tube passes through the fistulas into the esophagus with ease.

We conducted an observation program of neuroblastoma in infants, detected by mass screening at 6 months of age; we followed up with them for 15 years. No recurrence was observed after disappearance of tumors, and persistent tumors showed no malignant transformation or metastasis. Histology of the resected tumors showed age-related differentiation.

Cardiovascular mortality is elevated in patients with end-stage renal disease (ESRD), especially in those with diabetes mellitus. Although the higher cardiovascular death rate in diabetic ESRD patients may be the result of more advanced atherosclerotic changes of the arterial wall, this has not been documented previously. Aortic stiffness was compared between ESRD patients with and without diabetes, and the impact of aortic stiffness on cardiovascular mortality was examined in a prospective, observational cohort study. The cohort consisted of 265 ESRD patients on hemodialysis, including 50 diabetic patients studied between June 1992 and December 1998. At baseline, the diabetic ESRD patients had significantly higher aortic pulse wave velocity (PWV), a noninvasive measure of aortic stiffness, than the nondiabetic patients. During a mean follow-up period of 63 mo, 81 deaths, including 36 cardiovascular deaths, were recorded. Kaplan-Meier analysis revealed higher all-cause or cardiovascular mortality rates in the diabetic as compared with the nondiabetic patients and also in those with higher aortic PWV than those with lower aortic PWV. The effect of diabetes on cardiovascular death was significant in the Cox model, including age, years on hemodialysis, gender, smoking, C-reactive protein, hematocrit, and body mass index as covariates. However, when aortic PWV was included as a covariate, the impact of diabetes was no longer significant, whereas aortic PWV was a significant predictor. In a model including 13 covariates, aortic PWV remained a significant predictor for cardiovascular and overall mortality but not for non-cardiovascular death. These results demonstrate that the increased aortic stiffness of the ESRD patients with diabetes mellitus contributed to the higher all-cause and cardiovascular mortality rates.

OBJECTIVE—To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS—This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 ± 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c RESULTS—Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1.133 per 1.0% increment of HbA1c, 95% CI 1.028–1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS—Good glycemic control (HbA1c