Preconditioning with whole-body or regional hyperthermia attenuates exercise-induced muscle damage in rodents.

Our aim was to investigate whether hyperthermia before exercise protects against exercise-induced skeletal muscle damage. Two hyperthermia protocols were evaluated. In the first, male ICR mice were exposed to 30 min of whole-body heat in an environmental chamber at an ambient temperature of 42 °C. Heat-exposed and non-heat-exposed mice subsequently completed 60 min of downhill running on a treadmill, 24 h after exposure. Heat exposure significantly increased HSP70 and HSP25 content in the soleus muscle compared to controls. Plasma creatine kinase, muscle beta-glucuronidase, and histochemical (hematoxylin and eosin stain) analysis demonstrated that muscle damage was lower in the heat-exposed mice than in the non-heat-exposed mice. In the second, the effect of regional heating of the legs, by microwave diathermy, on the prevention of exercise-induced muscle damage was evaluated in male Wistar rats. Microwave-treated and non-microwave-treated rats again completed the running protocol 24 h after exposure. Microwave diathermy increased the muscle temperature to 40 °C, significantly increased HSP70 and HSP25 content in the soleus muscle, and significantly attenuated exercise-induced muscle damage. Therefore, hyperthermia before exercise increases skeletal muscle HSPs and attenuates the risk of exercise-induced muscle injury.

Control system for the new RIKEN 28-GHz superconducting electron cyclotron resonance ion source for SRILAC.

A new RIKEN 28-GHz superconducting electron cyclotron resonance ion source (SC-ECRIS) has been installed for the superconducting RIKEN linear accelerator (SRILAC). The new SC-ECRIS control system mainly consists of programmable logic controllers (PLCs) embedded with the Experimental Physics and Industrial Control System. To improve the reliability as compared with previous control systems, two types of PLC central processing units, sequential and Linux, have been installed in the same unit. Past experience has shown that new types of designs that can rapidly respond to system scalability are key. By connecting PLC stations using star-topology field buses, their rapid and cost-effective response to system changes is realized for the new devices. Furthermore, a unique data acquisition system employing a 920-MHz-band radio was developed to measure analog data such as the temperature at the high-voltage stage.

Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

BACKGROUND: Decreases in cardiorespiratory fitness among breast cancer patients have often been reported in previous studies, affecting patients' health and survival. Peak oxygen uptake ([Formula: see text]) is the gold standard for assessing cardiorespiratory fitness and is inversely correlated with cardiovascular disease among women with breast cancer. Some previous studies have reported that aerobic exercise and proper diet positively influence [Formula: see text]. However, almost all studies have been conducted in the Western countries, and few studies are investigating on Asian women who have lower BMI compared with Western ones. PURPOSE: Investigating the effects of a combined exercise and diet program among Japanese cancer patients undergoing therapy on [Formula: see text]. METHODS: Thirty-two Japanese women with breast cancer undergoing endocrine therapy (age; 50 ± 6 years, body weight; 59 ± 10 kg) were voluntarily assigned to either intervention group (n = 21) or control group (n = 11). The intervention group completed a 12-week combined exercise plus diet program, consisting of weekly aerobic exercise and maintaining a nutritionally well-balanced 1200 kcal/day diet. The control group was instructed to continue with their usual activities. Anthropometric indices and [Formula: see text] were measured at baseline and after the 12-week program. RESULTS: All 21 women completed the 12-week program. The [Formula: see text] significantly increased from 26.7 to 30.4 mL/kg/min (1.57-1.62 L/min) in the intervention group, while it remained unchanged (26.9-26.9 mL/kg/min) in the control group. Mean reduction of body mass index was - 2.1 in the intervention group (P < .001) and + 0.1 in the control group. CONCLUSIONS: Our combined exercise plus diet program may contribute to improvement in cardiorespiratory fitness and body weight compared with control group.

Correction to: Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

In the original publication of this article, Table 1 was published incorrectly. The correct Table 1 is given in the following page.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

OBJECTIVE: To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). DESIGN: Retrospective case series study. SETTING: Tertiary perinatal care centre at a university hospital. POPULATION: Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. METHODS: The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. MAIN OUTCOME MEASURES: Obstetrical management and complication including the incidence of AD throughout the peripartum period. RESULTS: Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi-square test). CONCLUSIONS: Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. TWEETABLE ABSTRACT: MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma.

The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly (P<0.00001). An ACD4C<343 × 106/l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 106/l (73.7% (95% confidence interval (CI)=66.7-79.5) versus 50.3% (95% CI=39.0-60.6), P<0.00001 and 83.3% (95% CI=77.1-88.0) versus 59.0% (95% CI=47.9-68.5), P<0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3-3.7), P<0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.

Progressive Cortical Neuronal Damage and Extracranial-Intracranial Bypass Surgery in Patients with Misery Perfusion.

BACKGROUND AND PURPOSE: Misery perfusion may cause selective neuronal damage in atherosclerotic ICA or MCA disease. Bypass surgery can improve misery perfusion and may prevent neuronal damage. On the other hand, surgery conveys a risk for neuronal damage. The purpose of this retrospective study was to determine whether progression of cortical neuronal damage in surgically treated patients with misery perfusion is larger than that in surgically treated patients without misery perfusion or medically treated patients with misery perfusion. MATERIALS AND METHODS: We evaluated the distribution of benzodiazepine receptors twice by using PET and 11C-labeled flumazenil in 18 surgically treated patients with atherosclerotic ICA or MCA disease (9 with misery perfusion and 9 without) and no perioperative stroke before and after bypass surgery; in 8 medically treated patients with misery perfusion and no intervening ischemic event; and in 7 healthy controls. We quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the MCA distribution and compared changes in the benzodiazepine receptor index among the 3 groups. RESULTS: The change in the benzodiazepine receptor index in surgically treated patients with misery perfusion (27.5 ± 15.6) during 7 ± 5 months was significantly larger than that in surgically treated patients without misery perfusion (-5.2 ± 9.4) during 6 ± 4 months (P < .001) and in medically treated patients with misery perfusion (3.2 ± 15.4) during 16 ± 6 months (P < .01). CONCLUSIONS: Progression of cortical neuronal damage in surgically treated patients with misery perfusion and no perioperative stroke may occur and may be larger than that in medically treated patients with misery perfusion and no intervening ischemic event.

Cerebrovascular Accident Rate Is Different Between Centrifugal and Axial-Flow Pumps, but Survival and Driveline Infection Rates Are Similar.

OBJECTIVES: We analyzed the outcome of patients with implantable left ventricular assist devices (LVADs) at the University of Tokyo Hospital to compare those with centrifugal pumps (CE group: Duraheart and Evaheart) and those with axial-flow pumps (AX group: Heartmate II and Jarvik 2000). METHODS: A total of 68 patients who underwent implantation of LVADs (Duraheart: n = 15; Evaheart: n = 23; Heartmate II: n = 22; Jarvik 2000: n = 8) as a bridge to transplantation at our institution from May 2011 to April 2015 were retrospectively reviewed. All patients were followed through December 2015. RESULTS: The mean follow-up time of the CE group was 1.95 ± 0.92 year (total 74.1 patient-years) and that of the AX group was 1.56 ± 0.56 year (total 46.8 patient-years). Whether the patients underwent centrifugal or axial-flow pump implantations was not associated with survival or driveline infection according to log-rank test (1-year survival rate: 89% vs 100% [P = .221]; 1-year freedom rate: 40% vs 43% [P = .952]). The rates of freedom from cerebrovascular accident (CVA) at 1 year after LVAD implantation in the CE and AX groups were 70% and 96%, respectively (P < .001). The CE group showed a higher frequency of CVA (0.472 vs 0.021 event per patient-year). CONCLUSIONS: Our findings indicate that overall survival and driveline infection rates are similar between centrifugal and axial-flow pumps, but they suggest that patients with centrifugal pumps are more likely to develop CVAs than those with axial-flow pumps.

A novel single-ended readout depth-of-interaction PET detector fabricated using sub-surface laser engraving.

We propose a novel scintillation detector design for positron emission tomography (PET), which has depth of interaction (DOI) capability and uses a single-ended readout scheme. The DOI detector contains a pair of crystal bars segmented using sub-surface laser engraving (SSLE). The two crystal bars are optically coupled to each other at their top segments and are coupled to two photo-sensors at their bottom segments. Initially, we evaluated the performance of different designs of single crystal bars coupled to photomultiplier tubes at both ends. We found that segmentation by SSLE results in superior performance compared to the conventional method. As the next step, we constructed a crystal unit composed of a 3 × 3 × 20 mm3 crystal bar pair, with each bar containing four layers segmented using the SSLE. We measured the DOI performance by changing the optical conditions for the crystal unit. Based on the experimental results, we then assessed the detector performance in terms of the DOI capability by evaluating the position error, energy resolution, and light collection efficiency for various crystal unit designs with different bar sizes and a different number of layers (four to seven layers). DOI encoding with small position error was achieved for crystal units composed of a 3 × 3 × 20 mm3 LYSO bar pair having up to seven layers, and with those composed of a 2 × 2 × 20 mm3 LYSO bar pair having up to six layers. The energy resolution of the segment in the seven-layer 3 × 3 × 20 mm3 crystal bar pair was 9.3%-15.5% for 662 keV gamma-rays, where the segments closer to the photo-sensors provided better energy resolution. SSLE provides high geometrical accuracy at low production cost due to the simplicity of the crystal assembly. Therefore, the proposed DOI detector is expected to be an attractive choice for practical small-bore PET systems dedicated to imaging of the brain, breast, and small animals.

Prognosis after mastectomy versus repeat lumpectomy in patients with ipsilateral breast cancer recurrence: A propensity score analysis.

INTRODUCTION: Mastectomy is the current standard surgical procedure for ipsilateral breast tumor recurrence (IBTR). However, there is little evidence about the prognostic impact of the surgical procedure (mastectomy versus repeat lumpectomy) for IBTR. PATIENTS AND METHODS: A total of 271 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent definitive surgery for IBTR between 1989 and 2008 were included from eight institutions in Japan. The impact of the surgical procedure for IBTR on distant disease-free survival (DDFS) and overall survival (OS) was evaluated using and multivariable proportional hazards regression and propensity score matching methods. RESULTS: Of the 271 patients, 149 patients (55%) underwent repeat lumpectomy and 122 patients (45%) underwent mastectomy after IBTR. The median follow-up period from definitive surgery for IBTR was 55 months. There was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR, adjusted for various clinical and tumor characteristics. In addition, for the matched patient cohort, no difference in DDFS and OS was seen between the 2 groups. CONCLUSION: In our study, both multivariate analysis and the propensity score matching method demonstrated that there was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR. Further studies are warranted (UMIN-CTR number UMIN000008136).

A retrospective analysis of the risk factors for allergic reactions induced by the administration of oxaliplatin.

This study retrospectively investigated the clinical features and risk factors of allergic reactions induced by oxaliplatin administration. This study investigated the incidence of allergic reactions and analysed the background and laboratory data in patients with colorectal cancer treated with oxaliplatin-based chemotherapy at Kyushu Medical Center between April 2012 and September 2012. A total of 62 patients were included in this study. The number of patients in the allergic and non-allergic groups was 7 and 55 respectively. The incidence of allergic reactions was 11.3%. We compared the patients' characteristics and laboratory data between the two groups and found that the average dose of dexamethasone in the allergic group was significantly lower than that observed in the non-allergic group (P = 0.0111). Furthermore, the incidence of allergic reactions in the group that received prophylaxis of less than 12 mg of dexamethasone was significantly higher than that observed in the group that received more than 12 mg of dexamethasone (P = 0.0103). In conclusion, a lower dexamethasone dose is a possible risk factor for allergic reactions induced by the administration of oxaliplatin; however, given the retrospective design used in this study, further validation of this finding is warranted.

Molecular detection of lymph node metastasis in breast cancer patients treated with preoperative systemic chemotherapy: a prospective multicentre trial using the one-step nucleic acid amplification assay.

BACKGROUND: For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy. METHODS: In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes. RESULTS: The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively. CONCLUSION: The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.

Chronic hemodynamic compromise and cerebral ischemic events in asymptomatic or remote symptomatic large-artery intracranial occlusive disease.

BACKGROUND AND PURPOSE: In asymptomatic or remote symptomatic LAICOD, the risk of ischemic events is low in general, but there may be a subgroup of higher risk patients who require aggressive medical management. The purpose of this study was to determine whether chronic hemodynamic compromise is a predictor of ischemic events in asymptomatic or remote symptomatic LAICOD. MATERIALS AND METHODS: We prospectively studied 51 asymptomatic, 19 coexistent asymptomatic, and 19 remote (>6 months) symptomatic patients with atherosclerotic intracranial internal carotid artery or middle cerebral artery disease by using (15)O-PET. MP was defined as decreased CBF, increased OEF, and a decreased CBF/CBV ratio. All patients were followed up for 2 years or until occurrence of stroke or TIA or death. RESULTS: Bypass surgery was performed in 4 patients (2 with MP). Three cerebral ischemic events (1 TIA in an asymptomatic patient, 1 stroke, and 1 TIA in a remote symptomatic patient) occurred in the vascular territory ipsilateral to LAICOD. Kaplan-Meier analysis with censoring at the time of bypass surgery revealed that the incidence of ipsilateral ischemic events in patients with MP (2/5) was significantly higher than that in patients without MP (1/84) (log-rank test; P < .0001). The relative risk conferred by MP was 83.1 (95% confidence interval, 6.8-1017.4; P < .001). The incidence of ipsilateral ischemic events in patients with decreased CBF/CBV (2/9) was also significantly higher than that of patients without it (1/80) (P = .0001). CONCLUSIONS: Chronic hemodynamic compromise may be a predictor of ischemic events in both asymptomatic and remote symptomatic LAICOD.

Diffuse tract damage in the hemispheric deep white matter may correlate with global cognitive impairment and callosal atrophy in patients with extensive leukoaraiosis.

BACKGROUND AND PURPOSE: Patients with extensive leukoaraiosis are at high risk for vascular dementia. However, these patients exhibit variable severity of global cognitive impairment correlating with callosal atrophy. We hypothesized that callosal atrophy may reflect the severity of HDWM tract damage, which may explain global cognitive impairment. The purpose of this study was to evaluate HDWM tract damage by DTI and to investigate whether HDWM tract damage is associated with callosal atrophy and global cognitive impairment, in patients with extensive leukoaraiosis. MATERIALS AND METHODS: Twenty-four consecutive outpatients with extensive leukoaraiosis were enrolled prospectively. The patients underwent cognitive evaluation and 3T MR imaging. The intercorrelation between cognitive score, DA of the HDWM, callosal DA, and callosal volume was analyzed statistically. The correlation of the cognitive score with DA of the HDWM and the corpus callosum was also evaluated by voxel-based analyses by using TBSS. RESULTS: The patients' MMSE scores varied from 10 to 30 (mean, 25.1 ± 6.0). Reduced DA of the HDWM, reduced callosal DA, and callosal atrophy intercorrelated significantly. All of these parameters showed a significant correlation with global cognitive impairment. TBSS analyses showed a significant correlation between MMSE score decline and reduced DA in the diffuse HDWM and the corpus callosum. CONCLUSIONS: In patients with extensive leukoaraiosis, atrophy and reduced DA of the corpus callosum may indicate diffuse HDWM tract damage, which may explain global cognitive impairment and development of vascular dementia.

Dependence of the gradient between arterial and end-tidal P(CO(2)) on the fraction of inspired oxygen.

BACKGROUND: End-tidal P(CO(2)) (Pe'(CO(2))) is routinely used in the clinical assessment of the adequacy of ventilation because it provides an estimate of Pa(CO(2)). How well Pe'(CO(2)) reflects Pa(CO(2)) depends on the gradient between them, expressed as ΔPa-e'(CO(2)). The major determinant of ΔPa-e'(CO(2)) is alveolar dead space (Vd(alv)). The fraction of inspired O(2) (Fi(O(2))) is not thought to substantially affect ΔPa-e'(CO(2)) in anaesthetized patients. We hypothesized that a high Fi(O(2)) may indeed increase ΔPa-e'(CO(2)) by preferentially vasodilating well-perfused alveoli, resulting in the redistribution of blood flow to these alveoli from poorly perfused alveoli and an increase in Vd(alv). We therefore investigated the effects of changes in Fi(O(2)) on ΔPa-e'(CO(2)) and Vd(alv). METHODS: With Institutional Review Board approval and informed consent, we studied 20 ASA I-II supine patients undergoing elective lower abdominal surgery under combined general and epidural anaesthesia. At constant levels of ventilation, Fi(O(2)) levels of 0.21, 0.33, 0.5, 0.75, and 0.97 were applied in a random order and ΔPa-e'(CO(2)) and Vd(alv) were calculated. RESULTS: The ΔPa-e'(CO(2)) values were, in order of ascending Fi(O(2)), {mean [standard error of the mean (SEM)]} 0.13 (0.04), 0.28 (0.08), 0.29 (0.09), 0.44 (0.11), and 0.53 (0.09) kPa. The corresponding values of Vd(alv) were 25.5, 33.8, 35.8, 48.9, and 47.4 ml. Each successive hyperoxic level showed a significant increase in ΔPa-e'(CO(2)) except between the 0.33-0.5 and 0.75-0.97 Fi(O(2)) levels. CONCLUSIONS: These data demonstrate that ΔPa-e'(CO(2)), in anaesthetized patients depends on Fi(O(2)).

Thoracic mass in a cynomolgus macaque (Macaca fascicularis).

A male cynomolgus macaque at the age of 3 years and 11 months suffered sudden cardiac arrest during a surgical operation. This animal had been clinically asymptomatic for 6 months from the acclimatization period to death. At necropsy, a white mass approximately 5 cm in diameter was found at the base of the heart. Histopathologically, the mass consisted of a granuloma with a number of multinucleated giant cells and multiple necrotic foci. Fungal hyphae characterized by parallel cell walls, distinct septa, and branching were observed in the lesion. The granuloma extended into the thoracic lymph nodes and the subepicardium of the left atrium, compressed the bronchioli, and was separated from the pulmonary parenchyma by a thick fibrous layer. The hyphal morphology and results of polymerase chain reaction assays demonstrated that the pathogen was Aspergillus sp.

6-mercaptopurine (6-MP) induces p53-mediated apoptosis of neural progenitor cells in the developing fetal rodent brain.

6-mercaptopurine (6-MP), a DNA-damaging agent, induces apoptosis of neural progenitor cells, and causes malformation in the fetal brain. The aim of the present study is to clarify the molecular pathway of 6-MP-induced apoptosis of neural progenitor cells in the fetal telencephalon of rats and mice. p53 protein is activated by DNA damage and induces apoptosis through either the intrinsic pathway involving the mitochondria or the extrinsic pathway triggered by death receptors. In this study, the expression of puma and cleaved caspase-9 proteins, which are specific intrinsic pathway factors, increased in the rat telencephalon after 6-MP treatment. 6-MP-induced apoptosis of neural progenitor cells was completely absent in p53-deficient mice. On the other hand, the expression of Fas protein, an extrinsic pathway factor, did not change throughout the experimental period in the rat telencephalon treated with 6-MP. The number of apoptotic neural progenitor cells was similar among Fas-mutated lpr/lpr and wild-type mice, suggesting that the Fas pathway does not play a significant role in 6-MP-induced apoptosis of neural progenitor cells. These results may suggest that the p53-mediated intrinsic pathway is essential for 6-MP-induced apoptosis of neural progenitor cells in the developing telencephalon of rats and mice.

Time-course changes in neural cell apoptosis in the rat fetal brain from dams treated with 6-mercaptopurine (6-MP).

6-Mercaptopurine (6-MP), one of the major drugs for the therapy of acute lymphoblastic leukemia and autoimmune diseases, is incorporated as thioguanine in nucleic acid and it induces cytotoxicity and fetotoxicity. In the present study, pregnant rats were treated with 50 mg/kg of 6-MP on 13 embryonic days (E), and fetuses were collected from 12 to 96 h after the treatment to examine the mechanism and time-course changes in neural cell death in the developing brain. The weights of fetal telencephalon and the thickness of the dorsal telencephalic wall of the fetuses were significantly reduced at 96 h. The number of pyknotic neural cells in the fetal telencephalon began to increase at 24 h, peaked at 36 h, and then gradually decreased toward 72 h. The nuclei of most of these pyknotic cells were stained positively by TUNEL method, which detects DNA fragmentation. Moreover, pyknotic cells were immunohistochemically positive for cleaved caspase-3, one of the key executioners of apoptosis, and the increased expression of the protein from 30 to 48 h was confirmed by using Western blot analysis. Also, electron microscopical features of the pyknotic cells showed ultrastructural characteristics of apoptosis. On the other hand, the number of mitotic and BrdU-positive neural cells in the telencephalon decreased from 30 to 72 h. These results suggest that 6-MP induced apoptotic cell death in neural cells in the rat fetal brain is probably due to cytotoxic action of 6-MP.