Continuous in-vIvo measurement of the brain tissue and the ischemic muscle gas tension using MEDSPECT, MS-8

I MEDSPECT is a medical mass spectrometer for continuous in-vivo measurement of tissue, blood and respiratory gases. Interfacing catheter for tissue in measurement has Teflon membrane. The permeability and perfusion rate for various gases through its membrane varied with temperature. The temperature coefficient of Teflon catheter in the range of 15℃-40℃ is approximately constant with -2% of correction per degree for oxygen and carbon dioxide. Linear correlation was confirmed experimentally. II The brain tissue gas tensions were measured in ten dogs with intra-venous anesthesia at normothermia and deep hypothermia using perfusion cooling, including circulatory arrest for 30 minutes at 20°C of cerebral temperature. On average, the brain tissue P(O2) was 15mmHg in normothermia when the arterial P(O2) showed 95mmHg and the brain tissue P(CO2) was 49mmHg when the arterial PC02 showed 30mmHg. The brain tissue carbon dioxide tension gradually decreased by cooling and increased during circulatory arrest for 30 minutes; from 45mmHg to 72mmHg. The brain tissue oxygen tension increased during cooling from 15mmHg to 41mmHg and decreased in the circulatory arrest; from 41mmHg to 36mmHg. III The ischemic muscle gas tension was measured in a 22-year-old man, who was suffered from thromboangiitis obliterans bilaterally, and had the popliteal autovein bypass surgery 3 months ago. Control oxygen tensions in the both anterior tibial muscles showed about the same; 35mmHg and 36mmHg respectivelly, and the P(O2) of the non-operated side showed remarkable low level of 18mmHg as compared with the side of arterial reconstruction surgery after 5-minutes ankle exercise

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma

Optimal flow rate and studies in oxygen consumption during hemodilutional extracorporeal circulation

19世紀から多数の研究者により報告された体外での臓器潅流の研究は,1937年Gibbon(1))の酸素付加装置による猫の潅流実験ののちに,さらに進展の度を早め,臨床的には,1951年Dennisら(2))が心房中隔欠損症の手術に試み,ついで1953年Gibbonが本症の手術に成功して以来,直視下心臓手術は人工心肺装置ならびに体外循環手技などの改良により広くおこなわれるようになった.一方,体外循環の副作用として,血清肝炎(3)),赤血球のsludgingやaggregation(4)),blood pooling(5)6))や同種血症候群(7)8))が問題となり,また装置充填に多量の新鮮血を要することも欠点であった.当時,生理学的研究では臓器潅流に電解質液を使用していたこと,Gollanら(9))が低体温下では赤血球の無い液体でも溶存酸素のみで組織は酸素を摂取しうることを示したことにより,血液希釈体外循環が考えられた.1951年PanicoとNeptune(10))が生理的食塩水で充填したのに始まり,Longら(4))の低分子量デキストラン,Gooleyら(11)),Zuhdiら(12)),De WallとLilleheiら(13))の5% 糖液,そしてNevilleら(14))の乳酸加リンゲル液の使用により希釈体外循環が主流となった.しかし,血液希釈にともなう問題も生じた.すなわち血液希釈によるヘモグロビン濃度の低下した血液は,酸素運搬能力も低下し,この低下を代償するために潅流量を増加しなければならないと考えられる.従来は全血体外循環時に設定された潅流量を希釈体外循環にも用いられてきたが,その可否を酸素消費量および血行動態の面より検討した.Serial oxygen uptake determination were done in 39 patients and 24 mongrel dogs during 20% hemodilutional cardiopulmonary bypass at normothermia. In patients, the time of the bypass ranged from 37 to 161 minutes. In dogs, the bypass time was standardized at 120 minutes. In patients, average of the mean perfusion index was 2.03 l/M(2)/min in the group I (BSA≧1.2M(2),n=13), 2.47 l/M(2)/min in the group Ⅱ (0.8≦BSA<1.2M(2),n=6) and 2.72 l/M(2)/min in the group Ⅲ (BSA<0.8M(2),n=20). During total perfusion, the average of the mean arterial blood pressure was 75.7mmHg in group I, 53.6mmHg in group Ⅱ, and 44.1mmHg in group Ⅲ. The average of the mean oxygen saturation during perfusion were 60.5%, 64.2%, 56.7% and the average of the O(2) consumption were 72.5ml/M(2)/min, 94.7ml/M(2)/min and 112.6ml/M(2)/min respectively. O(2) consumption (during perfusion)/O(2) consumption (predicted) ranged 0.22 to 0.96 in all patients and 0.52, 0.62, 0.63 respectively. The average of the O(2) extraction rate during perfusion were 32.9% , 42.8% and 36.0% respectively. The average of hematocrit during perfusion was 24.4% in patients and 23.5% in dogs. In dogs, classified into 5 groups, group A perfused at rate 25ml/Kg/min had an average mean arterial blood pressure of 20.6mmHg, group B perfused at rate 50ml/Kg/min had 38.3mmHg, group C perfused at rate 75ml/Kg/min had 58.7mmHg, group D at rate 100ml/Kg/min had 67.7mmHg, group E at rate 125ml/Kg/min had 58.4mmHg. The average of the O(2) consumption were 1.66ml/Kg/min (group A), 2.87ml/Kg/min (group B), 4.10ml/Kg/min (group C), 3.62ml/Kg/min (group D), 5.91ml/Kg/min (group. E). 1) Mean arterial blood pressure varied directly with flow rate in dogs, but not in patients. During perfusion mean arterial blood pressure was maintained at a lower level and mean central venous pressure at a higher level than at pre-perfusion value. 2) There is a linear relationship between flow rate and oxygen consumption both in patients and dogs. Oxygen consumption during perfusion were considerably lower than normal oxygen consumption. 3) Venous oxygen saturation during perfusion was lower than pre-perfusion value. There is a linear relationship between flow rate and venous oxygen saturation in dogs, but not in patients. 4) In patients, relationship between perfusion index and O(2) consumption indicates that the perfusion index over than 2.7 l/M(2)/min will be desirable, and in dogs splanchnic pooling during perfusion suggested the flow rate 75-100ml/Kg/min will be desirable

Effect of home-based group conversation intervention using smartphone application on cognitive health and psychological well-being of older adults with subjective cognitive concerns in Japan: a randomized controlled trial protocol

BackgroundSocial activity is a key component in the prevention of cognitive decline. However, face-to-face social intervention has limited accessibility. To address this issue, we developed the “Photo-Integrated Conversation Moderated by Application” (PICMOA), a home-based group conversation intervention using smartphones. This paper introduces the PICMOA intervention and the protocol of the ongoing randomized controlled trial (RCT), which aims to evaluate the effects of PICMOA on the cognitive functioning and psychological well-being of Japanese community dwelling older adults at the risk of cognitive function decline.MethodsThis study uses an RCT design in two parallel group trials with 1:1 allocation. The participants are community dwelling older adults aged 65 years and above, living in an urban city in Japan, with subjective cognitive concerns. In total, 81 participants were allocated to the intervention or control groups. The intervention group receives 30 min of weekly PICMOA sessions at their home for 12 weeks. The PICMOA intervention consists of (1) a photo preparation period before the session and (2) a structured group conversation session talking about the photos that participants took according to a specific theme. The control group receives 30 min of weekly health education videos on a tablet device. The primary outcome is cognitive functioning at pre- and post-phases of the 12-week intervention measured using the Telephone Interview for Cognitive Status in Japanese, semantic and phonemic fluency tests, and the Digit Span Forward and Backward tests. The secondary outcomes are psychological and social aspects including mental status, well-being, loneliness, and social support.DiscussionInterest is growing in internet-based activities for preventing social isolation. However, the effect of remote conversation interventions on cognitive functioning remains unclear. This study addresses this issue and provides a new avenue of social participation for older adults.Clinical trial registrationhttps://www.umin.ac.jp/ctr/, identifier: UMIN000047247

Function of EWS-POU5F1 in Sarcomagenesis and Tumor Cell Maintenance

POU5F1 is a transcription factor essential for the self-renewal activity and pluripotency of embryonic stem cells and germ cells. We have previously reported that POU5F1 is fused to EWSR1 in a case of undifferentiated sarcoma with chromosomal translocation t(6;22)(p21;q12). In addition, the EWS-POU5F1 chimeras have been recently identified in human neoplasms of the skin and salivary glands. To clarify the roles of the EWS-POU5F1 chimera in tumorigenesis and tumor cell maintenance, we used small-interfering RNA-mediated gene silencing. Knockdown of EWS-POU5F1 in the t(6;22) sarcoma-derived GBS6 cell line resulted in a significant decrease of cell proliferation because of G1 cell cycle arrest associated with p27Kip1 up-regulation. Moreover, senescence-like morphological changes accompanied by actin polymerization were observed. In contrast, EWS-POU5F1 down-regulation markedly increased the cell migration and invasion as well as activation of metalloproteinase 2 and metalloproteinase 14. The results indicate that the proliferative activity of cancer cells and cell motility are discrete processes in multistep carcinogenesis. These findings reveal the functional role of the sarcoma-related chimeric protein as well as POU5F1 in the development and progression of human neoplasms