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Rapid percutaneous coronary intervention for acute myocardial infarction (AMI) reduces acute mortality, but there is an urgent need for treatment of left ventricular dysfunction and remodeling after AMI to improve the prognosis. The myocardium itself does not have a high regenerative capacity, and it is important to minimize the loss of cardiomyocytes and maintain the cardiac function after AMI. To overcome these problems, attention has been focused on myocardial regeneration therapy using cells derived from bone marrow. The clinical use of bone marrow stem cells is considered to have low safety concerns based on the experience of using bone marrow transplantation for blood diseases in clinical practice. It has been reported that bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (BM-MSC) differentiate into cardiomyocytes both in vitro and in vivo, and they have been considered a promising source for stem cell therapy. To prevent heart failure after human AMI, studies have been conducted to regenerate myocardial tissue by transplanting bone marrow stem cells, such as BM-MSCs and BM-MNCs. Therapies using those cells have been administered to animal models of AMI, and were effective to some extent, but the effect in clinical trials was limited. Recently, it was reported that multilineage-differentiating stress enduring cells (Muse cells), which are endogenous pluripotent stem cells obtainable from various tissues including the bone marrow, more markedly reduced the myocardial infarct size and improved the cardiac function via regeneration of cardiomyocytes and vessels and paracrine effects compared with BM-MSCs. Here, we describe stem cell therapies using conventional BM-MNCs and BM-MSCs, and Muse cells which have potential for clinical use for the treatment of AMI.

Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM).The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart.Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy.The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period.The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.

Diabetic cardiomyopathy, clinically diagnosed as ventricular dysfunction in the absence of coronary atherosclerosis or hypertension in diabetic patients, is a cardiac muscle-specific disease that increases the risk of heart failure and mortality. Its clinical course is characterized initially by diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure from an uncertain mechanism. Light microscopic features such as interstitial fibrosis, inflammation, and cardiomyocyte hypertrophy are observed in diabetic cardiomyopathy, but are common to failing hearts generally and are not specific to diabetic cardiomyopathy. Electron microscopic studies of biopsy samples from diabetic patients with heart failure have revealed that the essential mechanism underlying diabetic cardiomyopathy involves thickening of the capillary basement membrane, accumulation of lipid droplets, and glycogen as well as increased numbers of autophagic vacuoles within cardiomyocytes. Autophagy is a conserved mechanism that contributes to maintaining intracellular homeostasis by degrading long-lived proteins and damaged organelles and is observed more often in cardiomyocytes within failing hearts. Diabetes mellitus (DM) impairs cardiac metabolism and leads to dysregulation of energy substrates that contribute to cardiac autophagy. However, a "snapshot" showing greater numbers of autophagic vacuoles within cardiomyocytes may indicate that autophagy is activated into phagophore formation or is suppressed due to impairment of the lysosomal degradation step. Recent in vivo studies have shed light on the underlying molecular mechanism governing autophagy and its essential meaning in the diabetic heart. Autophagic responses to diabetic cardiomyopathy differ between diabetic types: they are enhanced in type 1 DM, but are suppressed in type 2 DM. This difference provides important insight into the pathophysiology of diabetic cardiomyopathy. Here, we review recent advances in our understanding of the pathophysiology of diabetic cardiomyopathy, paying particular attention to autophagy in the heart, and discuss the therapeutic potential of interventions modulating autophagy in diabetic cardiomyopathy.

Progranulin is a secreted growth factor associated with multiple physiological functions in ischemic pathophysiology. However, it is still not fully understood how progranulin is involved in ischemic lesion and cardiac remodeling after myocardial infarction (MI). In this study, we investigated the effects of progranulin on myocardial ischemia and reperfusion injury. We investigated progranulin expression using Western blotting and immunostaining after permanent left coronary artery (LCA) occlusion in mice. Infarct size and the number of infiltrating neutrophils were measured 24 h after permanent LCA occlusion. Recombinant mouse progranulin was administered before LCA occlusion. In addition, we evaluated cardiac function using cardiac catheterization and echocardiography, and fibrosis size by Masson’s trichrome staining after myocardial ischemia/reperfusion in rabbits. Recombinant human progranulin was administered immediately after induction of reperfusion. Progranulin expression increased in the myocardial ischemic area 1, 3, and 5 days after permanent LCA occlusion in mice. The administration of recombinant mouse progranulin significantly attenuated infarct size and infiltrating neutrophils 24 h after permanent LCA occlusion in mice. We also found that administration of recombinant human progranulin ameliorated the deterioration of cardiac dysfunction and fibrosis after myocardial ischemia/reperfusion in rabbits. These findings suggest that progranulin may protect myocardial ischemia/reperfusion injury.

Tolvaptan is an orally active vasopressin V

Background We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product. Method and result Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion. Semi-clinical grade human Muse cell product (1x107, Muse group, n = 5) or saline (Vehicle group, n = 7) were intravenously administered at 24 h after reperfusion. The infarct size, LV function and remodeling were evaluated by echocardiography. Arrhythmias were evaluated by an implantable loop recorder. The infarct size was significantly smaller in the Muse group (10.5±3.3%) than in the Vehicle group (21.0±2.0%). Both the LV ejection fraction and fractional shortening were significantly greater in the Muse group than in the Vehicle group. The LV end-systolic and end-diastolic dimensions were significantly smaller in the Muse group than in the Vehicle group. Human Muse cells homed into the infarct border area and expressed cardiac troponin I and vascular endothelial CD31. No arrhythmias and no blood test abnormality were observed. Conclusion Muse cell product might be promising for AMI therapy based on the efficiency and safety in a mini-pig AMI.

Background Multilineage differentiating stress-enduring (Muse) cells are SSEA3+and CD105+double-positive pluripotent-like stem cells. We aimed to examine the mobilization of Muse cells into peripheral blood after acute myocardial infarction (AMI) and their effects on left ventricular (LV) function and remodeling.Methods and Results:In 79 patients with AMI, 44 patients with coronary artery disease (CAD), and 64 normal subjects (Control), we measured the number of Muse cells in the peripheral blood by fluorescence-activated cell sorting. Muse cells were measured on days 0, 1, 7, 14, and 21 after AMI. Plasma sphingosine-1-phosphate (S1P) levels were measured. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. Muse cell number on day 1 was significantly higher in the AMI (276±137 cells/100 μL) than in the CAD (167±89 cells/100 μL) and Control (164±125 cells/100 μL) groups. Muse cell number peaked on day 1, and had gradually decreased on day 21. Muse cell number positively correlated with plasma S1P levels. Patients with a higher increase in the number of Muse cells in the peripheral blood but not those with a lower increase in number of Muse cells in the acute phase showed improved LV function and remodeling in the chronic phase. Conclusions Endogenous Muse cells were mobilized into the peripheral blood after AMI. The number of Muse cells could be a predictor of prognosis in patients with AMI.

Laser speckle flowgraphy (LSFG) can measure blood flow in the ocular fundus. We analyzed the relationship between retinal blood flow and panretinal photocoagulation (PRP) in diabetic retinopathy.This retrospective observational study examined the eyes of 35 patients with proliferative diabetic retinopathy (PDR) or non-PDR (NPDR). PRP was performed using a pattern scan laser. Using LSFG, blood flow was evaluated as the mean blur rate (MBR) or the relative flow volume (RFV). We also evaluated MBR in the vessels of the optic nerve head (MBR-V), RFV at the first retinal artery (RFV-A), and RFV at the first retinal vein (RFV-V) before bifurcation. Blood flows were measured prior to treatment initiation, during each PRP session, and after PRP.The total number of laser spots created was 4258 ± 461. Regression of neovascular activity at 6 months after PRP occurred in 29 (82.85%) eyes. MBR-V significantly decreased to 83.9 ± 16% (p = .0039), 79.3 ± 21% (p = .0001), and 73.5 ± 26% (p = .0001) after the first, second, and third PRP treatment sessions. MBR-V was also reduced to 75.0 ± 25% (p = .0001), 75.0 ± 25% (p = .0001), and 80.3 ± 22% (p = .0001) at 1, 3, and 6 months following PRP. During and at 6 months after the PRP treatments, RFV-A and RFV-V were also significantly reduced (p .01).During and after PRP treatments using pattern scan laser, retinal blood flow was reduced. Retinal blood flow may be an auxiliary measurement for effectively evaluating PRP or PDR.

Background Changes in the plasma adenosine concentration and the effects on left ventricular (LV) function and remodeling in patients with acute myocardial infarction (AMI) remain unclear. Methods and Results: In 58 patients with AMI and 14 subjects without cardiac disease (controls), we measured the plasma adenosine concentration by LC-MS/MS. Blood samples were taken from the antecubital vein on days 0, 1, 7, and 14 after AMI, and from the controls on admission. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. There were no significant differences in the plasma adenosine concentrations among days 0 (211.5±150.2 nmol/L), 1 (192.7±141.3 nmol/L), 7 (218.8±154.1 nmol/L), and the controls (136.0±50.9 nmol/L). The plasma adenosine concentration increased significantly on day 14 (321.1±195.4 nmol/L) after AMI as compared with days 0, 1 and 7. AMI patients with a greater increase in the plasma adenosine concentration in the subacute phase showed an attenuation of LV dilation in the chronic phase. The plasma adenosine concentration in the acute phase did not affect the LV ejection fraction in the chronic phase. Conclusions The plasma adenosine concentration significantly increased 14 days after AMI, which may contribute to attenuation of LV dilation in the chronic phase.

RATIONALE: Rifabutin is a broad-spectrum antibiotic known to cause deposits on the corneal endothelium and lens. We report a patient in whom cataracts developed and progressive pigment deposits were seen on the corneal endothelium, lens, and iridocorneal angle. PATIENT CONCERNS: The patient was a 45-year-old woman who had been received long-term treatment with a combination of various anti-mycobacterial drugs for multidrug-resistant tuberculosis starting in 2004. Rifabutin was started in 2009, and she was referred to our department in 2017 for detailed ophthalmological examination. DIAGNOSES: Both eyes showed pigmented deposits over the entire corneal endothelium, the entire periphery of the iridocorneal angle, and the anterior surface of the lens. Mild cataracts were also diagnosed bilaterally. Pigment deposits on the anterior surface of the lens and the cataracts in both eyes gradually progressed. These lesions were assumed to be associated with long term rifabutin intake. INTERVENTIONS: Rifabutin intake was discontinued after progression of intraocular deposits, cataracts, and ERG deterioration. OUTCOMES: Visual acuity improved, although cataracts, deposits, and ERG deterioration remained. LESSONS: Rifabutin may induce not only corneal endothelial deposits, but also cataracts and iridocorneal angle deposits., Medicine, 99(21), e20049; 2020

Acute myocardial infarction (AMI) is a common cause of morbidity and mortality worldwide. Severe MI leads to heart failure due to a marked loss of functional cardiomyocytes. First-line treatment for AMI is to reperfuse the occluded coronary artery by PCI as soon as possible. Besides PCI, there are several therapies to reduce the infarct size and improve the cardiac function and remodeling. These are drug therapies such as pharmacological pre- and postconditioning, cytokine therapies, and stem cell therapies. None of these therapies have been clinically developed as a standard treatment for AMI. Among many cell sources for stem cell therapies, the Muse cell is an endogenous non-tumorigenic pluripotent stem cell, which is able to differentiate into cells of all three germ layers from a single cell, suggesting that the Muse cell is a potential cell source for regenerative medicine. Endogenous Muse cell dynamics in the acute phase plays an important role in the prognosis of AMI patients; AMI patients with a higher number of Muse cells in the peripheral blood in the acute phase show more favorable improvement of the cardiac function and remodeling in the chronic phase, suggesting their innate reparative function for the heart. Intravenously administered exogenous Muse cells engrafted preferentially and efficiently to infarct border areas via the S1P-S1PR2 axis and differentiated spontaneously into working cardiomyocytes and vessels, showed paracrine effects, markedly reduced the myocardial infarct size, and delivered long-lasting improvement of the cardiac function and remodeling for 6 months. These findings suggest that Muse cells are reparative stem cells, and thus their clinical application is warranted.

BACKGROUND The role of endogenous adenosine in cardiac patients is still unclear, so we investigated the relationship between the plasma adenosine concentration and left ventricular (LV) function, LV dilation and LV wall thinning in cardiac patients.Methods and Results:In 97 cardiac patients, with angina pectoris, old myocardial infarction, dilated or hypertrophic cardiomyopathy, and valvular heart disease, plasma adenosine concentrations were measured using the LC-MS/MS system, and the LV function, LV end-diastolic dimension (LVDd), LV posterior wall thickness (LVPWth), and interventricular septum thickness (IVSth) were assessed by echocardiography. The plasma adenosine concentration was significantly higher in patients with a LV ejection fraction (EF), an indicator of the LV systolic function

Purpose: As laser speckle flowgraphy can measure blood flow distribution in the ocular fundus, the authors analyzed the relationship between retinal blood flow and aqueous vascular endothelial growth factor (VEGF) concentration in central retinal vein occlusion. Methods: This prospective observational study examined 45 eyes of 45 patients with central retinal vein occlusion before treatment. Blood flow in large vessels around and at the optic disk, aqueous VEGF concentration, and arteriovenous passage time were examined. Blood flow was evaluated as mean blur rate by laser speckle flowgraphy. Results: Fluorescein angiography found 20 ischemic and 25 nonischemic type eyes. Aqueous VEGF concentration in the ischemic type was significantly higher than that in the nonischemic type (P = 0.01). Arteriovenous passage time was significantly correlated to the logarithm of the aqueous VEGF concentration (P = 0.0001). Mean blur rate of the affected eye/ mean blur rate of the unaffected eye of the ischemic type was significantly lower than the nonischemic type (P = 0.039). Additionally, mean blur rate was significantly correlated both to the logarithm of the aqueous VEGF concentration (P , 0.0001) and to the arteriovenous passage time (P = 0.0001). Conclusion: Laser speckle flowgraphy may be useful for predicting aqueous VEGF concentration and severity of central retinal vein occlusion., Retina, 35(10), pp.2037-2042; 2015

Rationale: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3 + cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. Objective: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair. Methods and Results: In vivo dynamics of Nano-lantern–labeled Muse cells showed preferential homing of the cells to the postinfarct heart at 3 days and 2 weeks, with ≈14.5% of injected GFP (green fluorescent protein)-Muse cells estimated to be engrafted into the heart at 3 days. The migration and homing of the Muse cells was confirmed pharmacologically (S1PR2 [sphingosine monophosphate receptor 2]–specific antagonist JTE-013 coinjection) and genetically (S1PR2-siRNA [small interfering ribonucleic acid]–introduced Muse cells) to be mediated through the S1P (sphingosine monophosphate)–S1PR2 axis. They spontaneously differentiated into cells positive for cardiac markers, such as cardiac troponin-I, sarcomeric α-actinin, and connexin-43, and vascular markers. GCaMP3 (GFP-based Ca calmodulin probe)-labeled Muse cells that engrafted into the ischemic region exhibited increased GCaMP3 fluorescence during systole and decreased fluorescence during diastole. Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells. These effects were partially attenuated by the administration of GATA4 -gene–silenced Muse cells. Muse cell allografts and xenografts efficiently engrafted and recovered functions, and allografts remained in the tissue and sustained functional recovery for up to 6 months without immunosuppression. Conclusions: Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.

Purpose: To report retinal blood flow levels measured by Laser speckle flowgraphy in three patients after they received an intravitreal bevacizumab injection (IVB) for macular edema secondary to central retinal vein occlusion (CRVO). Methods: Three patients (3 eyes) being treated with IVB (1.25 mg/0.05 mL) for secondary macular edema of CRVO were examined. Laser speckle flowgraphy analyses of the blood flow were based on the examinations of mean blur rate (MBR) at the major vessels of the optic disk. Central retinal thickness (CRT) was measured by optical coherence tomography using Macular Cube 512 128 scanning protocol. Results: After the first IVB, Case 1 exhibited an increase in MBR and decrease in CRT. After 4months, an additional injectionwas required because of a subsequentMBR decrease and CRT increase, which led to an increase inMBR and decrease in CRT similar to that observed after the first treatment. Subsequently, blood flow has continued to improve without additional IVB. Macular edema recurrence in Case 2 led to 3 further IVBs over a 6-month period. Although increases inMBRanddecreases inCRTwerenoted,MBRvalues tendedtodeclineafter eachIVB. In Case 3, macular edema recurrence led to 5 additional IVBs being carried out within a 1-year period. Continuous MBR increases and CRT decreases were observed in the patient after each IVB. By measuringMBR using laser speckle flowgraphy,wemay predict the prognosis of CRVO. Conclusion: Mean blur rate increases after IVB were confirmed by laser speckle flowgraphy in three patients. Even though CRVO pathology backgrounds can vary, laser speckle flowgraphy may be useful in both determining the CRVO prognosis and in evaluating treatment efficacy., Retinal Cases & Brief Reports, 8(1), pp.60-66; 2014

Patients with local recurrence of soft tissue sarcomas are predisposed to future recurrences because treatment is challenging and complicated by prior therapy. This study investigated clinical outcomes following surgical procedures for locally recurrent soft tissue sarcomas and risk factors for re-recurrence and metastasis.A retrospective analysis was conducted with 105 patients (52 males, 53 females) who underwent surgical procedures for local recurrence without distant metastasis of soft tissue sarcoma between 1987 and 2009. Patient follow-up ranged from 1 to 12 years (mean 4.9 years).Overall 5- and 10-year survival rates were 83.4 and 67.7%, respectively. Twenty-one patients (20.0%) had additional local recurrences, and 23 (21.9%) had distant metastases. Amputation rate was 10.5% at the time of surgical procedures and 17.1% at final follow-up. Locations deep within muscles in the upper limb or trunk and surgical margins1 cm wide were risk factors for further local recurrence. Locations deep within muscles, tumor sizes10 cm, high-grade malignancy, and local recurrence after radical surgery were risk factors for distant metastasis.Surgical margin and location were independent prognostic factors for local control, and a wider margin was especially important for recurrent tumors located in the trunk and upper extremity. For high-grade sarcomas with local recurrence after radical surgery, new approaches are needed to prevent distant metastases.

Rhabdomyosarcoma has different extension patterns, including a higher propensity for lymph nodes metastasis, compared with other types of soft tissue sarcoma. The aims of this study were to investigate the patterns of regional and distant metastasis in patients with rhabdomyosarcomas, particularly lymphatic route metastasis, and clarify the clinical factors that affect the pattern of metastasis. Forty-four patients with rhabdomyosarcomas were enrolled in this study. The mean age of the patients was 26 (range 1–69) years, and 18 were males. The histological subtypes included alveolar (17 patients), embryonal (10 patients), pleomorphic (7 patients), and unknown (10 patients). Based on location, the sarcomas were divided into three groups: extremity (17 cases), favorable prognosis (10 cases), and unfavorable prognosis (15 cases). There were three cases (7 %) of local relapse, ten cases of regional lymph node relapse, and three cases of in-transit metastasis (total 30 %). Twenty-one patients (48 %) developed distant metastases. Initial sites of metastases were bone (9 patients, 20 %), lung (5 patients), and bone marrow dissemination (5 patients). Clinico-pathological variables affecting relapse patterns were analyzed. Of the three cases of local relapse, two were alveolar type and one was unknown. The three cases of in-transit metastasis were all alveolar type. Patients with alveolar type had a significantly high propensity for lymph node metastasis (P = 0.027). Excluding the pleomorphic type, alveolar type was still a significant factor for lymph node metastasis (P = 0.017). Physicians should be aware of in-transit spread, particularly in patients with alveolar-type rhabdomyosarcoma. Novel treatment modalities are required to detect and treat in-transit metastasis.

Background: To evaluate the prognostic factors for the best-corrected visual acuity (BCVA) and foveal average retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling for diabetic macular edema. Design: Retrospective, single-center study. Participants: This study involved 31 eyes of 27 patients who had undergone vitrectomy with ILM peeling between January 2005 and March 2008. Methods: Relationships between preoperative systemic or ocular factors and BCVA or foveal average retinal thickness before and 6 months after the operation were evaluated. Main Outcome Measures: BCVA and foveal average retinal thickness before and 6 months after the operation. Results: The mean logarithm of the minimum angle of resolution improved from 0.84 ± 0.64 (mean ± standard deviation) preoperatively to 0.64 ± 0.38 six months postoperatively (p = 0.393). Foveal average retinal thickness significantly improved from 473 ± 146 μm preoperatively to 318 ± 108 μm 6 months after the operation (p < 0.0001). Preoperative foveal average retinal thickness was significantly thicker with cardiovascular disease or cerebral infarction (p = 0.0019) or cystoid macular edema (p = 0.0028), while preoperative BCVA was significantly lower when an epiretinal membrane (p = 0.042) was present. Foveal average retinal thickness at the 6-month follow-up was significantly thicker when patients had a higher body mass index (p = 0.0088), were not on dialysis (p = 0.012), or did not have proliferative diabetic retinopathy (p = 0.013). BCVA at the 6-month follow-up was significantly lower in the group with no history of diabetes treatment until diabetic retinopathy was found (p = 0.023) and in patients with a higher preoperative glycosylated hemoglobin (p = 0.033). Conclusions: Preoperatively, BCVA and foveal average retinal thickness were primarily associated with ocular factors, while they were strongly associated with systemic factors, postoperatively. Ocular factor improvements may be related to the surgical procedure., Ophthalmologica, 229(3), pp.142-146; 2013

Several previous reports have described multiple cancers with regard to epithelial tumors, but few reports have focused on multiple primary malignancies including soft tissue sarcomas (STS). The purpose of this study was to analyze the clinical features of patients with high-grade STS with multiple malignancies and possible clinical problems, compared with those with STS as a single malignancy, focusing on elderly patients. This study enrolled 107 patients aged 65 years or over with high-grade STS. Eighty-four patients (79 %) had sarcomas only (S group), and 23 (21 %) had multiple primary malignancies (M group). STS preceded carcinoma in 10 patients, and carcinoma preceded STS in 13. In 7 patients (30 %), the interval between the first and second malignancy was less than a year. Of 7 patients who received treatment for sarcoma and carcinoma at the same time, the presence of other malignancies had an impact on determination of the treatment modality in 5 patients. The overall survival rate at 5 years was higher in M group (79 %) than in S group (69 %), although this difference was not significant (P = 0.095). This study demonstrates that the presence of multiple malignancies was not correlated with a poor prognosis, and was actually associated with a better prognosis in elderly patients with STS. Physicians should be aware of the possible occurrence of a second malignancy, and on occasion the treatment modalities and their logistical aspects need to be well organized and carefully selected for patients with ongoing multiple malignancies.

A retrospective observational case series study of 44 nonischemic central retinal vein occlusion (CRVO) patients was conducted and visual acuity, central retinal thickness, and blood flow were determined via the use of laser speckle flowgraphy. This study shows that blood flows after intravitreal bevacizumab can predict outcomes in patients with CRVO., Purpose: To investigate whether retinal blood flow levels after intravitreal bevacizumab (IVB) treatment are correlated with the outcomes of patients with macular edema secondary to central retinal vein occlusion. Methods: This retrospective observational case study enrolled 44 cases nonischemic central retinal vein occlusion. In each patient, visual acuity, central retinal thickness, and mean blur rate, which was measured by laser speckle flowgraphy and represents retinal blood flow velocity, were examined. Results: At the end of the follow-up period (19.8 ± 8.8 months), 4 of 44 eyes (9.1%) converted to the ischemic type (converted group), whereas 40 (90.9%) remained unchanged (nonischemic group). Mean central retinal thickness significantly decreased and mean visual acuity significantly improved at 1 month after the first IVB injection in each group. Mean mean blur rate in the nonischemic group significantly increased, whereas it was unchanged in the converted group. The difference between the two groups was already significant after the first IVB injection. Subsequently, visual acuity worsened in the converted group. Multiple linear regression analysis indicated that the strongest correlation was between the last visual acuity and the last mean blur rate. Conclusion: Blood flow measurements are useful for evaluating IVB treatments. Blood flow after IVB can predict outcomes in patients with central retinal vein occlusion.

Tissue characteristics of coronary plaque have been reported to be associated with cardiovascular events. The stabilization of vulnerable tissue components such as the lipid pool rather than regression of the plaque volume is considered to be of major benefit in the reduction of cardiovascular events. Conventional echocardiography, especially intravascular ultrasound imaging (IVUS), is widely used to determine calcification and the three layers of the arterial wall. However, differentiation of the lipid pool from fibrous tissue using the echo intensity is difficult. Recently, an integrated backscatter (IB) ultrasound technique was developed. The ultrasound IB power ratio is a function of the difference in acoustic characteristic impedance between the medium and target tissue, and the acoustic characteristic impedance is determined by the density of tissue multiplied by the speed of sound. For more comprehensive plaque analysis using IB-IVUS, three-dimensional IB-IVUS offers the potential for the quantitative volumetric tissue characterization of coronary atherosclerosis. Several large clinical trials demonstrated that lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduces cardiovascular events. The IB techniques provide useful clinical information on the effects of statins and other medications. The presence of lipid-rich plaque is associated with the incidence of atherosclerotic diseases; therefore, ultrasound IB techniques are useful to detect coronary atherosclerotic lesions.

Purpose To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials The records of 17 primary sacral chordoma patients treated since 1990 with surgery ( n =10) or carbon ion RT ( n =7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The median duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery.

PURPOSE: To report the long-term (>5 years) results of full macular translocation in patients with choroidal neovascularization (CNV). DESIGN: Retrospective, interventional case series. METHODS: This study involved 32 eyes of 32 patients who had undergone full macular translocation for CNV. The median follow-up was 6.5 years (range, 5.2 to 7.7 years). We evaluated the best-corrected visual acuity, fundus examination results obtained before and 1 and 5 years after operation, and postoperative complications. RESULTS: At the 1-year follow-up, foveal retinal pigment epithelium atrophy was observed in only 3 eyes (12%), and the mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) at that time (1.39 +/- 0.67) was not significantly changed from that before surgery (logMAR, 1.31 +/- 0.66) in 25 eyes with age-related macular degeneration (AMD). However, at 5-year follow-up, foveal retinal pigment epithelium atrophy increased (18 eyes; 72%), and final mean logMAR VA (1.88 +/- 0.76) was significantly lower (P < .01). Five eyes with myopic CNV maintained their VA from before operation (mean logMAR, 0.88 +/- 0.35) until final follow-up (mean logMAR, 0.73 +/- 0.31). The final VA was significantly better in myopic CNV than in exudative age-related macular degeneration on multiple regression analysis (P = .019). CONCLUSIONS: Long-term follow-up of full macular translocation showed that the final VA was poor in age-related macular degeneration, but relatively better in myopic CNV., American journal of ophthalmology, 149(3), pp.453-457; 2010

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder. Mutation in the SIL1 gene accounts for the majority of MSS cases. However, some individuals with typical MSS without SIL1 mutations have been reported. In this study, we identified two novel mutations in a Japanese pedigree with MSS, one of which was an intragenic deletion not detected using the PCR-direct sequencing protocol. This family consisted of three affected siblings, an unaffected sibling and unaffected parents. We found a homozygous 5-bp deletion, del598-602(GAAGA), in exon 6 of all affected siblings by PCR. Thus, we expected that both parents would be heterozygous for the mutation. As expected, the father was heterozygous, whereas the mother demonstrated no mutations. We then carried out array comparative genomic hybridization and quantitative PCR analyses, and identified an approximately 58 kb deletion in exon 6 in the patients and mother. As a result, the mother was hemizygous for a 58-kb deletion. The affected siblings contained two mutations, a 5-bp and a 58-kb deletion, resulting in SIL1 gene dysfunction. It is possible that some reported cases of MSS without base alterations in the SIL1 gene are caused by deletions rather than locus heterogeneity.

We determined the diagnostic accuracy rate of 207 cases that underwent CT-guided needle biopsy for musculoskeletal lesions during the past 10 years, and describe the efficacy and indications of this method. We retrospectively analyzed a consecutive series of 207 cases that presented to our oncology group and underwent CT-guided needle biopsy during the 10-year period between April 1998 and March 2008. Diagnostic accuracy was assessed statistically by anatomical location and final diagnosis. The biopsy site was the spine/sacrum in 70 cases, pelvis in 53, extremities in 51, rib/scapula in 20, and retroperitoneum in 13. Bone lesions were detected in 176 cases and soft tissue lesions in 31. The final diagnosis was metastatic tumor in 63 cases, primary bone tumor in 63, primary soft tissue tumor in 23, infection in 18, and hematopoietic malignancy in 16 and non-tumorous lesions in 24. The diagnostic accuracy rate for all cases was 90%. No serious complications were seen. No statistically significant difference was found by anatomical site. According to the final diagnosis, benign tumors/malignant tumors (p

Candesartan has been reported to produce nitric oxide (NO) and to decrease oxidative stress in animal studies. We investigated candesartan's effect on the production of NO and oxidative stress as well as on carotid intima-media thickness (IMT) in hypertensive patients. One-hundred age-matched hypertensive patients were enrolled into an angiotensin II receptor blocker (ARB) group (n=50) or a non-ARB group (n=50). The ARB group was treated with candesartan 8 mg and, when needed, Ca channel blockers, angiotesin-converting enzyme (ACE) inhibitors, and/or beta-blockers. The non-ARB group was treated with drugs other than ARB. Carotid IMT was assessed by echocardiography before and 12 and 24 months after treatment. The urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an indicator of oxidative stress, and the serum levels of NOx, an indicator of NO, were measured. Blood pressure decreased to below 140/90 mmHg to the same extent in both groups. Carotid IMT decreased significantly in the ARB group, but not in the non-ARB group, at 12 and 24 months after treatment. The urine levels of 8-OHdG decreased significantly at 6 and 12 months after treatment in the ARB group but did not decrease in the non-ARB group. The serum levels of NOx increased significantly at 6 and 12 months after treatment in the ARB group but not in the non-ARB group. In conclusion, candesartan decreases carotid IMT by enhancing NO production and decreasing oxidative stress in patients with hypertension.

Giant cell tumor of bone occasionally results in secondary osteoarthritic changes in adjacent joints. The purpose of this study was to determine the factors associated with the development of degenerative arthritis in surgically treated patients with giant cell tumor of the distal femur or proximal tibia and the effect of residual subchondral bone thickness on the location of recurrent giant cell tumor. We retrospectively studied 30 patients with giant cell tumor of bone arising around the knee joint treated with intralesional curettage, high-speed burring, and electrocauterization, followed by filling with polymethylmethacrylate or autogenous bone graft. There was no significant difference in factors of age, gender, tumor location, residual thickness of subchondral bone, or Campanacci grade correlated with the recurrence. Of the 10 recurrence cases, seven recurred on the articular side, and three on the contra-articular side of the primary lesion. Less than 5 mm of residual thickness of subchondral bone was correlated with recurrence on the articular side (p=0.038). There were 10 cases (33.3%), in which secondary degenerative arthritic change developed or progressed. Re-operation for local recurrence or post-operative fractures was a significant factor correlated with the progression of secondary osteoarthritis (p=0.010). Less residual thickness of subchondral bone tended to be associated with secondary osteoarthritis (p=0.068). Other factors were not correlated significantly with osteoarthritic change. These data support the contention that the residual thickness of subchondral bone could be a factor predicting the location of recurrence, and operative procedure to avoid re-operation might be critical to preserve knee function.

Few studies have analyzed Cathepsin K (CatK) expression in human osteoarthritic tissues. We investigated CatK expression and activation in human articular cartilage using clinical specimens. Human osteoarthritic cartilage was obtained during surgery of total hip arthroplasty (n = 10), and control cartilage was from that of femoral head replacement for femoral neck fracture (n = 10). CatB, CatK, CatL, CatS, and Cystatin C (CysC) expressions were evaluated immunohistochemically and by real-time PCR. Intracellular CatK protein was quantified by ELISA. Intracellular CatK activity was also investigated. Osteoarthritis (OA) chondrocytes were strongly stained with CatK, particularly in the superficial layer and more damaged areas. CatB, CatL, CatS, and CysC were weakly stained. CatK mRNA expression was significantly higher in OA group compared to that in control group (p = 0.043), whereas those of CatB, CatL, CatS, and CysC did not differ significantly. Mean CatK concentration (4.83 pmol/g protein) in OA chondrocytes was higher than that (3.91 pmol/g protein) in control chondrocytes (p = 0.001). CatK was enzymatically more activated in OA chondrocytes as compared with control chondrocytes. This study, for the first time, revealed increased CatK expression and activation in human OA cartilage, suggesting possible crucial roles for it in the pathogenesis of osteoarthritic change in articular cartilage.

The aim of this study was to assess the radiologic and clinical outcome when beta-tricalcium phosphate is used as a bone graft substitute to backfill the fibular defect that is created by harvesting the fibula. Fourteen patients who had fibula resections to be used as bone grafts for bone tumor resections were assessed radiographically. Callus formation bridging the beta-tricalcium phosphate was seen in 12 of 14 patients at an average of 1.4 months after surgery. In these 12 patients the beta-tricalcium phosphate mostly was absorbed and replaced by newly formed bone at an average of 9.3 months after surgery. In all children, beta-tricalcium phosphate was replaced by newly formed bone at an average of 3.2 months after surgery. Only one adult patient had complete regeneration of the fibula. Few patients had continuity between the regenerated fibula and the native fibula. In one patient in whom free vascularized fibula was harvested, regeneration of the fibula was not observed. Clinical functional outcome was not correlated with successful fibula regeneration and union with the native fibula, as determined using radiographs. The results of the study suggest that, in children, regeneration of the fibula by implanting beta-tricalcium phosphate into a bone defect can reduce morbidity of the fibula harvest sites.

In the reconstruction of extensive bone defects after massive resection of malignant musculoskeletal tumors, the clinical results of moderately heat-treated autogenous bone graft have rarely been documented. We evaluated the remodelling and healing process of moderately heat-treated autogenous bone graft by means of imaging features. The subjects of this study were 19 patients with bone and soft-tissue tumors treated by heat-treated bone graft at our institution between 1992 and 2001, the mean follow-up period was 4.8±2.8 years (range 1–9 years). The remodelling and healing process of heat-treated bone graft was evaluated by means of radiography, bone scintigraphy, and MRI. The mean period to obtain bone union between host bone and grafted bone was 9.4 months. Infection was noted in 1 patient, and fracture was present in 2 patients. In 6 patients, pseudoarthrosis was found. Bone scintigraphy showed an increased uptake at the host-graft junction in the period between 3 and 36 months (median 10.7 months) postoperatively. A gradually increased diffuse uptake on the grafted side was evident at an average of 29.1 months (range 19–41 months) postoperatively. High signal intensity on T2-weighted images was observed in the early period after surgery, and iso-intense or low signal intensity became evident after an average of 28.3 months. A gradually increased diffuse uptake on scintigraphy and iso-intense or low signal intensity on T2-weighted images indicated remodelling of the grafted bone. Bone union of a moderately heat-treated autogenous bone graft was noted at about 9 months, and its remodelling was proceeding at about 30 months. This method will be useful for bone defects after massive resection of soft-tissue and bone tumors.

Aims: The aim of this study was to investigate telomerase activity and to assess the correlation between telomerase activity, tumor proliferative activity and p53 overexpression in osteosarcoma tumor samples. Methods: Using a telomerase polymerase chain reaction-enzyme-linked immunoassay based on the telomeric repeat amplification protocol method, we examined telomerase activity in 26 primary osteosarcoma specimens. P53 overexpression was identified using immunohistochemical staining, and tumor proliferative activity was assessed by immunohistochemical staining of PCNA. Results: Telomerase activity was detected at a relatively low level in five of 26 osteosarcoma tissue specimens. P53 was detected in eight of 21 cases. There was no significant correlation between telomerase activity and p53 overexpression ( p =0.325). There was a significant correlation between PCNA staining and telomerase activity ( p =0.0075). Conclusion: Difference between the telomerase activity and p53 overexpression in osteosarcoma suggests that p53 and telomerase may not cooperate in tumor proliferation. Correlation of telomerase activity to PCNA expression suggests that telomerase activity may also useful for evaluate proliferative activity in osteosarcoma.

The aim of this study was to determine type I collagen turnover in giant cell tumor of bone (GCT) by biochemical markers of type I procollagen aminoterminal propeptide (PINP) and type I collagen carboxyterminal telopeptide (ICTP) as synthesis and degradation markers, respectively. The serum concentrations of PINP and ICTP were measured in 11 patients with GCT using radioimmunoassay, and analyzed by the correlation to the grades of GCT progression described by Campanacci. Serum of the 11 healthy subjects was available for comparison. The serum concentration of PINP was significantly higher in patients with GCT (82.4 +/- 46.2 ng/ml) than in controls (40.8 +/- 12.1 ng/ml) (P0.01), and that of ICTP was also significantly higher in GCT (5.3 +/- 2.0 ng/ml) than in controls (3.2 +/- 0.8 ng/ml) (P0.01). In GCT, the PINP concentration of grade 3 (127.6 +/- 38.8 ng/ml) was higher than that in grade 1 patients (46.9 +/- 4.8 ng/ ml) (P0.01). ICTP concentration of both grades 2 (7.1 +/- 1.4 ng/ml) and 3 (5.8 +/- 1.8 ng/ml) patients was significantly higher than that of grade 1 (3.5 +/- 0.6 ng/ ml) patients (P0.01, P0.05, respectively). Two cases of serum concentration of PINP and ICTP after resection of GCT demonstrated that these biomarkers decreased to the control levels in the absence of GCT. Our results indicated that type I collagen turnover evaluated by ICTP and PINP was stimulated in the presence of GCT. Moreover, this enhanced metabolic turnover reflects the grade of GCT.

This report describes a case of bone involvement by epithelioid sarcoma, which on imaging had the appearance of a primary intraosseous lesion of the scapula. The tumor initially presented as a subcutaneous nodule which was mistakenly diagnosed as "fibrosis" following initial resection. The lesion recurred locally and after several resections presented with several ulcerated subcutaneous nodules, at which time all imaging studies were performed. The patient was treated with en bloc upper humeral interscapulothoracic resection and shoulder reconstruction. Two years after the operation the patient is alive without local recurrence or metastasis.

A 7-year-old girl was diagnosed with alveolar rhabdomyosarcomas of the right crural region. The patient was initially treated with chemotherapy and surgery with wide surgical margins, with radiotherapy. The tumors relapsed in the popliteal region surrounding the popliteal vessels. The patient received sentinel lymph node biopsy for a recurrent tumor using isosulfan blue dye, with the "sentinel node" being malignant-negative, and a "nonsentinel node" positive. Sentinel lymph node biopsy with conventional blue dye alone might be insufficient to assess lymph node status in patients with recurrent rhabdomyosarcoma previously treated with surgery and/or radiotherapy.

We conducted a prospective randomized trial to assess the protective effect of continuous intravenous infusion of nicorandil against contrast-induced nephropathy (CIN) in patients with poor renal function.We randomly assigned 213 patients who would subsequently undergo elective percutaneous coronary intervention (PCI) and who had a high serum cystatin C level to a saline group (n=107) or a nicorandil group (n=106, nicorandil infused in addition to saline for 4h before and 24h after PCI). There were no significant differences in baseline characteristics between the two groups. However, the average percent increases in serum creatinine and cystatin C following PCI were significantly smaller in the nicorandil group than the saline group. Likewise, the average percent decline in the estimated glomerular filtration rate was smaller in the nicorandil group. Correspondingly, the incidence of CIN was dramatically lower in the nicorandil group than the saline group (2.0% vs. 10.7%, p0.02). Univariate regression analysis revealed nicorandil treatment to be the only significant predictor of CIN development (odds ratio: 0.173, 95% confidence interval: 0.037-0.812, p=0.026).Nicorandil strongly prevents CIN in patients with poor renal function undergoing PCI.

PURPOSE: To analyze the morphology of microaneurysms before and after direct photocoagulation using spectral domain optical coherence tomography.METHODS: In 13 eyes of diabetic patients who underwent focal photocoagulation for clinically significant macular edema, microaneurysms were evaluated before, immediately after, 1 month after, and 2 months after photocoagulation with spectral domain optical coherence tomography.The microaneurysms were also evaluated by fluorescein angiography and color fundus photography.The patients underwent focal photocoagulation for microaneurysm.RESULTS: The microaneurysms before photocoagulation in spectral domain optical coherence tomography were observed as circular or elliptical structures with hyperreflective foci within vessel walls.Immediately after photocoagulation, the microaneurysms were changed to indistinct lesions with hyperreflectivity around the microaneurysms.Acoustic shadows developed on the choroidal side of the microaneurysms.If photocoagulation for microaneurysms was appropriately done, retinal changes were limited to within the inner retina around the microaneurysms and no changes were observed in retinal pigment epithelium.Within 2 months after photocoagulation, the microaneurysms changed into fine scars and the retinal structure normalized.Average retinal thickness of the fovea was 432 ± 70 μm before the procedure but reduced to 373 ± 84 μm at 2 months post surgery.CONCLUSION: Focal photocoagulation may be a less invasive method for treating microaneurysms, and spectral domain optical coherence tomography is useful for evaluating the efficacy of photocoagulation., Retina, 33(4), pp.726-731; 2013

Although Paget’s disease of bone (PDB) is common in western countries, it is extremely rare in Asian ones including Japan. Recently, oral risedronate (17.5 mg once daily) was approved in Japan as a treatment of PDB besides calcitonin and etidronate. However, there are few data regarding the efficacy of this agent, dose for patients with PDB in Japan, or the durability of its effect. The purpose of this study was to evaluate the midterm outcome of oral risedronate (17.5 mg once daily) for patients with PDB in Japan. Seventeen patients with PDB were treated with risedronate (17.5 mg once daily) for 8 weeks. Efficacy and its durability were accessed based on serum total alkaline phosphatase (ALP) and symptoms. Risedronate effectively suppressed bone turnover evaluated with serum total ALP in all patients. In 8 of 10 patients with bone pain, risedronate reduced the pain. On the other hand, tinnitus and hearing loss did not disappear but somewhat improved. None of the patients suffered severe complications. Seven of 17 patients required readministration of oral bisphosphonate (risedronate, six; alendronate, one) due to elevated total ALP at 27 months (mean ranging from 9 to 39 months) after the initial administration of risedronate. Treatment of oral risedronate (17.5 mg once daily) for 8 weeks is safe and effective for patients with PDB in Japan. However, the durability of its effect is limited in some patients.

Pasteurized autografts used in limb salvage operations for malignant musculoskeletal tumors have several advantages, including reduced disease transmission, economic efficiency, accessibility, and anatomical conformation. However, their use has been associated with bone absorption, fracture, and pseudarthrosis. Few studies exist which have assessed the long-term outcomes of pasteurized autografts. The purpose of this study was to investigate the clinical outcomes of patients treated with pasteurized autografts and to compare these outcomes across various graft types.A retrospective analysis of 46 patients treated with pasteurized autografts between 1992 and 2010 was conducted. The analysis included 22 intercalary bone grafts, 17 inlay grafts, 4 composite grafts, and 3 osteochondral grafts, with the mean follow-up period of 8.7 years (2-17 years).The 10-year survival rate of the 46 pasteurized autograft cases analyzed was 93.5 %, and the average bone union time between host and pasteurized autogenous bone was 9.5 months. Infections were identified in 6 (13 %) patients, fractures in 7 (15 %) patients, non-union in 8 (17 %) patients, and bone absorption in 6 (13 %) patients. Inlay grafts were completely incorporated with the host bone at the follow-up period. Combination with a vascularized fibular graft significantly reduced the risk of non-union and bone absorption (p 0.05 and p 0.01, respectively), with an average functional score of 23.1/30 (83.8 %).Our findings show that pasteurized bone grafts in combination with vascularized fibular grafts have improved outcomes and potential clinical indications.

1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

We describe a case with an inguinal myxoid liposarcoma that showed a favorable postoperative course after wide resection followed by arterial reconstruction and pedicle omental flap transfer for a wide defect including the femoral artery and vein. To our knowledge, this is the first report of the vascular reconstruction combined with pedicle omental flap transfer. In the long postoperative follow-up of 6 years, the course has been both oncologically and functionally favorable. Therefore, this reconstruction technique can be considered as a good treatment option.

We evaluated central retinal thickness (CRT) in diabetic macular edema (DME) using two different spectral-domain (SD) optical coherence tomography (OCT) instruments: the Cirrus and Spectralis OCTs. CRT was measured in 63 eyes of 32 patients with DME using both instruments on the same day. CRT measurements were significantly greater for the Spectralis than the Cirrus (p

To determine the factors predicting the oncologic and functional outcomes in patients with distal upper extremity soft tissue sarcomas, and to compare functional outcomes with those occurring in the proximal upper extremity, 28 consecutive patients with a soft tissue sarcoma in a distal upper extremity (group I) and 20 patients with one in a proximal upper extremity (group II) were surgically treated. The 5-year survival rate in patients with soft tissue sarcomas at distal and proximal locations were 74% and 87% for local recurrence, 84% and 66% for metastasis free, and 89% and 66% for overall, respectively. A significant adverse prognostic factor for local recurrence was deep location (P0.01). For metastasis-free and overall survival, adjuvant therapy (P0.001) and high-grade malignancy (P0.01) were significant poor prognostic factors. Deep location (P = 0.02) and prereferral surgery (P = 0.02) correlated with poorer function as reflected in the Musculoskeletal Tumor Society (MSTS) and Disabilities of the Arm, Shoulder, and Hand (DASH) functional scores, respectively. Patients in groups I and II showed good oncologic and functional outcomes. In group I patients, high-grade malignancy, adjuvant chemotherapy, and deep location were poor oncologic factors, and deep location and prereferral surgery were adverse prognostic factors for functional score.

Intraosseous glomus tumors of bone are extremely rare. We report a case of an intraosseous glomus tumor of the ulna. The patient was a 25-year-old woman who had a three-month history of a palpable mass in her right forearm with spontaneous pain. Radiographs showed cortical hypertrophy and a shell-like bone formation surrounding the small osteolytic lesion within the cortex of the ulna diaphysis. The differential diagnosis included benign bone-forming tumors, such as osteoid osteoma. The patient was treated with an en-bloc resection and filling with beta-TCP. Up to one year after the operation there has been no evidence of recurrence.

Surgical treatment has been the mainstay for extremity and trunk desmoid tumors with a negative surgical margin. However, even when resection with a wide surgical margin is achieved, the local recurrence rate remains high. The purpose of this study was to analyze the clinical outcome of patients with extremity and trunk desmoid tumors after surgical treatment and to determine the factors influencing local recurrence.Between January 1991 and December 2003, 30 of 58 patients with desmoid tumors referred to our institutions and surgically treated and followed up for more than 2 years were selected for this study. Patient age, gender, tumor size, location, status of disease (primary or recurrent), and surgical margins were analyzed as possible risk factors for recurrence.Sixteen (53%) of the 30 patients had a local recurrence. Eight of the 19 patients (42.1%) with a negative surgical margin experienced a recurrence. Younger age (30 years) was a significant risk factor for local recurrence (P0.05). Tumor size, surgical margin and previous surgical history were not associated with local recurrence. Younger age and female gender had a propensity for local recurrence, suggesting that the biological behavior of desmoid tumor may depend on the status of the disease at presentation.These results suggest that radical surgical treatment causing severe functional impairment should be avoided in selected cases on the basis of patient characteristics, and that other novel therapeutic tools may be necessary for patients in whom a higher risk of local recurrence is assumed or severe complications after surgical treatment are predicted.

Isolated brachialis muscle tears are rare. The rarity causes the misdiagnosis of this injury. We report 2 cases of males with an isolated brachialis muscle tear who were referred to our hospital with a diagnosis of a neoplasm in the arm. Both of the patients improved completely without radical treatment.

Clear cell sarcoma of the tendons and aponeuroses is an aggressive, rare soft tissue tumor with frequent metastases to regional lymph nodes. Sentinel lymph node biopsy, which has dramatically changed the management of melanoma, was used for clear cell sarcoma for an evaluation of popliteal and groin lymph node status. Although all isosulfan blue-stained groin lymph nodes were negative for malignancy, a popliteal lymph node was positive. Adjuvant 50 Gy of radiotherapy to the popliteal node might have been effective for local control for one year.

Hemangiomas arising from tendon and tendon sheath are rarely reported, and may be confused with other lesions of tendons. In this case report, a 19-year-old woman was diagnosed with a cavernous hemangioma originating in the left gracilis tendon and tendon sheath. When her symptoms initially developed, MRI did not delineate the lesion due to the relatively small size of the tumor. Nine years after the onset of the patient's complaints of knee pain and swelling, the tumor was adequately diagnosed on physical examination and MRI, and was resected with complete relief of symptoms.