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A 2-year-old girl underwent the Fontan operation for aortic valve stenosis, mitral valve stenosis, a hypo-plastic left ventricle, and a non-compacted right ventricle. The patient's cardiac function reduced gradually thereafter, mainly due to systemic ventricular dysfunction. A Berlin Heart EXCOR (BHE) ventricular assist device with a 10-mL pump was implanted at 4 years of age. After 465 days, BHE support without major complications, the patient underwent heart transplantation. A safe and long-term BHE support was achieved with proper case selection and repeated examinations.

OBJECTIVES The goal of this study was to identify the clinical significance of the deoxyribonucleic acid (DNA) damage response marker, phosphorylated H2A histone variant X, on the bridge to recovery in low-weight paediatric patients with dilated cardiomyopathy (DCM) after having a Berlin Heart EXCOR implanted. METHODS Consecutive paediatric patients with DCM who had an EXCOR implanted for DCM at our hospital between 2013 and 2021 were reviewed. Patients were classified into 2 groups according to the degree of DNA damage in the left ventricular cardiomyocytes—the low DNA damage group and the high DNA damage group—using the median value as the threshold. We examined and compared the preoperative factors and histologic findings associated with cardiac functional recovery following the explant procedure in the 2 groups. RESULTS Competing outcome analysis of 18 patients (median body weight, 6.1 kg) showed that the incidence of an EXCOR explant was 40% at 1 year after the implant procedure. Serial echocardiography revealed significant left ventricular functional recovery in the low DNA damage group 3 months after the implant. The univariable Cox proportional hazards model revealed that the percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was the significant factor associated with cardiac recovery and the EXCOR explant (hazard ratio, 0.16; 95% confidence interval, 0.027–0.51; P = 0.0096). CONCLUSIONS The degree of DNA damage response to the EXCOR implant may aid in predicting the bridge to recovery with EXCOR among low-weight paediatric patients with DCM.

An atrial switch operation was successfully performed in an 11-month-old patient with transposition of the great arteries. Good cardiac function was noted on regular follow-ups. A severe inferior vena cava-baffle stenosis was detected following a ruptured hepatocellular carcinoma at the age of 39. Liver cirrhosis and hepatocellular carcinoma could have been associated with liver congestion due to the stenosis. Following a partial hepatectomy, we performed an inferior vena cava-superior vena cava bypass without a cardiopulmonary bypass. The postoperative course was uneventful, the level of liver enzymes decreased to normal limits, and distant recurrence of hepatocellular carcinoma has not been observed.

Women with implantable left-ventricular assist devices (LVADs) experience gynecological bleeding (GYN-bleeding). However, a few studies have investigated female-specific problems. Therefore, this study aimed to identify the risk factors for adverse GYN-bleeding after LVAD implantation. We retrospectively analyzed 59 women (mean age: 41 ± 15 years) with long-term implantable LVAD support (≥ 6 months) at our institution between 2005 and 2018. The history of GYN-bleeding before implantation was defined as abnormal utero-ovarian bleeding, excessive menstruation, uterine fibroids, and endometrial lesions. GYN-bleeding after implantation was defined as a requirement of emergency outpatient visits and/or hospitalization, blood transfusions, hormonal therapy, and/or surgery. Additionally, risk factors for GYN-bleeding were identified using the Cox regression model. Twenty-four GYN-bleeding cases were seen in 15 patients (two times: five patients, three times: two patients, 0.18 events per patient-year). The 1- and 2-year GYN-bleeding-free rates were 84% and 73%, respectively. Twelve patients (17 events) required RBC ≥ 4 units, and five patients (7 events) required FFP ≥ 4 units. Seven patients required pseudomenopausal treatment after blood transfusion, and four patients required surgical treatment. Fifteen patients with GYN-bleeding after implantation were significantly younger than the remaining 44 patients without GYN-bleeding (34 ± 12 years vs. 43 ± 16 years, P = 0.02). Multivariable risk analysis showed a history of GYN-bleeding before implantation was a significant risk factor (hazard ratio 3.7 [1.2-10.6], P = 0.004). Patients with a history of GYN-bleeding before LVAD implantation have a high risk of developing GYN-bleeding after implantation. We should identify the high-risk population and prepare for the management of GYN-bleeding.

Anomalous origin of a left coronary artery from the right sinus of Valsalva with a single coronary orifice is a rare congenital anomaly, which has been associated with myocardial ischemia and sudden death. Surgical repair is recommended upon its detection. A 14-year-old boy was diagnosed with anomalous origin of a left coronary artery from the right sinus of valsalva with a single coronary orifice after a syncope attack. The patient underwent relocation of the left coronary orifice. The postoperative course was uneventful, with no ventricular arrhythmia or syncope. The patient did not develop cardiac ischemia or infarction on exercise Tc-99 m myocardial scintigraphy 8 months after the procedure.

Impella is a device effective for the treatment of cardiogenic shock. However, among small children, its application has limitations due to left ventricle size and vasculature and the turning diameter of the aortic arch. Herein, we report an 11-year-old girl with fulminant myocarditis who was successfully managed with Impella CP implantation via the right subclavian artery using a polyethylene terephthalate chimney graft. Compared with insertion via the femoral artery, this method has several advantages. That is, it can address limitations in aortic arch diameter and facilitate equable fixation of the Impella device in small pediatric patients.

Introduction: Pulmonary valve replacement (PVR) for pulmonary regurgitation (PR) was reported to provide beneficial effects on patients late after repair of tetralogy of Fallot (TOF). However, the impact of the degree of residual pulmonary stenosis (PS) in patients with severe PR remains unclear. Furthermore, the assessment of residual PS was difficult in patients with reduced RVEF. This study aimed to identify the impact of residual PS on the incidence of cardiovascular adverse events after PVR in preserved RVEF (pEF) or reduced RVEF (rEF) patients with PR late after repair of TOF. Methods: This was a single-center, retrospective review of 64 patients (56 repaired TOF-PS and 8 repaired TOF-pulmonary atresia) who underwent PVR for moderate to severe PR between 2003 and 2020. The threshold dividing pEF and rEF was 40%. Regarding residual PS, the definition the pressure gradient at the pulmonary valve in PSR group was 25 mmHg or more and less than 50mmHg. Patients were divided into 4 groups according to RVEF and the degree of residual PS (20 in PR-pEF, 12 in PSR-pEF, 25 in PR-rEF, 7 in PSR-rEF). Cardiovascular adverse events included cardiac death, prosthetic valve dysfunction, arrhythmia requiring treatment, and hospitalization for heart failure. Based on the above, the influence of hemodynamic parameters before PVR was analyzed. Results: The median follow-up period was 6.1 years [interquartile range 2.7-10]. There was no cardiac death and prosthetic valve dysfunction. Two patients died due to non-cardiac reason. Twenty-two (34%) patients showed cardiovascular adverse events. The cardiovascular adverse event-free rates were the highest in PSR-pEF group (100% at 5 years) and the lowest in PSR-rEF group (43% at 5 years) after PVR (log-rank p < 0.01), and 60% in PR-pEF and 70% in PR-rEF. In comparison between PSR groups, PSR-rEF had higher RVEDP (8±2 vs 13±2 mmHg, p < 0.01) and larger RAVI (71±25 vs 105±42 ml/m 2 , p=0.043). Conclusion: Patients with PSR-rEF had a high incidence of cardiovascular adverse events, high RVEDP, and large RAVI, suggesting RV adverse remodeling. The association between the degree of residual PS and RVEF should be taken into consideration on deciding the timing of PVR for PR.

Background:In patients with tetralogy of Fallot with the diminutive pulmonary arteries, we sometimes have to give up the complete intra-cardiac repair due to insufficient growth of the pulmonary arteries. We have carried out palliative intra-cardiac repair using a fenestrated patch.Methods:Of all 202 patients with tetralogy of Fallot in our centre since 1996, five patients (2.5%) with the diminutive pulmonary arteries underwent palliative intra-cardiac repair using a fenestrated patch. Mean operative age was 1.8 years. Previous operation was Blalock–Taussig shunt in 4. At operation, the ventricular septal defect was closed using a fenestrated patch and the right ventricular outflow tract was enlarged. Follow-up period was 9.8 ± 2.6 years.Results:There were no operative and late deaths. Fenestration closed spontaneously on its own in four patients 2.7 ± 2.1 years after the intra-cardiac repair with a stable haemodynamics; however, the last patient with the smallest pulmonary artery index had supra-systemic pressure of the right ventricle post-operatively. The fenestration was emergently enlarged. Systemic arterial oxygen saturation was significantly and dramatically increased from 83.5 to 94% after the palliative intra-cardiac repair, and to 98% at the long term. A ratio of systolic pressure of the right ventricle to the left was significantly decreased to 0.76 ± 0.12 at the long term. Now all five patients were Ross classification class I.Conclusion:Although frequent catheter and surgical interventions were needed after the palliative intra-cardiac repair, this repair might be a choice improving quality of life with good results in patients with tetralogy of Fallot associated with the diminutive pulmonary arteries.

Berlin Heart EXCOR® (BHE) ventricular assist device (VAD) (Berlin Heart, Berlin Heart AG, Berlin, Germany) implantation is prevalent in patients with severe heart failure. However, clinical outcomes of pediatric patients on long-term BHE support remain mainly unknown. This study aimed to report our clinical experience with long-term support of pediatric patients with severe heart failure supported by BHE VAD. Clinical outcomes of 11 patients (median age 8.4 months; two male), who underwent LVAD implantation of the Berlin Heart EXCO® (BHE) VAD (Berlin Heart, Berlin Heart AG, Berlin, Germany) between 2013 and 2017 at our institution were reviewed. The median support period was 312 (range 45-661) days and five patients were supported for more than 1 year. The longest support duration was 661 days. No mortality occurred, and six patients were successfully bridged to heart transplantation, while three patients were successfully weaned off the device. Two patients are currently on BHE support while they await heart transplantation. Four patients had cerebral bleeding or infarction, but only one case of persistent neurological deficit occurred. No fatal device-related infection occurred during LVAD support. BHE VAD can provide long-term support for pediatric patients with severe heart failure with acceptable mortality and morbidity rates with long-term support.

Introduction: Restrictive right ventricular physiology (r-RVP) is common in late after repair of tetralogy of Fallot (TOF) and reported to reflect diastolic dysfunction. Right ventricular (RV) diastolic dysfunction sometimes remains after pulmonary valve replacement (PVR) and is associated with arrhythmia. Pulmonary arterial end-diastolic forward flow (EDFF) is considered as a marker of r-RVP, and associated with RV volume, right atrial (RA) function, and the degree of pulmonary valve regurgitation (PR). The aim of this study is to evaluate the impact of EDFF before PVR on the clinical outcomes after PVR in patients with repaired TOF. Methods: This was a single-center, retrospective review of 46 patients who underwent PVR for moderate to severe PR between 2003 and 2019. Cases were examined EDFF before PVR and divided into two groups: with EDFF (EDFF+, n=23) and without EDFF (EDFF-, n=23). Patients with histories of atrial tachyarrhythmia underwent concomitant maze procedure. RV and RA volume were evaluated by magnetic resonance imaging. Post-PVR survival and the development of arrhythmia were assessed. Results: Age at PVR was 38±14 in EDFF+ and 35±10 years old in EDFF- (p=0.41), and the incidence of preoperative arrhythmia was not different (30% and 35%, p=1.0). RVESVI (102±24 and 86±26 ml/m 2 , p=0.048) and RAVI (84±19 and 70±20 ml/m 2 , p=0.025) before PVR, and RVEDVI (116±27 and 100±24 ml/m 2 , p=0.04) and RVESVI (71±23 and 55±16 ml/m 2 , p=0.01) at one year after PVR were greater in EDFF+. One patient in each group died due to non-cardiac disease. 5-year atrial tachyarrhythmia free rate was 62% in EDFF+ and 100% in EDFF- (Log-rank p=0.004). Multivariate Cox regression analysis revealed EDFF before PVR was a risk factor for atrial tachyarrhythmia after PVR (Hazard ratio 17 (95% CI, 2.2-406), p=0.025). Conclusions: EDFF before PVR was a significant risk factor for the development of postoperative atrial tachyarrhythmia. EDFF can complement the current indication for PVR.

Introduction: Right ventricular (RV) failure following definitive repair of congenital heart diseases (CHD) have great impact on survival after surgical intervention. Recently, human induced pluripotent stem cell-derived cardiomyocyte (hiPS-CM) sheet transplantation ameliorated left ventricular dysfunction in preclinical study, associating possible efficacy in RV failure of CHD. Hypothesis: We hypothesized whether hiPS-CM patch could improve distressed RV function in rat pressure overload model. Methods: F344/NJcl- rnu/rnu rat (7-9 weeks old, male, 180-210g) underwent pulmonary artery banding (PAB) via left thoracotomy under general anesthesia. Four weeks after PAB, hiPS-CM patch transplantation to the RV was performed in the hiPS-CM patch transplantation group (n = 10), whereas a sham operation was performed in the sham group (n =10). We evaluated for cardiac catheterization (CATH) data and pathological findings 8 weeks after PAB. Results: In CATH, RV end diastolic pressure (sham; 10.0 ± 4.1 vs hiPS-CM; 5.5 ± 2.7 mmHg, P < 0.01), time constant of isovolumic relaxation (sham; 24.9 ± 8.6 vs hiPS-CM; 16.5 ± 6.4 ms, P < 0.01) and end-diastolic pressure volume-relation (sham; 365.6 ± 246.3 vs hiPS-CM; 214.0 ± 147.4 mmHg/mL, P 2 , P Conclusions: In a rat model of a pressure-overload RV, hiPS-CM patch transplantation improved the diastolic function with suppressed ventricular fibrosis and increased capillary density, suggesting a promising treatment for RV failure in CHD patients after surgical repair.

OBJECTIVES The clinical significance of persistent end-diastolic forward flow (EDFF) after pulmonary valve replacement (PVR) remains unclear in patients with repaired tetralogy of Fallot. This study aimed to identify the characteristics of these patients and the impact of persistent EDFF on outcomes. METHODS Of 46 consecutive patients who underwent PVR for moderate to severe pulmonary regurgitation between 2003 and 2019, 23 (50%) did not show EDFF before PVR [group (−)]. In the remaining 23 patients with EDFF before PVR, EDFF was diminished after PVR in 13 (28%) [group (+, −)] and persisted in 10 (22%) [group (+, +)]. The following variables were compared between these 3 groups: (i) preoperative right ventricular (RV) and right atrial volumes measured by magnetic resonance imaging, haemodynamic parameters measured by cardiac catheterization and the degree of RV myocardial fibrosis measured by RV biopsy obtained at PVR and (ii) the post-PVR course, development of atrial arrhythmia and need for intervention. RESULTS A high RV end-diastolic pressure, a greater right atrial volume index and a greater RV end-systolic volume index before PVR and a high degree of RV fibrosis were significantly associated with persistent EDFF 1 year after PVR. Persistent EDFF was a significant risk factor for postoperative atrial tachyarrhythmia, and catheter ablation and pacemaker implantation were required more frequently in these patients. CONCLUSIONS Persistent EDFF after PVR could predict a worse prognosis, especially an increased risk of arrhythmia. Close follow-up is required in patients with persistent EDFF for early detection of arrhythmia and prompt reintervention if necessary. Clinical trial registration number Institutional review board of Osaka University Hospital, number 16105

A 45-year-old woman with repaired complex congenital heart disease, who underwent placement of Jarvik 2000, a ventricular assist device (VAD) for 4 years, experienced abdominal pain due to outflow graft compression caused by seroma formation between the outflow graft and ringed Gore-Tex graft. We exchanged the pump of Jarvik 2000 and punched several small holes in the new ringed Gore-Tex graft. Seroma formation between the two grafts should be considered as a cause of outflow graft obstruction in patients with the long-term support of VAD, and additional surgical interventions to the ringed Gore-Tex graft may prevent this complication.

Pure restrictive cardiomyopathy is a strong risk factor for poor outcomes in children with cardiomyopathy on ventricular assist devices. Owing to concomitant right heart failure, children with end-staged restrictive cardiomyopathy who are supported with a ventricular assist device often require a biventricular assist device, which is another risk factor for waitlist mortality in heart transplantation candidates. Herein, we report the case of a 3-year-old boy with pure restrictive cardiomyopathy who successfully underwent heart transplantation after 12 months of support with staged biventricular assist devices. Owing to the progression of diastolic dysfunction, the left ventricular assist device could not provide adequate circulation support. Despite the provision of biventricular assist device support, the patient required a complex management strategy that involved balancing the left and right ventricular assist device supports. We were able to stabilize the patient by careful synchronization of the supports and proceeded to heart transplantation. TRIAL REGISTRATION: Clinical Registration No.: Institutional Review Board of Osaka University Hospital, approval no. 16105.

The surgical management of severe truncal valvular dysfunction is still challenging in neonates with persistent truncus arteriosus. This report describes a 14-day-old neonate with severe truncal valve insufficiency successfully undergoing truncal valve repairs, and followed by valve replacement at the age of 4 years. The truncal valve was quadricuspid with two large and two small leaflets, and all leaflets had severe dysplastic and myxomatous changes. We performed leaflet extension and bicuspidization valvuloplasty for this valve. This patient obtained somatic growth for 4 years without heart failure symptoms, and safely underwent prosthetic valve replacement. This technique would be effective for truncal valve dysfunction in neonates as the life-saving and the bridging procedure to valve replacement.

This report describes a 3-year-old infant with post-operative mediastinitis complicated by a contained rupture of the right ventricle. A contained rupture is recognised as the huge pulsating prominence of the anterior chest wall. CT confirmed blood communication between the right ventricular outflow tract and the cavity surrounded by the pectoral major musculocutaneous flap. This is a significant case in which severe adhesion between the right ventricle and the musculocutaneous flap could maintain her stable haemodynamics with a pulsating prominence.

The penalty avoiding rational policy making algorithm (PARP) [1] previously improved to save memory and cope with uncertainty, i.e., IPARP [2], requires that states be discretized in real environments with continuous state spaces, using function approximation or some other method. Especially, in PARP, a method that discretizes state using a basis functions is known [3]. Because this creates a new basis function based on the current input and its next observation, however, an unsuitable basis function may be generated in some asynchronous multiagent environments. We therefore propose a uniform basis function and range extent of the basis function is estimated before learning. We show the effectiveness of our proposal using a soccer game task called “Keepaway.”

Background and Purpose— Fibroblast growth factor-2 (FGF-2) administration and bone marrow stromal cell (MSC) transplantation could improve neurological deficits after occlusive cerebrovascular disease. In the present study, we examined the effects of neurological improvement after transient middle cerebral artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene–transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector. Methods— Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2–modified MSCs with HSV-1 1764/-4/pR19/ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours after transient right MCAO. All animals underwent behavioral tests for 21 days, and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and 14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2 production in the ipsilateral hemisphere of the MCAO was measured with ELISA. Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was applied. Results— The stroke animals receiving FGF-2–modified MSCs demonstrated significant functional recovery compared with the other groups. Fourteen days after the MCAO, there was a significant reduction in infarction volume only in FGF-2–modified MSC-treated group. FGF-2 production in the FGF-2–modified MSC-treated brain was significantly higher compared with the other groups at 3 and 7 days after MCAO. Administrated FGF-2–modified MSCs strongly expressed the FGF-2 protein, which was proven by ELISA. Conclusions— Our data suggest that the FGF-2 gene–modified MSCs with the HSV-1 vector can contribute to remarkable functional recovery after stroke compared with MSCs transplantation alone.

Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.

It has been shown that a wide variety of antioxidants inhibits macrophage scavenger and polylactosamine receptor activities. The activity of macrophage scavenger receptors to take up oxidized low density liporprotein is also inhibited by protein kinase inhibitors but enhanced by protein phosphatase inhibitors. We studied whether the antioxidants including lipid-soluble phenolic, water-soluble phenolic, glutathione-related and ascorbic acid-related antioxidants were effective to inhibit protein phosphorylation of macrophages. Lower than 100 μM of α-tocopherol, probucol, propyl gallate, nordihydroguaiaretic acid, curcumin, quercetin and Trolox inhibited total protein phosphorylation of thioglycollate-induced mouse macrophages as assessed by H332PO4 incorporation. Lower than 1 mM of α-tocopherol, probucol, butylated hydroxytoluene, curcumin, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, glutathione, glutathione isopropyl ester, N-acetylcysteine, ascorbic acid, erythorbic acid and dehydroascorbic acid inhibited protein tyrosine phosphorylation of macrophages in the presence of vanadate, a protein tyrosine phosphatase inhibitor, as assessed by Western-blot analysis using anti-phosphotyrosine IgG monoclonal antibody. Most of the antioxidants inhibited protein tyrosine phosphorylation of epidermal growth factor (EGF) receptor of A431 cells in a cell-free system. Oxidative satus of macrophages examined by using dihydrorhodamine 123, and all the catechins reduced their oxidative status. Above results suggest that oxidative stress in macrophages maintain or enhance protein phosphorylation, and that antioxidants reduce protein phosphorylation and the receptor activities by reducing oxidative status.

Several studies indicate that the poorer outcomes for African--Americans after transplantation may be due to decreased effectiveness of immunosuppressive agents. Using an in vitro test of immunocompetence (IMC), we measured the effects of immunosuppression on African-American, compared with Caucasian, kidney or liver transplantation recipients. The IMC result was the highest of three mixed lymphocyte culture responses using validated stimulator cell pools. A total of 293 tests were done in Caucasians and 144 in African-Americans. Overall, the IMC for African- Americans was 38, compared with 19 for Caucasians (p < 0.01). This decreased effect of immunosuppression (higher IMC) was the same for liver as for kidney transplant recipients, occurred at the 2--3-yr interval, and was largely in patients of tacrolimus (FK506), with a strong but not significant trend in cyclosporine (CYA) recipients. The two groups were on the same nominal immunosuppression and FK506 and C'YA levels were not different. We conclude that African-Americans retain more immune responsiveness on equivalent dose immunosuppression, notable particularly in years 2-3 after transplantation when earlier graft loss occurs in this group.

消化器癌術前貯血例において,保存自己血中のエンドトキシン (ET) と炎症性サイトカインとの関連性,および閉塞性黄疸とこれらの値との関係を検討した.対象は閉塞性黄疸合併担癌29例,非合併担癌39例の計68例で,貯血された自己血中ETおよびtumor necrosis factor α (TNF-α), interleukin-6 (IL-6) を測定し,相互間の関連や自己血保存期間との関係を検討した.黄疸群の自己血中ETは,非黄疸群に比し有意に高値を示し,保存期間の延長とともに上昇する傾向を示した.さらに,自己血中 TNF-α はETの上昇とともに高値を示し,両者の間には0.87と高い正の相関を認めた.閉塞性黄疸合併担癌患者では,末梢血あるいは自己血中ETが高値を示す例があり,その結果として炎症性サイトカインが上昇する可能性があると思われた.今後さらに両者の関連性に関し検討が必要と思われた.

Effect of exogenously added water-soluble antioxidants on the mouse macrophage lectin-like receptor activity for oxidized erythrocytes was investigated. A monolayer of thioglycollate-induced mouse peritoneal macrophages was preincubated with each of the antioxidants at 37 degrees C for 1 h, and the binding for mouse erythrocytes oxidized with ADP-chelated Fe(III) was examined. The binding was decreased by preincubation of macrophages with ascorbic acid-related compounds including ascorbic acid, erythorbic acid and dehydroascorbic acid in a dose-dependent fashion at relatively high concentrations above 10 microM. The binding was similarly decreased by preincubation of macrophages with catechin compounds including epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate in a dose-dependent fashion at 0.01-100 microM. The binding was more effectively decreased by preincubation of macrophages with thiol-related compounds including glutathione, oxidized glutathione, glutathione isopropyl ester and N-acetylcysteine in a dose dependent fashion at relatively low doses below 1 microM. These results showed that water-soluble antioxidants especially glutathione and its derivatives reduced the ability of macrophages to bind oxidized erythrocytes, suggesting that the activity of lectin-like receptors of macrophages for oxidized erythrocytes was regulated by oxidative mechanisms.

Effect of exogenously added antioxidants on the activity of the mouse macrophage scavenger receptors for oxidized low density lipoprotein (oxLDL) was investigated. Binding of oxLDL-coated erythrocytes and/or 125I-oxLDL to a monolayer of thioglycollate-induced peritoneal macrophages preincubated with antioxidants at 37°C for 2 h was examined. The binding was effectively or slightly decreased by preincubation of macrophages with probucol, butylated hydroxytoluene, α-tocopherol, sesamol, propyl gallate, quercetin, nordihydroguaiaretic acid, epicatechin gallate, epigallocatechin gallate (EGCg), glutathione isopropyl ester (GSH-Pr), N-acetylcysteine, ascorbic acid, erythorbic acid, and Desferal at concentrations lower than 100 μM. The binding was slightly enhanced by preincubation of macrophages with buthionine sulfoximine. The antioxidants and related compounds inhibited the formation of foam cells induced by oxLDL in the prolonged incubation for 24 h. Glutathione, oxidized glutathione and dehydroascorbic acid inhibited the foam cell formation, Total cholesterol accumulation induced by oxLDL in the prolonged incubation was reduced by the phenolic antioxidants. The number of scavenger receptors of macrophages was unchanged upon treatment with EGCg and GSH-Pr. The results indicate that the antioxidants at relatively high concentrations inhibited macrophage functions, binding of oxLDL, foam cell formation, and accumulation of cholesterol, and suggest that the scavenger receptor activity of macrophages was exerted by certain oxidative mechanisms.

Background: Homologous blood transfusion (HBT) has the risk of an immunosuppressive effect and may adversely affect the prognosis of patients with carcinomas. Autologous blood transfusion (ABT) has not yet become a standard procedure in gastroenteric cancer surgery. We investigated the usefulness and problems of ABT combined with the use of recombinant human erythropoietin (rh-EPO). Methods: An evaluation of autologous blood transfusion (ABT) combined with recombinant human erythropoietin (rh-EPO) treatment was conducted in 46 patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative autologous blood donation (ABD) was accomplished for 25 of the 46 patients. The preoperative changes in hemoglobin and hematocrit in relation to route of administration of erythropoietin were studied. In addition, intraoperative blood requirements and the postoperative complications for patients who predonated were compared with those of patients who underwent surgery without autologous predonation. Results: The proportion of patients not requiring additional homologous blood transfusions (HBT) during operation was significantly higher in the ABD group than in the non-ABD group (88% versus 38%). The incidence of postoperative complications was significantly higher in patients receiving HBT than in nontransfused patients and in those receiving ABT. Conclusions: Preoperative autologous blood donation in combination with rh-EPO therapy markedly reduced the requirement for homologous blood transfusion during surgery in patients with hepatocellular carcinoma having hepatectomy.

In a recent one decade, we experienced 461 cases of advanced colorectal cancer, 22 cases (4.5%) of which had small colorectal cancer (SCR) less than 20min in size. A clinicopathological study was made to compare SCR and ordinary colorectal cancers (OCR) over 21mm in size. There were no significant differences in the male-to-female ratio and location of the lesions between both groups. The mean age was young and the invasion depth of mp was common in SCRs compared to OCRs. Rates of vascular invasion and lymph nodes metastases were significantly lower in SCRs. Curative resection rate was higher in SCRs and the prognosis was significantly better in SCRs than OCRs. Another analysis of SCRs was conducted. As for the macroscopic type, 10 lesions were elevated type and 12 lesions were depressed type. As for the growth form, five lesions were PG type and 17 lesions were NPG type. In most of the invasive lesions, elevated type and PG type were inner circlar propria muscle. In most of the invasive lesions, depressed type and NPG type were deeper than outer longitudinal propria muscle. Lymphnode metastasis was found in 3 cases in which macroscopic type and growth form were all depressed type and NPG type. Recurrence occurred in two of those three cases. We conclude that depressed type and NPG type SCRs have a malignant potential. But as a whole, the prognosis of SCRs was better than OCRs. It is important to find out these small colorectal cancers (SCRs) .

A total of 110 patients who were operated on for gastrointesinal cancer were subjected to a study of elucidating the correlations between intraoperative blood transfusion and postoperative cellular immunological activity. All patients were classified into three groups; homologous transfusion group, autologous transfusion group, and no transfusion group by intraoperative transfusion method. The ratio of CD4 to CD8 (CD4/CD8), natural killer cell activity (NK cell) and immunosuppressive acidic protein (IAP) were compared among these three groups before and after the operation. The NK cell activity decreased after the operation and the decrease was prolonged in the homologous transfusion group with or without leukocyte depletion filter. IAP increased postoperatively in the hemologous group without the filter, which was significantly higher than those of homologous group with the filter and autologous transfusion group. Postoperative infections occurred in 36% of the homologous, 16% of autologous transfusion group, and 2% of no-transfusion group. A significantly higher incidence of postoperative infections complication was noted in homologous group than that of autologous group. Compared with homologous transfusion, autologous transfusion is thought to be very useful in surgeries for gastrointestinal cancers in terms of the maintenance of the cellular immunological activity.

Percutaneous transhepatic biliary drainage (PTBD) guided by color Doppler echography was performed on nine patients. By color Doppler echography, the segmental and subsegmental branches of both the portal vein and the hepatic artery could be identified and discriminated from the bile ducts because of their color flow mapping. We could select the safe pathway of needle advance, which did not injure the vessels. Thus, complication of bleeding did not occur in any of the patients. Color Doppler echography seems a very useful and safe method for the guidance of PTBD.

We have previously found that ability of mouse macrophages to bind and take up oxidized low-density lipoprotein (oxLDL) through scavenger receptors is significantly enhanced when the cells are plated on fibronectin (FN)-coated culture substrates. Here, the mechanisms of the enhancement of the scavenger receptor activity by the substrate-bound FN was investigated using thioglycollate-induced mouse peritoneal macrophages. A Ca(2+) channel blocker diltiazem and a calmodulin inhibitor W-7 reduced the scavenger receptor activity of the macrophages plated on FN-coated substrate to the level of the cells plated on uncoated substrate, as assessed by oxLDL binding, while the scavenger receptor activity of the macrophages on uncoated substrate was little affected. Similarly, FN-induced enhancement of the scavenger receptor activity assessed by oxLDL uptake was selectively inhibited by Ca(2+) channel blockers (diltiazem, nifedipine, verapamil) and calmodulin inhibitors (W-7, trifluoperazine). Intracellular free Ca(2+) level of the macrophages was increased, depending on extracellular Ca(2+), when plated on FN-coated substrate. This increase in the Ca(2+) level was inhibited by diltiazem and RGD-containing peptides present in cell adhesive region of FN. Like the substrate-bound FN, Ca(2+) ionophore A23187 enhanced the scavenger receptor activity of binding and taking up of oxLDL. These results indicate that substrate-bound FN enhances scavenger receptor activity of macrophages by increasing channel-dependent Ca(2+) influx. A microtubule disruptor, colchicine, and an actin filament disruptor, cytochalasin B, inhibited the FN-induced enhancement of the scavenger receptor activity, suggesting that these cytoskeletal structures are required for transmission of the adhesion signal of FN. The number of the scavenger receptors was found to increase by 1.4-fold upon adhesion signal of FN. We suggest that substrate-bound FN increases the number of the macrophage scavenger receptors as a result of induction of Ca(2+) influx and causes increased accumulation of oxLDL within the cells, rendering the cells more susceptible to conversion into foam cells.