43 results on '"Sasajima, T."'
Search Results
2. Design of a compact W-shaped pumped divertor in JT-60U
- Author
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Sakurai, S., primary, Hosogane, N., additional, Kodama, K., additional, Masaki, K., additional, Sasajima, T., additional, Kishiya, K., additional, Tsurumi, S., additional, Takahashi, S., additional, Saidoh, M., additional, Inoue, M., additional, Umakoshi, T., additional, Onozuka, M., additional, and Morimoto, M., additional
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- 1997
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3. OPERATION EXPERIENCES WITH JT-60U PLASMA FACING COMPONENTS AND EVALUATION TESTS OF B4C-OVERLAID CFC/GRAPHITES
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ANDO, T., primary, YAMAMOTO, M., additional, ARAI, T., additional, KAMINAGA, A., additional, SASAJIMA, T., additional, SAIDOH, M., additional, JIMBOU, R., additional, KODAMA, K., additional, SHIMIZU, M., additional, AKIBA, M., additional, NAKAMURA, K., additional, ARAKI, M., additional, SUZUKI, S., additional, DAIRAKU, M., additional, YOKOYAMA, K., additional, FUKAYA, K., additional, BOLT, H., additional, and LINKE, J., additional
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- 1993
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4. EFFECT OF VENOUS OCCLUSION ON SKIN PO2 OF LOWER EXTREMITIES WITH ARTERIAL OBSTRUCTIVE DISEASES AND SYMPATHECTOMY
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Sasajima, T., primary, Koyama, T., additional, Kokubo, M., additional, Kubo, Y., additional, Kikuchi, Y., additional, and Samejima, N, additional
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- 1981
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5. Prolonged infective SARS-CoV-2 omicron variant shedding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remdesivir.
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Nakamura K, Sugiyama M, Ishizuka H, Sasajima T, Minakawa Y, Sato H, Miyazawa M, Kitakawa K, Fujita S, Saito N, Kashiwabara N, Kohata H, Hara Y, Kanari Y, Shinka T, and Kanemitsu K
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- Male, Humans, Aged, SARS-CoV-2, BNT162 Vaccine, COVID-19 Drug Treatment, COVID-19, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
We report a case of prolonged shedding of the infective SARS-CoV-2 omicron variant BA.1.1.2 in a 79-year-old male patient with diffuse large B-cell lymphoma, after receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was admitted to our hospital in late March 2022 for the sixth course of R-CHOP chemotherapy. Initially, the patient tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in-hospital loop-mediated amplification assay with a nasopharyngeal swab, both on the day of admission and three days later. However, the patient developed fever and was diagnosed with coronavirus disease (COVID-19) six days after admission and was suspected to have contracted the infection in the ward. Viral shedding continued for more than three months, with confirmed viral infectivity. As compared to the original Wuhan-Hu-1/2019 strain, amino acid substitutions including S36 N in non-structural protein (NSP)2, S148P, S1265del and L1266I in NSP3, G105D in NSP4, G496S, A831V, or V987F in spike protein, and I45T in open-reading frame (ORF)9b were randomly detected in isolated viruses. Although the patient had received two doses of the BNT162b2 vaccine approximately six months earlier and the third dose on day 127 after the infection, both serum anti-spike and anti-nuclear protein IgG and IgM tests were negative at day 92, 114, and 149 after the infection. The patient finally cleared the virus after the third course of remdesivir and did not have further recurrence., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)
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- 2023
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6. Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study.
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Hide M, Fukunaga A, Suzuki T, Nakamura N, Kimura M, Sasajima T, Kiriyama J, and Igarashi A
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- Humans, Omalizumab adverse effects, East Asian People, Chronic Disease, Product Surveillance, Postmarketing, Treatment Outcome, Anti-Allergic Agents adverse effects, Chronic Urticaria drug therapy, Urticaria drug therapy, Urticaria chemically induced, Drug-Related Side Effects and Adverse Reactions
- Abstract
Background: The safety and efficacy of omalizumab in chronic spontaneous urticaria (CSU) patients has been established, but real-world long-term data remain scarce, especially in Japan., Methods: 52-week, open-label, single-arm, observational study evaluated the safety and effectiveness of first-time omalizumab in Japanese CSU patients responding inadequately to conventional therapies., Results: Overall, 235 of 280 patients completed the study. Most patients were aged ≥ 18 and < 65 years; adolescents (≥ 12 and ≤ 18 years) accounted for 9.6% of the total population. The mean ± standard deviation (SD) duration of CSU at baseline was 1.6 ± 3.1 years; 46.1% of patients had had CSU for < 6 months. At baseline, the mean ± SD of Urticaria Control Test (UCT) score, Weekly Urticaria Activity Score (UAS7), and Dermatology Life Quality Index (DLQI) were 5.1 ± 3.2, 25.2 ± 11.9, and 8.4 ± 5.9, respectively. The mean ± SD duration of the observation period was 330.3 ± 86.2 days. Relapse was reported in 65 patients, 51, 9, and 5 of whom required retreatment with omalizumab 1, 2, and ≥ 3 times, respectively. The incidence of adverse events (AEs), serious AEs, and adverse drug reactions (ADRs) was reported in 11.8%, 1.4%, and 3.9% of patients, respectively. The most common AEs were urticaria (1.8%) and eczema (1.1%). No adolescents experienced ADRs. A cumulative of 92.8% of patients responded in the Physician's Global Impression of Change, with 81.3%, 75.0%, and 95.1% of patients achieving UCT ≥ 12, UAS7 ≤ 6, and DLQI ≤ 5 up to Week 52, respectively., Conclusions: This study supports the safety and effectiveness of omalizumab in CSU patients who responded inadequately to conventional therapies in real-world clinical practice in Japan., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)
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- 2023
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7. Outcomes of Infrapopliteal Bypass for Chronic Limb-Threatening Ischemia are Worse in Renal Transplant Patients than in Hemodialysis-Dependent Patients.
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Kamada K, Kokubo T, Nagita H, Namiki Y, and Sasajima T
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- Humans, Chronic Limb-Threatening Ischemia, Treatment Outcome, Risk Factors, Limb Salvage, Lower Extremity blood supply, Renal Dialysis adverse effects, Ischemia, Retrospective Studies, Vascular Patency, Kidney Transplantation, Peripheral Arterial Disease
- Abstract
Background: Comparisons of distal bypass outcomes between hemodialysis-dependent (HD) and renal transplant (RT) patients have been reported, but the influences of immunosuppressive therapy on the outcomes remain unclear because of the limited number of RT patients who underwent distal bypass or cohort heterogenicity. We compared outcomes of distal bypass for chronic limb-threatening ischemia (CLTI) with homogenous ischemic limb pathology., Methods: Between January 2014 and December 2019, we performed 334 infrapopliteal bypass procedures using vein grafts for 275 consecutive CLTI patients with tissue loss. Among them, there were 130 HD patients (47.3%) (163 limbs) and 11 RT patients (4%) (15 limbs), and 30-day mortality, 5-year primary and secondary patency (PP and SP), limb salvage (LS), amputation-free survival rates, and wound healing (WH) status were compared between the HD and RT patient groups., Results: Nine HD patients died within 30 days after surgery (7%), whereas no deaths were observed among the RT patients. Five-year PP and SP rates in the RT group 39% and 41%, which were significantly worse compared to 64% and 82% in the HD group (P < 0.01). Unsuccessful rate of revision surgery including hemodynamically failed grafts after revision reached over 80% in the RT group, which was technically unfeasible pathology for graft salvage (vs. 3% in the HD group), and WH, and LS rates were significantly worse in the RT group., Conclusions: In comparison with HD patients, RT patients showed a lower LS rate for CLTI. The lower LS rate was associated with a lower SP rate, which was caused by disease progression of distal arteries in the foot., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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8. Real-life long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma: A post-marketing surveillance.
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Nakamura N, Kashitani Y, Yoshisue H, Nagasaki M, and Sasajima T
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- Adolescent, Anaphylaxis chemically induced, Child, Female, Fever chemically induced, Humans, Hypersensitivity, Immediate chemically induced, Japan, Male, Product Surveillance, Postmarketing, Severity of Illness Index, Treatment Outcome, Urticaria chemically induced, Anti-Asthmatic Agents therapeutic use, Asthma drug therapy, Omalizumab therapeutic use
- Abstract
Background: Omalizumab is approved as add-on therapy for pediatric asthma since 2013 in Japan, however, its data in clinical practice is limited. This post-marketing surveillance aimed to evaluate long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma in real-life setting., Methods: This 104-week, multicenter surveillance was conducted from September 2013 to May 2019 by central registration method. Patients with severe allergic asthma aged ≥6 and < 15 years at initiation of treatment who were first-time omalizumab users were included. The primary endpoints included incidence of adverse drug reactions and physician's Global Evaluation of Treatment Effectiveness (GETE). The secondary endpoints included incidence of serious adverse events, adverse events and adverse drug reactions of special interest and asthma exacerbation-related events., Results: Of the 128 patients enrolled, 127 completed the surveillance and were included for safety and effectiveness analysis. Thirteen patients experienced 20 adverse drug reactions with an incidence rate of 10.2%. The most frequent adverse drug reactions were pyrexia (2.4%) and urticaria (1.6%). In total, adverse events and serious adverse events occurred in 60 (47.2%) and 30 patients (23.6%) respectively. Two patients experienced anaphylactic reaction and 1 patient experienced type 1 hypersensitivity. 77.2% had an effective response to omalizumab according to GETE at final assessment, and frequency of all asthma exacerbation-related events decreased in post-treatment versus pre-treatment., Conclusions: Long-term omalizumab treatment showed no new safety signals in pediatric patients with severe allergic asthma. The observed safety and effectiveness profile was consistent with previous studies., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)
- Published
- 2021
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9. Arterial Reconstruction for Patients with Chronic Limb Ischemia Improves Ambulatory Function and Health-related Quality of Life.
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Sasajima T, Sasajima Y, Akazawa K, and Saito Y
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- Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Humans, Intermittent Claudication diagnosis, Intermittent Claudication physiopathology, Ischemia diagnosis, Ischemia physiopathology, Japan, Longitudinal Studies, Male, Middle Aged, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease physiopathology, Prospective Studies, Recovery of Function, Severity of Illness Index, Time Factors, Treatment Outcome, Vascular Patency, Endovascular Procedures adverse effects, Exercise Tolerance, Intermittent Claudication surgery, Ischemia surgery, Peripheral Arterial Disease surgery, Quality of Life, Vascular Grafting adverse effects, Walking
- Abstract
Background: Arterial reconstruction (AR) for limb ischemia may improve ambulatory function (AF) and health-related quality of life (HR-QoL). However, the efficacy of AR in terms of HR-QoL varies in studies, probably because of cohort differences in disease severity, hemodynamic outcomes, and observation duration. We assessed HR-QoL for patients with various severities of ischemia in a 3-year observational study., Methods: We conducted a single-center 3-year observational study using Short Form 36 in patients with chronic limb ischemia. Between 2001 and 2009, 515 consecutive patients had AR, and 330 who underwent elective AR consented to the study. Of the 330 patients (claudicants 49%, critical limb ischemia [CLI] 51%), 307 underwent bypass and 23 endovascular therapy. Postal questionnaires were sent after AR, and 8 domains, the physical and mental component summary (PCS and MCS) scores, and the patient-reported AF were compared, and negative predictors were identified., Results: Overall, the MCS was minimally affected, but AF and the PCS were impaired. After AR, these measures were significantly improved, and maximum recovery was attained at 6 months. In subgroup analysis, significant predictors of a negative impact on postoperative PCS included age ≥80, CLI, physical aftereffects of stroke (PAS), and previous major amputation (PMA). Of these, PMA was associated with the lowest PCS score, followed by PAS; for these patients, AR contributed minimally to HR-QoL recovery. PCS scores of claudicants attained a maximum value at 6 months; however, PCS scores of CLI patients were significantly lower than intermittent claudication patients (P < 0.0001), and patients with major tissue loss required 2 years to attain maximum PCS recovery., Conclusions: This 3-year observational study verified the efficacy of AR in improving AF and HR-QoL. Age ≥80, CLI, PAS, and PMA were definitive predictors, and for patients with the latter 2, AR contributed minimally to improving HR-QoL., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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10. Development of gene therapy with a cyclic adenosine monophosphate response element decoy oligodeoxynucleotide to prevent vascular intimal hyperplasia.
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Uchida D, Saito Y, Kikuchi S, Yoshida Y, Hirata S, Sasajima T, and Azuma N
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- Animals, CREB-Binding Protein genetics, CREB-Binding Protein metabolism, Cell Movement, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, LIM Domain Proteins genetics, LIM Domain Proteins metabolism, Male, Mice, Inbred C57BL, Muscle, Smooth, Vascular injuries, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle pathology, Oligodeoxyribonucleotides metabolism, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Transcription Factors genetics, Transcription Factors metabolism, Vascular System Injuries genetics, Vascular System Injuries metabolism, Vascular System Injuries pathology, Cyclic AMP metabolism, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Neointima, Oligodeoxyribonucleotides genetics, Response Elements genetics, Vascular System Injuries prevention & control
- Abstract
Objective: Intimal hyperplasia (IH) is the main cause of therapeutic failure after vascular and endovascular surgery. However, there is currently no targeted therapy for the treatment of IH. We recently reported that the inhibition of cyclic adenosine monophosphate response element (CRE) binding protein (CREB) activation is important in vein graft IH. We focused on a decoy oligodeoxynucleotide (ODN) therapeutic strategy for suppressing IH as a clinical application. The objective of this study was to confirm the therapeutic effect of a CRE decoy ODN in an animal model as a novel therapy for preventing intimal hyperplasia as the first step of the preclinical study of our strategy., Methods: We designed two phosphorothioate CREs and two scramble decoy ODNs and screened them using a CREB transcription assay to check their ability to bind to a CRE sequence. We chose a CRE decoy ODN with high first-binding ability and transfected it into vascular smooth muscle cells (VSMCs) in vitro. Proliferation and migration were assessed using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays and modified Boyden chamber assays. We examined CRE activity using a luciferase reporter gene assay. We assessed the expression of messenger RNAs by quantitative real-time polymerase chain reaction. In a wire-injury mouse model (C57BL6, n = 6), CRE decoy ODN was transfected into the injured vessel wall using an ultrasound-sonoporation method in vivo. Mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four and a half LIM domains 5 (FHL5) expression of pregrafting vein remnants were assessed by immunohistologic analyses., Results: Compared with scramble decoy ODN, the selected CRE decoy ODN could significantly decrease CRE activity (mean ± standard error of the mean: 0.20 ± 0.03 vs 1.00 ± 0.16, n = 6; P < .05) as shown by a luciferase reporter gene assay, VSMC proliferation (0.73 ± 0.04 vs 0.89 ± 0.02, n = 6; P < .05) and migration (96.4 ± 6.1 vs 311.4 ± 19.1 migrated VSMCs/well, n = 6; P < .05) after 24-hour transfection. The CRE decoy ODN significantly suppressed the formation of IH at injured vessel walls in an animal model, as analyzed by pathologic staining (0.20 ± 0.02 vs 0.56 ± 0.08, area of the intima/area of the artery vs the control after 21 days' transfection, n = 6; P < .05). Furthermore, MAPKAPK3 and FHL5, which are CREB activators, were significantly expressed in pregrafting vein remnants in diabetes mellitus patients., Conclusions: CREB-CRE signaling is an important mechanism of IH formation, and CRE decoy therapy can help preventing IH. This study is the first part of the preclinical study of our strategy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2020
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11. Real-world safety and efficacy of omalizumab in patients with severe allergic asthma: A long-term post-marketing study in Japan.
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Adachi M, Kozawa M, Yoshisue H, Lee Milligan K, Nagasaki M, Sasajima T, Miyamoto T, and Ohta K
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- Adult, Aged, Antibodies, Monoclonal, Humanized therapeutic use, Asthma immunology, Disease Progression, Female, Humans, Hypersensitivity, Japan epidemiology, Male, Middle Aged, Omalizumab administration & dosage, Omalizumab adverse effects, Prospective Studies, Severity of Illness Index, Treatment Outcome, Anti-Asthmatic Agents pharmacology, Asthma drug therapy, Marketing methods, Omalizumab pharmacology
- Abstract
Background: Omalizumab (anti-IgE monoclonal antibody) is an approved add-on therapy for Japanese patients with severe allergic asthma. As directed by the Ministry of Health, Labor and Welfare Japan, a post-marketing surveillance (PMS) study on omalizumab was conducted between 2009 and 2017., Methods: The PMS observed safety and efficacy of omalizumab in patients treated with open-label omalizumab for 52 weeks (with optional 2-year extension period). Primary safety outcomes included incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs). Primary efficacy outcomes included physician-assessed global evaluation of treatment effectiveness (GETE). Asthma-exacerbation-related events including requirement for additional systemic steroid therapy, hospitalization, emergency room visits, unscheduled doctor visits, and absenteeism were also evaluated., Results: Of 3893 patients registered, 3620 (age [mean ± SD] 59.3 ± 16.11 years) were evaluated for 52 weeks; 44.12% were aged ≥65 years and 64.45% were women. Overall, 32.24% reported AEs and 15.30% reported serious AEs. ADRs were seen in 292 (8.07%) patients. GETE results showed that the majority of patients experienced clinical improvements (58.29% at 16 weeks and 62.40% at 52 weeks). Nearly half of all patients (47.96%) were free from asthma exacerbations after therapy. Omalizumab also reduced all events related to asthma exacerbations. No specific ADRs were observed in the elderly population., Conclusions: This post-marketing study confirmed the clinically meaningful benefits of omalizumab in a majority of patients from Japan, and showed safety and efficacy in a real-life clinical setting to be consistent with previous reports., (Copyright © 2018. Published by Elsevier Ltd.)
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- 2018
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12. Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis-dependent patients with critical limb ischemia.
- Author
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Kikuchi S, Sasajima T, Inaba M, Uchida D, Kokubo T, Saito Y, Koya A, Uchida H, and Azuma N
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- Age Factors, Aged, Aged, 80 and over, Amputation, Surgical, Arteriosclerosis Obliterans diagnosis, Arteriosclerosis Obliterans mortality, Arteriosclerosis Obliterans physiopathology, Comorbidity, Critical Illness, Disease-Free Survival, Female, Humans, Ischemia diagnosis, Ischemia mortality, Ischemia physiopathology, Kaplan-Meier Estimate, Kidney physiopathology, Limb Salvage, Male, Middle Aged, Proportional Hazards Models, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic mortality, Renal Insufficiency, Chronic physiopathology, Retrospective Studies, Risk Factors, Saphenous Vein physiopathology, Sex Factors, Time Factors, Treatment Outcome, Vascular Grafting adverse effects, Vascular Grafting mortality, Vascular Patency, Arm blood supply, Arteriosclerosis Obliterans surgery, Ischemia surgery, Renal Dialysis adverse effects, Renal Dialysis mortality, Renal Insufficiency, Chronic surgery, Saphenous Vein transplantation, Vascular Grafting methods
- Abstract
Objective: The aim of this study was to elucidate the efficacy of paramalleolar or inframalleolar bypass (PIMB) in hemodialysis-dependent (HD) patients with critical limb ischemia (CLI) and nonhemodialysis-dependent (NHD) patients in terms of clinical outcomes., Methods: Between January 2000 and December 2013, there were 333 consecutive arteriosclerosis obliterans patients with CLI who underwent 401 PIMB procedures for limb salvage (LS). Of the 333 patients, 188 (56.5%) were HD patients. Vein grafts were exclusively used, and 172 paramalleolar and 229 inframalleolar bypasses were performed. Five-year primary and secondary cumulative graft patency, LS, and amputation-free survival (AFS) rates were compared between the two groups, and the independent determinants of these outcomes were identified in each group., Results: The 5-year primary and secondary cumulative graft patency rates were 53% and 82% in HD patients and 69% and 92% in NHD patients (primary cumulative graft patency, P < .05; secondary cumulative graft patency, nonsignificant), respectively. The LS rates were 87% and 99% (P < .01) in HD patients and NHD patients, respectively. Overall, 48% and 70% of HD and NHD patients were ambulatory before PIMB (P < .01), and 73% and 85% of HD and NHD patients were ambulatory 12 months after PIMB (including 1-year survivors; nonsignificant), respectively, demonstrating drastic post-PIMB improvement in HD patients. The 5-year AFS rates in the HD and NHD groups were 27% and 69% (P < .01), respectively, demonstrating very poor AFS rates in HD patients. In HD patients, factors negatively associated with AFS were female gender (hazard ratio [HR], 2.102; 95% confidence interval [CI], 1.254-3.524), history of congestive heart failure (HR, 2.075; 95% CI, 1.395-3.085), and preoperative nonambulatory status (HR, 1.974; 95% CI, 1.305-2.986), whereas older age (HR, 2.601; 95% CI, 1.372-4.931) and history of congestive heart failure (HR, 2.928; 95% CI, 1.496-5.731) were identified as independent factors negatively associated with AFS in NHD patients., Conclusions: The use of PIMB for CLI was associated with excellent LS rates in both HD and NHD patients with low operative mortality and complications. However, the AFS rate observed in HD patients was significantly lower than that observed in NHD patients, indicating the necessity of a specific management program to improve AFS after LS in HD patients., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2018
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13. Amino acid PET tracers are reliable markers of treatment responses to single-agent or combination therapies including temozolomide, interferon-β, and/or bevacizumab for glioblastoma.
- Author
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Ono T, Sasajima T, Doi Y, Oka S, Ono M, Kanagawa M, Baden A, Mizoi K, and Shimizu H
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- Animals, Antineoplastic Agents administration & dosage, Bevacizumab administration & dosage, Biomarkers, Tumor metabolism, Brain Neoplasms diagnostic imaging, Cell Line, Tumor, Dacarbazine administration & dosage, Dacarbazine analogs & derivatives, Glioblastoma diagnostic imaging, Humans, Interferon-beta administration & dosage, Male, Positron-Emission Tomography methods, Radiopharmaceuticals pharmacokinetics, Rats, Rats, Inbred F344, Rats, Nude, Reproducibility of Results, Sensitivity and Specificity, Temozolomide, Tissue Distribution, Treatment Outcome, Amino Acids pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Brain Neoplasms drug therapy, Brain Neoplasms metabolism, Glioblastoma drug therapy, Glioblastoma metabolism
- Abstract
Introduction: We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-β (IFN), and bevacizumab (Bev) in glioblastoma., Methods: Human glioblastoma U87MG (U87) cells were incubated with low dose TMZ to induce chemoresistance. Both trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) uptake were quantified using triple-label accumulation assays to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation) in vitro. U87 and U87R (TMZ-resistant subculture) cells were inoculated into the right and left basal ganglia, respectively, of F344/N-rnu rats. The efficacy of single-agent (TMZ, Bev) and combination therapy (TMZ/IFN, TMZ/Bev, TMZ/IFN/Bev) was examined in orthotopic gliomas using MRI, Evans blue extravasation, anti-(14)C-FACBC, and (3)H-Met autoradiography, and MIB-1 immunostaining., Results: TMZ treatment decreased (3)H-TdR accumulation and the volume distribution of anti-(14)C-FACBC and (3)H-Met in U87 but not U87R cells. TMZ/IFN combination therapy significantly decreased these parameters in U87R cells; however, Bev had no additional effect in vitro. In vivo, U87R-derived gliomas were observed as equivocal tumors on MRI and T2-high intensity lesions. Bev treatment, either alone or in combination, markedly decreased U87 enhancing lesions. By contrast, autoradiographic images using anti-(14)C-FACBC and (3)H-Met clearly delineated tumor extent, which spread widely beyond T2-high intensity lesions and enhancing lesions. TMZ therapy significantly decreased tracer accumulation and proliferation of U87- but not U87R-derived tumors. TMZ/IFN combination treatment significantly decreased these parameters in U87R tumors, which were further reduced (in both tumor types) by Bev addition. Tracer uptake correlated with the MIB-1 proliferation index. However, MRI was unsuitable for tumor delineation and assessment of Bev treatment response., Conclusions: Triple-agent therapy (TMZ/IFN/Bev) was effective against even TMZ-resistant glioblastomas. PET with amino acid tracers provides useful information on the early response of glioblastomas to single-agent and combination therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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14. Clinical results of cystic excision for popliteal artery cystic adventitial disease: long-term benefits of preserving the intact intima.
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Kikuchi S, Sasajima T, Kokubo T, Koya A, Uchida H, and Azuma N
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- Adventitia diagnostic imaging, Adventitia pathology, Aged, Constriction, Pathologic, Cysts diagnosis, Cysts physiopathology, Humans, Male, Middle Aged, Popliteal Artery diagnostic imaging, Popliteal Artery pathology, Popliteal Artery physiopathology, Severity of Illness Index, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Tunica Intima diagnostic imaging, Tunica Intima pathology, Vascular Diseases diagnosis, Vascular Diseases physiopathology, Vascular Patency, Adventitia surgery, Cysts surgery, Popliteal Artery surgery, Tunica Intima surgery, Vascular Diseases surgery
- Abstract
Surgical treatment for popliteal artery cystic adventitial disease (PACAD) is still controversial. PACAD often occurs in young or middle-aged adults. Therefore, the maintenance of graft patency for very long periods is a concern if a prosthesis is used. Because the intima is intact in PACAD patients with popliteal artery stenosis, a treatment that preserves the healthy intima is ideal. We describe the cases of 3 patients who underwent cystic excision for PACAD with severe stenosis. No recurrence was observed for up to 11 years, and these long-term results revealed that cystic excision could be reconsidered as one of the first-line therapeutic methods., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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15. Trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) is a feasible alternative to 11C-methyl-L-methionine and magnetic resonance imaging for monitoring treatment response in gliomas.
- Author
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Sasajima T, Ono T, Shimada N, Doi Y, Oka S, Kanagawa M, Baden A, and Mizoi K
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- Animals, Blood-Brain Barrier metabolism, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Dacarbazine analogs & derivatives, Dacarbazine pharmacology, Dacarbazine therapeutic use, Feasibility Studies, Glioma metabolism, Glioma pathology, Male, Methionine metabolism, Permeability, Rats, Temozolomide, Treatment Outcome, Brain Neoplasms diagnosis, Brain Neoplasms drug therapy, Carboxylic Acids metabolism, Cyclobutanes metabolism, Glioma diagnosis, Glioma drug therapy, Magnetic Resonance Imaging methods, Methionine analogs & derivatives
- Abstract
Introduction: Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo., Methods: C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-(14)C-FACBC and (3)H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-(14)C-FACBC and (3)H-Met autoradiography, and MIB-5 proliferation index., Results: The (3)H-TdR accumulation rate and amino acid tracer (anti-(14)C-FACBC and (3)H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-(14)C-FACBC uptake correlated significantly with (3)H-Met uptake and the (3)H-TdR accumulation rate. In the intracerebral glioma model, anti-(14)C-FACBC and (3)H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-(14)C-FACBC and (3)H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI., Conclusions: Anti-(14)C-FACBC, like (3)H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-(18)F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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16. Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia.
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Nakanishi K, Saito Y, Azuma N, and Sasajima T
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- Aged, Animals, Cell Movement, Cell Proliferation, Cells, Cultured, Constriction, Pathologic, Cyclic AMP Response Element-Binding Protein genetics, Disease Models, Animal, Gene Expression Profiling methods, Genetic Therapy, Graft Occlusion, Vascular etiology, Graft Occlusion, Vascular genetics, Graft Occlusion, Vascular pathology, Graft Occlusion, Vascular prevention & control, Humans, Hyperplasia, Intracellular Signaling Peptides and Proteins genetics, LIM Domain Proteins genetics, Male, Mice, Mice, Inbred C57BL, Muscle, Smooth, Vascular enzymology, Muscle, Smooth, Vascular pathology, Mutation, Myocytes, Smooth Muscle enzymology, Myocytes, Smooth Muscle pathology, Neointima, Oligonucleotide Array Sequence Analysis, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases genetics, Time Factors, Transcription Factors genetics, Transfection, Vascular System Injuries enzymology, Vascular System Injuries genetics, Vascular System Injuries pathology, Vascular System Injuries prevention & control, Veins enzymology, Veins injuries, Veins pathology, Cyclic AMP Response Element-Binding Protein metabolism, Graft Occlusion, Vascular enzymology, Intracellular Signaling Peptides and Proteins metabolism, LIM Domain Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Transcription Factors metabolism, Vascular Grafting adverse effects, Veins transplantation
- Abstract
Objective: Intimal hyperplasia (IH) is the main cause of vein graft stenosis or failure after bypass surgery. Basic investigations are proceeding in an animal model of mechanically desquamated arteries, and numerous molecules for potential IH treatments have been identified; however, neither insights into the mechanism of IH nor substantially effective treatments for its suppression have been developed. The goals of the present study are to use human vein graft samples to identify therapeutic target genes that control IH and to investigate the therapeutic efficacy of these candidate molecules in animal models., Methods: Using microarray analysis of human vein graft samples, we identified two previously unrecognized IH-related genes, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5)., Results: Transfer of either candidate gene resulted in significantly elevated vascular smooth muscle cell (VSMC) proliferation and migration. Interestingly, cotransfection of both genes increased VSMC proliferation in an additive manner. These genes activated cyclic adenosine monophosphate response-element (CRE) binding protein (CREB), but their mechanisms of activation were different. MAPKAPK3 phosphorylated CREB, but FHL5 bound directly to CREB. A CREB dominant-negative protein, KCREB, which blocks its ability to bind CRE, repressed VSMC proliferation and migration. In a wire-injury mouse model, gene transfer of KCREB plasmid significantly repressed IH. In this vessel tissue, CRE-activated gene expression was repressed. Furthermore, we confirmed the changes in MAPKAPK3 and FHL5 expression using vein graft samples from eight patients., Conclusions: We successively identified two previously unrecognized IH activators, MAPKAPK3 and FHL5, using human vein graft samples. Gene transfer of KCREB repressed IH in an animal model. Inhibition of CREB function is a promising gene therapy strategy for IH., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)
- Published
- 2013
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17. Factors related to postoperative delirium in patients with lower limb ischaemia: a prospective cohort study.
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Sasajima Y, Sasajima T, Azuma N, Akazawa K, Saito Y, Inaba M, and Uchida H
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- Age Factors, Aged, Delirium diagnosis, Delirium epidemiology, Female, Follow-Up Studies, Humans, Incidence, Japan epidemiology, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Severity of Illness Index, Time Factors, Arteriosclerosis Obliterans surgery, Delirium etiology, Leg blood supply, Postoperative Complications, Vascular Surgical Procedures
- Abstract
Objectives: To preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery., Design: A prospective cohort study., Patients and Methods: 299 patients (age ≥ 60 years) who underwent bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used, and severity was graded as Grade I-III (mild to severe) based on the Delirium Rating Scale. All patients were followed for 3 years., Results: POD occurred in 88 patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1) days postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive in 89% and was Grade I, II, and III in 11%, 68%, and 21% respectively. Multiple logistic regression analysis identified the following risk factors for POD: age ≥ 72 years (<0.0001), end-stage renal failure (0.001), multiple occlusive lesions (<0.0001), cognitive impairment (0.003), and critical limb ischaemia (0.034). The 3-year survival rate was similar when comparing POD and non-POD patients (84% vs. 88%, NS)., Conclusions: This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were similar when comparing the patients who experienced POD with those who did not., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)
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- 2012
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18. Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?
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Azuma N, Uchida H, Kokubo T, Koya A, Akasaka N, and Sasajima T
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- Adult, Aged, Aged, 80 and over, Amputation, Surgical statistics & numerical data, Arterial Occlusive Diseases epidemiology, Arterial Occlusive Diseases physiopathology, Blood Vessel Prosthesis, Comorbidity, Diabetes Mellitus epidemiology, Disease-Free Survival, Female, Foot physiopathology, Foot Ulcer epidemiology, Gangrene epidemiology, Humans, Ischemia epidemiology, Kidney Failure, Chronic epidemiology, Male, Middle Aged, Postoperative Care methods, Retrospective Studies, Survival Rate, Treatment Outcome, Vascular Surgical Procedures methods, Vascular Surgical Procedures mortality, Arterial Occlusive Diseases surgery, Arteries surgery, Foot blood supply, Ischemia physiopathology, Ischemia surgery, Limb Salvage methods, Wound Healing
- Abstract
Objectives: The aim of the study is to determine factors affecting ischaemic wound healing and role of the angiosome concept in bypass surgery., Design: Single-centre, retrospective clinical study., Materials and Methods: A total of 249 consecutive critical ischaemic limbs with tissue loss in 228 patients who underwent distal bypasses from 2003 to 2009 were reviewed. A total of 81% of patients were diabetic, and 49% of patients had dialysis-dependent renal disease (end-stage renal disease, ESRD). Distal targets of bypasses were the crural artery (57%) and the pedal artery (43%)., Results: The complete healing of ischaemic wounds was achieved in 211 limbs (84.7%). ESRD (odds ratio (OR) 0.127, p < 0.001), diabetes (OR 0.216, p = 0.030), Rutherford category 6 (R6) with heel ulcer/gangrene (OR 0.134, p < 0.001), R6 except heel (OR 0.336, p = 0.025) and low albuminaemia (OR 0.387, p = 0.049) were negative predictors of wound healing. Regarding the angiosome, the healing rate in the indirect revascularisation (IR) group was slower than in the direct revascularisation (DR) group, especially in patients with ESRD (p < 0.001). However, the healing rates of the DR and IR groups were similar after minimising background differences with propensity score methods (p = 0.185)., Conclusions: In the field of bypass surgery, the angiosome concept seems unimportant, at least in non-ESRD cases. The location and extent of ischaemic wounds as well as co-morbidities may be more relevant than the angiosome in terms of wound healing., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)
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- 2012
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19. Combined distal venous arterialization and free flap for patients with extensive tissue loss.
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Sasajima T, Azuma N, Uchida H, Asada H, Inaba M, and Akasaka N
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- Aged, Amputation, Surgical, Arteries surgery, Arteriosclerosis Obliterans diagnostic imaging, Arteriosclerosis Obliterans physiopathology, Blood Vessel Prosthesis Implantation, Collateral Circulation, Female, Gangrene, Humans, Ischemia diagnostic imaging, Ischemia physiopathology, Limb Salvage, Male, Microcirculation, Middle Aged, Radiography, Reoperation, Thromboangiitis Obliterans diagnostic imaging, Thromboangiitis Obliterans physiopathology, Time Factors, Treatment Outcome, Vascular Patency, Veins transplantation, Arteriosclerosis Obliterans surgery, Ischemia surgery, Lower Extremity blood supply, Surgical Flaps, Thromboangiitis Obliterans surgery, Vascular Surgical Procedures
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Background: We evaluated the mid-term outcome of distal venous arterialization (DVA) and the role of a combined free flap as a bridgehead for blood supply., Methods: In the past 5 years, nine patients with extensive tissue loss and lacking graftable distal arteries underwent DVA. These consisted of four primary DVAs, three combined DVA and free flap procedures, and two adjuvant DVAs for hemodynamically failed distal bypasses. After nine primary DVAs, three redo DVAs were performed for early failure. Etiologies were four Buerger disease and five arteriosclerosis obliterans, including three dialysis patients., Results: Among the nine DVA cases, there were five primary failures: two underwent amputation, two had successful redo DVA, and the remaining one did not require redo DVA. Primary patency, secondary patency, and limb salvage rates were 44.4%, 55.6%, and 77.8%, respectively. The postoperative period was 1-36 months (median 12). Angiography demonstrated DVA was effective in the early period, and development of collaterals or a capillary network from the free flap replaced the DVA function in the intermediate period., Conclusion: DVA can be effective as a procedure for limb salvage in patients without graftable distal arteries, and a combined free flap is effective and functions as a bridgehead for blood supply to the ischemic zone., (Copyright (c) 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)
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- 2010
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20. Vacuum-assisted closure for pediatric post-sternotomy mediastinitis: are low negative pressures sufficient?
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Kadohama T, Akasaka N, Nagamine A, Nakanishi K, Kiyokawa K, Goh K, and Sasajima T
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- Child, Preschool, Female, Humans, Infant, Male, Mediastinitis microbiology, Sternum surgery, Cardiac Surgical Procedures adverse effects, Mediastinitis etiology, Mediastinitis therapy, Negative-Pressure Wound Therapy, Staphylococcal Infections therapy
- Abstract
We present 3 cases of pediatric post-sternotomy mediastinitis treated by a vacuum-assisted closure (VAC). The patients 2 girls, aged 6 months and 10 months, and a 2-year-old boy. The onset of infection was at 9, 14, and 32 postoperative days. The culture examination detected coagulase-negative Staphylococci strains in 2 cases, and Staphylococcus aureus in 1 case. A VAC was performed at -50 mm Hg for 10, 12, and 7 days. The wounds were closed without vascularized soft tissue. A VAC under a low negative pressure is a useful and safe procedure for the management of pediatric post-sternotomy mediastinitis.
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- 2008
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21. Hepatic artery aneurysm involving the proper hepatic and gastroduodenal artery treated using a gastroepiploic artery in situ bypass.
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Kadohama T, Ohtani N, and Sasajima T
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- Aneurysm diagnostic imaging, Humans, Male, Mesenteric Artery, Superior diagnostic imaging, Middle Aged, Radiography, Vascular Patency, Vascular Surgical Procedures, Aneurysm surgery, Gastroepiploic Artery transplantation, Hepatic Artery diagnostic imaging
- Abstract
We herein present the first known case of common hepatic artery aneurysm involving the proper hepatic artery treated with in situ bypass by using right gastroepiploic artery. A 55-year-old man was hospitalized after the incidental discovery of a low-echogenic mass with blood flow in the hepatic artery. Selective visceral arteriography demonstrated a hepatic artery aneurysm that filled via the superior mesenteric artery. The most proximal part of the common hepatic artery was occluded. A resection of aneurysm was performed, and the arterial blood flow was restored to the liver by mobilizing the right gastroepiploic artery and anastomosing the proper hepatic artery. This technique is preferable to grafting in that only one anastomosis is necessary and predicts that the results may be at least as good as with vein or prosthetic grafts.
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- 2007
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22. Total arch replacement for a distal aortic arch aneurysm with right aortic arch.
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Kiokawa K, Goh K, Akasaka N, Azuma N, Inaba M, and Sasajima T
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- Aged, Aorta, Thoracic diagnostic imaging, Aortic Aneurysm diagnostic imaging, Female, Humans, Radiography, Thoracic, Sternum surgery, Tomography, X-Ray Computed, Aorta, Thoracic abnormalities, Aorta, Thoracic surgery, Aortic Aneurysm surgery, Blood Vessel Prosthesis Implantation, Subclavian Artery abnormalities
- Abstract
Right-sided aortic arch accompanied by an aberrant origin of the left subclavian artery is rare and seen in 0.05% approximately 0.1% of the population. A 73-year-old woman with this anomaly was admitted to our institution because of the enlargement of the distal aortic arch aneurysm. She also had mild dysphagia. The size of the aneurysm was 70 mm in diameter and she underwent total arch replacement using selective cerebral perfusion through a median sternotomy. Additional right thoracotomy was not required and four cervical vessels were reconstructed. The postoperative course was uneventful. This case report shows median sternotomy alone may provide sufficient access for this pathology.
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- 2007
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23. Homocysteine promotes p38-dependent chemotaxis in bovine aortic smooth muscle cells.
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Akasaka K, Akasaka N, Di Luozzo G, Sasajima T, and Sumpio BE
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- Animals, Blotting, Western, Cattle, Enzyme Inhibitors pharmacology, Imidazoles pharmacology, Phosphorylation, Pyridines pharmacology, Chemotaxis drug effects, Homocysteine pharmacology, Muscle, Smooth, Vascular cytology, p38 Mitogen-Activated Protein Kinases physiology
- Abstract
Objective: Increased levels of homocysteine in the blood are a risk factor for atherosclerosis. The purpose of this study was to examine the effects of homocysteine on smooth muscle cell (SMC) migration and to determine whether p38 was involved in this process., Methods: The effect of 0.5 to 2.0 mmol/L d , l -homocysteine as a chemoattractant for SMCs was assayed with a modified Boyden chamber. To determine the functional role of p38 in SMC chemotaxis induced by d , l -homocysteine, we treated SMCs with a p38 inhibitor, SB203580, before the assay., Results: The number of migrated cells was increased 7.0 +/- 1.2-fold (n = 15; P < .001) by 2.0 mmol/L d , l -homocysteine. SB203580 partially prevented the migration of SMCs toward homocysteine. Preconditioning SMCs with 2.0 mmol/L d , l -homocysteine significantly enhanced chemotaxis toward 10% fetal bovine serum compared with nonconditioned control SMCs (28.9 +/- 3.3-fold vs 15.6 +/- 2.8-fold; P < .05). There was a fourfold p38 activation after exposure of SMCs to 2.0 mmol/L d , l -homocysteine by immunoblot., Conclusions: These results suggest that homocysteine not only is a chemoattractant for SMC but can also enhance SMC chemotactic potential. The mechanism of these effects may involve p38 activation., Clinical Relevance: This study demonstrates that homocysteine can promote chemotaxis of SMCs through a p38-dependent pathway. To our knowledge, this is the first report that homocysteine may influence SMC chemotaxis. It may be an important mechanism for homocysteine-induced atherogenesis, because the migration of SMCs from the media is believed to play a critical role in progressive intimal thickening. Although homocysteine promotes atherogenesis and thrombosis by a variety of mechanisms, the effects of homocysteine on SMC proliferation and migration might be critical elements that may have potential therapeutic implications, because selective blockade of the p38 pathway is feasible.
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- 2005
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24. Biologic degeneration of vein grafts after thrombotic occlusion: thrombectomy within 3 days results in better indices of viability.
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Kawai S, Sasajima T, Satoh K, Inaba M, Azuma N, Yamazaki K, and Oikawa K
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- Animals, Cell Survival physiology, Dogs, Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Epoprostenol biosynthesis, Female, Femoral Artery surgery, Graft Occlusion, Vascular etiology, Male, Thrombectomy, Time Factors, Veins surgery, Venous Thrombosis etiology, Venous Thrombosis metabolism, Blood Vessel Prosthesis adverse effects, Graft Occlusion, Vascular physiopathology, Vascular Patency physiology, Veins pathology, Venous Thrombosis pathology, Venous Thrombosis surgery
- Abstract
Objectives: To clarify the mechanism for poor patency of vein grafts after thrombectomy and the time limit for successful salvage operation, we investigated the time course of biologic degenerative changes in thrombosed vein grafts. Materials and methods The right femoral artery was replaced with a femoral vein graft in 25 mongrel dogs. After 3 months, grafts were explanted in 5 dogs (control grafts), and the remaining 20 dogs underwent femoral artery ligation to create a thrombosed graft. Of the 20 grafts, 5 were explanted at 3 days after ligation (group I-3) and 5 were explanted at 5 days after ligation (group I-5). Of the remaining 10 grafts, 5 underwent thrombectomy at 3 days after ligation (group II-3) and 5 underwent thrombectomy at 5 days after ligation, and were reimplanted into the left femoral artery, then explanted 28 days after reimplantation. The grafts were assessed with immunohistochemistry and prostaglandin (PG) I(2) assay (6-keto-PGI(1alpha))., Results: Of the 25 grafts, occlusion recurred in 3 in group II-5 within 28 days after reimplantation. There were significant differences between group I-5 and group I-3 or control grafts for percentage of areas positive for alpha-actin, total number of cells per field, and proliferating cell nuclear antigen (PCNA)-positive cells in layer of thickened intima and atrophied media (I/M), and for total cell and PCNA- positive cell numbers per field in the adventitia. Mean 6-ketoPGF(1alpha) was 40 +/- 14.1 pg/mg/min in control dogs, 84 +/- 18.9 pg/mg/min in group I-3, and 15.4 +/- 7.7 pg/mg/min in group I-5, demonstrating a significant reduction in group I-5 (P =.009)., Conclusion: Graft wall cell viability and PGI(2) production in thrombosed vein grafts are well preserved for up to 3 days. Therefore graft salvage operations no later than 3 days after thrombotic occlusion may provide acceptable long-term patency of salvaged grafts.
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- 2003
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25. Novel anastomotic method enables aortofemoral bypass for patients with porcelain aorta.
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Sasajima T, Inaba M, Azuma N, Akasaka N, Asada H, Uchida H, Sasajima Y, and Goh K
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- Aged, Aorta physiopathology, Aortic Diseases diagnostic imaging, Aortic Diseases physiopathology, Aortography, Female, Femoral Artery diagnostic imaging, Femoral Artery physiopathology, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Anastomosis, Surgical methods, Aorta surgery, Aortic Diseases surgery, Femoral Artery surgery
- Abstract
Purpose: Porcelain aorta is an indication for axillofemoral bypass. However, the procedure has definitive flaws. We present a new method for achievement of aortofemoral bypass., Methods: The portion of the distal aorta for anastomosis is wrapped with a double polytetrafluoroethylene mesh and fixed to the adventitia with continuous sutures. The adventitia of the anastomotic site is cut over the mesh until the calcified surface is disclosed. Margins of the mesh and the peeled adventitia are fixed along the anastomotic margin with continuous sutures. After the aorta and distal arteries are occluded with balloon catheters, an opening on the bared calcification is made with an airdrill and enlarged with a laminectomy rongeur. The anastomosis is performed between a graft and the mesh-reinforced adventitia with continuous sutures. Over 6 years, this method has been applied to nine patients with porcelain aorta who are diabetic or undergoing dialysis. The indications were disabling claudication in three patients and limb salvage in six patients., Results: No anastomotic complications or operative deaths were seen, and satisfactory mid-term results were obtained, with follow-up ranging from 3 to 62 months after surgery. One patient died of coronary heart disease 3 years after surgery, but the grafts retained a good function., Conclusion: This method is safe and effective, and more liberal application of this method may help improve outcome and quality of life.
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- 2002
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26. Limitations in the use of rifampicin-gelatin grafts against virulent organisms.
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Koshiko S, Sasajima T, Muraki S, Azuma N, Yamazaki K, Chiba K, Tachibana M, and Inaba M
- Subjects
- Animals, Antibiotics, Antitubercular administration & dosage, Blood Vessel Prosthesis Implantation, Dogs, Escherichia coli drug effects, Gelatin, Methicillin Resistance, Microbial Sensitivity Tests, Rifampin administration & dosage, Staphylococcus aureus drug effects, Staphylococcus epidermidis drug effects, Time Factors, Antibiotics, Antitubercular pharmacology, Blood Vessel Prosthesis adverse effects, Escherichia coli Infections prevention & control, Prosthesis-Related Infections drug therapy, Rifampin pharmacology, Staphylococcal Infections prevention & control
- Abstract
Objective: Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model., Materials and Methods: Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone., Results: In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 +/- 0.3 mm, 36.0 +/- 0.2 mm, and 11.8 +/- 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 +/- 1.1 mm and 7.6 +/- 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 +/- 0.2 mm and 18.5 +/- 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitory concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection., Conclusion: These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitory concentration MRSA strains or poor susceptibility.
- Published
- 2002
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27. Effect of a serotonin receptor antagonist on interleukin-6-induced pulmonary hypertension in rats.
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Miyata M, Ito M, Sasajima T, Ohira H, and Kasukawa R
- Subjects
- Animals, Hypertrophy, Right Ventricular pathology, Interleukin-6, Male, Muscle, Smooth, Vascular physiology, Pulmonary Artery pathology, RNA, Messenger metabolism, Random Allocation, Rats, Rats, Sprague-Dawley, Serotonin Antagonists pharmacology, Hypertension, Pulmonary physiopathology, Muscle, Smooth, Vascular drug effects, Serotonin physiology
- Abstract
Study Objectives: To determine the significance of serotonin in the pathogenesis of interleukin (IL) 6-induced pulmonary hypertension (IL-6-PH) in rats, the plasma serotonin concentrations, and the effects of a specific antagonist of the serotonin (5-hydroxytryptamine [5-HT]) receptor, 1-[o-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride (MCI) on the degree of pulmonary hypertension (PH) were investigated in MCI-treated IL-6-PH (IL-6-MCI-PH) rats., Measurements: The thickness of the media of small pulmonary arteries and the ratio of the weight of the right ventricle free wall (RV) to that of the left ventricle with the septum (LV + S) were measured as indexes of the degree of PH. Serotonin concentrations in plasma and in supernatants of cultured vascular smooth muscle cells (VSMCs) stimulated by IL-6 were measured by high-performance liquid chromatography. The amplification of DNA encoding the 5-HT receptor in the lung specimen and VSMCs was performed by polymerase chain reaction., Results: The degree of PH, as determined by the medial thickness of small pulmonary arteries, was significantly increased in IL-6-PH rats as compared with normal control rats (p<0.05), and that in IL-6-MCI-PH rats was not significantly different from that in normal control rats. The RV/LV + S weight ratio in the IL-6-PH rats was significantly higher than that in normal control rats (p < 0.01). The RV/LV + S weight ratio in IL-6-MCI-PH rats was significantly lower than that in IL-6-PH rats (p < 0.01) and was not significantly different from that in normal control rats. The serotonin concentration was significantly higher in IL-6-PH rats than in normal control rats (p < 0.02), and the serotonin concentration in IL-6-MCI-PH rats was not significantly different from that in the normal control rats. The expression levels of the 5-HT receptor messenger RNA in the lung tissue tended to increase in IL-6-PH rats but was suppressed in IL-6-MCI-PH rats. IL-6 significantly increased the amount of serotonin released from VSMCs (p < 0.02). The expression of the 5-HT receptor messenger RNA was observed with IL-6 stimulation as was observed with serotonin stimulation in VSMCs., Conclusions: Serotonin receptor antagonists could be considered as potentially useful agents for the treatment of chronic thromboembolic PH, as well as for that of primary PH and PH associated with collagen vascular diseases.
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- 2001
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28. Endothelial cell response to different mechanical forces.
- Author
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Azuma N, Duzgun SA, Ikeda M, Kito H, Akasaka N, Sasajima T, and Sumpio BE
- Subjects
- Animals, Aorta cytology, Cattle, Cells, Cultured, Enzyme Activation, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesions physiology, Humans, Immunoblotting, JNK Mitogen-Activated Protein Kinases, Mechanoreceptors physiology, Phosphorylation, Protein-Tyrosine Kinases physiology, Stress, Mechanical, Endothelium, Vascular physiology, Mitogen-Activated Protein Kinases physiology, Signal Transduction physiology
- Abstract
Purpose: Endothelial cells (ECs) are subjected to the physical forces induced by blood flow. The aim of this study was to directly compare the EC signaling pathway in response to cyclic strain and shear stress in cultured bovine aortic ECs., Materials and Methods: The ECs were seeded on flexible collagen I-coated silicone membranes to examine the effect of cyclic strain. The membranes were deformed with a 150-mm Hg vacuum at a rate of 60 cycle/min for up to 120 minutes. For a comparison of the effect of shear stress, ECs from the same batch as used in the strain experiments were seeded on collagen I-coated silicone sheets. The ECs were then subjected to 10 dyne/cm(2) shear with the use of a parallel flow chamber for up to 120 minutes. Activation of the mitogen- activated protein kinases was assessed by determining phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 with immunoblotting., Results: ERK, JNK, and p38 were activated by both cyclic strain and shear stress. Both cyclic strain and shear stress activated JNK with a similar temporal pattern and magnitude and a peak at 30 minutes. However, shear stress induced a more robust and rapid activation of ERK and p38, compared with cyclic strain., Conclusions: Our results indicate that different mechanical forces induced differential activation of mitogen-activated protein kinases. This suggests that there may be different mechanoreceptors in ECs to detect the different forces or alternative coupling pathways from a single receptor.
- Published
- 2000
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29. Anastomotic complications after bronchoplastic procedures for nonsmall cell lung cancer.
- Author
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Yatsuyanagi E, Hirata S, Yamazaki K, Sasajima T, and Kubo Y
- Subjects
- Adult, Aged, Anastomosis, Surgical adverse effects, Carcinoma, Squamous Cell surgery, Female, Humans, Logistic Models, Male, Middle Aged, Surgical Wound Dehiscence etiology, Sutures, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Thoracic Surgical Procedures adverse effects
- Abstract
Background: Anastomotic complications associated with bronchoplastic procedures cannot be completely avoided despite the improvements made in surgical techniques and suture materials. Thus, the present study attempted to clearly define the significant factors influencing anastomotic complications., Methods: Between 1978 and 1998, 47 patients with primary nonsmall cell lung cancer underwent bronchoplastic procedures. The incidences of anastomotic complications were calculated according to each of the following clinical factors: primary site, age, pathologic type, pT factor, pN factor, pulmonary arterioplasty, surgical procedure, suture material, coverage of the anastomotic line, positive resection margin, and preoperative chemotherapy. The results were analyzed using univariate and multiple logistic regression analysis., Results: Anastomotic complications occurred in 8 patients. Four had anastomotic dehiscence and 4 had stenosis. Of these 8 patients, the resection margin was diagnosed as being positive in 6 patients. Three showed metastasis of the most distal mediastinal lymph node whereas the others had a residual tumor at the bronchial resection margin. According to multiple logistic regression analysis, only pN factor (p = 0.04) and positive resection margin (p = 0.02) had a significant influence on the complications., Conclusions: Thus, pN2 patients, especially those with metastasis of the most distal mediastinal lymph node and patients with a residual tumor at the bronchial resection margin, have a significantly higher risk of anastomotic complications.
- Published
- 2000
- Full Text
- View/download PDF
30. High accumulation of plasminogen and tissue plasminogen activator at the flow surface of mural fibrin in the human arterial system.
- Author
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Sasajima T, Takano Y, Hiraishi Y, Goh K, Inaba M, Azuma N, Sasajima Y, Yamazaki K, and Yamamoto H
- Subjects
- Aged, Female, Fibrinolysin physiology, Humans, Immunoblotting, Immunohistochemistry, Male, Middle Aged, Neutrophils, Pancreatic Elastase metabolism, Regional Blood Flow, Aneurysm metabolism, Aneurysm pathology, Arteries metabolism, Blood Vessel Prosthesis, Fibrin metabolism, Fibrinolysis physiology, Plasminogen metabolism, Thrombosis metabolism, Thrombosis pathology, Tissue Plasminogen Activator metabolism
- Abstract
Purpose: We assessed the fibrinolytic activity of the organized mural thrombus lining of aneurysms and prosthetic grafts., Methods: Between May 1995 and April 1998, the full-thickness mural thrombi of aneurysms and the pseudointima lining of vascular grafts were obtained from 12 patients, ranging from 55 to 78 years in age, who underwent elective surgery. These included five aortic arch aneurysms, four abdominal aortic aneurysms, and three patent synthetic vascular grafts. The specimens were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot and immunohistochemistry for human plasmin/plasminogen, tissue plasminogen activator (tPA), and fibrin degradation product (D-dimer)., Results: In the SDS-PAGE/immunoblot, 25- and 27-kd bands appeared specifically in experimental fibrin plates after limited digestion by plasmin and were also recognized in the mural thrombi. The presence of bands at 25 and 27 kd, which were most prominent in sections near the flow surface layer, was consistent with the hypothesis that the mural fibrin was digested by the endogenous plasmin. Apparent immunoreactivity was found at the flow surface of the masses at a thickness of 10 to 400 micrometer suggesting the presence of a plasminogen and tPA-rich layer, with D-dimer as a consequential product of fibrinolysis., Conclusion: The hypothesis that fibrin surfaces in the arterial system acquire fibrinolytic activity because of digestion by circulating endogenous plasmin was confirmed; this may contribute to the antithrombogenicity of these flow surfaces.
- Published
- 2000
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31. Postoperative delirium in patients with chronic lower limb ischaemia: what are the specific markers?
- Author
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Sasajima Y, Sasajima T, Uchida H, Kawai S, Haga M, Akasaka N, Kusakabe M, Inaba M, Goh K, and Yamamoto H
- Subjects
- Age Distribution, Age Factors, Aged, Aged, 80 and over, Arteriosclerosis Obliterans blood, Arteriosclerosis Obliterans complications, Biomarkers, Delirium diagnosis, Discriminant Analysis, Female, Humans, Incidence, Ischemia blood, Ischemia complications, Male, Mental Status Schedule, Middle Aged, Peripheral Vascular Diseases blood, Peripheral Vascular Diseases complications, Postoperative Complications diagnosis, Regression Analysis, Risk Factors, Serum Albumin analysis, Severity of Illness Index, Arteriosclerosis Obliterans surgery, Delirium etiology, Ischemia surgery, Leg blood supply, Peripheral Vascular Diseases surgery, Postoperative Complications etiology
- Abstract
Objectives: we determined the incidence and specific markers of postoperative delirium in elderly patients with chronic lower limb ischaemia., Patients and Methods: since April, 1995, 110 patients aged 60 years or older (mean: 71.6+/-6.6 years) who underwent bypass surgery were assessed regarding aetiological factors of delirium: age, sex, dementia, body-mass index, hypertension, diabetes, cerebral disease, laboratory test results, severity of limb ischaemia, type of arterial occlusion, operative time, and blood transfusion., Results: discriminant analysis showed statistical significance in the following five variables: age >/=70 years; critical limb ischaemia (and/or ankle pressure <40 mmHg); dementia; duration of operation >/=7 hours; low serum albumin. The overall percentage of cases correctly classified was 78.2% (Wilks>> Lambda=0.695, p<0.001); the standardized regression coefficients of the five variables were 0.648, 0.500, 0.329, 0.218, and 0.200, respectively. In logistic regression, the regression coefficients for old age and critical limb ischaemia were 2.646 (14.1 of odds ratio; 95% confidence interval, 2.7-72.0) and 1.337 (3.8; 1.3-10.9), respectively., Conclusions: the incidence of postoperative delirium in elderly patients with chronic lower-limb ischaemia was as high as 42.3%, and an age of over 70 years and critical limb ischaemia were identified as specific markers, with 14.1 times and 3.8 times the odds of suffering from delirium after bypass surgery., (Copyright 2000 Harcourt Publishers Ltd.)
- Published
- 2000
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32. Revascularization of canine cryopreserved tracheal allografts.
- Author
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Moriyama H, Sasajima T, Hirata S, Yamazaki K, Yatsuyanagi E, and Kubo Y
- Subjects
- Animals, Arteries pathology, Atrophy, Dogs, Female, Male, Trachea blood supply, Trachea pathology, Transplantation, Autologous, Transplantation, Homologous, Cryopreservation, Microsurgery, Organ Preservation, Reperfusion Injury pathology, Trachea transplantation
- Abstract
Background: We examined the blood supply of a cryopreserved tracheal allograft and its morphohistologic changes after transplantation., Methods: In each of 22 dogs, a five-ring tracheal segment was replaced by one of the following tracheal grafts: fresh autografts (n = 8), cryopreserved tracheal allografts (n = 8), or fresh allografts (n = 6). The cryopreserved tracheal allografts were preserved at -196 degrees C for 60 days. No immunosuppressant was given to any of the animals. All grafts were retrieved at 1 and 12 weeks and assessed by microangiography and histology., Results: The epithelial denudation and the revascularization of the transverse intercartilaginous arteries were recognized within 7 days as common to each of the three types of grafts. In the cryopreserved tracheal allografts, neither cartilage degradation nor graft shrinkage occurred at 7 days. However, the recanalized transverse intercartilaginous arteries completely disappeared at 12 weeks, and marked shrinkage occurred; the cartilage cells were accompanied by karyolysis and were significantly decreased in number (p < 0.05). Recanalization of the transverse intercartilaginous arteries was also demonstrated in the fresh allografts; however, necrosis abruptly occurred as a result of acute rejection responses., Conclusions: Cryopreservation of a tracheal allograft provided sufficient reduction of the acute rejection responses, and blood supply to the cryopreserved tracheal allograft was established through the recanalized transverse intercartilaginous arteries within 7 days; however, subsequent chronic rejection responses resulted in occlusion of the transverse intercartilaginous arteries and atrophy.
- Published
- 2000
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33. Konno procedure for infective endocarditis involving aortic valve in a small child.
- Author
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Goh K, Yamamoto H, Tsuda N, and Sasajima T
- Subjects
- Aortic Aneurysm complications, Aortic Aneurysm diagnostic imaging, Blood Vessel Prosthesis Implantation, Endocarditis, Bacterial complications, Female, Heart Valve Diseases complications, Heart Valve Diseases surgery, Humans, Infant, Pneumococcal Infections complications, Ultrasonography, Aortic Valve, Cardiac Surgical Procedures, Endocarditis, Bacterial surgery, Pneumococcal Infections surgery
- Abstract
The Konno procedure was performed to replace the aortic valve and the sinus of Valsalva in a 1-year-old child with pneumococcal infective endocarditis. A Dacron (C.R. Bard, Haverhill, PA) graft and a 16 AP ATS Medical valve (ATS Medical Inc, Minneapolis, MN) were used. Adequate debridement could be easily performed. Postoperative recovery was uneventful. The procedure, originally developed for a narrow aortic annulus, could be a good option for the treatment of a small child with aortic valve endocarditis.
- Published
- 2000
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34. Vascular clamp for hemostasis and stabilization during minimally invasive direct coronary artery bypass.
- Author
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Goh K, Inaba M, Yamamoto H, Akasaka N, and Sasajima T
- Subjects
- Arteries transplantation, Coronary Vessels surgery, Equipment Design, Humans, Coronary Artery Bypass instrumentation, Hemostasis, Surgical instrumentation, Minimally Invasive Surgical Procedures instrumentation, Surgical Instruments
- Abstract
A soft vascular clamp was used for hemostasis and stabilization of the operative field during minimally invasive direct coronary artery bypass (MIDCAB). The instrument was gently applied so that it clamps the coronary artery by grasping the adjacent myocardium. The method offered dry and stable operative field without a special instrument or technique. The surgical results have been satisfactory. We found application of the vascular clamp to be very helpful for MIDCAB.
- Published
- 1999
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35. Morphology and histology of human and canine internal thoracic arteries.
- Author
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Sasajima T, Bhattacharya V, Wu MH, Shi Q, Hayashida N, and Sauvage LR
- Subjects
- Adolescent, Adult, Aged, Animals, Blood Flow Velocity, Dogs, Female, Humans, Male, Middle Aged, Tunica Intima anatomy & histology, Tunica Media anatomy & histology, Vasa Vasorum anatomy & histology, Mammary Arteries anatomy & histology
- Abstract
Background: We evaluated human and canine internal thoracic arteries (ITAs) to determine whether the latter is valid for studies relevant to clinical use., Methods: We studied 19 human ITAs obtained from 1 female and 14 male victims of recent fatal accidents who had no evidence of cardiovascular disease (mean age = 39+/-19 years; range = 15 to 79 years), and ITAs of 21 randomly-selected mongrel dogs of both sexes, weighing 18-40 kg (average = 24.3+/-5.7 kg). Specimens were fixed in formalin at a controlled pressure of 120 mm Hg, before extensive assessment that included intimal thickening, condition of the internal elastic lamina, and number of medial elastic lamellae and vasa vasorum., Results: The canine morphology and histology were similar to the human ITAs, but there was no intimal hyperplasia, and the media and adventitia were thinner (ITAs of humans older than 40 years had significant increases in medial thickness, as well as in overall length). Morphologically and histologically, the left and right canine ITAs were almost completely the same., Conclusions: Canine ITAs are valid for bilateral comparative studies and are a useful tissue source and model for clinically-relevant experimental studies.
- Published
- 1999
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36. Immunosuppression with FK506 in rat arterial allografts: fate of allogeneic endothelial cells.
- Author
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Azuma N, Sasajima T, and Kubo Y
- Subjects
- Animals, Immunohistochemistry, Male, Rats, Rats, Inbred ACI, Rats, Inbred Lew, Regeneration physiology, Tacrolimus administration & dosage, Transplantation, Homologous, Arteries transplantation, Endothelium, Vascular cytology, Immunosuppression Therapy, Tacrolimus pharmacology
- Abstract
Purpose: This study clarified the efficacy of low-dose FK506 and the possibility of discontinuing the use of FK506., Methods: Fresh carotid arteries were allografted from ACI rats to Lewis rats. FK506 (0.2 mg/kg/day) was given intramuscularly from day 3 after transplantation until the rats were killed (group III), or it was given for 4 weeks and then discontinued (group IV). Isogeneic (group I) and allogeneic (group II) models served as untreated control groups. Grafts were harvested on days 0, 1, 3, 7, 14, 21, 28, 70, and 105 after transplantation. Histological evaluation and measurement of the endothelial cell (EC)-covered area were performed by means of scanning electron microscopy., Results: In group I, ECs were denuded immediately after transplantation and subsequently regenerated within 2 weeks. In group II, after denudation and regeneration of ECs, massive leukocyte adhesion and subsequent destruction of regenerated ECs, followed by intimal hyperplasia, were observed. In group III, FK506 suppressed rejection almost completely, without intimal hyperplasia. In group IV, severe rejection and denudation of regenerated intima appeared 2 weeks after the use of FK506 ended., Conclusion: The denudation and regeneration of ECs may play an important role in the process of rejection and graft performance. FK506 proved to be successful in rat arterial allografting, and ECs of donor origin could survive on the allograft as long as FK506 was effective; however, cessation of the use of FK506 resulted in severe destruction of intima. To prevent allograft failure, long-term administration of an immunosuppressant is essential.
- Published
- 1999
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37. Tube device for facilitating distal anastomosis in aortic arch replacement.
- Author
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Sasajima T, Goh K, Asada H, Sugawara T, and Ohtani N
- Subjects
- Anastomosis, Surgical instrumentation, Anastomosis, Surgical methods, Blood Vessel Prosthesis Implantation methods, Humans, Aorta, Thoracic surgery, Blood Vessel Prosthesis Implantation instrumentation
- Abstract
The technique of placing an inverted graft into the descending thoracic aorta facilitates and secures the distal anastomosis in aortic arch replacement, especially in the anastomosis beyond the transverse arch. We developed a simple technique using a pair of thin-walled tubes to enable the arch graft, with its four branches, to be smoothly inserted into the flaccid, normal-caliber descending aorta. The use of these tubes simplified the procedure, resulting in time saving.
- Published
- 1998
- Full Text
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38. Effect of skeletonizing dissection on the internal thoracic artery.
- Author
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Sasajima T, Wu MH, Shi Q, Hayashida N, and Sauvage LR
- Subjects
- Animals, Dogs, Elastic Tissue pathology, Endothelium, Vascular pathology, Female, Fibrosis, Fixatives, Formaldehyde, Graft Survival, Hematoma pathology, Hemorrhage pathology, Male, Necrosis, Regional Blood Flow physiology, Thoracic Arteries pathology, Thoracic Arteries physiopathology, Thoracic Arteries transplantation, Time Factors, Tissue Fixation, Tunica Media pathology, Vascular Patency physiology, Coronary Artery Bypass, Dissection methods, Thoracic Arteries surgery
- Abstract
Background: Skeletonization of the internal thoracic artery (ITA) produces greater length for coronary bypass grafting. We studied the effect of skeletonization on the morphology, histology, and tissue viability of the ITA wall., Methods: Six mongrel dogs underwent unilateral ITA dissection; the contralateral ITA was the control. Study periods were 3 weeks (n=3) and 12 weeks (n=3). At sacrifice, the entire anterior chest wall was removed and dynamically fixed with formalin. Extensive histologic comparisons were performed on three tissue blocks taken from each ITA, 2, 8, and 24 cm from their origin., Results: Flows at the end of the study were comparable to measurements taken during operation, immediately after skeletonization. Grossly, the ITA wall was not injured by skeletonization and there was no adventitial hematoma or bleeding from the sealed branch ends. Microscopic observations showed intact, normal wall structures. Histologic data showed no major significant difference between controls and skeletonized ITAs., Conclusions: Careful skeletonizing dissection is not detrimental to the integrity of ITAs, which justifies their use for myocardial revascularization.
- Published
- 1998
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39. Role of medial smooth muscle cell function in antithrombogenicity of vein grafts.
- Author
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Yatsuyanagi E, Sasajima T, Goh K, Inaba M, and Kubo Y
- Subjects
- Animals, Aorta, Abdominal surgery, Dogs, Female, Fibrinolysis, In Vitro Techniques, Male, Microscopy, Electron, Scanning, Muscle, Smooth, Vascular ultrastructure, Radioimmunoassay, Random Allocation, Reference Values, Transplantation, Autologous, Epoprostenol biosynthesis, Muscle, Smooth, Vascular metabolism, Veins metabolism, Veins transplantation
- Abstract
Objectives: To determine the significance of prostaglandin I2 (PGI2) production by medial smooth muscle cells (SMCs), we assessed PGI2 production from denuded vein grafts and their antithrombogenicity., Materials and Methods: A total of 30 dogs were divided into two groups: in group I, 14 dogs (27 veins, 188 segments) were used to assay PGI2 production, which was measured as 6-keto-PGF1 alpha. In group II, 16 dogs were used for an implantation study and the thrombus-free surface (TFS) score was calculated 24 h after implantation. Both groups contained the following subgroups: subgroup A, freshly harvested veins; subgroup B, endothelial denuded veins; subgroup C, veins frozen and cryopreserved; subgroup D, veins treated with protease., Results: Values of 6-keto-PGF1 alpha (pg/mg/min) for basal and stimulated states in subgroup I-A through I-D were 58.0 +/- 8.9 and 530.6 +/- 74.7, 26.3 +/- 4.7 and 82.3 +/- 11.4, 17.9 +/- 1.3 and 39.4 +/- 3.3, and 13.3 +/- 1.8 and 32.2 +/- 6.2, respectively. The PGI2 production in subgroup I-A were significantly higher than those in the other three subgroups (p < 0.01 for basal and stimulated), while the production in subgroup I-B was also significantly higher than those in the remaining two (p < 0.05 for basal and stimulated). The TFS scores in subgroup II-A through II-D were 98 +/- 2%, 90 +/- 2%, 38 +/- 5%, and 15 +/- 7%, respectively, showing significantly superior antithrombogenicity in subgroup II-B, as well as in II-A, when compared with the remaining two (p = 0.014)., Conclusion: The amount of PGI2 generated by the medial SMCs may be sufficient for maintaining the antithrombogenicity of the endothelial denuded AVGs.
- Published
- 1998
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40. Isolated right ventricular hypoplasia: intraoperative balloon occlusion test.
- Author
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Goh K, Sasajima T, Inaba M, Yamamoto H, Kawashima E, and Kubo Y
- Subjects
- Adult, Female, Heart Defects, Congenital diagnosis, Heart Defects, Congenital surgery, Heart Septal Defects, Atrial complications, Heart Septal Defects, Atrial diagnosis, Humans, Intraoperative Period, Catheterization, Heart Septal Defects, Atrial surgery, Heart Ventricles abnormalities
- Abstract
A 42-year-old woman with isolated right ventricular hypoplasia underwent operation. To determine the optimal procedure, we temporarily occluded the atrial septal defect with a balloon catheter that was introduced through the right atrial appendage. The hemodynamics were stable throughout the occlusion test. Simple closure of the atrial septal defect was safely accomplished. Intraoperative occlusion test with the balloon catheter was a good alternative to preoperative occlusion test.
- Published
- 1998
- Full Text
- View/download PDF
41. Role of infrainguinal bypass in Buerger's disease: an eighteen-year experience.
- Author
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Sasajima T, Kubo Y, Inaba M, Goh K, and Azuma N
- Subjects
- Adult, Aged, Angiography, Female, Graft Survival, Humans, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Thromboangiitis Obliterans diagnostic imaging, Vascular Patency, Veins transplantation, Leg blood supply, Thromboangiitis Obliterans surgery, Vascular Surgical Procedures
- Abstract
Objectives: The role of bypass to the distal arteries for patients with Buerger's disease (thromboangiitis or TAO) remains controversial because of the high incidence of graft failure. We retrospectively reviewed the results of 71 bypasses to evaluate their efficacy., Materials and Methods: We performed 71 autogenous vein bypasses in 61 patients with TAO. Of the patients, 97% were heavy smokers. The indications for surgery were claudication in 41%, and ischaemic ulcer or gangrene in 59%. Of the bypasses 85% were to the crural arteries or to the arteries below the ankle. The grafts used were 53 single saphenous veins, and 18 venovenous composite grafts., Results: There were 38 graft failures, the main causes including anastomosis to a diseased artery, disease progression (which occurred in smokers after surgery), and vein graft stenosis. Of 38, 10 were restored to patency by revision surgery. Primary and secondary patency rates were 48.8% and 62.5% at 5 years, and 43.0% and 56.3% at 10 years, respectively. The patency rates of the postoperative non-smoking group was significantly higher than that of the smoking group (66.8% vs. 34.7%, p < 0.05). Thirty-six patients (59%) had successful revascularisation and returned to full-time work. However, of 28 with secondary failure, 11 underwent amputation, while 14 had persistent disabling claudication., Conclusion: Bypass to the distal arteries is an effective treatment for TAO patients, and the long-term patency is quite satisfactory as long as patients stop smoking.
- Published
- 1997
- Full Text
- View/download PDF
42. Re-endothelialisation in autogenous vein grafts.
- Author
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Ishikawa M, Sasajima T, and Kubo Y
- Subjects
- Animals, Blood, Cell Division, Dogs, Femoral Artery surgery, Femoral Vein cytology, Heparin pharmacology, Sodium Chloride, Transplantation, Autologous, Endothelium, Vascular cytology, Femoral Vein transplantation
- Abstract
Objectives: To clarify the course of re-endothelialisation (Re-E) in an entire graft and to establish the effect of immersion media for the preservation of endothelial cells., Methods: Autogenous femoral veins of dogs were immersed in heparinised saline solution (n = 18) or heparinized autogenous blood (n = 18). After immersion, the grafts were implanted into bilateral femoral artery, and were retrieved 1 day to 4-8 weeks after implantation., Results: For the grafts immersed in the heparinised saline solution, the values for % area of endothelial cell coverage before implantation, and at 1 day, 1 week, and 4 weeks after implantation were 44.9%, 6.2%, 14.5%, and 81.3%, respectively. For the grafts immersed in heparinised autogenous blood, the values were 73.5%, 20.6%, 79.2% and 95.5%, respectively. However, such relatively rapid speed of Re-E slowed down considerably after 1 week following implantation in this group., Conclusions: The use of heparinized autogenous blood is strongly recommended as a preparation media for autogenous vein grafts. Almost all of the endothelial cells fall away in the earlier period after implantation and regenerate multifocally and irregularly. Re-E is incomplete even at 8 weeks after surgery, and we suggest that the area of incomplete Re-E may develop into intimal hyperplasia.
- Published
- 1996
- Full Text
- View/download PDF
43. Plantar or dorsalis pedis artery bypass in Buerger's disease.
- Author
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Sasajima T, Kubo Y, Izumi Y, Inaba M, and Goh K
- Subjects
- Adult, Anastomosis, Surgical, Angiography, Ankle blood supply, Arteries surgery, Female, Follow-Up Studies, Foot Ulcer surgery, Graft Occlusion, Vascular etiology, Graft Occlusion, Vascular physiopathology, Humans, Ischemia surgery, Male, Middle Aged, Popliteal Artery surgery, Regional Blood Flow physiology, Saphenous Vein diagnostic imaging, Saphenous Vein physiopathology, Smoking physiopathology, Thromboangiitis Obliterans diagnostic imaging, Thromboangiitis Obliterans physiopathology, Thrombosis etiology, Vascular Patency, Foot blood supply, Saphenous Vein transplantation, Thromboangiitis Obliterans surgery
- Abstract
The peripheral type of Buerger's disease is unresponsive to conservative therapy when accompanied by multisegmental occlusion at the level of the ankle. Between November 1983 and April 1993, we performed 15 bypasses below the ankle for this type of thromboangiitis obliterans in 13 patients (mean age 45.7 years), including four females. Ten patients had intractable toe ulcers with severe pain, and five had foot-threatening ischemia or disabling foot claudication. Eleven patients were heavy smokers, two were passive smokers, and six had a history of sympathectomy. All patients had occlusion of the three main crural arteries or both of the tibial arteries at the ankle. Of the 15 bypasses, 10 were to the medial or lateral plantar arteries, two were to the common plantar artery, and three were to the dorsalis pedis artery. There were three early and three late graft failures. The causes of early graft failure were thrombosis at the site of cross-clamping, anastomosis to a diseased segment, and arterial spasm. The three late failures (> 3 months) were due to disease progression in patients who continued to smoke, whereas all grafts remained patent and functioned well in patients who stopped smoking. Because patients with thromboangiitis obliterans are relatively young and active, early healing of ulcers and restoration of normal limb function are important objectives in their treatment. Bypass to the foot arteries can provide an excellent outcome, although special techniques and postoperative cessation of smoking are essential for success.
- Published
- 1994
- Full Text
- View/download PDF
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