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Objective In the past five decades, many small caliber vascular grafts have been developed as bypasses for infrapopliteal or coronary arteries. However, reliable grafts have not been obtained owing to poor patency, mainly caused by early thrombosis or neointimal hyperplasia in the intermediate period after implantation. We developed a novel small caliber heparin-loaded polyethylene terephthalate ultrafine microfiber (HL-PET) graft and evaluated the feasibility to overcome those main causes of graft failure in canine carotid artery implantation. Methods The HL-PET graft with a diameter of 3 mm and length of 30 mm was made with combination of three key technologies: (1) weaving with PET ultrafine microfiber with a high biological porosity allowing for cell ingrowth, (2) heparin loading on microfiber surfaces, and (3) an outer coating with a flexible bioabsorbable polymer for prevention of blood leakage and graft kinking. Kink resistance, water permeability, and loaded heparin were assessed. One HL-PET graft each was implanted into a carotid artery of six animals. Graft patency rate and healing were assessed 24 weeks after implantation. Results Among the six grafts, five were deemed patent (patency rate of >83%), with one occluded 20 weeks after implantation. Histopathology of the patent grafts showed neointima formation with confluent endothelial cell lining (estimated mean endothelial cell coverage area, 89 ± 18%). Intimal hyperplasia at the anastomotic sites and severe chronic inflammatory responses were not observed. Immunohistochemistry with antibodies to endothelial nitric oxide synthase, alpha 2 smooth muscle actin and calponin 1 revealed luminal surface endothelial cell layer with expression of endothelial nitric oxide synthase and vascular smooth muscle cells with contractile phenotype in the subintimal layer. Conclusions The HL-PET graft showed no early postoperative thrombosis and was able to demonstrate a high patency rate with no severe biological response observed after 24 weeks. These results strongly suggest the potential of the HL-PET graft to be used for distal bypasses., Clinical Relevance The HL-PET graft achieved a high patency rate without early postoperative thrombosis or intimal hyperplasia in a small caliber artery implantation study. The histopathologic analysis demonstrated favorable healing property with a high antithrombogenicity. These results strongly suggested the possible use of the HL-PET graft as a bypass for infrapopliteal or coronary arteries.

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.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.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.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.

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.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.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.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.

Objective: This multicenter observational study was conducted in order to investigate the incidence of cancer in patients with critical limb ischemia. Materials and Methods: We prospectively investigated the incidence of cancer in 68 patients with critical limb ischemia over a two-year period. Patients underwent an intensive examination at enrollment, which included tumor marker levels and chest and abdominal computed tomography, as well as one- and two-year follow-up examinations. We compared the observed incidence of cancer with the expected incidence calculated from national cancer rates by the standardized incidence ratio (SIR). Results: The majority (83.6%) of the patients were men, and 92.5% of the patients had a peripheral arterial disease that was classified as Fontaine stage III or IV. During enrollment, newly diagnosed cancers were detected in seven patients. Four additional cancers were detected during the follow-up period. All of the detected cancers were asymptomatic. We observed an increased risk of cancer (SIR, 4.04; 95% confidence interval, 1.31-9.42) in patients with critical limb ischemia. Conclusion: This study suggests that critical limb ischemia is associated with an increased risk of cancer. Our findings should be taken into serious consideration by future investigators considering the use of therapeutic angiogenesis.

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.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.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.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.

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.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.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.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.

To rescue severely affected hind limbs from amputation, the surgery of the distal vein arterialization DVA technique has been used and refined in respect of different theoretical and pathophysiological aspects; tissue cylinder model, total venular length, oxygen diffusion to muscles, water movements are discussed under the surgically introduced unusual circumstances. All these variables are interrelated to support the fundamental oxygen utilization of muscle tissues to survive. Separately carried out studies and techniques are summarized here. The therapeutic results of DVA surgery were compared with angiogenic and pharmacological treatments in respect of peripheral arterial disease.Key words: peripheral arterial disease, distal vein arterialization, tissue cylinder model, oxygen diffusion, angiogenetic treatment, pharmacological treatment

Patients with symptomatic peripheral artery disease (PAD) have an elevated prevalence of internal carotid artery (ICA) stenosis and cerebral infarction, although the correlations between the severity of PAD and cerebral infarction, cerebral white matter lesion (WML), or intracranial or extracranial artery stenosis are unclear.We evaluated the prevalence of cardiovascular risk factors, cerebral infarction, and WML on magnetic resonance imaging and intracranial and extracranial carotid artery stenoses on magnetic resonance angiography in patients with symptomatic PAD (n = 136; males/females [M/F] 109/27) and a control group comprised of patients without PAD (n = 92; M/F 57/35). PAD was classified by Fontaine stage (stage II, n = 46; stage III, n = 20; stage IV, n = 70). Cerebral infarctions were classified into symptomatic or asymptomatic groups. WMLs were evaluated according to Fazekas stage. Artery stenosis was classified as normal (no stenosis), mild (stenosis50%), moderate (stenosis ≥ 50%), severe (tight stenosis), and obstruction on magnetic resonance angiography.Diabetes mellitus (DM), dyslipidemia, coronary artery disease (CAD), and chronic kidney disease (CKD), as well as symptomatic cerebral infarction and WML, were more frequent in patients with Fontaine III/IV PAD than without PAD. The prevalence rates of cerebral infarction and WML in patients with Fontaine stage II PAD were between those of the control and Fontaine III/IV PAD patients. Supraclinoid and cervical ICA stenoses (50%) were more frequent in patients with Fontaine stage IV PAD than without PAD.Our results indicate that patients with advanced PAD have an increased prevalence of symptomatic cerebral infarction, WML, and intracranial and cervical ICA stenosis as well as DM, CAD, and CKD.

ObjectivesTo preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery.DesignA prospective cohort study.Patients and methods299 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.ResultsPOD 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 (

Mammographic breast arterial calcifications (BACs) are regarded as aging-related benign changes in breast cancer screening practices. BACs have recently attracted attention, because several researchers proposed using them as a surrogate marker of arteriosclerosis or osteoporosis. No studies have thus far evaluated an association between BACs and breast cancer, however.The percentage of BAC positivity was compared between a group of women aged 40 years or older with breast cancer detected in 2004 through 2009, and a group of women of the same age range in whom breast cancer was not detected by screening mammography in 2009.The BAC-positive rate in the group of 243 breast cancer patients was 9.88% (24 of the 243) and was lower than that in the group of women without breast cancer, 14.34% (506 of 3528 women). The analysis by age revealed that the differences in this parameter between the two groups were significant in women aged 60 years or older. Multivariate analysis including demographic characteristics revealed that when adjusted for age and body weight, BAC positivity was a significant risk factor for breast cancer.The study results suggest that BAC positivity and, in turn, arteriosclerosis may have an antinomic relationship with breast cancer.

Hepatocyte growth factor (HGF) is a potent angiogenic factor. The efficacy and safety of intramuscular injection of a naked plasmid encoding human HGF gene (beperminogene perplasmid, Collategene) was investigated in patients with critical limb ischemia (CLI) in a multicenter, randomized, double-blind, placebo-controlled trial. The randomization ratio for plasmid to placebo was 2:1. Injection sites were selected in each patient limb based on angiographic findings. Placebo or plasmid was injected on days 0 and 28. Evaluation of efficacy was carried out after 12 weeks. The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5). Secondary end points were ankle-brachial pressure index, amputation, and quality of life (QOL). Forty-four patients were treated, and we performed interim analysis of efficacy in 40 patients. The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P=0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P=0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI.

Rationnelle Nous avons evalue les resultats a moyen terme de l’arterialisation veineuse distale (AVD) et le role d’un lambeau libre associe pour support de la revascularisation. Methodes Au cours des 5 dernieres annees, neuf patients avec une perte de substance etendue sans arteres distales pontables ont eu une AVD. Il s’agissait de quatre AVD primaires, dont trois associees a un lambeau libre, et de deux AVD adjuvantes pour des pontages distaux hemodynamiquement defaillants. Apres neuf AVD primaires, trois AVD iteratives ont ete faites pour echec precoce. Les etiologies etaient quatre maladies de Buerger et cinq arterioscleroses obliterantes, dont trois chez des dialyses. Resultats Parmi les neuf cas d’AVD, il y eut cinq echecs primaires : deux ont eu une amputation, deux ont eu un succes de l’AVD iterative, et le dernier n’a pas necessite d’AVD iterative. La permeabilite primaire, la permeabilite secondaire, et les taux de sauvetage de membre etaient respectivement de 44,4%, 55,6%, et 77,8%. Le suivi postoperatoire etait de 1-36 mois (mediane 12). L’angiographie a montre que l’AVD etait efficace pendant la periode precoce, et que le developpement de collaterales ou d’un reseau capillaire du lambeau libre remplacait la fonction de l’AVD a moyen terme. Conclusion L’AVD peut etre efficace comme procede de sauvetage de membre chez les patients sans artere distale pontable, et un lambeau libre associe est efficace et fonctionne comme tete de pont pour l’approvisionnement sanguin dans la zone ischemique.

http://dx.doi.org/10.1016/j.avsg.2009.07.001, 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.

We present here in the case of a patient who underwent resection of clear cell carcinoma of the lung, a rare histological type. A screening test of the 71-year-old woman revealed a 2.0-cm lesion in S4 of the right lung with a diagnosis of bronchioloalveolar carcinoma before resection. Under the guidance of video-assisted thoracoscopy, right middle lobe resection and mediastinal lymph node dissection were performed. The histopathological examination showed clear, slightly acidophilic tumor cells rich in fine granular components proliferating in an alveolar fashion. Immunostaining was diagnostically useful, distinguishing clear cell carcinoma from lung metastasis of renal clear cell carcinoma or clear cell squamous cell carcinoma.

Na(+)/K(+) pump activation induced by normothermic reperfusion with high potassium cardioplegia may exert a protective effect on reperfusion-induced myocardial damage. We investigated (1) temperature dependency and extracellular potassium dependency of the Na(+)/K(+) pump current (Ip), (2) effects of high potassium or ouabain during reperfusion on the post-ischemic left ventricular (LV) function. Ip-voltage relation was constructed at 5.0 and 20 mM of KCl (37 degrees C) using a whole-cell clamp technique in guinea pig myocytes. Ip at -40 mV was measured at 37, 27 and 18 degrees C (KCl: 5.0 mM). Isolated rat hearts were Langendorff-perfused and subjected to 20 min of global ischemia (37 degrees C) followed by 35 min of reperfusion (37 degrees C). The post-ischemic recovery of LV developed pressure (%LVDP) was assessed in the four reperfusate groups (4.8 mM KCl, 10 mM KCl, 20 mM KCl, or 4.8 mM KCl plus 50 microM ouabain during the first 10 min of reperfusion). The 4.8 mM KCl and 10.0 mM KCl groups were compared under metabolic inhibition (glucose-free, NaCN, or hypoxia) during reperfusion. The Ip-voltage relation shifted upward when extracellular KCl was increased from 5.0 to 20 mM. Ip was significantly greater at 37 degrees C than at 18 degrees C (114.3+/-17.2 vs. 22.7+/-1.2 pA, respectively). %LVDP was significantly greater at the 10.0 mM KCl group than at the 4.8 mM KCl group (54.9+/-5.5% vs. 34.2+/-5.9%, respectively). Metabolic inhibition abolished the difference between the two groups. Ouabain significantly decreased %LVDP (15.9+/-1.6%). Potassium-induced cardiac arrest during normothermic reperfusion may exert a cardioprotective effect by inducing Na(+)/K(+) pump activation, which may be supported by aerobic metabolism during reoxygenation rather than by energy saving during cardiac arrest.

Dual-targeted therapy for antiangiogenesis and antilymphangiogenesis represents a potentially effective strategy for the treatment of various malignancies. Therefore, the goal of the present study was to identify genes that encode inhibitors of both angiogenesis and lymphangiogenesis. Using a cDNA library obtained from Lewis lung carcinoma (LL/2), a candidate gene was identified by the evaluation of growth inhibition in aortic and lymphatic endothelial cells (EC) as that coding for the mouse cold shock domain protein A (mCSDA). Overexpression of mCSDA significantly repressed cell proliferation and c-fos promoter activity in aortic, venous and lymphatic ECs. CSDA is a DNA-binding protein that binds to the hypoxia response element (HRE). Furthermore, of importance, we revealed that CSDA could directly bind to the serum response element (SRE) sequence, resulting in the inhibition of SRE activity, which may lead to growth inhibition in ECs. In an LL/2-inoculated mouse model, tumor growth was significantly repressed in an mCSDA-injected group. Histopathological analysis revealed that expression of blood and lymphatic EC markers was significantly decreased in mCSDA-injected groups. In conclusion, these data suggest that expression of CSDA can repress angiogenesis and lymphangiogenesis via direct binding to SRE in addition to HRE.

We present the case of a 59-year-old male Jehovah's Witness who underwent staged repair for a thoracic aortic aneurysm with no transfusion. The primary operation to replace the distal portion of the aortic arch and left subclavian artery reconstruction were performed. We applied axilla femoral artery temporary external bypass. A second operation was carried out 8 months later. We replaced the descending aorta and reconstructed the intercostal arteries under temporary bypass in the same manner as was done during the previous operation. The blood losses and minimum hemoglobin values during the two operations were 2235 and 13,941 ml, respectively, 8.8 and 5.9 g/dl, respectively. Administration of erythropoietin and a drainage blood recovery device were useful. Surgical repair for a thoracic aortic aneurysm using a temporary bypass is thus considered a viable surgical option in such situations and is important for conducting effective perioperative management.

We attempted to clarify the effect of different types of shear stress on endothelial cell (EC) proliferation and survival. Bovine aortic ECs were subjected to either steady laminar, 1 Hz pulsatile, or 1 Hz to and fro shear at 14 dyne/cm(2). % of BrdU positive EC was 14.3 +/- 1.6% in steady, 21.5 +/- 3.2% in pulsatile, and 11.4 +/- 2.4% in to and fro after 4 h, respectively (P < 0.05). Pulsatile shear compared with static control. Rapamycin reduced BrdU incorporation in all shear regimens (P < 0.001). However, it was still higher in EC exposed to pulsatile shear than the other regimens (P < 0.005). PD98059 completely abolished the increased BrdU incorporation in all shear regimens, including pulsatile shear. Pulsatile shear had significantly elevated ERK1/2 phosphorylation at 5 min compared with steady (P < 0.05) and to and fro shear (P < 0.01) while there was no significant difference in pp70(S6k) phosphorylation between any shear regimen. The ratio of apoptotic cells in serum deprived EC in the presence of steady laminar, pulsatile and to and fro shear for 4 h were 2.7 +/- 0.78%, 2.7 +/- 0.42%, and 2.9 +/- 0.62%, respectively while after the addition of serum for 4 h, it was 4.3 +/- 0.73%. All shear regimens phosphorylated AKT in a time-dependent manner with no significant difference between regimens. Our results demonstrate that different types of shear stress regimens have different effects on EC and may account for the variable response of EC to hemodynamics in the circulation.

血胸を契機に発見された胸腔内悪性末梢神経鞘腫（malignant peripheral nerve sheath tumor; MPNST）の1例を経験した．症例は22歳，女性，von Recklinghausen病．胸痛と息切れを主訴に当院を受診した．胸部CTで最大径12cmの左胸腔内腫瘍と胸水を認め，針生検でMPNSTと診断された．手術は胸腔鏡補助下，左第5肋間開胸，第8肋間小開胸にて，左胸腔内腫瘍摘出術と荒廃した左肺下葉切除を施行し，術後7日目に退院となった．MPNSTは予後不良な疾患であり，血胸を引き起こし致命的な経過をとることも念頭に置かなければならない．

Introduction: Lesions causing coronary and peripheral vein graft failure often occur at valves. To test the hypothesis that intrinsic differences in cells of the valve wall contribute to graft failure we measured cell migration from tissue explants and migration and proliferation of cultured cells from valve and non-valve sections of human saphenous vein (HSV). Methods: After removal of endothelium, HSVs were dissected into an outer wall with adventitia and some media and an inner wall with intima and some media. Cell migration from explants and migration (microchemotaxis chambers) and proliferation of cultured cells at passage 6 were measured. Results: Cells migrated faster from valve compared to non-valve tissue of the inner wall (Figure A; P Conclusion: The increased migration and proliferation of VSMC compared to NVSMC is largely mediated by FGF2.

Background— Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Treatment for this disabling condition remains limited and largely ineffective. The goal of the present study was to investigate the therapeutic efficacy of hepatocyte growth factor (HGF) in animal models of lymphedema. Methods and Results— Immunofluorescent analysis demonstrated that canine primary lymphatic endothelial cells (cLECs) were positive for lymphatic-specific markers (vascular endothelial growth factor receptor-3, LYVE-1, podoplanin, and Prox1) and the HGF receptor c-Met. Treating cLECs with human recombinant HGF resulted in a dose-dependent increase in cell growth and migration and increased activity of extracellular signal-regulated kinase and Akt. In human LECs, c-Met also was expressed, and treatment with HGF increased cell growth and migration in a dose-dependent manner. Transfection of human HGF plasmid DNA in cLECs also increased the c- fos promoter activity. Furthermore, weekly HGF gene transfer in a rat tail lymphedema model by disruption of lymphatic vessels resulted in a decrease in lymphedema thickness. Although expression of the endothelial cell marker PECAM-1 was increased in both HGF- and vascular endothelial growth factor 165–injected groups, expression of LEC markers (LYVE-1 and Prox1) was increased only in the HGF-injected group. Conclusions— These data demonstrate that expression of HGF via plasmid transfer improves lymphedema via promotion of lymphangiogenesis. Further studies to determine the clinical utility of this approach would be of benefit to patients with lymphedema.

Copyright 2004 by The American Society for Biochemistry and Molecular Biology, Inc. author, Visinin-like protein-3, which is one of the neuronal calcium sensors, has been shown to be mainly expressed in cerebellar Purkinje cells, but cellular function of this protein has not yet been elucidated. We examined the tissue distribution of murine visinin-like protein-3 transcripts using real-time reverse transcription-PCR. Visinin-like protein-3 mRNA was found to be expressed in peripheral tissues. Particularly, the expression of the transcript in the thymus was significantly higher than in other peripheral tissues. In addition, B6RVTC1 thymoma cells robustly expressed visinin-like protein-3 mRNA. To identify a target protein of visinin-like protein-3, we performed a pull-down experiment using glutathione S-transferase-tagged visinin-like protein-3 and two-dimensional electrophoresis. We demonstrated that microsomal cytochrome b(5) was a Ca(2+)-dependent binding partner of visinin-like protein-3. In a co-immunoprecipitation experiment, it was observed that hippocalcin, as well as visinin-like protein-3, could interact with cytochrome b(5). Furthermore, we confirmed that the sequence Val(114)-Tyr(127) at the C-terminal tail of cytochrome b(5) is the minimal structural requirement for binding to visinin-like protein-3. In addition, the loop His(19)-His(25) at the N terminus of visinin-like protein-3 is essential for binding to cytochrome b(5). Microsomal cytochrome b(5) was also shown to be a potential activator of cytochrome P450. The present findings raise the possibility that visinin-like protein-3 may link Ca(2+) signaling to the machinery of microsomal monooxygenase complex composed of cytochrome b(5), cytochrome P450, and some reductases. This report provides the first evidence of an interaction between visinin-like protein-3 and microsomal cytochrome b(5).

Objective To improve the estimation of 9 9 m Tc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts. Methods Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140′14 keV; sub, 122.5 t 3.5 keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tennesen's formula, and linear combination of scatter fraction and Tennesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated. Results One-sample clearance ranged from 11 to 404 ml.min - 1 per 1.73 m 2 . More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P

症例は69歳,男性.脳梗塞で当院脳外科入院中の腹部CTで,偶然最大径5cmの腹部大動脈瘤指摘され当科紹介となった.マントルサインは明らかではなかった.術前消化管精査でS状結腸にII型腫瘍を認めた.手術は二期的に行う方針とし,最初にS状結腸切除術, D1を施行した.病理組織検査では中分化型腺癌, mp, ly0, v1, INFβ, ow (-), aw (-), Stage IIであった. 36日後に腹部大動脈瘤に対し後腹膜経路で瘤切除人工血管置換術を施行した.瘤壁は白色陶器様であり病理組織検査で炎症性腹部大動脈瘤の診断が得られた.炎症性腹部大動脈瘤と大腸癌が合併した稀な症例と考え,文献的考察を加え報告する.

我々は特異な形態, 内容物を有する肺内気管支性嚢胞の1手術例を経験したので報告する.症例は55歳, 男性.CT上右S7末梢にダンベル状の腫瘤像を認め, BFではB7が膜様に閉塞していた.画像上肺内気管支性嚢胞が疑われたが, 確定診断に至らず, 充実性腫瘍も否定できなかった為, 診断および治療目的にて手術を行った.手術は腫瘤が肺底区気管支と近接しており, 腫瘤切除術およびS3区域切除術はともに困難と判断し, 右肺底区区域切除術を施行した.腫瘤は被膜を有し, 内部にはチーズ様の内容物が充満しており, 病理組織学的にBronchogenic cystと診断された.

A 69-year-old lady was discovered unconscious. Computed tomography showed pericardial effusion and a coronary artery aneurysm of 25 mm in diameter in front of the main pulmonary artery. Emergency surgery revealed a coronary-pulmonary artery fistula and coronary aneurysm surrounded by a large hematoma. The inflow and outflow of the fistula were closed, and no cardioplegic leakage was noted. Postoperative angiography showed residual fistulas that were successfully closed by transcatheter embolization.

The immunological screening of breast cancer was performed with IgG autoantibodies by the serological analysis of recombinant cDNA expression library methods to explore novel tumor associated antigens. We have focused on a small zinc finger protein metallopanstimulin-1 (MPS-1). MPS-1 mRNA was ubiquitously expressed in normal human tissues except the brain and the placenta. In Western blot analysis, MPS-1 was easily detected strongly in actively proliferating cells and three breast cancer cell lines. In the tissue the protein of MPS-1 in cancer cells was more abundant than that of surrounding normal cells. Screening of tissue specimens by immunohistochemistry revealed 50.4% positive for MPS-1 in 125 cancer patients. These data suggest that MPS-1 could be applicable to the immunotherapy of breast cancer.

Forced retrograde perfusion through the venous system with arterial blood can provide adequate oxygen to peripheral tissues at rest through veno-capillary networks which is the basis for surgical restoration of blood flow by distal vein arterialization (DVA). To be successful such surgery requires disruption of valve leaflets in the veins, which can be accomplished easily in the larger vessels. However, the smallest veins (venules) of less than 100 μm in diameter, also possess valves, are distributed widely throughout all tissues and are too fine for any effective surgical interference. Thus venular valves cannot be disrupted or dissected with presently available technology. Nevertheless, clinical observations suggest that retrograde peripheral blood flow is rapidly established after DVA surgery. There is as yet no rational explanation for this phenomenon. In the present study, using Laplace's law, we attempt to elucidate the mechanical properties of venules and their valves. We speculate that the remarkably thin venular walls (and especially those of the smaller vessels which have the thinnest walls), are capable of considerable, rapid distension when subjected to increased hemostatic pressure. The increase in diameter of venules in response to the increased blood pressure renders their valve leaflets incompetent, so that the valves themselves cannot close the vessel lumen. In addition, the thin bicuspid leaflets may also be forced open retrogradely by the increased blood pressure.

Vascular surgery for distal vein arterialization (DVA) has been adopted clinically as a strategy for saving arteriosclerotic lower limbs from amputation. To gain more detailed information on DVA, the present study investigated the procedure in hind limbs of rats under isoflurane anesthesia. Since successful DVA requires destruction of venous valves, a coronary angioplasty catheter guidewire was used to destroy valves either solely in the femoral vein or in both femoral and popliteal veins. The femoral artery was then anastomosed to the femoral vein with sutures under binocular microsopic control. Changes in the distribution of skin blood flow in the hind limbs were studied with a thermal camera. Skin temperature increased in the thigh and knee after femoral venous valve destruction, but hyperthermia was observed in the distal leg and foot only when the valves in the popliteal vein were also disrupted. These results showed that increased arterial blood flow could be established by DVA surgery in both the proximal and distal regions of the hind limbs.

Vascular surgery for distal vein arterialization (DVA) has been adopted clinically as a strategy for saving arteriosclerotic lower limbs from amputation. To gain more detailed information on DVA, the present study investigated the procedure in hind limbs of rats under isoflurane anesthesia. Since successful DVA requires destruction of venous valves, a coronary angioplasty catheter guidewire was used to destroy valves either solely in the femoral vein or in both femoral and popliteal veins. The femoral artery was then anastomosed to the femoral vein with sutures under binocular microsopic control. Changes in the distribution of skin blood flow in the hind limbs were studied with a thermal camera. Skin temperature increased in the thigh and knee after femoral venous valve destruction, but hyperthermia was observed in the distal leg and foot only when the valves in the popliteal vein were also disrupted. These results showed that increased arterial blood flow could be established by DVA surgery in both the proximal and distal regions of the hind limbs.

Forced retrograde perfusion through the venous system with arterial blood can provide adequate oxygen to peripheral tissues at rest through veno-capillary networks which is the basis for surgical restoration of blood flow by distal vein arterialization (DVA). To be successful such surgery requires disruption of valve leaflets in the veins, which can be accomplished easily in the larger vessels. However, the smallest veins (venules) of less than 100 μm in diameter, also possess valves, are distributed widely throughout all tissues and are too fine for any effective surgical interference. Thus venular valves cannot be disrupted or dissected with presently available technology. Nevertheless, clinical observations suggest that retrograde peripheral blood flow is rapidly established after DVA surgery. There is as yet no rational explanation for this phenomenon. In the present study, using Laplace’s law, we attempt to elucidate the mechanical properties of venules and their valves. We speculate that the remarkably thin venular walls (and especially those of the smaller vessels which have the thinnest walls), are capable of considerable, rapid distension when subjected to increased hemostatic pressure. The increase in diameter of venules in response to the increased blood pressure renders their valve leaflets incompetent, so that the valves themselves cannot close the vessel lumen. In addition, the thin bicuspid leaflets may also be forced open retrogradely by the increased blood pressure.

腹腔鏡下手術後に発生したRichter's hernia 3例を経験した. 3例とも術後1週間以内に,嘔気,嘔吐,腹痛の症状にて発症した.腹部X線写真では,鏡面像を認め,また腹部超音波検査では,腸管が腹壁に嵌入している所見を認め, Richter's herniaと診断し手術を施行した.発生部位は初回手術時のポート挿入部であり,小腸が腹壁に嵌入していた. 1例は腸管壊死を起こしていたため,小腸切除に至ったが,他の2例は,イレウス解除術にて終了した.全例術後順調に経過し退院となった. 3例とも初回手術時に10mmのポートを使用し,挿入部の腹膜の縫合が行われていなかったことが原因と考えられ, 10mm以上のポートを使用した際には,腹膜の縫合が必須であると考えられた.

乳癌術後胸骨転移3例に対し, 胸壁全層切除再建術を施行した.症例は, 48-62才の女性.胸筋合併乳房切除術後3～13年で, 1例は右胸鎖関節部, 他の2例は胸骨に転移再発を認めた.手術は, 1) 胸骨柄'体部分切除, 両側鎖骨骨頭及び第1～3肋軟骨切除術, 2) 胸骨全切除, 左鎖骨及び第1～3肋骨部分切除術, 3) 胸骨柄・体部分切除, 左鎖骨及び第1～3肋骨部分切除術を施行した.再建は, マーレックスメッシュ単独, チタンプレート単独, マーレックスメッシュ+チタンプレートにて行い, 組織補填には, 有茎対側乳房, 有茎又は遊離腹直筋皮弁を用いた.胸壁の欠損が小さければ, マーレックスメッシュ単独の再建が可能であるが, 胸骨体に及ぶ切除には, チタンプレートにマーレックスメッシュを固定する方法が有効であり, 術後早期の抜管が可能であった.皮膚軟部組織の再建には遊離腹直筋皮弁が最適と考えられた.

We examined the blood supply of a cryopreserved tracheal allograft and its morphohistologic changes after transplantation.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.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 (p0.05). Recanalization of the transverse intercartilaginous arteries was also demonstrated in the fresh allografts; however, necrosis abruptly occurred as a result of acute rejection responses.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.

教室における過去10年間の腹部大動脈瘤症例160例中, 78例を開腹到達法 (TP群), 82例を腹膜外到達法 (EP群) で施行した. このうち下腸間膜動脈, 腎動脈, 下肢末梢動脈など合併再建のない, TP群42例, EP群40例を対象とし比較した. 手術時間, 術中出血量, 術中および術後輸血量は両群間に差はなかったが (TP群: 328.1分, 965.9ml, 633ml, EP群: 359.5分, 1,020ml, 420ml), 術後, 経口摂取開始までの期間, 補液を必要とした期間はTP群に比べEP群で有意に短く (TP群: 9.9日, 15.7日, EP群: 6.6日, 10.4日), 腹膜外到達法は早期離床のために有用であると考えられた. 術後合併症のうち, 腹壁瘢痕ヘルニアはEP群に有意に多く, 後腹膜乳糜漏, 後腹膜液貯留はEP群にのみ生じたが, 手術手技の習熟により回避され得ると考えられた.

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.

To evaluate the role of three-dimensional computed tomographic angiography (3D-CT) in peripheral artery bypass surgery, 49 patients with chronic lower limb ischemia underwent 3D-CT before and after a bypass operation. 3D-CT had a sensitivity of 96.8%, a specificity of 95.0% and an overall accuracy of 96.1% for the diagnosis of arterial and graft stenosis or obstructions. The ability to observe the acquired images at any angle was very useful for assessing the implanted graft in both aortoiliac and infrainguinal bypasses. Although these images equally identified arterial stenosis, obstruction, and the anastomotic morphology of bypass grafts as well as conventional angiography, the diagnostic accuracy was not helpful in the small arteries and grafts. 3D-CT is a low-invasive imaging method that is sufficient for forming strategies for bypass operations. In aortofemoral or femoropopliteal bypass surgery, 3D-CT thus provides sufficient imaging accuracy for bypasses up to the popliteal artery below the knee in patients with chronic limb ischemia.

症例は41歳, 女性.背部痛と労作時呼吸困難を主訴に当科紹介.胸部X線写真, CTにて左胸腔内に巨大腫瘍 (20×15cm) が存在し, 第6肋間動脈造影では腫瘍への強いfeedingをみとめた.手術は左第6肋骨床開胸にて施行.腫瘍は表面が易出血性であり, 背側の第6肋骨と強く癒着していた.第6肋間との癒着を剥離第6肋間動静脈の合併切除をしたのちは腫瘍は比較的容易に摘出できた.その後は圧排されていた左下葉も充分換気出来るようになった。術後経過は良好であり術後21日に退院となった.病理はAncient Neurilemmoma (変性型神経鞘腫) であった