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A 17-year-old Japanese male athlete presented to the emergency department at our hospital with a chief complaint of exertional dyspnea. Although there were no significant findings in the right and left upper extremities on a physical examination, a chest computed tomography scan showed bilateral multiple thrombosis in the pulmonary arteries, indicating pulmonary thromboembolism, and deep vein thrombosis in the left subclavian vein. Upper limb venography showed interruption of the left subclavian vein (so-called Paget-Schroetter syndrome; PSS). We herein report this rare case of PSS that led to pulmonary thromboembolism in a young, male field athlete.

In atherosclerosis progression, calcium deposition may have an impact on the natural history of coronary atherosclerosis, and the amount of calcium may affect the success rate of percutaneous coronary intervention (PCI). Coronary stent dislodgement does not commonly occur in the modern PCI era; however, it may lead to fatal death. If it occurs, retrieval of a dislodged stent can be performed either surgically or percutaneously using a variety of retrieval techniques, including inflating a catheter balloon distal to the undeployed stent, twirling 2 wires around the stent, a loop snare, or forceps. Here, we report a rare case that coronary artery stent dislodgement and aortic dissection simultaneously occurred during PCI for a severely calcified lesion in the proximal right coronary artery with shepherd's crook morphology. The situation was successfully rectified by using balloons to deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection. Learning objective: During percutaneous coronary intervention (PCI), stent dislodgement and aortic dissection are extremely rare, but life-threatening complications. In this rare case of simultaneous stent dislodgement in the coronary artery and aortic dissection during PCI for a severely calcified lesion in the right coronary artery with shepherd's crook morphology, the situation was successfully rectified by using balloons to retrieve and deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection.

Background Thromboangiitis obliterans, also known as Buerger's disease, is characterized by peripheral occlusive changes in the arteries of the upper and lower limbs and treatment is often ineffective. Intramuscular transplantation of autologous bone marrow-mononuclear cells (BM-MNC) has been recently reported as improving the symptoms and clinical manifestations in patients with severely ischemic limbs, mostly caused by arteriosclerosis obliterans. The present study focused on the patients with Buerger's disease presenting with rest pain and/or skin ulcer uncontrolled by conventional treatments. Methods and Results Fourteen patients with Buerger's disease (Fontaine III: n=2, Fontaine IV: n=12) underwent transplantation of autologous BM-MNC into ischemic skeletal muscles of either the upper or lower limb. After 4 weeks, rest pain was significantly reduced. In 19 skin ulcers of 9 patients, 8 ulcers were healed and 8 were diminished in the size. These improvements were maintained for 24 weeks without complications. Conclusions In patients with Buerger's disease, intramuscular transplantation of autologous BM-MNC improved symptoms and clinical manifestations, especially skin ulcer. (Circ J 2007; 71: 1187 - 1192)

Object. The authors determined the factors that predict the coexistence of coronary artery disease (CAD) in patients who undergo carotid endarterectomy (CEA). Methods. Data from 200 consecutive Japanese patients who underwent CEA for extracranial carotid artery stenosis were studied. Among 73 patients with CAD, 35 (48%) had three-vessel or left main CAD (that is, severe CAD). Peripheral artery disease was an independent predictor of CAD (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.08–6.3). In addition, diabetes mellitus ([DM]; OR 2.8, 95% CI 1.24–6.32) and peripheral artery disease (PAD) (OR 2.83, 95% CI 1.05–7.57) were independent predictors of severe CAD in the 200 patients. The percentage of patients with CAD as well as those with the severe form of the disease increased stepwise as the number of major coronary risk factors in patients increased. Asymptomatic CAD was newly detected during the pre-CEA assessment in 18 (25%) of the 73 patients in whom CAD was eventually diagnosed. Diabetes mellitus was an independent predictor of occult CAD among the 200 patients (OR 4.83, 95% CI 1.53–15.2). Conclusions. In patients with DM, PAD, or multiple major coronary risk factors who have been scheduled for CEA, one should carefully search for concomitant CAD, especially severe CAD, even when the patient has had no previous episode of angina.

Advanced systemic atherosclerotic disease is increasing in Japan. The patients with severe carotid steno-tic lesion have frequently (30-40%) associated with coronary artery disease, especially in those with diabetes mellitus and peripheral arterial disease. The new concept of acute neurovascular syndrome is similar to that of acute coronary syndrome, and both are based on the therapeutic standpoint. It becomes more important to protect the advanced atherosclerotic patients from both cerebral and myocardial ischemia/infarction, although the technology and safety of the surgery and stenting for carotid and coronary artery is remarkably improving. Clinical evidence from Japanese large clinical research should be clarified near future. The various approaches to carotid and coronary atherosclerosis tend to be less invasive.

Background— The effects of aging on angiogenesis (vascular sprouting) and vasculogenesis (endothelial precursor cell [EPC] incorporation into vessels) are not well known. We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in klotho ( kl ) mutant mice, an animal model of typical aging. Methods and Results— After unilateral hindlimb ischemia, laser Doppler blood-flow (LDBF) analysis revealed a decreased ischemic-normal LDBF ratio in kl mice. Tissue capillary density was also suppressed in kl mice ( +/+ > +/kl > kl/kl ). Aortic-ring culture assay showed impaired angiogenesis in kl/kl mice, accompanied by reduced endothelium-derived nitric oxide release. Moreover, the rate of transplanted homologous bone marrow cells incorporated into capillaries in ischemic tissues (vasculogenesis) was lower in kl/kl mice than in wild-type ( +/+ ) mice, which was associated with a decrease in the number of c-Kit + CD31 + EPC-like mononuclear cells in bone marrow and in peripheral blood. Finally, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin restored the impaired neovascularization in kl/kl mice, accompanied by an increase in c-Kit + CD31 + cells in bone marrow and peripheral blood, and enhanced angiogenesis in the aortic-ring culture. Conclusions— Angiogenesis and vasculogenesis are impaired in kl mutant mice, a model of typical aging. Moreover, the age-associated impairment of neovascularization might be a new target of statin therapy.

Objectives We sought to investigate the role of endogenous monocyte chemoattractant protein (MCP)-1 in ischemia-induced neovascularization. Background Roles of inflammatory changes including macrophage infiltration are suggested in ischemic neovascularization. Methods Unilateral hindlimb ischemia was induced by excising surgically the entire femoral artery and vein in mice. Immediately after operation, plasmid deoxyribonucleic acid encoding a dominant negative mutant of MCP-1 (7ND) or the empty plasmid (mock) was injected into the ipsilateral thigh adductor muscle. Results In mock-treated mice, MCP-1 was upregulated transiently in ischemic hindlimb peaking at day 3. Serial laser Doppler blood flow (LDBF) analysis showed an abrupt decrease in blood flow, followed by a recovery to the near-normal levels in mock-treated mice; 7ND treatment had no effects on the initial decrease in LDBF but deteriorated the recovery. At day 3, macrophage infiltration and inductions of tumor necrosis factor (TNF)-alpha and vascular endothelial growth factor (VEGF) were prominent in the ischemic adductor muscle in mock-treated mice; 7ND treatment significantly reduced macrophage infiltration and suppressed TNF-alpha and VEGF inductions in response to ischemia. At day 21, postmortem angiography and anti-CD31 immunohistostaining revealed well-developed collateral vessels and capillary formation, respectively, in the ischemic muscle of mock-treated mice; 7ND overexpression remarkably suppressed the collateral vessel formation and capillary formation. Conclusions Endogenous MCP-1 may play a role in ischemia-induced neovascularization by recruiting macrophages that activate TNF-alpha and VEGF inductions.

大腸癌の同時性卵巣転移の2症例を報告した.症例1, 25歳,女性.下腹部腫瘤を主訴に当院産婦人科を受診し,左卵巣腫瘍の診断にて,開腹手術を受けた.開腹時,卵巣とは別個にS状結腸にも全周性腫瘍病変が認められたため,ハルトマン手術を併施した.病理検査の結果, S状結腸癌の左卵巣転移と診断された.症例2, 56歳,閉経女性.腹痛,嘔吐を主訴に当科を受診し,下行結腸腫瘍による腸閉塞の診断にて,緊急的に横行結腸に人工肛門を造設した.その後の精査により,右卵巣腫瘍も認められたため,結腸左半切除術,子宮全摘術,両側附属器切除術を施行した.病理検査の結果,下行結腸癌の右卵巣転移と診断された.本邦における転移性卵巣腫瘍の原発巣としては胃癌が最も多く,大腸癌は比較的稀である.今回,大腸癌同時性卵巣転移の2例を経験したので,若干の文献的考察を加え報告する.

We report a patient who developed reversible posterior leukoencephalopathy syndrome (RPLS) in puerperium without preeclampsia-eclampsia or chronic hypertension. The woman suddenly complained of visual loss and headache 10 days after delivery caused by edematous lesions mainly distributed in the bilateral occipital lobe. Apparent diffusion coefficient map was useful for distinction of this vasogenic edema from cytotoxic edema due to brain infarction. Under the diagnosis of RPLS, we successfully treated her disease using a trinitroglycerin as an antihypertensive, a hyperosmolar agent, methylprednisolone, and a free radical scavenger. Postpartum women may have the risk of development of RPLS even without preeclampsia-eclampsia. Vascular endothelial dysfunction may trigger RPLS, in addition to acute and modest increase in systemic pressure.

症例は51歳, 女性.10年前, 検診にて胸部X線の異常陰影を指摘され, 近医を受診.精査の結果, 前縦隔腫瘍の診断を受けるが放置.今回, 再び, 胸部X線異常影を指摘されたため同医を受診.腫瘍の増大およびCA19-9の高値 (672IU/ml) を認めたため, 当科紹介となり, 嚢胞性前縦隔腫瘍の診断にて, 腫瘍切除および胸腺全摘術を施行した.腫瘍は嚢胞成分が主体であるが, 一部充実性部分も認めた.切除標本の病理学的診断は胸腺原発mucoepidermoidcarcinoma, low gradeであった.嚢胞内液を採取し, 各種腫瘍マーカーを測定したところ, CA19-9が260×105IU/mlと高値を示していた.術後経過は良好であり, 術後第22病日に退院した.高値を示していた血清CA19-9値は術後2ヶ月目に正常化した.胸腺原発のmucoepidermoid carcinomaはわれわれが調べた限りにおいて, 本邦では本症例が10例目となり, 極めてまれな疾患である.若干の文献的考察を加え報告する.

症例は70歳,男性.平成13年9月より当院泌尿器科で左腎癌の肺多発転移の診断にて経過観察中,同年11月,下血,下腹部痛を認め,当院消化器内科に入院.腹痛の増強および腹部膨満感があり,腹部単純X線検査にてniveau像を認めたため,当科紹介となった.腹部造影CT検査にて拡張した回腸の内部に良好に造影される腫瘤を認め,腸重積による腸閉塞が疑われた.このため,緊急手術を施行したところ,回盲部より10cm口側に腸重積を認めた.先進部には腫瘤を触知し,整復後,腫瘤を中心に約10cm回腸を切除した.病理組織学的に腎細胞癌の小腸転移と診断された.術後経過は良好であり,第18病日に退院となり,術後4カ月の現在,経過観察中である. 腎癌の小腸転移は極めて稀であり,本邦では自験例も含め17例の報告があるに過ぎない.若干の文献的考察を加え報告する

Abstract —Hyperhomocysteinemia (HH) is an independent risk factor for atherosclerosis, including peripheral arterial occlusive disease (PAOD). Because angiogenesis and collateral vessel formation are important self-salvage mechanisms for ischemic PAOD, we examined whether HH modulates angiogenesis in vivo in a rat model of hindlimb ischemia. Rats were divided into 3 groups: the control group was given tap water, the HH group was given water containing l-methionine (1 g · kg −1 · d −1 ), and the HH+L-arg group was given water containing methionine (1 g · kg −1 · d −1 ) and l-arginine (2.25 vol%). At day 14 of the dietary modifications, the left femoral artery and vein were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 4 weeks. Plasma homocysteine levels significantly increased ( P P P P P P P P P

An unruptured intracranial aneurysm is an uncommon but possible embolic source to the brain. We report a young patient who developed recurrent ischemic strokes occurring mainly in the left internal carotid arterial territory within a short interval; the first stroke occurred midway through a long-distance race, and the second stroke occurred immediately following a bowel movement. The angiographical contrast deficit indicated a thrombus in the left anterior cerebral artery as a result of the embolism. A saccular aneurysm of the left distal internal carotid artery was the only detectable potential embolic source. Initially anticoagulant therapy was given, and then surgical clipping of the aneurysm was performed. The patient has been free from stroke recurrence. As a cause of ischemic stroke in young adults, a carotid saccular aneurysm should be considered. Hard exercise and a Valsalva maneuver may be important triggers of thrombus detachment from the aneurysm.

Recently we experienced a case of cancer in adenoma of the stomach (gastric epithelial type) prolapsing into the duodenum. A 63-year-old woman was admitted to the hospital because of upper abdominal discomfort. Gastric endoscopy revealed an elevated lesion of Yamada type III with the diameter of about 4 cm prolapsing into the duodenum from pylorus ring. Polypectomy with an incision of the pylorus of the stomach was carried out. Intraoperative frozen section diagnosis resulted in adenoma. Postoperative examination, however, indicated papillary adenocarcinoma in adenoma with a possible remnant malignancy in the polypectomy stump. Distal gastrectomy was added. Gastric epithelial type of papillary adenoma which has been reported to represent less than 3% of all gastric adenomas prones to cancer change in a high frequency. This adenoma should be treated accordingto cancers. Reports on an elevated lesion prolapsing into the duodenum are so rare and only 100 cases have been seen in the Japanese literature in a recent 4 decades.

Hyperhomocysteinemia is thought to cause ischemic strokes. We report two middle-aged widowers with frequent recurrences of small-artery strokes, two capsular infarcts and a thalamic hemorrhage in one patient, and two thalamic and pontine infarcts in the other. Blood tests following the final stroke showed hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T gene mutation, with low concentration of vitamin B6. Multivitamin supplementation normalized plasma homocysteine levels in both patients. Hyperhomocysteinemia is treatable; therefore, serum homocysteine should be measured as a potential risk factor for stroke recurrence in relatively young patients with recurrent small-artery infarctions or hemorrhage, especially those with insufficient lifestyle factors.

To determine whether fibril length is correlated with graft healing as well as cellular and capillary ingrowth in a canine carotid implantation model.Expanded polytetrafluoroethylene (ePTFE) vascular grafts with three different fibril lengths (30, 60, and 90 microm) were implanted into the carotid artery in dogs. They were retrieved 4 weeks later, and subjected to histomorphometric analysis.Endothelial healing was best in the 60-microm grafts. Not only cellular ingrowth but also capillary ingrowth was most evident in the 60-microm grafts, followed by the 90-microm grafts and then the 30-microm grafts.Better endothelial healing of ePTFE vascular grafts is correlated with more cellular and capillary ingrowth, but more cellular and capillary ingrowth is not correlated with longer fibril length or higher air porosity.

To evaluate the intermediate performance of small-caliber, long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent bonding of fibronectin in dogs.Small-caliber (4 mm), long-fibril (60 microm), ePTFE vascular grafts, 10 cm in length, were pretreated by covalent bonding of fibronectin. Bilateral iliac grafting was done in dogs using a fibronectin-bonded graft on one side and a nonbonded control graft on the other side. The grafts were retrieved 12 weeks after implantation, and subjected to histomorphometric analysis.Although the patency rates of the fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin-bonded grafts showed almost complete neointimal healing, whereas the nonbonded control grafts showed only partial neointimal healing, proximally and distally.Small-caliber, long-fibril ePTFE vascular grafts with covalent bonding of fibronectin achieved almost complete neointimal healing by the time of retrieval at 12 weeks. This indicates that, with further modifications, our new technique for covalent bonding of fibronectin has great potential in the development of small-caliber arterial prosthetic grafts.

Although the renin angiotensin system (RAS) is a major regulator of vascular homeostasis, the role of the RAS in tumor angiogenesis is little understood. Here we show that host angiotensin II (ATII) type 1 (AT1) receptor plays an important role in angiogenesis and growth of tumor cells engrafted in mice. Subcutaneous B16-F1 melanoma-induced angiogenesis as assessed by tissue capillary density and microangiography was prominent in WT mice but was reduced in AT1a receptor-deficient (AT1a-/-) mice. Consequently, tumor growth rate was significantly slower, and the mouse survival rate was greater, in AT1a-/- mice than in WT mice. Tumor growth was also reduced in WT mice treated with TCV-116, a selective blocker of AT1 receptor. Because the beta-galactosidase gene was inserted into the AT1a gene locus in AT1a-/- mice, the site of beta-galactosidase expression represents the AT1a receptor expression in these mutant mice. In tumor-implanted AT1a-/- mice, the major site of the beta-galactosidase expression was macrophages in tissues surrounding tumors. Moreover, the number of infiltrated macrophages was significantly lower in AT1a-/- mice than in WT mice, and double-immunofluorescence staining revealed that these macrophages expressed VEGF protein intensively. Therefore, the host ATII-AT1 receptor pathway supports tumor-associated macrophage infiltration, which results in enhanced tissue VEGF protein levels. The host ATII-AT1 receptor pathway thereby plays important roles in tumor-related angiogenesis and growth in vivo.

A subset of human peripheral blood mononuclear cells (PB-MNCs) differentiate into endothelial progenitor cells (EPCs) that participate in postnatal neovascularization. Although tissue ischemia can mobilize EPCs from bone marrow, the effects of hypoxia on differentiation and angiogenic function of EPCs are little known. We examined whether hypoxic conditioning would modulate differentiation and function of human PB-MNC-derived EPCs. A subset of PB-MNCs gave rise to EPC-like attaching (AT) cells under either normoxic or hypoxic conditions. However, hypoxia much enhanced the differentiation of AT cells from PB-MNCs compared with normoxia. AT cells released vascular endothelial growth factor (VEGF) protein and expressed CD31 and kinase insert domain receptor/VEGFR-2, endothelial lineage markers, on their surface, which were also enhanced by hypoxia. Both a neutralizing anti-VEGF mAb and a KDR-specific receptor tyrosine kinase inhibitor, SU1498, suppressed PB-MNC differentiation into EPC-like AT cells in a dose-dependent manner. Migration of AT cells in response to VEGF as examined by a modified Boyden chamber apparatus was also enhanced by hypoxia. Finally, in vivo neovascularization efficacy was significantly enhanced by in vitro hypoxic conditioning of AT cells when cells were transplanted into the ischemic hindlimb of immunodeficient nude rats. In conclusion, hypoxia directly stimulated differentiation of EPC-like AT cells from human PB-MNC culture. Moreover, hypoxic preconditioning of AT cells before in vivo transplantation is a useful means to enhance therapeutic vasculogenesis.

We describe a case of bacteremic, leukopenic pneumococcal pneumonia with respiratory failure, accompanied by diabetic ketoacidosis and hypothermia. Pulmonary leukostasis may play a role in the pathogenesis of the acute respiratory distress syndrome (ARDS) in pneumococcal pneumonia. The patient recovered with mechanical ventilation, intravenous antibiotics, pulse-steroid therapy, and continuous hemodiafiltration (CHDF). In particular, administration of steroid and the use of CHDF may improve the status of pulmonary leukostasis in leukopenic pneumococcal infection.

The role of the renin-angiotensin system (RAS) in angiogenesis is little known. Here, we show that the angiotensin II (ATII) type 1 (AT1) receptor plays an important role in ischemia-induced angiogenesis. Well-developed collateral vessels and angiogenesis were observed in wild-type (WT) mice in response to hindlimb ischemia, whereas these responses were reduced in ATII type 1a receptor knockout (AT1a(-/-)) mice. Ischemia-induced angiogenesis was also impaired in WT mice treated with the AT1 receptor blocker TCV-116. These effects were not due to reduced systemic blood pressure (SBP), because hydralazine treatment preserved angiogenesis in WT mice although it reduced SBP to a level similar to that of AT1a(-/-) mice. Infiltration of inflammatory mononuclear cells (MNCs), including macrophages and T lymphocytes, was suppressed in the ischemic tissues of AT1a(-/-) mice compared with WT mice. Double immunofluorescence staining revealed that infiltrated macrophages and T lymphocytes expressed VEGF, and the expression of VEGF and monocyte chemoattractant protein-1 was also decreased in AT1a(-/-). Finally, the impaired angiogenesis in AT1a(-/-) mice was rescued by intramuscular transplantation of MNCs obtained from WT mice, further indicating the importance of MNC infiltration in ischemia-induced angiogenesis. Thus, the ATII--AT1 receptor pathway promotes early angiogenesis by supporting inflammatory cell infiltration and angiogenic cytokine expression.

Background —Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNC CD34+ ), are mobilized into PB in acute ischemic events in humans. Methods and Results —Flow cytometry revealed that circulating MNC CD34+ counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNC CD34+ counts ( r =0.35, P =0.01). Conclusions —This is the first clinical demonstration showing that lineage-committed EPCs and MNC CD34+ , their putative precursors, are mobilized during an acute ischemic event in humans.

ObjectivesWe examined whether oral folate supplementation would rescue a hypercholesterolemia (HC)-related impairment of ischemia-induced angiogenesis.BackgroundFolate protects against endothelial dysfunction, but the effect of folate supplementation on angiogenesis is little known.MethodsSprague-Dawley rats were divided into four groups. Control rats were fed a normal diet (n = 18); HC rats (n = 18) were fed 2% cholesterol diet; and HC + folate (HC+F) rats were fed an HC diet with oral folate (0.003% in water). The left femoral artery and vein were surgically excised, and angiogenesis in the ischemic limb was evaluated. We also examined the effects of NΩ-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on angiogenesis in the HC+F state.ResultsLaser Doppler blood flow (LDBF) analysis showed lower ischemic/normal LDBF ratio in the HC group than in the control group. Angiographic and histologic analyses on day 14 revealed a smaller angiographic score (p < 0.001) and capillary density (p < 0.001) in the HC group than in controls, which were associated with reduced tissue NOx and cyclic guanosine monophosphate (cGMP) levels. The LDBF ratio, angiographic score, and capillary density were significantly restored in the HC+F group (p < 0.01 vs. HC), which were associated with increased serum folate and tissue NOx and cGMP levels. Finally, L-NAME treatment abolished the beneficial action of folate on angiogenesis in the HC state.ConclusionsIschemia-induced angiogenesis was inhibited by HC, which was rescued by oral folate supplementation, at least in part, via an NO-dependent manner.