Non-anastomotic midgraft stenosis of a knitted Dacron graft after arterial reconstruction. Report of a case.

Midgraft stenosis of the prosthesis after bypass surgery has seldom been reported. A man presented with an ischemic ulcer of the left foot. He had undergone bilateral femoropopliteal bypass surgery as well as left-sided iliofemoral bypass surgery with a knitted Dacron graft. The graft in his left thigh was occluded. A knitted Dacron conduit with 8-mm diameter was interposed between the iliofemoral bypass graft and the left profunda femoris artery, and graft-popliteal jumping bypass surgery was added. The postoperative angiogram showed a short-segmental severe stenosis of the interposed graft neighboring the proximal anastomosis. Repeat surgery showed that the stenotic lesion was located separately from the anastomosis. This midgraft stenosis was considered to consist of dissection of pseudointima associated with the intraoperative procedures. In cases of repeat surgery around the inguinal ligament, procedures should be performed with great care.

Rare complication of saccular aneurysm and histological dissection: an autopsy study of 5865 elderly cases.

The purpose of this study was to examine complicated lesions of saccular aneurysm and dissection. We investigated the ascending aortae in 5865 consecutive elderly autopsy cases, and 5 cases (0.085%) of aortic saccular aneurysms associated with dissection at the edges were selected. Their edges characteristically protruded like a shelf, which histologically consisted of an inner part of the dissected media. All patients were female and their mean age was 76.8 (67-89) years. The aneurysmal walls at the center showed severe fragmentation and disappearance of the elastic lamellae of the remaining outer media. Thus, partial sections of these lesions were not sufficient but cross-sections of the whole diseased regions including the edges were essential for diagnosis. One patient had 3 saccular aneurysms and an adjacent shallow depression, which we called "healed microscopic dissection". Histologically, it showed disappearance of the inner media and was replaced by fibrosis in continuation from the intima. This lesion showed no findings of intramural hemorrhage or thrombus, and thus it will differ from organized thrombi in the dissected false lumen. Another patient presented had an aneurysmal rupture which resulted in cardiac tamponade. This case implies the need for surgical treatment of this entity.

Localization of oxidized HDL in atheromatous plaques and oxidized HDL binding sites on human aortic endothelial cells.

We examined the localization of oxidized high-density lipoprotein (HDL) in atheromatous plaques and the oxidized HDL binding sites on endothelial cells. Histochemical analysis using CuSO4-oxidized HDL-specific 9F5-3a antibody indicated the presence of oxidized HDL in the intima of atheromatous plaques in human abdominal aortae. The cell surface binding of 125I-oxidized HDL to cultured human aortic endothelial cells (HAEC) was saturable, with an apparent dissociation constant (Kd) of 1.43 micromol/L. Competition for 125I-oxidized HDL binding was strong for oxidized HDL, moderate for native HDL and low for acetylated low-density lipoprotein (LDL) or oxidized LDL. Using oxidized HDL as a ligand for blotting, a major 130-kDa band was detected in HAEC. These results suggest that oxidized HDL and its putative binding protein are present in atheromatous plaques and endothelial cells, respectively.

Immunolocalization of bone morphogenetic protein and its receptors in degeneration of intervertebral disc.

STUDY DESIGN: Immunohistochemical study of expression and localization of bone morphogenetic protein (BMP)-2/4 and type I and II receptors on intervertebral disc. OBJECTIVES: To determine the biologic functions of BMPs and their receptors in the process of degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Biologic and pathologic processes in the cell during the degeneration of the intervertebral disc are as yet poorly understood. METHODS: The cervical spines of 15 male senescence-accelerated mice aged 8, 24, or 50 weeks were used for histologic and immunohistochemical examination of BMP-2/4 and BMP receptors IA, IB, and II. Immunostaining was performed with the avidin-biotin-peroxidase complex method. RESULTS: Degenerative change was recognized within intervertebral discs of senescence-accelerated mice aged 50 weeks. BMP-2/4 and its receptors were abundant in hyaline cartilaginous cells within the endplate of the vertebrae at 8 and 24 weeks of age. However, the expression of BMP-2/4 and its receptors moved from the hyaline cartilage of the endplate of the vertebrae to fibrous cells within the anulus and to the calcified cartilage at the site of enthesis of mice aged 50 weeks. CONCLUSIONS: BMP-2/4 and its receptors may play roles in degenerative change of intervertebral disc.

The development of a pancreatic abscess, suppurative pylethrombosis, and multiple hepatic abscesses after a pancreatojejunostomy for chronic pancreatitis: report of a case.

We present herein an autopsy case of 63-year-old Japanese man who died as a result of pancreatic abscess, suppurative pylethrombosis, and multiple liver abscesses that had developed 10 years after a pancreato- and cystojejunostomy with side-to-side anastomosis for chronic pancreatitis. Even after this operation, the patient had continued to consume excessive amounts of alcohol. He had first experienced back pain with leukocytosis 9 years after the operation, which relapsed the following year. Despite percutaneous transhepatic gallbladder drainage, his icterus had deteriorated into hepatic insufficiency. Computed tomographic scans of the abdomen had disclosed multiple liver abscesses. At autopsy, a pancreatic abscess and suppurative pylethrombosis as well as multiple liver abscesses were found. There have been few reported cases of such lethal complications developing after a pancreato- and cystojejunostomy for chronic pancreatitis. As the consumption of alcohol would have exacerbated the chronic pancreatitis, such patients should be strongly advised to abstain from drinking alcohol.

The spatial and temporal immunolocalization of TGF-beta 1 and bone morphogenetic protein-2/-4 in phallic bone formation in inbred Sprague Dawley male rats.

In male rats and mice, the membranous bone is rapidly formed in the proximal segment (p-segment) of the os penis, and then endochondral ossification proceeds in the proximal half. The spatial and temporal patterns of expression of transforming growth factor-beta 1 (TGF-beta 1) and bone morphogentic protein-2/-4 (BMP-2/-4) were examined immunohistochemically until 14 days after birth and compared. BMP-2/-4 expression was weak in the mesenchymal condensation just at birth, and up-regulated in the membranous bone and cartilage 3 days after birth. BMP-2/-4 was strongly expressed in proliferating and mature chondrocytes 7 days after birth. At birth, TGF-beta 1 expression was diffuse and very strong in mesenchymal condensation. Thereafter, TGF-beta 1 expression was continuously strong in membranous bone and cartilage. Seven days after birth, TGF-beta 1 was actively expressed in proliferating chondrocytes. TGF-beta 1 and BMP-2/-4 seemed to act co-operatively. In particular, TGF-beta 1 appeared to strongly regulate immature stage and BMP-2/-4 may regulate the mature stage.

Aneurysm induced by periarterial application of elastase heals spontaneously.

BACKGROUND: The pathogenesis of aortic aneurysms remains largely unknown, despite aneurysmal rupture being an increasingly common catastrophe. METHODS: This study was designed to elucidate the mechanism of arterial dilatation histologically and electron microscopically, utilising a new animal model. Elastase, 3.0 mg/ml, was applied to the abdominal aortae of 18 New Zealand white rabbits from the adventitia side for 3 hours. The rabbits were sacrificed at 0, 3, 14, 28, 42 and 90 days after the procedure (n=4, 3, 2, 2, 2, 3). RESULTS: Two rabbits were found to have developed aortic rupture. On day 0, elastase application induced fusiform aneurysms up to 1.62+/-0.14 times the pre-elastase application aortic diameter. Dilated walls revealed medial elastolysis, degeneration of smooth muscle cells (SMCs) and damaged endothelial cells. By day 3, the smooth muscle cells had changed to the synthetic type. Aneurysms did not progress, and after 42 days, showed gradual shrinkage. By day 90, aortic diameters had nearly normalised. CONCLUSIONS: Aortic walls also returned to the pre-elastase application thickness and some mature medial elastic lamellae showed regeneration. Medial smooth muscle cells reverted to the contractile type. Aortic dilatation induced by peri-aortic application of elastase heals spontaneously, accompanied by regeneration of smooth muscle cells. Irreversible degeneration of medial smooth muscle cells appears to be more critical to aneurysm formation than degeneration of elastic lamellae.

Immunohistochemical localization of bone morphogenetic proteins and the receptors in epiphyseal growth plate.

The expression of bone morphogenetic proteins (BMPs) and BMP receptors (BMPRs) in the epiphyseal growth plate has not been clarified. In this study, we studied immunohistochemically the spatial and temporal localization of BMP-2/4, osteogenic protein-1 (OP-1, or BMP-7), and BMP receptors (BMPR-IA, BMPR-IB, and BMPR-II) in the epiphyseal plate of growing rats. The proximal parts of tibia in growing rats were observed. At 12 weeks after birth, BMP-2/4 and OP-1 were expressed markedly in proliferating and maturing chondrocytes. BMPR-IA, IB and II were clearly co-expressed in proliferating and maturing chondrocytes, and the expression was decreased in hypertrophic chondrocytes. At 24 weeks, the expression of BMP-2/4 and OP-1 was decreased, but BMPRs were still well-expressed in proliferating chondrocytes. The temporal and spatial expression of BMP and BMPR suggests that BMP and BMP receptors play roles in the multistep cascade of enchondral ossification in the epiphyseal growth plate.

Pancreatic mucin-producing adenocarcinoma associated with a pancreatic stone: report of a case.

We present an autopsy case of an 83-year-old Japanese man with a mucin-producing adenocarcinoma accompanied by pancreatolithiasis in the head of the pancreas. He suffered from obstructive jaundice and died of disseminated intravascular coagulation. He did not normally drink alcohol and had no history of chronic pancreatitis. The autopsy findings revealed a mucinous cystic tumor, composed of multiple dilatated branches, in the head of the pancreas. Histological examinations showed papillary adenocarcinoma, which scirrhously infiltrated the distal common bile duct with perineural invasion and lymph node involvement. He was thus diagnosed to have mucin-producing branch-type cancer in the head of the pancreas. The main pancreatic duct was dilated, and the residual pancreatic tissue showed moderate fibrosis and parenchymal atrophy. A stone was observed in a dilated branch of the primary lesion. To the best of our knowledge, there have only been five previously reported cases of mucin-producing tumor associated with pancreatolithiasis. Intraductal calcification is a major characteristic of chronic pancreatitis, but it is clinically important not to misdiagnose cancers associated with pancreatolithiasis such as chronic pancreatitis.

Grossly punched-out lesions in the aorto-iliac region can be histologically classified as false, pseudo-false, or disguised aneurysm.

Aneurysms are morphologically classified as true or false based on the nature of their walls. True aneurysms are composed of all or parts of layers of the vessel. False aneurysms are the result of rupture and their walls have only fibrous tissues. The orifice of false aneurysms is narrow relative to the aneurysmal diameter and thus they are grossly or angiographically referred to as punched-out lesions. Hence false aneurysms present with punched-out lesions, but in reverse, are all of punched-out lesions false aneurysms? We experienced some cases of punched-out lesions which histologically contained traces of elastin, and the purpose of this report was to histologically investigate grossly punched-out lesions. We examined 671 elderly autopsy cases, and a total of 21 grossly punched-out lesions in the aorto-iliac region were selected. They were histologically classified as false, "pseudo-false", or "disguised" aneurysm. False aneurysms were found in 3 patients (0.45%), and were histologically mycotic. A total of 5 "pseudo-false" aneurysms were found in 3 patients (0.45%). They histologically contained traces of elastin, and thus they were categorised in true aneurysms. A total of 13 "disguised" aneurysms were found in 6 patients (0.89%). They were true fusiform aneurysms with an eccentric thrombus, on which a fibrin-cap formed a narrow orifice. Partial sections are insufficient for diagnosis; cross-sections are necessary. To the best of our knowledge, there have been no reports of "pseudo-false" or "disguised" aneurysms in the aorto-iliac region.

Anplag, a selective 5-HT2 receptor antagonist, reduces stenosis induced by balloon injury in the hypercholesterolaemic rabbit.

The purpose of this study was to examine the effect of anplag, a 5-HT2 receptor antagonist, on intimal hyperplasia (IH) after balloon injury. In 39 male New Zealand white rabbits, the left carotid artery was denuded of endothelium by an inflated balloon. The injury not only damaged the endothelium, but also caused damage to underlying smooth muscle cells. Twelve rabbits fed normal chow were divided into 2 groups: Group A; anplag was not administered, and Group B; anplag, 100 mg/kg, was given by gavage, including on the day of ballooning. The remaining 27 rabbits were fed chow containing 1% cholesterol and divided into 3 groups: Group C; anplag was not administered, Group D; anplag, 100 mg/kg, was given orally except on the day of ballooning, and Group E; anplag, 100 mg/kg, was given orally including on the day of ballooning. IH in Group B was 13.2% less than that in Group A and IH in Group D was 11.7% less than that in Group C. However, neither of these differences was significant. IH in Group E was significantly less (by 40.1%) than that in Group C. In conclusion, anplag significantly reduced IH after balloon injury in the hypercholesterolaemic rabbit by inhibiting proliferation of smooth muscle cells and cholesterol-uptake by macrophages when it was administered immediately before the procedure.

Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.

To clarify the pathogenesis of ossification of the ligamentum flavum (OLF), we examined the expression and localization of bone morphogenetic proteins (BMPs) and their receptors (BMPRs) in the ligamentum flavum of the patients with OLF by immunohistochemical staining and compared them with staining patterns in control patients. The BMPRs appeared extensively in mature and immature chondrocytes around the calcified zone and in spindle-shaped cells and round cells in the remote part from ossified foci in examined tissue of OLF. The ligands for BMPRs, BMP-2/-4 and osteogenic protein-1 (OP-1)/BMP-7, colocalized in OLF patients. In the control cases, expression of BMPs and BMPRs was observed around the calcified zone at the insertion of the ligamentum flavum to the bone, and limited expression was found in the smaller range. Thus, the expression profile of BMPs and BMPRs in OLF patients was entirely different from the control patients, suggesting that BMPs may be involved in promoting endochondral ossification at ectopic ossification sites in OLF, and that ossification activity is continuous in these patients.

Orthotopic ossification of the spinal ligaments of Zucker fatty rats: a possible animal model for ossification of the human posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament is a human genetic disease in which pathological ectopic ossification of the spinal ligaments develops. This leads to myelopathy or radiculopathy due to compression of the spinal cord. In this study, we investigated the histological features of orthotopic ossification of the spinal ligaments of senile Zucker fatty rats. A remarkably high incidence of orthotopic ossification was observed mainly in the thoracic spinal ligaments as compared with controls. The histopathological findings were similar to those for ossification of the human posterior longitudinal ligament. Bone morphogenetic proteins and activins, which exert their effects by way of specific type-I and type-II serine/threonine kinase receptors, play important roles in the formation of bone and cartilage. In the spinal ligaments of Zucker fatty rats, bone morphogenetic protein receptors and activin receptors were immunohistochemically detected around the ossified foci in a manner similar to that previously shown for the ossified tissue from patients who had ossification of the posterior longitudinal ligament. Thus, bone morphogenetic proteins and activin receptors might play important roles in orthotopic ossification of the spinal ligaments of Zucker fatty rats as well as in ossification of the posterior longitudinal ligament of humans. In addition, bone morphogenetic protein-receptor-IA was expressed in the nonossified ligament, suggesting that the spinal ligaments, of the rats may have a predisposition to orthotopic ossification. In the controls, no expression of bone morphogenetic protein receptors or of activin receptors was observed. In conclusion, there is a great degree of similarity between orthotopic ossification of the spinal ligaments of Zucker fatty rats and ossification of the posterior longitudinal ligament of humans. Thus, the rats provide a useful animal model for the study of ossification of the human posterior longitudinal ligament.

Mucin-producing adenoma associated with pancreas divisum and hepatic hilar carcinoma: an autopsy case.

We present the autopsy case of an 82-year-old Japanese woman with a mucin-producing adenoma accompanied by pancreas divisum and a hepatic hilar carcinoma. She had suffered from a cholangiocellular carcinoma at the hepatic hilus for 2 months, which was treated with radiation and chemotherapy. She did not complain of any abdominal pain. Obstructive jaundice deteriorated despite percutaneous transhepatic bile duct drainage, and she died of hepatic insufficiency. At autopsy, a hepatic tumor was confirmed to have caused severe obstructive jaundice. Histological examinations showed moderately to poorly differentiated cholangiocellular adenocarcinoma with squamous metaplasia, probably due to radiation. A yellowish mucinous tumor was found in the head of the pancreas near the minor papilla. It consisted of multiple rice-sized cystic lesions with thin septa. Although it had no capsule, its margin was clear. Neither a wide opening of the major or minor papilla nor mucous drainage was observed. Gross examinations revealed unfused pancreatic ducts. The slightly dilatated dorsal duct and a branch of the mildly dilatated ventral duct showed tumor involvement. Histological examinations showed mild atypia of the epithelia, and this pancreatic tumor was diagnosed as branch duct-type mucin-producing adenoma with postradiation dysplasia. The combination of a mucin-producing tumor and pancreas divisum is rare, and this is only the third reported case.

Spontaneous perforation of a non-aneurysmal atherosclerotic abdominal aorta or femoral artery.

The spontaneous perforation of a non-aneurysmal atherosclerotic abdominal aorta or femoral artery is reported. Over the past 14 years, four perforations have been found in the abdominal aorta and one in the femoral artery; the incidence of each was 1.1% and 5.9%, respectively. Computed tomography scanning was useful for diagnosing pseudoaneurysms in all cases, since it revealed haematoma outside the arterial wall. One of these cases presented with an aortoduodenal fistula. The arteries were severely atherosclerotic with calcification. All of the patients underwent a graft replacement. Operative findings confirmed pseudoaneurysm. One patient died from pneumonia 4 months after the operation, and the other four have remained well during the follow-up period ranging from 2-9 years.

A clinicopathological study of familial abdominal aortic aneurysms.

The purpose of this report is to document what we have observed in patients with familial abdominal aortic aneurysms (FAAAs) between 1987 and 1993. Patients with FAAAs were reviewed and compared with those without familial clustering with regard to age, sex, past history, laboratory data, smoking habits, and type of implanted graft. We identified 7 families among which a total of 15 members had AAAs. The incidence of familial clustering reached 5.4%. The mean age of the FAAA group was significantly younger than that of the non-FAAA group (mean age: 65.8 +/- 10.3 versus 71.0 +/- 7.3 years). In the FAAA group, furthermore, patients in the second generation were significantly younger than those in the first generation (mean age: 55.3 +/- 10.5 versus 69.6 +/- 7.4 years). FAAA was significantly more often complicated by ischemic cardiac diseases. There were no significant differences in other risk factors. Interestingly, however, we observed a morphological similarity in the shape of the aneurysms within each family. Histological examinations showed moderate or severe lymphocytic infiltration into the aortic adventitia in 6 out of 9 cases. FAAA is clinically important, because it can represent a high-risk group that may benefit from a screening program for early detection and elective management of AAA. Studies of FAAAs will be useful for elucidating the pathogenesis of AAAs.

[A clinicopathological study of ruptured infectious aneurysms].

We investigated 952 consecutive autopsy cases between January 1990 and May 1994 to identify ruptured infectious aneurysms (IAs) of the aorta or iliac artery. Twenty patients (2.1%) died of artrial rupture, including 9 men and 11 women. The cause of rupture was IA in four cases (0.42%), atherosclerotic aneurysm (AA) in nine (0.95%), dissection (D) in six (0.63%), and aortoenteric fistula due to irradiation in one (0.11%). Infection of pre-existing aneurysms was considered to be AA rather than IA and the patient with aorto-enteric fistula was excluded from the study. Patients with IA were significantly older than other patients (IA: 85.8 +/- 4.3, AA: 80.2 +/- 4.1, and D: 77.7 +/- 5.0 years old), and were less frequently accompanied by leukocytosis than patients with AA, although this difference was not significant (11,100 vs 13,000). The four patients with IA consisted of one man and three women, all of whom died suddenly. Two patients had perforation in the atherosclerotic descending aorta and the other two had perforation in the atherosclerotic common iliac artery. Histological examinations revealed marked neutrophilic infiltration in all four cases, and bacterial colonies in three cases. In conclusion, IAs were not rare. Since they often cause sudden death, special attention should be given to elderly patients who develop infection.