Review: role of cerebral vessels in ischaemic injury of the brain.

This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also.

Common occurrence of everolimus-associated aphthous stomatitis in Japanese heart transplant recipients.

Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects with less nephrotoxicity than calcineurin inhibitors. However, clinical use of mTOR inhibitors can be associated with a series of adverse events. We experienced cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese heart transplant recipients treated at the target trough EVL blood level after a switch from mycophenolate mofetil between April and December 2007. All four patients developed aphthous stomatitis; three required reduction of the exposure and one, EVL discontinuation due to stomatitis as well as other side effects. All patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we considered that EVL-related stomatitis might occur commonly among the Japanese population. The proper dosage, effects, and frequency of the side effects of mTOR inhibitors may vary by ethnic population.

Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report.

Tacrolimus is a potent immunosuppressant that is frequently used in organ transplantation. However, adverse effects include cardiac toxicity. Herein we describe transient myocardial hypertrophy induced by tacrolimus after heart transplantation. The hypertrophy caused no clinical symptoms but was noted because of elevation of plasma brain natriuretic peptide concentration and confirmed at echocardiography. Initially, allograft rejection was feared; however, myocardial biopsy samples revealed only interstitial edema and mild myocardial hypertrophy; neither cellular nor humoral rejection was detected. The blood tacrolimus concentration was higher than usual at that time; thus, tacrolimus dosage was reduced. Myocardial hypertrophy completely resolved upon reducing the target concentration of tacrolimus and did not recur, as confirmed at echocardiography and myocardial biopsy. Thus, we conclude that tacrolimus induces reversible myocardial hypertrophy. In patients receiving tacrolimus therapy, blood concentration should be carefully controlled and extreme attention paid to cardiac involvement.

Development of microporous covered stents: geometrical design of the luminal surface.

To reduce in-stent restenosis rates we have developed newly designed covered stents, in which a stent strut is buried into a microporous elastomeric cover film to provide a physical barrier against tissue ingrowth and a pharmacological reservoir for drug-eluting. The covered stents were prepared by dip-coating balloon expandable stents mounted on a stainless steel rod in a segmented polyurethane (SPU) solution, and were subsequently subjected to laser-processed microporing (pore diameter, 100 microm; interpore distance, 200 microm). The covered stents, which possessed flat luminal surfaces and micropores that were homogeneously arranged on the whole surface of the covering film, were deployed into the bilateral common carotid arteries of normal New Zealand white rabbits. Angiography after one month of implantation showed all stents were patent with little thrombus formation. The mean thickness of the formed neointimal layers was 292 +/- 177 microm (n=8), which was close to the size in non-covered bare stent (231 +/- 58 microm, n=7), but markedly decreased (about 2/3) from that in the previously developed wrapping-type covered stents (415 +/- 173 microm, P<0.01, n=8).

Perioperative hemodynamics in patients undergoing partial left ventriculectomy.

OBJECTIVES: Effects of partial left ventriculectomy (PLV) were studied by analyzing perioperative hemodynamics with measurements of left ventricular (LV) pressure-volume (PV) relationships and thermodilution catheter measurements in the pulmonary artery. METHODS: Between July and October 1996, 43 consecutive patients underwent PLV with and without mitral valvuloplasty with a thermodilution catheter and PV loop analysis immediately before and after surgery. Patients were 52+/-13 years and 67+/-13 kg, with reduced functional capacity (New York Heart Association 3.3+/-0.3) due to cardiomyopathy (24), ischemic disease (13), valvular disease (3), and Chagas' disease (3). RESULTS: PLV required cardiopulmonary bypass for 44+/-24 minutes, with the heart arrested in 10 patients for 26+/-22 minutes for coronary artery bypass grafting (8), aortic valve replacement (2), and autotransplantation (2). Two patients failed to come off bypass, six died in the hospital and 35 (35 [81.4%] of 43) were discharged. Changes in PV loops included decreased end-diastolic and end-systolic volume, resulting in no change in stroke volume. Pulmonary artery wedge pressure decreased despite elevated end-diastolic pressure. Ejection fraction, end-systolic elastance (E-max), afterload recruitable stroke work, and volume intercepts all improved and resulted in similar stroke work with less energy expenditure (less PV area), thus improving myocardial energetic efficiency. CONCLUSION: Results suggest that PLV improves systolic function but decreases diastolic compliance, which results in reduced net ventricular function immediately after surgery. Thus, immediate hemodynamic improvements appeared to derive from reduced severity in mitral regurgitation and perioperative load manipulation. Improved myocardial energetics may ameliorate LV function and improve the course of underlying myocardial disease.

Histopathology of resected myocardium and outcome of partial left ventriculectomy.

BACKGROUND: Since preoperative hemodynamics are not proven to be a predictor of effects of partial left ventriculectomy (PLV), myocardial histopathology may be better correlated with effects and outcome of PLV. METHODS: Myocyte size (micron) in the excised myocardium was measured in 338 patients undergoing PLV. Endocardial fibrosis, interstitial fibrosis, and inflammatory cell infiltration were enumerated as none = 0, mild = 1, moderate = 2, and severe = 3. These histopathologic observations were correlated with patients' postoperative survival. RESULTS: Reduced survival was seen in patients with advanced (> or = moderate) interstitial fibrosis in all patients (n = 338, p = 0.064) and in the subgroup with nonischemic etiology (n = 229, p = 0.0039). Although correlation between endocardial and interstitial fibrosis was significant (r = 0.55, p < 0.01), endocardial fibrosis failed to correlate with postoperative survival. While Chagas' disease was associated with severe inflammation and poor survival, the presence of inflammatory cell infiltration had no effect on survival in all patients combined (p = 0.943). Although most patients (n = 266, 79%) had myocyte diameter over 30 micron, those with less hypertrophy (< 30 micron, n = 70, 21%) had a tendency toward increased survival (p = 0.067) regardless of underlying etiology. CONCLUSION: Interstitial fibrosis may be an important factor in stratification of patients for repair (PLV) or replacement (transplantation). PLV may be more beneficial in patients with less hypertrophy, before develqpment of interstitial fibrosis. Endomyocardial biopsy might not predict the extent or variation in degree of interstitial fibrosis, which may be better evaluated by other metabolic or perfusion studies that measure overall myocardial histopathology and viability.

Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease.

We describe two pregnancies of a young woman with mixed connective tissue disease. In June 1983, she was diagnosed as having Raynaud's phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications. Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.

A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral position exhibiting primary tissue failure in adults in comparison with Ionescu-Shiley pericardial xenografts.

OBJECTIVE: We sought to investigate the durability and mechanism of the Carpentier-Edwards pericardial xenograft in the mitral position in comparison with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284 patients who received the Ionescu-Shiley pericardial xenograft in the mitral position between 1980 and 1984 and 84 patients who received the Carpentier-Edwards pericardial xenograft in the mitral position between 1984 and 1999 were included in the study. The freedom from reoperation rates for both graft types were determined. For morphologic study, the pathologic findings of 23 valves of 123 explanted Ionescu-Shiley pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both were determined and compared with those of 20 explanted Carpentier-Edwards pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both. Each pathologic finding was graded and assigned a score. Both types were matched for age at reoperation (50-75 years) and duration of valve function (8-11 years). RESULTS: Freedom from reoperation caused by structural valve deterioration, nonstructural valve deterioration, or both was significantly better for Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial xenografts at 8 years after the operation (Carpentier-Edwards pericardial xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but it was similar for both types at 12 years (Carpentier-Edwards pericardial xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts. The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular surface, or both was the cause of structural valve deterioration, nonstructural valve deterioration, or both of Carpentier-Edwards pericardial xenografts in adults. This was different from Ionescu-Shiley pericardial xenograft failure, which resulted from severe calcification and leaflet tears. Organized thrombi on cusps, in addition to valve design, may have contributed to such tissue overgrowth on Carpentier-Edwards pericardial xenografts.

Cause of residual hypertension after adrenalectomy in patients with primary aldosteronism.

The cause of residual hypertension after adrenalectomy for primary aldosteronism (PA) is unknown. The purpose of this study is to investigate the characteristic pathological kidney features associated with PA. Between 1977 and 1999 at our hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge renal biopsy. Patients were categorized into two groups: (1) those with normotension with diastolic blood pressure less than 90 mm Hg who were not administered antihypertensive drugs, and (2) those with residual hypertension with diastolic blood pressure of 90 mm Hg or greater who were administered medication for 6 months after surgery. Thirteen patients were cured of hypertension postoperatively, and 12 patients were administered antihypertensive medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left ventricular mass (LVM) index were worse in the group with residual hypertension than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01; 2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus 139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial injury, preoperative duration of hypertension, preoperative severity of proteinuria, plasma aldosterone level, and serum potassium concentration were not significantly different between the two groups. In conclusion, severity of glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure after adrenalectomy in patients with PA.

Tricuspid valve replacement with bioprostheses: long-term results and causes of valve dysfunction.

BACKGROUND: Although the clinical performance of bioprostheses after valve replacement in the aortic and mitral position has been reported, little is known of the performance of tricuspid bioprostheses. The mechanism of bioprosthetic valve dysfunction after tricuspid valve replacement (TVR) is not clear. METHODS: We reviewed 98 cases of TVR with bioprostheses. To clarify the causes of valve dysfunction, pathologic examination of the explanted valve at the reoperation was performed. RESULTS: Actuarial survival at 18 years was 68.7% +/- 5.8%. There were 12 redo TVRs. In six of the 12 cases, isolated redo TVR was performed. In the other cases, concomitant cardiac procedures were performed. The causes of prosthetic valve dysfunction were pannus formation on the cusps of the right ventricle side (four cases), native valve attachment (two cases), pannus formation + native valve attachment (two cases), sclerotic change (one case), pannus formation + sclerotic change (one case), and native valve attachment + valve infection (one case). Freedom from reoperation, structural valve deterioration, and nonstructural dysfunction at 18 years was 62.7% +/- 10.7%, 96.0% +/- 2.9%, and 76.7% +/- 8.3%, respectively. CONCLUSIONS: In our 18 years of experience, although the survival after TVR with bioprostheses is acceptable, the reoperation free rate is not satisfactory. Pannus formation on the cusps of the ventricular side seems to be a serious problem that causes bioprosthetic dysfunction in the tricuspid position.

Long-term pathological changes of expanded polytetrafluoroethylene (ePTFE) suture in the human heart.

Expanded PTFE (ePTFE) sutures have been used widely as a mitral chordal substitute. We present a structural analysis of ePTFE sutures implanted as artificial chordae for 7.5 years and 8.6 years in patients with mitral regurgitation. No calcification was found either macroscopically or microscopically, and the ePTFE suture retained its normal flexibility. The suture was totally encapsulated with host tissues composed of dense fibrous tissue covered with endothelial cells.

Partial left ventriculectomy for patients with ischemic cardiomyopathy.

BACKGROUND: Partial left ventriculectomy (PLV) has been performed in patients with dilated cardiomyopathy (DCM), but improved myocardial energetics may make PLV useful also for ischemic cardiomyopathy (ICM) unamenable to conventional treatment. METHODS: Of 262 patients undergoing PLV, 94 patients with ICM as the underlying pathology were analyzed and compared with 168 patients with DCM. RESULTS: ICM patients were older (57.3 years vs 50.9 years, p = 0.0001) and heavier (69.7 kg vs 65.9 kg, p = 0.039) than those with DCM, but ventricular end-diastolic and end-systolic dimensions were similar with comparably depressed fractional shortening (16% vs 15%, p = 0.294) and equally severe functional limitation [New York Heart Association (NYHA) Class 3.7 vs 3.6, p = 0.734]. A majority of patients in both groups underwent lateral PLV (76% vs 74%, p = 0.883) with myocardium excised between papillary muscles and simultaneous mitral valvuloplasty (41% vs 74%, p < 0.0001). Because ICM patients required coronary artery bypass grafting (CABG) more frequently (79% vs 0.6%, p < 0.0001), operation was more extensive in terms of bypass time (74 minutes vs 47 minutes, p < 0.0001), percentage requiring cardiac arrest (43% vs 19%, p < 0.0001), and arrest duration (34 minutes vs 28 minutes, p = 0.280), but all had similar resection and postoperative ventricular dimensions. Nonetheless, ICM patients required shorter intensive care unit (ICU) time (4.4 days vs 5.9 days, p = 0.048) and similar postoperative hospital stays, resulting in similar hospital survival rates (69% vs 71%, p = 0.778) and functional capacity in long-term follow-up. CONCLUSIONS: Results suggest that PLV can be performed in patients with ICM with comparable risks and benefits as in DCM. Relative efficacy of CABG and mitral repair as compared to volume reduction remains to be studied.

Cerebral primitive neuroectodermal tumor in an adult male. A case report.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are very rare. Malignant tumors of the cerebrum in young individuals are composed predominantly of undifferentiated cells, with moderate differentiation along either neuronal or glial lines. To our knowledge, cerebral PNETs in adults are extraordinarily rare and have been reported in only 11 cases, with little cytologic documentation in the literature. The cytopathologic, immunohistochemical and ultrastructural features of cerebral PNET arising in an adult male are presented. CASE: A cystic tumor, on computed tomography and magnetic resonance imaging, arose from the left frontal lobe in a 39-year-old man and contained histopathologic features of PNET. Specimens obtained from surgery revealed the presence of an undifferentiated type of PNET with moderate neuronal and glial differentiation and mild characteristic findings of peripheral PNET. The cytologic and histologic specimens showed evidence of a scattered pattern of blastic and undifferentiated tumor cells and a neural arrangement with Homer-Wright-like rosettes. Immunohistochemically, the tumor cells were glial fibrillary acidic protein, neuron-specific enolase, synaptophysin and CD-99 positive and epithelial membrane antigen, S-100 protein and vimentin negative. Ultrastructurally, neither microtubular structures nor intermediate filaments, except neurosecretory granules, were found in the tumor cells. CONCLUSION: Both immunohistochemical and ultrastructural studies on cytologic and histologic slides were important for the diagnosis of PNET because of establishing not only undifferentiated tumor cells but also neural and glial differentiation.

Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli.

A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.

Surface microarchitectural design in biomedical applications: in vivo analysis of tissue ingrowth in excimer laser-directed micropored scaffold for cardiovascular tissue engineering.

A micropatterned microporous segmented polyurethane film (20 x 12 mm in size, 30 micrometer thick) with four regions was prepared by excimer laser microprocessing to provide an in vivo model of transmural tissue ingrowth in an open cell-structured scaffold specially designed for cardiovascular tissue engineering. Three microporous regions had the same circular micropores (30 micrometer diameter) but different pore density arrangements (percentage of total pore area against unit area was 0.3%, 1.1%, and 4.5%), and the other region remained nonporous. The covered stent, prepared by wrapping the regionally different density-microporous film on an expandable metallic stent (approximately 3.1 mm in diameter), was delivered to the luminal surface of canine common carotid arteries and placed after expansion of the stent to a diameter of approximately 8 mm using a balloon catheter. At 4 weeks of implantation, all the covered stents (n = 10) were patent. The luminal surfaces of the covered stents were almost confluently endothelialized both in nonporous and microporous regions. Histological examination showed that the neointimal wall was formed by tissue ingrowth from host through micropores (transmural) and anastomotic sites. Thrombus formation occurred frequently in the lowest density porous region and nonporous region. With an increase in pore density, the thickness of the neointimal wall decreased. This study demonstrated how the micropore density of implanted devices influences tissue ingrowth in arterial implantation.