Ruptured cerebral aneurysm and acute coronary artery dissection in the setting of multivascular fibromuscular dysplasia: a case report.

Fibromuscular dysplasia (FMD) is a segmental noninflammatory nonatherosclerotic vascular disease that has been described in almost every arterial bed, including the cerebral and coronary arteries. FMD of cerebral vessels has been associated with development of saccular aneurysms in the involved vessels. Acute dissection of coronary arteries is also a rare complication of FMD. Herein, we report the first case of both complications of FMD occurring in a single patient-a ruptured anterior communicating artery aneurysm and a right coronary artery dissection occurring in a 38-year-old woman. At autopsy, FMD was found in multiple vascular beds. Our findings reveal the potential for involvement of several vascular beds in patients with FMD, resulting in multiple vascular complications.

Estrogen and progesterone receptors expression in gastrointestinal stromal tumors and intramural gastrointestinal leiomyomas.

Gastrointestinal stromal tumors (GISTs) and leiomyomas of the gastrointestinal tract both may present as intramural smooth muscle cell tumors. Immunohistochemically, these tumors demonstrate different spectrums of protein expression, which helps in differential diagnosis. Leiomyomas of the uterine type are similar by the spectrum of protein expression to gastrointestinal leiomyomas, but they express in addition both estrogen (ER) and progesterone (PR) receptors, which makes hormonal therapy possible for these tumors. In the current study, we investigated expression of ER and PR in GISTs and intramural gastrointestinal leiomyomas. Our data demonstrate that none of the 22 cases of gastrointestinal leiomyomas nor 19 cases of GIST were positive for either ER or PR expression. In contrast, leiomyomas of the uterine type were strongly positive for both ER and PR. Our data demonstrate that GIST and gastrointestinal leiomyomas differ from leiomyomas of the uterine type by the expression of ER and PR. Immunostaining for ER and PR may be a useful tool to distinguish these tumors and more precisely to plan further clinical interventions.

Atherosclerotic pseudoaneurysm of the ascending aorta.

Pseudoaneurysms in the ascending aorta most commonly occur as a complication of surgical procedures at this site. They have also been reported in association with trauma, infection, aortitis, and other disorders. Pseudoaneurysm formation in the descending aorta or arch may occur as a result of penetrating ulcers in the presence of severe atherosclerotic plaque. Pseudoaneurysm as a result of atherosclerotic disease has only rarely been noted in the ascending aorta, where complex plaque is less common. We report here the finding with transesophageal echocardiography of a pseudoaneurysm in the ascending aorta as a result of atherosclerotic disease and penetrating ulcer.

Intestinal ischemia.

CONTEXT: As rejection in renal transplantation has become better controlled, gastrointestinal complications have become increasingly important. Ischemic colitis and colonic perforation are the most common of these lesions, contributing to morbidity and mortality in the early postoperative period. OBJECTIVE: We undertook this study to identify factors contributing to the risk of intestinal ischemia in patients undergoing renal transplantation and to define circumstances that may affect that risk. METHODS: We studied 356 patients undergoing renal transplantation during a 40-month period. We reviewed medical records, surgical pathology reports, autopsy reports, and pathology slides. RESULTS: Eleven (3.1%) of the patients developed ischemia of the small or large bowel or both within 20 days after transplantation, and 6 (54.5%) died as a result. Ten of these patients had received cadaveric kidneys and were older than 40 years. There was no sex predilection. The most common segment involved was the terminal ileum and ascending colon. We discuss possible reasons underlying these observations in this article. CONCLUSION: The mechanism behind posttransplantation intestinal ischemia is multifactorial, but regardless of etiology, it is important to emphasize the risk of intestinal ischemia in patients who develop abdominal symptoms during the early posttransplantation period, particularly in patients older than 40 years who have received cadaveric kidneys.

Hyaluronic acid nanofiber wound dressing--production, characterization, and in vivo behavior.

Hyaluronic acid (HA) was electrospun. The effects of flow rate, spin length, and the applied voltage on the diameter of the HA nanofibers were analyzed. The average thickness of the webs was 0.041 cm. The air permeability of sterilized HA nanofiber wound dressing was much higher than that of gauze with Vaseline. The degree of crystallinity of HA nanofibers was characterized using powder X-ray technique and was found to be 20.6%. A preclinical study was conducted to compare healing of wounds covered by an adhesive bandage, a sterilized solid HA, gauze with Vaseline, an antibiotic dressing, and a sterilized HA nanofiber wound dressing. Results of the two methods of appraisal showed that the sterilized HA nanofiber wound dressing was the best type of dressing out of the five types of dressings compared.

Myocardial bridging of coronary arteries: A risk factor for myocardial fibrosis?

Myocardial bridging of a coronary artery is an anatomic anomaly in which a major epicardial coronary artery extends intramurally into the myocardium for a part of the vessel's course. The left anterior descending coronary artery (LAD) is most frequently involved. Myocardial bridging is often asymptomatic, although myocardial pathology, arrhythmias and sudden cardiac death have been reported. In this study we quantitated the degree of myocardial intersitial fibrosis in histological sections of the anterior wall of the left ventricle obtained from the hearts of 6 individuals with myocardial bridging of the LAD and compared it to age-, weight-, and sex-matched controls without bridging. We found that patients with the bridging of the LAD had 33% increased myocardial interstitial fibrosis as compared to the control group (P=0.0006). Our data suggest that myocardial bridging may be an independent risk factor for development of myocardial ischemia and interstitial fibrosis.

Dynamics of circulating microparticles in liver transplant patients.

BACKGROUND & AIMS: Microparticles are small membrane vesicles released from the cell plasma membrane, particularly in cell stress, apoptosis and altered cellular viability. Hepatocellular carcinoma (HCC) is a hypervascular neoplasm with high levels of apoptosis and necrosis. We investigated the levels of circulating microparticles of both tumor and endothelial origins in liver transplant patients with hepatitis C (HepC) cirrhosis with and without HCC and compared them with healthy people and patients with partial hepatectomy. METHODS: Using immunolabeling of microparticles of different origin and flow cytometry-based enumeration of microparticles, the levels of circulating microparticles were studied in 8 patients with HepC and 8 patients with both HepC and HCC before and within two weeks after the transplant. RESULTS: The initial levels of circulating microparticles were increased in patients with HepC and HCC as compared to patients with HepC alone. They were also increased in liver transplant patients as compared to patients with partial hepatectomy or healthy people. Levels of circulating microparticles were dynamically changing after the transplant, showing an initial increase with a subsequent decrease by the end of the second week after surgery. In some patients with a complicated clinical outcome, the levels of microparticles were continuously increasing after the surgery. CONCLUSION: The levels of circulating microparticles of endothelial and hepatic origin in liver transplant patients dynamically change after surgery and correlate with the clinical outcome. Perspectively, the levels of circulating microparticles may be used in clinical practice as a marker of the functional status of the transplanted liver.

Vascular density and VEGF expression in hepatic lesions.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide and the third most common cause of cancer-related death. HCC is a hypervascular tumor expressing several angiogenic factors. The correlation between plasma levels of Vascular Endothelial Growth Factor (VEGF) and the survival of patients with HCC was demonstrated earlier. However, a relationship between the expression of VEGF and vascular density in the HCC and non-malignant hepatic parenchyma has not been investigated. MATERIAL AND METHODS: We studied the expression of VEGF and vascular density in normal hepatic parenchyma, cirrhosis and HCC using a computer-based analysis of immunohistochemical stainings and confirmed it by Western Blot. RESULTS: The vascular density in the areas of HCC and internodular fibrotic tissue in cirrhotic liver was significantly higher (185%; 146% respectively) than in non-neoplastic hepatic parenchyma. Additionally, cirrhotic nodules were characterized by significantly lower vascularization (71%) compared with normal liver. There was a strong correlation between the levels of VEGF expression in tissue and the number of vessels (r=0.98, R2=0.9696). CONCLUSION: Cirrhosis and HCC are characterized by different degrees of vascularization, which has been quantitated by a novel computer-based analysis of immunohistochemical stainings. One of the major stimuli for angiogenesis in these liver diseases could be VEGF, as the VEGF expression was higher in HCC and diminished in cirrhotic nodules, thus strongly correlating with the degree of vascularization. Our findings demonstrate that angiogenesis may play an important role in the pathogenesis of these conditions.

Epstein-Barr virus-associated multifocal leiomyosarcomas arising in a cardiac transplant recipient: autopsy case report and review of the literature.

Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) have been described in patients with acquired immune deficiency syndrome (AIDS) and, more recently, in association with immunosuppression after solid-organ transplantation. We present the autopsy findings of multiple leiomyosarcomas (LMSs) in a 24-year old man who died 18 months after undergoing orthotopic cardiac transplantation for idiopathic cardiomyopathy. The recognition of EBV-driven LMS developing in cardiac transplant recipients in multiple unusual sites is crucial for the management of these patients and should include complete surgical removal anti-viral therapy and modulation of immunosuppression.

Primary extracranial meningioma of the pelvis: a light microscopic, immunohistochemical, and ultrastructural study.

BACKGROUND: Extracranial meningiomas are rare tumors which have been described in head and neck. The occurrence in mediastinum and retroperitoneum is even rarer. This presented case records a unique location, a meningioma arising in pelvis. CASE: A 52-year-old woman presented with an ovarian mass. The histology of the resected tumor revealed sheets of bland epithelioid cells arranged in prominent whorls with psammoma bodies typical of meningothelial meningioma. Immunohistochemical analysis demonstrated diffuse strong positivity for vimentin and epithelial membrane antigen (EMA). There was moderate reactivity for cytokeratin, estrogen (ER) and progesterone (PR) receptors. By electron microscopy, the tumor cells expressed desmosomes and abundant intermediate filaments. CONCLUSION: According to our review of literature, this is the first reported case of a primary pelvic meningioma. Its benign appearance and 4-year disease-free survival without clinical or radiological evidence of intracranial disease favors the pelvis as the primary site.

Potentiation of acetaminophen hepatotoxicity by phenytoin, leading to liver transplantation.

We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the "nontoxic" range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.

CA 125 levels in the preoperative assessment of advanced-stage uterine cancer.

OBJECTIVE: The purpose of this study was too evaluate preoperative levels of CA 125 in for the prediction of advanced uterine cancer. STUDY DESIGN: We conducted a retrospective analysis of the correlation of preoperative CA 125 with grade, depth of invasion, lymph vascular space involvement, lymph node status, and stage. RESULTS: High CA 125 levels correlated with advanced-stage (P <.0001) and positive (P <.0001) lymph node status. High levels of CA 125 also correlated with the deepest myometrial invasion, the presence of lymph vascular space involvement, and the highest grade. Receiver-operator characteristic curves demonstrated that depth of invasion, lymph vascular space involvement, and grade accurately predicted advanced-stage disease 73%, 77% and 80% of the time, respectively. CA 125 levels, however, correctly predicted advanced stage 94% of the time. The sensitivity and specificity of a CA 125 cutoff level of 37 IU/mL were 95% and 90%, respectively, with a positive predictive value of 78% and a negative predictive value of 97%. CONCLUSION: CA 125 appears to be a significant independent predictor of positive lymph node status and the extrauterine spread of disease.

Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest.

Epidemiological surveys indicate that intake of cruciferous vegetables is inversely related to prostate cancer incidence, although the responsible dietary factors have not been identified. Our studies demonstrated that exposure of human prostate cancer cells in culture to the N-acetylcysteine (NAC) conjugate of phenethyl isothiocyanate (PEITC-NAC), the major metabolite of PEITC that is abundant in watercress, inhibited proliferation and tumorigenesis. The PEITC-NAC is known to mediate cytoprotection at initiation of carcinogenesis. The relevance of PEITC-NAC in diets on the growth of prostate tumor cells has been evaluated in immunodeficient mice with xenografted tumors of human prostate cancer PC-3 cells. The daily PEITC-NAC (8 micromol/g) supplemented diet group showed a significant reduction in tumor size in 100% of the mice during the 9-week treatment period. Tumor weight at autopsy was reduced by 50% compared with mice on the diet without PEITC-NAC (P = 0.05). Mitosis and in vivo 5-bromo-2'-deoxyuridine labeled proliferating cells were reduced in these tumors. The PEITC-NAC diet up-regulated the inhibitors of cyclin-dependent kinases p21WAF-1/Cip-1 and p27Kip1, and reduced the expression of cyclins D and E, indicating they were potential molecular targets. As a result, phosphorylated Rb was significantly decreased and the G1- to S-phase transition retarded. The treated tumors also showed a significant increase in apoptosis as determined by in situ end-labeling, and by poly ADP-ribose polymerase cleavage. This study demonstrates the first in vivo evidence of dietary PEITC-NAC inhibiting tumorigenesis of prostate cancer cells. PEITC-NAC may prevent initiation of carcinogenesis and modulate the post-initiation phase by targeting cell cycle regulators and apoptosis induction.

BUBR1 deficiency results in abnormal megakaryopoiesis.

The physiologic function of BUBR1, a key component of the spindle checkpoint, was examined by generating BUBR1-mutant mice. BUBR1(-/-) embryos failed to survive beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1(+/-) blastocysts grew relatively normally in vitro, BUBR1(-/-) blastocysts exhibited impaired proliferation and atrophied. Adult BUBR1(+/-) mice manifested splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in an increase in the number of splenic megakaryocytes, which was correlated with an increase in megakaryocytic, but a decrease in erythroid, progenitors in bone marrow cells. RNA interference-mediated down-regulation of BUBR1 also caused an increase in polyploidy formation in murine embryonic fibroblast cells and enhanced megakaryopoiesis in bone marrow progenitor cells. However, enhanced megakaryopoiesis in BUBR1(+/-) mice was not correlated with a significant increase in platelets in peripheral blood, which was at least partly due to a defect in the formation of proplatelet-producing megakaryocytes. Together, these results indicate that BUBR1 is essential for early embryonic development and normal hematopoiesis.