bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic Basal Cell Carcinoma from Head and Neck Primary Lesions
Authors: Andrews Robert J. , Sercarz Joel A. , Fu Yao S. , Calcaterra Thomas C.
Published: June 2007

Basal cell carcinoma is the most common cutaneous neoplasm and involves the head and neck in more than 85% of cases. Metastatic lesions occur in less than 0.1% of cases. In this report, four cases of metastatic basal cell carcinoma of the head and neck are presented. Previous reports indicate that metastases typically arise from long-standing, large and deep locally invasive lesions that are refractory to surgical or radiation therapy. Although three of the four cases follow this pattern, one case demonstrates that a small but rapidly enlarging lesion also has the potential for metastasis. The relationship of metastasis to tumor growth, histologic subtype, and host immune function is discussed.
Xanthogranulomatous Pyelonephritis Associated with Systemic Amyloidosis
Authors: Val-Bernal J. Fernando , Garijo M. Francisca
Published: June 2007

Xanthogranulomatous pyelonephritis is rarely associated with systemic amyloidosis. To the best of our knowledge, this association has been described in only nine cases, including the present report. Our first patient, a 76-year-old woman, presented with chronic renal failure and xanthogranulomatous pyelonephritis in the right kidney associated with amyloidosis in the same kidney and ipsilateral adrenal. She has been followed up for 44 months and continues to do well with stable renal function and mild proteinuria. Our second patient, a 54-year-old woman, had a 25-year history of recurrent Proteus mirabilis urinary tract infections. She developed anuric chronic renal failure, becoming dependent on dialysis, and xanthogranulomatous pyelonephritis in the left kidney associated with amyloidosis in the same kidney. She died at 8 days postsurgery. The combination of lesions has been described in childhood and in adults presenting with chronic renal failure or nephrotic syndrome. Clinical remission of amyloidosis develops in a majority of the patients after the removal of the renal lesion. From a pathologic point of view our cases underline the importance of careful histologic examination of removed kidneys, even in conditions characterized by extensive destruction of renal tissue. To prevent the association with amyloidosis we emphasize the importance of early diagnosis and treatment of xanthogranulomatous pyelonephritis.
Marker Panel Predictive of Lymph Node Metastasis in Young Patients with Breast Carcinoma
Authors: Gattuso Paolo , Bloom Kenneth , Yaremko Lisa , Borok Raphael , Cobleigh Melody , Madsen Krista , Gould Victor E. , Reddy Vijaya
Published: June 2007

Breast cancer is being diagnosed more frequently in young women. It is important to identify tumors with greater metastatic potential since this information will provide a basis for noninvasive staging of the axilla. The studied population consisted of 66 patients with infiltrating breast carcinoma (56 ductal, 10 lobular) aged 20-34 (mean 29) years. Lymph node status was correlated with the following parameters: size, grade, p53 expression, MIB-1, CD44, c-Erb-2, estrogen, progesterone receptors, and a family history of breast cancer. Immunohistochemical studies utilizing avidinbiotin-peroxidase complex method were performed on formalin-fixed, paraffinembedded tissue. Thirty-nine patients (59%) had positive lymph nodes and 27 (41%) had negative lymph nodes. In multivariate logistic regression analysis, two models with size (p=.0002) and p53 (p=.0379) or size (p=.0002) and MIB-1 (p=.0462) were predictive of nodal involvement. For TI lesions, p53 positivity increased the probability of nodal involvement from 18% to 46% and, for T2 lesions, from 65% to 89%. In the second model, for TI lesions MIB-1 positivity increased the probability of nodal involvement from 10% to 36% and, for T2 lesions, from 48% to 82%. Size, p53, and MIB-1 were found to be valid independent predictors of lymph node metastasis in TI and T2 breast carcinomas in young women. The combination of size with p53 or MIB-1 increases dramatically the predictive impact of these parameters on nodal status. These data may prove useful in selecting patients with increased risk of dissemination and provide a basis for staging the axilla noninvasively.
Primary Rhabdomyosarcoma Mimicking a Small Cell Sarcoma of Bone: A Nude Mice Xenograft, Cytogenetic, and Molecular Approach
Authors: Llombart-Bosch A. , Peydro-Olaya A. , Carda C. , Lopez-Gines C. , Boix-Ferrero J. , Pellin A.
Published: June 2007

Small cell sarcomas of bone are difficult to classify and diagnose. The present case deals with such a tumor in which the original biopsy and the resected specimen, studied by histology before chemotherapy, provided no final information about its real nature. Thus several techniques were applied to discern its histogenesis and biology. Myogenin proved positive in isolated cells of the primary neoplasm but was extensively expressed in nude mice xenografts. Electron microscopy confirmed the existence of myofilaments. The cytogenetic analysis revealed a large number of chromo somal abnormalities, but not those found in the Ewing's/PNET (peripheral neuroectodermal tumor) family of tumors. This was confirmed by polymerase chain reaction (RT-PCR) wherein no EWS/Fli 1 or PAX3/FKHR gene rearrangements were detected. Based upon these studies, a rhabdomyosarcoma of bone was diagnosed. Clinically the neoplasm showed a highly aggressive behavior, causing death of the patient within 2 years after diagnosis.
Immunohistologic Evaluation of Putatively Mutant p53 Protein in Cutaneous Melanocytic Neoplasms
Authors: Kaleem Zahid , Lind Anne C. , Humphrey Peter A. , Swanson Paul E. , Sueper Robert H. , Ritter Jon H. , Wick Mark R.
Published: June 2007

Mutations in the p53 tumor suppressor gene, located at chromosomal locus 17pI3, are the most commonly seen genetic alterations found in human malignancies. Their role in the pathogenesis of malignant melanoma is thought to be limited, although variable results have been reported in reference to immunoreactivity for putatively mutant p53 protein (mp53) in melanocytic lesions in general. In that light, the authors undertook an immunohistologic evaluation of 256 well-characterized tumors in that category, including common nevi (CN; n=73); Spitz nevi (SN; n=40); nodular melanomas (NMMs; n=32), superficial spreading melanomas (SMMs; n=65); lentigo maligna melanomas (LMMs; n=23); and melanomas arising in preexisting nevi (MANs; n=23). One hundred cells were counted manually in randomly selected high-power microscopic fields, in regard to nuclear labeling for mp53. Results were recorded semiquantitatively, as negative, positive (1-4% of tumor cells); and positive (>5% of tumor cells). No examples of CN or SN demonstrated any immunoreactivity whatever for mp53, whereas 105 of 143 melanomas (73%) did so. However, an mp53 index of >50% was seen in only 29% of the latter lesions. NMMs were most often mp53-positive and showed the highest numerical level of nuclear labeling, followed in respective order by SMMs, and LMMs/MANs. These results suggest that negative mp53-immunostaining cannot be equated with the diagnostic interpretation of a benign melanocytic neoplasm, because 27% of melanomas also failed to label for that determinant. However, the presence of mp53-immunolabeling in a melanocytic proliferation-even if at low levels-should conversely prompt careful consideration of melanoma as the favored diagnosis in the confined setting of morphologically difficult cases, inasmuch as no example of CN or SN in this series had that characteristic.
Morphologic and Immunohistochemical Evidence of Continuity Between Different Components of Malignant Mesenchymoma of the Retroperitoneum
Authors: Berenson Mark , Drachenberg Cinthia B. , Papadimitriou John C. , Mergner Wolfgang J.
Published: June 2007

A malignant mesenchymoma with predominant leiomyosarcomatous component and significant chondrosarcomatous and focal osteosarcomatous elements is presented. Transitional areas with overlapping morphologic and immunohistochemical features were found between the smooth muscle and cartilaginous components. Stains for actin were strongly positive in leiomyosarcoma, and in scattered malignant chondrocytes. Malignant chondrocytes and scattered neoplastic smooth muscle cells were positive for S-100. Both components were strongly positive for p53. Ultrastructurally there were calcified particles in the matrix of both chondrosarcoma and leiomyosarcoma. These findings support the concept that malignant mesenchymoma results from divergent differentiation of primitive mesenchymal cell with pluripotential capability. A literature review of retroperitoneal malignant mesenchymomas with similar differentiation is presented.
Solitary Fibrous Tumor of the Liver
Authors: Bejarano Pablo A. , Blanco Ramon , Hanto Douglas W.
Published: June 2007

A rare case of solitary fibrous tumor (SFT) of the liver is described. The patient was a 49-year-old man who had a 17x12xlO cm mass (2,750 g) with a firm and vaguely whorled cut surface, a scar-like central area, and pushing rather than infiltrating borders. It was located in the subcapsular parenchyma of the left lobe. The histologic, immunohistochemical, and ultrastructural features are identical to those seen in the more common SFTs of the pleura. Those features include a variable spindle cell proliferation, scant mitotic activity, immunoreactivity for CD34 and vimentin, and the absence of necrosis. The patient underwent a partial hepatectomy and the surgical margins were free of tumor. No recurrence was detected 15 months after excision. This case adds to 12 similar previously reported cases involving the liver. A review of the literature indicates that SFT of the liver behaves in a benign fashion.
Malignant Mixed Mullerian Tumor of the Uterus with Prominent Neuroectodermal Differentiation
Authors: Yöriükoğlu Kutsal , Aktaş Safiye , Göre Oya , Özen Emek
Published: June 2007

A case of malignant mixed Müllerian tumor of the uterus with prominent neuroectodermal differentiation is reported. The most notable feature of the tumor was its large component of primitive neuroepithelium lining tubules. The islands of neuroectodermal tissue were admixed with conventional endometrioid adenocarcinoma and sarcomatous elements resembling malignant fibrous histiocytoma only in a small focus.
Ectopic Hamartomatous Thymoma
Authors: Sheikh Salwa , Picken Catherine , Montgomery Elizabeth
Published: June 2007

The authors report an example of an unusual lower neck lesion, ectopic hamartomatous thymoma. Like other examples of this entity, the lesion was well marginated and characterized by cysts lined by squamous epithelium, adipose tissue, and spindle cells. The lesion was initially mistaken for a malignant neoplasm (at the time of frozen section) and the correct interpretation was rendered upon review of the permanent sections. They review the literature and clinicopathologic differential diagnosis of this entity.
Gastrointestinal Autonomic Nerve Tumor of the Colon
Authors: Wang Beverly Y. , Brandwein Margaret S. , Gordon Ronald E. , Chahinian Philippe A. , Strauchen James A. , Harpaz Noam
Published: June 2007

Gastrointestinal autonomic nerve tumor (GANT) is an uncommon subtype of gastrointestinal stromal tumor that is morphologically similar to conventional stromal tumors but has ultrastructural features of neural differentiation. Of the approximately 58 cases of GANT reported to date, most have arisen in the small intestine or stomach, but none, to our knowledge, in the colon or rectum. Accordingly, we report the first case of colonic GANT and document its histologic, ultrastructural, and immunohistochemical characteristics. These were not unlike those of GANT arising elsewhere in the alimentary tract, including interlacing spindle cells, skenoid fibers, axonal cytoplasmic processes, dense core neurosecretory granules, and immunoreactivity to vimentin and NSE. The rarity of GANT in the large intestine should not preclude ultrastructural evaluation of colorectal stromal tumors for neural features.
Microinvasive Carcinoma of the Breast
Authors: Schnitt Stuart J.
Published: June 2007

Microinvasive carcinoma of the breast is a controversial entity for a number of reasons. First, the identification of areas of microinvasion is often problematic for the pathologist. Second, varying definitions for this lesion have been used by different authors. Third, studies of microinvasive carcinoma have been limited by small patient numbers. As a consequence, there are differences of opinion regarding both the clinical significance of microinvasion and the management of patients with this lesion. The purpose of this article is to review the controversies surrounding microinvasive carcinoma of the breast.
Paratesticular Pleomorphic Rhabdomyosarcoma in the Elderly
Authors: Lanzafame Salvatore , Fraggetta Filippo , Emmanuele Carmela , Muda Andrea Onetti , Torrisi Antonietta , Magro Gaetano
Published: June 2007

A case of paratesticular pleomorphic rhabdomyosarcoma, presenting as an ulcerated mass in the left hemiscrotum of an 83-year-old man, is reported. By light microscopy, this neoplasm could not be distinguished from other pleomorphic sarcomas, such as malignant fibrous histiocytoma, leiomyosarcoma, and liposarcoma. Immunohistochemistry showed that most tumor cells were strongly reactive with antibodies directed against myoglobin, desmin, a-sarcomeric actin, and myogenin, whereas x-smooth muscle actin expression was less extensive. Electron microscopic examination demonstrated thick and thin filaments with condensations of electron-dense material reminiscent of structures of Z-lines in the large pleomorphic cells. On the basis of these findings, the neoplasm was classified as a pleomorphic rhabdomyosarcoma. According to a review of the literature, this is the first well-documented example of paratesticular pleomorphic rhabdomyosarcoma in an elderly person.
Soft Tissue Metastasis as Initial Manifestation of Pleural Malignant Mesothelioma
Authors: Laurini Javier A. , Castiglioni Teresa , Elsner Boris , Avagnina Alejandra , Ferreiro Santiago , Belloti Marta
Published: June 2007

Distant metastases of pleural malignant mesothelioma (MM) are infrequent. We report a case of MM that presented as a skeletal muscle metastasis. This type of presentation has not been previously reported. A 38-year-old male complained about a mass in his right forearm. The tumor showed the histologic pattern, immunohistochemical phenotype, and ultrastructural features of an MM. In the clinical work-up, the x-ray film and computed tomography scan demonstrated pleural effusion and diffuse pleural thickening in the right hemithorax. The pleural biopsy showed an epithelial MM. The patient died from local progression of the disease 6 months after the diagnosis. No other distant metastases were clinically evident. Our case shows the importance of including MM in the differential diagnosis of metastatic neoplasms in skeletal muscle and the usefulness of ancillary techniques in the diagnosis of mesothelial neoplasms.
Use of Monoclonal Antibody MIB-1 in Differential Diagnosis of Uterine Cervical Glandular Neoplasm
Authors: Lee Eungseok , Kim Insun
Published: June 2007

This study was undertaken to evaluate the significance of MIB-1 immunoreactivity in the discrimination of differential diagnosis of benign cervical lesion, endocervical glandular dysplasia, and endocervical adenocarcinoma on formalin-fixed, paraffinembedded tissue. Fifty-two cases were selected from the pathology files of Korea University Hospital from 1994 to 1998 and were composed of 25 cases of endocervical adenocarcinoma, including three cases in which squamous cell carcinoma coexists; six cases of endocervical glandular dysplasia associated with squamous cell carcinoma or cervical intraepithelial neoplasia (CIN); and 21 cases of chronic endocervicitis. Immunohistochemical staining for MIB-1 was performed after microwave treatment on formalin-fixed, paraffin-embedded tissue sections. MIB-1 expression was evaluated according to the labeling indexes. The labeling indexes were calculated for 52 specimens by means of image analysis (Quantification of Proliferation Index). The results are as follows; There was diffuse strong MIB-1 reactivity in endocervical adenocarcinoma (labeling index 37.6-61.4%, mean 54.9%), moderate spotty reactivity in endocervical glandular dysplasia (labeling index 27.9-42.6%, mean 35.1%), and minimal to focal reactivity in chronic endocervicitis (labeling index 0-24.4%, mean 5.2%). Significant differences in MIB-1 labeling indexes existed among the chronic endocervicitis group, the endocervical glandular dysplasia group, and endocervical adenocarcinoma group. In conclusion, MIB-1 immunostaining is of value in the differential diagnosis among benign cervical lesions, endocervical glandular dysplasia, and endocervical adenocarcinoma.
Prognostic Factors in Supraglottic Squamous Cell Carcinoma
Authors: de Lima Andrea Paes , Bellotti Marta S. , Elsner Boris , Caminoa Alejandra , Hortas Andrea
Published: June 2007

To establish its prognostic value in supraglottic squamous cell carcinoma proliferative activity, the usefulness of Ki67 and p53 protein expression by immunohistochemistry and of DNA ploidy by image analysis was studied in 41 patients who were treated with a partial horizontal laryngectomy and had a mean follow-up of 4 years. Histologically 24% were well differentiated, 44% moderately, and 32% poorly differentiated. No correlation was found between clinical stage, histologic differentiation, and survival. In 29 cases (71%) p53 staining was observed (mean score 32%). There was a statistically significant correlation between p53 and histologic differentiation (p=0.03), clinical stage (p=0.01), and follow-up (p=0.02). Mean proliferation index (Ki67) was 20%. Statistically significant correlation was observed between Ki67 and p53 (p=0.02). All tumors were aneuploid. Correlation between 5c exceeding events and follow-up was found (p=0.04). These data suggest that p53 overexpression and the presence of 5c exceeding events provide useful prognostic information concerning behavior of supraglottic squamous cell carcinoma.
‘Sclerosing’ Perineurioma: A Tumor Variant?
Authors: Hirose Takanori , Scheithauer Bernd W.
Published: June 2007

We describe two examples of soft tissue perineurioma, a hard tumor, 1.7 cm in diameter, involving the dermis and superficial subcutaneous tissue of the left thumb, and the other a massive, lobulated lesion of the pelvis. Both occurred in 49-year-old men. Both were mobile and well demarcated but unencapsulated. Their cut surfaces were white and collagenous. Microscopically, each consisted of spindle-shaped or epithelioid tumor cells in a dense stroma of haphazardly oriented collagen bundles. Spindle-shaped cells were individually distributed, whereas epithelioid cells were often arranged in cords or clusters. Cytologic atypia was conspicuous in the massive tumor, but no mitotic activity was observed. Immunostains showed diffuse reactivity for vimentin, membrane pattern staining for epithelial membrane antigen and type IV collagen, as well as patchy CD34 reactivity. Stains for S-100 protein, Leu-7, smooth muscle actin, desmin, and cytokeratin were negative. Ultrastructural studies showed perineurial cell characteristics, including slender cytoplasmic processes, numerous pinocytotic vesicles, occasional tight junctions, and discontinuous surface basement membrane. Perineuriomas featuring marked stromal sclerosis often occur in the hands of young adults, as has recently been reported; the authors considered it a clinicopathologic variant. Herein we report two sclerotic perineuriomas, one a small tumor of the thumb and the other a centrally situated, massive pelvic tumor with sclerosis and degenerative cytologic atypia. We believe that exaggerated collagen deposition in perineuriomas, occasionally associated with degenerative nuclear changes, is not a manifestation of a unique, clinically relevant tumor variant but rather a manifestation of chronicity akin to that seen in “ancient schwannoma” and ‘atypical neurofibroma.’
Mammary Dirofilariasis
Authors: Mrad Karima , Romani-Ramah Soumaya , Driss Maha , Bougrine Fethi , Hechiche Monia , Maalej Mongi , Romdhane Khaled Ben
Published: June 2007

We report a case of a dirofilariasis manifesting as a breast nodule in a 32-year-old Tunisian woman. It appeared as a relatively well-circumscribed and slightly dense nodule on mammography and was hypoechogenic with enhanced through transmission on ultrasonographic examination. The patient was treated by surgical resection. Histopathologic analysis could identify viable female and male worms as Dirofilaria repens. Dirofilaria is rare in Tunisia and this is the second human case reported. The patient lived all her life in Tunisia and had never been abroad.
Strong Epidermal Growth Factor Receptor Expression But Not HER2/neu Expression Correlates with Cell Proliferation in Anal Canal Carcinomas
Authors: Hui Yun Zhong , Noffsinger Amy E. , Miller Mary Ann , Hurtubise Paul , Fenoglio-Preiser Cecilia M.
Published: June 2007

Twenty-eight anal carcinomas were analyzed for their proliferative status and immunoreactivity to epidermal growth factor receptor (EGFR), HER2/neu, and proliferating cell nuclear antigen (PCNA). EGFR was expressed in 97.3% of tumors. Strong EGFR immunoreactivity correlated with a high proliferative rate (p=0.0 14). No obvious relationship existed between HER2/neu immunoreactivity and proliferative rate. The strong correlation between strong EGFR immunoreactivity and tumor proliferation suggests that the EGFR may represent a therapeutic target in anal cancers.
A Clinicopathologic Study of Solitary Myeloma
Authors: Sariya D. R. , Jambhekar N. A. , Srinivas V. , Advani S. H. , Dinshaw K. A.
Published: June 2007

A retrospective clinicopathologic review of 17 solitary myelomas (SMs) including 13 osseous (solitary plasmacytomas of bone [SPB]) and four extraosseous (extramedullary plasmacytomas [EMP]) tumors in 14 male and three female patients was undertaken. The average age of patients with SPB and EMP was 47.2 years and 48.75 years, respectively, and the most common site was the spine and the head and neck, respectively. The possible utility of histologic and cytologic characteristics of the tumor cells to predict evolution to multiple myeloma (MM) was studied. Follow-up was 63 months (SPB) and 107 months (EMP). No consistent cytohistologic features emerged in patients ultimately evolving either into MM (three patients) or developing recurrences (two patients). Thus, although the correct recognition of SM, as distinct from MM, has clinical relevance, morphology does not help further prognostication.
Japanese Plutonium Stockpiles: A Transportation, Storage, and Public Relations Challenge
Authors: Turner William D.
Published: June 2007

In accordance with Japan's nuclear policies, Japanese nuclear power companies have regularly shipped depleted uranium fuel to reprocessing plants in the United Kingdom and France. These British and French companies extract plutonium from Japanese spent fuel; the newly reprocessed plutonium may be used to create a derivative nuclear fuel called MOX (mixed oxide fuel). Currently, the Japanese government seeks to use MOX fuel to serve Japan's economic growth, energy self-sufficiency, and national security needs. The Japanese government suggests that reprocessed plutonium must be used as MOX fuel to prevent others from using the plutonium to create weapons. Currently, large stockpiles of highly reactive plutonium and reprocessing wastes wait in the United Kingdom and France for transport back to Japan, raising many safety concerns for nations that lie along the shipping route. This article examines the advantages and disadvantages to Japan's MOX program and considers alternatives to MOX fuel.
Fenoldopam Infusion Associated with Preserving Renal Function After Aortic Cross-Clamping for Aneurysm Repair
Authors: Gilbert Timothy B. , Hasnain Jawad U. , Flinn William R. , Lilly Michael P. , Benjamin Marshall E.
Published: June 2007

Background: Cross-clamping of the descending aorta during operative repairs causes sudden, significant reductions in renal function that may persist well beyond arterial clamp release. Commonly used agents, such as dopamine and mannitol, have not consistently affected renal outcome in these high-risk patients. Fenoldopam mesylate is a novel, highly selective dopamine type-I agonist that preferentially dilates the renal and splanchnic vasculature, but has not been investigated in patients undergoing prolonged aortic clamping for whom adverse renal outcomes should be more likely.

Methods and Results: Twenty-two adult patients without significant pre-existing renal dysfunction and presenting for elective repairs of abdominal aortic aneurysms were studied. Fenoldopain mesylate was infused after obtaining baseline values ranging from 0.1 to 1.0 pg/kg/min for the first 24 hours postoperatively to maintain mean arterial pressure ±25% baseline. Serial renal function indices, including creatinine clearance and electrolyte fractional excretions, were measured at baseline, at aortic clamping and unclamping, and post-clamp release, and were estimated through hospital discharge. Creatinine clearance fell during abdominal exploration and clamping, reaching a nadir with clamp removal. Partial recovery occurred by 2 hours after clamp removal, and returned to baseline values by postoperative day 1 and thereafter. Fractional excretions rose rapidly throughout the operative phase. Total fenoldopam dose was directly related to the baseline creatinine clearance; after clamp removal, creatinine clearance was directly related to the mean arterial pressure at the lowest dose of fenoldopam, and inversely related to the mean arterial pressure at clamp release.

Conclusions: In elderly patients with severe vascular disease undergoing aneurysmal repairs, the use of a fenoldopam infusion in this open-label, uncontrolled trial was associated with a relatively rapid return of renal function to baseline values, despite profound decreases during aortic cross-clamping. Further studies will be necessary to investigate how fenoldopam infusions compare with traditional therapies.
Renal Artery Stenosis in Minority Patients Undergoing Diagnostic Cardiac Catheterization: Prevalence and Risk Factors
Authors: Alhaddad Imad A. , Blum Steve , Heller Eliot N. , Beato Milton A. , Bhalodkar Narendra C. , Keriaky Ghassan E. , Brown Edward J.
Published: June 2007

Background: Atherosclerotic renal artery stenosis (RAS) is a frequently overlooked clinical entity that can cause progressive renal failure and uncontrolled hypertension. Revascularization of a stenosed renal artery is associated with improved clinical outcomes including the prevention of renal failure. Thus, it is important to recognize all potential candidates for renal artery revascularization. In a general population referred for diagnostic cardiac catheterization, RAS of any severity was found in 30% of patients and significant stenosis (> 50% diameter narrowing) was found in 15% of patients. The number of minority groups is increasing in the US population, and RAS in this population is not well investigated. Our purpose was to determine the prevalence and risk factors associated with RAS in minority patients referred for diagnostic cardiac catheterization.

Methods: Abdominal aortography was performed in 171 consecutive minority patients referred for diagnostic cardiac catheterization (hispanics = 115, African Americans = 56). The association of clinical and angiographic variables with RAS was examined using univariate and multivariate logistic regression analyses.

Results: Renal artery stenosis of any severity was identified in 13.5% of patients (unilateral 7.7%, bilateral 5.8%). Significant RAS was found in 7.7% of patients (unilateral 4.8%, bilateral 2.9%). Independent predictors of RAS included age (mean ±SD, 68 ±0 vs 57 ± yr, P < 0.001, for patients with vs without RAS), coronary artery disease, and elevated serum creatinine levels (> 115,umolVL). Race/ethnicity (hispanics vs African Americans), sex, smoking, congestive heart failure, diabetes mellitus, peripheral vascular disease, and hyper-tension were not independent predictors.

Conclusions: Renal artery stenosis in minority patients undergoing diagnostic cardiac catheterization is less common than reported in white patients, is similar in hispanics and African Americans, and is similar in women and men. The clinical and angiographic features are helpful in predicting its presence.
Ventricular Free Wall Rupture in Acute Myocardial Infarction
Authors: Khalil Mohammed E. , Heller Eliot N. , Boctor Fouad , Brown Edward J. , Alhaddad Imad A.
Published: June 2007

Despite a progressive reduction in acute myocardial infarction mortality over the years, death related to ventricular free wall rupture has not changed. This is mostly related to the catastrophic presentation and death within minutes in the majority of these patients. Once rupture is suspected, bedside echocardiography should be performed immediately, followed by pericardiocentesis and repair of the rupture site as quickly as possible. Measures to prevent cardiac rupture include the administration of 5-blockers and angiotensin-converting enzyme inhibitors unless contraindications exist, and the avoidance of steroidal and nonsteroidal antiinflammatory agents such as ibuprofen and indomethacin.
Electrophysiologic Effects of a Novel Selective Adenosine A1 Agonist (CVT-510) on Atrioventricular Nodal Conduction in Humans
Authors: Lerman Bruce B. , Ellenbogen Kenneth A. , Kadish Alan , Platia Edward , Stein Kenneth M. , Markowitz Steven M. , Mittal Suneet , Slotwiner David J. , Scheiner Marc , Iwai Sei , Belardinelli Luiz , Jerling Markus , Shreeniwas Revati , Wolff Andrew A.
Published: June 2007

Background: CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A,-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-5 10 on AV nodal conduction and hemodynamics.

Methods and Results: Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-5 10. AH and HV intervals were measured during sinus rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after the bolus. Increasing doses of CVT-510 (0.3 to 10 pg/kg) caused a dosedependent increase in the AH interval. At 1 minute, a dose of 10,ug/kg increased the AH interval during sinus rhythm from 93 ± 23 msec to 114 ± 37 msec, p = 0.01 and from 114 ± 31 msec to 146 ± 44 msec during atrial pacing at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT-510 at doses of 0.3 to 10,ug/kg had no effect on sinus rate, HV interval, or systemic blood pressure, and was not associated with serious adverse effects. At doses of 15 and 30 pg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated. One of these patients also had a prolonged sedative effect that was reversed with aminophylline.

Conclusions: CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure. Selective stimulation of the A,-adenosine receptor by CVT-510 may be useful for immediate control of heart rate in atrial fibrillation/flutter and to convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding vasodilatation mediated by the A2-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with 3-adrenergic receptor blockade and/or calcium channel blockers.
Female Gender Does Not Influence the Magnitude of Ibutilide-Induced Repolarization Delay and Incidence of Torsades de Pointes in an In Vivo Rabbit Model of the Acquired Long QT Syndrome
Authors: Johansson Marie , Carlsson Leif
Published: June 2007

Background: Clinical and experimental in vitro observations indicate that female gender is associated with a higher risk of developing torsades de pointes with repolarizing-delaying agents. The present study addressed the question of gender difference in the susceptibility towards developing torsades de pointes in a rabbit model of the acquired long QT syndrome in vivo.

Methods and Results: Female (F, n = 40) or male (M, n = 40) NZW rabbits, characterized as young (Y, n = 20) or adult (A, n = 20) were anesthetized with oc-chloralose and sensitized to developing torsades de pointes by a continuous infusion of methoxamine. The class III antiarrhythmic agent ibutilide was subsequently infused at a rate of 8 nmol/kg/min for 30 minutes maximum. Before commencement of drug infusion, no gender-related differences in the QT interval were observed (121 ± 1.9 msec and 126 ± 3.3 msec in FA and in MA and 116 ± 1.6 msec and 113 ± 1.7 msec in the FY and MY, respectively). Infusion of ibutilide was associated with a rapid and marked increase in the QT interval, which did not differ significantly between the groups. Hence, the maximal QT lengthening observed was 39 ± 3.1% in FA, 46 ± 5.7% in MA, 38 ± 3.9% in FY and 36 ± 3.4% in MY, respectively (p > 0.05 between gender). In the adults, the incidence of torsades de pointes in F was 70% and in M 90% (p = 0.235), whereas in the young, the incidence in F was 45% and in M 70% (p = 0.200). The cumulative doses of ibutilide causing torsades de pointes were not statistically significantly different between the four groups of rabbits (70 ± 15.5 nmol/kg in FA, 50 ± 5.3 nmol/kg in MA, 59 ± 17.2 nmol/kg in FY and 61 ± 15.9 nmol/kg in MY, respectively).

Conclusions: In this in vivo rabbit model of the acquired long QT syndrome, female gender was not associated with a longer repolarization time (QT interval), an excessive change in the baseline QT interval or a higher incidence of torsades de pointes in response to ibutilide challenge.
Reactive Oxygen Species and Endotoxic Shock: Effect of Dimethylthiourea
Authors: Pattanaik Uttara , Prasad Kailash
Published: June 2007

The effects of endotoxemia on the cardiac function and contractility, oxygen radical production by polymorphonuclear leukocytes (PMNL-CL), cardiac antioxidant reserve (LV-CL), antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GSHPx]) and malondialdehyde (MDA); and plasma creatine kinase (CK) and lactate in the absence or presence of dimethylthiourea (DMTU), an antioxidant, in anesthetized dogs were studied. Dogs were assigned to three groups: group 1, control; group II, endotoxin (ET) (5 mg/kg body wt intravenously), and group III, ET + DMTU (500 mg/kg intravenously). ET produced decreases in the cardiac function and contractility, antioxidant reserve, antioxidant enzymes; and increases in PMNL-CL, cardiac MDA, plasma CK, and lactate. Pretreatment with DMTU attenuated the ET-induced cardiac dysfunction and changes in the cardiac MDA, antioxidant reserve, and antioxidant enzymes, PMNL-CL, and plasma CK and lactate levels. These results suggest that reactive oxygen species may be involved in the deterioration of cardiac function and contractility, and cellular injury during endotoxic shock and that antioxidants may be of value in the treatment of endotoxic shock.
Local Delivery of a Hydrophobic Heparin Reduces Neointimal Hyperplasia After Balloon Injury in Rat Carotid but not Pig Coronary Arteries
Authors: Sasseen Brett M. , Gray Brian D. , Gal Dov , Lorinc Robert , Carpenter Donald C. , Klugherz Bruce D. , Wilensky Robert L.
Published: June 2007

Background: Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy of local delivery of hydrophobic heparin (PTIR-RS-1), exhibiting increased intramural binding, on neointimal hyperplasia after angioplasty injury.

Methods and Results: PTIR-RS-1 was delivered locally into rat carotid arteries at three doses: 0.1 mM (440 IU), 0.3 mM (1320 IU), or 1.0 mM (4400 IU). Animals were killed at 14 days. In the pig, the doses tested were the low dose in the rat and a high dose 1 log higher. Animals were killed 28 days later. Morphometric analysis was performed to evaluate the intima:media ratio in rats and the normalized neointimal area in pigs. In rats a significant reduction in neointimal to medial area ratio from 0.73 ± 0.15 for control vs 0.80 ± 0.27 for sodium heparin (P = NS) and 0.15 ± 0.07 for the 0.1 mM PTIR-RS-l dose (P < 0.008). In pigs, PTIR-RS-1 the high dose reduced the normalized neointimal area by 16%, a difference that was not statistically significant.

Conclusions: Increased hydrophobicity of heparin reduced neointimal area following balloon overstretch injury in the rat carotid but not the pig coronary artery model. This study attests to the importance of performing studies evaluating the pharmacologic effect of local delivery of a medication in at least two animal models of restenosis.
Delta Opioid Receptors Inhibit Vagal Bradycardia in the Sinoatrial Node
Authors: Jackson Keith E. , Farias Martin , Stanfill Amber , Caffrey James L.
Published: June 2007

Background: Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP.

Methods and Results: Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 μL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/μ,L and a half-maximal response near 0.1 nmoles/,uL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/,uL with the half-maximal response near 0.1 nmoles/,L, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the 6 opiate receptor antagonist, naltrindole. Selected, μ (endomorphin, super DALDA) and κ (dynorphin, U50488) receptor agonists and,μ (CTAP) and κ (norBNI) receptor antagonists were completely ineffective in this system.

Conclusions: These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.
Methods of Evaluation and Quantification of Microangiopathy in High Perfusion Microangiopathy (Chronic Venous Insufficiency and Diabetic Microangiopathy)
Authors: DeSanctis M. T. , Cesarone M. R. , Incandela L. , Belcaro G. , Acerbi G.
Published: June 2007

Noninvasive macro- and microcirculatory tests provide quantitative information that offers answers to most questions posed in venous diseases. Duplex scanning is used to assess the macrocirculation, and microcirculatory methods are used to assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess perfusion. Transcutaneous Po2 and Pco2 measurements are used to study venous hypertension, and strain-gauge plethysmography is used to assess capillary filtration. In venous hypertension, fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration, two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and, therefore, are an indication of the formation of edema, the most frequent sign in venous hypertension. Other methods, such as the vacuum suction chamber and the edema tester, can be used to assess changes due to treatments in venous hypertension. The techniques described in this article should be used in controlled environmental conditions
HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides) in Venous Hypertensive Microangiopathy: A Prospective, Placebo-Controlled, Randomized Trial
Authors: Incandela L. , Belcaro G. , Renton S. , DeSanctis M. T. , Cesarone M. R. , Bavera P. , Ippolito E. , Bucci M. , Griffin M. , Geroulakos G. , Dugall M. , Golden G. , Acerbi G.
Published: June 2007

The aim of this study was to demonstrate whether HR (Paroven-Venoruton; 0-(β-hydroxyethyl)-rutosides), was effective in improving the microcirculation in venous hypertension and microangiopathy. Sixty patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment group and a placebo group. Patients in the treatment group received oral HR (2 g/day for 8 weeks); those in the placebo group received a comparable placebo.

Results: The two groups were comparable for age and sex distribution. The mean age was 45 years (SD 9) in the treatment group (31 patients) and 45.5 (SD 10) in the placebo group (29 patients). There were no differences between the placebo and treatment groups at inclusion. There was no change between inclusion and measurements at 8 weeks in the placebo group. A significant decrease (P < 0.05) in flux at rest and rate of ankle swelling was observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (P < 0.05). The difference in flux, sign and symptoms, and filtration was clinically important at 8 weeks in the treatment group when compared with the placebo group. No adverse effects were observed.

Conclusion: Venous microangiopathy was improved by HR treatment.
Downregulation of Immunodetectable Atrial Connexin4O in a Canine Model of Chronic Left Ventricular Myocardial Infarction: Implications to Atrial Fibrillation
Authors: Oahara Keiko , Miyauchi Yasushi , Ohara Toshihiko , Fishbein Michael C. , Zhou Shengmei , Lee Moon-Hyoung , Mandel William J. , Chen Peng-Sheng , Karagueuzian Hrayr S.
Published: June 2007

Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability.

Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (< 5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 pm vs. 10.2 ± 1.2 pm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09% vs. 0.82 ± 0.13%; P < 0.01).

Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.
Mechanism of the Positive Inotropic Effect of Lysophosphatidic Acid in Rat Heart
Authors: Xu Yan-Jun , Rathi Satyajeet S. , Zhang Ming , Bhugra Praveen , Dhalla Naranjan S.
Published: June 2007

Background: Lysophosphatidic acid, a bioactive phospholipid, is mainly released from the activated platelets. The concentration of lysophosphatidic acid in serum is elevated under conditions such as ischemia, hypertension, and thrombosis; however, its effect on cardiac function, as well as the mechanisms of its action, have not been fully understood.

Methods and Results: Cardiovascular effects of lysophosphatidic acid were studied in vivo in rats as well as in vitro by using the isolated perfused heart and cardiomyocyte preparations. Intravenous injection of lysophosphatidic acid (2.8 to 14 μgI/00 g body wt) increased the left ventricular systolic and diastolic pressures, rate of pressure development, and rate of pressure decay in rats. The positive inotropic effect of lysophosphatidic acid in vivo was not affected by the blockers of angiotensin II, endothelin-1, or adrenergic receptors, but this action was abolished by pretreatment with neurokinin type I receptor antagonist (L703606) as well as Ca2+-channel antagonist (verapamil). In the isolated heart, lysophosphatidic acid (1-10 μM) had no significant effect on cardiac function but higher concentrations (20-50 μM) elevated the left ventricular end diastolic pressure, significantly. Lysophosphatidic acid (1-30 μM) neither showed any effect on the basal intracellular concentration of free Ca2+ nor modified the KCl-induced increase in [Ca2+]i in freshly isolated cardiomyocytes.

Conclusions: These results indicate that lysophosphatidic acid stimulated heart function under in vivo but not in vitro conditions. The positive inotropic effect of lysophosphatidic acid in vivo may be indirectly mediated by the activation of neurokinin type 1 receptors.
Plasma Levels of Brain Natriuretic Peptide: A Potential Marker for HIV-Related Cardiomyopathy
Authors: Carrillo-Jimenez Rodolfo , Lamas Gervasio A. , Hennekens Charles H.
Published: June 2007

One of the most common and life-threatening cardiovascular complications of HIV-infection is severe global left ventricular dysfunction due to primary heart muscle disease. At present, there is no single, cost-effective and reliable method of identifying the highly prevalent HIV-related cardiac dysfunction. Nonetheless, growing evidence supports the hypothesis that brain natriuretic peptide measurement has the potential to detect patients who develop HIV-related cardiomyopathy. If true, this hypothesis would have important clinical and public health implications.