bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal Stromal Tumor Colliding With Angiosarcoma
Authors: Adhikari Mala , Li-cheng Wu Mark , Zhao Xiaohui
Published: June 2007

The collision of gastric tumors is rare, and those involving gastrointestinal stromal tumor and angiosarcoma have not been previously reported. This article reports a gastric tumor involving collision of gastrointestinal stromal tumor and angiosarcoma. The patient was an 81-year-old man who presented with dyspepsia and large gastric mass. The mass showed a proliferation of spindle cells expanding the muscularis propria. Most of the tumor consisted of spindle cells with low-grade cytology that were positive for CD117 (c-kit), indicating gastrointestinal stromal tumor. Occasional prominent foci showed dissecting and anastomosing channels of ectatic vascular spaces lined by cytologically malignant cells that were positive focally for CD117 and diffusely positive for multiple vascular markers, indicating angiosarcoma.
Predicting Sentinel Lymph Node Metastases in Infiltrating Breast Carcinoma With Vascular Invasion
Authors: Jonjić Nives , Mustać Elvira , Dekanić Andrea , Marijić Blažen , Gašpar Božena , Kolić Ivana , Čoklo Miran , Sasso Franco
Published: June 2007

Sentinel lymph node and clinically negative axillary node status was compared with well-known clinicopathological characteristics such as tumor size, histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER-2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph nodes were found in 29 of 100 patients: 19 with metastases detected by hematoxylin and eosin staining and 10 with micrometastases confirmed by immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present in larger carcinomas ( P < 0.03), more frequently in tumors with negative PR status ( P < 0.037) and evident lymphovascular invasion ( P < 0.002). Lymphovascular invasion was also associated with breast cancer of higher histologic ( P = 0.011) and nuclear grade ( P = 0.039). Tumor size and the presence of lymphovascular invasion were found to be significant predictors of pathologically positive sentinel lymph node in T1 and T2.
Incidental Rectal Mucosa Obtained via Transrectal Ultrasound-Guided Prostatic Core Biopsies
Authors: Ashton-Sager Amanda , Wu Mark Li-cheng
Published: June 2007

A retrospective review was conducted of material from 782 transrectal ultrasound-guided prostatic core biopsies to determine whether incidental pieces of rectal mucosa obtained in this manner could harbor clinically significant rectal pathology or incur artifacts that cause diagnostic difficulty. Material from 114 biopsies (14.6%) showed rectal mucosa, and material from 19 (16.7%) showed rectal pathology, including a hyper-plastic polyp in 1, changes consistent with ulcerative proctitis in 8, focal active proctitis in 7, and granulomas in 3. The original pathologist overlooked the hyperplastic polyp. In 1 specimen, rectal lymphocytes and plasma cells that were displaced over prostatic tissue closely mimicked prostatic adenocarcinoma (Gleason score 5). Conversely, in another specimen, prostatic adenocarcinoma (Gleason score 5) that was displaced near rectal mucosa closely mimicked a rectal lymphoid aggregate. Incidental rectal mucosa obtained via transrectal ultrasound-guided prostatic core biopsies occasionally harbors clinically significant rectal pathology and rarely incurs artifacts that cause diagnostic difficulty.
Segmental Arterial Mediolysis With Accompanying Venous Angiopathy: A Clinical Pathologic Review, Report of 3 New Cases, and Comments on the Role of Endothelin-1 in Its Pathogenesis
Authors: Slavin Richard E. , Inada Kiyoshi
Published: June 2007

The authors review 20 cases of segmental arterial mediolysis (SAM) including 3 newly reported cases. SAM developed in areas of vascular distention in 2 of the latter cases: 1 in utero in the heart of a recipient of a twin transfusion syndrome and the other in the jejunum secondary to partial venous obstruction. In the third case, it occurred in a patient with Raynaud disease. Characterizing SAM are injurious and reparative lesions that occur in the media and/or at the adventitial medial junction. Four distinctive alterations are recognized: (1) mediolysis, (2) a tearing separation of the outer media from adventitia, (3) arterial gaps, and (4) a florid reparative response that replaces zones of mediolysis and fills areas of medial adventitial separation. The repair can transform SAM into lesions indistinguishable from common types of fibromuscular dysplasia (FMD.) A venous angiopathy involving large and medium-sized veins accompanies SAM. It features medial muscle vacuolar change with lysis leading to apparent separation of residual muscle bundles. Immunostaining shows endothelin-1 (ET-1) decorating adventitial capillaries in SAM and neighboring arteries, in capillaries of adjoining tissues, and outlining smooth muscle cell membranes in adjacent veins including those of the venous angiopathy. The significance of these changes is uncertain. Vasospasm is believed to cause SAM, but ET-1 is not the direct pressor agent responsible for this condition. The reason(s) for synthesis and release of ET-1 in SAM are still hypothetical, but local perturbations in vascular tone may be an important factor. ET-1 may be indirectly play a role in SAM by cross-talking and potentiating the activities of other vasoconstrictors such as norepinephrine and by orchestrating its reparative phase.
Uterine Carcinoma With Serous and Choriocarcinomatous Differentiation
Authors: Molina P. , Torres J. V. , Navarro S. , Llombart-Bosch A.
Published: June 2007

Nongestational, nongonadal, and nonteratoma-related choriocarcinoma is an extremely rare entity. The tumor may be pure or associated with carcinoma. Six cases of primary endometrial carcinomas with the presence of syncytiotrophoblastlike beta-human chorionic gonadotropin (beta-HCG)-positive cells have been reported. We describe a case of endometrial carcinoma in a postmenopausal woman, that was composed almost entirely of syncytiotrophoblastic and cytotrophoblastic elements, except in the areas of lymphatic and myometrial invasion, where the neoplasm expressed a papillary serous carcinoma conformation with numerous psammoma bodies. There was not a clear transition between choriocarcinoma and serous carcinoma components. Immunohistochemically, beta-HCG was strongly positive in trophoblastic cells, whereas papillary areas expressed epithelial membrane antigen. These results suggest a double differentiation from malignant stem cells toward an extraembryonal germinal line and a papillary epithelial line. A poor prognosis is expected for this type of neoplasm with extraembryonic differentiation. In the present case, the histologic subtype of uterine papillary serous carcinoma could be an additional risk factor.
Oncogene Expression and Amplification in Barrett Adenocarcinoma
Authors: Gramlich Terry L. , Fritsch Christine , Cohen Cynthia , Samuel Marsha , Hunt Dirk , Dean Patrick J. , Gansler Ted
Published: June 2007

Oncogene activation by amplification and/or overexpression has been implicated in the development and progression of a number of malignancies. To better define the role of oncogene activation in adenocarcinomas arising in the setting of Barrett esophagus, we examined 44 resected Barrett adenocarcinomas for c-erb B-2, epidermal growth factor receptor (EGFR), c-myc, and cyclin DI gene amplification as well as c-erb B-2 and EGFR expression. DNA was extracted from formalin-fixed paraffin-embedded tissue and analyzed by differential polymerase chain reaction, a technique that permits semiquantitative analysis of gene dosage on archival material. Formalinfixed paraffin-embedded sections were stained with monoclonal antibodies directed against either the internal domain of c-erb B-2 or the extracellular domain of EGFR with a labeled streptavidin biotin technique. C-erb B-2 amplification was identified in three (7%) cases. A plasma membrane pattern of c-erb B-2 immunoreactivity in >50% of tumor cells correlated highly with c-erb B-2 amplification ( P=.00008). EGFR amplification was noted in 18% of cases and correlated highly with the intensity of EGFR immunoreactivity ( P=.0004). C-myc amplification was present in 18% of cases. No tumors showed cyclin DI amplification. Follow-up was available regarding 29 patients and showed decreased mean survival ( P=.029) in patients with strong EGFR immunoreactivity (5.8 months) versus those with weak or absent EGFR labeling (11.8 months), and a trend toward decreased one-year survival (P=.069) for patients with (17%) versus those without (52%) c-myc amplification. Our results indicate one or more selected oncogenes are amplified/overexpressed in some Barrett adenocarcinomas and that EGFR and c-erb B-2 overexpression correlates with amplification. Additionally, strong EGFR expression in tumor cells indicates a poorer prognosis.
p53 Accumulation in Malignant Bone Tumors: An Immunohistochemical Analysis of 217 Cases
Authors: Naka Takahiko , Iwamoto Yukihide , Shinohara Norio , Chuman Hirokazu , Tsuneyoshi Masazumi
Published: June 2007

Using formalin-fixed paraffin-embedded tissue specimens, the authors studied the accumulation of p53 protein in various malignant bone tumors. p53 accumulation was detected in osteosarcoma (16.7%), malignant fibrous histiocytoma (MFH) of bone (30.4%), and chordoma (16.7%). In osteosarcoma, no difference was seen in the incidence of p53 accumulation according to the histologic grade of malignancy and any clinical factors including prognosis, but the incidence was significantly higher in conventional osteosarcoma than in other subtypes of osteosarcoma. In MFH of bone, the p53-positive group had a significantly worse prognosis compared with the p53-negative group. p53 accumulation is thus considered to be related to the prognosis of MFH of bone although it did not demonstrate any prognostic value for osteosarcoma in the current study.
Eosinophilic Enteritis Due to Anisakis: A Call for Pathologists' Attention
Authors: Tuñon T. , Zozaya E. , Tabar A. I. , Dorronsoro M. L. G. , Gomez B. , Valenti C.
Published: June 2007

Anisakis simplex, a common parasite of the fish we eat, can cause eosinophilic enteriis by direct parasitization. The authors describe six cases of intestinal anisakiasis dignosed by morphologic and immunologic studies in vivo and in vitro, five being retospective cases of unclassified eosinophilic enteritis. All patients presented with symptoms of acute abdomen requiring urgent surgery. They all had segmental lesions in the jejunum and/or ileum. Histologically the authors observed eosinophilic miroabscesses; in two cases Anisakis larvae were found. None of the patients declared having eaten raw fish. The surgical pathologist plays a basic role in detecting this disase, although additional serologic investigation of anti-Anisakis IgE and a skin test should be done whenever possible.
Pulmonary Teratoma with Malignant Transformation
Authors: Chen Karl T. K.
Published: June 2007

A rare case of pulmonary teratoma with malignant transformation that occurred in a 58-year-old man is reported. The patient was treated initially with lobectomy. The tumor was composed of well-differentiated adenocarcinoma and mature teratomatous tissue that included squamous epithelium, sebaceous glands, cartilage, and pancreatic tissue. The patient developed recurrent adenocarcinoma in the lung 3 years later and was also found to have a renal cell carcinoma. Both the renal tumor and recur rent lung tumor were resected and adjuvant chemotherapy was given. He died of brain metastasis and further lung recurrence 9 months later.
Pyoderma Gangrenosum Associated with Acute Megakaryoblastic Leukemia
Authors: Crawford Byron E.
Published: June 2007

Pyoderma gangrenosum (PG) is an unusual ulcerating cutaneous process frequently representing a dermatologic manifestation of a systemic disease including myeloproliferative disorders. This article describes the first case of PG associated with acute megakaryoblastic leukemia (AML-M7). This case determined that the morphology of blast forms present within the lesion represented by PG, including elongated cytoplasmic projections, frayed shaggy cytoplasm, and appearance of adhesion of blasts to each other, are suggestive, though not diagnostic, of megakaryoblast. Identification of microthrombi within PG, suggestion of adhesion of circulating megakaryoblasts, and previous reported cases of patients with AML-M7 and patients with PG associated with myeloproliferative disorders exhibiting thrombotic or coagulopathies suggest that a localized microangiopathic consumptive coagulopathy or microthrombotic ischemic process might be considered in the etiology and pathogenesis of PG.
Solitary Fibrous Tumor of Soft Tissue Clinically Simulating a Chemodectoma
Authors: Ortiz-Hidalgo Carlos , Baquera-Heredia Javier , Rojas-Reyna Guillermo , Craig Robert J.
Published: June 2007

We present a case of a 48-year-old woman with a solitary fibrous tumor localized in the carotid bifurcation clinically simulating a chemodectoma. The tumor was composed of spindle cells with abundant intercellular collagen. These spindle cells were positive for CD34 and negative for chromogranin, S-100 protein, NSE, GFAP, and cytokeratin. This is the first solitary fibrous tumor reported in this location, in the English literature.
Juxtaglomerular Cell Tumor of the Kidney
Authors: Kim Chul H. , Park Yong W. , Ordonez Nelson G. , Ayala Alberto G. , Burroughs Judy F. , Ro Jae Y.
Published: June 2007

We present a case of juxtaglomerular cell tumor (JGCT) that developed in a 44-year-old woman with hypertension, which subsided after the tumor was removed. The tumor was 8.5 cm in greatest dimension and is thought to be the largest such tumor reported to date. Ultrastructural study confirmed the diagnosis of JGCT by the demonstration of the typical cytoplasmic rhomboidal secretory granules on electron microscopy. The tumor cells were also strongly reactive for CD34, a finding that has not been previously reported and that may be an adjunct to the diagnosis of JGCT in a patient with hypertension, hyperreninemia, and/or hypokalemia. At present, however, further studies on additional cases for CD34 expression will be necessary to fully evaluate the diagnostic utility of this marker in the diagnosing of JGCT.
Apoptotic and Mitotic Index in Squamous Cell Carcinomas and Premalignant Lesions of the Uterine Cervix
Authors: Sagol Ozgul , Yörükoglu Kutsal , Sagol Sermet , Koyuncuoglu Meral , Uslu Turhan
Published: June 2007

The aim of this study was to determine the frequency of apoptotic and mitotic cells in different grades of premalignant lesions and in different stages of squamous cell carcinoma (SCC) of the uterine cervix. The apoptotic and mitotic indices (A! and MI) of 55 H&E-stained sections of cervical intraepithelial neoplasia (CIN) and 30 SCCs were evaluated in light microscopy by a morphometric method. Twenty, 16, and 19 of 55 CIN cases were classified in CIN I, CIN II, and CIN III group, respectively. No apoptosis was observed in the normal epithelium next to the dysplastic mucosa. There was no statistically significant difference between CIN I and CIN II as well as CIN II and CIN III groups in terms of apoptotic and mitotic cell counts. Mitotic cell counts were found significantly higher in CIN III group when compared with CIN I and CIN II groups together. There was no statistically significant difference in the apoptotic and mitotic cell counts between nonkeratinizing and keratinizing types of SCC. In the SCC group, apoptotic cell counts did not show significant difference between tumor stages. But mitotic counts were significantly higher in advanced stage tumors. The SCC group showed significantly higher mitotic and apoptotic cell counts when compared with preneoplastic lesions. This study suggests that apoptotic function is not altered during progressive stages of dysplastic change in cervical epithelium, while proliferation is triggered only in late stages of dysplasia. Both apoptosis and mitosis are markedly increased in progression to malignancy in cervix epithelium. Mitotic cell counts may be helpful in predicting the extent of the disease in SCC. Resistance of cell death by apoptosis after invasion may accelerate the net growth of the tumor resulting in advanced disease.
HMB-45 Immunostaining and Ultrastructure of Melanocytic Hyperplasia in Pigmented Basal Cell Carcinomas
Authors: Monteagudo Carlos , Carda Carmen , Ferrández Antonio , Llombart-Bosch Antonio
Published: June 2007

The pigmented variant of basal cell carcinoma (PBCC) may be clinically misinterpreted as malignant melanoma. Histologically this variant is characterized by the presence of functional melanocytes distributed among epithelial tumor cells, particularly in superficial areas. Our finding of a case of PBCC with numerous atypical HMB-45-positive melanocytes prompted us to analyze the morphologic and immunohistochemical features of 20 consecutive cases of PBCC. Four additional cases with numerous large HMB-45-positive melanocytes, also present in the most invasive tumor nests, were found. Ultrastructural examination was performed in two selected cases. Large melanocytes with immature (stages I and II) and mature melanosomes were found between epithelial tumor cells having desmosomes and tonofilaments. Our cases highlight the presence of immature melanosomes and subsequent HMB-45 immunostaining in hyperplastic melanocytes within PBCC, an underrecognized feature that should be considered to avoid a misdiagnosis of malignant melanoma.
Flight Microangiopathy in Medium-to-Long Distance Flights: Prevention of Edema and Microcirculation Alterations with HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides): A Prospective, Randomized, Controlled Trial
Authors: Cesarone M. R. , Belcaro G. , Incandela L. , Geroulakos G. , Griffin M. , Lennox A. , DeSanctis M. T. , Acerbi G.
Published: June 2007

This study evaluated the effects of HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides) on the prevention and control of flight microangiopathy, and particularly on edema, in subjects with varicose veins flying for more than 7 hours. Forty patients with varicose veins, edema, and initial skin alterations due to chronic venous hypertension were included. Measurements of skin laser Doppler flowmetry resting flux, Po2 and rate of ankle swelling, were made before and after the flights (within 4 hours before the flights and within 2 hours after the flights). The length of the flights was between 7 and 9 hours; all seats were in coach class. The 2 groups were comparable for distribution. The variation of Po2 was significant in both groups. However, in subjects treated with HR, the decrease in Po2 was smaller (P < 0.05). The decrease in laser Doppler flowmetry resting flux was also significant in both groups, with a higher flux at the end of the control period in the treated subjects (P < 0.05). The venoarteriolar response progressively decreased at 7 and 9 hours. The decrease was less evident in the treatment group (P < 0.05). The rate of ankle swelling was progressively increased in the control group; the increase was not significant in the HR group. In long-haul flights, HR is useful for reducing the increased capillary filtration and in controlling edema in patients with venous hypertension and is effective in controlling perfusion disorders and microangiopathy, particularly swelling and edema, due to flights.
Spontaneous Adverse Event Reports of Serious Ventricular Arrhythmias, QT Prolongation, Syncope, and Sudden Death in Patients Treated with Cisapride
Authors: Barbey Jean T. , Lazzara Ralph , Zipes Douglas P.
Published: June 2007

Context: Adverse cardiac events, typically long QT syndrome, have been reported in patients treated with the gastrointestinal prokinetic agent cisapride.

Objective: To analyze cases of cisapride-associated long QT syndrome and ascertain the degree of confidence in the diagnosis of long QT syndrome and the presence of risk factors.

Design: Review of all cases reported to the manufacturer, health authorities, or in the medical literature as of October 1999.

Methods: Before review, specific definitions and a classification scheme were agreed upon. Each case was classified by confidence in the long QT syndrome diagnosis and the presence of recognized risk factors (cofactors) or other medical conditions that were listed as contraindications in the June 1998 United States labeling (labeled conditions).

Results: Of 574 cases reviewed, 391 cases of long QT syndrome or isolated QT prolongation were confirmed. Most of these were classified as long QT syndrome with high (145, 37%) or medium (92, 23.5%) confidence in the diagnosis. Recognized cofactors were present in 262 (67%) cases. The proportion of cases with recognized cofactors rose with confidence in the diagnosis (P < 0.001) from 42.2% in the low-confidence group to 68.5% and 82.1% in the medium- and high-confidence groups, respectively. Conversely, the proportion of cases with other labeled conditions decreased with confidence in the diagnosis, from 33.3% for low confidence to 13% and 8.3% for medium and high confidence, respectively. Analysis of cases and prescribing data showed reporting rates decreased in studied months in 1999 compared with the average study period.

Conclusion: In most cases with high or medium confidence in the diagnosis of cisapride associated long QT syndrome, recognized cofactors for long QT syndrome were present. The risk of cisapride-related long QT syndrome may be minimized by avoiding cofactors.
Beneficial Effects of Therapy on the Progression of Structural Remodeling During Healing After Reperfused and Nonreperfused Myocardial Infarction: Different Effects on Different Parameters
Authors: Jugdutt Bodh I. , Menon Vijayan
Published: June 2007

Background: Structural left ventricular remodeling after myocardial infarction is a complex process with several pathophysiologic descriptors that can be modified by pharmacotherapy. However, the possibility that different classes of antiremodeling agents might exert different effects on different remodeling parameters after reperfused and nonreperfused myocardial infarction has not been systematically studied.

Methods and Results: We measured detailed left ventricular remodeling parameters in vivo (echocardiograms) repeatedly over 6 weeks and ex vivo (planimetry) at 6 weeks after myocardial infarction in 36 dogs randomized (factorial design) after reperfused or nonreperfused myocardial infarction to 6 weeks of twice daily oral therapy with the calcium channel blocker amlodipine (5 mg), the angiotensin-converting enzyme inhibitor enalapril (5 mg) or placebo, and 18 matching sham or control animals. Compared to placebo and control groups over 6 weeks, both agents reduced left ventricular loading and limited overall remodeling in both reperfused and nonreperfused groups, but there were pertinent differences. Enalapril limited the increase in left ventricular asynergy in the reperfused group. Both enalapril and amlodipine limited infarct zone thinning in the nonreperfused groups but increased infarct zone thinning in the reperfused groups, despite preserved infarct zone collagen with amlodipine. Enalapril decreased left ventricular diastolic volume and mass more than amlodipine in the reperfused group and increased left ventricular ejection fraction in the nonreperfused group. Both agents limited regional and global shape deformation in reperfused and nonreperfused groups. Diastolic wall stress in the infarct zone decreased with amlodipine, and increased with enalapril and reperfusion.

Conclusions: Different antiremodeling therapies may exert different effects on different remodeling parameters during healing after reperfused myocardial infarction. Significant interactions occur during reperfusion. More than one variable may be needed for the comprehensive assessment of the antiremodeling efficacy of different therapies.
Azimilide Inhibits Multiple Cardiac Potassium Currents in Human Atrial Myocytes
Authors: Chen Fuhua , Esmailian Fardad , Sun Wei , Wetzel Glenn T. , Sarma Jonnalagedda S. M. , Singh Bramah N. , Klitzner Thomas S.
Published: June 2007

Background: Studies in animal cell preparations suggest that azimilide may produce a more desirable rate-dependent profile of class III action as a result of its effects on both the slowly (IKS) and rapidly (I cr) activating components of potassium current (IK). However, relatively little is known about the effects of azimilide on K+ currents in human atrial cells. The present study investigated the effect of azimilide on the inward rectifier potassium current (IKI), delayed rectifier potassium current (IK), ultrarapid delayed rectifier current (IKJ,), and transient outward potassium current (Ito) in isolated single human atrial myocytes.

Methods: The tight-seal, whole-cell voltage clamp technique was used to investigate the acute effects of azimilide on K+ currents in single human atrial myocytes. The cells were isolated enzymatically from atrial tissues that were obtained from patients undergoing open heart surgeries, with the approval of the local Institutional Review Board.

Results: The average cell capacitance of the human atrial myocytes was 77.5 ± 2.8 pF (Mean ± standard error of mean, total 28 cells from 17 patients). We found that 100,uM of azimilide in the extracellular solution significantly inhibited the inward rectifier potassium current (12.3 ± 3.1 vs 6.7 ± 2.0 pA/pF, n = 12, P < 0.05) at the testing potential of -100 mV. Superfusion with 100,uM of azimilide for 10 minutes inhibited IK by 51.7 ± 5.1% (from 3.4 ± 0.5 to 1.6 ± 0.2 pA/pF, n = 9, P < 0.01) at the clamping membrane potential of +40 mV. Human atrial cell IK, was inhibited with 100 jM of azimilide by 38.6 ± 4.4% (from 3.9 ± 0.5 to 2.3 ± 0.2 pA/pF, n = 9, P < 0.01, test potential = 40 mV). We also found that the average peak current amplitude of I,. in these cells was significantly inhibited with 100,uM of azimilide by 60.3 ± 5.9% (from 10.3 ± 1.5 to 3.6 ± 0.3 pA/pF, n = 6, P < 0.01, test potential = 50 mV).

Conclusion: The present study provides direct evidence that azimilide inhibits multiple cellular transmembrane K+ currents in freshly isolated human atrial myocytes. Inhibition of these K+ currents by azimilide, especially of IKS and IKu, is likely to be the electrophysiologic basis for the prolongation of the action potential duration in the human atria which mediates its known antifibrillatory effects in atrial fibrillation and flutter.
Anti-inflammatory Effects of Statins in Patients with Aortic Stenosis
Authors: Pate Gordon E. , Tahir M. Naeem , Murphy Ross T. , Foley J. Brendan
Published: June 2007

Background: Aortic stenosis is an inflammatory process, as evidenced by increased tissue expression and serum levels of various endothelial cellular adhesion molecules. Aortic stenosis and atherosclerosis have many risk factors in common, including hypercholesterolemia. In atherosclerosis, statins lower cholesterol and display some anti-inflammatory activity. We hypothesized that statins might also have anti-inflammatory effects in patients with aortic stenosis.

Methods: This observational cross-sectional study measured levels of cellular adhesion molecules in 129 patients (88 male, mean age 68) with aortic stenosis (mean echo gradient 49 mm Hg, range 22 to 112) and compared levels in patients already on statin therapy for primary or secondary prevention of coronary artery disease, to those not on treatment. Concomitant conditions included hypertension (47%), diabetes (10%), and ischemic heart disease (54%). A comparison group consisted of 45 patients with stable ischemic heart disease.

Results: Patients on statins (35) were more likely to have hypertension (62% vs 42%, P = .05), but no significant differences existed in sex, age, concomitant ischemic heart disease, or diabetes. Statin-treated patients had a 20% lower vascular cellular adhesion molecule level than those without (484 ± 143 ng/L vs 604 ± 245 ng/L, P = .006). The reduction in cellular adhesion molecule levels was consistent in patients with aortic stenosis alone, aortic stenosis and ischemic heart disease, or ischemic heart disease alone. There were no differences in the levels of the other adhesion molecules between the three groups, or related to statin therapy.

Conclusion: Statin therapy is associated with reduced serum levels of vascular cellular adhesion molecules in patients with aortic stenosis. Vascular cellular adhesion molecule levels are similar in patients who have aortic stenosis, ischemic heart disease, or both. A prospective study is required to confirm this finding and to determine whether this suppression of endothelial inflammation translates into a slowing of the progression of aortic stenosis.
Cardioprotection by Carvedilol: Antiapoptosis is Independent of β-Adrenoceptor Blockage in the Rat Heart
Authors: Schwarz Ernst R. , Kersting Philipp H. , Reffelmann Thorsten , Meven Dennis A. , Al-Dashti Raja , Skobel Erik C. , Klosterhalfen Bernd , Hanrath Peter
Published: June 2007

Background: Carvedilol, a β-blocking agent with α-blocking properties is now widely used for the treatment of congestive heart failure. In addition to its β-adrenergic receptor blockage, antiapoptotic effects have been demonstrated in experimental animals.

Objective: The cardioprotective effects of carvedilol and its hydroxylated analogue BM-91.0228 were tested with regard to their infarct-limiting and antiapoptotic properties in an experimental infarct model in the rat heart.

Methods: Anesthetized rats were subjected to either 30 (groups I to 3) or 60 minutes (groups. 4 to 6) of coronary artery occlusion followed by 30 minutes of reperfusion. Groups 1 and 4 served as the control; groups 2 and 5 received intravenous Carvedilol (1 mg/kg) and groups 3 and 6 received intravenous administration of BM-91.0228 (1 mg/kg), respectively, 5 minutes prior to coronary occlusion. Infarct sizes were measured by triphenyltetrazolium chloride staining. In situ visualization of apoptosis was measured by nick end labeling.

Results: Carvedilol reduced infarct size after 30 minutes of coronary occlusion compared to controls (8.7% ± 2.7% versus 27.3% ± 3.4%, P < .001), while BM-91.0228 showed no significant infarct size reduction (23.7% ± 5.9%, NS). Neither Carvedilol (36.9% ± 3.9%) nor BM-91.0228 (42.4% ± 3.6%) reduced infarct size after 60 minutes of coronary occlusion compared to controls (47.7% ± 3.9%, NS). Carvedilol reduced apoptosis after 30 minutes (4.9% ± 1.3% versus 16.7% ± 3.2%, P < .01) and after 60 minutes (11.7% ± 1.8% versus 25.5% ± 0.5%, P < .001) of coronary occlusion compared to controls. BM-91.0228 reduced apoptosis after 30 minutes (7.3% ± 1.4% versus 16.7% ± 3.2%, P < .01) and after 60 minutes (13.4% ± 1.8% versus 25.5% ± 0.5%, P < .001) of coronary occlusion compared to controls.

Conclusion: Carvedilol is cardioprotective by preventing ischemia-perfusion-induced necrosis and apoptosis of cardiomyocytes. The antiapoptotic effects of Carvedilol are independent of its β-adrenoceptor blocking effects, but its effects might be caused by antioxidant properties and by modulation of the signalling pathway.
Effects of Flaxseed Oil on Serum Lipids and Atherosclerosis in Hypercholesterolemic Rabbits
Authors: Lee Paul , Prasad Kailash
Published: June 2007

Objective: Flaxseed oil has very high content of ox-linolenic acid (C18:3n-3, omega-3 [n-3] fatty acid). Based on the usefulness of n-3 fatty acid in fish oil against cardiovascular diseases, flaxseed oil is marketed as a health food. The n-3 fatty acid in flaxseed oil is different than that of fish oil. Indirect evidence suggests that the omega-3 fatty acid in flaxseed oil is not effective in lowering serum lipids and hypercholesterolemic atherosclerosis. The effects of flaxseed oil on serum lipids and hypercholesterolemic atherosclerosis are not known. An investigation, therefore, was made of flaxseed oil on high-cholesterol diet-induced atherosclerosis, serum lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, risk ratio of total cholesterol to high-density lipoprotein cholesterol), serum and aortic malondialdehyde, an index of levels of reactive oxygen species, aortic chemiluminescence (a measure of antioxidant reserve), and reactive oxygen species-producing activity of white blood cell chemiluminescence in rabbits.

Methods: The rabbits were assigned to four groups: Group I, regular diet (control); Group II, 5% flaxseed oil in regular diet; Group III, 0.5% cholesterol diet; Group IV, diet containing 0.5% cholesterol and 5% flaxseed oil. Blood samples were collected before and after 4 and 8 weeks of experimental diets for measurement of serum lipids, serum malondialdehyde, and white blood cell chemiluminescence. At the end of 8 weeks of the experimental diet, aortas were removed for measurement of atherosclerotic plaques, aortic malondialdehyde, and antioxidant reserve.

Results: Serum total cholesterol, triglycerides, and low-density and high-density lipoprotein cholesterol, and risk ratio of total cholesterol to high-density lipoprotein cholesterol, were elevated to a similar extent in Groups III and IV compared to Groups I and II. The extent of atherosclerosis in Groups III and IV was similar (56.74% ± 11.14% vs 58.01% ± 10.95%). Groups III and IV both had similar increases in serum and aortic malondialdehyde and antioxidant reserve. Reactive oxygen species-producing activity of white blood cells increased in Group III, and flaxseed oil prevented the cholesterol-induced increase in white blood cell chemiluminescence in Group IV.

Conclusion: These results suggest that flaxseed oil does not produce an alteration in serum lipids or in the extent of hypercholesterolemic atherosclerosis; however, it decreases white blood cell chemiluminescence. The ineffectiveness of flaxseed oil was associated with its ineffectiveness in altering the levels of oxidative stress.
Atherosclerosis in Type 2 Diabetes Mellitus: The Role of Insulin Resistance
Authors: Watson Karol E. , Peters Harmel Anne L. , Matson Gary
Published: June 2007

Type 2 diabetes mellitus is associated with a marked increase in the risk of atherosclerotic diseases, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease. Insulin resistance is a key factor in the pathogenesis of type 2 diabetes mellitus. Insulin resistance and its attendant metabolic abnormalities may cause much of the increased cardiovascular risk of type 2 diabetes mellitus. Among the abnormalities associated with insulin resistance are dyslipidemia, hypertension, systemic inflammation, and a prothrombotic state. This review discusses the role that each of these disorders plays in the cardiovascular risk of type 2 diabetes mellitus.
Correlation of Angiotensin-Converting Enzyme Gene Polymorphism with Effect of Antihypertensive Therapy by Angiotensin-Converting Enzyme Inhibitor
Authors: Li Xiaotao , Du Yanmei , Du Yanfang , Huang Xizheng
Published: June 2007

Background: The correlation of the angiotensin-converting enzyme insertion/deletion polymorphism with essential hypertension shown in previous studies is controversial, and the responses of hypertensive patients with different angiotensin-converting enzyme genotypes to treatment with an angiotensin-converting enzyme inhibitor merits investigation.

Methods: Eighty-nine patients with essential hypertension and 102 normotensive subjects were included in this study. All subjects were genotyped by polymerase chain reaction for the insertion/deletion polymorphism of the angiotensin-converting enzyme gene. Blood pressure was measured before and after taking Benazepril 10 mg, once daily, for 2 months.

Results: The genotype and allele frequencies were similar (X2 = 0.64, P = .73; x2 = 0.36, P = .55, respectively). The reduction of both systolic and diastolic blood pressure in the DD genotype was significantly greater than in the II genotype (10.13 ± 4.91 vs 5.37 ± 2.79, P < .01; 7.47 + 3.50 vs 4.71 ± 2.40, P < .05, respectively).

Conclusions: No significant association of angiotensin-converting enzyme gene polymorphism with essential hypertension was found. Angiotensin-converting enzyme gene polymorphism might be related to the antihypertensive response to an angiotensin-converting enzyme inhibitor in hypertensive patients.
Separate and Combined Effects of Local and Continuous Intravenous Administration of β-Cyclodextrin Tetradecasulfate on Intimal Hyperplasia after Angioplasty in Porcine Coronary Arteries
Authors: Meneveau Nicolas F. , Klugherz Bruce D. , Chaquor Brahim , Golden Michael A. , Jouille Madeleine M. , Macarek Edward , Weisz Paul B. , Wilensky Robert L.
Published: June 2007

Background: Beta-Cyclodextrin tetradecasulfate binds fibroblast growth factors and possesses anticoagulant properties. This study was designed to assess the separate and combined effects of local intramural delivery and intravenous administration of β-cyclodextrin tetradecasulfate on neointimal formation and arterial damage following angioplasty.

Methods and Results: Fifty-two pigs randomized into four groups underwent coronary artery angioplasty: 1) control, 2) continuous intravenous infusion of 100 mg/kg/d of β-cyclodextrin tetradecasulfate, 3) intramural delivery of 1250 mg β-cyclodextrin tetradecasulfate, 4) intramural delivery of 1250 mg β-cyclodextrin tetradecasulfate followed by continuous intravenous infusion of 100 mg/kg/d. Fourteen days after injury, morphometric analysis revealed that arteries randomized to the intravenous β-cyclodextrin tetradecasulfate groups had a decreased normalized neointima area: control, 3.03 ± 0.75 mm2; intravenous, 1.67 ± 0.73 mm2 (40% decrease; P < 10-7); intravenous plus local, 1.95 ± 0.76 mm2 (30% decrease; P < 10-5). There was no difference in neointimal response following local β-cyclodextrin tetradecasulfate delivery only (2.82 ± 1.14 mm2). Coronary arterial damage, defined as aneurysm, dissection, adventitial rupture, and retromedial hematoma was similar in all groups (12% in control and local groups, 10% in the intravenous group, 14% in the intravenous plus local; NS). Bleeding complications were more frequent in the intravenous and intravenous plus local groups compared to the local and control groups (23%vs 7.6% and 0%, respectively; P < 0.05).

Conclusions: Continuous intravenous administration of β-cyclodextrin tetradecasulfate substantially reduced intimal hyperplasia, while intramural delivery had no effect, indicating that a single bolus of β-cyclodextrin tetradecasulfate did not reduce intimal hyperplasia. There was no additive effect of local intramural delivery of β-cyclodextrin tetradecasulfate. However, local delivery of β-cyclodextrin tetradecasulfate induced less bleeding complications and did not lead to additional arterial injury, indicating that local delivery of an anticoagulant does not cause additional arterial injury.
Suppression of Oxidative Stress as a Mechanism of Reduction of Hypercholesterolemic Atherosclerosis by Aspirin
Authors: Prasad Kailash , Lee Paul
Published: June 2007

Background: Hypercholesterolemia increases the formation of arachidonic acid and thereby synthesis of prostaglandins and leukotrienes. During synthesis of these eicosanoids, oxyradicals are produced. Oxyradicals have been implicated in the development of hypercholesterolemic atherosclerosis. Aspirin, an inhibitor of synthesis of prostaglandins, would prevent the generation of oxyradicals and hence would prevent the development of atherosclerosis. The purpose of the investigation was to determine if aspirin attenuates the development of hypercholesterolemic atherosclerosis, and if this attenuation is associated with a decrease in the oxidative stress.

Methods and Results: Three groups of rabbits were used for this study: Group I, control; Group II, 0.5% cholesterol; Group III, 0.5% cholesterol plus 0.068% aspirin. Blood samples were collected before and after 1 and 2 months of experimental diets for measurement of serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum malondialdehyde, and white blood cell chemiluminescence, a measure of oxyradicals produced by white blood cells. Aortas were removed at the end of the protocol for the measurement of atherosclerotic plaques, malondialdehyde and aortic chemiluminescence, a measure of antioxidant reserve. Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and ratio of total cholesterol to highdensity lipoprotein cholesterol increased to a similar extent in Groups II and III compared to Group I. Serum triglycerides increased in both Groups II and III; however, the increase was greater in Group III than in Group II. Levels of serum and aortic malondialdehyde, and white blood cell-chemiluminescence were higher in Group II compared to Group I. Aspirin decreased the levels of these parameters. Antioxidant reserve increased in both Groups II and III, the increase being greater in the latter than the former. White blood cell-chemiluminescence increased in Group II compared to Group I, but remained unaltered in Group III compared to Group I. Aspirin treatment reduced the development of atherosclerosis by approximately 47%.

Conclusion: These results suggest that aspirin, an inhibitor of cyclooxygenase, reduced the development of hypercholesterolemic atherosclerosis, and this effect was associated with a decrease in the oxidative stress.
Nitric Oxide and Other Novel Therapies for Pulmonary Hypertension
Authors: Napoli Claudio , Loscalzo Joseph
Published: June 2007

Pulmonary hypertension is an uncommon, yet devastating, syndrome with a complex underlying pathobiology. Hypoxia, inflammation, and increased shear stress appear to be the primary pathogenic events; however, mechanisms by which these processes lead to pulmonary hypertension remain incompletely understood. The ultimate increase in pulmonary vascular resistance is attributed to remodelling of the walls of resistance vessels, which can lead to encroachment on and reduction of the vascular lumen. The number of blood vessels per unit of cross-sectional area in the hypertensive lung is also reduced, which can contribute to increased vascular resistance. Regardless of its etiology, endothelial dysfunction underlies pulmonary hypertension, one manifestation of which is the attenuated production of bioactive nitric oxide. Nitric oxide administration can exert beneficial effects at various stages of the disease. Here we review the known pathobiology of pulmonary hypertension, with a principal focus on endothelial nitric oxide, and also summarize the data on nitric oxide replacement therapy and other novel therapies that relate to nitric oxide as one approach to treatment.
Ventricular Arrhythmias: Antiadrenergic Therapy for the Patient with Coronary Artery Disease
Authors: Hohnloser Stefan H.
Published: June 2007

Patients who have had a recent myocardial infarction (MI) are at high risk of ventricular arrhythmias that often cause sudden cardiac death. It is believed that sympathetic overactivity in the peri-infarction period may alter the electrophysiology and structure of the myocardium, thus placing these patients at risk of developing rhythm disturbances. A number of pharmacologic and nonpharmacologic therapies have been shown to reduce the risk of post-MI mortality, including sudden cardiac death. β-Adrenergic blockers are recommended for all post-MI patients without contraindications because of overwhelming clinical evidence of their benefit in reducing mortality in this patient population. Recent clinical trials of implantable cardioverter defibrillators have provided compelling support that they are effective in both the primary and secondary prevention of sudden cardiac death. In addition, several studies have shown that combination therapy with β-blockers and implantable cardioverter defibrillators have synergistic effects that optimize the benefits of both therapies.
Antiadrenergic Therapy in the Control of Atrial Fibrillation
Authors: Naccarelli Gerald V.
Published: June 2007

Atrial fibrillation (AF) in heart failure develops commonly in older individuals and its prevalence increases as heart failure severity progresses. Because of deteriorating hemodynamics, patients with heart failure are at increased risk for developing AF and, conversely, AF in heart failure patients is associated with adverse hemodynamic changes. AF is believed to increase the mortality risk in heart failure, which may be minimized by treatment that includes the control of ventricular rate, prevention of thrombotic events, and conversion to normal sinus rhythm. Clinical guidelines recommend amiodarone or dofetilide in heart failure patients, but these drugs have certain drawbacks, such as an increased risk for bradyarrhythmias with amiodarone and proarrhythmic reaction with dofetilide. Some but not all clinical trials have suggested that rate control should be the primary therapeutic goal in high-risk heart failure patients with AF and, if unsuccessful, followed by rhythm control. The former is effectively achieved with rate-lowering β-blockers alone or in combination with digoxin. Recent studies evaluating the effects of combination carvedilol/digoxin therapy demonstrate synergistic effects between the two drugs. This combination therapy decreased heart failure symptoms, effectively reduced ventricular rate, and improved ventricular function to a greater extent compared with that produced by either drug alone. Although digoxin alone is an effective heart failure treatment, its use as a single rate-control therapy is often ineffective in heart failure patients with AF associated with rapid ventricular response. Carvedilol is effective, alone or in combination, with digoxin in such heart failure patients with AF, and has been shown to reduce mortality risk in patients with chronic heart failure during prolonged therapy.
Postconditioning Markedly Attenuates Ventricular Arrhythmias After Ischemia-Reperfusion
Authors: Kloner Robert A. , Dow Joan , Bhandari Anil
Published: June 2007

Background: Brief periods of reocclusion (postconditioning) during early reperfusion reduce myocardial infarct size. Whether postconditioning has an effect on lethal ventricular arrhythmias independent of infarction in an in-vivo regional ischemia model is unknown. The purpose of this study was to determine if postconditioning limited reperfusion arrhythmias in a necrosis-free model.

Methods: Anesthetized rats were subjected to 5 minutes of proximal coronary artery occlusion; they were randomized to a control group (n = 15) that underwent reperfusion alone or a postconditioning group (n = 15) that received four cycles of 20 seconds reperfusion, 20 seconds reocclusion before final reperfusion.

Results: During the final reperfusion phase, ventricular arrhythmias occurred in 14 of 15 control rats and 8 of 15 postconditioning rats ( P = .017). Ventricular tachycardia occurred in 10 of 15 control rats vs 4 of 15 postconditioning rats ( P = .028). Control rats demonstrated 1.3 runs of ventricular tachycardia per minute vs 0.4 runs in postconditioning rats ( P = .026). The average duration of ventricular tachycardia runs was 8.8 ± 3.2 seconds in the control group vs 5.0 ± 3.9 seconds in postconditioning rats ( P = NS).

Conclusion: This in-vivo study showed that postconditioning markedly attenuates ventricular arrhythmia after regional ischemia in a noninfarct model.