bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative strategies using SUDAAN for analysis of health surveys with complex samples
Authors: LaVange Lisa M , Steams Sally C , Lafata Jennifer E , Koch Gary G , Shah Babubhai V
Published: November 2007

Large-scale health surveys provide a wealth of information for addressing problems in health sciences research. Designed for multiple purposes, these surveys frequently have large sample sizes and extensive measurements of demographic and socioeconomic characteristics, risk factors, disease outcomes and health care service use and costs. Complex features of the sampling design typically employed to select the survey sample, coupled with the vast amount of information available from the survey database, underlie issues that must be addressed during data processing and analysis. Numerous articles in the literature have focused on the debate of whether or not, and how, to control for features of the sample design during data analysis. Traditional statistical methods for simple random samples and the software that accompanies them have historically not had the capacity to account for the survey design. Recent advancements in statistical methodology for survey data analysis have greatly expanded the analytical tools available to the survey analyst. Commercial software packages that incorporate these methods offer the analyst convenient ways for applying such tools to large survey databases in an easy and efficient manner. We present an overview of analysis strategies for survey data and illustrate their application via the SUDAAN software system. Examples for analyses are provided through data from two large US health surveys, the National Health Interview Survey and the Longitudinal Study of Aging. Questions of both a cross-sectional and longitudinal nature are addressed. The examples involve logistic regression, time-to- event analysis, and repeated measures analysis.
Robustness considerations in Bayesian analysis
Authors: Gustafson Paul
Published: November 2007

All statistical analyses demand uncertain inputs or assumptions. This is especially true of Bayesian analyses. In addition to the usual concerns about the agreement of the data and model, a Bayesian must contemplate the effect of an uncertain prior specification. The degree to which inferences are robust to changes in the prior is of primary interest. This article discusses some robust techniques that have been suggested in the literature. One goal is to make apparent the relevance of some of these techniques to biostatistical work.
Bayesian inference for hierarchical mixtures-of-experts with applications to regression and classification
Authors: Jacobs Robert A , Tanner Martin A , Peng Fengchun
Published: November 2007

This paper studies the problems of inference and prediction in a class of models known as hierarchical mixtures-of-experts (HME). The statistical model underlying an HME is a mixture model in which both the mixture coefficients and the mixture components are generalized linear models. Bayesian inference regarding an HME's parameters is presented in the contexts of regression and classification using Markov chain Monte Carlo methods. A benefit of this Bayesian approach is the ability to obtain a sample from the posterior distribution of any functional of the parameters of the given model. In this way, more information is obtained than provided by a point estimate. The methods are illustrated on a nonlinear regression problem and on a breast cancer classification problem. The results indicate that the HME showed good prediction performance, and also gave the additional benefit of providing for the opportunity to assess the degree of certainty of the model in its predictions.
Multicystic Congenital Mesoblastic Nephroma
Authors: Drut Ricardo
Published: November 2007

This report describes an unusual example of congenital mesoblastic nephroma cellu lar variant that presented in a 1-week-old neonate as a multicystic tumor of the kid ney. Extensive pseudocystic cavitation resulted from progressive accumulation of ground substance in a loosely myxoid tissue composed of stellate- and spindle-shaped cells that compressed and infiltrated renal tissue. The cells of the tumor were positive for vimentin and smooth muscle actin. The patient is alive and well 16 years after surgery. Differential diagnosis from segmental cystic dysplasia, cystic intralobar nephrogenic rest, cystic nephroma, cystic partially differentiated nephroblastoma, cystic nephroblastoma, and cystic clear cell sarcoma of the kidney, all of which may present at this age, is discussed. Int J Surg Pathol 10(1):59-63, 2002
Initial Diagnosis of Unsuspected Primary Amyloidosis (AL) by Liver Biopsy
Authors: Haddad Michel G. , Silverman Jan F. , Larkin Ernest W. , Dellasega Mark
Published: November 2007

While the liver is commonly involved in systemic amyloidosis, review of the literature indicates that clinically evident hepatic amyloidosis is not usually encountered. Three patients with clinically unsuspected primary amyloid light chain (AL) type of amyloid osis diagnosed by liver biopsy are described. All patients presented with signs, symp toms, and biochemical abnormalities consistent with intrinsic liver disease. The first patient had cholestatic hepatitis with jaundice, the second had hepatomegaly and weight loss, and the third had cholestatic liver disease. All three liver biopsies showed extensive sinusoidal deposition of amyloid material that stained positively with Congo red with and without prior potassium permanganate digestion, consistent with AL type amyloid. Ultrastructural examination of one of the cases showed straight, non- branching fibrils having the characteristic appearance of amyloid. Immunocytochemi cal staining in another case revealed the hyaline material to be positive for lambda light chains and negative for kappa light chains. These cases demonstrate that primary amyloidosis can present with liver abnormalities that dominate the clinical picture and that liver biopsy may be the initial diagnostic procedure of unsuspected primary amyloidosis. Int J Surg Pathol 1 (1): 57-64, 1993
Pseudoepithelialization of Breast Implant Capsules
Authors: Chase Donald R. , Oberg Kerby C. , Chase Resa L. , Malott Richelle L. , Weeks Douglas A.
Published: November 2007

A review of 11 breast implant capsules revealed that 5 (45%) possessed a pseudoepithe lial lining virtually indistinguishable morphologically from true synovium. These cap sules showed a spectrum of connective tissue metaplasia that culminated in an ex tremely well-ordered double layer of columnar-appearing cells marking only for vimentin intermediate filaments and failing to stain for various cytokeratins and human factor VIII. Neither trichrome stains nor electron microscopy showed evidence of a basement membrane. The cases indicate that under appropriate conditions breast tissues can undergo mesenchymal metaplasia as well as the much more common epithelial metaplasia. Furthermore, a process morphologically identical to that previ ously described as "synovial metaplasia" in other locations also occurs in some breast capsules where, as in the dermis and in periarticular sites, its development may be dependent upon local factors such as friction and micromotion. Int J Surg Pathol 1 (3): 151-154, 1994
Adenocarcinoma and Adenosquamous Carcinoma of the Uterine Cervix
Authors: Costa Michael J. , Kenny Mary B. , Judd Randy
Published: November 2007

A series of 53 carcinomas of the uterine cervix with a component of glandular differen tiation were identified and included 29 pure adenocarcinomas and 24 adenosquamous carcinomas. Cervical adenosquamous carcinomas were defined as glandular carcino mas mixed with a squamous carcinoma component. Cervical pure adenocarcinomas were classified into various Mullerian subtypes analogous to other portions of the female genital tract yielding 14 mucinous/endocervical, 11 serous, 2 clear cell, and 2 endometrioid adenocarcinomas. A panel of immunostains including monoclonal carcinoembryonic antigen (CEA-M), polyclonal carcinoembryonic antigen (CEA-P), CA 125, CA 19-9, placental alkaline phosphatase, and vimentin showed no association with histologic differentiation except for mucinous/endocervical subtype (7 of 11 CEA- M or CEA-P positive and 7 of 11 CA 19-9 positive). Recurrent disease in adenocarci noma and adenosquamous carcinoma was associated with stage III or IV disease at presentation (P < .001), serous histology (P < .05), absence of strong CEA-M staining (P < .025), absence of strong CEA-P staining (P < 05), and presence of vimentin staining (P < .05). No association was found between survival and other histologic subtypes of adenocarcinoma (mucinous/endocervical, endometrioid, or clear cell), ad enosquamous carcinoma, histologic grade, lymphatic invasion, age, or immunohisto chemical staining for CA 125, CA 19-9, or placental alkaline phosphatase. When only stage I and II disease was considered, there was no correlation between histology or immunohistochemistry and outcome. Int J Surg Pathol 1(3):181-190, 1994
Argyrophilic Nucleolar Organizer Regions in Recurrent Lipomatous Tumors
Authors: Golouh R. , Bračko M. , Cör A.
Published: November 2007

To analyze the proliferation rate in liposarcomas, we studied two silver staining nucleo lar organizing region (AgNOR) counts in a series of 18 patients with multiple recur rences. In a retrospective analysis of corresponding primary and recurrent tumors, cell nuclear characteristics were assessed by the mean number of AgNORs and the percent age of nuclei with more than five AgNORs per nucleus. The computer-assisted analysis of AgNORs compared with clinicopathologic data showed that two AgNOR counts varied considerably in primary lipomatous tumors and in subsequent recurrences along the course of disease. In most patients, proliferative activity of recurrent tumors varied randomly, without any consistent pattern, except in some liposarcomas that showed transformation to a more aggressive histologic picture. In individual patients, decrease in both AgNOR counts paralleled the prolongation of the recurrence-free interval and vice versa. In this limited series, the AgNOR counts did not prove to be an independent prognostic factor in patients with liposarcoma. Int J Surg Pathol 1 (4) :245-252, 1994
Synovial Sarcoma With a Predominant Epithelial Component
Authors: Ishida Tsuyoshi , Kojima Tatsuyoshi , Iijima Takuo , Oka Teruaki , Kuroda Masahiko , Horiuchi Hajime , Imamura Tetsuo , Machinami Rikuo
Published: November 2007

A case of synovial sarcoma of the lower leg in a 59-year-old woman with a predomi nant epithelial component is reported. Histologically, the tumor showed a well-devel oped epithelial component with a sheet-like and cribriform pattern with a sparsely distributed spindle cell component. Immunohistochemically, the epithelial component was positive for cytokeratins and epithelial membrane antigen, while the spindle cell component was positive for cytokeratins, epithelial membrane antigen, and vimentin. The epithelial component of synovial sarcoma is indistinguishable from carcinoma morphologically and immunohistochemically, therefore the presence of a biphasic pattern, even with a paucity of spindle cell component, is a crucial finding to establish a diagnosis of synovial sarcoma. The recognition and subclassification of this type of synovial sarcoma is important in arriving at a correct prognosis. Int J Surg Pathol 1(4): 261-268, 1994
Disseminated Acanthamoeba Infection Masquerading as Bacillary Angiomatosis in a Patient With AIDS
Authors: Khalife Ghada E. , Pambuccian Stefan E. , Visvesvara Govinda S. , Horten Bruce
Published: November 2007

Disseminated Acanthamoeba infections and bacillary angiomatosis are among the un usual opportunistic infections encountered in patients with AIDS. We report a fatal case of disseminated Acanthamoeba palestinensis infection involving the skin, palate, brain, lungs, and testes in a patient with AIDS in whom the mucocutaneous lesions were initially interpreted clinically and pathologically as bacillary angiomatosis. Int J Surg Pathol 2(1):11-16, 1994
Lack of Evidence of Pathogenetic Role of Epstein-Barr Virus in Thymic Lymphoid Hyperplasia and Thymomas in the Chinese Population of Hong Kong
Authors: Chan John K. C. , Yip Timothy T. C. , Tsang William Y. W. , Seneviratne S. , Poon Y.F. , Wong Cesar S. C. , Ma Victor W. S.
Published: November 2007

A previous study from Hong Kong by McGuire et al. reported frequent demonstration of Epstein-Barr virus (EBV) DNA by Southern blot analysis in thymoma, thymic lymphoepithelioma-like carcinoma, and thymic lymphoid hyperplasia. This provoca tive finding, however, could not be confirmed by studies in the Western populations using the Southern blot technique and/or polymerase chain reaction to detect EBV- DNA or in situ hybridization to detect EBV encoded RNA (EBER), raising the possibility that the association with EBV may be restricted to Asians. This study was performed to clarify this issue by using a highly sensitive localization technique for EBER on a larger series from the Asian population of Hong Kong. Paraffin sections obtained from 10 cases of thymic lymphoid hyperplasia, 42 noninvasive thymomas (including one case previously reported to be EBV positive), 11 invasive thymomas, and 9 thymic carcinomas (including 5 cases of lymphoepithelioma-like carcinoma) were studied. EBER signal was not detected in the epithelial cells in any of the cases except for two cases of lymphoepithelioma-like carcinoma. In two thymomas, a few small lympho cytes (<0.1%) were EBER positive. Failure to detect EBER was not an artifact due to RNA denaturation, because preserved mRNA could be demonstrated by oligo-dT labelling in 56 of the 72 cases. Thus, the results of this study on Hong Kong Chinese are in keeping with those reported in Caucasians, and more recently in Japanese and Taiwan Chinese, in that there is no association of EBV with thymic lymphoid hyperpla sia or thymoma, and that EBV may be demonstrated in a proportion of thymic lymph oepithelioma-like carcinomas. The positive results previously reported cannot be ex plained, because the occasional EBV-carrying lymphocytes detected in rare cases of thymoma should be insufficient to give a positive EBV result by Southern blot tech nique. Int J Surg Pathol 2(1):17-22, 1994
Patterns of Healing in the Appendix
Authors: Carr N.J. , Montgomery E.
Published: November 2007

We compared the histologic features of healing acute appendicitis (20 cases) with those of Crohn's disease at the appendix (54 cases), including the presence of granulomas, extrasubmucosal lymphoid aggregates, and subserosal fibrosis. Healing appendicitis assumed two basic patterns: the "usual" pattern, sometimes with an intraluminal cord of granulation tissue, and a xanthogranulomatous pattern. Epithelioid cell granulomas were seen exclusively in Crohn's disease (19/54; 35%). Furthermore, large numbers of lymphoid aggregates involving the muscularis propria or dense concentric subserosal fibrosis exceeding half the width of the muscularis propria in cross-section were signifi cantly associated with Crohn's disease. Xanthogranulomatous features were not seen in the Crohn's cases. The presence of granulomas, extrasubmucosal lymphoid aggre gates, and concentric subserosal fibrosis in an appendectomy specimen may suggest the diagnosis of Crohn's disease. Int J Surg Pathol 2(1):23-30, 1994
Primary Pulmonary Alveolar Soft-part Sarcoma
Authors: Sonobe Hiroshi , Ro Jae Y. , Mackay Bruce , Ordóñez Nelson G. , Rundell Marion M. , Ayala Alberto G.
Published: November 2007

Alveolar soft-part sarcoma rarely arises in the lung. Only two patients with tumors that were apparently primary in the lung have been documented in the literature. We report an additional case in a 25-year-old woman. The tumor formed a solitary 5 cm, solid mass in the left perihilar region. Clinical examination, radiologic studies, and follow-up examination of more than 1 year have failed to reveal tumor in an extrapul monary location. The light microscopic appearance was typical for alveolar soft-part sarcoma, and crystalloids were identified in the tumor cells by the periodic acid-Schiff stain and by electron microscopy, confirming the diagnosis. Immunocytochemical studies did not show evidence of myogenic, epithelial, or neuroendocrine differentia tion. Int J Surg Pathol 2(1):57-62, 1994
Angiomatoid Malignant Fibrous Histiocytoma
Authors: Fukunaga Masaharu , Moriya Takuya , Miyazawa Yoshio , Ushigome Shinichiro , Ishikawa Eisei
Published: November 2007

This study reports the immunohistochemical, ultrastructural, and flow cytometric find ings of two cases of angiomatoid malignant fibrous histiocytoma that developed in the subcutis of the temple of a 10-year-old girl and the shoulder region of a 5-year- old boy. The neoplasm of the temple developed a local recurrence 6 months after the initial excision. Both patients were well and free from tumor at 24 months and 12 months, respectively. Immunohistochemically, many tumor cells of both cases posi tively expressed vimentin, desmin, HHF-35, and KP1. In one case many tumor cells also showed lectin binding for ulex europaeus agglutinin 1, and the other case pre sented ultrastructural features of immature endothelial cells. All tumors, including the recurrent lesion, were diploid. Divergent antigenic phenotypes along with many types of cells were considered; including myogenic cell, fibroblastic cell, and immature endo thelial cell. This study suggests that angiomatoid malignant fibrous histiocytomas show a wide range of pluripotential differentiation. Int J Surg Pathol 2(2):99-104, 1994
p53 Protein and Proliferating Cell Nuclear Antigen (PCNA) Expression in Small Round Cell Tumors of Bone and Adjacent Soft Tissue
Authors: Devaney Kenneth , Abbondanzo Susan L. , Shekitka Kris M. , Wolov Robert B. , Sweet Donald E.
Published: November 2007

Sixty small cell tumors of bone and adjacent soft tissue were studied in an attempt to define the incidence of immunohistochemically detectable p53 protein and cor relate these findings with the results of proliferating cell nuclear antigen (PCNA) immunohistochemical staining and mitotic counts. All of the lesions had been for malin-fixed and paraffin-embedded; half were subjected to decalcification prior to processing. The study population included 12 Ewing's sarcomas of bone, 3 atypical Ewing's sarcomas of bone, 3 primitive neuroectodermal tumors of bone, 11 Askin tumors of the thoracopulmonary region, 11 small cell osteosarcomas of bone, 10 mesenchymal chondrosarcomas of bone, and 10 malignant lymphomas involving bone. The patients ranged in age at the time of presentation from 17 to 67 years. Overall, the incidence of p53 positivity was extremely low in these lesions, irre spective of tumor type. Positive nuclear staining with an antibody to p53 was found in none of the 12 Ewing's sarcomas, none of the 3 atypical Ewing's sarcomas, none of the 3 primitive neuroectodermal tumors of bone, 1 of the 11 Askin tumors of the thoracopulmonary region (1.5% of tumor cells positive), 1 of the 11 small cell osteosarcomas (2% of tumor cells positive), 1 of the 10 mesenchymal chondrosar comas of bone (7% of tumor cells positive), and 2 of the 10 malignant lymphomas involving bone (0.5% and 1% of tumor cells positive, respectively). The majority of tumors showed PCNA positivity within the tumor cells, although the incidence of PCNA positivity within the histologic types varied greatly; in general, the higher PCNA counts corresponded to higher mitotic counts within the individual lesions. The present study did not demonstrate any correlation between mutant p53 accu mulation detected by immunohistochemistry and tumor type, and so it is unlikely that p53 positivity will prove to be of great use in the differential diagnosis of these lesions. A correlation between p53 positivity and PCNA staining or mitotic activity was not apparent. Int J Surg Pathol 2(4):259-268, 1995
The Importance of Considering Trial Design When Interpreting Clinical Trial Results
Authors: Reiffel James A.
Published: November 2007

Background: In recent decades, clinical trials have played an increasingly important role in determining how we practice. Trial results proving that a clinical finding poses risk have led to interventions that try to reduce risk. Clinical trials proving that a particular therapy provides better outcome than another therapy have changed the therapies we now use. Unfortunately, the results of clinical trials are too often affected by biases or design issues that may overtly or covertly alter the results or the way they should really be used. In addition, these biases and design and analysis issues are rarely evident in the abstract sections or key figures and tables in the publications reporting the trials, which may be all the busy physician either reads or remembers.

Methods and Materials: This manuscript discusses the issues involved in optimally under standing clinical trial design and interpretation so that practitioners can better understand how to intelligently read and apply trial results to clinical practice.

Conclusions: Clinical trial results can not be properly applied without consideration of trial design features and intertrial comparisons.
Digoxin's Minimal Inotropic Effect Is Not Limited by Sodium—Calcium Exchange in the Intact Immature Rabbit Heart
Authors: Phoon Colin K. , Wu Shao T. , Parmley William W.
Published: November 2007

Background: In the intact immature heart, how much digoxin can drive sodium-calcium exchange has not been studied in the context of sodium-calcium exchanger abundance. Methods and Results: The effects of digoxin and low potassium on contractility in the intact, paced and isovolumically contracting immature rabbit heart were studied in both the absence and presence of L-type calcium channel blockade. Without calcium channel block ade, digoxin increased contractility minimally and only at 10-6 M/L. In contrast, low potas sium (2.2 mM/L) substantially increased contractility in all experiments, a result indicating abundant sodium-calcium exchanger activity. During nifedipine-induced calcium channel blockade, digoxin (10-6 M/L) allowed modest recovery of contractility, whereas digoxin and low potassium together allowed complete recovery as assessed by dP/dtmax; however, all hearts so perfused subsequently developed ventricular fibrillation, presumably because of calcium overload.

Conclusions: In intact immature rabbit heart, digoxin can drive sodium-calcium exchange and thus increase contractility to only a minimal extent. This effect does not appear to be lim ited by intrinsic exchanger activity, which appears abundant in this preparation. Rather, digoxin's inability to drive the sodium-calcium exchanger may be due to developmental dif ferences in binding to the sodium pump. The sodium-calcium exchanger itself seems capable not only of providing enough intracellular calcium for normal contraction, but also of over loading the myocardium with calcium, despite L-type calcium channel blockade.
Sotalol Is More Powerful Than Propranolol in Suppressing Complex Ventricular Arrhythmias
Authors: Deedwania Prakash C.
Published: November 2007

Background: Sotalol has combined type II and type III antiarrhythmic properties. Although the β-blocking action of sotalol is thought to contribute to its antiarrhythmic actions, few data are available from direct comparative clinical trials with pure β-blocking drugs.

Methods and Results: In this double-blind, randomized, multicenter, placebo-controlled, parallel study, we have compared the antiarrhythmic efficacy and safety of treatment with sotalol vs propranolol in 181 patients with organic heart disease and frequent (> 30 ventricu lar premature complexes [VPCs]/h) repetitive ventricular premature complexes. Eighty-seven were randomized to receive sotalol and 94 received propranolol. The demographic and clini cal characteristics of the two groups were identical, and the majority of patients had coronary artery disease or hypertensive heart disease. Most patients had a long-standing history (> 5 years) of ventricular arrhythmias and, in a significant proportion, antiarrhythmic therapy with other drugs had failed in the past. After withdrawal of all antiarrhythmic drugs and 1 week of placebo, qualified patients were randomized to sotalol (320 mg/day) or propranolol (120 mg/day). Patients not achieving adequate response were given higher doses of sotalol (640 mg/day) or propranolol (240 mg/day). At baseline, both groups had comparable frequency of total VPCs/hour (274/h and 255/h for sotalol and propranolol groups, respectively) which was reduced to 71 VPCs/h and 109/VPCs/h, respectively, at the end of phase 1. At final eval uation there was a significantly greater response to sotalol as demonstrated by 80% reduction in VPCs/hour with sotalol compared with only 50% reduction noted in the propranolol group. Adequate therapeutic response was also achieved in a significantly greater percentage of patients on sotalol compared with propranolol (56% vs 29%. P = .02). Sotalol was also superior to propranolol in suppressing the VT events/day during phase 1 (89% vs 78% reduc tion in VT events/days, P < .05). Sotalol was more effective than propranolol in all subgroups and in patients with heart rate < 75 beats per minute.

Conclusions: Sotalol is more powerful than propranolol in suppressing ventricular arrhyth mias documented on Holter recordings. The superiority of sotalol appears to be related to its combined class II and class III antiarrhythmic actions.
Different Effects of Amiodarone and Quinidine on the Homogeneity of Myocardial Refractoriness in Patients With Intraventricular Conduction Delay
Authors: Cui Guanggen , Sager Philip T. , Singh Bramah N. , Sen Luyi
Published: November 2007

Background: Increases in QT and JT dispersion have been suggested as indicative of a proarrhythmic potential as a result of heterogeneity in myocardial refractoriness, the reduc tion of which by antiarrhythmic agents might be associated with a beneficial effect on the development of serious ventricular arrhythmias.

Methods: To test the hypothesis that amiodarone reduces the heter-ogeneity of ventricular refractoriness to a significantly greater extent than quinidine in patients with intraventricu lar conduction defects under treatment for ventricular arrhythmias, the corrected and uncorrected QT and JT intervals and dispersions from 12-lead surface electrocardiograms were determined in 120 patients with intraventricular conduction defects with cardiac arrhythmias before and during treatment with amiodarone (n = 60) and quinidine (n = 60).

Rcsults: Amiodarone increased QT from 403 ± 50 ms to 459 ± 47 ms ( P < .001), with a sim ilar increase in the corrected QT interval (QTc) ( P < .001). Amiodarone reduced QT disper sion by 40% ( P < .001), whereas quinidine increased by 18% ( P < .001). The net effects of both drugs were similar for QTc. Amiodarone, but not quinidine, reduced heart rate signifi cantly; amiodarone had no effect on the QRS; but quinidine increased it ( P < .001). Quini dine as well as amiodarone increased the JT and JTc intervals significantly, but the effect of quinidine was quantitatively less striking. Amiodarone decreased the JT dispersion by 33% ( P < .001) and JTc dispersion by 37% ( P < .001). On the other hand, quinidine increased the corresponding values for JT and JTc by 18% ( P < .001) and 21 % ( P < .001), respectively. The overall data on QT and JT dispersions indicate an improvement in the homogeneity of myo cardial refractoriness with amiodarone treatment and the converse with quinidine treatment; this observation is consistent with a lower proarrhythmic propensity and mortality with amio darone than with quinidine. Quinidine increased the QRS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization.

Conclusions: Amiodarone and quinidine both increased the corrected and uncorrected QT and JT intervals; amiodarone decreased and quinidine increased the dispersion of these intervals, and these results suggested an improvement in the homogeneity of myocardial refractoriness as a result of amiodarone treatment and the converse as a result of quinidine treatment. Quinidine increased the QTS interval more than amiodarone, and the data indi cate that in patients with intraventricular conduction defects, the monitoring of the JT inter val might more accurately reflect changes in myocardial repolarization.
Nitric Oxide Regulates Renin Release During Salt Depletion but Does Not Alter Angiotensin Responses in Normal Humans
Authors: Davidson Neil C. , Struthers Allan D.
Published: November 2007

Background: Animal studies suggest that nitric oxide regulates the renin-angiotensin- aldosterone system, but this effect varies among species. The effects of nitric oxide on the renin-angiotensin-aldosterone system in humans were assessed using L-nitrosomonomethyl arginine (L-NMMA), an antagonist of nitric oxide synthase.

Methods and Results: In experiment 1, subjects were pretreated with furosemide to induce salt depletion and received placebo-controlled infusions of L-NMMA followed by measure ments of plasma renin activity. In experiment 2, subjects were given angiotensin I and II intravenously with and without L-NMMA to assess the effects of nitric oxide on systemic pressor and aldosterone responses. In experiment 3, brachial arterial infusions of angio tensin I and II were given with and without L-NMMA, and forearm blood flow was mea sured to assess the effects of nitric oxide on vascular responses to the angiotensin peptides. During salt depletion, L-NMMA infusion resulted in significantly higher plasma renin activ ity. L-NMMA had no effect on systemic or forearm pressor responses or aldosterone responses to angiotensin I and II infusions.

Conclusions: These results indicate that nitric oxide regulates the renin response to salt depletion in healthy humans but does not affect responses to angiotensin.
Effects of Palmitoyl Carnitine on Perfused Heart and Papillary Muscle
Authors: Patel Manoj K. , Economides Apollo P. , Byrne Nicholas G.
Published: November 2007

Background: Palmitoyl carnitine accumulation during ischemia causes profound electro physiological changes, resulting in arrhythmias. We studied the electrophysiological and contractile effects of palmitoyl carnitine.

Methods and Results: Extracellular recordings made by using the endocardial unipolar paced evoked response (PER) in isolated perfused rabbit hearts were compared with action potentials (AP) recorded from septal artery perfused rabbit papillary muscle. Left ventricu lar pressure was monitored in isolated hearts. In perfused hearts palmitoyl carnitine (30 μmol/L, 30 minutes) significantly ( P < .001) increased the latency of activation (St-R inter val) by 58% ± 8% and reduced repolarization time (R-E interval) by 39% ± 4%. PER duration (St-E interval), was reduced by 30% ± 3%. Palmitoyl carnitine (30 μmol/L) signif icantly ( P < .001) decreased resting membrane potential (19 ± 2 mV) of AP, reduced peak amplitude (33.5 ± 8 mV) and rate of rise of phase 0 (41 ± 8 V/s). Significant reductions ( P < .001) in the action potential duration 50% (129.4 ± 28 ms) and 90% (139.8 ± 32 ms) were also observed. An initial positive inotropic effect, which declined as irreversible con tracture developed, was also observed. Verapamil (1 μmol/L), nifedipine (1 μmol/L), and caffeine (10 mmol/L) failed to abolish the positive inotropy.

Conclusions: We suggest that palmitoyl carnitine disrupts intracellular calcium homeostasis leading to disturbances in electrical and contractile activity. Its accumulation during myo cardial ischemia could contribute to calcium overloading and initiate lethal arrhythmias.
Hypoxic Hypoperfusion Fails to Induce Myocardial Hibernation in Anesthetized Swine
Authors: Schwarz Ernst R. , Reffelmann Thorsten , Schoendube Friedrich , Herrmanns Benita , Chakupurakal Raj , Doerge Hilmar , Schuetz Thorsten , Foresti Mike , Messmer Bruno J. , Radke Peter W. , vom Dahl Juergen , Hanrath Peter
Published: November 2007

Background: Congenital origin of the left coronary artery from the pulmonary artery (ALCAPA) results in chronically dysfunctional myocardium with the partial ability to recover after revascularization. We attempted to establish an ALCAPA syndrome in anes thetized pigs for 24 hours and to compare it with stunned and infarcted myocardium.

Methods and Results: In group 1 (n = 12), a bypass graft was interposed between the pul monary artery and the left anterior descending coronary artery (LAD). Reduction of flow in the LAD with gradual increases in flow from the pulmonary artery resulted in an incre mental reduction of segment shortening (8.9 ± 5.3% at 24 hours vs 26.6 ± 10% at baseline, P < .005). In group 2 (n = 5), 2 cycles of 10-minute LAD occlusion resulted in decreased segment shortening with slow recovery (at 24 hours 18.7 ± 1.3% vs 24.2 ± 4% at bascline, P < .05). In group 3 (n = 6), 1-hour LAD occlusion reduced segment shortening at 24 hours to 4.7 ± 5.2% ( P < .005 vs baseline). Histological analysis of the LAD territory revealed severe degeneration, myolysis, and alteration of the chromatin structure in group 1 compa rable to ischemic cell death in group 3, whereas control areas and the LAD area in group 2 showed only minor structural alterations. Infarct size/risk area, as measured by tetrazolium staining, was 49.8 ± 11.2% in group 1,9.3 ± 8.1 % in group 2 ( P < .005), and 60.3 ± 9% in group 3.

Conclusion: Hypoxic myocardial hypoperfusion from the pulmonary artery results in myo cardial necrosis in anesthetized pigs. These findings are in contrast to the concept of myocar dial hibernation in the ALCAPA syndrome because in this model, hypoxic hypoperfusion failed to induce adaptation to preserve myocardial structure.
Review : Viagra and Cardiovascular Disease
Authors: Speakman Mark T. , Kloner Robert A.
Published: November 2007

Background: The introduction of the drug sildenafil (Viagra; Pfizer, New York, NY) into the armamentarium for treatment of erectile dysfunction is a major advance. Many of the patients who will benefit from its use have cardiovascular disease. Erectile dysfunction and cardiovascular disease share common risk factors. Although the metabolic demands of sex ual activity are modest and the associated risk for coronary events is low, the clinician car ing for cardiac patients needs to be aware of the pharmacology and hemodynamic profile of sildenafil in those with heart disease who use cardioactive drugs.

Methods and Results: We reviewed the current literature relating to the pharmacology, hemodynamic profile, efficacy, safety, and clinical application of sildenafil in patients with cardiovascular disease. Sildenafil is highly effective in the treatment of erectile dysfunction. The overall incidence of cardiovascular adverse events is low and similar to placebo. Cur rent postmarketing data do not suggest an increase in cardiovascular death in sildenafil users. The drug is contraindicated in those taking organic nitrates. It should be used with caution and on an individual basis in patients who have active coronary ischemia and heart failure with tenous blood pressure and volume status.

Conclusion: When used with discretion, sildenafil is safe, effective, and has the potential to greatly enhance quality of life in the relatively large proportion of the population with heart disease.
L-Asparaginase-Provoked Seizures as Singular Expression of Central Nervous Toxicity
Authors: Hamdan Muhammad Y. , Frenkel Eugene P. , Bick Rodger
Published: November 2007

Patients treated with L-asparaginase may present with hemorrhagic and thrombotic cerebrovascular events. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Compli cations appear to result from depletion of plasma proteins in volved in coagulation and fibrinolysis. Seizures are uncommon symptoms, and are always caused by cerebrovascular events. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebro vascular events.
Effect of Bezafibrate on Soluble Adhesion Molecules and Platelet Activation Markers in Patients With Connective Tissue Diseases and Secondary Hyperlipidemia
Authors: Kagawa Hideo , Nomura Shosaku , Nagahama Minori , Ozaki Yoshio , Fukuhara Shirou
Published: November 2007

We evaluated the plasma concentrations of soluble adhesion molecules, platelet activation markers, and platelet-derived microparticles (PMPs) in patients with connective tissue diseases who had secondary hyperlipidemia caused by long-term steroid administration (n = 22) before and after treatment with bezafibrate. There were differences in levels of platelet. activation markers both before and after treatment (platelet CD62p: 15.11 ± 2.03 vs 10.38 ± 8.53%. P < 0.05; ptatetet CD63: t2.i2 ± 9.17 vs 9.90 ± 7.20%, P < 0.05). There were also differences in the levels of PMPs and soluble adheSion molecules both before and after treatment (PMP: 514 ± 273 vs 401 ± 201 /104 platelet, P < 0.05; soluble vascular cell adhesion molecule-1 : 724 ± 191 vs 666 ± 157 ng/mL, P < 0.01). After 6 months of treatment, serum lipid concentrations were reduced by 9% for total cholesterol (TC) and 32% for triglyceride (TG). The level of PMPs, activated platelets, and soluble adhesion molecules were all significantly decreased after treatment with bezafibrate. These findings suggest that bezafibrate may be useful for inhibiting both PMP-dependent and -independent vascular damage in patients with connective tissue diseases complaining of secondary hyperlipidemia.
Individual Dosing of ASA Prophylaxis by Controlling Platelet Aggregation
Authors: Syrbe Günter , Redlich Helge , Weidlich Bärbel , Ludwig Jochen , Kopitzsch Sibylle , Göckeritz Anke , Herzog Karin
Published: November 2007

Acetylsalicylic acid is widely used in the primary and secondary prevention of cardiovascular diseases. In the current study, we used platelet aggregation ex vivo in platelet-rich plasma induced with arachidonic acid as a routine method for the determination of the individual dose of acetylsalicylic acid necessary to inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40% of all patients studied, a dose of 30 mg/day was sufficient. to block the arachidonic acid-induced platelet aggregation nearly completely. In 50% of all patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose had to be further increased to 300 mg/day or even to 500 mg/day to inhibit platelet aggregation nearly completely. These results demonstrate that platelet aggregation can be used as a simple routine laboratory method to control acetylsalicylic acid treatment in patients with cardiovascular diseases and to determine individual doses of acetylsalicylic acid for a nearly complete inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of the patients were nonresponders.
Tissue Factor Pathway Inhibitor Release Induced by Defibrotide and Heparins
Authors: Cella Giuseppe , Sbarai Alessandra , Mazzaro Gabriella , Motta Giovanna , Carraro Paolo , Andreozzi Giuseppe M. , Hoppensteadt Debra A. , Fareed Jawed
Published: November 2007

We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide extracted from mammalian organ. Ten normal volunteers were injected with an intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In addition, three volunteers were also injected with an intravenous bolus of 2,000 anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a decrease that was parallel to the heparin level measured by the anti-Xa assay. However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase of TFPI that was 2-fold higher than the baseline level, with a steady state achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to basal level. This pattern was not coincident with the clearance of DF and at 40 minutes, the concentration of DF was still one third of the levels at 5 minutes (25.4 ± 4.04 μg/mL). Both of the LMWHs induced a similar TFPI peak level at 5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the initial levels, At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity than UFH, which was detectable even at 80 minutes. The current study demonstrated that one of the mechanisms of the antithrombotic activity of DF is mediated via TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin III binding fragments. Thus, polyanionic electrolytes are capable of releasing TFPI irrespective of their antithrombin III effect.
Plasma Levels of Total Plasminogen Activator Inhibitor-I (PAI-I) and tPA/PAI-1 Complex in Patients With Disseminated Intravascular Coagulation and Thrombotic Thrombocytopenic Purpura
Authors: Watanabe Rika , Wada Hideo , Miura Youichi , Murata Youichi , Watanabe Yasuyuki , Sakakura Miho , Okugawa Yoshinaga , Nakasaki Takahiro , Mod Yositaka , Nishikawa Masakatsu , Gabazza Esteban C. , Shiku Hiroshi , Nobori Tsutomu
Published: November 2007

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure, The plasma levels of total PAI-I and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-1, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.
Factor V Leiden, Prothrombin Gene G20210A Variant, and Methylenetetrahydrofolate Reductase C677T Genotype in Young Adults With Ischemic Stroke
Authors: Lopaciuk Stanislaw , Bykowska Ksenia , Kwiecinski Hubert , Mickielewicz Anatol , Czlcankawska Anna , Mendel Tadeusz , Kuczynska-Zardzewialy Arletta , Szelagowska Dorota , Windyga Jerzy , Schröder Winnie , Herrmann Falko H. , Jedrzejowska Hanna
Published: November 2007

Ischemic stroke in young adults is a well-known disease, but despite extensive clinical and laboratory investigations, its etiology remains unclear in approximately half of the cases. We examined the prevalence of factor V Leiden, the prothrombin G20210A genotype, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in 100 patients (51 males and 49 females) who survived an ischemic stroke without a cardiac embolic source at an age ≤45 years, and in 238 healthy control subjects from the same geographic area. The patients were selected for study only if the diagnosis of stroke was documented by computed tomography scan or nuclear magnetic resonance (NMR) of the brain, or both. Heterozygosity for the FV Leiden mutation was found in 3 patients (3.0%) and in 10 control subjects (4.2%). Two patients (2.0%) and five control subjects (2.1%) were heterozygous for the prothrombin G20210A mutation. The frequencies of the MTHFR 677TT, CT, and CC genotypes in the patient group were 12%, 37%, and 51%, respectively, and were not significantly different from those in control subjects (11%, 40%, and 49%, respectively). In conclusion, our results indicate that FV Leiden mutation, prothrombin G20210A genotype, and homozygosity for the C677T mutation in the MTHFR gene are not associated with an increased risk for ischemic stroke in young adults.
A Technique for von Willebrand Multimer Analysis Applicable to the Clinical Laboratory
Authors: Coon Michael R. , Bayer William L.
Published: November 2007

In type I von Willebrand disease, the whole series of von Willebrand factor multimers is present in plasma. However, in type II von Willebrand disease qual itative defects of the von Willebrand factor proteins exist. Using a novel semidry horizontal gel electrophoresis ap paratus combined with a discontinuous buffer system, high-resolution analysis of von Willebrand factor multi meric composition is possible. When applied in clinical practice, this technique allows for easy discrimination be tween type I and type II defects.
Characterization of Platelet Gamma Glutamyltransferase and Its Alteration in Cases of Atherosclerosis
Authors: Yardimci Turay , Yaman Azize , Ulutin Orhan
Published: November 2007

Among the various functional and biochemical alterations in the platelets of cases of atherosclerosis, the membrane alterations occupy an important place. The platelet intrinsic membrane protein gamma glutamyltransferase (GGT), which is involved in glutathione metabolism, has shown decreased activity in cases of atherosclerosis. To add new insights into the pathogenesis of atherosclerosis, GGT is characterized and correlated with other alterations. Triton X-100 solubilized membrane fractions of frozen and thawed platelets of atherosclerotic and normal subjects had 18.66 ± 2.86 mU/109 platelets and 35.67 ± 3.01 mU/109 platelets, respectively. The Km values were the same, 2.08 mmol/L for gamma glutamyl- p-nitroanilide and 5.87 mmol/L for glycylglycine. The Vmax values were reduced from 100 mU/109 platelets to 41.66 mU/109 platelets for gamma glutamyl- p-nitroanilide and from 45.45 mU/109 platelets to 38.46 mU/109 platelets for glycylglycine. Optimum pH of GGT activity was 8.2, and optimum temperature was 37°C. It had thermal stability with a 64% relative activity at 36°C for 30 min. Serine against borate was detected as the competitive inhibitor and bromcresol green as the noncompetitive inhibitor. In vivo administration of the antithrombotic drug defibrotide increased the platelet GGT levels to those of normals, from 14.72 ± 7.27 mU/109 platelets to 31.80 ± 12.21 mU/109 platelets in 2 hs. Cholesterol, high-density lipoprotein cholesterol in the membrane fractions, and platelet glutathione levels were unaltered. The lipid per-oxidation (membrane malondialdehyde) level was increased, and glucose and histidine active transport systems were impaired in atherosclerotics. All of these changes are discussed in relation to GGT. Key Words: Human platelets—Atherosclerosis—Gamma glutamyltransferase—Gamma glutamyl transpeptidase— Defibrotide—Biological membranes.
Fresh-Frozen Plasma: The Lack of Need for Surgical Hemostasis in a Plasma-Exchanged Patient
Authors: Bayer William L.
Published: November 2007

Three consecutive daily plasma volume plasma exchanges were done using no coagulation factor-containing materials on a patient who then underwent thymectomy without any hemostatic problems immediately after the third exchange. Key Words: Plasma exchange-Coagulation factor-Hemostasis.