bluuebunny/crossref_metadata_2025 huggingface dataset:
Calculating unbiased tree-ring indices for the study of climatic and environmental change
Authors: Cook Edward R. , Peters Kenneth
Published: November 2007

In dendroclimatology, tree-ring indices are traditionally calculated as part of the tree-ring chronology development process. This is accomplished by fitting a growth curve to the ring-width series and using it as a series of expectations for more or less well specified null conditions (uniform climate perhaps) of annual radial growth. The ratio of the actual ring widths to these expectations produces a set of dimensionless indices that can be averaged arithmetically with cross-dated indices from other trees into a mean chronology suitable for studies of climatic and environmental change. We show that tree-ring indices calculated in this manner can be systematically biased. The shape of this bias is defined by the reciprocal of the growth curve used to calculate the indices, and its magnitude depends on the proximity of the growth curve to the time axis and its intercept. The underlying cause, however, is lack of fit. To avoid this bias, residuals from the growth curve, rather than ratios, can be computed. If this is done, in conjunction with appropriate transformations to stabilize the variance, the resulting tree-ring chronology will not be biased in the way that ratios can be. This bias problem is demonstrated in an annual tree-ring chronology of bristlecone pine from Campito Mountain, which has been used previously in global change studies. We show that persistent growth increase since AD 1900 in that series is over-estimated by 23.6% on average when ratios are used instead of residuals, depending on how the ring widths are transformed. Such bias in ratios is not always serious, as it depends on the joint behaviour of the growth curve and data, particularly near the ends of the data interval. Consequently, ratios can still be used safely in many situations. However, to avoid the possibility of ratio bias problems, we recommend that variance-stabilized residuals be used.
Holocene vegetation dynamics of the southeast Kola Peninsula, Russia
Authors: Kremenetski Constantin V. , Patyk-Kara Natalia G.
Published: November 2007

Two lakes on the southeast Kola Peninsula were investigated by pollen analysis and radiocarbon dating. At c. 11 000-10 000 BP some areas in the southeast of the Kola Peninsula became ice free and sedimen tation in the lakes began. Forest tundra with Betula grew in the region at c. 10 000 BP. The maximum spread of birch forests occurred between 9000 and 8000 BP. Pinus sylvestris expanded from 9000 BP, when the birch- tree cover became more dense. Alnus incana expanded from c. 7500 BP as the area of pine forest increased and the birch forest area reduced. At 7000 BP, Picea obovata expanded. The pine forest and total forested area was probably maximal between 6500 and 5500 BP. Paludification of the area occurred c. 6500 BP. Climatic deterioration after 4500 BP led to the reduction of the area of pine forest and peat bogs expanded, especially during the last 1000 years. During the last 2500-2000 years the structure of the modern vegetation developed.
Age and nature of paraglacial debris cones along the margins of the San Rafael Glacier, Chilean Patagonia
Authors: Harrison Stephan , Winchester Vanessa
Published: November 2007

This study employs sedimentological indices and lichenometric dating on the lichen species Plac opsis patagonica to investigate the nature and age of debris cones which have accumulated at the margins of the downwasting San Rafael Glacier in Chilean Patagonia. These cones appear to have accumulated by the resedimentation of glacigenic deposits by debris flows, with debris movement starting in the early 1980s. Cone activity follows a pattern of intense initial activity and sediment mobilisation followed by increased stability and colonization by vegetation. Three of the four cones had stabilized within 15 years of sediment movement initiation. These features may be seen as being conditioned by glacial activity with second order controls provided by the local climate and sediment supply. The cones have accumulated in a 'paraglacial' environment.
Statistical methods in diagnosis
Authors: Hand DJ
Published: November 2007

Motivations are presented for exploring formal statistical methods for use in medical diagnosis and the advantages and disadvantages are discussed. A brief review is presented of classical linear discriminant analysis, quadratic discriminant analysis, logistic regression, nearest neighbour and kernel methods, recursive partitioning methods, the independence model, regularized discriminant analysis, structured conditional probability distributions, methods for categorical data, and other methods. Criteria on which a choice might be made are presented and methods for assessing diagnostic performance are outlined. Particular applications of screening and chromosome analysis are used as illustrations and available software is described.
Measurement of reliability for categorical data in medical research
Authors: Kraemer Helena Chmura
Published: November 2007

The problem of measuring reliability of categorical measurements, particularly diagnostic categorizations, is addressed. The approach is based on classical measurement theory and requires interpretability of the reliability coefficients in terms of loss of precision in estimation or power in statistical tests. A general model is proposed, leading to definition of reliability indices. Design and estimation approaches are discussed. Issues and approaches found in the research literature that either lead to confusing or misleading results are presented. The signs and symptoms of unreliable diagnoses are identified, and strategies for improving the reliability of such diagnoses are discussed.
Review papers : Longitudinal studies with continuous responses
Authors: Laird Nan M , Donnelly Christl , Ware James H
Published: November 2007

The analysis of serial measurements obtained in longitudinal studies plays an increasingly prominent role in applied research. The last few years have seen the development of many new techniques for carrying out analyses, including computer software. These methods can be used in a variety of standard problems, including repeated measures and cross-over designs, as well as growth curve analyses. We review these new methods, their application, and available computer packages. Data from a longitudinal study of lung function is used to illustrate the methods.
Analysing the temporal effects of age, period and cohort
Authors: Holford Theodore R
Published: November 2007

Longitudinal trends can be analysed in terms of the effect of age, birth cohort or year of diagnosis. All three temporal effects are thought to be useful by epidemiologists, but they are not identifiable when assessed simultaneously. Partitioning the effects in terms of linear and curvature components is one approach to understanding the problem and finding a reasonable summary of trends. Other solutions can be expressed in terms of these components, and they can also be used to understand both subgroup and temporal interactions. One approach that may offer a way of understanding the effect of risk factor trends on population based rates is to use models that incorporate an effect due to the risk factors. These methods are discussed using lung cancer incidence and mortality to illustrate the underlying concepts.
Review papers : Statistical models for estimating prevalence and incidence of parasitic diseases
Authors: de Vlas SJ , Nagelkerke Njd , Habbema Jdf , van Oortmarssen GJ
Published: November 2007

The estimation of prevalence and incidence of parasitic infections is considered. As the detectability of such infections is not 100% and may furthermore depend on their intensity, statistical methods are often required to arrive at meaningful results. It appears to be essential to distinguish between parasities that multiply within the (human) host and those that do not. An overview of some models discussed in the literature is presented. These models can indeed be used in assessing detectability of infection, and they indicate that observations may lead to considerable misinterpretation of 'true' prevalences and incidences.
The logic and role of meta-analysis in clinical research
Authors: Sandoz M Oakes
Published: November 2007

The term meta-analysis refers to the quantitative combination of data from independent trials. Where the result of such combination is a descriptive summary of the weight of the available evidence, the exercise is of undoubted value. Attempts to apply inferential methods, however, are subject to considerable methodolo gical and logical difficulties. The selection and quality of the trials included, population bias, and the specification of the population to which inference may properly be made are problems to which no satisfactory solutions have been proposed. Insightful quantitative description ought not to differ materially from inferential conclusions; where discrepancies exist the inferential techniques should be regarded with extreme caution.
Metropolis sampling in pedigree analysis
Authors: Sobel E. , Lange K.
Published: November 2007

This paper reviews and develops the applications of Markov chain Monte Carlo methods in pedigree analysis, with particular stress on the Metropolis algorithm. In likelihood based genetic analyses, standard deterministic algorithms often fail because of the computational complexity of the observed pedigree data under a proposed genetic model. The new Monte Carlo methods permit approximate maximum likelihood estimation in the presence of such complexity. Monte Carlo implementation of the EM algorithm is the key to successful maximum likelihood analysis. Gibbs sampling and the Metropolis algorithm are alternative ways of defining Markov chains for performing the E step of the EM algorithm. Two applications illustrate the power and simplicity of the Metropolis algorithm. One of these applications involves a discrete model for variance component analysis of quantitative traits; the other application involves a Monte Carlo version of location scores for multipoint linkage analysis.
Some computational and statistical tools for paired comparisons of digital images
Authors: Lange Nicholas
Published: November 2007

This article is a case-based review that introduces applied statisticians to a number of issues and methods that arise in clinical studies with paired digital images as outcomes. Single photon emission computed tomography (SPECT) is the imaging modality used in two examples. The first is a physical simulation of relevant clinical features of SPECT images using a customized head phantom scanned under different experimental conditions. The objective is to demonstrate and compare several current methods for image registration, i.e., image superimposition in some optimal manner to obtain a common frame of reference within which to make pixel-by-pixel comparisons. Image registration together with image normalization to correct for spurious differences in background activity levels enable quantification of differences in paired images. The physical simulation assesses quantification accuracy. The second example involves two SPECT images of the same brain tumour patient taken about two months apart. The objective here is to demonstrate several tools from morphological image analysis for image segmentation, i.e., separation of 'figure' and 'ground', and simple image regression to detect patterns of differences in time, again after registration and normalization. The clinical context of both examples helps to keep the review in practical focus and is a useful starting point for descriptions of many standard tools in applied medical image analysis. References to relevant literature are provided for readers wanting to study particular subjects in depth. As medical image analysis becomes more sophisticated, more cost-conscious and scrutinized more intensively, proper attention to the computational and statistical bases for practical conclusions become even more crucial.
Statistical methods in neuroimaging with particular application to emission tomography
Authors: McColl JH , Holmes AP , Ford I.
Published: November 2007

We review statistical methods being applied in four key areas connected with PET and SPECT neuroimaging: (i) image reconstruction (briefly); (ii) tracer-kinetic, or compartmental, modelling; (iii) inference from region-of-interest data; (iv) inference at the pixel or voxel level. Under the last heading, we pay particular attention to the analysis of data from serial scans. We conclude by identifying some topics for future statistical research.
The analysis of binary and categorical data from crossover trials
Authors: Kenward MG , Jones B.
Published: November 2007

A review is presented of methods for the analysis of discrete data from crossover trials. The definition and interpretation of the model for the data is used as a central theme. Distinctions are drawn between different types of model, particularly marginal and subject specific. It is seen how much recent methodology for analysing correlated categorical data can be applied successfully to the crossover setting. The current accessibility of each method is considered and the different approaches are illustrated and compared using two examples.
Analysing geographically-related disease data
Authors: Cliff AD
Published: November 2007

This issue of Statistical Methods in Medical Research is devoted to four papers that show how we may identify and model the geographical factors that not only shape disease distributions in time and space but also, in the case of transmissible diseases, affect the spread of disease from one geographical area to another. The purpose of this editorial introduction is to outline some of the problems that arise when studying geographical distributions of disease, and so provide a general framework within which the various specialist papers may be placed.
Spatial heterogeneity, nonlinear dynamics and chaos in infectious diseases
Authors: Grenfell BT , Kleczkowski A. , Gilligan CA , Bolker BM
Published: November 2007

There is currently considerable interest in the role of nonlinear phenomena in the population dynamics of infectious diseases. Childhood diseases such as measles are particularly well documented dynamically, and have recently been the subject of analyses (of both models and notification data) to establish whether the pattern of epidemics is chaotic. Though the spatial dynamics of measles have also been extensively studied, spatial and nonlinear dynamics have only recently been brought together. The present review concentrates mainly on describing this synthesis. We begin with a general review of the nonlinear dynamics of measles models, in a spatially homogeneous environment. Simple compartmental models (specifically the SEIR model) can behave chaotically, under the influence of strong seasonal 'forcing' of infection rate associated with patterns of schooling. However, adding observed heterogeneities such as age structure can simplify the deterministic dynamics back to limit cycles. By contrast all current strongly seasonally forced stochastic models show large amplitude irregular fluctuations, with many more 'fadeouts' of infection that is observed in real communities of similar size. This indicates that (social and/ or geographical) spatial heterogeneity is needed in the models. We review the exploration of this problem with nonlinear spatiotemporal models. The few studies to date indicate that spatial heterogeneity can help to increase the realism of models. However, a review of nonlinear analyses of spatially subdivided measles data show that more refinements of the models (particularly in representing the impact of human demo graphic changes on infection dynamics) are required. We conclude with a discussion of the implication of these results for the dynamics of infectious diseases in general and, in particular, the possibilities of cross fertilization between human disease epidemiology and the study of plant and animal diseases.
Sample size determination in epidemiologic studies
Authors: Wickramaratne Priya J.
Published: November 2007

Sample size determination is an important issue in epidemiologic studies. Standard methods for determining sample size in cohort and case-control studies have generally been restricted to dichotomous disease and exposure variables and discrete confounding variables, and are based on simplifying assumptions that could often be unrealistic. Methods for sample size determination that make less restrictive and more realistic assumptions regarding the distribution of disease, exposure and confounding variables and which more closely parallel the analyses that are performed on the data, after the study has been conducted, have been developed in recent years. In this article some recent developments in the methodology for sample size determination in epidemiologic studies are reviewed.
An introduction to finite mixture distributions
Authors: Everitt BS
Published: November 2007

Finite mixture densities can be used to model data from populations known or suspected to contain a number of separate subpopulations. Most commonly used are mixture densities with Gaussian (univariate or multivariate) components, but mixtures with other types of component are also increas ingly used to model, for example, survival times. This paper gives a general introduction to the topic which should help when considering the other more specialized papers in this issue.
Handling missing data in survey research
Authors: Brick JM , Kalton G.
Published: November 2007

Missing data occur in survey research because an element in the target population is not included on the survey's sampling frame (noncoverage), because a sampled element does not participate in the survey (total nonresponse) and because a responding sampled element fails to provide acceptable responses to one or more of the survey items (item nonresponse). A variety of methods have been developed to attempt to compensate for missing survey data in a general purpose way that enables the survey's data file to be analysed without regard for the missing data. Weighting adjustments are often used to compensate for noncoverage and total nonresponse. Imputation methods that assign values for missing responses are used to compensate for item nonresponses. This paper describes the various weighting and imputation methods that have been developed, and discusses their benefits and limitations.
Modelling the sampling design in the analysis of health surveys
Authors: Graubard Barry I , Korn Edward L
Published: November 2007

Health surveys typically have stratified multistage clustered designs in which individuals are sampled with differing probabilities. The sampling design is taken into account in a classical survey analysis by using sample-weighted estimators and variance estimators calculated at the primary-sampling-unit level. In this paper we investigate the possibility of modelling the sampling design using fixed and random effects to redefine target parameters, improve estimators of standard target parameters and improve standard variance estimators. References in which this type of additional modelling was used in health surveys are given. The problem of estimating population variance components is discussed in some detail, with an application involving estimation of between- and within-family variance components in the Hispanic Health and Nutrition Examination Survey.
Markov chain Monte Carlo methods in biostatistics
Authors: Gelman Andrew , Rubin Donald B
Published: November 2007

Appropriate models in biostatistics are often quite complicated. Such models are typically most easily fit using Bayesian methods, which can often be implemented using simulation techniques. Markov chain Monte Carlo (MCMC) methods are an important set of tools for such simulations. We give an overview and references of this rapidly emerging technology along with a relatively simple example. MCMC techniques can be viewed as extensions of iterative maximization techniques, but with random jumps rather than maximizations at each step. Special care is needed when implementing iterative maximization procedures rather than closed-form methods, and even more care is needed with iterative simulation procedures: it is substantially more difficult to monitor convergence to a distribution than to a point. The most reliable implementations of MCMC build upon results from simpler models fit using combinations of maximization algorithms and noniterative simulations, so that the user has a rough idea of the location and scale of the posterior distribution of the quantities of interest under the more complicated model. These concerns with implementation, however, should not deter the biostatistician from using MCMC methods, but rather help to ensure wise use of these powerful techniques.
The Association of Benign and Malignant Ovarian Adenofibromas with Breast Cancer and Thyroid Disorders
Authors: Silva Elvio G. , Tornos Carmen , Malpica Anais , Deavers Michael T. , Tortolero-Luna Guillermo , Gershenson David M.
Published: November 2007

An unexpected association with breast cancer and thyroid disorders was found dur ing a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papil lary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibro mas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thy roid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast can cer and 16% of each one of these groups had thyroid disorders. This unexpected as sociation found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits. Int J Surg Pathol 10(1):33-39, 2002
Clear Cell Sarcoma of Tendons and Aponeuroses
Authors: Montgomery Elizabeth A. , Meis Jeanne M. , Ramos Augusto G. , Frisman Dennis M. , Martz Karen L.
Published: November 2007

Fifty-eight previously unreported cases of clear cell sarcoma of tendons and apo neuroses occurring in 29 males and 29 females with a median age of 31 years are presented. The distal extremities were most frequently involved (58%), followed by the limbs and limb girdles (33%), and trunk (9%). Median tumor size was 2.5 cm (range, 0.6-9 cm). Kaplan-Meier estimates revealed a 5-year survival rate of 63%. Eleven of 43 patients (26%) had local recurrences at a median interval of 33 months. Metastases occurred in 20 of 45 cases (44%) at a median interval of 26 months; 19 of 20 patients with metastases died of the disease. The most common metastatic site was the lungs (11 cases), followed by bone (9 cases), and lymph nodes (8 cases). Clear cell sarcoma had a stereotypic morphology consisting of packeted arrangements of uniform, round to fusiform cells with eosinophilic to clear glycogen-rich cytoplasm, and prominent nucleoli, as well as multinucleated tumor cells with a wreath-like arrangement of nuclei. S100 protein was detected in all 44 cases studied, vimentin in 36, and HMB45 stained 36. Twenty-six cases were studied with antibodies directed against proliferating cell nuclear antigen. Neither the intensity of proliferating cell nuclear antigen staining, percentage of positive cells, nor the combined score of these two variables corresponded with mitotic rate or survival. Increasing size (as a continu ous variable) and necrosis were found to be independent adverse prognostic factors by multivariate analysis. Int J Surg Pathol 1 (2):89-100, 1993
Waldenström's Macroglobulinemia Associated With Generalized AA-Amyloidosis
Authors: Shah Ifat A. , Netto Dymphna , Ashfaq Raheela , Krieger Christine
Published: November 2007

The authors present a case of Waldenström's macroglobulinemia (WM) associated with generalized amyloidosis of amyloid-A type. A 77-year-old man with a 25-year history of degenerative joint disease and a 13-year history of WM died of multisystemic failure. At autopsy, generalized and severe amyloid deposits were detected. Special conventional stains and immunohistochemical examination revealed amyloid-A de posits, which are extinguishingly rare in WM. This is probably related to the disease being chronic, which results in excessive production of precursor protein. The detection of amyloid-A type fibrils was possible only through the application of the immunohis tochemical procedure. The authors emphasize using the immunohistochemical typing of amyloid deposits for the purpose of classification, therapy, and prognosis. Int J Surg Pathol 1 (2):123-128, 1993
Pathologic Findings in Ribs Removed at the Time of Radical Nephrectomy for Renal Cell Carcinoma
Authors: DeLong William H. , Grignon David J.
Published: November 2007

Departmental policy to forego microscopic examination on some specimens can result from constraints of time, departmental budgets, and negligible yield of significant addi tional information. With this in mind, the value of microscopic examination of grossly normal ribs removed at the time of radical nephrectomy for renal cell carcinoma was evaluated. From 1926 to 1988, 391 radical nephrectomies were performed for renal cell carcinoma. Rib sections were not present with any cases prior to 1969. In the 256 cases dating from 1969, 94 (36.7%) had a section of rib available for review. Significant pathologic findings were present in five cases (5.3%) and consisted of metastatic renal cell carcinoma (3 cases), multiple myeloma (1 case), and a myeloproliferative disorder (1 case). On chart review it became apparent that in only two cases was the abnormal ity detected clinically expected. In all cases the ribs had been described as being grossly normal, and clinical information provided did not suggest an abnormality. Int J Surg Pathol 1 (3):177-180, 1994
Alpha-fetoprotein-producing Collecting Duct Carcinoma of the Kidney
Authors: Davies J.H. , Fisher C.
Published: November 2007

A case of collecting duct carcinoma of the kidney, with bone marrow metastases, in which there was production of alpha-fetoprotein is described. The tumor showed the typical light microscopic and immunohistochemical characteristics of collecting duct carcinoma. Alpha-fetoprotein was demonstrated immunohistochemically within tumor cells in both the primary and metastatic lesions. The clinical course was aggres sive ; the patient died within a few months of diagnosis. Int J Surg Pathol 1(4):239-244, 1994
Malignant Melanoma Metastatic to Gastrointestinal Tract
Authors: Adair Carol , Ro Jae Y. , Sahin Aysegul A. , El-Naggar Adel K. , Ordónēz Nelson G. , Ayala Alberto G.
Published: November 2007

Malignant melanomas metastatic to the gastrointestinal (GI) tract show a wide range of histologic features, many of which can mimic primary GI malignancies. In this study, we evaluated the clinicopathologic features of 41 cases of malignant melanoma involving the GI tract. Thirty-two patients were men and nine were women; the average patient age was 51.7 years (range, 26-74 years). Twenty-eight patients had a history of malignant melanoma. Thirteen patients, however, did not have a prior history of malignant melanoma; on the basis of the clinical presentation and the behav ior of the GI lesions of these cases, they were presumed to be metastases from regressed or clinically undetected melanomas. The small intestine was the most common site. 12 patients had involvement of multiple GI sites. Clinical diagnoses at presentation included GI bleeding of unknown etiology, small bowel obstruction, rectal carcinoma, gastric ulcer, lymphoma, and cholelithiasis. The three major histologic patterns that mimicked primary GI neoplasms were carcinoma-like, carcinoid-like, and stromal sarcoma-like. The average survival times were 61.9 months after the diagnosis of primary melanoma and 14.4 months from the time of GI tract involvement. Site of malignant melanoma in the GI tract, histologic pattern, and history of a primary lesion outside GI tract did not show any prognostic significance. Although metastatic malig nant melanomas of the GI tract are rare, they should be considered in the differential diagnosis of primary GI tumors. Int J Surg Pathol 2(1):3-10, 1994
Invited Review : The Origin of Mediastinal Germ Cell Tumors in Men
Authors: Rosai Juan , Parkash Vinita , Reuter Victor E.
Published: November 2007

Mediastinal germ-cell tumors in men are generally thought to be primary at this site and to arise from extragonadal germ cells located in the thymus gland. Recent cytoge netic data have cast some doubt on this hypothesis and revived the alternative possibil ity of a testicular origin for these lesions. However, a review of the available evidence suggests that a primary mediastinal origin still remains the most likely explanation. The suggestion is made that the difficulties in identifying normal germ cells in the thymus gland may be due to their evolving into some type of somatic cell such as a myoid cell. Int J Surg Pathol 2(1):73-78, 1994
Smooth Muscle and Nerve Sheath Tumors of the Breast
Authors: Jones Mirka W. , Norris Henry J. , Wargotz Eric S.
Published: November 2007

The clinical and pathological features of 22 smooth muscle tumors and 23 nerve sheath tumors of the breast are presented. The smooth muscle tumors included 18 leiomyomas and 4 leiomyosarcomas. Two types were found: those superficial in the nipple or in the skin overlying the breast and those located within the breast parenchyma. Superficial leiomyomas were small and had ill-defined, infiltrating margins. Leiomyomas located within the breast were circumscribed and larger than the superficial ones. Mitotic activity did not exceed 1 mitotic figure per 10 high-power field and only 2 of the 18 showed 1 + and 2 + atypia. None recurred after local excision. The four leiomyosarco mas had 2 + and 3 + nuclear atypia and mitotic activity ranging from 3 to 28 mitotic figures per 10 high-power field. Recurrences occurred in two, but none metastasized. Nerve sheath tumors included 5 neurilemomas, 15 neurofibromas and 3 malignant schwannomas. All neurilemomas were encapsulated and showed no mitotic activity or cytologic atypia. Of the 15 neurofibromas, 6 were encapsulated, 4 had circumscribed margins with focal infiltration, and 2 had infiltrative margins. Focal cytologic atypia was seen in 4. All 3 malignant shwannomas had infiltrative margins, nuclear atypia, and noticeable, often abnormal, mitotic figures. Two of the 11 patients with neurofi broma had von Recklinghausen's disease and developed recurrences. None of the 3 patients with malignant schwannoma developed a recurrence. Int J Surg Pathol 2(2): 85-92, 1994
Spontaneous Isolated Coronary Artery Dissection With Myocardial Infarction Treated With Heart Transplantation
Authors: Fernando Val-Bernal J. , Alvarez-Cañas Concepción , Vega José L. , Olalla Juan J.
Published: November 2007

A case of spontaneous isolated dissecting aneurysm of the left main and anterior descending branches of the left coronary artery in a 42-year-old woman is described. The patient survived the dissection, and resultant myocardial infarct with cardiogenic shock was treated with an orthotopic cardiac transplant. She died from a bilateral pneumonia caused by Candida tropicalis 3 weeks later. Spontaneous isolated dissection of a coronary artery is rare and usually described in necropsy studies. To our knowl edge, this is the third report of an isolated primary dissecting aneurysm of a coronary artery treated by an orthotopic cardiac allograft. It is likely that surgical pathologists will encounter this entity more frequently in the future due to involvement in trans plantation teams. Int J Surg Pathol 2(3):227-230, 1995
Hemangiopericytoma of the Thyroid
Authors: Ostrowski Mary L. , Cartwright Joiner , Maldonado Joyce E. , Mody Dina , LiVolsi Virginia A.
Published: November 2007

A 52-year-old woman presented with a painless right thyroid mass of 4 months dura tion, with a recent increase in size in the last few weeks. The neoplasm was character ized by bland spindle cells with a low mitotic rate arranged around vascular elements of variable shape and caliber. Multiple immunohistochemical stains failed to show evi dence of epithelial, neuroendocrine, or specific mesenchymal differentiation. Electron microscopic studies revealed spindle cells with micropinocytotic vesicles, surrounded by variable but sometimes abundant basement lamina-like material. To the authors' knowledge, this is the first report of a typical hemangiopericytoma of the thyroid gland. This lesion must be distinguished from epithelial and neuroendocrine tumors with spindle cells and from other mesenchymal neoplasms that may occur in the thyroid. Int J Surg Pathol 2(4):311-318, 1995
Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease) Involving the Ovary
Authors: Pelizzari Giovanni , Bettini Lamberto , Sleiman Intissar , Spandrio Sara , Balestrieri Gian Paolo , Facchetti Fabio
Published: November 2007

A 66-year-old woman affected by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is described. She presented with renal and ovarian masses. Percutaneous fine-needle aspiration was performed. Histologic specimens showed numer ous histiocytes that contained lymphocytes or plasma cells in their cytoplasm. Strong reac tivity for histiocyte-associated antigens was diffusely present in these cells. She was treated with prednisone and cyclophosphamide; a partial remission was obtained. Int J Surg Pathol 2(4) :329-332, 1995
Efficacy of Atorvastatin Compared With Simvastatin in Patients With Hypercholesterolemia
Authors: Farnier Michel , Portal Jean-Jacques , Maigret Pascal
Published: November 2007

Background: Atorvastatin, a new enantiomerically pure synthetic statin, has shown a marked low-density lipoprotein (LDL) cholesterol reduction at doses ranging from 10 to 80 mg/d. This trial was designed to compare the efficacy of atorvastatin 10 mg with simvastatin 10 mg and 20 mg, the latter dose being commonly used in some countries.

Methods and Results: A parallel group, randomized, PROBE, multicenter study was con ducted to compare the efficacy of 10 mg/d atorvastatin with that of 10 mg/d simvastatin and 20 mg/d simvastatin in patients with primary hypercholesterolemia. After a 6-week diet- placebo lead-in period, 272 patients with LDL cholesterol ≥ 160 mg/dL and triglycerides ≤ 300 mg/dL were randomized to 6 weeks of treatment with atorvastatin 10 mg (109 patients), simvastatin 20 mg (109 patients), or simvastatin 10 mg (54 patients). In the main analysis, which tested the equivalence of atorvastatin 10 mg and simvastatin 20 mg, the mean percent change in LDL cholesterol for atorvastatin 10 mg (-37.0%) was greater than and not equiva lent to simvastatin 20 mg (-33.8%). In the secondary analysis, which compared the efficacy of atorvastatin 10 mg with that of simvastatin 10 mg, the mean decrease in LDL cholesterol was significantly greater (P < .001) for atorvastatin 10 mg than for simvastatin 10 mg (-37.0% vs. -28.9%). The two drugs were well tolerated, with an incidence of clinical and biochemical side effects similar among the 3 treatment groups.

Conclusion: In primary hypercholesterolemia, atorvastatin 10 mg was more effective and nonequivalent to simvastatin 20 mg and significantly more effective than simvastatin 10 mg for reducing LDL cholesterol levels.
A New Model of Ventricular Plication: A Suturing Technique to Decrease Left Ventricular Dimensions, Improve Contractility, and Attenuate Ventricular Remodeling After Myocardial Infarction in the Rat Heart
Authors: Schwarz Ernst R. , Speakman Mark T. , Kloner Robert A.
Published: November 2007

Background: The Batista procedure (cardioreduction) is a surgical technique in patients with dilated cardiomyopathy that results in improvement of ventricular function. The purpose of this study was to test a new suturing technique without resection for cardioreduction of myocardial infarct scars in rats.

Methods and Results: Myocardial infarction (MI) was induced by occluding the left coronary artery 4 weeks before enrollment. Animals then were randomized to a control (n = 11) or treatment group (n = 11). A pursestring suture was placed within the border zones of the infarcted area and was either tightened (treated) or not (controls). Echocardiography was used to measure left ventricular diameters before, 1 hour, and 6 to 7 weeks after plication. Acutely after plication, end-diastolic length (EDL) decreased from 0.70 ± 0.03 cm to 0.53 ± 0.02 cm, P < .001; end-systolic length (ESL) decreased from 0.51 ± 0.03 cm to 0.23 ± 0.02 cm, P < .001; and fractional shortening (FS) increased from 27.6 ± 1.5% to 57.6 ± 2.3%, P < .001, whereas controls were unchanged. In control rats EDL increased from baseline at 0.73 ± 0.02 cm to 0.82 ± 0.04 cm at 6 weeks postsurgery, P < .05; ESL increased from 0.54 ± 0.02 cm to 0.66 ± 0.04 cm, P < .005; and FS decreased from 26.9 ± 1.1% to 19.2 ± 1.2% at 6 weeks, P < .05. In contrast, at 6 weeks in plicated animals, EDL was significantly less than controls at 0.64 ± 0.02 cm, P < .005; ESL was significantly less than controls at 0.39 ± 0.03 cm, P < .005, and FS was significantly better than controls at 40.5 ± 2.2%, P < .005.

Conclusion: The progressive LV enlargement between 4 and 10 weeks after MI reflects late ventricular remodeling. Plication by suturing infarcted tissue acutely decreases diameters and improves function. At 6 weeks, function remains improved over untreated animals.
Electrophysiologic Effects of Beta-blocking Agent, Tilisolol; on Isolated Guinea Pig Ventricular Myocytes
Authors: Sakai Fumio , Kawano Seiko , Hiraoka Masayasu
Published: November 2007

Background: Electrophysiologic effects of a beta-blocking agent, tilisolol, were studied with isolated guinea pig ventricular myocytes using the whole cell patch clamp technique.

Methods and Results:. Tilisolol at 10 μM or higher concentrations prolonged action poten tial duration (APD) at 90% repolarization (APD90) and at 100 μM or higher concentrations shortened APD at 20% repolarization (APD20) without changes in resting membrane poten tial. At 10 μM concentration tilisolol prolonged APD90 from 236.6 ± 55.3 ms in the control to 253.4 ± 52.4 ms (n = 16; P < .0 L), while APD20 was unaffected. At 100 μM tilisolol, APD20 was shortened from 143.6 ± 15.7 ms in the control to 133.7 ± 22.6 ms (n = 8; P < .05). Under voltage clamp, tilisolol decreased the delayed rectifier K+ current (IK), while the drug little affected the inward rectified K+ current (IKI). Applications of 10 μM and 100 μM tilisolol reduced the maximal conductance of IK by 35.7 ± 3.5% and 47.4 ± 3.5% of the control, respectively, without changes in voltage dependence (n = 10). Tilisolol at 100 μM decreased the L-type Ca2+, current (I Ca.L) by 22.0 ± 9.8% (n = 6) of the control, and the inactivation curve was shifted to a hyperpolarizing direction.

Conclusions: Tilisolol has a direct membrane action to depress IK and ICa.L, in addition to its beta-receptor blocking action.
Electrophysiology of Myocardial Cells in the Epicardial, Midmyocardial, and Endocardial Layers of the Ventricle
Authors: Lukas Anton
Published: November 2007

The recent discovery of multiple myocardial cell types in the ventricular wall of most species has prompted a reevaluation of several electrophysiologic and electrocardiographic findings. This review briefly presents the salient electrophysiologic features of myocardial cells in the epicardial, midmyocardial and endocardial regions of the ventricle. The epicardial action potential exhibits a prominent notch between phase I and phase 2 that results in a spike and dome configuration. The notch is smaller in midmyocardial cells and absent in endocardial cells. The action potential notch is due to the presence of a transient outward current (Ito), which diminishes in amplitude from the epicardial to endocardial surfaces. Midmyocardial or "M cells" exhibit electrophysiologic features intermediate between those of myocardial and conducting cells. M cells differ from epicardial and endocardial cells primarily in their response to slowing of the stimulation rate. These cells display an exaggerated prolongation of action potential duration at moderate to slow rates of stimulation. The atypical response in M cells reflects decreased levels of the delayed rectifier K+ current (IK) in this cell type. Another distinguishing feature of M cells is a greater rate of rise of the upstroke of phase 0 (dV/dt) compared to epicardial or endocardial cells. These electrophysiologic distinctions contribute to differences in the responsiveness of the various cell types to pharmacologic agents and disease. Also, the dispersion of repolarization created between epicardium and endocardium in the early phases of the action potential, and between M cells and other ven tricular layers during late repolarization, may explain the J wave and U wave of the electro cardiogram, respectively.
Urinary Nitrotyrosine Content as a Marker of Peroxynitrite-induced Tolerance to Organic Nitrates
Authors: Skatchkov M. , Larina L.L. , Larin A.A. , Fink N. , Bassenge E.
Published: November 2007

Background: Anti-ischemic therapy with nitrovasodilators as NO-donors is complicated by the induction of tolerance. When nitrovasodilators are metabolized to release NO there is a considerable coproduction of oxygen-derived radicals leading to a diminished cyclic GMP production and to impaired vasomotory responses. We analyzed in vivo the glyceroltrinitrate- induced generation of strong oxidative/nitrating compounds contributing to development of tolerance.

Methods and Results: In 16 patients we studied the urinary nitrotyrosine excretion during either (1) placebo control conditions, (2) 2-day nonintermittent transdermal nitroglycerin administration (0.4 mg/h), (3) 2-day nonintermittent glyceroltrinitrate administration (0.4 mg/h) along with a continuous infusion of vitamin C (55 μg/kg/min) as an antioxidant, or (4) with vitamin C but without glyceroltrinitrate (diminished urinary nitrotyrosine content of 34 ± 18 μg/day observed). Glyceroltrinitrate administration augmented urinary nitrotyrosine from 56 ± 24 (basal) to 186 ± 32 μg/day (glyceroltrinitrate tolerance). Coadministration of vitamin C caused complete elimination of tolerance and a decrease in urinary nitrotyrosine to 130 ± 28 μg/day. Glyceroltrinitrate-induced formation of oxidants was confirmed in vitro comparing glyceroltrinitrate-induced and peroxynitrite-induced tachyphylaxis in isolated perfused rabbit hearts and analyzing tolerance-induced inactivation of soluble guanylyl cyclase in cultured aortic smooth muscle cells.

Conclusions: Augmented urinary nitrotyrosine excretion during glyceroltrinitrate adminis tration reflects enhanced formation of peroxynitrite and of nitrotyrosine. Glyceroltrinitrate- induced tolerance is the result of oxidative stress and can be suppressed by additional antiox idant therapy aimed to prevent glyceroltrinitrate-induced formation and/or actions of peroxynitrite.
Alterations in β-Adrenoceptor Mechanisms in Hearts Perfused with Xanthine Plus Xanthine Oxidase
Authors: Persad Sujata , Takeda Satoshi , Dhalla Naranjan S.
Published: November 2007

Background: Although β-adrenoceptors and adenylyl cyclase are known to be affected upon exposing cardiac membranes to some oxyradical generating systems, the results are conflict ing. Furthermore, functional significance of alterations in the β-adrenoceptor-adenylyl cyclase system in terms of changes in the inotropic responses to catecholamines is not clear.

Methods and Results: The positive inotropic effect of isoproterenol was augmented on per fusing the isolated rat hearts with xanthine (X) plus xanthine oxidase (XO) for 5 minutes but was attenuated by perfusion for 15 minutes. The isoproterenol-stimulated adenylyl cyclase activity in cardiac membranes showed an increase at 10 minutes and a decrease at 30 minutes perfusion of hearts with X plus XO. The density of β-adrenoceptors in cardiac membranes was reduced after 10 minutes and 30 minutes of perfusion with X plus XO, whereas the affin ity of β-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although β-adrenoceptors were unaltered by 10 minutes of perfusion with X plus XO, their affinity was increased and density was decreased by 30 minutes of perfusion. The agonist competition curves using isoproterenol indicated an increase in the number of coupled recep tors in the high affinity state on 10 minutes of perfusion and an increase in the low affinity state of coupled receptor due to 30 minutes of perfusion with X plus XO. The basal as well as forskolin-, NaF- and Gpp(NH)p-stimulated adenylyl cyclase activities in cardiac membranes exhibited an increase after 10 minutes and decrease after 30 minutes of perfusion with X plus XO. Although the presence of superoxide dismutase plus catalase in the perfusion medium prevented most of the alterations due to X plus XO, it did not alter the increased affinity of the β-adrenoceptor upon perfusing hearts for 10 minutes with X plus XO.

Conclusions: The results in this study suggest the biphasic nature of the oxyradical-induced alterations in both the inotropic responses to catecholamines and the β-adrenoceptor-medi ated signal transduction mechanism in the heart.
Effects of Phentolamine on Responses to PAMP in the Hindquarters Vascular Bed of the Rat
Authors: Nossaman Bobby D. , Kaye Alan D. , Champion Hunter C. , Bin Kang  , Feng Chang J. , Kadowitz Philip J.
Published: November 2007

Background: Responses to proadrenomedullin NH2-terminal 20 peptide (PAMP), a novel hypotensive peptide formed from preproadrenomedullin, and the effects of inhibition of adrenergic vasomotor tone with the α-receptor antagonist, phentolamine, on responses to PAMP were investigated in the systemic and hindquarters vascular bed of the rat.

Methods and Results: Intravenous injections of PAMP decreased systemic arterial pressure and in the hindquarters vascular bed of the rat under conditions of controlled hindquarters blood flow, intra-arterial injections of PAMP decreased perfusion pressure in a dose-related manner. Following administration of the alpha receptor blocking agent, phentolamine, sys temic depressor and hindquarters vasodilator responses to PAMP were not significantly decreased, whereas phentolamine significantly decreased systemic and hindquarters pressor responses to norepinephrine. Phentolamine had no significant effect on vasodilator responses to bradykinin, albuterol, or to nitroglycerin.

Conelusions: The present data show that PAMP has significant systemic vasodepressor and vasodilator activity in the hindquarters vascular bed of the rat and suggest that vasodepressor and hindquarters vasodilator responses to PAMP are not dependent upon the presence of adrenergic vasomotor tone.