bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory of vibratory mobilization on nonwetting fluids entrapped in pore constrictions
Authors: Beresnev Igor A.
Published: November 2006

Quantitative dynamics of a nonwetting ganglion of residual oil entrapped in a pore constriction and subjected to vibrations of the pore wall can be approximated by the equation of motion of an oscillator moving under the effect of the external pressure gradient, inertial oscillatory force, and restoring capillary force. The solution of the equation provides the conditions under which the droplet experiences forced oscillations without being mobilized or is liberated from its entrapped configuration if the acceleration of the wall exceeds an unplugging value. This solution provides a quantitative tool for estimating the parameters of vibratory fields needed to liberate entrapped, nonwetting fluids. For typical pore sizes encountered in reservoir rock, wall accelerations must exceed at least several [Formula: see text] and even much higher levels to mobilize the droplets of oil; however, in the populations of ganglia entrapped in natural porous environments, many may reside very near their mobilization thresholds and may be mobilized by extremely low accelerations as well. For given acceleration, lower seismic frequencies are more efficient in liberating the ganglia.
A new method for determination of magnetization direction
Authors: Dannemiller Neal , Li Yaoguo
Published: November 2006

The characterization and interpretation of magnetic anomalies rely upon knowledge of the total magnetization direction. Magnetization is usually assumed to consist solely, or primarily, of induced magnetization. The presence of strong remanent magnetization can alter the direction significantly and consequently adversely affect the interpretation, leading to erroneous sizes or shapes of causative bodies. Therefore, it is imperative to have some understanding of the total magnetization direction. We propose a method based upon the correlation between two quantities in magnetic data interpretation: the vertical gradient and the total gradient of the reduced-to-pole (RTP) field. This method is tested on both synthetic and field data sets. The results show that the method is effective in a variety of situations, including those with two-dimensional and three-dimensional dipping bodies and a field example that has a large deviation between the inducing field direction and the total magnetization direction.
Seismic reflections of gas hydrate from perturbational forward modeling
Authors: Cordon Ingrid , Dvorkin Jack , Mavko Gary
Published: November 2006

We perturb the elastic properties and attenuation in the Arctic Mallik methane-hydrate reservoir to produce a set of plausible seismic signatures away from the existing well. These perturbations are driven by the changes we impose on porosity, clay content, hydrate saturation, and geometry. The key is a data-guided, theoretical, rock-physics model that we adopt to link velocity and attenuation to porosity, mineralogy, and amount of hydrate. We find that the seismic amplitude is very sensitive to the hydrate saturation in the host sand and its porosity as well as the porosity of the overburden shale. However, changes to the amount of clay in the sand only weakly alter the amplitude. Attenuation, which may be substantial, must be taken into account during hydrate reservoir characterization because it lowers the amplitude to an extent that may affect the hydrate-volume prediction. The spatial structure of the reservoir affects the seismic reflection: A thinly-layered reservoir produces a noticeably different amplitude than a massive reservoir with the same hydrate volume.
Autotracking of faults on 3D seismic data
Authors: Admasu Fitsum , Back Stefan , Toennies Klaus
Published: November 2006

Manual fault mapping in 3D seismic interpretation is labor-intensive and time-consuming. Complex fault geometries and the distortion of the seismic signal close to faults complicate full automation of the fault-mapping process. We present a semiautomatic fault-tracking method for 3D seismic data that consists of fault highlighting followed by model-based fault tracking. Fault highlighting uses log-Gabor filters for emphasizing oriented amplitude discontinuities at faults in the presence of noise. Subsequent fault tracking fits an active contour to the highlighted fault voxels. The active contour searches for a connected, smooth curve which fits the data and disambiguates misleading or missing information. The fault tracker requires the interpreter to place the active contour close to a fault on one initial seismic inline (2D pick). The active contour deforms to the closest amplitude dis-continuity highlighted. This tracking result is then projected forward to the next inline, providing an initial fault pick on this section that is again optimized by the active contour. Tracking results on a series of successive seismic sections, finally, constitute a 3D fault surface. User interaction is solely required for an approximate fault pick on the first inline, and in cases where the fault line is lost due to insufficient signal. Use of the autotracker prototype provides a fast solution for the mapping of complete 3D fault surfaces of constant dip, and for the automated tracking of fault portions within distinct dip domains, if fault surfaces are curved (i.e., listric). The method was applied to a series of high-quality reflectivity sections extracted from a 3D seismic volume from shallow-offshore Nigeria, with the tracking results (generated within seconds) comparing well with manually interpreted fault surfaces.
Elastic-wave propagation in deviated wells in anisotropic formations
Authors: Sinha Bikash K. , Şimşek Ergün , Liu Qing-Huo
Published: November 2006

A finite-difference time-domain (FDTD) formulation with perfectly matched layer (PML) enables analysis of elastic-wave propagation in a fluid-filled borehole in an arbitrarily anisotropic formation. The FDTD formulation yields synthetic waveforms at an array of receivers produced by a monopole or dipole source placed on the borehole axis. Synthetic waveforms are then processed by a modified matrix pencil algorithm to isolate both nondispersive and dispersive arrivals in the wavetrain. The processing algorithm used in this study extracts phase slownesses of plane waves that agree well with the corresponding phase slownesses calculated for propagation along an arbitrary direction in an anisotropic formation. The tube-wave phase velocity obtained from the zero-frequency intercept of the Stoneley dispersion compares well with the analytical results for deviated wellbores in both fast and slow transversely isotropic (TI) formations. Good agreement is also obtained between the low-frequencyasymptotes of borehole flexural dispersion and the corresponding shear-wave velocities from a numerically exact solution of Kelvin-Christoffel equations for plane-wave velocities in anisotropic formations. Numerical results indicate that the Stoneley dispersion changes by a rather small amount, whereas the dipole flexural dispersions exhibit larger changes with wellbore deviations. The influence of a sonic tool structure on borehole elastic-waves can be described by an equivalent heavy-fluid column placed concentrically with the borehole axis. The effect of a heavy-fluid column on the borehole flexural mode is larger in fast than in slow formations. However, the Stoneley dispersion at low frequencies is affected by the presence of the tool structure in both the fast and slow formations. The present study confirms that the two orthogonal dipole flexural dispersions are nearly parallel to each other in slow formations and nonintersecting in fast formations, even in deviated wellbores and in the presence of a sonic tool structure described by a heavy-fluid column.
Integral equation method for 3D modeling of electromagnetic fields in complex structures with inhomogeneous background conductivity
Authors: Zhdanov Michael S. , Lee Seong Kon , Yoshioka Ken
Published: November 2006

We present a new formulation of the integral equation (IE) method for three-dimensional (3D) electromagnetic (EM) modeling in complex structures with inhomogeneous background conductivity (IBC). This method overcomes the standard limitation of the conventional IE method related to the use of a horizontally layered background only. The new 3D IE EM modeling method still employs the Green’s functions for a horizontally layered 1D model. However, the new method allows us to use an inhomogeneous background with the IE method. We also introduce an approach for accuracy control of the IBC IE method. This new approach provides us with the ability to improve the accuracy of computations by applying the IBC technique iteratively. This approach seems to be extremely useful in computing EM data for multiple geologic models with some common geoelectrical features, like terrain, bathymetry, or other known structures. It may find wide application in an inverse problem solution, where we have to keep some known geologic structures unchanged during the iterative inversion. The method was carefully tested for modeling the EM field for complex structures with a known variable background conductivity. The effectiveness of this approach is illustrated by modeling marine controlled-source electromagnetic (MCSEM) data in the area of Gemini Prospect, Gulf of Mexico.
Validation of first-order diffraction theory for the traveltimes and amplitudes of propagating waves
Authors: Jocker Jeroen , Spetzler Jesper , Smeulders David , Trampert Jeannot
Published: November 2006

Ultrasonic measurements of acoustic wavefields scattered by single spheres placed in a homogenous background medium (water) are presented. The dimensions of the spheres are comparable to the wavelength and the wavelength and represent both positive (rubber) and negative (teflon) velocity anomalies with respect to the background medium. The sensitivity of the recorded wavefield to scattering in terms of traveltime delay and amplitude variation is investigated. The results validate a linear (first-order) diffraction theory for wavefields propagating in heterogeneous media with anomaly contrasts on the order of [Formula: see text]. The diffraction theory is compared further with the exact results known from literature for scattering from an elastic sphere, formulated in terms of Legendre polynomials. To investigate the 2D case, the first-order scattering theory is tested against 2D elastic finite-difference calculations. As the presented theory involves a volume integral, it is applicable to any geometric shape, and the scattering object does not need to be spherical or any other specific symmetrical shape. Furthermore, it can be implemented easily in seismic data inversion schemes, which is illustrated with examples from seismic crosswell tomography and a reflection experiment.
A pore-size scale model for the dielectric properties of water-saturated clean rocks and soils
Authors: Endres Anthony L. , Bertrand Edward A.
Published: November 2006

The dielectric properties of water-saturated rock and soils are strongly dependent on the amount and nature of their porosity; interpretation of these geophysical data requires petrophysical models that incorporate both of these elements. The differential effective medium approximation (DEMA) is used to develop a dielectric permittivity model for clean (i.e., clay free) media that divides the pore spaces into elements corresponding to three categories of relative size scale: microscopic porosity (e.g., intergranular cracks), mesoscopic porosity (e.g., main pore volumes), and macroscopic porosity (e.g., vugs and fractures). The hierarchical size-scale structure imposed by the DEMA iterative embedding process is used to assign each pore space category its role in model construction. Use of this model demonstrates that the relationship between dielectric permittivity and porosity is significantly affected by the size scales of pores present in the rock models. A region of realizable permittivity-porosity values is obtained by varying the pore structure in the scaled-porosity model. The bounds of this region correspond to end-member porosity models. Analysis of experimental permittivity data for water-saturated sandstones and carbonates that cover a substantial range of porosity values found that the scaled-porosity models account for a significant part of the variability in experimental data.
Effective elasticity of fractured rocks: A snapshot of the work in progress
Authors: Grechka Vladimir , Kachanov Mark
Published: November 2006

Exploration and development of naturally fractured reservoirs rely on understanding and interpretation of certain signatures associated with seismic waves propagating through cracked rocks. This understanding comes primarily from the effective media theories that predict an overall elastic behavior of a solid containing many inhomogeneities (cracks, in particular) whose sizes are too small to be “seen” individually by the waves. To model seismic responses of fractured formations, a geophysicist typically has a choice between the effective media schemes of Hudson and Schoenberg. While the two predictions usually deviate slightly for liquid-filled cracks, the differences are significant when the fractures are dry. Explaining the origin of these differences and selecting a more accurate scheme is the first goal of this tutorial. Our second, more challenging task, is to prove that simply adding the compliance contributions of cracks as if they were isolated and noninteracting remains sufficiently accurate even for fractures that grossly violate the basic theoretical assumption, of penny-shaped cracks. Real fractures have notoriously irregular shapes, might be partially closed, and often form interconnected networks. Yet, these details of fracture microgeometry turn out to be unimportant for the effective elasticity given a typical noise level in seismic data. No closed-form theory exists for irregular fracture shapes. However, take into account finite-element simulations on so-called digital rocks demonstrate which features of the crack geometry have to be taken into account because they influence propagation of long (compared to the size of fractures) seismic waves and which features can be ignored.
Joint analysis of refractions with surface waves: An inverse solution to the refraction-traveltime problem
Authors: Ivanov Julian , Miller Richard D. , Xia Jianghai , Steeples Don , Park Choon B.
Published: November 2006

We describe a possible solution to the inverse refraction-traveltime problem (IRTP) that reduces the range of possible solutions (nonuniqueness). This approach uses a reference model, derived from surface-wave shear-wave velocity estimates, as a constraint. The application of the joint analysis of refractions with surface waves (JARS) method provided a more realistic solution than the conventional refraction/tomography methods, which did not benefit from a reference model derived from real data. This confirmed our conclusion that the proposed method is an advancement in the IRTP analysis. The unique basic principles of the JARS method might be applicable to other inverse geophysical problems.
Paragangliomas
Authors: YOUNG WILLIAM F.
Published: November 2006

Abstract:  Paragangliomas are rare tumors that arise from extra‐adrenal paraganglia. The effective diagnosis and management of the paraganglioma patient involves the close collaboration of endocrinologists, endocrine surgeons, anesthesiologists, geneticists, laboratory specialists, radiologists, oncologists, and pathologists. Paragangliomas are diagnosed in the following clinical settings: signs and symptoms related to catecholamine hypersecretion, mass effect symptoms (e.g., with head and neck paragangliomas), incidental finding on imaging, or family screening for hereditary paraganglioma. Paragangliomas that hypersecrete catecholamines may cause signs and symptoms identical to those in patients with hyperfunctioning adrenal pheochromocytoma. When a catecholamine‐secreting tumor is suspected in a patient because of paroxysmal symptoms, biochemical documentation of catecholamine and fractionated metanephrine hypersecretion should precede any form of imaging study. Catecholamine‐secreting paragangliomas are found where chromaffin tissue is located (e.g., along the para‐aortic sympathetic chain, or within the organs of Zuckerkandl at the origin of the inferior mesenteric artery, the wall of the urinary bladder, and the sympathetic chain in the neck or mediastinum). As many as 50% of paragangliomas are hereditary and may be associated with familial paraganglioma, neurofibromatosis Type 1, von Hippel–Lindau disease, the Carney triad, and, rarely, with multiple endocrine neoplasia Type 2. Genetic testing should be considered in all patients with paraganglioma. The treatment of choice for paraganglioma is surgical resection; most tumors are benign and can be excised totally. Following surgical cure, annual biochemical testing assesses for metastatic disease, tumor recurrence or delayed appearance of multiple primary tumors.
Genetic Testing in Pheochromocytoma‐ and Paraganglioma‐Associated Syndromes
Authors: BENN DIANA E. , RICHARDSON ANNE LOUISE , MARSH DEBORAH J. , ROBINSON BRUCE G.
Published: November 2006

Abstract:  Genetic understanding of pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes has recently expanded with the identification of the involvement of the mitochondrial complex II peptides, namely the succinate dehydrogenase subunit B (SDHB), subunit C (SDHC), and subunit D (SDHD). In patients with PHEO and/or PGL genetic testing for germline mutations in SDHD and SDHB has been recommended, in addition to the PHEO susceptibility genes VHL and RET. After careful clinical assessment of the patient, suspected familial disease may direct the clinician to the appropriate gene for testing. In the absence of obvious features of familial disease, the decision regarding the appropriate gene for testing is more difficult. Such testing can be costly and time consuming, but a rational prioritization of gene testing can streamline the process. Therefore in order to achieve this for apparently sporadic cases we propose a decision matrix based on site of tumor, functionality, and age at presentation.
Frequent Genetic Changes in Childhood Pheochromocytomas
Authors: DE KRIJGER RONALD R. , VAN NEDERVEEN FRANCIEN H. , KORPERSHOEK ESTHER , DE HERDER WOUTER W. , DE MUINCK KEIZER‐SCHRAMA SABINE M.P.F. , DINJENS WINAND N.M.
Published: November 2006

Abstract:  Pheochromocytomas (PCCs) are rare catecholamine‐producing tumors of the adrenal gland which may also occur elsewhere in the abdomen and are then called paragangliomas. A proportion of PCCs occurs in hereditary cancer syndromes, including multiple endocrine neoplasia Type 2 (MEN2), caused by mutations in the RET proto‐oncogene, von Hippel–Lindau (VHL) disease, caused by VHL gene abnormalities, and the pheochromocytoma–paraganglioma (PCC–PGL) syndrome, caused by mutations in SDHB and SDHD. Since a proportion of PCCs occurs in children we hypothesized that germline mutations in RET, VHL, succinate dehydrogenase subunit B (SDHB), and subunit D (SDHD) occur more frequently in the pediatric age range. From our single‐institution collection of PCCs, we have selected 10 cases that occurred in individuals up to 18 years of age at diagnosis. In these, we have performed mutation analysis on normal and tumor tissues for exons 10, 11, and 16 of RET and for the entire coding sequence of VHL, SDHB, and SDHD. The 10 patients include 7 boys and 3 girls, with an average age of 15.5 years (range 9–18 years). Two patients had germline RET exon 11 mutations (C634R) and 1 patient had an R64P germline mutation in the VHL gene. In the remaining 7 patients there was one patient from a family fulfilling the clinical criteria for VHL disease. All tumors were benign (average follow‐up: 12 years) and were located in the adrenal. From our findings we conclude that (a) a large proportion (40%) of pediatric PCC patients is diagnosed in the context of inherited cancer syndromes, and (b) candidate gene analysis appears to be indicated to detect germline mutations.
Germline Mutation of von Hippel–Lindau (VHL) Gene 695 G>A (R161Q) in a Patient with a Peculiar Phenotype with Type 2C VHL Syndrome
Authors: SANTARPIA LIBERO , LAPA DANIELA , BENVENGA SALVATORE
Published: November 2006

Abstract:  Von Hippel–Lindau (VHL) disease is an autosomal dominant familial neoplastic disorder with an estimated birth incidence of approximately 1:36000 live. VHL has intrafamilial variability expression and it is characterized by the predisposition to develop hemangioblastomas of the central nervous system and retina, pheochromocytomas, clear‐cell renal carcinoma, adenomas, and carcinomas of the pancreas, paragangliomas, renal and pancreatic cysts, papillary cystadenomas of the epididymis and, rarely, cystadenomas of the endolymphatic sac tumor and broad ligament. We describe a Sicilian girl with type 2C VHL who showed the apparently de novo mutation R161Q in association with an extra‐axial supratentorial frontal meningioma, which can be included as a characteristic sign in VHL.
Von Hippel–Lindau Gene Mutation in Non‐Syndromic Familial Pheochromocytomas
Authors: TONG AN‐LI , ZENG ZHENG‐PEI , LI HAN‐ZHONG , YANG DI , LU LIN , LI MING , ZHOU YA‐RU , ZHANG JING , CHEN SHI , LIANG WEI
Published: November 2006

Abstract:  Approximately 50% of patients with non‐syndromic familial pheochromocytomas had germline von Hippel–Lindau (VHL) gene mutations, but no reports on the subject were available in China. A total of five unrelated Chinese families with non‐syndromic familial pheochromocytomas were screened for VHL gene mutation by polymerase chain reaction (PCR) and subsequent direct sequencing. Missense germline mutations of VHL gene were detected in four of the five families. Arg161Gln (695G‐A) mutation was found in two families, and the other two families had Leu163Phe (700C‐T) and Arg167Trp (712C‐T) mutation, respectively. In conclusion, VHL gene may have frequent mutation in Chinese patients with non‐syndromic familial pheochromocytomas.
Molecular Implications of RET Mutations for Pheochromocytoma Risk in Multiple Endocrine Neoplasia 2
Authors: GUJRAL TARANJIT S. , MULLIGAN LOIS M.
Published: November 2006

Abstract:  Multiple endocrine neoplasia Type 2 (MEN 2) is an inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC). The disease has three subtypes, which are distinguished by the presence of additional phenotypes. In particular, pheochromocytoma occurs in approximately 50% of patients with the MEN 2A or MEN 2B subtypes, but is not found in patients with the milder disease subtype, familial MTC (FMTC). All subtypes of MEN 2 are caused by activating mutations of the RET (REarranged in Transfection) proto‐oncogene. RET encodes a transmembrane receptor tyrosine kinase, required for development of neuroendocrine cell types and the kidneys. All MEN 2 subtypes are associated with single amino acid substitution mutations that are found in either the extracellular domain or in the kinase domain of RET. There are strong genotype–phenotype correlations in MEN 2 between patient phenotype and the specific residue that is mutated. MEN 2A is primarily associated with substitutions at five extracellular cysteine residues, while 95% of MEN 2B is associated with a single methionine to threonine mutation in the kinase domain (M918T). In FMTC, RET mutations are more broadly distributed, with both extracellular cysteines and intracellular sites implicated. In all cases, MEN 2‐RET mutations result in constitutive activation of the receptor, although the mechanism and relative functional effects of the mutations vary. Recent advances in functional characterization and development of molecular models of RET and of various MEN 2‐RET mutants are helping us understand tissue‐specific differences in oncogenic potential conferred by the different RET mutations. Here, we discuss and compare several well‐characterized mutations of the extracellular and kinase domains, which have quite varied functional implications.
The Norepinephrine Transporter and Pheochromocytoma
Authors: CLEARY SUSANNAH , PHILLIPS JACQUELINE K
Published: November 2006

Abstract:  Pheochromocytomas are rare neuroendocrine tumors of chromaffin cell origin that synthesize and secrete excess quantities of catecholamines and other vasoactive peptides. Pheochromocytomas also express the norepinephrine transporter (NET), a molecule that is used clinically as a means of incorporating radiolabelled substrates such as 131I‐MIBG (iodo‐metaiodobenzylguanidine) into pheochromocytoma tumor cells. This allows the diagnostic localization of these tumors and, more recently, 131I‐MIBG has been used in trials in the treatment of pheochromocytoma, potentially giving rise to NET as a therapeutic target. However, because of varying levels or activities of the transporter, the ability of 131I‐MIBG to be consistently incorporated into tumor cells is limited, and therefore various strategies to increase NET functional activity are being investigated, including the use of traditional chemotherapeutic agents such as cisplatin or doxorubicin. Other aspects of NET discussed in this short review include the regulation of the transporter and how novel protein–protein interactions between NET and structures such as syntaxin 1A may hold the key to innovative ways to increase the therapeutic value of 131I‐MIBG.
Expression and Effect of Adrenomedullin in Pheochromocytoma
Authors: ZENG ZHENG‐PEI , LIU DONG‐MEI , LI HAN‐ZHONG , FAN XIN‐RONG , LIU GUO‐QIANG , YAN WEI‐GANG , TONG AN‐LI , ZHENG XIN
Published: November 2006

Abstract:  This study investigates the expression of human adrenomedullin (ADM) and its receptor–receptor activity modifying protein 2/calcitonin receptor‐like receptor (RAMP2/CRLR) mRNA in pheochromocytoma by reverse transcriptase polymerase chain reaction (RT‐PCR) and its effect on the proliferation of pheochromocytoma cells by MTT. The mRNA expression of ADM and its receptor RAMP2/CRLR was present in normal adrenal medulla and pheochromocytoma tissues. The mRNA expression of ADM, RAMP2, and CRLR is markedly higher in pheochromocytomas than in normal medulla. ADM inhibits the proliferation of human pheochromocytoma cells and exerts a possible autocrine or paracrine effect in the adrenal.
Gene Expression Profiling of Rat Pheochromocytoma
Authors: ELKAHLOUN ABDEL G. , POWERS JAMES F. , NYSKA ABRAHAM , EISENHOFER GRAEME , TISCHLER ARTHUR S.
Published: November 2006

Abstract:  Sporadic and syndrome‐associated human pheochromocytomas exhibit a spectrum of common and distinctive phenotypic markers. Animal models may contribute to understanding of common denominators leading to development and progression of pheochromocytoma, and to mechanisms that underlie distinctive phenotypes. Rat pheochromocytomas are common, in contrast to their human counterparts, and their frequency is increased by a variety of genotoxic or nongenotoxic agents. Toxicological studies of rats are therefore a potentially rich source of information on pheochromocytoma biology. To compare the molecular profiles of rat and human pheochromocytomas and to identify pathways potentially involved in pathogenesis of rat pheochromocytomas, we conducted a gene expression profiling study comparing 31 pheochromocytomas obtained from the National Toxicology Program to normal adult rat adrenal medulla. The microarray chips were generated from 31,769‐oligomer set representing over 27,200 unique Mouse Ensembl genes. The analysis showed over 1,900 genes that were up‐ or downregulated in the tumors. More than half of the former are involved in protein synthesis and signal transduction, including oncogenes of the RAS family and several heat shock proteins and chaperones. Downregulated genes included receptors and tumor‐suppressor genes, including NF2 and Dmbt1. Specific genes related to neuroendocrine function were either upregulated or downregulated in subsets of tumors. Cross‐comparison with a human pheochromocytoma database showed greater than 60% correlation. Results of this study reveal both generic and specific parallels between rat and human pheochromocytomas.
Biochemical Diagnosis and Localization of Pheochromocytoma
Authors: GROSSMAN ASHLEY , PACAK KAREL , SAWKA ANNA , LENDERS JACQUES W. M. , HARLANDER DEBRA , PEASTON ROBERT T. , REZNEK RODNEY , SISSON JAMES , EISENHOFER GRAEME
Published: November 2006

Abstract:  Pheochromocytomas can have a highly variable presentation, making diagnosis challenging. To think of the tumor represents the crucial initial step, but establishing the diagnosis requires biochemical evidence of excessive catecholamine production and imaging studies to localize the source. Currently, however, there exist no generally agreed upon guidelines based on which tests and testing algorithms should be used to confirm and locate or exclude a suspected pheochromocytoma. Choice of biochemical tests and imaging studies instead usually depends on institutional experience. At the First International Symposium on Pheochromocytoma (ISP2005), held in Bethesda in October 2005, a panel of experts and patient representatives discussed current problems and available options for tumor diagnosis and localization and formulated recommendations, which were subsequently agreed upon by those in attendance at the meeting. This article summarizes the discussion and recommendations derived from that session.
Changes in Urinary Total Metanephrine Excretion in Recurrent and Malignant Pheochromocytomas and Secreting Paragangliomas
Authors: AMAR LAURENCE , PEYRARD SÉVERINE , ROSSIGNOL PATRICK , ZINZINDOHOUE FRANCK , GIMENEZ‐ROQUEPLO ANNE‐PAULE , PLOUIN PIERRE‐FRANÇOIS
Published: November 2006

Abstract:  We quantified urinary excretion of total metanephrines (metanephrine plus normetanephrine) (UETM) in 261 patients with pheochromocytoma (PH) or secreting paraganglioma, before primary tumor resection. We then determined UETM 2 weeks after primary tumor resection and once per year thereafter. The tumor was considered benign in 242 patients and malignant in 19 patients. Patients with malignant tumors had higher UETM and tumor diameters, lower plasma epinephrine concentrations, and were more likely to have secreting paragangliomas than patients with benign tumors. In the 215 patients with a single‐benign primary tumor, preoperative UETM and tumor diameter were significantly correlated. Thirty‐six patients subsequently developed recurrences or new tumors, which were malignant in 18 cases. All recurrent or new tumors could be detected before the onset of symptoms, on the basis of an increase in metanephrine concentration. We followed one patient with von Hippel–Lindau disease and a new tumor for 50 months before reoperation and found that UETM and tumor diameter were significantly correlated. In patients with malignant tumors, the logarithm of UETM was significantly correlated with time, suggesting an exponential increase in tumor activity and, presumably, tumor burden. Urinary metanephrine excretion is a marker of tumor activity and a surrogate of tumor burden in patients with pheochromocytoma or secreting paraganglioma. UETM excretion could be used to assess treatment response in malignant cases.
AT2 Receptor Stimulation May Halt Progression of Pheochromocytoma
Authors: BROWN MORRIS J. , MACKENZIE ISLA S. , ASHBY MICHAEL J. , BALAN KOTTEKKATTU K. , APPLETON DEREK S.
Published: November 2006

Abstract:  Two patients with pheochromocytoma are described in whom treatment with a high dose of an angiotensin receptor blocker was associated with cessation of tumor growth as assessed by serial CT scanning and plasma norepinephrine estimation. If the association with drug treatment is causal, the mechanism may be through stimulation of the AT2 receptor consequent upon the elevation of plasma angiotensin II levels induced by AT1 receptor blockade. Similar observations in further patients should lead to a placebo‐controlled study in patients with malignant or familial pheochromocytoma, or other tumors found to express the AT2 receptor.
Malignant Pheochromocytomas and Paragangliomas
Authors: FITZGERALD PAUL A. , GOLDSBY ROBERT E. , HUBERTY JOHN P. , PRICE DAVID C. , HAWKINS RANDALL A. , VEATCH JANET J. , CRUZ FILEMON DELA , JAHAN THIERRY M. , LINKER CHARLES A. , DAMON LLOYD , MATTHAY KATHERINE K.
Published: November 2006

Abstract:  Thirty patients with malignant pheochromocytoma (PHEO) or paraganglioma (PGL) were treated with high‐dose 131I‐MIBG. Pa tients were 11–62 (mean 39) years old: 19 patients males and 11 females. Nineteen patients had PGL, three of which were multifocal. Six PGLs were nonsecretory. Eleven patients had PHEO. All 30 patients had prior surgery. Fourteen patients were refractory to prior radiation or chemotherapy before 131I‐MIBG. Peripheral blood stem cells (PBSCs) were collected and cryopreserved. 131I‐MIBG was synthesized on‐site, by exchange‐labeling 131I with 127I‐MIBG in a solid‐phase Cu2+‐catalyzed exchange reaction. 131I‐MIBG was infused over 2 h via a peripheral IV. Doses ranged from 557 mCi to 1185 mCi (7.4 mCi/kg to 18.75 mCi/kg). Median dose was 833 mCi (12.55 mCi/kg). Marrow hypoplasia commenced 3 weeks after 131I‐MIBG therapy. After the first 131I‐MIBG therapy, 19 patients required platelet transfusions; 19 received GCSF; 12 received epoeitin or RBCs. Four patients received a PBSC infusion. High‐dose 131I‐MIBG resulted in the following overall tumor responses in 30 patients: 4 sustained complete remissions (CRs); 15 sustained partial remissions (PRs); 1 sustained stable disease (SD); 5 progressive disease (PD); 5 initial PRs or SD but relapsed to PD. Twenty‐three of the 30 patients remain alive; deaths were from PD (5), myelodysplasia (1), and unrelated cause (1). Overall predicted survival at 5 years is 75% (Kaplan Meier estimate).
For patients with metastatic PHEO or PGL, who have good *I‐MIBG uptake on diagnostic scanning, high‐dose 131I‐MIBG therapy was effective in producing a sustained CR, PR, or SD in 67% of patients, with tolerable toxicity.
Can Quantification of VMAT and SSTR Expression Be Helpful for Planning Radionuclide Therapy of Malignant Pheochromocytomas?
Authors: KÖLBY LARS , BERNHARDT PETER , JOHANSON VIKTOR , WÄNGBERG BO , MUTH ANDREAS , JANSSON SVANTE , FORSSELL‐ARONSSON EVA , NILSSON OLA , AHLMAN HÅKAN
Published: November 2006

Abstract:  Tumor‐specific uptake of the radio‐iodinated norepinephrine analogue meta‐iodobenzylguanidine (MIBG) or uptake of radiolabeled somatostatin analogues via somatostatin receptors (SSTRs) are possibilities to diagnose and treat malignant pheochromocytomas/paragangliomas (PCs/PGs)
. The aims of this study were to investigate the quantitative expression of vesicular monoamine transporters (VMAT 1, 2) and all five SSTRs in malignant pheochromocytoma/paraganglioma (PC/PG) to evaluate the possibilities for tumor‐specific radionuclide therapy. High scintigraphic 123I‐MIBG uptake was found in two malignant PGs with high VMAT expression (500–730 copies of VMAT 1, 1,500–1,700 copies of VMAT 2 per 1,000 β‐actin), while no 123I‐MIBG uptake was found in the malignant PG with low VMAT expression (330 copies of VMAT 1, 350 copies of VMAT 2 per 1,000 β‐actin). The two patients with high VMAT expression and high 123I‐MIBG uptake were treated with 131I‐MIBG (2–3 × 8 GBq). In vitro, the VMAT antagonist, reserpine, and the membrane pump inhibitor, clomipramine, inhibited the uptake of 123I‐MIBG into tumor cells equally well (48% and 53% reduction respectively, P < 0.001). SSTR2 was the most abundant receptor subtype, but in the two malignant PGs its expression was only 110–260 copies/1,000 β‐actin. The transporters at the cell membrane and in the vesicular membrane both appear to be of importance for the uptake of 123I‐MIBG into malignant PC/PG. Quantitative determination of VMAT expression may be helpful in selecting patients suitable for radionuclide therapy with 131I‐MIBG. The present data indicate that SSTR‐mediated radionuclide therapy will not be effective treatment of malignant PC/PG.
Comparison of Laboratory Values Obtained by Phlebotomy versus Saline Lock Devices
Authors: Corbo Jill , Fu Lequan , Silver Matthew , Atallah Hany , Bijur Polly
Published: November 2006

Objectives

To assess the utility of a peripheral saline lock device (SLD) as an alternative to a second venipuncture for obtaining selected blood samples.

Methods

This prospective study used a comparative design and was conducted in an urban emergency department (ED). Adult patients with an existing SLD in place who required serial phlebotomy were eligible for inclusion in the study. Each subject had blood samples obtained by venipuncture (control) with a Vacutainer adapter according to standard protocols. Within 5 minutes of obtaining the control samples, a sample was obtained from the patients' SLDs; a tourniquet was applied proximal to the intravenous line, a 5‐mL waste portion was obtained, and a Vacutainer adapter was placed to draw specimens for testing. Each of the paired samples was analyzed for hematocrit, electrolytes, and cardiac enzymes. The Bland‐Altman method was used to analyze the concordance between each pair of measurements. Paired t‐tests for each of the eight laboratory tests were used to assess whether the values were statistically different from each other. The 95% limits of agreement around the mean differences were calculated. Differences between SLD aspirates and venipuncture aspirates also were compared with the federal regulatory standards that ensure reliable and accurate laboratory testing.

Results

Eighty‐one patients were eligible for the study; in 73 (90.1%; 95% confidence interval [CI] = 81.5% to 95.6%) of the patients, the SLD could be aspirated for testing. The paired t‐tests indicated that there were no statistically significant differences between the mean values of the two methods of testing. Of the 584 paired values analyzed, 35 (6.0%; 95% CI = 4.3% to 8.2%) exceeded the Bland‐Altman limits of agreement, and 43 (7.4%; 95% CI = 5.4% to 9.8%) fell outside the acceptable range determined by the federal regulation of clinical laboratories. Of those values that exceeded the acceptable Bland‐Altman limits of agreement, none would have resulted in clinical intervention.

Conclusions

Aspirating blood via an SLD is an acceptable method of obtaining serial laboratory values in a group of stable, consenting adult ED patients.
Confidence Interval Calculation Methods Are Infrequently Reported in Emergency‐medicine Literature
Authors: Marr Amy , Kurz Michael , Stern Jessica , Kulstad Erik
Published: November 2006

Background

There are many different confidence interval calculation methods, each providing different as well as in some cases inadequate interval estimates. Readers who know which method is used are better able to understand potentially significant limitations in study reports.

Objectives

To quantify how often confidence interval calculation methods are disclosed by authors in four peer‐reviewed North American emergency‐medicine journals.

Methods

The authors independently performed searches of four journals for all studies in which comparisons were made between means, medians, proportions, odds ratios, or relative risks. Case reports, editorials, subject reviews, and letters were excluded. Using a standardized abstraction form developed on a spreadsheet, the authors evaluated each article for the reporting of confidence intervals and evaluated the description of methodology used to calculate the confidence intervals.

Results

A total of 212 articles met the inclusion criteria. Confidence intervals were reported in 123 articles (58%; 95% CI = 51% to 64%); of these, a description of methodology was reported in 12 (9.8%; 95% CI = 5.7% to 16%).

Conclusions

Confidence interval methods of calculation are disclosed infrequently in emergency medicine literature.
Prognostic Significance of Human Epidermal Growth Factor Receptor Positivity for the Development of Brain Metastasis After Newly Diagnosed Breast Cancer
Authors: Gabos Zsolt , Sinha Richie , Hanson John , Chauhan Nitin , Hugh Judith , Mackey John R. , Abdulkarim Bassam
Published: November 2006

Purpose

As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) –overexpressing breast cancer patients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2–positive breast cancer patients in comparison with HER-2–negative patients.

Patients and Methods

To determine the incidence of brain metastases in HER-2–overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2–positive and 363 HER-2–negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis.

Results

Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2–overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective.

Conclusion

Our study shows that newly diagnosed HER-2–overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2–inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.
Delineating Culture
Authors: Aaker Jennifer L.
Published: November 2006

How are notions of hierarchy and equality structured cognitively, how do they link to the self‐concept, and how do they develop? Building on the base of work on horizontal/vertical cultural distinctions (Shavitt, Lalwani, Zhang, & Torelli, 2006), this commentary discusses possible answers to these questions, focusing specifically on beliefs (e.g., egalitarianism versus group‐based dominance) and self views (e.g., active versus passive), which may allow for a deeper examination of the horizontal/vertical dimensions. Integrating insights with those from anthropology and sociology, this commentary calls for more work on silence and time, as well as research that examines the antecedents of status and the dynamics underlying “boundary‐shifting”.
Voices Unheard: The Psychology of Consumption in Poverty and Development
Authors: Chakravarti Dipankar
Published: November 2006

Many facets of contemporary global problems posed by poverty pertain to the deprivation of consumption capability and are within the consumer psychologist's expertise domain. This article (based on my 2004 Presidential Address to the Society for Consumer Psychology [SCP]) outlines how consumer psychology research can contribute an understanding of the cognitive, motivational, and sociocultural dimensions of poverty, and how poverty depletes and alters the human need and capacity to consume. Consumer psychology research can also help suggest the nature and function of material and psychological interventions that can help ameliorate these conditions, focusing their design and monitoring their effects. These are important research priorities for consumer psychologists and deserve more and sustained attention from our community. Apart from garnering voice in policy conversations in government, industry, and academe, such research eventually will enhance our field's substantive contribution to improving the contemporary human condition.
Phonotactics and Articulatory Coordination Interact in Phonology: Evidence from Nonnative Production
Authors: Davidson Lisa
Published: November 2006

A core area of phonology is the study of phonotactics, or how sounds are linearly combined. Recent cross‐linguistic analyses have shown that the phonology determines not only phonotactics but also the articulatory coordination or timing of adjacent sounds. In this article, I explore how the relation between coordination and phonotactics affects speakers producing nonnative sequences. Recent experimental results (Davidson 2005, 2006) have shown that English speakers often repair unattested word‐initial sequences (e.g., /zg/, /vz/) by producing the consonants with a less overlapping coordination. A theoretical account of the experimental results employs Gafos's (2002) constraint‐based grammar of coordination. In addition to Gafos's Alignment constraints establishing temporal relations between consonants, a family of Release constraints is proposed to encode phonotactic restrictions. The interaction of Alignment and Release constraints accounts for why speakers produce nonnative sequences by failing to adequately overlap the articulation of the consonants. The optimality theoretic analysis also incorporates floating constraints to explain why speakers are not equally accurate on all unattested clusters.
Dynamics of Phonological Cognition
Authors: Gafos Adamantios I. , Benus Stefan
Published: November 2006

A fundamental problem in spoken language is the duality between the continuous aspects of phonetic performance and the discrete aspects of phonological competence. We study 2 instances of this problem from the phenomenon of voicing neutralization and vowel harmony. In each case, we present a model where the experimentally observed continuous distinctions are linked to the discreteness of phonological form using the mathematics of nonlinear dynamics.
Faithful Contrastive Features in Learning
Authors: Tesar Bruce
Published: November 2006

This article pursues the idea of inferring aspects of phonological underlying forms directly from surface contrasts by looking at optimality theoretic linguistic systems (Prince & Smolensky, 1993/2004). The main result proves that linguistic systems satisfying certain conditions have the faithful contrastive feature property: Whenever 2 distinct morphemes contrast on the surface in a particular environment, at least 1 of the underlying features on which the 2 differ must be realized faithfully on the surface. A learning procedure exploiting the faithful contrastive feature property, contrast analysis, can set the underlying values of some features, even where featural minimal pairs do not exist, but is nevertheless fundamentally limited in what it can set. This work suggests that observation of surface contrasts between pairs of words can contribute to the learning of underlying forms, while still supporting the view that interaction with the phonological mapping will be necessary to fully determine underlying forms.