bluuebunny/crossref_metadata_2025 huggingface dataset:
A follow‐up study of patients with subjective symptoms related to dental materials
Authors: Lygre Gunvor Bentung , Gjerdet Nils Roar , Björkman Lars
Published: April 2005

Abstract –  Objectives:  The extent to which substances released from dental materials cause adverse health effects and whether removal of dental materials results in improvement of health is a matter of dispute. The aim of the study was to investigate changes in the intensity of subjective symptoms after replacement of dental materials in patients referred for adverse reactions related to dental materials, and to compare the profiles of symptoms with those found in the general population.

Methods:  Information was obtained from 142 patients referred to the Dental Biomaterials Adverse Reaction Unit in Bergen, Norway. At the time of examination, all patients completed a questionnaire regarding a range of subjective symptoms. A follow‐up questionnaire was sent to all patients 1 to 2 years later. Similar questionnaires were sent to a reference group of 800 persons drawn from the general population.

Results:  The follow‐up questionnaires were completed and returned by 84 patients, and 441 persons in the reference group. The patient group presented higher symptom indices than the reference group (P < 0.001). Generally, there was some decrease in the intensity of different symptoms in patients who had replaced dental materials. The decrease was evident regarding intraoral symptoms (P = 0.022) and total symptom index (P = 0.041). The group of patients who had replaced materials still had significantly higher symptom indices than those of the reference group. Patients who had not replaced dental materials did not present any reduction in symptom indices.

Conclusion:  The pattern of symptoms was similar for the groups investigated. At the group level, the intensity of local and some general subjective symptoms was reduced after replacement of the materials, but not to the level found in the general population.
FREE VIBRATION ANALYSIS OF TIMOSHENKO BEAMS AND MINDLIN PLATES BY RADIAL BASIS FUNCTIONS
Authors: FERREIRA A. J. M.
Published: April 2005

A study of free vibration of Timoshenko beams and Mindlin plates is presented whereby the analysis is based on the radial basis function method. Various approaches for computing eigenvalues using radial basis functions are also discussed together with the numerical results for various thickness-to-length ratios.
FRACTALS IN LOGIC
Authors: SACALUGA DAVID LUQUE
Published: April 2005

The main target of this document is to propose a new graphical method to find prime implicants, necessary prime implicants and minimum sum-of-product expressions for digital systems with any number of variables. Moreover, a simple example of application of the same method is included to be compared with Karnaugh's method. As a consequence of this proposed method, a few conditions are established and a fractal image is created, which explains why it is not possible to have more than one binary variable changing simultaneously and why the change between two non adjacent states has to be realized always going through an intermediate state.
A HIGH ORDER KINETIC FLUX-SPLITTING METHOD FOR THE SPECIAL RELATIVISTIC HYDRODYNAMICS
Authors: QAMAR SHAMSUL , WARNECKE GERALD
Published: April 2005

In this article we present a flux splitting method based on gas-kinetic theory for the special relativistic hydrodynamics (SRHD) [Landau and Lifshitz, Fluid Mechanics, Pergamon New York, 1987] in one and two space dimensions. This kinetic method is based on the direct splitting of the macroscopic flux functions with the consideration of particle transport. At the same time, particle "collisions" are implemented in the free transport process to reduce numerical dissipation. Due to the nonlinear relations between conservative and primitive variables and the consequent complexity of the Jacobian matrix, the multi-dimensional shock-capturing numerical schemes for SRHD are computationally more expensive. All the previous methods presented for the solution of these equations were based on the macroscopic continuum description. These upwind high-resolution shock-capturing (HRSC) schemes, which were originally made for non-relativistic flows, were extended to SRHD. However our method, which is based on kinetic theory is more related to the physics of these equations and is very efficient, robust, and easy to implement. In order to get high order accuracy in space, we use a third order central weighted essentially non-oscillatory (CWENO) finite difference interpolation routine. To achieve high order accuracy in time we use a Runge-Kutta time stepping method. The one- and two-dimensional computations reported in this paper show the desired accuracy, high resolution, and robustness of the method.
COMPUTATIONAL FEATURES OF AGENT-BASED MODELS
Authors: BERNASCHI MASSIMO , CASTIGLIONE FILIPPO
Published: April 2005

Agent-based modeling allows the description of very complex systems. To run large scale simulations of agent-based models in a reasonable time, it is crucial to carefully design data structures and algorithms. We describe the main computational features of agent-based models and report about the solutions we adopted in two applications: The simulation of the immune system response and the simulation of the stock market dynamics.
The Lens Has a Specific Influence on Optic Nerve and Tectum Development in the Blind Cavefish Astyanax
Authors: Soares Daphne , Yamamoto Yoshiyuki , Strickler Allen G. , Jeffery William R.
Published: April 2005

We used the teleost Astyanaxmexicanus to examine the role of the lens in optic nerve and tectum development. This speciesis unusually suited for studies of nervous system development and evolution because of its two extant forms: an eyed surface dwelling (surface fish) and several blind cave dwelling (cavefish) forms. Cavefish embryos initially form eye primordia, but the lens eventually dies by apoptosis, then the retina ceases to grow, and finally the degenerating eyes sink into the orbits. Transplantation of an embryonic surface fish lens into a cavefish optic cup restores eye development. We show here that retinal nerve fibers are formed and project to the optic tectum in cavefish embryos. In adult cavefish that have completed lens degeneration, however, the number of retinal axons in the optic nerve is substantially reduced compared to surface fish. The presumptive brain domains of embryonic cavefish are not altered relative to surface fish based on expression of the regional marker genes Pax6, Pax2.1, and engrailed2. In contrast, the adult cavefish brain is elongated, the optic tectum is diminished in volume, and the number of tectal neurons is reduced relative to surface fish. Unilateral transplantation of an embryonic surface fish lens into a cavefish optic cup increases the size of the optic nerve, the number of retinotectal projections from the restored eye, and the volume and neuronal content of the contralateral optic tectum. The results suggest that the lens has a specific influence on optic nerve and tectum development during eye growth in Astyanax.
Pax-6 Expression in Posthatch Chick Retina during and Recovery from Form-Deprivation Myopia
Authors: Bhat Suraj P. , Rayner Sylvia A. , Chau Scott C. , Ariyasu Reginald G.
Published: April 2005

The expression of Pax-6 in fully-differentiated chick retina remains largely confined to the amacrine and ganglion cell layers. In the developing posthatch chick retina, Pax-6 expression shows a biphasic pattern; a decrease by posthatch day 17 followed by a steady increase in the adult eye. Interestingly, we find that this biphasic expression of Pax-6 is reflected in the biphasic growth pattern of the posthatch chick eye, which is disrupted by form-deprivation myopia (FDM). We have now examined the pattern of Pax-6 accumulation in 3-day-old chick eyes subjected to 2 weeks of FDM followed by 2 weeks of recovery from FDM. Quantitative RT-PCR (with a homologous internal control) revealed that after 2 weeks of occlusion the contralateral non occluded eyes, the occluded eyes and the normal nonexperimental chick eyes did not show any drastic changes in the number of Pax-6 transcripts. The data obtained suggests that the contralateral eye does not represent a ‘normal’ control eye; similar but nonidentical changes are seen, at the molecular level, in both the contralateral and the occluded eyes. Comparisons with the control nonexperimental animals, however, are meaningful. Even after 2 weeks of recovery under normal light conditions, the occluded eyes do not seem to reach the same level of Pax-6 expression (number of molecules per mg tissue) as seen in normal control eyes, suggesting that exposure of the posthatch chick eye to FDM impedes developmental progression that normally culminates in emmetropia.
Transplantation of Neural Progenitor Cells into the Developing Retina of the Brazilian Opossum: An in vivo System for Studying Stem/Progenitor Cell Plasticity
Authors: Sakaguchi D.S. , van Hoffelen S.J. , Theusch E. , Parker E. , Orasky J. , Harper M.M. , Benediktsson A. , Young M.J.
Published: April 2005

In developing cell transplant strategies to repair the diseased or injured retina is essential to consider host-graft interactions and how they may influence the outcome of the transplants. In the present study we evaluated the influence of the host microenvironment upon neural progenitor cells (NPCs) transplanted into the developing and mature retina of the Brazilian opossum, Monodelphis domestica. Monodelphis pups are born in an extremely immature state and the neonatal pups provide a fetal-like environment in which to study the interactions between host tissues and transplanted NPCs. Three different populations of GFP-expressing NPCs were transplanted by intraocular injection in hosts ranging in age from 5 days postnatal to adult. Extensive survival, differentiation and morphological integration of NPCs were observed within the developing retina. These results suggest that the age of the host environment can strongly influence NPC differentiation and integration.
The Role of Hedgehog Signaling in the Development of the Zebrafish Visual System
Authors: Stadler Jochen A. , Shkumatava Alena , Neumann Carl J.
Published: April 2005

The vertebrate visual system is a region of the nervous system that is characterized by relative simplicity, and its development has hence been studied intensively, to serve as a paradigm for the rest of the central nervous system. The zebrafish model organism offers an impressive array of tools to dissect this process experimentally, and in recent years has helped to significantly deepen our understanding of the development of the visual system. A number of these studies have focused on the role of the Hedgehog family of secreted signaling molecules in eye development, and this is the main topic of this review. Hedgehog signaling plays an important role in all major steps of visual system development, starting with the regionalization of the eye primordium into proximal and distal territories, continuing with the control of cellular differentiation in the retina, and ending with the guidance of axonal projections from the retina to the optic centers of the brain.
Wnt/Frizzled Signaling during Vertebrate Retinal Development
Authors: van Raay Terence J. , Vetter Monica L.
Published: April 2005

Multiple signaling pathways are known to be involved in regulating development of the vertebrate neural retina. Recent publications have demonstrated that Wnt/Frizzled (Fz) signaling components are expressed in the developing retina and may play a fundamental role in retinogenesis. In this review, we summarize Wnt/Fz expression patterns in the developing vertebrate retina, mainly from chick and mouse, and compare them with Wnt/β-catenin reporter activity. Consistent with the dynamic expression patterns of Wnt pathway components, evidence suggests that Wnt/Fz signaling has multiple roles during retinal development.
Ciliary Neurotrophic Factor Promotes Müller Glia Differentiation from the Postnatal Retinal Progenitor Pool
Authors: Goureau Olivier , Rhee Kun Do , Yang Xian-Jie
Published: April 2005

Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects during vertebrate retinal development, including regulating the differentiation of photoreceptor cells and promoting the survival and axonal growth of ganglion cells. We report here that in addition to affecting the differentiation of retinal neurons, CNTF also promotes Müller glia genesis in the postnatal mouse retina. In both retinal monolayer and explant cultures, CNTF increases the number of progenitor cells adopting the Müller cell fate. Exogenous CNTF induces phosphorylation of signal transducers and activators of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) among neonatal progenitor cells and newborn Müller cells. In addition, increased levels of endogenous STAT3 and ERK phosphorylation have been observed at around postnatal day 5, coinciding with the peak of Müller glia genesis. Perturbation of STAT and ERK signaling using protein kinase inhibitors and a dominant-negative STAT3 mutant demonstrates that both CNTF-induced STAT and ERK activation are involved in promoting Müller cell production. Moreover, absorbing epidermal growth factor (EGF) signals with a neutralizing antibody did not affect CNTF-induced Müller glial genesis, indicating that the effect of CNTF is not mediated by the known Müller-enhancing activity of EGF. Together, these results support a novel function of CNTF-like cytokines in retinal gliogenesis.
MARCKS in Advanced Stages of Neural Retina Histogenesis
Authors: Zolessi Flavio R. , Arruti Cristina
Published: April 2005

Myristoylated alanine-rich kinase C substrate (MARCKS), an actin-binding protein, is involved in several signal transduction pathways. It is susceptible to be phosphorylated by protein kinases as protein kinase C and some proline-directed kinases. These phosphorylations differently modulate its functions. We previously showed that a phosphorylation at its Ser25 (S25p-MARCKS) in chickens is a signature of this ubiquitous protein in neuron differentiation. To gain insight into the possible involvement of MARCKS in late retinal histogenesis, we compared the developmental expression patterns of the total protein and its S25p variants. Here we show that the most outstanding modifications occur at the outer retina, where S25p disappears at the end of embryonic development and where MARCKS is missing in adults. These results suggest diverse functional specializations in the different retinal layers.
5A11/Basigin Gene Products Are Necessary for Proper Maturation and Function of the Retina
Authors: Ochrietor Judith D. , Linser Paul J.
Published: April 2005

5A11/Basigin gene products are important membrane glycoproteins for development and maturation of the retina. The gene encodes two immunoglobulin-like, membrane-bound glycoproteins as a result of splice variation. The smaller protein product, named 5A11/Basigin, is expressed by many tissues within the mouse, whereas the larger protein product, named 5A11/Basigin-2, is expressed only by the photoreceptor cells (PCs) of the retina. Mice in which the gene for 5A11/Basigin has been deleted have several abnormalities, including blindness from the time of eye opening with subsequent degeneration of the PCs. Studies by this laboratory suggest that a developmental deficiency is the underlying cause of the blindness. However, definitive biological functions for 5A11/Basigin and 5A11/Basigin-2 have yet to be defined. It is known that 5A11/Basigin is multifunctional and can interact with several different proteins. Preliminary studies indicate that 5A11/Basigin-2 may be multifunctional as well. Studies by this laboratory and others have demonstrated that 5A11/Basigin (and probably 5A11/Basigin-2) acts as a chaperone for monocarboxylate transporter-1 (MCT-1) translocation to the cell membrane. We have proposed that a lactate metabolon exists within the retina and functions to shuttle lactate, an energy source, from glial cells to the PCs. This metabolon is not present within 5A11/Basigin null mouse retinas, which may be the underlying cause of the retinal dysfunction and subsequent degeneration. Further studies will be necessary to determine which of the functions are critical for proper development of the retina.
‘One Receptor’ Rules in Sensory Neurons
Authors: Mazzoni Esteban O. , Desplan Claude , Çelik Arzu
Published: April 2005

With the recent explosion in the characterization of different sensory systems, a general rule is emerging: only one type of sensory receptor molecule is expressed per receptor neuron. The visual system is no exception and, in most cases, photoreceptors express only one visual pigment per cell. However, the mechanisms underlying the exclusion of sensory receptors are poorly understood. As expression of a given receptor in a given cell is often stochastic, a decision must first be made to express one of the many receptors of the same family (i.e. one particular rhodopsin) and this expression must correlate with the silencing of the other receptors. Furthermore, the projection center for the receptors in the brain must be informed of the decision in order to process this information. Although cells can choose from up to hundreds of sensory receptors (e.g. in the olfactory system), they make almost no mistakes. Evidence has recently emerged that the exclusion mechanism involves the sensory receptor molecules themselves. Here, we describe the findings from various systems in mammals and Drosophila, and review evidence that in the simple visual system of the fly, rhodopsin molecules play an important role in sensory receptor exclusion.
Long-Term Treatment of the Developing Retina with the Metabotropic Glutamate Agonist APB Induces Long-Term Changes in the Stratification of Retinal Ganglion Cell Dendrites
Authors: Deplano Stefania , Gargini Claudia , Maccarone Rita , Chalupa Leo M. , Bisti Silvia
Published: April 2005

The gradual restriction of initially multistratified retinal ganglion cell (RGC) dendrites into ON and OFF sublaminae of the inner plexiform layer (IPL) can be effectively blocked by treating the developing retina with 2-amino-4-phosphonobutyrate (APB), the metabotropic glutamate agonist, or by light deprivation. Previous studies have focused on the short-term consequences of such manipulations, so the long-term effects of arresting dendritic stratification on the structural development of RGCs are as yet unknown. In the present study, we have addressed this issue by performing a morphological analysis of α RGCs labeled by retrograde transport of horseradish peroxidase injected into the dorsal lateral geniculate nucleus of adult cats that received monocular injections of APB from postnatal (P) day 2 until P30. A large proportion of the α cells in the APB-treated eye (44%) were found to have multistratified dendrites that terminated in both the ON and OFF sublaminae of the IPL. The dendritic arborization pattern in the sublaminae of the IPL of these cells was asymmetric, showing a variety of forms. Immunolabeling of retinal cross-sections showed that mGLUR6 receptors appeared normal in density and location, while qualitative observation suggested an increase in the axonal arborization of rod bipolar cells. These findings indicate that long-term treatment of the neonatal retina with APB induces a long- lasting structural reorganization in retinal circuitry that most likely accounts for some of the previously described changes in the functional properties of RGCs.
Emergence of Realistic Retinal Networks in Culture Promoted by the Superior Colliculus
Authors: Colicos Michael A. , Firth Sally I. , Bosze Jenel , Goldstein Jennifer , Feller Marla B.
Published: April 2005

The developing retina is characterized by ‘retinal waves’, spontaneous depolarizations that propagate through a developing network of interneurons and retinal ganglion cells. Although the circuitry underlying retinal waves is well characterized, the secreted factors that are critical for its normal development are not defined. Dissociated cell culture provides an ideal system for defining these factors; however, it is difficult to recapitulate retinal circuitry in culture. Here we demonstrate that by culturing dissociated retinal neurons in the presence of cells from the superior colliculus (SC), retinal neurons form networks that are similar to those described in the intact retina. Whole-cell voltage clamp recordings reveal the presence of a spontaneously active network of interneurons. In addition, we observed spontaneous, propagating activity reminiscent of that observed in the intact retina. We propose that the presence of factors secreted from the SC results in the development of networks that reproduce critical features of the intact retina.
Distinct Capacities of Individual E2Fs to Induce Cell Cycle Re-Entry in Postmitotic Lens Fiber Cells of Transgenic Mice
Authors: Chen Qin , Liang Dongcai , Yang Tao , Leone Gustavo , Overbeek Paul A.
Published: April 2005

Purpose: Inactivation of the retinoblastoma gene in human retinoblasts or mouse lens fiber cells causes inappropriate cell cycle entry, presumably as a consequence of elevated activity of the E2F transcription factors. Although E2Fs are known to be critical regulators of the cell cycle, it is still unclear whether family members E2F3a, E2F4 or E2F5 are individually capable of inducing cell cycle entry in vivo. In this study, we designed experiments to test whether lens-specific expression of these E2F family members would induce postmitotic fiber cells to re-enter the cell cycle. Methods: Transgenic mice were generated by microinjection of constructs that contained E2F cDNAs (E2F3a, E2F4 or E2F5) linked to the mouse lens-specific αA-crystallin promoter. The mice were characterized by histology, in situ hybridization, immunohistochemistry, BrdU incorporation, TUNEL assay and Western blots. Results: E2F3a expression was sufficient to induce cell cycle entry in lens fiber cells. Cell cycle re-entry was accompanied by apoptotic cell death resulting in microphthalmia. E2F4 expression stimulated a modest level of cell cycle re-entry, but the transgenic lenses remained normal in size and did not show significant apoptosis. Transgenic mice expressing E2F5 did not show lens defects. In both the E2F3a and E2F4 transgenic lenses, cyclin A2 and cyclin B1 expression were upregulated. Phosphorylated histone H3, a marker for mitosis, was detected in the E2F3a fiber cells. Western blots showed that both p53 and p73α were upregulated in the E2F3a lenses. However, expression of p21, a well-known p53 target gene, was not activated, suggesting that p73α might be responsible for inducing apoptosis and blocking unregulated proliferation in lens cells overexpressing E2F3a. Conclusions: E2F3a and E2F4, but not E2F5, function to induce cell cycle entry, although E2F4 has more modest activity. E2F3a may induce cell death primarily through activation of p73α.
Deregulation of Lens Epithelial Cell Proliferation and Differentiation during the Development of TGFβ-Induced Anterior Subcapsular Cataract
Authors: Lovicu F.J. , Ang S. , Chorazyczewska M. , McAvoy J.W.
Published: April 2005

Normal lens development and growth is dependent on the tight spatial and temporal regulation of lens cell proliferation and fiber cell differentiation. The present study reports that these same cellular processes contribute to lens pathology as they become deregulated in the process of anterior subcapsular cataract development in a transgenic mouse model. During the formation and growth of transforming growth factor (TGF)β-induced subcapsular plaques, lens epithelial cells lose key phenotypic markers including E-cadherin and connexin 43, they multilayer and subsequently differentiate into myofibroblastic and/or fiber-like cells. Growth of the subcapsular plaques in the transgenic mouse is sustained by an ordered process of cell proliferation, exit from the cell cycle and differentiation. As reiterating ordered growth and differentiation patterns is atypical of the direct effects of TGFβ on lens cells in vitro, we propose that other growth factors in the eye, namely fibroblast growth factor, may also play a role in the establishment and regulation of the key cellular processes leading to lens pathology. Obtaining a better understanding of the molecular aspects and cellular dynamics of cataract formation and growth is central to devising strategies for slowing or preventing this disease.
Looking at an Oft-Overlooked Part of the Eye: A New Perspective on Ciliary Body Development in Chick
Authors: Hyer Jeanette
Published: April 2005

The ciliary body is an essential tissue for the development and homeostasis of the vertebrate eye. Embryonically, the epithelial portion of the ciliary body derives from the neuroepithelium of the optic cup, however, it differentiates into a secretory tissue and produces an aqueous humor that sustains the lens and cornea, and maintains the requisite pressure within the orb. The unique differentiation of this portion of the optic cup is little understood. This article reviews what is known about the development of the ciliary body and presents some preliminary findings that may lead to a new model for the formation of the ciliary body.
Psychopathology in First-Episode Schizophrenia and Antibodies to Toxoplasma gondii
Authors: Bachmann S. , Schröder J. , Bottmer C. , Torrey E.F. , Yolken R.H.
Published: April 2005

Objective: Environmental factors such as infectious agents may contribute to the psychopathology and aetiology of schizophrenia. Toxoplasma gondii (TG) is a candidate infectious agent as it is known to replicate within the human central nervous system and to alter behaviour in experimental animals. Method: The relationship between antibodies to TG and psychopathological symptoms was examined in 34 first-episode patients with schizophrenia. Results: Results of regression analyses revealed that symptoms on admission, predictors of outcome, age and family history of psychiatric disease influenced the levels of antibodies to TG. Conclusions: These results indicate that TG infections may play a role in the clinical manifestation of psychopathology in a subgroup of patients with schizophrenia.
A Three-Axes Approach of Subtyping the Alcohol Dependence Syndrome
Authors: Wiesbeck Gerhard A. , Dürsteler-MacFarland Kenneth M. , Walter Marc , Weijers Heinz-Gerd , Boening Jobst
Published: April 2005

Subtyping of alcoholics according to specific characteristics has a long tradition in alcoholism research with a number of different typologies that emerged in the literature. The goal of the present study was to test a multidimensional approach of subtyping with characteristics from different axes. Therefore, male inpatients meeting ICD-10 criteria for alcohol dependence were rated on three axes by assessing their degree of sensation seeking (personality axis), age of alcoholism onset (clinical axis) and level of dopamine activity (neurobiological axis). By using a configuration frequency analysis, we identified a subtype that was characterized by high sensation seeking early age of alcoholism onset and high dopamine activity. This subtype, which is in accordance with clinical experience and cannot be explained by antisocial personality disorder, embodied a significantly greater proportion of alcoholics than expected. The result emphasizes the usefulness of multidimensional approaches integrating personality, clinical and neurobiological characteristics.
Changes of Lymphocyte Populations in Pediatric Steroid-Sensitive Nephrotic Syndrome Are More Pronounced in Remission than in Relapse
Authors: Kemper Markus J. , Zepf Kristina , Klaassen Ilka , Link Amrey , Müller-Wiefel Dirk E.
Published: April 2005

Background/Aim: Although clinical and immunological findings in steroid-sensitive nephrotic syndrome (SSNS) favor an immunopathogenesis, many issues remain unsolved. Comprehensive studies analyzing cellular and humoral immunity in SSNS are scarce, and few studies addressed the effect of steroids on immunological factors. Methods: We therefore performed a cross-sectional study of T and B lymphocyte populations in 89 children during the different stages of the disease and related the findings to parameters of humoral immunity and treatment with steroids. Results: In untreated relapse, an increase in the proportion of activated CD3+ lymphocytes with a concomitant reduction of CD19+ B cells was noted compared to healthy controls. Conversely, patients with steroid dependency, relapsing on alternate-day steroids, showed a decline of the absolute numbers as well as proportion of CD4+ lymphocytes but a relative increase in CD19+ B cells, compared to healthy controls. Also untreated remission was characterized by an absolute and relative decrease in CD4+ lymphocytes compared to healthy controls which was accompanied by a significant increase in the proportion of CD8+ and also activated CD3+ lymphocytes. Steroid-induced remission resulted in suppression of absolute and relative CD4+, while absolute and relative B cells were upregulated in this group compared to untreated remission. Summary and Conclusion: Alterations of lymphocyte populations in SSNS are not limited to relapse but seem to be more pronounced in remission and show a different profile with steroid treatment. Changes of lymphocyte populations do not only affect T but also B lymphocytes, which may be of relevance in the pathogenesis of this disorder.
Differential Effects of Antihypertensive Drugs on Renal and Glomerular Hemodynamics and Injury in the Chronic Nitric-Oxide-Suppressed Rat
Authors: Zhou Xiaoyan , Frohlich Edward D.
Published: April 2005

Background/Aims: Prolonged nitric oxide synthase (NOS) inhibition with Nω-nitro-L-arginine methylester in normotensive and hypertensive rats has been demonstrated to produce severe systemic and glomerular hypertension with glomerular sclerosis, and these changes have become a useful experimental model of hypertensive nephrosclerosis. This review summarizes data from our serial studies as well as work of others who are also investigating the effects of the commonly used antihypertensive drugs (including calcium antagonist, angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blocker, aldosterone antagonist and thiazide diuretic) on renal and glomerular hemodynamics, renal function and glomerular histopathology using this model. Methods: A Medline search was performed to identify the relevant literature describing renal effects of antihypertensive drugs in models of hypertension and nephrosclerosis produced or exacerbated by NOS inhibition. Results: Existing data have indicated that most of these drug classes have produced dramatic renoprotective effects, structurally or functionally, on nephrosclerosis induced by prolonged NOS inhibition. Conclusion: This review of experimental studies has provided strong evidence supporting the clinical benefits of antihypertensive drugs for hypertensive patients with renal impairment particularly those with endothelial dysfunction associated with NOS deficiency.
Patient Selection for Cardiac Resynchronization Therapy
Authors: Strickberger S. Adam , Conti Jamie , Daoud Emile G. , Havranek Edward , Mehra Mandeep R. , Piña Ileana L. , Young James
Published: April 2005

Cardiac resynchronization therapy (CRT) is a relatively new therapy for patients with symptomatic heart failure resulting from systolic dysfunction. CRT is achieved by simultaneously pacing both the left and right ventricles. Biventricular pacing resynchronizes the timing of global left ventricular depolarization and improves mechanical contractility and mitral regurgitation. Published clinical trials have demonstrated that CRT results in improved clinical status and lower mortality rate when selected patients with systolic ventricular dysfunction and heart failure are treated with CRT. This advisory identifies appropriate candidates for CRT on the basis of the inclusion criteria and results from the published clinical trials.
Effectiveness and Safety of Sirolimus-Eluting Stents in the Treatment of Restenosis After Coronary Stent Placement
Authors: Neumann Franz-Josef , Desmet Walter , Grube Eberhard , Brachmann Johannes , Presbitero Patrizia , Rubartelli Paolo , Mügge Andreas , Di Pede Francesco , Füllgraf Diana , Aengevaeren Wim , Spedicato Leonardo , Popma Jeffrey J.
Published: April 2005

Background—

In-stent restenosis is notoriously difficult to treat by repeat catheter intervention because of its propensity for aggressive recurrent neointimal formation. This study sought to assess the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis.

Methods and Results—

The study was designed as a prospective multicenter registry. We included 162 patients with in-stent restenosis of a native coronary artery who had a clinical indication for repeat intervention. Patients were scheduled for follow-up angiography at 6 months. The primary end point was in-lesion late loss. Follow-up angiography was performed in 155 patients. We obtained an in-lesion late loss of 0.08±0.49 mm and a binary restenosis rate of 9.7% (15/155), which prompted reintervention in 7.4% (12/162) at 9 months. The 9-month rate of death was 1.2% (2/162) and that of nonfatal myocardial infarction was 1.2% (2/162).

Conclusions—

Sirolimus-eluting stents were highly efficacious and safe in the treatment of in-stent restenosis. Our study provides rationale for the use of sirolimus-eluting stents in the treatment of in-stent restenosis.
Progressive Attenuation of Myocardial Vascular Endothelial Growth Factor Expression Is a Seminal Event in Diabetic Cardiomyopathy
Authors: Yoon Young-sup , Uchida Shigeki , Masuo Osamu , Cejna Manfred , Park Jong-Seon , Gwon Hyeon-cheol , Kirchmair Rudolf , Bahlman Ferdinand , Walter Dirk , Curry Cynthia , Hanley Allison , Isner Jeffrey M. , Losordo Douglas W.
Published: April 2005

Background—

Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis, which leads to progressive heart failure; however, the pathogenesis of DCM remains uncertain.

Methods and Results—

Using the streptozotocin-induced diabetic rat model, we evaluated the natural course of DCM over a period of 1 year by serial echocardiography, Western blot analysis for vascular endothelial growth factor (VEGF), endothelial progenitor cell assays, myocardial blood flow measurements, and histopathologic analysis that included terminal dUTP nick end-labeling (TUNEL), capillary and cardiomyocyte density, and fibrosis area. Downregulation of myocardial VEGF expression preceded all other features of DCM and was followed by increased apoptosis of endothelial cells, decreased numbers of circulating endothelial progenitor cells, decreased capillary density, and impaired myocardial perfusion. Apoptosis and necrosis of cardiomyocytes ensued, along with fibrosis and progressive diastolic and then systolic dysfunction. To provide further evidence of the central role of VEGF in the pathophysiology of DCM, we replenished myocardial VEGF expression using naked DNA gene therapy via direct intramyocardial injection of plasmid DNA encoding VEGF (phVEGF
165
). VEGF-replenished rats showed increased capillary density, decreased endothelial cell and cardiomyocyte apoptosis, and in situ differentiation of bone marrow–derived endothelial progenitor cells into endothelial cells. These anatomic findings were accompanied by significant improvements in cardiac function.

Conclusions—

These findings suggest that downregulation of VEGF may compromise microvascular homeostasis in the myocardium and thereby play a central role in the pathogenesis of DCM.
Arterial Hemodynamics in Patients After Kawasaki Disease
Authors: Senzaki Hideaki , Chen Chen-Huan , Ishido Hirotaka , Masutani Satoshi , Matsunaga Tamotsu , Taketazu Mio , Kobayashi Toshiki , Sasaki Nozomu , Kyo Shunei , Yokote Yuji
Published: April 2005

Background—

Histopathological findings in the acute stage of Kawasaki disease (KD) indicate widespread vascular inflammation that involves not only coronary arteries but also systemic arteries. This may cause changes in systemic arterial wall properties after KD, which could have adverse effects on arterial hemodynamics (an important predictor of cardiovascular morbidity and mortality).

Methods and Results—

Systemic arterial hemodynamics were investigated by measuring aortic input impedance during cardiac catheterization in 42 KD patients who had developed coronary artery lesions (CALs) in the acute stage of KD. The KD patients were subdivided into 2 groups according to the angiographic findings (group 1A, 26 patients with persistent CALs; group 1B, 16 patients with regressed CALs), and results were compared with those of 36 referents (group 2). Compared with referents, characteristic impedance was significantly higher for KD patients (137.0±5.1, 125.7±8.2, and 97.9±4.1 dyne · s · cm
−5
· m
2
for group 1A, group 1B, and group 2, respectively), and total peripheral arterial compliance indexed to age-specific values was significantly lower for KD patients (group 1A 72.9±4.2% of normal; group 1B 70.6±5.9% of normal; group 2 97.7±4.0% of normal; for both variables,
P
<0.05 for each KD group versus group 2;
P
=NS between KD groups), which suggests that both central and peripheral arterial wall stiffness increase after KD regardless of persistence of CALs. Also, indices of arterial wave reflection (reflection coefficient, reflection factor, and augmentation index) were all significantly higher in KD patients than in referents (
P
<0.05), with the result that the aortic pressure waveforms of the present KD patients resembled those generally observed in the elderly. In addition, levels of circulating markers of endothelial dysfunction (ACE and von Willebrand factor) were associated with increased vascular stiffening in KD patients but not in referents.

Conclusions—

These results indicating abnormal arterial hemodynamics after KD highlight the importance of regular monitoring of the systemic arterial bed and potentially relevant cardiovascular events in long-term follow-up of KD.
Hyperhomocysteinemia, a Cardiac Metabolic Disease
Authors: Becker Justin S. , Adler Alexandra , Schneeberger Aaron , Huang Harer , Wang Zipping , Walsh Erin , Koller Akos , Hintze Thomas H.
Published: April 2005

Background—

Hyperhomocysteinemia (HHcy) is a reliable indicator of cardiovascular disease, in part because of the production of superoxide and scavenging of nitric oxide (NO). The present study assessed the impact of HHcy on the NO-dependent control of cardiac O
2
consumption and examined enzymatic sources of superoxide.

Methods and Results—

Rats and mice were fed methionine in drinking water for 5 to 9 weeks to increase plasma homocysteine, a process that did not cause significant changes in hemodynamic function. The ability of the NO agonists bradykinin and carbachol to reduce myocardial O
2
consumption in vitro was impaired by ≈40% in methionine-fed rats, and this impairment was proportional to their individual plasma homocysteine concentration. However, responses were restored in the presence of ascorbic acid, tempol, and apocynin, which inhibits NADPH oxidase assembly. Western blots showed no difference in Cu/Zn or Mn superoxide dismutase, endothelial NO synthase, or inducible NO synthase protein, but HHcy caused a 100% increase in the p22

phox

subunit of NADPH oxidase. Western blots with plasma membrane–enriched fractions of cell lysate detected elevated levels of p22

phox

, p67

phox

, and rac-1, which indicates increased oxidase assembly. Finally, mice lacking a functional gp91

phox

subunit of NADPH oxidase demonstrated normal NO-dependent regulation of myocardial O
2
consumption after methionine feeding.

Conclusions—

In HHcy, superoxide produced by NADPH oxidase reduces the ability of NO to regulate mitochondrial function in the myocardium. The severity of this effect is proportional to the increase in homocysteine.
Juvenile Decertification
Authors: Marczyk Geoffrey R. , Heilbrun Kirk , Lander Tammy , Dematteo David
Published: April 2005

This study considers the impact of data from the Psychopathy Checklist: Youth Version (PCL:YV), the Massachusetts Youth Screening Instrument (MAYSI), and the Youth Level of Service Case Management Inventory (YLS/CMI) on the court’s decision whether to decertify an adolescent defendant back to juvenile court or keep the defendant in criminal court. There are significant positive relationships between certification status and age; number of violent charges; total charges; PCL:YV, YLS/CMI, and MAYSI total scores; and select subscales of the MAYSI and the YLS/CMI. Significant differences are found between those who remained in the adult criminal justice system and those who were decertified to the juvenile justice system for age, YLS/CMI total score, and the Prior and Current Offenses and Dispositions and Personality and Behavior subscales of the YLS/CMI. The combination of PCL:YV total score and select subscales from the MAYSI and YLS/CMI provided the most accurate model for predicting certification status.
Reliability and Validity Analyses of the Youth Level of Service/Case Management Inventory
Authors: Schmidt Fred , Hoge Robert D. , Gomes Lezlie
Published: April 2005

The Youth Level of Service/Case Management Inventory (YLS/CMI) is a structured assessment tool designed to facilitate the effective intervention and rehabilitation of juvenile offenders by assessing each youth’s risk level and criminogenic needs. The present study examined the YLS/CMI’s reliability and validity in a sample of 107 juvenile offenders who were court-referred for mental health assessments. Results demonstrated the YLS/CMI’s internal consistency and interrater reliability. Moreover, the instrument’s predictive validity was substantiated on a number of recidivism measures for both males and females. Limitations of the current findings are discussed.
Development and Validation of a Role-Play Test for Assessing Crisis (Hostage) Negotiation Skills
Authors: Van Hasselt Vincent B. , Baker Monty T. , Romano Stephen J. , Sellers Alfred H. , Noesner Gary W. , Smith Stan
Published: April 2005

The purpose of this article is to (a) describe the construction of a role-play test (RPT), which is based on actual negotiated encounters by the Crisis Negotiation Unit of the FBI and employed specifically for evaluation and training of negotiation skills, and (b) provide preliminary validational support for the RPT. The first part of the study includes an overview of RPT item development and the role of active-listening skills, and the second part involves the validation of the RPT. Both groups were also administered self-report measures of social problem-solving skills and emotional empathy. Results indicate that in comparison to experts, nonexpert negotiators show deficiencies across active-listening skill categories. Relationships between use of active listening and emotional empathy are observed.
Defining Higher Order Dimensions of Self-Reported Health
Authors: Cella David , Chang Chih-Hung , Wright Benjamin D. , Von Roenn Jamie H. , Skeel Roland T.
Published: April 2005

We illustrate a method for understanding the extent to which a pool of fairly diverse health status questions can be examined for their dimensionality, by first fitting the data to a unidimensional measurement model, then examining item fit and residual factor analysis to determine the pattern of deviations from unidimensionality. We simultaneously administered five questionnaires to 1,714 people with cancer and HIV disease and combined all responses into one analysis. Item responses were cocalibrated onto one presumed underlying construct, often referred to as health-related quality of life (HRQOL). To identify significant, higher order substructures in the data, we then conducted a factor analysis of the data residuals, revealing two definable higher order dimensions: physical well-being and mental well-being. These results agree with other research and provide direction for further studies defining these dimensions within an item response theory (IRT) tradition.
Data Pooling and Analysis to Build a Preliminary Item Bank
Authors: Eton David T. , Lai Jin-Shei , Cella David , Reeve Bryce B. , Talcott James A. , Clark Jack A. , McPherson Carol P. , Litwin Mark S. , Moinpour Carol M.
Published: April 2005

Assessing bowel function (BF) in prostate cancer can help determine therapeutic trade-offs. We determined the components of BF commonly assessed in prostate cancer studies as an initial step in creating an item bank for clinical and research application. We analyzed six archived data sets representing 4,246 men with prostate cancer. Thirty-one items from validated instruments were available for analysis. Items were classified into domains (diarrhea, rectal urgency, pain, bleeding, bother/distress, and other) then subjected to conventional psychometric and item response theory (IRT) analyses. Items fit the IRT model if the ratio between observed and expected item variance was between 0.60 and 1.40. Four of 31 items had inadequate fit in at least one analysis. Poorly fitting items included bleeding (2), rectal urgency (1), and bother/distress (1). A fifth item assessing hemorrhoids was poorly correlated with other items. Our analyses supported four related components of BF: diarrhea, rectal urgency, pain, and bother/distress.
Combining Distribution- and Anchor-Based Approaches to Determine Minimally Important Differences
Authors: Yost Kathleen J. , Eton David T.
Published: April 2005

Health-related quality of life (HRQOL) is an important endpoint in cancer clinical trials and in cancer treatment in general; however, the meaningfulness of HRQOL scores may not be apparent to clinicians or researchers. Minimally important differences (MIDs) can enhance the interpretability of HRQOL scores by identifying differences likely to be meaningful to patients and clinicians. This article’s objective is to describe and provide examples of approaches we have used to identify MIDs for instruments in the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. Distribution- and anchor-based approaches are described and illustrated. We also discuss the importance of assessing the appropriateness of anchors, and we provide suggestions for combining results into a single range of plausible MIDs. MIDs for FACIT instruments established to date are summarized, and general guidelines that can be used to estimate MIDs for other FACIT instruments are provided. Applications of MIDs in research are illustrated.
General Population and Cancer Patient Norms for the Functional Assessment of Cancer Therapy-General (FACT-G)
Authors: Brucker Penny S. , Yost Kathleen , Cashy John , Webster Kimberly , Cella David
Published: April 2005

Given the number of new cancer cases diagnosed each year and the increases in survival rates, the importance of having a clinically useful health-related quality of life (HRQOL) instrument has increased. The Functional Assessment of Cancer Therapy-General (FACT-G) is one such instrument that has been used worldwide to assess HRQOL. Previously, the use of the FACT-G had been limited because of a lack of published normative data. Normative data are useful for consumers to place their results in an appropriate context by comparing their scores of individuals or group of individuals to a reference group. Here, we present normative data for the FACT-G for two reference groups: (a) a sample of the general U.S. adult population and (b) a large, heterogeneous sample of adult patients with cancer. In addition, we demonstrate various uses of the normative data.