bluuebunny/crossref_metadata_2025 huggingface dataset:
APPLICATIONS OF A NEW HAMILTONIAN OF INTERACTION TO ONE-DIMENSIONAL AND TWO-DIMENSIONAL STRUCTURES
Authors: DOLOCAN ANDREI , DOLOCAN VOICU
Published: March 2004

We apply a new interaction Hamiltonian (Ref. 1) to two-dimensional and one-dimensional structures. We have found that, for small values of the wavevector, the interaction energy presents a logarithmic divergence and in a one-dimensional lattice, a cotangent divergence in addition. But, in a two-dimensional lattice the divergence terms may cancel, and from the point of view of the interactions the crystal structure is possible. The interaction energy has a polynomial dependence on the form 1/an where the maximum value of n is 7; a is the lattice constant.
ROLE OF HYBRIDIZATION IN THE SUPERCONDUCTING PROPERTIES OF AN EXTENDED d–p HUBBARD MODEL
Authors: CALEGARI E. J. , MAGALHÃES S. G. , GOMES A. A.
Published: March 2004

In this work the variational Roth's approach previously developed by the present authors to describe cuprate systems is extended to include the superconducting properties. We extend the Beenen and Edwards approach by including the d–p hybridization. The role of the d–p hybridization in modifying the values of superconducting order parameter is then studied in terms of the adopted values of the parameters defining the Hamiltonian of the system.
ON LOWER AND UPPER BOUNDS FOR ENERGY EIGENVALUES OF QUANTUM DOTS
Authors: SOLDATOV A. V.
Published: March 2004

The problem of precise estimation of the low-lying discrete energy spectrum of quantum dots was addressed rigorously by means of the methods of upper and lower bounds for eigenvalues of linear Hermitian operators in Hilbert space. It was shown that the method of intermediate problems for eigenvalues and the classical Rayleigh–Ritz method may be fused into effective tool of analytical and numerical investigation of the energy spectrum of quantum dots thus enabling and facilitating calculation of eigenvalues with controlled or prescribed precision. As an example, the energy spectrum problem for a simple two-electron quantum dot with harmonic-oscillator spherical confinement potential was thoroughly analyzed. Precise numerical calculations corroborated that in the absence of external magnetic field the ground state of the dot is the spin singlet for quantum dots of arbitrary characteristic size, so that no spontaneous singlet-triplet "phase transition" can occur.
A COMPUTER MODEL OF THE FERROELECTRIC PROPERTIES OF MICROTUBULES
Authors: CAMPBELL ROBERT D. J.
Published: March 2004

The tubulin dimers of microtubules are arranged in a crystalline lattice which is wrapped to form a long cylinder. Two different arrangements of monomers within the lattice have been postulated: the A-lattice and the B-lattice. Previous studies have assumed that both lattice types are hexagonal with each dimer surrounded by six nearest-neighbors. Based on recent biochemical studies I argue that both lattice types can also be formed with each dimer having four nearest-neighbors. This has important consequences for the overall behavior of the model. It is generally assumed that tubulin dimers possess a mobile electric dipole which can exist in one of two discrete Ising spin states: -1 (down) or +1 (up). The average of all these states within a microtubule is the mean polarization and is a measure of the dipole ordering within the lattice. Microtubule models with six nearest-neighbors behave like models of ferroelectric substances: at low temperatures the lattice is highly ordered with most (if not all) dipoles pointing in the same direction, but as the temperature increases, the degree of ordering decreases due to random thermal flipping of the dipoles. The mean polarization is particularly erratic at physiological temperatures. In contrast, when the microtubule lattice is modeled with four nearest-neighbors, the mean lattice polarization is quite stable and remains close to zero over a wide temperature range that includes 37°C (310K). This raises new questions about the biophysical role of microtubules.
PREDICTING EFFICACY OF PROTON PUMP INHIBITORS IN REGULATING GASTRIC ACID SECRETION
Authors: SUD DHRUV , JOSEPH IAN M. P. , KIRSCHNER DENISE
Published: March 2004

Developing drugs to treat gastric acid related illnesses such as ulcers and acid reflux disease is the leading focus of pharmaceutical companies. In fact, expenditure for treating these disorders is highest among all illnesses in the US. Over the last few decades, a class of drugs known as a proton pump inhibitors (PPIs) appeared on the market and are highly effective at abating gastric illnesses by raising stomach pH (reducing gastric acid levels). While much is known about the action of PPIs , there are still open questions regarding their efficacy, dosing and long-term effects. Here we extend a previous gastric acid secretion model developed by our group to incorporate a pharmacodynamic/pharmacokinetic model to study proton pump inhibitor (PPI) action. Model-relevant parameters for specific drugs such as omeprazole (OPZ) , lansoprazole (LPZ) and pantoprazole (PPZ) were used from published data, and we conducted simulations to study various aspects of PPI treatment. Clinical data suggests that duration of acid suppression is dependent on proton pump turnover rates and this is supported by our model. We found the order of efficacy of the different PPIs to be OPZ>PPZ>LPZ for clinically recommended dose values, and OPZ>PPZ=LPZ for equal doses. Our results indicate that a breakfast dose for once-daily dosing regimens and a breakfast-lunch dose for twice-daily dosing regimens is recommended. Simulation of other gastric disorders using our model provides atypical applications for the study of drug treatment on homeostatic systems and identification of potential side-effects.
A MODEL FOR THE EFFECT OF TIME DELAY ON THE DYNAMICS OF A POPULATION LIVING IN A POLLUTED ENVIRONMENT
Authors: DUBEY B.
Published: March 2004

In this paper, a mathematical model is proposed and analyzed to study the effect of time delay on the dynamics of a single-species population living in a polluted environment. It is shown that time delay in the model has destabilizing effect on the system.
ENDOPRIMAL TORSION-FREE SEPARABLE ABELIAN GROUPS
Authors: GÖBEL R. , KAARLI K. , MÁRKI L. , WALLUTIS S. L.
Published: March 2004

We give a characterization for the groups in the title in terms of the graph structure of the critical types occurring in the group. Moreover, we give an example of arbitrarily large endoprimal indecomposable groups.
REPRESENTATIONS OF SIMPLE POINTED HOPF ALGEBRAS
Authors: YANG SHILIN
Published: March 2004

In this paper, the representation type of a class of pointed Hopf algebras is determined. As an application, all indecomposable modules of a simple-pointed Hopf algebra R(q,α) are classified. The Clebsch–Gordan-like formula for the decomposition of the tensor product, taken on the ground field, of two indecomposable modules of R(q,α) is obtained.
"WEAK" SYMMETRIES AND ADAPTED VARIABLES FOR DIFFERENTIAL EQUATIONS
Authors: CICOGNA GIAMPAOLO
Published: March 2004

It is shown that the introduction of suitable "symmetry-adapted" variables for the study of differential equations can be efficient and useful even if the problem does not admit symmetries. This method not only provides new solutions but also leads to the introduction of weaker notions of symmetry, and allows a natural classification of the possible types of symmetry, each of which is characterized by a specific form of the equation when written in the appropriate variables. Some simple examples are briefly proposed.
A PORT SYSTEM SIMULATION FACILITY WITH AN OPTIMIZATION CAPABILITY
Authors: DAHAL KESHAV , GALLOWAY STUART , BURT GRAEME , MCDONALD JIM , HOPKINS IAN
Published: March 2004

This paper details the optimization of bulk material port handling systems through the use of an evolutionary based approach. The effective management of port systems requires effective solutions for the design, operation and maintenance of these facilities. This has to be achieved through a reduction in financial costs, and an increase in the utilization of equipment and other resources. The operation of a port system is complex and difficult to model mathematically. Consequently, through the explicit characterization of port components, a port modeling tool was developed that permits the generic construction of port simulation models. A genetic algorithm based approach was developed to provide an optimization capability to the port simulation tool. Two case studies based on real world port systems are presented and the results are discussed. A significant improvement is demonstrated in both the operational and economic performance as a result of the GA/model interaction.
Chemokines inInnate andAdaptiveHostDefense: Basic Chemokinese Grammar for Immune Cells
Authors: Rot Antal , von Andrian Ulrich H.
Published: March 2004

▪ Abstract  Chemokines compose a sophisticated communication system used by all our cell types, including immune cells. Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular. Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via “silent” chemokine receptors (interceptors) leading either to their transcytosis or to degradation. These regulatory mechanisms of chemokine histotopography, as well as the promiscuous and overlapping receptor specificities of inflammation-induced chemokines, shape innate responses to infections and tissue damage. Conversely, the specific patterns of homeostatic chemokines, where each chemokine is perceived by a single receptor, are charting lymphocyte navigation routes for immune surveillance. This review presents our current understanding of the mechanisms that regulate the cellular perception and pathophysiologic meaning of chemokines.
The Role of Complement in the Development of Systemic Lupus Erythematosus
Authors: Manderson Anthony P. , Botto Marina , Walport Mark J.
Published: March 2004

▪ Abstract  Complement has both beneficial and deleterious roles in the pathogenesis of systemic lupus erythematosus (SLE). On the one hand, patients with SLE present with decreased complement levels and with complement deposition in inflammed tissues, suggestive of a harmful role of complement in the effector phase of disease. On the other hand, homozygous deficiency of any of the classical pathway proteins is strongly associated with the development of SLE. There are two main hypotheses to explain these observations. The first invokes an important role for complement in the physiological waste-disposal mechanisms of dying cells and immune complexes. The second hypothesis is based around the role of complement in determining the activation thresholds of B and T lymphocytes, with the proposal that complement deficiency causes incomplete maintenance of peripheral tolerance. These two hypotheses are not mutually exclusive. In addition, there is evidence for a contribution from other genetic factors in determining the phenotype of disease in the absence of complement.
CD1: Antigen Presentation and T Cell Function
Authors: Brigl Manfred , Brenner Michael B.
Published: March 2004

▪ Abstract  This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCRα chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells. This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity.
Integrins and T Cell–Mediated Immunity
Authors: Pribila Jonathan T. , Quale Angie C. , Mueller Kristen L. , Shimizu Yoji
Published: March 2004

Integrin receptors mediate adhesive events that are critical for a specific and effective immune response to foreign pathogens. Integrin-dependent interactions of lymphocytes and antigen-presenting cells (APCs) to endothelium regulate the efficiency and specificity of trafficking into secondary lymphoid organs and peripheral tissue. Within these sites, integrins facilitate cell movement via interactions with the extracellular matrix, and promote and stabilize antigen-specific interactions between T lymphocytes and APCs that are critical for initiating T cell–activation events. In this review, we discuss the role of integrins in T cell–mediated immunity, with a focus on how these receptors participate in lymphocyte recirculation and T cell activation, how antigen stimulation regulates integrin activity, and how integrins define functionally unique subsets of T cells and APCs.
Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
Authors: Sallusto Federica , Geginat Jens , Lanzavecchia Antonio
Published: March 2004

The memory T cell pool functions as a dynamic repository of antigen-experienced T lymphocytes that accumulate over the lifetime of the individual. Recent studies indicate that memory T lymphocytes contain distinct populations of central memory (TCM) and effector memory (TEM) cells characterized by distinct homing capacity and effector function. This review addresses the heterogeneity of TCMand TEM, their differentiation stages, and the current models for their generation and maintenance in humans and mice.
Asthma: Mechanisms of Disease Persistence and Progression
Authors: Cohn Lauren , Elias Jack A. , Chupp Geoffrey L.
Published: March 2004

▪ Abstract  When asthma is diagnosed, eosinophilic inflammation and airway remodeling are established in the bronchial airways and can no longer be separated as cause and effect because both processes contribute to persistence and progression of disease, despite anti-inflammatory therapy. Th2 cells are continually active in the airways, even when disease is quiescent. IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-β and promotes epithelial damage, mucus production, and eosinophilia. The production of IL-13 and other Th2 cytokines by non-T cells augments the inflammatory response. Inflammation is amplified by local responses of the epithelium, smooth muscle, and fibroblasts through the production of chemokines, cytokines, and proteases. Injured cells produce adenosine that enhances IL-13 production. We review human and animal data detailing the cellular and molecular interactions in established allergic asthma that promote persistent disease, amplify inflammation, and, in turn, cause disease progression.
PhysiologicalControl ofImmuneResponse andInflammatoryTissueDamage byHypoxia-InducibleFactors andAdenosineA2AReceptors
Authors: Sitkovsky Michail V. , Lukashev Dmitriy , Apasov Sergey , Kojima Hidefumi , Koshiba Masahiro , Caldwell Charles , Ohta Akio , Thiel Manfred
Published: March 2004

▪ Abstract  Immune cell–mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause immunopathologies. The search for physiological mechanisms that downregulate activated immune cells has revealed a critical role for extracellular adenosine and for immunosuppressive A2Aadenosine receptors in protecting tissue from inflammatory damage. Tissue damage–associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A2Areceptors triggering “OFF” signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as “reporters,” while A2Aadenosine receptors serve as “sensors” of excessive tissue damage. The A2Areceptor–triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A2Aadenosine receptors may have important clinical applications.
The Three Es of Cancer Immunoediting
Authors: Dunn Gavin P. , Old Lloyd J. , Schreiber Robert D.
Published: March 2004

After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models—together with compelling data from human patients—indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed “cancer immunoediting.” In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting—elimination, equilibrium, and escape.
Panic Attacks and the Risk of Depression among Young Adults in the Community
Authors: Goodwin Renee D. , Fergusson David M. , Horwood L. John
Published: March 2004

Objective: To determine the association between panic attacks and the risk of major depression among young adults in the community. Method: Data were drawn from a 21-year longitudinal birth cohort study (n = 1, 265). Multiple logistic regression analyses were used to determine the association between panic attacks in adolescence (age 15–21 years) and the risk of current major depression (past month). Results: Having a panic attack in the preceding 3 years was significantly associated with elevated risk of current major depression (past month) at the ages of 18 and 21. This association persisted after adjusting for a range of fixed social, family and individual risk factors for psychopathology, history of major depression, comorbid psychiatric disorder and life adversity among both males (OR = 8.9; 95% CI = 3.9–20.4) and females (OR = 2.3; 95% CI = 1.2–4.2). Conclusions: These data are consistent with and extend previous work by showing that panic attack increases the risk of current major depression, independent of the effects of psychiatric comorbidity and other early risk factors for psychopathology, though much of this relationship appears to be explained by common risk factors and comorbidity. These data show new evidence of interaction between gender and panic attacks in the risk of depression among young persons. Replication of these findings is needed, as are future studies that further investigate the underlying mechanism of this association.
Prediction of Treatment Outcome of Patients with Functional Gastrointestinal Disorders by the Diagnostic Criteria for Psychosomatic Research
Authors: Porcelli Piero , De Carne Massimo , Todarello Orlando
Published: March 2004

Background: The Diagnostic Criteria for Psychosomatic Research (DCPR) have been demonstrated to be useful in identifying specific psychological conditions of medical patients. The aim of this study was to evaluate the clinical utility of the DCPR in predicting the treatment outcome of patients with functional gastrointestinal disorders (FGID). Methods: FGID outpatients were allocated to improved (n = 65) and unimproved (n = 40) groups on the basis of preestablished criteria following 6 months of treatment. Patients were administered the structured interview for DCPR at baseline and the Gastrointestinal Symptom Rating Scale both at baseline and follow-up. Results: In the unimproved patients, the prevalence of the DCPR categories of alexithymia (82.2%) and persistent somatization (72.5%) was significantly higher while health anxiety was more prevalent in improved patients (21.5%). No unimproved patient lacked a DCPR diagnosis while multiple DCPR diagnoses were significantly higher in the unimproved group (90%). In the regression analysis, alexithymia, persistent somatization, a higher number of DCPR diagnoses for each patient and, to a lesser extent, greater symptom severity at baseline were significant predictors of unimprovement. Health anxiety, even after controlling for gastrointestinal symptoms, was a significant predictor of improvement. Conclusion: The ability to predict treatment outcome indicates the clinical utility of the DCPR. Clinicians may improve treatment outcome for FGID patients by identifying particular psychosomatic syndromes (alexithymia, persistent somatization, and health anxiety) and patients with multiple DCPR clusters, and attempting to address specific therapeutic interventions.
Expansion of TcRαβ+CD3+CD4–CD8– (CD4/CD8 Double-Negative) T Lymphocytes in a Case of Staphylococcal Toxic Shock Syndrome
Authors: Carulli Giovanni , Lagomarsini Ginetta , Azzarà Antonio , Testi Rossana , Riccioni Rossella , Petrini Mario
Published: March 2004

A 55-year-old woman presented with staphylococcal toxic shock syndrome (TSS). During the course of the disease a significant lymphocytosis appeared, and a high number of TcRαβ+CD3+CD4–CD8– (double-negative, DN) lymphocytes was observed both in bone marrow and in peripheral blood samples. Correction of the altered lymphocyte immunophenotype was observed only 6 weeks after recovery from TSS. The immunophenotype of circulating and bone marrow lymphocytes was also studied during a phase of an aspecific febrile episode observed 2 months after recovery, but no subset of DN lymphocytes was found. A small subset of DN lymphocytes can be found in normal bone marrow, liver, thymus, and skin. These cells show peculiar immune regulatory properties and can increase in certain autoimmune diseases. Our findings may represent a specific effect of lymphocyte stimulation by the staphylococcal exotoxin, which is the effector agent of TSS.
T Cell Prolymphocytic Leukemia with New Chromosome Rearrangements
Authors: Zver Samo , Kokalj Vokac Nadja , Zagradisnik Boris , Erjavec Alenka , Zagorac Andreja , Preloznik Zupan Irena , Cernelc Peter
Published: March 2004

A 77-year-old woman presented to the outpatient hematology clinic in August 2001 with leukocytosis, recurrent bacterial infections, sweating and weight loss. Bone marrow biopsy showed 80% infiltration with lymphoid cells having a prolymphocytic morphology. Flow-cytometric immunophenotype analysis showed that over 80% of the cells were positive for CD2, CD3, CD4, CD5 and CD7 antigens and negative for terminal deoxynucleotidyl transferase and CD1a antigens. T cell prolymphocytic leukemia (T-PLL) was diagnosed on the basis of these findings. The diagnosis was later confirmed by cytogenetic analysis and fluorescence in situ hibridization. The patient had the following karyotype: 46,X,der(X)t(X;3) (q28;p25) t(X;16)(p14;q12), der(3) t(X;3)(q28;p25), der(6) t (X;6) (p14;q25), (8) (q10), del(11) (q14q23), der(13) t (5;13) (q34;p11), der(13) t(13;14)(q22;q11), inv(14)(q11q32), der (16) t(X;16)(q28;q12), r(17)(p13q21), der(20) t(17;20) (q21; q13),22p+. The cytogenetic rearrangements der(6)t(X;6) (p14;q25), der(13)t(13;14)(q22;q11),t(5;13)(q34;p11), r(17) (p13q21) and t(17;20)(q21;q13) have not been described previously in the literature in patients with T-PLL.
The Role of Itraconazole in Preventing and Treating Systemic Fungal Infections in Immunocompromised Patients
Authors: Potter M. , Donnelly J.P.
Published: March 2004

The increasing use of immunosuppressive chemotherapy and allogeneic transplants for haematological malignancies has increased the number of patients at risk of systemic fungal infections (SFIs). A number of antifungal agents are now available. This paper reports the deliberations of an expert panel that considered the role of itraconazole. It concluded that itraconazole has an important role in the prophylaxis and treatment of SFIs whether proven or not.
Increased Prevalence of Perennial Allergic Rhinitis in Patients with Obstructive Sleep Apnea
Authors: Canova C.R. , Downs S.H. , Knoblauch A. , Andersson M. , Tamm M. , Leuppi J.D.
Published: March 2004

Background: Impaired nasal breathing is a risk factor for obstructive sleep apnea syndrome (OSAS). Objectives: The aim of this study was to determine whether atopy to perennial allergens and existence of perennial allergic rhinitis was a risk factor for OSAS. Methods: In a case-control study, we compared the proportions of OSAS patients with atopy to perennial allergens and perennial allergic rhinitis to the proportions in patients with chronic obstructive pulmonary disease (COPD). Seventy-two OSAS patients (mean age 60.7 years; 79.4% male) and 44 COPD patients (mean age 63.6 years; 88.6% male) were selected from a hospital outpatients’ clinic in Switzerland. All patients completed a respiratory symptom questionnaire, performed spirometry and had a skin prick test for atopy. Results: OSAS patients were significantly heavier than COPD patients (BMI 32.4 ± (SD) 6.6 vs. 29.2 ± 6.6 kg/m2, p = 0.04) and had a better lung function than COPD patients (FEV1% predicted 91.3 ± 19.2 vs. 51.6 ± 18.9%, p < 0.001). Patients with OSAS were more likely to be sensitized to perennial allergens such as house dust mite (23.6 vs. 4.5%, p = 0.009) and dog (18 vs. 4.5%, p = 0.04) than the COPD patients. Perennial allergic rhinitis (having nose problems [nasal obstruction and/or runny nose and/or sneezing] all year and being atopic to at least one perennial allergen) was reported in 11% of OSAS patients but in only 2.3% of COPD patients (p = 0.15). Conclusion: We conclude that subjects with OSAS may have an increased risk of being allergic to perennial allergens and suffer from perennial rhinitis. Awareness of this risk may have important consideration in the clinical situation.
Potential Limitations of Clinical Criteria for the Diagnosis of Idiopathic Pulmonary Fibrosis/Cryptogenic Fibrosing Alveolitis
Authors: Peckham Russell M. , Shorr Andrew F. , Helman Jr Donald L.
Published: March 2004

Background: The need to perform surgical lung biopsy (SLB) in all cases of suspected idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (IPF/CFA) is controversial. The American Thoracic Society (ATS) and the European Respiratory Society (ERS) recently endorsed explicit clinical criteria for the diagnosis of IPF/CFA in the absence of SLB. Prior studies evaluating clinical criteria for the diagnosis of IPF/CFA have been limited in that either they were performed by clinicians with expertise in the diagnosis of IPF/CFA or they did not utilize explicit diagnostic criteria. We investigated the accuracy of the ATS/ERS criteria when applied in a general pulmonary medicine setting. Objectives: To determine the interobserver variability of clinical criteria for the diagnosis of IPF/CFA. Methods: This was a retrospective, blinded evaluation by three board certified pulmonary physicians without extensive experience in the evaluation of IPF/CFA performed at a United States Army tertiary care academic medical center. Patients referred for surgical lung biopsy as part of a diagnostic evaluation of interstitial lung disease (ILD) were evaluated. The physicians reviewed high-resolution computed tomography scans of the chest (HRCT) and clinical data for each patient. The physicians were blinded to all other data and to the opinions of other study participants. Employing the histologic presence of usual interstitial pneumonia (UIP) coupled with appropriate clinical findings as the gold standard for a diagnosis of IPF/CFA we determined the accuracy and interobserver variability for a diagnosis of IPF/CFA based on HRCT alone and based on the ATS/ERS clinical criteria. Results: The sensitivity and positive predictive value for a HRCT diagnosis of IPF/CFA were 71% each while specificity and negative predictive value were 67% each. For the ATS/ERS criteria sensitivity, specificity, positive predictive value and negative predictive value were 71, 75, 77 and 69%, respectively. The interobserver variability, expressed as a kappa coefficient, for HRCT and the ATS/ERS criteria were 0.59 and 0.53, respectively. Conclusions: Both HRCT and the ATS/ERS clinical criteria may lead to misdiagnosis of patients with ILD. Further studies are needed to fully characterize the accuracy of these tests when applied in a routine pulmonary medicine practice setting.
Bronchoscopy with the Vision Sciences BF100 Disposable-Sheath Device: French Experience after 328 Procedures
Authors: Margery Jacques , Vaylet Fabien , Guigay Joël , Grassin Frédéric , Dot Jean-Marc , Morel Vincent , Vaures Evelyne , Marotel Claude , Demuys Christelle , L’Her Pierre
Published: March 2004

Background: In spite of adhesion to recommended disinfection procedures, the transmission of infections by bronchoscopes is a permanent problem. Objective: The new device may prevent nosocomial infections because it consists of two parts: a specific bronchoscope Vision Sciences BF100 and a single-use protective sheath for each procedure. The aim of this paper is to report our practice and the difficulties encountered when using this system. Methods: We report our experience from 1997 to 2002 after 328 elective and emergency endoscopic procedures with the BF100 device. In a retrospective study, we describe the population and the incidents during procedure. We discuss the impact of the use of BF100 on the cost of bronchoscopies. Results: The major constraint is the care required in assembling the optical device and disposable sheath. The intrinsic qualities of the optics are confirmed; any sample may be taken although image quality and suction capacity are inferior to videoscopes. Maneuverability is inferior to videoscopes, but improves with a short experience. In addition, this device is expensive. Conclusions: The technical performances of the BF100 device are inferior to those of videoscopes but the concept of sterile single-use sheaths is able to prevent the nosocomial infections related to bronchoscopes. Because of the cost, examination with the BF100 should be reserved to patients with proved or suspected infection (multiresistant bacteria, tuberculosis, hepatitis C and B virus, HIV, prions) and immunosuppression (hematologic diseases).
Long-Term Survival of a Patient with Congenital Central Hypoventilation Syndrome despite the Lack of Continuous Ventilatory Support
Authors: Windisch Wolfram , Hennings Ellen , Storre Jan Hendrik , Matthys Heinrich , Sorichter Stephan
Published: March 2004

Untreated idiopathic congenital central hypoventilation syndrome (CCHS) is thought to cause infant death within 1–2 months. Here we present an adult patient with CCHS who survived without continuous ventilatory support, despite hypoventilation from early childhood onward. The diagnosis was confirmed at the age of 22 years, when the patient presented with hypoventilation during the night (PaCO2 60 mm Hg, PaO2 56 mm Hg, pH 7.32 HCO–3 30 mmol/l) but hyperventilation when awake (PaCO2 26 mm Hg, PaO2 81 mm Hg, pH 7.56, HCO–3 23 mmol/l). The maximal hematocrit was 77%. Despite mental retardation, noninvasive positive pressure ventilation (NPPV) could be successfully established. NPPV-supported ventilation during the night (PaCO2 36, PaO2 84 mm Hg, pH 7.47, HCO–3 25 mmol/l) reduced hematocrit values (40.6 to 36.8%) over a period of 4 years. In conclusion, long-term survival with CCHS is possible without continuous ventilatory support. Spontaneous improvement of hypoventilation during sleep throughout childhood is possible and hyperventilation during wakefulness may occur in patients with CCHS. CCHS can be managed with NPPV despite mental retardation, even over a long-term period.
Family-Based Association Study between the Monoamine Oxidase A Gene and Obesity: Implications for Psychopharmacogenetic Studies
Authors: Camarena Beatriz , Santiago Haydee , Aguilar Alejandro , Ruvinskis Elsa , González-Barranco Jorge , Nicolini Humberto
Published: March 2004

Family studies have reported that obesity has a strong heritable component. It has been suggested that a neurotransmitter dysfunction could be involved in mental disorders and obesity; therefore, candidate genes in psychiatric disorders could be a risk factor for obesity. We investigated the association between the monoamine oxidase A (MAO-A) gene and obesity. Fifty obese subjects and their parents were included in the study. Two polymorphisms designated EcoRV and upstream variable number tandem repeats of the MAO-A gene were analysed using polymerase chain reaction. For analysis of the families, the transmission disequilibrium test (TDT) was applied. The TDT analysis of the EcoRV polymorphism showed in obese subjects with a body mass index (BMI) ≧35 kg/m2 a preferential transmission of the low activity-related allele (χ2TDT = 8.0, p = 0.005). Our findings may provide evidence of a candidate gene involved in obese subjects with a BMI ≧35 kg/m2.
Exophthalmos in Obesity
Authors: Smolders M.H. , Graniewski-Wijnands H.S. , Meinders A.E. , Fogteloo A.J. , Pijl H. , de Keizer R.J.W.
Published: March 2004

Aims: To establish the relationship between exophthalmos and obesity. Methods: A group of 19 obese patients (body mass index, BMI ≧30 kg/m2) was compared with a control group of 45 nonobese individuals (26 > BMI ≧ 20 kg/m2). Both groups underwent Hertel’s exophthalmometry, Goldmann applanation tonometry and measurement of the medial rectus muscle by echography. Results: Obese patients had higher Hertel values and enlarged medial rectus muscle diameter (p < 0.05). Indeed, bilateral exophthalmos was observed in 33% of obese subjects. However, this did not cause any ocular morbidity. In some cases the difference in intraocular pressure was enlarged but together with the exophthalmos not statistically significant. Conclusions: Standard values for exophthalmometry and orbital echography may have to be adapted for obese individuals. In several cases the eye signs had a remarkable resemblance to patients with Graves’ orbitopathy. So in each patient with bilateral exophthalmos and eye signs suspicious of Graves’ orbitopathy obesity should be considered as a possible cause.
Association of a Homozygous Nonsense Mutation in the ABCA4 (ABCR) Gene with Cone-Rod Dystrophy Phenotype in an Italian Family
Authors: Simonelli Francesca , Testa Francesco , Zernant Jana , Nesti Anna , Rossi Settimio , Rinaldi Ernesto , Allikmets Rando
Published: March 2004

Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull’s eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology.
Diquafosol Elicits Increases in Net Cl– Transport through P2Y2 Receptor Stimulation in Rabbit Conjunctiva
Authors: Murakami Tadahiro , Fujihara Tsutomu , Horibe Yoshihide , Nakamura Masatsugu
Published: March 2004

The purpose of the present study was to understand the mechanisms of action of diquafosol, a stable derivative of uridine 5′-triphosphate, on Cl– transport across the isolated rabbit conjunctiva. Rabbit conjunctivas were isolated and mounted in a modified Ussing chamber. Under short-circuit conditions, the effects were determined of mucosal (tear) side diquafosol application on the short-circuit current (Isc). Diquafosol rapidly and dose-dependently increased the Isc at concentrations ranging from 0.1 to 968 µM when added to the mucosal side of the conjunctiva. In the absence of the serosal Cl–, the Isc induced by 10 µM diquafosol was substantially reduced. On the contrary, in the absence of mucosal side Na+, the diquafosol-induced increases in Isc were unchanged. Following 45-min preincubation, the P2Y2 antagonist suramin inhibited the diquafosol-induced increases in the Isc whereas the P2Y1 antagonist pyridoxal-phosphate-6-azophenyl-2′4′-disulfonic acid had no effect. These studies suggest that diquafosol stimulates net Cl– secretion from the serosal to the mucosal side via stimulation of P2Y2 receptors in the rabbit conjunctiva.
Effects of Glucose on Blood Pressure and Production of Vascular Aldosterone and Corticosterone
Authors: Zhang Yongsheng , Chu Liyun , Yu Wengone , Pang Jien
Published: March 2004

Objective: The aims of this study were to search for the role of glucose in the regulation blood pressure of rats and to investigate the effects of glucose on the production of vascular aldosterone and corticosterone in rats. Methods: Male Wistar rats received glucose 15.0 g· kg–1·d–1 (glucose-treated group 1) or 25.0 g·kg–1·d–1 (glucose-treated group 2) or 35.0 g·kg–1·d–1 (glucose-treated group 3), orally, for 3 months, and blood pressure was monitored by a pressure transducer. Mesenteric artery perfusion ex vivo was performed and pressor responses to norepinephrine were determined in Wistar rats. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high-performance liquid chromatography and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Reverse transcriptase ploymerase chain reaction was used to measure the expression of 11β-HSD2 and CYP11B2 mRNA in mesenteric arteries. Results: Blood pressure increased in Wistar rats treated with glucose compared to control rats. The pressor responses to norepinephrine in mesenteric arteries treated with glucose were significantly increased. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with glucose. Reverse transcriptase ploymerase chain reaction showed that glucose inhibited the expression of 11β-HSD2 and CYP11B2 mRNA in mesenteric arteries. Conclusion: These results reveal that glucose able to induce hypertension and provide evidence that glucose inhibits the transcriptions of both 11β-HSD2 and CYP 11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.
Lipoprotein(a)-Associated Atherothrombotic Risk in Hemodialysis Patients
Authors: Emanuele Enzo , Lusignani Luigi Segagni , Peros Emmanouil , Montagna Giovanni , D’Angelo Angela , Montagna Lorenza , Geroldi Diego
Published: March 2004

Background: Hemodialysis patients show a considerably higher risk of atherothrombotic disease than the general population. We investigated both lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of atherothrombotic events in hemodialysis patients compared with subjects showing a normal kidney function. Methods: Lp(a) levels and apo(a) isoforms were determined in 118 hemodialysis patients, including 59 with prior atherothrombotic events, and in 182 subjects with normal creatinine clearance, including 82 who experienced a prior atherothrombotic event. Results: Lp(a) levels in hemodialysis patients (median; 20 mg/dl) were higher (p < 0.01) than in age- and sex-matched subjects with normal renal function without a history of atherothrombosis (11.3 mg/dl). Among hemodialysis patients, median Lp(a) levels were higher in subjects with than in those without prior atherothrombosis (34 vs. 15 mg/dl, p < 0.05). In hemodialysis patients and in subjects without nephropathy, the percentage of low-molecular-weight apo(a) phenotypes were significantly higher in patients with than in those without a history of prior atherothrombotic events (56.9% vs. 33.9%, p < 0.05; 62.2% vs. 25%, p < 0.00001,respectively). Stepwise regression analysis indicated that the presence of at least one apo(a) isoform of low molecular weight was an independent predictor of atherothrombosis in hemodialysis patients (p < 0.05). Conclusions: Elevated Lp(a) plasma levels appear to be associated with atherothrombosis, independent of their origin due to genetic factors or related to the impaired kidney function. Low-molecular-weight apo(a) isoforms are reliable genetic markers of atherothrombosis both in patients with impaired kidney function and in subjects without nephropathy.
Mechanisms of Single and Multiple Borderzone Infarct: Transcranial Doppler Ultrasound/Magnetic Resonance Imaging Correlates
Authors: Kumral Emre , Bayülkem Gamze , Sağcan Abdi
Published: March 2004

Background and Purpose: Hemodynamic patterns after borderzone (BZ) infarction are variable and dynamic. However, stroke mechanisms in different types of BZ infarctions have not been systematically studied by magnetic resonance angiography (MRA) and transcranial Doppler ultrasonography (TCD). Methods: Forty-nine patients who experienced a stroke limited to the territory of either the superficial or internal borderzone proved on MRI included in our registry, corresponding to 4% of 1,200 patients with ischemic stroke, were studied. All these patients underwent MRA, extracranial Doppler ultrasonography, TCD and other investigations from the standard protocol of our registry. Twenty of them (41%) had a posterior BZ infarct, 14 (29%) an anterior BZ infarct, 10 (20%) a subcortical BZ infarct and 5 (10%) bilateral BZ infarcts. Results: Unilateral internal carotid artery (ICA) tight stenosis or occlusion ipsilateral to the lesion was present in 14 patients (70%) with a posterior BZ infarct, in 72% of those with an anterior BZ infarct, in 80% of those with a subcortical BZ infarct and in 80% of those with bilateral BZ infarcts. TCD showed cross-filling of the middle cerebral artery via the anterior communicating artery in 5 patients (25%) with a posterior BZ infarct and 10% had an increased mean flow velocity (MFV) in the ipsilateral P1 posterior cerebral artery (PCA). In patients with an anterior BZ infarct, 3 (23%) had an MFV increase in the contralateral A1 anterior cerebral artery (ACA), and 2 (15%) had a higher MFV in the ipsilateral PCA. An elevated velocity at midline depths with reversed A1 ACA flow direction was seen in 2 patients (20%) with a subcortical infarct, and 1 patient (10%) had an MFV increase in the ipsilateral P1 PCA. Left ventricular systolic dysfunction (ejection fraction <40%) was present in 50% of patients with a posterior BZ infarct, in 36% of those with an anterior BZ infarct, in 20% of those with a subcortical BZ infarct and bilateral BZ infarcts each. Conclusion: The association of severe ICA stenosis or occlusion with cardiopathies and left ventricular dysfunction may play a critical role in those with BZ infarcts having inadequate collateral supply, while a cardioembolism or acute ICA dissection may also cause BZ infarction due to the rapidity of the occlusive process and the inability of the cerebral vasculature to recruit collateral pathways quickly enough.
Ligation of the Inferior Mesenteric Artery in the Surgery of Rectal Cancer: Anatomical Considerations
Authors: Nano Mario , Dal Corso Herbert , Ferronato Marco , Solej Mario , Hornung Jean Pierre , Dei Poli Marcello
Published: March 2004

Background: No agreement has been found in the literature concerning the safest point of ligation of the inferior mesenteric artery (ima) in order to avoid nerve damage during the surgery of rectal cancer. Study Design: The distance between the origin of the ima and the left paraortic trunk was measured, as was the distance between the left paraortic trunk and the origin of the left colic artery (lca). The measurements were carried out on 20 cadavers and during 22 operations for rectal cancer. Results: The left paraortic trunk always runs posterior to the ima: its distance from the origin of the ima is on average 1.2 cm; the distance of the left paraortic trunk from the origin of the lca is on average 0.4 cm. The point at which the ima and the left paraortic trunk cross varies greatly, but it is never near the origin of the ima. Conclusions: From an anatomical point of view the safest point of ligation of the ima is at its origin. At this point, the left paraortic trunk never runs; so there isn’t any risk to damage the nerve involving it during the ligation of the artery.
Prognostic Variables for Cancer-Related Survival in Node-Negative Colorectal Carcinomas
Authors: Di Fabio Francesco , Nascimbeni Riccardo , Villanacci Vincenzo , Baronchelli Carla , Bianchi Denise , Fabbretti Giovanna , Casella Claudio , Salerni Bruno
Published: March 2004

Background/Aim: The efficacy of adjuvant treatment in node-negative colorectal carcinoma is unproven. The purpose of this study was to analyze the prognostic value of routinely detectable clinicopathological variables in order to identify subgroups of node-negative colorectal cancer patients at a high risk of a recurrence. Methods: Seventy-three patients who did not receive radio- or chemotherapy were selected among 112 node-negative colorectal cancer patients who underwent curative resection. Follow-up was a minimum of 5 years or until death. The influence of 17 demographic, clinical, and pathological variables on the 5-year cancer-related survival was assessed using univariate and multivariate analyses. Results: The compliance with follow-up was 99%. The 5-year survival rate was 81%. Univariate analysis showed that T4 lesions (p < 0.001), age >70 years (p = 0.008), lymphatic invasion (p = 0.001), and neural invasion (p = 0.02) were significantly associated with a decreased survival. T4 stage (hazard ratio 12.75, p < 0.001) and age >70 (hazard ratio 3.08, p = 0.04) significantly affected the cancer-related survival on multivariate analysis. Conclusions: Node-negative colorectal cancer patients with T4 carcinoma or those aged over 70 years have a higher risk of recurrences after resection. They should receive adjuvant or neoadjuvant treatment compatible with their performance status.