bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single and multiple metachronous osteosarcoma tumors after therapy
Authors: Jaffe Norman , Pearson Peggy , Yasko Alan W. , Lin Patrick , Herzog Cynthia , Raymond Kevin 
Published: November 2003

AbstractBACKGROUNDThe objective of the current study was to determine the incidence, clinical and pathologic characteristics, and outcome of patients with conventional osteosarcoma who developed metachronous tumors after treatment for the primary tumor and prevention of pulmonary metastases.METHODSThe medical records of 270 pediatric patients (younger than age 18 years) were reviewed. The prevention and absence of pulmonary metastases was confirmed by chest radiographs and computerized scans of the lungs. Radionuclide bone scans were used to confirm the absence of skeletal metastases.RESULTSEleven patients with metachronous tumors were identified. Index primary tumors involved the femur (n = 8), the tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n = 4). Two patients later developed second metachronous tumors. The interval between identification of the primary tumor to development of the single metachronous tumors varied from 11 months to 78 months and from 12 months to 42 months for synchronous multifocal tumors. Metachronous tumors were treated with single‐agent cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis. Pulmonary metastases were not detected in 10 of 11 patients at the time metachronous tumors were discovered. In the 11th patient, synchronous pulmonary metastasis with the metachronous tumor was noted. Three patients had a prior history of bilateral retinoblastoma. The Li–Fraumeni syndrome may have been present in another patient. Six patients died. Five patients have survived for 20+ to 50+ months after the appearance, treatment, and resection of metachronous tumors.CONCLUSIONSWith improvement in the cure rate, metachronous osteosarcoma should be recognized as an important sequela in long‐term survivors. The etiology of this disease is unknown. Speculation rests on a skeletal multicentric origin, which includes an inherited predisposition to develop osteosarcoma in retinoblastoma and in the Li–Fraumeni syndrome. Meticulous follow‐up is required to permit early detection and successful therapeutic intervention. Cancer 2003. © 2003 American Cancer Society.
Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses
Authors: Wu Hillary H. , Talpaz Moshe , Champlin Richard E. , Pilat Susan R. , Kurzrock Razelle 
Published: November 2003

AbstractBACKGROUNDInterleukin‐3 (IL‐3) and granulocyte‐macrophage–colony stimulating factor (GM‐CSF) have synergistic, hematopoietic growth‐promoting activity in preclinical studies. Because of the paucity of effective therapies for patients with chronic bone marrow failure states, the authors studied the biologic activity of sequential IL‐3/GM‐CSF in such patients.METHODSIL‐3 was given subcutaneously for 5 days (at escalating doses of 0.15 μg/kg, 0.3 μg/kg, 0.6 μg/kg, 1.2 μg/kg, 2.5 μg/kg, 5.0 μg/kg, 10.0 μg/kg, or 15.0 μg/kg per day), and GM‐CSF for was given subcutaneously for 9 days (at a dose of 5 μg/kg per day; Phase I 3 + 3 design) followed by 14 days of rest (total, 2 courses), then maintenance therapy.RESULTSThe majority of 38 evaluable patients had aplastic anemia or myelodysplastic syndrome. Most patients (79%) had neutrophil responses. Ten patients (26%), all of whom were treated with IL‐3 doses ≥ 1.2 μg/kg per day, had platelet responses, with a median increase of 132 × 109/L (range, 41–180 × 109/L) over baseline in responders. Six patients (16%) had trilineage recovery, which could be durable (the longest ongoing at 6.5 years after therapy completion). The most common toxicities were low‐grade fever, headache, and fatigue. The maximum tolerated doses were IL‐3 at 10 μg/kg per day and GM‐CSF at 5 μg/kg per day.CONCLUSIONSSequential IL‐3/GM‐CSF effectively raised blood counts in some patients with bone marrow failure at doses that were tolerated well. These results indicate that early‐acting growth factors can induce durable, multilineage responses in a subset of individuals with bone marrow failure. Cancer 2003. © 2003 American Cancer Society.
Imatinib mesylate causes hypopigmentation in the skin
Authors: Tsao Anne S. , Kantarjian Hagop , Cortes Jorge , O'Brien Susan , Talpaz Moshe 
Published: November 2003

AbstractBACKGROUNDImatinib mesylate is a tyrosine kinase inhibitor that targets the BCR‐ABL protein in CML, c‐kit (KIT) and platelet‐derived growth factor receptors. In clinical trials with imatinib mesylate, common side effects of nausea, emesis, diarrhea, periorbital edema, fluid retention, and myelosuppression have been documented.METHODSIn this case series, the authors describe unique clinical findings of skin hypopigmentation in six patients with CML who were treated with imatinib mesylate.RESULTSMost patients developed onset of skin hypopigmentation within the first month of treatment and all of the patients experienced additional drug toxicity. Despite patient susceptibility to toxicity, the presence of hypopigmentation did not appear to predict leukemic cell response or clinical outcome. All six patients established a hematologic response but only two patients had a complete cytogenetic response. Imatinib mesylate induced hypopigmentation also appeared to be reversible and potentially dose related.CONCLUSIONSkin hypopigmentation is a benign side effect from imatinib mesylate treatment that appears to be reversible upon discontinuation or dose reduction. Several lines of evidence have previously reported that KIT and its ligand stem cell factor (SCF) have a regulatory role in melanocyte development and survival, suggesting a rational mechanism of action for imatinib mesylate in the pathogenesis of hypopigmentation. The signal transduction mechanism currently is believed to involve SCF ligand binding of KIT and downstream activation of MAP kinase (Erk‐2). Microphthalmia (Mi), a basic helix‐loop‐helix leucine zipper (bHLHZip) transcription factor, is phosphorylated by MAP kinase at a serine residue (S73). Once phosphorylated, Mi transactivates the tyrosine pigmentation gene promoter and affects pigment production. Cancer 2003. © 2003 American Cancer Society.
Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome–related Kaposi sarcoma
Authors: Nasti Guglielmo , Martellotta Ferdinando , Berretta Massimiliano , Mena Maurizio , Fasan Marco , Di Perri Giovanni , Talamini Renato , Pagano Gabriella , Montroni Maria , Cinelli Roberta , Vaccher Emanuela , D'Arminio Monforte Antonella , Tirelli Umberto 
Published: November 2003

AbstractBACKGROUNDThe objective of the current study was to evaluate the impact of highly active antiretroviral therapy (HAART) on clinical characteristics of presentation and the natural history of Kaposi sarcoma (KS) in patients already receiving HAART at the time of KS diagnosis.METHODSThe authors conducted a retrospective cohort study comparing epidemiologic, clinical, and outcome data for 160 patients who were naive to HAART at the time of KS diagnosis (KS‐naive) with the corresponding data for 51 patients already receiving HAART at the time of KS diagnosis (KS‐HAART). The analysis included all patients with a diagnosis of KS since January 1996 within two Italian cohorts of patients with human immunodeficiency virus.RESULTSImmunologic and virologic status at the time of KS diagnosis were significantly more favorable in the KS‐HAART group than in the KS‐naive group. The frequency of cutaneous involvement was similar in both groups, but cutaneous disease was more indolent among KS‐HAART patients, with 1 anatomic site of involvement in 9 patients (21%) and less than 10 lesions in 26 patients (60%), compared with 16 patients (12%; P = 0.06) and 47 patients (34%; P = 0.01), respectively, in the KS‐naive group. A smaller proportion of KS‐HAART patients presented with visceral disease (24% vs. 39%; P = 0.06); in particular, gastrointestinal tract involvement was significantly less frequent among KS‐HAART patients (14%) compared with KS‐naive patients (28%; P = 0.05). Median survival was not reached in either group, and the 3‐year survival rates of KS‐HAART patients (64%) and KS‐naive patients (78%) were not significantly different.CONCLUSIONSThe data from the current study indicate that KS exhibits a less aggressive presentation in patients already receiving HAART compared with patients who are naive to HAART at KS diagnosis. Natural history and outcome do not appear to be influenced by the initiation of HAART before development of KS. Cancer 2003. © 2003 American Cancer Society.
Implicit enthalpy formulation of phase‐change problems on unstructured grid
Authors: Caldwell J. , Date A. W. 
Published: November 2003

AbstractThis paper presents an implicit finite‐volume enthalpy formulation of the multidimensional phase‐change problems involving a unique phase‐change temperature. The derived formulation provides a simple method for local tracking of interface using the enthalpy variable on both structured as well as unstructured grids in a novel way. Results of economic computations of previously published problems are presented. Copyright © 2003 John Wiley & Sons, Ltd.
An improved version of DYNAMIC‐Q for simulation‐based optimization using response surface gradients and an adaptive trust region
Authors: Craig K. J. , Stander Nielen 
Published: November 2003

AbstractThis paper proposes an improvement on the DYNAMIC‐Q method for optimization of applications requiring expensive and (often) noisy numerical simulations for function evaluations. The original DYNAMIC‐Q method requires the selection of a step size and a move limit by the user. For noisy responses, the success of the original method depends on the correct choice of step size and move limit. The improved version uses the adaptive trust region features of an existing successive response surface method (SRSM) algorithm to replace the selection of the step size and move limit with one parameter, the initial trust region size. For the testing of the new method, DYNAMIC‐Q(RSG), an arbitrary selection from the well‐known Hock and Schittkowski problems as well as a non‐linear structural engineering problem are used. It is shown that for problems where the gradient information is reliable, the original DYNAMIC‐Q method is superior as expected. However, where noisy responses cause inaccurate and unreliable gradient information, the SRSM and DYNAMIC‐Q(RSG) methods are proven to be more robust with SRSM superior in its ability to converge more stably. The performance of DYNAMIC‐Q(RSG) is encouraging as it maintains the robustness and minimum user input of SRSM, but has faster convergence for analytical problems. Copyright © 2003 John Wiley & Sons, Ltd
Can services lead to radical eco‐efficiency improvements? – a review of the debate and evidence
Authors: Heiskanen Eva , Jalas Mikko 
Published: November 2003

AbstractEco‐efficient services, or sustainable product–service systems, are a popular topic in discussions on sustainability and eco‐efficiency. In these discussions, ‘service’ actually refers to many different things. It may refer to the role of the service sector in the economy, or to a new business strategy, or to the service (utility) provided by a product. Furthermore, the discussion on eco‐efficient services has been linked to concepts such as the ‘new’, ‘experience’ or ‘customized’ economy. The article analyses the central arguments and evidence put forth in the discussion on eco‐efficient services. The findings address questions occupying policy‐makers, managers and researchers: how relevant are eco‐efficient services in environmental management, and what might be the next steps in exploring their potential? Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Adaptive zone routing protocol forad hocnetwork nodes with non‐uniform mobilities
Authors: Zhang Xiaofeng , Jacob Lillykutty 
Published: November 2003

AbstractIn recent years, a variety of new routing protocols for mobilead hocwireless NETworks (MANETs) have been developed. Performance evaluation and comparison of many of these routing protocols have been performed using detailed simulation models. Zone routing protocol (ZRP) is one of these routing protocols, which is a hybrid routing protocol that proactively maintains routing information for a local neighbourhood (routing zone), while reactively acquiring routes to destinations beyond the routing zone. The studies on ZRP have assumed homogeneous scenarios where all mobile nodes have uniform mobility and are statistically identical, lacking the studies on heterogeneous scenarios where mobile nodes move with non‐uniform mobilities in the same network. In this paper, we study the performance of ZRP in such scenarios. We propose an efficient scheme for ZRP to adapt to the non‐uniform mobilities scenario and study its performance for different mobility scenarios, network loads and network sizes. Copyright © 2003 John Wiley & Sons, Ltd.
CD8+ T cell‐mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages
Authors: Brookes Roger H. , Pathan Ansar A. , McShane Helen , Hensmann Meike , Price David A. , Hill Adrian V. S. 
Published: November 2003

AbstractAnimal models of tuberculosis point to a protective role for MHC class I‐restricted CD8+ T cells, yet it is unclear how these cells protect or whether such findings extend to humans. Here we report that macrophages infected with Mycobacterium tuberculosis, rapidly process and present an early secreted antigenic target (ESAT‐6)‐specific HLA class I‐restricted CD8+ T cell epitope. When cocultured with CD8+ T cells restricted through classical HLA class I molecules the growth of bacilli within macrophages is significantly impaired after 7 days. Thisslow antimycobacterial activity did not correlate with macrophage lysis but required cell contact. We also found that inhibitors of apoptosis either had no effect or augmented the CD8‐mediated suppressive activity, suggesting that an activation signal might be involved. Indeed we show that CD8+ T cells were able to activate macrophages through receptors that include CD95 (Fas). Consistent with these findings the CD8‐mediated suppression of mycobacterial growth was partially reversed by Fas blockade. These data identify a previously unrecognized CD8+ T cell‐mediated mechanismused to control an intracellular infection of macrophages.
Maintenance of B lymphocyte‐related clones in the cerebrospinal fluid of multiple sclerosis patients
Authors: Colombo Monica , Dono Mariella , Gazzola Paola , Chiorazzi Nicholas , Mancardi Gianluigi , Ferrarini Manlio 
Published: November 2003

AbstractA longitudinal study of Ig V gene segments utilized by B cells from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS) was carried out using RT‐PCR methodologies. One patient with a relapsing‐remitting (RR)‐MS was investigated at onset and at relapse, 1 year later. A patient with secondary‐progressive (SP)‐MS was tested 9 and 13 years after disease onset. Sequenceanalyses of VHDJH segments bearing VH3 and VH4 that were obtained from Cγ cDNA genes demonstrated a substantial proportion of shared clones in the samples taken at different times; these clones were identical or closely related, i.e. had the same third complementary determining region (CDR) of the H chain variable region gene (HCDR3) with different mutations in the VH segment. Collectively, these data demonstrate that in MS patients there is a strong selective pressure, which could be exerted by antigen (or autoantigen) stimulation, for the maintenance and partial diversification of certain VHDJH Cγ sequences.
Inflammatory pathogenesis of snake venom metalloproteinase‐induced skin necrosis
Authors: Laing Gavin David , Clissa Patricia Bianca , Theakston Robert David Geoffrey , Moura‐da‐Silva Ana Maria , Taylor Mark John 
Published: November 2003

AbstractLocal tissue damage, characterized by edema, hemorrhage and necrosis, is a common consequence of envenoming by many vipers. We have investigated the contribution of inflammatory responses induced by the venom metalloproteinase jararhagin (isolated from Bothrops jararaca venom) in the development of these lesions. Local venom effects (edema, hemorrhage and necrosis) were inducedexperimentally in knockout mice deficient in the TNF receptors TNFR1 or TNFR2, IL‐1βR, IL‐6 and iNOS. Jararhagin‐induced dermal necrosis was abolished in mice deficient in the TNF receptors TNFR1 and TNFR2, and the same activity was significantly reduced in IL‐6–/– mice. There was no significant difference in edema and hemorrhage activities following jararhagin insult between knockout and WT strains, indicating that these local venom metalloproteinase‐induced effects are independent of these pro‐inflammatory mediators. The contribution of both TNF receptors and IL‐6 in local tissue necrosis raises important therapeutic issues regarding the treatment of local envenoming.
Characterization of the Surface Electrode Reaction in the Presence of Uniform Interaction: The Case of Mo(VI) Reduction in the Presence of Phenanthroline and an Excess of Fulvic Acids
Authors: Quentel François , Mirčeski Valentin 
Published: November 2003

AbstractSurface electrode reactions involving lateral uniform interactions between adsorbed species is studied by means of square‐wave voltammetry (SWV). Interactions are represented by the interaction product aΘ, were a is the Frumkin interaction parameter (a is positive for attraction and negative for repulsion forces) and Θ is the surface coverage. The properties of the SW voltammetric response enable detection of interactions and recognition of the type of interaction forces by a simple procedure. The influence of the interactions on the apparent electrochemical reversibility of the surface electrode reaction is studied in detail. Utilizing “quasireversible maximum” the simple methodology for estimation of the standard redox rate constant without knowing the exact value of the interaction product aΘ is developed. Theoretical predictions are illustrated and confirmed by experiments with Mo(VI) in the presence of phenantroline and an excess of fulvic acids.
Volatile components of papaya (Carica papaya L., Maradol variety) fruit
Authors: Pino Jorge A. , Almora Karina , Marbot Rolando 
Published: November 2003

AbstractVolatile compounds were isolated from fresh papaya fruit by simultaneous steam distillation‐solvent extraction according to Likens–Nickerson. Compounds were identiﬁed by capillary GC–MS and sensorially characterized by snifﬁng GC. One hundred and sixty‐six compounds were identiﬁed in the aroma concentrate, of which 77 were identiﬁed for the ﬁrst time as papaya volatiles. Among the identiﬁed compounds, methyl butanoate, ethyl butanoate, 3‐methyl‐1‐butanol and 1‐butanol were found to be the major components. The esters of lower fatty acids were considered to contribute much to the typical papaya ﬂavour. Copyright © 2003 John Wiley & Sons, Ltd.
Essential oil analysis of Teucrium libanitis and T. turredanum by GC and GC–MS
Authors: Blázquez M. Amparo , Pérez Isabel , Boira Herminio 
Published: November 2003

AbstractThe chemical composition of the six essential oils obtained from Teucrium libanitis and Teucrium turredanum collected at different localities was analysed by GC and GC–MS. Fifty‐three constituents were identiﬁed. The oil of T. libanitis is characterized by the monoterpene α‐pinene (9.9–21.2%) and the sesquiterpene δ‐cadinene (5.3–9.7%), while that of T. turredanum had a higher content of sesquiterpenoids: β‐caryophyllene (15.6–32.6%), α‐humulene (4.7–10.1%) and β‐bisabolol (6.4–8.3%), and a lower percentage of monoterpenoids (<1%). A multivariate procedure (hierarchical clustering) for detecting natural grouping established that T. libanitis and T. turredanum constitute two independent taxa. Copyright © 2003 John Wiley & Sons, Ltd.
Composition and chemical variability of the bark oil of Cedrelopsis grevei H. Baillon from Madagascar
Authors: Cavalli Jean‐François , Tomi Félix , Bernardini Antoine‐François , Casanova Joseph 
Published: November 2003

AbstractA commercial sample of Cedrelopsis grevei H. Baillon from Madagascar was repeatedly chromatographed and the combined analysis of all the fractions by GC, GC–MS and 13C‐NMR led to the identiﬁcation of 114 components. The major constituents were (E)‐β‐caryophyllene (9.3%), α‐copaene (7.7%), α‐selinene (5.8%), δ‐cadinene (4.9%), β‐selinene (4.5%), α‐humulene (3.3%) and β‐bisabolene (2.8%). Analysis of ﬁve other commercial samples conﬁrmed the pre‐eminence of sesquiterpene hydrocarbons and exhibited a variation in the contents of the main components: ishwarane (1.0–17.4%), (E)‐β‐caryophyllene (1.3–12.5%), α‐copaene (4.9–11.0%), β‐elemene (0.2–9.6%) and α‐selinene (1.1–9.4%). Copyright © 2003 John Wiley & Sons, Ltd.
Adjustment for competing risk in kin‐cohort estimation
Authors: Chatterjee Nilanjan , Hartge Patricia , Wacholder Sholom 
Published: November 2003

AbstractKin‐cohort design can be used to study the effect of a genetic mutation on the risk of multiple events, using the same study. In this design, the outcome data consist of the event history of the relatives of a sample of genotyped subjects. Existing methods for kin‐cohort estimation allow estimation of the risk of one event at a time with the assumption that the censoring events are unrelated to the genetic mutation under study. These methods, however, may produce biased estimates of risk when multiple events are related to the genetic mutation, and follow‐up of some of the events may be censored by the onset of other events. Using a competing risk framework to address this problem, we show that cause‐specific hazard functions for carriers and noncarriers are identifiable from kin‐cohort data. For estimation, we propose an extension of a composite‐likelihood approach we described previously. We illustrate the use of the proposed method for estimation of the risk of ovarian cancer from BRCA1/2 mutations in the absence of breast cancer, based on data from the Washington Ashkenazi Kin‐Cohort Study. We also evaluate the performance of the proposed estimation method, based on simulated data that were generated following the setup of the Washington Ashkenazi Study.Genet Epidemiol25:303–313. Published 2003 Wiley‐Liss, Inc.