bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is ‘insignificant’ prostate carcinoma?
Authors: Klein Eric A. 
Published: September 2004

In the absence of clinical context, current definitions of insignificant prostate carcinoma are not useful in assessing the need for definitive treatment. Nonetheless, the findings of Bastian and colleagues, which are reported in the current issue of Cancer, strongly suggest that the Epstein criteria select for a subset of patients who may not require immediate therapy and who, at least initially, may be followed safely. The remaining challenge for the urologic community is to design clinical trials aimed at prospectively identifying individuals who require further intervention and determining when such intervention is necessary. Only after the completion of trials such as these can an accurate definition of ‘insignificant’ prostate carcinoma be put forth.See pages 2001–5.
Characteristics of insignificant clinical T1c prostate tumors
Authors: Bastian Patrick J. , Mangold Leslie A. , Epstein Jonathan I. , Partin Alan W. 
Published: September 2004

AbstractBACKGROUNDThe authors examined the cases of men who had undergone radical prostatectomy for low‐volume clinical T1c prostate carcinoma that was judged to be ‘insignificant’ on the basis of previously established preoperative clinicopathologic parameters. Pathologic findings subsequently were analyzed for correlations with extent of disease in an attempt to validate the contemporary usefulness of existing parameters for predicting the ‘significance’ of prostate tumors.METHODSA series of 237 men who had undergone radical prostatectomy for T1c disease between December 2000 and August 2003 was evaluated. Insignificant prostate carcinoma as assessed on biopsy was defined according to the 1994 Epstein criteria, which were as follows: prostate‐specific antigen density < 0.15 ng/mL, Gleason score ≤ 6, fewer than 3 cores containing prostate carcinoma, and ≤ 50% involvement of any core with prostate carcinoma. Postsurgical pathologic findings were analyzed for potential correlations with the Epstein criteria.RESULTSAccording to the Epstein needle biopsy criteria, organ‐confined prostate carcinoma was detected in 91.6% of all patients, whereas the remaining 8.4% of patients were found to have non‐organ‐confined disease. Comparison of pathologic findings and Epstein biopsy criteria revealed that alteration of the original criteria did not improve the detection of non‐organ‐confined prostate carcinoma.CONCLUSIONSThe findings made in the current study suggest that the majority of patients with T1c prostate carcinoma have insignificant disease. Furthermore, it was found that the Epstein criteria for identifying insignificant prostate carcinoma remained a useful tool in the making of treatment‐related decisions. Cancer 2004. © 2004 American Cancer Society.
Invasive cutaneous malignant melanoma in Sweden, 1990–1999
Authors: Lindholm Christer , Andersson Ronny , Dufmats Monika , Hansson Johan , Ingvar Christian , Möller Torgil , Sjödin Helena , Stierner Ulrika , Wagenius Gunnar ,   for the Swedish Melanoma Study Group
Published: September 2004

AbstractBACKGROUNDThe objective of the current study was to compile prospective, population‐based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data.METHODSTwelve thousand five hundred thirty‐three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors.RESULTSThere was no significant change in melanoma incidence during 1990–1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5‐year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender.CONCLUSIONSDuring the period from 1990 to 1999, the 5‐year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population‐based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns. Cancer 2004. © 2004 American Cancer Society.
Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy
Authors: Brandes Alba Ariela , Tosoni Alicia , Vastola Francesca , Pasetto Lara Maria , Coria Bartolomea , Danieli Daniela , Iuzzolino Paolo , Gardiman Marina , Talacchi Andrea , Ermani Mario 
Published: September 2004

AbstractBACKGROUNDTo the authors' knowledge, there is a scarcity of accurate data regarding the feasibility of standard chemotherapy with procarbazine, lomustine, and vincristine (PCV) in a homogeneous series of patients with primary anaplastic oligodendroglioma (AO) and oligoastrocytoma (AOA) that was recurrent after surgery and standard radiotherapy. The aim of the current study was to evaluate the overall response rate, toxicity, and time to progression (TTP) with the use of standard PCV in this setting.METHODSBetween November 1994 and September 2000, 37 patients were enrolled in the current study. Of these, 23 had AO (62%) and 14 had AOA (38%). All patients received standard PCV comprised of lomustine (110 mg/m2) on Day 1, procarbazine (60 mg/m2) on Days 8–21, and vincristine (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. Cycles were repeated every 6 weeks.RESULTSThere were 11 complete responses (CR; 29.7%) and 11 partial responses (PR; 29.7%) reported and 8 patients had stable disease (SD; 21.6%). The response rate was higher in patients with AO compared with patients with AOA (77.2% vs. 22.7%;P= 0. 02). The median TTP, which was 12.3 months overall, was 30.3 months in patients who achieved a CR, 19.1 months in patients who achieved a PR, and 6.1 months in patients with SD. The median TTP was 18.6 months in AO patients and 6.14 in AOA patients. There were no cases of severe toxicity reported although in 16 patients (43%) who were free of disease progression, PCV was discontinued because of toxicity or inadequate recovery after 2 weeks of delay.CONCLUSIONSPCV chemotherapy was reported to achieved a high response rate and TTP but incurred a high risk of persistent toxicity. Cancer 2004. © 2004 American Cancer Society.
Acute graft‐versus‐host disease: Pathophysiology, clinical manifestations, and management
Authors: Couriel Daniel , Caldera Humberto , Champlin Richard , Komanduri Krishna 
Published: September 2004

AbstractHematopoietic stem cell transplantation has evolved as a central treatment modality in the management of different hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute graft‐versus‐host disease (GVHD) remains a major cause of morbidity and mortality in the hematopoietic stem cell transplantation setting, even in patients who receive human leukemic antigen (HLA) identical sibling grafts. Up to 30% of the recipients of stem cells or bone marrow transplantation from HLA‐identical related donors and most patients who receive cells from other sources (matched‐unrelated, non‐HLA‐identical siblings, cord blood) will develop > Grade 2 acute GVHD despite immunosuppressive prophylaxis. Thus, GVHD continues to be a major limitation to successful hematopoietic stem cell transplantation. In this review, the authors summarize the most current knowledge on the pathophysiology, clinical manifestations, and management of this potentially life‐threatening transplantation complication. Cancer 2004. © 2004 American Cancer Society.
A new model for predicting infectious complications during fludarabine‐based combination chemotherapy among patients with indolent lymphoid malignancies
Authors: Tam Constantine S. , Wolf Max M. , Januszewicz E. Henry , Grigg Andrew P. , Prince H. Miles , Westerman David , Seymour John F. 
Published: September 2004

AbstractBACKGROUNDFludarabine‐containing combination chemotherapy regimens are increasingly used in the treatment of indolent lymphoid malignancies, with the associated risk of infection being the major toxicity. Predictors of infection during fludarabine‐containing combination therapy are poorly defined and optimal strategies for infection prophylaxis are not known. The authors analyzed their experience with patients treated with the fludarabine‐mitoxantrone (FM) or fludarabine‐cyclophosphamide (FC) regimens to develop a predictive model for infections.METHODSNinety‐two patients with indolent lymphoid malignancies were treated with FM (n = 29) or FC (n = 63). Baseline variables including age, gender, regimen, disease histology, previous therapy, time from diagnosis to current treatment, performance status, renal function, absolute neutrophil count (ANC), lymphocyte count, and immunoglobulin G levels were examined retrospectively for their association with risk of infectious complications during or within 4 weeks of therapy.RESULTSSix risk factors were associated with infectious complications: age > 60 years, ≥ 3 previous therapies, previous fludarabine exposure, time from diagnosis to current treatment of > 3 years, performance status ≥ 2, and baseline ANC < 2.0 × 109/L. Compared with patients with 0–2 risk factors, patients with ≥ 3 risk factors had higher infection rates (26% vs. 7% per cycle, P < 0.0001), more Grade 4 neutropenia (41% vs. 8% per cycle, P < 0.0001), and more neutropenic sepsis (15% vs. 1% per cycle, P < 0.0001).CONCLUSIONSInfection risk during fludarabine‐containing combination chemotherapy was predicted with a model comprising six baseline risk factors. Patients predicted to be at high risk of infection were an appropriate group for consideration of prophylactic strategies. Cancer 2004. © 2004 American Cancer Society.
Imatinib mesylate in chordoma
Authors: Casali Paolo G. , Messina Antonella , Stacchiotti Silvia , Tamborini Elena , Crippa Flavio , Gronchi Alessandro , Orlandi Rosaria , Ripamonti Carla , Spreafico Carlo , Bertieri Raffaello , Bertulli Rossella , Colecchia Maurizio , Fumagalli Elena , Greco Angela , Grosso Federica , Olmi Patrizia , Pierotti Marco A. , Pilotti Silvana 
Published: September 2004

AbstractBACKGROUNDTo the authors' knowledge, no effective medical therapy currently is available for advanced chordoma. Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet‐derived growth factor receptor‐β (PDGFRB), BCR‐ABL, and KIT.METHODSSix patients with advanced chordoma were treated with imatinib mesylate at a dose of 800 mg daily. In all patients, the tumor was found to be positive for PDGFRB, and in four patients PDGFRB was shown to be phosphorylated/expressed.RESULTSAfter a treatment period of ≥ 1 year, overt tumor liquefaction was evident on computed tomography (CT) scan in the first patient. In previous months, a decrease in contrast enhancement on magnetic resonance imaging (MRI) and a decrease in glucose uptake on positron emission tomography (PET) were detected. Similar signs on MRI and PET were observed in subsequent patients, who had a shorter treatment period. One of these patients initially was removed from therapy and then was readmitted to therapy because of difficulties with regard to tumor response assessment; 1 month after the reinitiation of therapy, an overt decrease in tumor density was visible on CT scan in this patient. In four of five symptomatic patients, a subjective improvement was observed early in the course of treatment. The first patient died after 17 months, with a sizeable, mostly liquefied mass. Another patient died early, apparently of unrelated causes. The remaining patients were on therapy at the time of last follow‐up.CONCLUSIONSImatinib mesylate has been found to have antitumor activity in patients with chordoma. This activity might be mediated by inactivation of PDGFRB. Tumor response manifests through patterns that are similar to those observed in patients with gastrointestinal stromal tumors who respond to molecular‐targeted therapy, but evolves more slowly. The benefit to the patient entailed by this pattern of tumor response in chordoma needs to be elucidated, but may be limited in the presence of significant local disease. Cancer 2004. © 2004 American Cancer Society.
A range of memory possibilities: the challenge of the false memory debate for clinicians and researchers
Authors: Madill Anna , Holch Patricia 
Published: September 2004

AbstractThe aim of this article is to present a succinct review and evaluation of the main areas of contention in the false memory debate and, from this basis, to suggest ways in which the best from both sides can be utilized. We examine the potential pitfalls of therapy in terms of the fallibility and suggestibility of autobiographical memory and therapists and therapeutic techniques as the architects of false memories. We then evaluate the case for false memory formation examining if some researchers hold misconceived views of psychotherapy, if experimental studies lack ecological validity, and the effect of trauma on memory. Finally, we explore how the potential pitfalls of therapy can be avoided in practice, reflecting on the usefulness of British Psychological Society guidelines, how clinicians can implement research findings, and how research on the false memory debate can be improved. We conclude that the way forward is researcher–clinician collaboration in the development of ecologically valid research paradigms. Copyright © 2004 John Wiley & Sons, Ltd.
Tools and tenets of schema therapy: toward the construct validity of the early maladaptive schema questionnaire–research version (EMSQ‐R)
Authors: Cecero John J. , Nelson Joshua D. , Gillie Jacqueline M. 
Published: September 2004

AbstractThis study investigated the scale reliability, factor structure, and convergent validity of the Early Maladaptive Schema Questionnaire–Research Version (EMSQ‐R), a 75‐item self‐report inventory that is a revised version of the Young Schema Questionnaire (YSQ) and that measures the presence and severity of 15 early maladaptive schemas (EMS), in an undergraduate sample of 292 participants. Eleven EMS scales were found to have adequate reliability, and 14 hypothesized EMS factors emerged during factor analysis. In addition, findings provided support for the underlying tenets of Schema Therapy (ST), by demonstrating correlations between EMS and measures of both adult attachment and childhood trauma. Future clinical and research directions are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Is one assessment enough? Patterns of helping alliance development and outcome
Authors: de Roten Yves , Fischer Mélanie , Drapeau Martin , Beretta Véronique , Kramer Ueli , Favre Nathalie , Despland Jean‐Nicolas 
Published: September 2004

AbstractEarly therapeutic alliance is usually measured by the rating of a single session (between the third and the fifth sessions). However, there is a strong argument in favor of viewing early alliance as a developing process.This study examined the relationship between patient's rating of the helping alliance (HAq) at each session and therapy outcome. This comparison was repeated using patterns of alliance over the course of treatment. Patterns of therapeutic alliance development were detected by clustering ratings of a sample of N = 70 outpatients across four sessions of very brief psychotherapeutic intervention.Cluster analysis revealed two main patterns (shapes) of alliance development: (i) stable alliance, and (ii) linear growth pattern. These patterns are more predictive of symptom improvement and social adjustment than single ratings, whereas single ratings measuring the strength of alliance are more correlated with patient's satisfaction. Copyright © 2004 John Wiley & Sons, Ltd.
Both IL‐12 and IL‐18 contribute to small intestinal Th1‐type immunopathology following oral infection with Toxoplasma gondii, but IL‐12 is dominant over IL‐18 in parasite control
Authors: Vossenkämper Anna , Struck Daniela , Alvarado‐Esquivel Cosme , Went Tobias , Takeda Kioyshi , Akira Shizuo , Pfeffer Klaus , Alber Gottfried , Lochner Matthias , Förster Irmgard , Liesenfeld Oliver 
Published: September 2004

AbstractOral infection of C57BL/6 mice with Toxoplasma gondii results in small intestinal Th1‐type immunopathology mediated by local production of IFN‐γ, TNF‐α, and NO. To analyze whether the proinflammatory cytokines IL‐12 and IL‐18 play a role in the induction of immunopathology, IL‐12p35/p40–/– and IL‐18–/– mice were orally infected with T. gondii. Wild‐type mice developed massive necrosis in their small intestines and died 7–10 days post infection. Even though IL‐12p35/40–/– mice did not develop the necrosis they all died between day 9 and 11 after infection. In contrast, 50% of IL‐18–/– mice died during the acute phase of infection. Compared to wild‐type mice, IL‐12p35/p40–/– but not IL‐18–/– mice showed significantly higher parasite numbers in their small intestines and significantly higher numbers of parasite‐associated inflammatory foci in their livers. IFN‐γ production was similar in infected wild‐type and IL‐18–/– mice but significantly decreased in IL‐12p35/p40–/– mice. Treatment of mice with anti‐IL‐12‐ or anti‐IL‐18 antibodies after infection prevented the development of intestinal necrosis. These results reveal that both IL‐12 and IL‐18 play an important role in the development of intestinal immunopathology following oral infection with T. gondii. However, IL‐12 is dominant over IL‐18 in the host defense against parasite replication. Therefore, neutralization of IL‐18 (rather than TNF‐α, IL‐12, and IFN‐γ) may be a safe strategy for the treatment of Th1‐associated diseases.
Increased sensitivity of early apoptotic cells to complement‐mediated lysis
Authors: Attali Gitit , Gancz Dana , Fishelson Zvi 
Published: September 2004

AbstractOpsonization of apoptotic cells with complement proteins contributes to their clearance by phagocytes. Little is known about the lytic effects of complement on apoptotic cells. Sensitivity of cells treated with anti‐Fas antibody (Jurkat cells), staurosporine or etoposide (Raji cells) to lysis by complement was examined. As shown here, early apoptotic cells are more sensitive to lysis by antibody and complement than control cells. More complement C3 and C9 bound to apoptotic than to control cells, even though antibody binding was similar. Enhanced killing and C3/C9 deposition were blocked by benzyloxy‐Val‐Ala‐Asp‐fluoromethylketone, a pan‐caspase inhibitor. Complement‐mediated lysis of early apoptotic cells was also prevented by inhibitors of caspases 6, 8, 9 or 10. In contrast, caspase inhibitors had no effect on the lysis of non‐apoptotic Jurkat and Raji cells. Early apoptotic Jurkat cells were also more sensitive to lysis by the pore formers streptolysin O and melittin. Sensitivity of Jurkat Bcl‐2 transfectants to lysis by complement was analyzed. Enhanced Bcl‐2 expression was associated with reduced C3 deposition and lower sensitivity to complement‐mediated lysis. These results demonstrate that at an early stage in apoptosis, following caspase activation, cells become sensitive to necrotic‐type death by complement and other pore formers. Furthermore, they suggest that Bcl‐2 is actively protecting Jurkat cells from complement‐mediated lysis.
Prevention of diabetes in NOD mice at a late stage by targeting OX40/OX40 ligand interactions
Authors: Pakala Syamasundar V. , Bansal‐Pakala Pratima , Halteman Beth S. , Croft Michael 
Published: September 2004

AbstractAutoreactive T cells play a major role in the development of insulin‐dependent diabetes mellitus, suggesting that costimulatory molecules that regulate T cell responses might be essential for disease progression. In NOD mice, CD28/B7 and CD40/CD40 ligand (L) interactions control the onset of diabetes from 2 to 4 weeks of age, but blocking these molecules has little effect after this time. Hence, it is possible that other ligand/receptor pairs control a later phase of disease. We now show that OX40 is expressed on CD4 and CD8 T cells several weeks prior to islet destruction, which is initiated around weeks 12–14, and that OX40L is present on dendritic cells in both secondary lymphoid organs and the pancreas from 11 to 13 weeks of age. Blocking OX40L at 6, 9, or 15 weeks after birth had little effect on disease; however, inhibiting OX40/OX40L interactions at week 12, or continuous treatment from week 12 onwards, significantly reduced the incidence of diabetes. Histological examination showed that islet destruction was prevented and insulitis reduced by targeting OX40L. These studies show that OX40/OX40L interactions form a late checkpoint in diabetes development and suggest that these molecules are realistic targets for therapeutic intervention.
Lipopeptide epitopes extended by an Nϵ‐palmitoyl‐lysine moiety increase uptake and maturation of dendritic cells through a Toll‐like receptor‐2 pathway and trigger a Th1‐dependent protective immunity
Authors: Zhu Xiaoming , Ramos Thomas V. , Gras‐Masse Helene , Kaplan Bruce E. , BenMohamed Lbachir 
Published: September 2004

AbstractLipopeptides, a form of peptide immunogens, are currently under intense investigation as human vaccines for many infectious pathogens and cancers. However, the cellular and molecular mechanisms of lipopeptide immunogenicity are only partially understood. We have investigated the influence of the lipid content on the immunogenicity of lipopeptides using the herpes simplex virus type 1 (HSV‐1) gD1–23 peptide as a model antigen. Totally synthetic lipopeptides were constructed by covalent attachment to the peptide backbone of either Nϵ‐palmitoyl‐lysine (palmitoyl‐lipidated peptide, palmitoyl‐LP) or cholesterol‐lysine (cholesterol‐lipidated peptide, cholesterol‐LP). Immunization of mice with the palmitoyl‐LP, but not with its cholesterol‐LP analog, induced a strong T cell‐dependent protective immunity against lethal HSV‐1 infection. Analysis of cytokine profiles and IgG2a/IgG1 ratios revealed that a dominant Th1‐type immune response was stimulated by the palmitoyl‐LP, as opposed to a Th2 response generated by its cholesterol‐LP analog. The palmitoyl‐LP was efficiently taken up in vitro by immature dendritic cells (DC) in a time‐ and dose‐dependent manner, and induced phenotypic maturation and production of pro‐inflammatory cytokines by DC. Finally, DC stimulated with the palmitoyl‐LP induced antigen‐specific T cell responses through the Toll‐like receptor‐2 pathway. These findings have important implications for the development of effective lipopeptide immunization strategies against infectious pathogens.