bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of Navigated Knee Stability Examination
Authors: Pearle Andrew D. , Solomon Daniel J. , Wanich Tony , Moreau-Gaudry Alexandre , Granchi Carinne C. , Wickiewicz Thomas L. , Warren Russell F. 
Published: April 2007

Background Clinical examination remains empirical and may be confusing in the setting of rotatory knee instabilities. Computerized navigation systems provide the ability to visualize and quantify coupled knee motions during knee stability examination. Hypothesis An image-free navigation system can reliably register and collect multiplanar knee kinematics during knee stability examination. Study Design Controlled laboratory study. Methods Coupled knee motions were determined by a robotic/UFS testing system and by an image-free navigation system in 6 cadaveric knees that were subjected to (1) isolated varus stress and (2) combined varus and external rotation force at 0°, 30°, and 60°. This protocol was performed in intact knees and after complete sectioning of the posterolateral corner (lateral collateral ligament, popliteus tendon, and popliteofibular ligament). The correlation between data from the surgical navigation system and the robotic positional sensor was assessed using the intraclass correlation coefficient. The 3-dimensional motion paths of the intact and sectioned knees were assessed qualitatively using the navigation display system. Results Intraclass correlation coefficients between the robotic sensor and the navigation system for varus and external rotation at 0°, 30°, and 60° were all statistically significant at P < .01. The overall intraclass correlation coefficient for all tests was 0.9976 (P < .0001). Real-time visualization of the coupled motions was possible with the navigation system. Post hoc analysis of the knee motion paths during loading distinguished distinct rotatory patterns. Conclusion Surgical navigation is a precise intraoperative tool to quantify knee stability examination and may help delineate pathologic multiplanar or coupled knee motions, particularly in the setting of complex rotatory instability patterns. Repeatability of load application during clinical stability testing remains problematic. Clinical Relevance Surgical navigation may refine the diagnostic evaluation of knee instability.
Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro
Authors: Goodrum Felicia , Reeves Matthew , Sinclair John , High Kevin , Shenk Thomas 
Published: April 2007

AbstractLatency enables human cytomegalovirus (HCMV) to persist in the hematopoietic cells of infected individuals indefinitely and prevents clearance of the pathogen. Despite its critical importance to the viral infectious cycle, viral mechanisms that contribute to latency have not been identified. We compared the ability of low-passage clinical and laboratory-adapted strains of HCMV to establish a latent infection in primary human CD34+ cells. The low-passage strains, Toledo and FIX, established an infection with the hallmarks of latency, whereas the laboratory strains, AD169 and Towne, replicated producing progeny virus. We hypothesized that ULb′ region of the genome, which is unique to low-passage strains, may encode a latency-promoting activity. We created and analyzed recombinant viruses lacking segments or individual open reading frames (ORFs) in the ULb′ region. One 5-kb segment, and more specifically the UL138 ORF, was required for HCMV to establish and/or maintain a latent infection in hematopoietic progenitor cells infected in vitro. This is the first functional demonstration of a virus-coded sequence required for HCMV latency. Importantly, UL138 RNA was expressed in CD34+ cells and monocytes from HCMV-seropositive, healthy individuals. UL138 might be a target for antivirals against latent virus.
The incidence and clinical significance of nucleophosmin mutations in childhood AML
Authors: Brown Patrick , McIntyre Emily , Rau Rachel , Meshinchi Soheil , Lacayo Norman , Dahl Gary , Alonzo Todd A. , Chang Myron , Arceci Robert J. , Small Donald 
Published: April 2007

Abstract
Frameshift mutations in exon 12 of the nucleophosmin gene (NPM1) result in aberrant cytoplasmic localization of the NPM protein (NPMc+) and occur in 25% to 35% of adult acute myeloid leukemia (AML). In adults with AML, NPMc+ has been associated with normal karyotype, FLT3/ITD mutations, high remission induction rates, and improved survival (particularly in patients lacking FLT3/ITD). NPMc+ has not been well characterized in childhood AML. This study examines the incidence and clinical significance of NPMc+ in 295 children with newly diagnosed AML treated on a large cooperative group clinical trial (POG-9421). We find that NPMc+ is relatively uncommon in childhood AML (23 of 295 patients, 8%); and is significantly associated with FLT3/ITD mutations (P = .046), female sex (P = .029), older age (P = .047), and normal cytogenetics (P < .001). There is a favorable impact of NPMc+ on survival in children lacking FLT3/ITD (5-year EFS, 69% vs 35%; hazard ratio, 0.39; P = .051), which is similar in magnitude to the favorable impact of t(8;21) and inv(16). We conclude that NPMc+ is relatively rare in childhood AML, particularly in younger children. NPMc+ does not abrogate the negative prognostic influence of FLT3/ITD mutations, but may contribute to risk stratification in children who lack FLT3/ITD mutations by identifying a group with superior prognosis.
Transcriptional response of human dendritic cells toBorrelia garinii—defective CD38 and CCR7 expression detected
Authors: Hartiala Pauliina , Hytönen Jukka , Pelkonen Jenni , Kimppa Katja , West Anne , Penttinen Markus A , Suhonen Juha , Lahesmaa Riitta , Viljanen Matti K 
Published: April 2007

AbstractLyme borreliosis is a disease, which can affect several organs and cause a variety of symptoms. In some patients, the infection may become chronic, even after antibiotic therapy, and cause persisting damage. Dendritic cells (DC) are involved in the initiation of innate and adaptive immune responses. To study interactions between Borrelia garinii (Bg), one of the causative agents of Lyme borreliosis, and human DC, we used a cDNA microarray to compare the Bg-induced DC transcriptional response with the response induced by LPS. The Bg-induced response consisted of a smaller number of genes than the LPS-induced response. The microarray showed that the ectoenzyme CD38, which has an important role in DC chemotaxis and migration to lymph nodes, was strongly up-regulated by LPS but practically not at all by Bg. This finding was confirmed with quantitative RT-PCR and with flow cytometry at the protein level. In addition, RT-PCR showed that CCR7 expression was 11-fold greater in LPS-stimulated than in Bg-stimulated cells. These findings suggest that Bg may affect crucial DC functions by blocking the up-regulation of important molecules in DC migration to lymph nodes, thus affecting further immune responses in Lyme borreliosis infection.
High Body Mass Index Increases the Risk for Osteonecrosis in Children With Acute Lymphoblastic Leukemia
Authors: Niinimäki Riitta A. , Harila-Saari Arja H. , Jartti Airi E. , Seuri Raija M. , Riikonen Pekka V. , Pääkkö Eija L. , Möttönen Merja I. , Lanning Marjatta 
Published: April 2007

Purpose The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. Patients and Methods Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. Results Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). Conclusion ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.
Thromboembolic Events in Children and Young Adults With Pediatric Sarcoma
Authors: Paz-Priel Ido , Long Lauren , Helman Lee J. , Mackall Crystal L. , Wayne Alan S. 
Published: April 2007

Purpose Adults with malignancy are at increased risk for venous thromboembolic events (TEs). However, data in children and young adults with cancer are limited. Patients and Methods To determine the risk and clinical features of TEs in children and young adults with sarcoma, we reviewed records on 122 consecutive patients with sarcoma treated from October 1980 to July 2002. Results Twenty-three TEs were diagnosed in 19 of 122 (16%; 95% CI, 10% to 23%) patients. Prevalence by diagnosis was Ewing sarcoma, eight of 61 (13%); osteosarcoma, two of 20 (10%); rhabdomyosarcoma, four of 26 (15%); and other sarcomas, five of 15 (33%). TEs developed in 23% of patients with metastases at presentation versus 10% with localized disease (odds ratio, 2.59; 95% CI, 0.9 to 7.1; P < .06). Fifty-three percent of patients with thrombosis had a clot at presentation. A lupus anticoagulant was detected in four of five evaluated patients. There was a single fatality due to pulmonary embolism. Patients who were diagnosed with cancer after 1993 had a higher rate of TE (7% v 23%; P < .015). Of the 23 events, 43% were asymptomatic. Main sites of thromboses were deep veins of the extremities (10 of 23; 43%), pulmonary embolism (five of 23; 22%), and the inferior vena cava (four of 23; 17%). TEs were associated with tumor compression in eight of 23 (35%) and with venous catheters in three of 23 (13%). Conclusion Thromboembolism is common in pediatric patients with sarcomas. Thromboses are detected frequently around the time of oncologic presentation, may be asymptomatic, and seem to be associated with a higher disease burden. Children and young adults with sarcoma should be monitored closely for thrombosis.
Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes
Authors: Govindarajan Rangaswamy , Ratnasinghe Luke , Simmons Debra L. , Siegel Eric R. , Midathada Madhu V. , Kim Lawrence , Kim Peter J. , Owens Randall J. , Lang Nicholas P. 
Published: April 2007

Purpose Peroxisome proliferator-activated receptor gamma (PPARγ) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPARγ ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted. Patients and Methods Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents). Results Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance. Conclusion TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.
Sentinel Lymph Node Molecular Ultrastaging in Patients With Melanoma: A Systematic Review and Meta-Analysis of Prognosis
Authors: Mocellin Simone , Hoon Dave S.B. , Pilati Pierluigi , Rossi Carlo R. , Nitti Donato 
Published: April 2007

Purpose Molecular biology-based ultrastaging of cancer is already part of the standard management of patients with hematologic malignancies, whereas the evidence for solid tumors is much more debated. Polymerase chain reaction (PCR) –based detection of melanoma cells in sentinel lymph nodes (SLN) of patients with melanoma represents an appealing prognostic tool. However, no consensus exists on the clinical implementation of this prognostic indicator for the management of these patients. Methods Twenty-two studies enrolling 4,019 patients who underwent SLN biopsy for clinical stage I to II cutaneous melanoma were reviewed. Correlation of PCR status with TNM stage, disease recurrence rates, and survival was assessed by means of association statistics and formal meta-analysis, respectively. Results PCR status correlated with both TNM stage (stage I to II v III; PCR positivity, 95.1% v 46.6%; P < .0001) and disease recurrence (PCR positive v negative; relapse rate, 16.8% v 8.7%; P < .0001). PCR positivity was also associated with worse overall (hazard ratio [HR], 5.08; 95% CI, 1.83 to 14.08; P = .002) and disease-free (HR, 3.41; 95% CI, 1.86 to 6.24; P < .0001) survival. Statistical heterogeneity was significant, underscoring the variability among overall effect estimates across studies; metaregression and subgroup analysis did not identify clear-cut sources of heterogeneity, although some study design variables were suggested as potential causes. Conclusion PCR status of SLN appears to have a clinically valuable prognostic power in patients with melanoma. Although the heterogeneity of the studies so far published warrants caution to avoid overestimating the favorable results of pooled data, our findings strongly support additional investigation in this field.
Phase I Trial of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Doxorubicin and Cyclophosphamide in Children With Relapsed Solid Tumors: A Children's Oncology Group Study
Authors: Rheingold Susan R. , Hogarty Michael D. , Blaney Susan M. , Zwiebel James A. , Sauk-Schubert Calies , Chandula Reddy , Krailo Mark D. , Adamson Peter C. 
Published: April 2007

Purpose To determine the maximum-tolerated dose, toxicity, pharmacokinetics, and biologic effects of G3139 when administered with doxorubicin and cyclophosphamide to children with relapsed solid tumors. Patients and Methods Patients received a 7-day continuous infusion of 3, 5, or 7 mg/kg/d of G3139 every 21 days. Doxorubicin, cyclophosphamide, and dexrazoxane were administered on days 5 and 6 of the infusion. Pharmacokinetics and biology studies were performed during the first course. Results Thirty-seven patients, median age 14 years (range, 1 to 19 years), were enrolled, of whom 29 were fully assessable for toxicity. Because of dose-limiting neutropenia, doses of doxorubicin 30 mg/m2/d for 2 days, dexrazoxane 300 mg/m2/d for 2 days, and cyclophosphamide 500 mg/m2/d for 2 days were reduced initially, but with the addition of granulocyte colony-stimulating factor (GCSF), could be re-escalated to starting doses. At the 7 mg/kg/d dose level, only one of six patients experienced DLT (neutropenia > 7 days). At this dose, the average (± standard deviation) steady-state G3139 concentration was 2.04 ± 1 μg/mL, a concentration associated with biologic activity. Eleven of 15 patients had reduced bcl-2 expression in peripheral-blood mononuclear cells at the first assessable time point of G3139 exposure, and in eight of 14 patients with serial specimens this reduction persisted through day 6. Conclusion The recommended phase II dose of G3139 is 7 mg/kg/d as a 7-day continuous infusion, with cyclophosphamide 500 mg/m2/d and doxorubicin 30 mg/m2/d on days 5 and 6, followed by GCSF. G3139 may accentuate the myelosuppressive effects of doxorubicin and cyclophosphamide. Evidence for biologic effects of G3139 was demonstrated.
Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200
Authors: Giantonio Bruce J. , Catalano Paul J. , Meropol Neal J. , O'Dwyer Peter J. , Mitchell Edith P. , Alberts Steven R. , Schwartz Michael A. , Benson Al B. 
Published: April 2007

Purpose Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer. Patients and Methods Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity. Results The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting. Conclusion The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.
Survival and Late Mortality in Long-Term Survivors of Pediatric CNS Tumors
Authors: Morris E. Brannon , Gajjar Amar , Okuma James O. , Yasui Yutaka , Wallace Dana , Kun Larry E. , Merchant Thomas E. , Fouladi Maryam , Broniscer Alberto , Robison Leslie L. , Hudson Melissa M. 
Published: April 2007

Purpose To describe the pattern of survival and late mortality among contemporary long-term survivors of pediatric CNS tumor. Patients and Methods The study population comprised 643 pediatric patients with primary CNS tumor treated at St Jude Children's Research Hospital (Memphis, TN) from 1985 to 2000 who survived ≥ 5 years from diagnosis. Patients were classified according to primary tumor type, location of tumor, and survival. Cause of death was obtained from the medical record and categorized as progression, malignant transformation, second malignancy, medical complication, or external cause. Results Overall survival estimates for patients who survived at least 5 years postdiagnosis was 91.3% ± 2% and 86% ± 3% at 10 and 15 years postdiagnosis, respectively. A significant difference in the survival rates according to original tumor type (P = .001) was seen. Sixty-six (10%) of 643 patients experienced late mortality: 38 patients (58%) died of progressive disease while 14 patients (21%) died of second malignant tumor. Twelve patients (18%), predominantly with diencephalic tumor location, died of a specific medical cause: cardiovascular disease (n = 2), cerebrovascular accident (n = 1), metabolic collapse and/or sepsis (n = 7), respiratory failure (n = 1), or shunt malfunction (n = 1). Conclusion Late mortality occurs in a substantial number of long-term survivors of pediatric CNS tumors and is most influenced by the initial tumor histopathology. Progressive disease remains the most common cause of death within the first decade of diagnosis. Teenage patients requiring treatment for panhypopituitarism may be especially vulnerable and deserve significant medical surveillance.
Optimal Capacity Investment Decisions with Two-Sided Fixed-Capacity Adjustment Costs
Authors: Ye Qing , Duenyas Izak 
Published: April 2007

In this paper, we consider the optimal management of capacity when a firm faces fixed costs and variable costs to purchase capacity. The firm can also salvage capacity and receive a variable value per unit capacity salvaged, but faces a (different) fixed cost in this case. Each period, the firm faces a stochastic demand, and maintenance costs for capacity that it decides to keep. The firm would thus like to decide how much capacity it should purchase or salvage each period. We introduce a new concept, which we call (K1, K2)-concavity, and show that the profit-to-go function satisfies this property. This enables us to characterize the structure of an optimal policy, which is rather complex, consisting of multiple regions in which different decisions are made. We show how special cases of this problem (e.g., no fixed costs, expansion or contraction not allowed) reduce to well-known results, and how (K1, K2)-concavity is a generalization of concavity, K-concavity, and sym-K-concavity. We also show how different lead times for purchasing or salvaging capacity can be integrated into the model. Finally, we extend the model to the case where demand is Markov modulated, and a portion of capacity can deteriorate in each period.