bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applications of Evidence‐Based Medicine: Cranial Cruciate Ligament Injury Repair in the Dog
Authors: Aragon Carlos L. , Budsberg Steven C. 
Published: April 2005

Objective—To evaluate the literature reporting surgical interventions pertaining to canine cranial cruciate ligament (CCL) injury using an evidence‐based medicine paradigm.Study Design—Systematic literature review.Methods—An on‐line bibliographic search through Medline, PubMed, Veterinary Information Network, and Commonwealth Agricultural Bureau Abstracts was performed during August 2004. Two hundred and forty resources of information were identified. Studies were compared and evaluated with regard to study design (retrospective, prospective, randomization), surgical technique, short‐ and long‐term follow‐up, and evidence classification.Results—Twenty‐eight resources qualified to assist with evidence classification. No class I or class II studies were present, 5 studies were categorized as a class III and 23 studies were categorized as a class IV. Seventeen studies were retrospectively designed and 11 studies were prospectively designed. Proposed results ranged from a wide variety of subjective findings including clinical impression, radiographic analysis, synovial fluid analysis, gross pathology, and histopathology. Objective results, although infrequent, included force plate analysis and cadaveric biomechanical testing.Conclusions—At this time, the application of evidence‐based medicine in analyzing the current available evidence suggests that there is not a single surgical procedure that has enough data to recommend that it can consistently return dogs to normal function after CCL injury. The requirement for assessing and categorizing the available evidence becomes increasingly important as more data becomes available and the quality of research improves.Clinical Relevance—An evidence‐based medicine paradigm did not provide sufficient evidence favoring 1 surgical technique for management of canine CCL injury.
Ultrasonographic and Radiographic Assessment of Uncomplicated Secondary Fracture Healing of Long Bones in Dogs and Cats
Authors: Risselada Marije , Kramer Martin , De Rooster Hilde , Taeymans Olivier , Verleyen Piet , Van Bree Henri 
Published: April 2005

Objectives— To evaluate the use of ultrasonography (US) to detect bone healing in uncomplicated diaphyseal fractures of dogs and cats, and to compare these observations with detection of healing by radiography (RG).Study Design— Clinical study.Animals— Dogs (33) and cats (11).Methods— RG and brightness mode US were used to follow uncomplicated secondary fracture healing. Fractures were examined at admission and then every 2–4 weeks until healed or implant removal. Temporal differences in definitive detection of healed fracture by imaging technique were examined by species, patient age, bone, and fracture type.Results— US images obtained during uncomplicated secondary fracture healing were consistent with images of fracture healing described in humans. Mean time to US diagnosis of a healed fracture (mean 46 days) was significantly shorter than by RG (mean 66 days). Mean time until diagnosis of a healed fracture (US and RG) did not differ significantly between open and closed treatment. Patients ≤7 months (n=9) healed significantly faster (P<.05) than animals aged 7–36 months (n=24) and animals >36 months (n=11), but there was no significant difference between the latter 2 groups. Diagnosis of a healed simple fracture by US was significantly quicker than for a comminuted fracture (P<.05), but no difference was noted when using RG.Conclusions— US can be used to evaluate secondary fracture healing in biologically treated fractures in dogs and cats. US permits detection of a healed fracture earlier than RG.Clinical Relevance— Earlier diagnosis of a healed fracture by US can prevent unnecessarily long limb immobilization and allow earlier dynamization.
Long‐Term Radiographic Comparison of Tibial Plateau Leveling Osteotomy Versus Extracapsular Stabilization for Cranial Cruciate Ligament Rupture in the Dog
Authors: Lazar Tibor P. , Berry Clifford R. , Dehaan Jacek J. , Peck Jeffrey N. , Correa Maria 
Published: April 2005

Objective—Comparison of 2 methods of surgical management of cranial cruciate ligament (CCL) injury in large‐breed dogs using a radiographic osteoarthrosis (OA) scoring system.Study design—Retrospective study.Animals—Client‐owned dogs (n=66).Methods—Radiographs were evaluated from dogs weighing ≥22.7 kg, with surgical management of CCL rupture using extracapsular repair (ECR) or tibial plateau leveling osteotomy (TPLO). Radiographs were taken immediately before surgery and ≥12 months later. An OA score was assigned to each set of radiographs taken at the preoperative and final examinations by evaluating 32 specific features of stifle OA. The difference between preoperative and final OA scores were subtracted and 2 final score categories of a change ≤5 or >5 were created. A logistic regression model was used to evaluate the effect of right versus left pelvic limb, age, preoperative weight, postoperative weight, days from surgery until final radiographic recheck, cranial cruciate status at surgery, medial meniscus status at surgery, and ECR versus TPLO.Results—The ECR group had 27 stifles (22 dogs) and the TPLO group had 52 stifles (44 dogs). ECR dogs had a preoperative weight of 33.4±9.3 kg (range 22.7–54.1 kg) and a preoperative OA score of 13.0±8.4 (range 1–34) compared with TPLO dogs that had a preoperative weight of 38.9±9.1 kg (range 25–63.9 kg) and preoperative OA score of 15.9±8.4 (range 4–44). Postoperative weights for ECR and TPLO dogs were 33.6±9 kg (range 21.8–54.6 kg) and 39.4±10.1 kg (range 24–72 kg), respectively. Final OA scores were: ECR dogs, 26.3±10.8 (range, 10–54); TPLO dogs, 23.3±9.5 (range, 12–50). Dogs with a final change in OA score of ≥6 were 5.78 times more likely to have had ECR compared with those that had TPLO as stabilization procedure (odds ratio=5.78; Log‐likelihood testP‐value=.025). Other dependent variables were not significant.Conclusions—Based on logistic regression analysis, dogs with larger OA score differences were 5.78 times more likely to have had ECR than TPLO.Clinical Relevance—Prospective, randomized surgical trials with pre‐defined objective measures would be required to further evaluate the clinical importance of these preliminary findings which suggest that TPLO may help stabilize the cranial tibial thrust as originally proposed.
Use of an Ultrasonically Activated Scalpel for Splenectomy in 10 Dogs with Naturally Occurring Splenic Disease
Authors: Royals Stephen R. , Ellison Gary W. , Adin Chris A. , Wheeler Jason L. , Sereda Colin W. , Krotscheck Ursula 
Published: April 2005

Objective— To evaluate the safety and efficacy of an ultrasonically activated scalpel for performing splenectomy, with minimal ligation, in dogs.Study Design— Prospective clinical study.Animals— Dogs (10) with naturally occurring splenic disease.Methods— Between October 2003 and February 2004, splenectomy was performed using an ultrasonically activated scalpel and a double seal method, in 10 dogs with naturally occurring splenic disease. Time for splenectomy and number of ligatures required were recorded. Intraoperative hemostasis, device ease of use, postoperative hemorrhage, and short‐term survival were evaluated.Results— Mean operative time for splenectomy, exclusive of celiotomy and closure, was 18 minutes (range, 8–25 minutes). The mean number of ligatures needed to perform splenectomy was 1 (range, 0–2 ligatures). One dog hemorrhaged from the splenic vein after ultrasonic scalpel transection of a vessel >5‐mm diameter and required a ligature. The ultrasonic scalpel was easy to use, with a minimal learning curve. None of the dogs had postoperative abdominal hemorrhage; 9 dogs were discharged and 1 dog was euthanatized because of septicemia.Conclusion— Ultrasonic activated scalpel may be used to achieve efficient and safe hemostasis of the splenic vascular pedicle in dogs with minimal need for vascular ligation.Clinical Relevance— Ultrasonic scalpels can be used to perform splenectomy in dogs with naturally occurring splenic disease.
Strong convergence theorems for infinite families of nonexpansive mappings in general Banach spaces
Authors: Suzuki Tomonari 
Published: April 2005

AbstractIn 1979, Ishikawa proved a strong convergence theorem for finite families of nonexpansive mappings in general Banach spaces. Motivated by Ishikawa's result, we prove strong convergence theorems for infinite families of nonexpansive mappings.
Phenotypic and functional characteristics of CD34+ cells are related to their anatomical environment: is their versatility a prerequisite for their bio-availability?
Authors: Lataillade Jean-Jacques , Clay Denis , David Catherine , Boutin Laetitia , Guerton Bernadette , Drouet Michel , Hérodin Françis , Le Bousse-Kerdilès Marie-Caroline 
Published: April 2005

AbstractHuman CD34+ hematopoietic progenitors (HP) are mainly resident in adult bone marrow (BM). However, their recent revelation in nonhematopoietic tissues implies their circulation through peripheral blood (PB). The intimate mechanisms of this physiological process are not yet understood. Our results showed that steady-state CD34+ HP exhibit a differential phenotypic profile according to their BM versus PB localization. We demonstrated that this phenotype could be modulated by incubation in the presence of their counterpart mononuclear cells (MNC) through cell interactions and cytokine production. Such a modulation mainly concerns migration-mediated cytokine and chemokine receptors as well as some adhesion molecules and partly results from MNC specificity. These phenotypic profiles are associated with distinct cell-cycle position, cloning efficiency, and migration capacity of CD34+ cells from the different anatomical sources. We therefore propose a definition for a circulating versus resident CD34+ cell profile, which mostly depends on their cellular environment. We suggest that blood would represent a supply of cells for which phenotypic and functional characteristics would be a prerequisite for their bio-availability.
Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver
Authors: Uhrig Anja , Banafsche Ramin , Kremer Michael , Hegenbarth Silke , Hamann Alf , Neurath Markus , Gerken Guido , Limmer Andreas , Knolle Percy A 
Published: April 2005

AbstractKupffer cells and liver sinusoidal endothelial cells (LSEC) clear portal venous blood from gut-derived bacterial degradation products such as lipopolysaccharide (LPS) without inducing a local inflammatory reaction. LPS tolerance was reported for Kupffer cells, but little is known whether sensitivity of LSEC toward LPS is dynamically regulated. Here, we demonstrate that LSEC react to LPS directly as a function of constitutive Toll-like receptor 4 (TLR4)/CD14 expression but gain a LPS-refractory state upon repetitive stimulation without loss of scavenger activity. LPS tolerance in LSEC is characterized by reduced nuclear localization of nuclear factor-κB upon LPS rechallenge. In contrast to monocytes, however, TLR4 surface expression of LSEC is not altered by LPS stimulation and thus does not account for LPS tolerance. Mechanistically, LPS tolerance in LSEC is linked to prostanoid production and may account for cross-tolerance of LPS-treated LSEC to interferon-γ stimulation. Functionally, LPS tolerance in LSEC results in reduced leukocyte adhesion following LPS rechallenge as a consequence of decreased CD54 surface expression. Furthermore, LPS tolerance is operative in vivo, as we observed by intravital microscopy-reduced leukocyte adhesion to LSEC and improved sinusoidal microcirculation in the liver after repetitive LPS challenges. Our results support the notion that LPS tolerance in organ-resident scavenger LSEC contributes to local hepatic control of inflammation.
Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation
Authors: Pinho Vanessa , Souza Danielle G , Barsante Michele M , Hamer Fabiana P , De Freitas Marta S , Rossi Adriano G , Teixeira Mauro M 
Published: April 2005

AbstractThe phosphatidylinositol-3 kinase (PI3K) family of signaling enzymes plays a crucial role in leukocyte recruitment and activation and hence, likely regulates the induction and propagation phases of inflammation. However, little data have emerged showing a role for these processes in the resolution phase in models of in vivo inflammation. Here, we have evaluated the role of PI3K for the migration and survival of eosinophils in a model of allergic pleurisy in mice. Eosinophil accumulation in PI3Kγ-deficient mice was inhibited at 48 h, as compared with wild-type mice but not at earlier time-points (6 and 24 h). Experiments with adoptive transfer of bone marrow showed that PI3Kγ in eosinophils but not in non-bone marrow-derived cells was required for their accumulation. Systemic treatment with PI3K inhibitors before antigen challenge prevented the recruitment of eosinophils. This was associated with decreased Akt phosphorylation, interleukin-5 production, and eosinophil release from the bone marrow. Treatment with PI3K inhibitors 24 h after antigen challenge markedly cleared the accumulated eosinophils, an effect associated with inhibition of Akt phosphorylation and an increased number of apoptotic events. Altogether, our data demonstrate an important role of PI3Kγ for the maintenance of eosinophilic inflammation in vivo, whereas other isoforms of PI3K may be relevant for the recruitment process.
Heterogeneity of functional responses in differentiated myeloid cell lines reveals EPRO cells as a valid model of murine neutrophil functional activation
Authors: Gaines Peter , Chi Jeffrey , Berliner Nancy 
Published: April 2005

AbstractMature neutrophils display multiple functional responses upon activation that include chemotaxis, adhesion to and transmigration across endothelial cells, phagocytosis, and pathogen destruction via potent microbicidal enzymes and reactive oxygen species. We are using myeloid cell line models to investigate the signaling pathways that govern neutrophil functional activation. To facilitate these studies, we have performed a direct comparison of functional responses of human and murine myeloid cell line models upon neutrophil differentiation. Our results show that EPRO cells, promyelocytes that undergo complete neutrophil maturation, demonstrate a full spectrum of functional responses, including respiratory burst, chemotaxis toward two murine chemokines, and phagocytosis. We also extend previous studies of granulocyte-colony stimulating actor-induced 32Dcl3 cells, showing they domonstrate chemotaxis and phogocytosis but completely lack a respiratory burst as a result of the absent expression of a critical oxidase subunit, gp91phox. Induced human leukemic NB4 and HL-60 cells display a respiratory burst and phagocytosis but have defective chemotaxis to multiple chemoattractants. We also tested each cell line for the ability to up-regulate cell-surface membrane-activated complex-1 (Mac-1) expression upon activation, a response mediating neutrophil adhesion and a surrogate marker for degranulation. We show that EPRO cells, but not 32Dcl3 or NB4, significantly increase Mac-1 surface expression upon functional activation. Together, these data show that EPRO and MPRO cells demonstrate complete, functional activation upon neutrophil differentiation, suggesting these promyelocytic models accurately reflect the functional capacity of mature murine neutrophils.
Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote intercellular spreading following initial transfection
Authors: Mwangi Waithaka , Brown Wendy C , Splitter Gary A , Zhuang Yan , Kegerreis Kimberly , Palmer Guy H 
Published: April 2005

AbstractInduction of immune responses against microbial antigens using DNA is an attractive strategy to mimic the immunity induced by live vaccines. Although DNA vaccines are efficacious in murine models, the requirement for multiple immunizations using high doses in outbred animals and humans has hindered deployment. This requirement is, in part, a result of poor vaccine spreading and suboptimal DC transfection efficiency. Incorporation of a signal that directs intercellular spreading of a DNA-encoded antigen is proposed to mimic live vaccine spreading and increase dendritic cell (DC) presentation. Bovine herpes virus 1 tegument protein, BVP22, is capable of trafficking to surrounding cells. To test the hypothesis that BVP22 enhances spreading and antigen presentation to CD4+ T cells, a DNA construct containing BVP22, fused in-frame to a sequence encoding a T cell epitope of Anaplasma marginale, was generated. A construct with reversed BVP22 sequence served as a negative control. Immunocytometric analysis of transfected primary keratinocytes, human embryonic kidney 293, COS-7, and Chinese hamster ovary cells showed that BVP22 enhanced intercellular spreading by ≥150-fold. Flow cytometric analysis of antigen-presenting cells (APCs) positively selected from cocultures of transfected cells and APCs showed that 5% of test APCs were antigen-positive, compared with 0.6% of control APCs. Antigen-specific CD4+ T cell proliferation demonstrated that BVP22 enhanced DC antigen presentation by ≥20-fold. This first report of the ability of BVP22 to increase DNA-encoded antigen acquisition by DCs and macrophages, with subsequent enhancement of major histocompatibility complex class II-restricted CD4+ T cell responses, supports incorporating a spreading motif in a DNA vaccine to target CD4+ T cell-dependent immunity in outbred animals.
Evaluation of Epothilone B Analog in Advanced Soft Tissue Sarcoma: A Phase II Study of the Phase II Consortium
Authors: Okuno Scott , Maples William J. , Mahoney Michelle R. , Fitch Tom , Stewart James , Fracasso Paula M. , Kraut Michael , Ettinger David S. , Dawkins Fitzroy , Erlichman Charles 
Published: April 2005

Purpose Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease. Patients and Methods Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later. Results Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%). Conclusion BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.
Natural History of Rising Serum Prostate-Specific Antigen in Men With Castrate Nonmetastatic Prostate Cancer
Authors: Smith Matthew R. , Kabbinavar Fairooz , Saad Fred , Hussain Arif , Gittelman Marc C. , Bilhartz David L. , Wynne Chris , Murray Robin , Zinner Norman R. , Schulman Claude , Linnartz Ronald , Zheng Ming , Goessl Carsten , Hei Yong-Jiang , Small Eric J. , Cook Richard , Higano Celestia S. 
Published: April 2005

Purpose To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. Patients and Methods: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. Results At 2 years, 33% of patients had developed bone metastases. Median bone metastasis–free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. Conclusion Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.
Phase III Randomized Trial of Doxorubicin and Docetaxel Versus Doxorubicin and Cyclophosphamide As Primary Medical Therapy in Women With Breast Cancer: An Anglo-Celtic Cooperative Oncology Group Study
Authors: Evans T.R. Jeffry , Yellowlees Ann , Foster Elizabeth , Earl Helena , Cameron David A. , Hutcheon Andrew W. , Coleman Robert E. , Perren Timothy , Gallagher Christopher J. , Quigley Mary , Crown John , Jones Alison L. , Highley Martin , Leonard Robert C.F. , Mansi Janine L. 
Published: April 2005

Purpose To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. Patients and Methods Eligible patients with histologically proven breast cancer with primary tumors ≥ 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m2) plus docetaxel (75 mg/m2) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. Conclusion In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.