Cost Variation in Temporizing External Fixation of Tibial Plateau Fractures.

Background: Rising health care expenditures and declining reimbursements have generated interest in providing interventions of value. The use of external fixation is a commonly used intermediate procedure for the staged treatment of unstable fractures. External fixator constructs can vary in design and costs based on selected component configuration.

Ankle Fractures: An Expert Survey of Orthopaedic Trauma Association Members and Evidence-Based Treatment Recommendations.

Objectives: To describe current practice patterns of orthopaedic trauma experts regarding the management of ankle fractures, to review the current literature, and to provide recommendations for care based on a standardized grading system.

Design: Web-based survey.

Participants: Orthopaedic Trauma Association (OTA) members.

Acute Compartment Syndrome: An Expert Survey of Orthopaedic Trauma Association Members.

Objectives: The goal of this study was to describe current opinions of orthopaedic trauma experts regarding acute compartment syndrome (ACS).

Design: Web-based survey.

Participants: Active Orthopaedic Trauma Association (OTA) members.

Screw Stripping After Repeated Cortical Screw Insertion-Can We Trust the Cancellous "Bailout" Screw?

Background: During osteosynthesis standard nonlocking cortical screws often require reinsertion, raising concern over possible decrease in their effectiveness. This study aims to quantify that potential loss of fixation with reinsertions as well as examine the ability of a cancellous "bailout screw" to regain insertion torque in a previously stripped screw hole.

Methods: Four different types of bone surrogates were chosen to represent normal cortical bone, osteoporotic cortical bone, high-density (normal) cancellous bone, and low-density (osteoporotic) cancellous bone; nonlocked 3.

Complications and Predictors of Need for Return to the Operating Room in the Treatment of Supracondylar Humerus Fractures in Children.

Unlabelled: Supracondylar humerus fractures are common pediatric injuries. Little is known about the risk factors for repeat operative procedures. A retrospective chart review of 709 patients treated for a displaced supracondylar humerus fracture was performed to identify risk factors for return to the operating room during the initial post-operative period.

The perfect reduction: approaches and techniques.

Anatomic reduction of femoral neck fractures is difficult to obtain in a closed fashion. Open reduction provides for direct and controlled manipulation of fracture fragments. This can be accomplished via multiple approaches.

Detection of periprosthetic infections with use of ribosomal RNA-based polymerase chain reaction.

Background: Previously described molecular biology techniques used to detect periprosthetic infections have been complicated by false-positive results. We have reported the development of a messenger RNA (mRNA)-based procedure to reduce these false-positive results. The limitations of this procedure are the lack of a universal target and reduced sensitivity due to a low concentration of bacterial mRNAs in test samples.

Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells.

Background: A variety of arginine-rich peptide sequences similar to those found in viral proteins have been conjugated to other molecules to facilitate their transport into the cytoplasm and nucleus of targeted cells. The selective high affinity ligand (SHAL) (DvLPBaPPP)2LLDo, which was developed to bind only to cells expressing HLA-DR10, has been conjugated to one of these peptide transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL uptake and internalization by Raji cells, a B-cell lymphoma.

Results: An analog of the SHAL (DvLPBaPPP)2LLDo containing a hexa-arginine peptide was created by adding six D-arginine residues sequentially to a lysine inserted in the SHAL's linker.

Molecular specific and cell selective cytotoxicity induced by a novel synthetic HLA-DR antibody mimic for lymphoma and leukemia.

Like rituximab, monoclonal antibodies reactive with human leukocyte antigen have potent antilymphoma activity. However, size limits their vascular and tissue penetration. To mimic monoclonal antibody binding, nanomolecules have been synthesized, shown specific for the beta subunit of HLA-DR10, and selective for cells expressing this protein.

Nanomolecular HLA-DR10 antibody mimics: A potent system for molecular targeted therapy and imaging.

To mimic the molecular specificity and cell selectivity of monoclonal antibody (mAb) binding while decreasing size, nanomolecules (selective high-affinity ligands; SHALs), based on in silico modeling, have been created to bind to human leukocyte antigen-DR (HLA-DR10), a signaling receptor protein upregulated on the malignant B-lymphocytes of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. SHALs were synthesized with a biotin or DOTA chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), using a solid-phase lysine-polyethyleneglycol backbone to link sets of ligands shown previously to bind to HLA-DR10. Using cell-binding and death assays and confocal microscopy, SHAL uptake, residualization, and cytocidal activity were evaluated in HLA-DR10 expressing and nonexpressing live, human lymphoma cell lines.

Development of TNKase-specific cleavable peptide-linked radioimmunoconjugates for radioimmunotherapy.

Radioimmunotherapy (RIT) is a method for selectively delivering radionuclides to cancer cells while reducing the radiation dose to normal tissues. However, because of slow clearance of MAbs, normal tissues also received radiotoxicity. One of the promising strategies is linking on-demand cleavable (ODC) peptides between radiometal chelates and the tumor targeting agents.

Pre-clinical evaluation and efficacy studies of a melanin-binding IgM antibody labeled with 188Re against experimental human metastatic melanoma in nude mice.

Purpose: Currently there is no satisfactory treatment for metastatic melanoma. Radioimmunotherapy (RIT) uses the antigen-antibody interaction to deliver lethal radiation to target cells. Recently we established the feasibility of targeting melanin in tumors with 188-Rhenium ((188)Re)-labeled 6D2 mAb to melanin.

NanoFerrite particle based radioimmunonanoparticles: binding affinity and in vivo pharmacokinetics.

Dextran and PEG-coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal antibodies, scFv, and peptides conjugated to 20 nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NPs can affect their in vivo performance.

Short communication: nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells.

Unlabelled: Nanoparticle thermotherapy (NPTT) uses monoclonal antibody-linked iron oxide magnetic nanoparticles (bioprobes) for the tumor-specific thermotherapy of cancer by hysteretic heating of the magnetic component of the probes through an externally applied alternating magnetic field (AMF). The present study investigated the effect of NPTT on a human prostate cancer cell line, DU145. The concept of total heat dose (THD) as a measure for NPTT was validated on a cellular level and THD was correlated to cell death in vitro.

Selective high-affinity ligand antibody mimics for cancer diagnosis and therapy: initial application to lymphoma/leukemia.

Purpose: More than two decades of research and clinical trials have shown radioimmunotherapy to be a promising approach for treating various forms of cancer. Lym-1 antibody, which binds selectively to HLA-DR10 on malignant B-cell lymphocytes, has proved to be effective in delivering radionuclides to non-Hodgkin's lymphoma and leukemia. Using a new approach to create small synthetic molecules that mimic the targeting properties of the Lym-1 antibody, a prototype, selective high-affinity ligand (SHAL), has been developed to bind to a unique region located within the Lym-1 epitope on HLA-DR10.

Characteristics of dimeric (bis) bidentate selective high affinity ligands as HLA-DR10 beta antibody mimics targeting non-Hodgkin's lymphoma.

Despite their large size, antibodies have proven to be suitable radioisotope carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. To mimic antibody (Ab) targeting behavior while decreasing size by 50-100x, a combination of computational and experimental methods were used to generate molecules that bind to unique sites within the HLA-DR epitopic region of Lym-1, an Ab shown effective in patients. Lym-1 Ab mimics (synthetic high afinity ligands; SHALs) were generated and studied in vitro, using live cell binding assays, and/or pharmacokinetic studies over 24 h in xenografted mice given 1 or 20 microg SHAL doses i.

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Unlabelled: Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab.

Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies.

Background: About one-third of patients with relapsed B-cell malignancies develop human anti-mouse antibody (HAMA) following mouse antibody treatment. The purpose of this study was to assess the relationship between HAMA and survival in patients given a mouse anti-lymphoma monoclonal antibody (mAb), Lym-1, directed against a unique epitope of HLA-DR antigen that is up-regulated on malignant B-cells.

Methods: ELISA was used to quantify HAMA in 51 patients with B-cell malignancies treated with iodine-131 (131I) labeled Lym-1.

A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients.

Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies.

Alpha-synuclein (alphaS) is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson's disease (PD) and the related disorder, dementia with Lewy bodies (DLB). A central question about the role of alphaS in the pathogenesis of PD and DLB concerns how this normally soluble protein assembles into insoluble aggregates associated with neuronal dysfunction. We recently detected highly soluble oligomers of alphaS in normal brain supernatants and observed their augmentation in PD and DLB brains.

Characterization of human IgG antimouse antibody in patients with B-cell malignancies.

Purpose: Immunotherapeutic approaches to cancer offer an attractive adjunct to conventional modalities, although human antiglobulin responses can be an obstacle to repeated treatment. This study of a large number of patients with B-cell malignancies, over an extended period of time, characterized their human antimouse antibody (HAMA) seroconversion.

Experimental Design: A total of 617 samples from 112 subjects were analyzed for HAMA titers.

Documentation of idiotypic cascade after Lym-1 radioimmunotherapy in a patient with non-Hodgkin's lymphoma: basis for extended survival?

Purpose: The purpose of this study was to examine idiotypic cascade mechanisms in the plasma of a prolonged survivor patient with aggressive non-Hodgkin's lymphoma (NHL). It is a follow-up to previously published seminal studies by this laboratory showing survival benefit associated with radioimmunotherapy in NHL patients. Immunoglobulin from the patient's plasma was purified, characterized, and shown to possess the activities expected of idiotypic antibodies.

Effect of molecular size of pegylated peptide on the pharmacokinetics and tumor targeting in lymphoma-bearing mice.

Purpose: Rapid blood and body clearances have hampered effective tumor targeting by small molecules. We used branched poly(ethylene glycol) (pegylated) polymers (M(r) 40,000, M(r) 70,000, M(r) 100,000, and M(r) 150,000) conjugated to tumor-specific and control peptides to assess the effect of both molecular weight and tumor specificity on pharmacokinetics and biodistribution.

Experimental Design: Pegylated specific lymphoma-binding peptide and control peptide (containing stereoisomers of proline and aspartate) were synthesized, radiolabeled with (111)In, fractionated by size, and injected into Raji lymphoma-bearing athymic mice (4-6 mice/group).

Selection and characterization of anti-MUC-1 scFvs intended for targeted therapy.

Purpose: The selection and characterization of anti-MUC-1 single-chain antibody fragments (scFv) is a first step toward the construction of new anticancer molecules designed for optimal blood clearance and tumor penetration. The mucin MUC-1 was chosen as an antigen because it is abundantly expressed on epithelial cancers in an aberrantly glycosylated form, making it structurally and antigenically distinct from MUC-1 expressed on normal cells.

Experimental Design: A previously constructed anti-MUC-1 phage display library from hyperimmunized mice, with 5 x 10(5) calculated variants, was screened for the selection of anti-MUC-1 scFvs.

Calix[4]arene, calix[4]resorcarene, and cyclodextrin derivatives and their lanthanide complexes as chiral NMR shift reagents.

Calix[4]arenes, calix[4]resorcarenes, and anionic cyclodextrin derivatives were examined as chiral NMR solvating agents. The calix[4]arenes were prepared by attachment of amino acids through the hydroxyl groups of the phenol rings. Chloroform-, methanol-, and water-soluble derivatives were prepared and tested with a range of substrates.