A model for harmonizing flow cytometry in clinical trials.

Complexities in sample handling, instrument setup and data analysis are barriers to the effective use of flow cytometry to monitor immunological parameters in clinical trials. The novel use of a central laboratory may help mitigate these issues.

Guidelines for management of actual or suspected inadvertent intra-arterial injection of sclerosants.

BACKGROUND: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. OBJECTIVES: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. METHODS: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. RESULTS: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. CONCLUSION: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

New and improved proteomics technologies for understanding complex biological systems: addressing a grand challenge in the life sciences.

This White Paper sets out a Life Sciences Grand Challenge for Proteomics Technologies to enhance our understanding of complex biological systems, link genomes with phenotypes, and bring broad benefits to the biosciences and the US economy. The paper is based on a workshop hosted by the National Institute of Standards and Technology (NIST) in Gaithersburg, MD, 14-15 February 2011, with participants from many federal R&D agencies and research communities, under the aegis of the US National Science and Technology Council (NSTC). Opportunities are identified for a coordinated R&D effort to achieve major technology-based goals and address societal challenges in health, agriculture, nutrition, energy, environment, national security, and economic development.

Autotransplantation of teeth: an overview.

UNLABELLED: Autotransplantation is the surgical repositioning of a tooth within the same patient. It can be thought of as a controlled avulsion and re-implantation of a tooth in a new, surgically prepared socket. The indications for its use are discussed, as too are factors affecting the success and the clinical procedures. The preservation and regeneration of the periodontal ligament is the key to success of this treatment. A case involving the transplantation of a premolar tooth into the central incisor location in a child is presented to show the different stages of the process. CLINICAL RELEVANCE: Autotransplantation is an underutilized technique which, when used within a multidisciplinary team, can offer an ideal treatment option for child or adolescent patients with missing or failing anterior teeth.

Quantitation of HER2 and telomerase biomarkers in solid tumors with IgY antibodies and nanocrystal detection.

In an effort to improve affinity biomarker validation in fixed patient tissue specimens, we have developed a novel quantum dot-based bioimaging system that utilizes chicken IgY antibody for high sensitivity and specificity relative quantitation of cancer proteins. Monospecific, polyclonal IgYs were generated against human HER2 and telomerase, and analytically validated for specificity by western blot and immunohistochemistry on tumor and normal cells and for relative affinity by layered peptide array (LPA). IgYs bound desired targets in cell lines and fixed tissues and showed greater affinity than commercial mammalian antibodies for both HER2 and telomerase proteins. In tissue microarray experiments, HER2 quantitation with IgY antibody and quantum dot imaging correlated well with chromogenic in situ hybridization (CISH), whereas telomerase quantitation suggested a trend toward correlation with prostate cancer Gleason Grade and differentiation. Although patient numbers were small, these findings demonstrate the feasibility of relative quantitation of cancer biomarkers with IgY and quantum dot fluorophores, and show promise for rigorous clinical validation in large patient cohorts.

Standards for autoantibody testing; addressing future needs for autoimmune disease and cancer diagnosis.

It is widely held that determination of increased levels of serum autoantibodies can play an important role in the diagnosis and, in some cases, management of many autoimmune diseases. It is also widely held that such testing is fraught with problems relating to accuracy and detection of clinically relevant autoantibodies. Attempts to standardize autoantibody testing by making available standard reference sera, have helped to some degree to improve the testing. Nevertheless, problems still exist and may be causing the delayed diagnosis of severely debilitating and sometimes fatal autoimmune diseases. This paper discusses current practice, as well as, possible new approaches intended to make more robust, autoantibody determinations in all fields of medicine.