Optimizing Therapeutic Effect of Aurora B Inhibition in Acute Myeloid Leukemia with AZD2811 Nanoparticles.

Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective Aurora kinase B inhibitor AZD2811 (formerly known as AZD1152-hQPA) in preclinical models of AML.

Selection of LNA-containing DNA aptamers against recombinant human CD73.

LNA-containing DNA aptamers against CD73 (human ecto-5'-nucleotidase), a protein frequently overexpressed in solid tumours, were isolated by SELEX. A pre-defined stem-loop library, containing LNA in the forward primer region, was enriched with CD73 binding sequences through six rounds of SELEX with recombinant his-tagged CD73 immobilised on anti-his plates. Enriched pools isolated from rounds one, three and six were subjected to next-generation sequencing and analysed for enrichment using custom bioinformatics software.

Toggled RNA aptamers against aminoglycosides allowing facile detection of antibiotics using gold nanoparticle assays.

We have used systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers against aminoglycoside antibiotics. The SELEX rounds were toggled against four pairs of aminoglycosides with the goal of isolating reagents that recognize conserved structural features. The resulting aptamers bind both of their selection targets with nanomolar affinities.

Evaluation of novel renal biomarkers with a cisplatin model of kidney injury: gender and dosage differences.

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We use two novel multiplex assays to quantify biomarker concentration in multiple urine collections made prior to and following administration of cisplatin, a common nephrotoxicant, to rats. We investigate the correlation of the magnitude of biomarker changes with the severity of histopathological observations and explore the relationship of these to both dose and sex.

Evaluation of novel urinary renal biomarkers: biological variation and reference change values.

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin. From these data, we calculate inter-individual variation and reference ranges from predose animals and intra-individual variation and reference change values from undosed control animals.

Evaluation of novel urinary renal biomarkers with a cisplatin model of kidney injury: effects of collection period.

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. To date, all evaluation studies have been made using 18 to 24 hour collection periods. However, shorter, more welfare friendly, urine collection periods are also used in industry.

Cerebral venous sinus thrombosis following cervical disc arthroplasty.

Cerebral venous sinus thrombosis is a rare condition, which is difficult to diagnose. It has not previously been reported following surgery to the cervical spine . We report such a case in a 45-year-old man after cervical disc replacement.

An approach to the validation of flow cytometry methods.

This publication outlines an approach for the validation of flow cytometry methods used in the analysis of a wide range of biomarkers. It is written as a guidance document for method validation in a GLP environment, and from the viewpoint of the pharmaceutical industry, but its relevance is wide-ranging. The approach to method validation described is intended as a starting point for further discussion, as well as providing reference material to colleagues developing fit-for-purpose flow cytometry methods.

Time-course study of the immunotoxic effects of the anticancer drug chlorambucil in the rat.

In 2005, the International conference on harmonization (ICH) recommended that all new human pharmaceuticals be tested for unintended immunomodulatory potential via a tiered approach. Included in this approach is a semiquantitative description of changes in the separate compartments of lymphoid tissue (also called enhanced histopathology). Chlorambucil was administered to Hanover Wistar rats at regular time points, followed by a treatment-free (recovery) period.

Considering the impact of medicine label design characteristics on patient safety.

Medication errors involving patients receiving the wrong medicines, the wrong dosages or failure to take medicines according to the prescribed schedule are a substantial threat to patient safety. In the medical domain, research evidence on the benefits of improved labelling are piecemeal and often single-product or single-manufacturer driven and often do not inform the more general process of label design. Government and other guidelines on this topic are often low level and non-specific, often failing to give evidence-based guidance.

The potentiation of two components of the reach-to-grasp action during object categorisation in visual memory.

Stimulus-Response Compatibility Effects have been reported for several components of the reach-to-grasp action during visual object recognition [Tucker, M., & Ellis, R. (1998).

Opportunistic screening for abdominal aortic aneurysm.

Objective: To contribute to the current debate on screening for abdominal aortic aneurysm (AAA).

Setting: Radiology department of the John Radcliffe Hospital, Oxford.

Methods: The prevalence of AAA in 317 clinically referred male patients aged 65-74 undergoing abdominal ultrasonography with no clinical suspicion of an AAA was investigated over a period of one year.

Retrieval and allocation of organs for transplantation: the Michigan experience.

The Organ Procurement Agency of Michigan (OPAM) is now in its twenty-third year of service to the transplant community in Michigan. From a beginning with one coordinator in 1971, it now employs 53 individuals, including 8 laboratory technologists for its own on-site histocompatibility laboratory, a dozen procurement coordinators stationed throughout the state, 6 organ placement coordinators in the main office, 6 screening coordinators who provide around-the-clock coverage at the office, a tissue recovery section, as well as additional finance, education, and administrative support staff. This chapter outlines the history and growth in organ recoveries of the organization.

A role for ultrasound in limb lengthening.

The distraction gap at eight sites in six patients undergoing limb lengthening was monitored by both standard radiographs and ultrasound. Using the measurements obtained we were able to assess the rate and quality of callus formation at the distraction site, something that radiographs alone do not enable one to do. We suggest that ultrasound has a valuable role to play in guaging the optimum rate of lengthening for a particular patient and commend it as a technique to complement radiographs in the follow-up of the increasing numbers of patients undergoing distraction osteogenesis.

Pharmacokinetics of teicoplanin in subjects with varying degrees of renal function.

The pharmacokinetics of teicoplanin were studied in 20 subjects with varying degrees of renal function after administration of a single 200 mg intravenous dose. Pharmacokinetic parameters were calculated with a three compartment open model and by non-compartmental analysis. The elimination half-life increased as creatinine clearance decreased (rs = -0.

Hypercalcaemia as a manifestation of malignant urothelial change in analgesic nephropathy.

We report two cases of patients with analgesic nephropathy presenting with the symptoms of hypercalcaemia, and who were found to have transitional cell carcinomas of the renal pelvis. On removal of the tumours, calcium levels fell to normal, indicating that a humoral factor produced by the tumour caused the hypercalcaemia. We suggest that hypercalcaemia in a patient with analgesic nephropathy may indicate a malignant change, and that serum calcium should be assessed when such patients are reviewed.