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. In this article, we quantify urinary biomarker concentration in serial paired sequential short and long urine collections from male rats administered varying concentrations of cisplatin. We calculate the rate of biomarker excretion in normal animals for both collection periods and the bias and correlation in urinary biomarker concentration between collection periods in dosed and control animals, and we estimate the level of agreement in biomarker concentration between both collection periods. We conclude that although there are minor differences in the concentration of some urinary biomarkers that are dependent upon the time and duration of collection, shorter collection protocols do not influence subsequent interpretation of normalized urinary biomarker data for most biomarkers.     

Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.     

Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions

Chemically defined medium (CDM) conditions for controlling human embryonic stem cell (hESC) fate will not only facilitate the practical application of hESCs in research and therapy but also provide an excellent system for studying the molecular mechanisms underlying self-renewal and differentiation, without the multiple unknown and variable factors associated with feeder cells and serum. Here we report a simple CDM that supports efficient self-renewal of hESCs grown on a Matrigel-coated surface over multiple passages. Expanded hESCs under such conditions maintain expression of multiple hESC-specific markers, retain the characteristic hESC morphology, possess a normal karyotype in vitro, as well as develop teratomas in vivo. Additionally, several growth factors were found to selectively induce monolayer differentiation of hESC cultures toward neural, definitive endoderm/pancreatic and early cardiac muscle cells, respectively, in our CDM conditions. Therefore, this CDM condition provides a basic platform for further characterization of hESC self-renewal and directed differentiation, as well as the development of novel therapies.     

The effects of a treatment protocol for cardiac surgical patients with excessive blood loss on clinical outcomes

BACKGROUND AND OBJECTIVES: Excessive blood loss (EBL) is a common complication of cardiac surgery that is associated with adverse events. The objective of this before/after study was to determine whether the implementation of a protocol for management of cardiac surgical patients with EBL was associated with improved clinical outcomes. MATERIALS AND METHODS: In November 2002, a protocol for prompt identification and aggressive management of cardiac surgical patients with EBL was implemented at our institution. The independent relationship between protocol implementation and adverse outcomes was measured by comparing the outcomes of patients who received > or = 4 RBC (red blood cell) units within 1 day of surgery and were operated on before protocol implementation (2000-02) with those operated on after protocol implementation (2003-05), using multivariable logistic regression analysis to control for the effects of confounders. The primary outcome was a composite of adverse events that included death, renal failure, stroke, and sepsis. Bootstrapping was used to confirm the validity of the results. RESULTS: Of the 11,314 patients who underwent surgery during the study period, 1875 (16.6%) received > or = 4 RBC units within 1 day of surgery, with 958 and 917 in the pre- and postprotocol periods, respectively. The composite adverse outcome occurred in 164 (17.1%) patients in the preprotocol period and 115 (12.5%) patients in the postprotocol period (P = 0.005). Protocol implementation was independently associated with reduced odds of the composite adverse outcome (odds ratio 0.67; 95% confidence interval 0.50, 0.91; P = 0.01). This estimate was stable in bootstrap sampling. CONCLUSION: Implementation of a protocol to manage EBL in cardiac surgery was independently associated with improved outcomes.     

Clinical diagnosis of fractures in a paediatric population.

Diagnosing fractures in the paediatric population is a problematical process for which there are currently no accepted clinical criteria. We studied the physical signs sought by accident and emergency staff in 126 children with suspected fractures. We found a significant correlation between 'point tenderness' and fracture, as demonstrated by plain radiograph. 'Swelling' and 'redness' approached significance. These results correlate well with previous work in this area, but further research using a larger sample is required as confirmation.