Survey of the definition and screening of neonatal hypoglycaemia in Australia

Objective : To determine the approach to identifying neonatal hypoglycaemia and the definition of neonatal hypoglycaemia used by neonatal paediatricians in Australian Level 3 neonatal intensive care units (NICU).
Methodology : A questionnaire was sent to the 101 neonatal paediatricians in the 22 Level 3 NICU in Australia asking their method of screening for, and definition of, neonatal hypoglycaemia.
Results : Responses were received from 70 neonatal paediatricians, including all 22 directors. A bedside glucose meter is used in 19 of 22 NICU to screen for hypoglycaemia, whilst one NICU uses a glucose analyzer and another NICU uses a visual colour comparison method. One NICU does not screen, but has blood glucose measured in a satellite laboratory. If the screening method suggests hypoglycaemia, 62 of 63 neonatal paediatricians proceed to blood glucose determination in a laboratory, mostly using plasma samples. Based on the laboratory measurement, the definition of neonatal hypoglycaemia ranged from <1.1 to 3.0 mmol/L.
Conclusions : The majority of neonatal paediatricians in Australian NICU screen for neonatal hypoglycaemia using a bedside glucose meter. There is a wide range in the definition of neonatal hypoglycaemia from <1.1 to 3.0mmol/L.     

MR imaging of blood vessels using three-dimensional reconstruction: methodology

Multisection, dual-echo magnetic resonance (MR) transaxial images of blood vessels contain both anatomic and qualitative information about flow. Even so, the images are produced as a series of two-dimensional tomographic sections from which full visualization of connected structures is difficult. A computer algorithm was developed that automatically detects flowing blood based on pixel intensity and calculated T2 and provides reconstructed views of vessels while analyzing and displaying flow characteristics. Images of abdominal vessels, aortic aneurysms, and the heart were encoded by flow and color to demonstrate depth. In addition, these data were reconstructed to derive a more accurate assessment of patency. With this technique, transaxial images can be used to analyze flow patterns, determine patent areas, and visualize all levels of vessels in a single image.     

Similarities and dissimilarities between calmodulin and a Chlamydomonas flagellar protein.

A protein that resembles vertebrate calmodulins and troponin C has been isolated from Chlamydomonas flagella by using a calmodulin purification protocol that included calcium-dependent affinity-based adsorption chromatography on phenothiazine-Sepharose conjugates. The flagellar protein resembled calmodulin in elution from reverse-phase columns, had a peptide map similar to that of calmodulin, and competed with vertebrate calmodulin in a radioimmunoassay using antisera against vertebrate calmodulin. However, this flagellar protein did not activate phosphodiesterase, lacked N epsilon-trimethyllysine, and had an isoelectric point approximately 0.3 pH unit higher than that of vertebrate calmodulin. When analyzed by polyacrylamide gel electrophoresis under various conditions, the Chlamydomonas protein migrated between vertebrate calmodulins and rabbit skeletal muscle troponin C and did not manifest a large calcium-dependent mobility shift. This calmodulin-like protein was identified as one of the approximately 200 35S-labeled components in Chlamydomonas flagella resolved by two-dimensional gel electrophoresis. These studies indicate that calmodulin and a structurally and functionally homologous protein are present in the same cell. These studies also demonstrate that caution is necessary: (i) in identifying a protein as a calmodulin, (ii) in using phenothiazines or antisera directed against vertebrate calmodulins as specific probes for calmodulin, and (iii) in the interpretation of experiments on biological systems in which calmodulin is substituted for the homologous calmodulin-like protein.     

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

Background  

To prospectively evaluate the efficacy and safety of selective internal radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy.     

Psychometric characteristics of simulation-based assessment in anaesthesia and accuracy of self-assessed scores

The purpose of this study was to define the psychometric properties of a simulation-based assessment of anaesthetists. Twenty-one anaesthetic trainees took part in three highly standardised simulations of anaesthetic emergencies. Scenarios were videotaped and rated independently by four judges. Trainees also assessed their own performance in the simulations. Results were analysed using generalisability theory to determine the influence of subject, case and judge on the variance in judges' scores and to determine the number of cases and judges required to produce a reliable result. Self-assessed scores were compared to the mean score of the judges. The results suggest that 12-15 cases are required to rank trainees reliably on their ability to manage simulated crises. Greater reliability is gained by increasing the number of cases than by increasing the number of judges. There was modest but significant correlation between self-assessed scores and external assessors' scores (rho = 0.321; p = 0.01). At the lower levels of performance, trainees consistently overrated their performance compared to those performing at higher levels (p = 0.0001).     

Dermatologic Surgical Research and the Institutional Review Board

BACKGROUND: Dermatologic surgical techniques have transformed cosmetic surgery over the last two decades. Many of the advances in cutaneous laser surgery, botulinum toxin injections, tumescent liposuction, and the latest filler agents have been evaluated on willing volunteers as part of organized trials under the auspices of an Institutional Review Board (IRB). OBJECTIVES: To review the developmental history of today's IRB and to provide relevance to cosmetic dermatologic research. RESULTS: Although an IRB must evaluate the "voluntariness" of a proposed research protocol, the risk-benefit ratio, particularly of elective cosmetic dermatologic surgical human studies, is of even greater importance. CONCLUSION: As more dermatologic surgeons become involved in clinical research, an understanding of the function and purpose of the IRB has become increasingly important. Research relating to cosmetic dermatologic procedures raises challenging and perplexing problems for an IRB.     

Validation of the neuroinflammation cycle as a drug discovery target using integrative chemical biology and lead compound development with an Alzheimer's disease-related mouse model

The neuroinflammation cycle has been proposed as a potential therapeutic target in the development of new approaches to altering Alzheimer's disease (AD) progression. However, the efficacy and toxicological profile of compounds that focus only on classical NSAID targets have been disappointing to date. Therefore, we recently initiated an unbiased, integrative chemical biology approach that used a hierarchal set of cell-based screens, followed by efficacy analysis in a new AD-relevant animal model that more closely resembles human pathology endpoints in terms of neuroinflammation and neuronal loss. The prior investigations provided a proof of concept that targeting the neuroinflammation cycle may be a viable drug discovery approach for AD. However, recent informatics analyses of the high attrition rate in drug development have identified the need for starting drug development with lead compounds that are well below cut off values in computed molecular properties in order to facilitate late stage medicinal chemistry refinement to improve in vivo functions. We describe here how we are leveraging our novel, unbiased, integrative chemical biology approach for the rapid discovery of potential lead compounds for AD drug discovery. Specifically, we show that orally bioavailable compounds with the desired physical properties and in vivo functions can be identified in focused synthetic libraries composed of chemical diversifications of the inactive but privileged pyridazine molecular fragment.