A rapid reversed phase high performance liquid chromatographic method for determination of etoposide (VP-16) in human plasma

A rapid, simple and sensitive isocratic High Performance Liquid Chromatography (HPLC) method was developed to measure the concentration of etoposide in plasma samples with UV detection at 220 nm. The method uses a Bondapac C18 column at 60 degrees C. The mobile phase consists of Methanol: water (45:55 v/v) at a flow rate of 2.8 ml/min. Phenacetin was used as an internal standard. The plasma samples were extracted using ether with the organic layer evaporated under nitrogen. The residue was dissolved in 200 microl methanol with 20 microl injected into the HPLC column. The extraction method showed a recovery of 91.5+/-3% for etoposide. In this system, the retention time of phenacetin and etoposide were 3.3 and 4.4 min, respectively. The limit of detection of etoposide in plasma is 20 ng/ml and the limit of quantitation is 40 ng/ml. This analytical method has very good reproducibility (8.1% between-day variability at a concentration of 50 ng/ml). It is a fast, sensitive and economic method applicable for clinical and pharmacokinetic studies.     

The value of Bayes theorem in the interpretation of subjective diagnostic findings: what can we learn from agreement studies?

The Bayes theorem is advocated as the appropriate measure for the weight of evidence in medical decision making. It is based on the calculation of posttest probability as a function of the accuracy of the test and pretest probability. Nevertheless, for subjective diagnostic findings, there might be substantial variability in the accuracy among human observers, making the point estimate of posttest probability imprecise. Although there is limited evidence regarding the actual variability of accuracy among observers for the majority of diagnostic findings, classical observer agreement studies provide us with an indirect estimate of such variability. The aim of this work was to explicate the relationship between observer disagreement and variability of posttest probability. Using a random effects signal detection model with 3 stochastic components (between subject, between observer, and residual variations), the authors modeled diagnostic tests with various characteristics and calculated the expected between-observer disagreement and 95% interval of the observers' posttest probability. For the majority of simulated conditions, variation in posttest probability was surprisingly high, even in the presence of substantial agreement. Although the model is based on parametric assumptions, these results are a clue to a source of inaccuracy in the calculation of posttest probability. Practitioners should be aware of such variation in their clinical practice, and diagnostic studies need to develop strategies to address this uncertainty.     

Behavioural changes related to olfactory mucosal metaplasia and bulbar glial fibrillary acidic protein (GFAP) induction in methylsulphonyl-dichlorobenzene-treated mice

Methylsulphonyl-2,6-dichlorobenzene [2,6-(diCl-MeSO(2)-B)], and its 2,5-chlorinated isomer [2,5-(diCl-MeSO(2)-B)] bind firmly in the olfactory mucosa of mice. Both isomers are also selectively localised in the olfactory bulb. Persistent olfactory mucosal metaplasia is induced by 2,6-(diCl-MeSO(2)-B) whereas 2,5-(diCl-MeSO(2)-B) has no effects. Furthermore, a strong induction of glial fibrillary acidic protein (GFAP) restricted to the olfactory bulb has been reported in 2,6-(diCl-MeSO(2)-B)-treated mice. To explore whether these lesions give rise to early or long-lasting changes in behaviour, spontaneous motor activity and radial arm maze (RAM) learning were examined at 1, 2, 4 and 12 weeks following an intraperitoneal injection of a single low (32 mg/kg) or high (65 mg/kg) dose of 2,6-(diCl-MeSO(2)-B). 2,5-(DiCl-MeSO(2)-B) (65 mg/kg) was used as a negative control. Hyperactivity was observed in all treatment groups while deficits in the RAM performance was only seen in the 2,6-(diCl-MeSO(2)-B)-treated groups. Alterations in motor activity and impaired performance in the RAM-test induced by 2,6-(diCl-MeSO(2)-B) persisted up to 2 weeks in the low-dose group and 12 weeks in the high-dose group. The low-dose group consistently showed a less pronounced effect than the high-dose group. The 2,5-(diCl-MeSO(2)-B)-induced changes in motor activity declined rapidly and did not remain after 2 weeks. As determined by immunohistochemistry, 2,6-(diCl-MeSO(2)-B)-induced GFAP immunoreactivity was mainly confined to the glomerular layer of the olfactory bulb. We propose that the behavioural deficits caused by 2,6-(diCl-MeSO(2)-B) result from a primary loss of sensory neurons in the olfactory mucosa with consequent astrocyte proliferation in the glomerular layer of the olfactory bulb. A targeted uptake of metabolites into the olfactory bulb could also contribute to the GFAP induction and/or behaviour response.     

The effectiveness of personal education plans in continuing professional development: an evaluation

The aim of this study was to evaluate the use of personal education plans (PEPs) as a method of continuing professional development (CPD), by means of a questionnaire, analysis of completed PEP reports, and in-depth interviews. The setting was the Yorkshire Deanery, and the participants were general practitioners (GPs) who had completed a PEP. The main outcome measures were reported identification of learning needs, educational methods used, and support received. GPs' views were received on their experiences of undertaking PEPs, personal and professional development, and changes in patient care that resulted from their PEPs. Personal impression was the most frequently used method of deciding on learning needs. A variety of educational methods were used, the most frequent being personal reading, practical sessions, and taught courses. The majority of respondents felt that they were well supported by their GP tutors, and that the PEP had helped them to enhance their personal knowledge and skills, as well as to improve service to patients. There were gains in terms of increased confidence and self-awareness. Most were keen to use PEPs in future, and hoped to involve other members of the practice. Our results suggest that PEPs are an effective method of CPD in that they frequently lead to reported changes in patient care, and personal and professional development of the learner.     

Self-esteem and anxiety in human figure drawing of Iranian children with ADHD

This study is aimed at investigating the self-esteem and anxiety of children with Attention Deficit/Hyperactivity Disorder compared with normal children by means of Draw-A-Person Test. 30 children with ADHD were selected from psychiatric clinics of Isfahan, Iran using multi-cluster sampling. 30 normal children were also selected from public schools of Isfahan by the same method. The results were analyzed using analysis of variance and Chi-square. In this research, six criteria were selected from Draw-A-Person Test. The results revealed significant differences between the performance of the children with ADHD and normal children in terms of size and line characteristic (P < 0.05). For the other criteria no significant difference was found between these groups. Based on this finding, some aspects of drawing may be more meaningful than other aspects in drawings of children with ADHD.     

Layer-specific longitudinal strain detects transmural dysfunction in chronic severe aortic regurgitation before and after aortic valve surgery

The International Journal of Cardiovascular Imaging - To assess if layer-specific longitudinal strain (LS) provides incremental diagnostic and prognostic value compared to global longitudinal...     

Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study

Neurological Sciences - The preva lence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We...     

Comparative Analysis of the Stress–Strain State of a Lightweight 3D-Printed Shoulder Implant

Biomedical Engineering - The use of 3D printing in orthopedics has several advantages, one of which is a reduction of the implant weight due to the use of honeycomb structures. In this work, a...