Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Impact of Management Practices on Employee Effectiveness in South Asia

South Asian organizations in countries like Bangladesh, India, Pakistan, and Sri Lanka are trying to professionalize management practices in recent years. Inspite of such efforts, employees indiscipline, politicised labor unions, low individual productivity, and unsatisfactory enterprise performance are some of the commonly observed realities in most of the organizations. Because of the prevalent socioeconomic conditions, these countries are placed at a competitive disadvantage even when they have huge reservoirs of technically competent human resources. Most professional managers in these countries express frustration over the situation but seem to suffer from a withdrawal syndrome symptomatic of inaction and helplessness. Recently, several attempts have been made to explain the ineffective utilization of human resources in India (Kanungo & Misra, 1985), Bangladesh (Miyan, 1991), and Pakistan (Qureshi, 1986). These attempts provide different perspectives for our understanding, but argue for developing a systemic rather than piecemeal approach to the study of human resource management (HRM) practices. Taking a lead from such earlier attempts, the present paper explores the nature of HRM practices in South Asian organizations using a framework that relates such practices to employee effectiveness. The findings reported in the paper are consultant observations about organizations the data has generated a number of conclusions research. The paper also offers some guidance action plans to improve HRM practices.management practices, human resource management

Performance Challenges at Masood Textile Mills

Shahid Nazir, Chief Executive Officer of Masood Textile Mills in Faisalabad, Pakistan wanted to turn his company into one of the leading apparel companies in the world. To achieve this vision, Nazir wanted to transform his employees into what he called 'corporate athletes' through his vision and a more credible Performance Appraisal System. However, the results of an employee survey earlier in the year indicated that the company's performance appraisal was perceived by the employees to be subjective, inadequate and lacked credibility. This was of serious concern to Nazir. He therefore developed a new Performance Appraisal and Reward System. Implementation of the new system, however, was delayed temporarily due to the events of 9/11 and Nazir now aimed at its enforcement by mid 2002. He was of the opinion that the implementation of the new system would help in improving the motivation of his employees which, in turn, would lead to sustained high performance so essential to realize his vision. This case is useful in examining the design and implementation of an employee performance appraisal and reward system.

Učinak levamisol hidroklorida na titrove protutijela za slinavku i šap u krvnom serumu i kolostrumu u cijepljenih bivolica (Bubalus bubalis).

A study was conducted to ascertain whether post-vaccination antibody titres in serum and colostrum against foot and mouth disease virus in pregnant buffaloes (Bubalus bubalis) could be enhanced by simultaneous administration of levamisole hydrochloride. Twenty-four pregnant buffaloes were divided into three groups of equal size: unvaccinated, vaccinated control, and levamisole-treated vaccinated. The vaccination was given 10 weeks prior to expected parturition. Weekly serum samples were collected until parturition, while colostrum samples were obtained within 1h after parturition. Passive haemagglutination test was applied to determine antibody titres. Levamisole-treated animals showed a progressive rise in antibody titre until week 6, reaching a peak value of 70.0 ± 4.3 (SD) during that same week. Levamisole hydrochloride significantly (P<0.05) increased antibody titres in serum, although results of statistical analysis of colostral antibody titres were not significantly different between experimental groups.Istraživanje je provedeno da se utvrdi da li se može post-vakcinalni titar protutijela za slinavku i šap u serumu i u kolostrumu gravidnih bivolica povečati istovremenim davanjem levamisol hidroklorida. Dvadeset i četiri gravidne bivolice (Bubalus bubalis) su podijeljene u 3 jednake skupine: necijepljene, cijepljene kontrolne i cijepljene uz tretman levamisolom. Cijepivo je davano 10 tjedana prije očekivanog telenja. Tjedni uzorci seruma su uzimani do telenja, a kolostruma 1 sat nakon telenja. Za utvr|ivanje titra protutijela rabljen je test pasivne hemaglutinacije. Životinje tretirane levamisolom pokazale su progresivan rast titra protutijela do šestog tjedna kada su dosegle najvišu vrijednost od 70,0±4,3 (SD). Levamisol hidroklorid je značajno (P<0,05) povisio titar protutijela u serumu ali se rezultati statističke analize titra kolostralnih protutijela nisu značajno razlikovali među skupinama pokusnih životinja