A simple technique for evaluation of methods of cell separation

A simple method is described for labelling cells with fluorescein and using them in artificial mixtures to assess cell separation procedures. The method facilitates the examination of the variables in a separation procedure. It is thus possible to tailor a separation procedure (for example panning with monoclonal antibody) to suit the specific requirements of the experiment.     

Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs

Background

Concerns exist that women are underrepresented in trials of cardiovascular medications.

Analysis of Reported Adverse Events with Uterine Artery Embolization for Leiomyomas

Study Objective

To analyze and investigate reports associated with uterine artery embolization used for treatment of myomas using this database.

Comparison of carbon fibre and aluminium materials in the construction of ultralight wheelchairs

Abstract

Carbon fibre-reinforced polymers have been used in the sporting goods industry for decades, and wheelchairs have incorporated the material since the late 1980s. There is no independently collected data available on carbon fibre-reinforced polymer wheelchairs’ performance on the ANSI/RESNA testing standards, however. This study evaluated three full carbon fibre wheelchair specimens to determine their performance versus similar wheelchairs. Testing determined that while the frames survived more testing cycles than any other wheelchair, the casters and rear tires failed similarly to other devices. Overall, due to the purchase cost, the cost benefit of the tested wheelchair model was similar to aluminium wheelchairs.

• Implications for rehabilitation

• Carbon fibre wheelchair construction is a viable alternative to aluminium, titanium, or steel construction, and decreasing costs will continue to improve the benefits of carbon fibre over these models

• Carbon fibre wheelchair found to be more durable than aluminium models, but are also much more expensive. The additional cost may be justified for some users that need the increased durability, however

• Increased durability will reduce the number of repairs and warranty claims, potentially reducing the burden on a wheelchair user, and also improving their ability to travel and participate in their community

• The low weight of carbon fibre wheelchairs may increase the mobility of some users by allowing them to transfer more easily into and out of vehicles and manoeuvre throughout the environment

     

Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors.     

Optimizing endoscopic placement of expandable stents throughout the GI tract

Expandable stents have now become accepted for the relief of malignant obstruction throughout the GI tract and biliary system. Almost all expandable stents are composed of metal. More recently, an expandable plastic stent has been developed for the treatment of benign esophageal conditions. The clinical response to these devices is dependent on proper stent placement and anatomical location. Proper stent placement, in turn, is dependent on being familiar with the characteristics of the devices, having knowledge of the length of the stricture and anatomy, and the location of the obstruction within the GI tract. This review summarizes the available devices and techniques for optimal placement of expandable stents.     

QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system

BACKGROUND: Recent case series have associated the synthetic opioid, methadone, with QT prolongation and torsades de pointes (TdP) ventricular arrhythmia. STUDY OBJECTIVE: To review and analyze adverse events (QT prolongation and TdP) reported to the Food and Drug Administration (FDA) to determine the patient characteristics, dosages of methadone, and outcomes of methadone-treated patients. METHODS: The study design was a retrieval and retrospective analysis of reports of adverse events associated with methadone voluntarily reported to the FDA MedWatch program from 1969 to October 2002. Reports were accessed via QSCAN (DrugLogic, Reston, VA), a commercially available software interface. RESULTS: In a total of 5,503 reports of adverse events associated with methadone, 43 (0.78%) noted the occurrence of TdP and 16 (0.29%) QT prolongation. Doses were reported in 42/59 (71%) of cases; mean dose was 410 +/- 349 mg/day (median 345, range 29-1680). The dosages for 10 of the 42 cases (29%) were within the recommended range for methadone maintenance treatment, 60-100 mg/day. Female gender, interacting medications, hypokalemia, hypomagnesemia, and structural heart disease, risk factors previously identified with other drugs known to cause TdP, were found in 44 (75%) cases. Most adverse events required hospitalization or resulted in prolonged hospitalization (28/59, 47%) and 5/59 (8%) were fatal. CONCLUSIONS: Cases of TdP associated with methadone have been reported to the FDA MedWatch system. Analysis of the cases provides evidence that prolonged QT and TdP can occur over a wide range of dosages including those usually recommended for addiction treatment.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.