Advances in the assessment and control of the effector functions of therapeutic antibodies

The Fc (crystallizable fragment) region of therapeutic antibodies can have an important role in their safety and efficacy. Although much is known about the structure-activity relationship of antibodies and the factors that influence Fc effector functions, a process has not yet been defined to clearly delineate how Fc functionality should be assessed and controlled during antibody development and manufacturing. In this article, we summarize the current knowledge of antibody Fc functionality, provide a strategy for assessing the effector functions of different classes of therapeutic antibodies (including Fc fusion proteins) and propose a path for routine testing and controls for manufacturers of antibody products.     

A novel Global Assessment Scale for Wilson's Disease (GAS for WD)

Wilson's disease (WD) is an inherited disorder of copper metabolism. Despite being treatable, patients with WD suffer severe disabilities due to delay in initiation and difficulty in monitoring treatment. We propose a two tier, Global Assessment Scale for Wilson's Disease (GAS for WD) that grades the multisystemic manifestations of the disease. Tier 1 scores the global disability in four domains: Liver, Cognition and behavior, Motor, and Osseomuscular. Tier 2 is multidimensional scale for a fine grained evaluation of the neurological dysfunction. We prospectively validated this scale in 30 patients with WD. Both tiers had a high inter‐rater reliability (Intraclass correlation coefficient ICC (A, 2) = 0.96–1.0). Tier 2 items were internally consistent (Cronbach's α = 0.89) and factorial analysis showed that 90.3% of the Tier 2 total score variance was determined by seven factors. Scores of both tiers were commensurate with the disease burden as assessed by standard disability scales (Child Pugh, UPDRS, SS3, and CGI) and satisfied criteria for validity. Longitudinal follow‐up over 1.5 years showed that the scale was sensitive to clinical change. This suggests that GAS for WD is a practical tool with potential applications in management of patients, and in testing and comparison of treatment regimens. © 2008 Movement Disorder Society     

Brief Report: Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants

Absolute quantification measurements (copies per cell) of peptide major histocompatibility complex (pMHC) antigens are necessary to inform targeted immunotherapy drug design; however, existing methods for absolute quantification have critical limitations. Here, we present a platform termed SureQuant-IsoMHC, utilizing a series of pMHC isotopologues and internal standard-triggered targeted mass spectrometry to generate an embedded multipoint calibration curve to determine endogenous pMHC concentrations for a panel of 18 tumor antigens. We apply SureQuant-IsoMHC to measure changes in expression of our target panel in a melanoma cell line treated with a MEK inhibitor and translate this approach to estimate antigen concentrations in melanoma tumor biopsies.     

Manuka honey dressing: An effective treatment for chronic wound infections

The battle against methicillin-resistant Staphylococcus aureus (MRSA) wound infection is becoming more difficult as drug resistance is widespread and the incidence of MRSA in the community increases. Manuka honey dressing has long been available as a non-antibiotic treatment in the management of chronic wound infections. We have been using honey-impregnated dressings successfully in our wound care clinic and on the maxillofacial ward for over a year.     

Significance of non-intraocular pressure (IOP)-related factors particularly in normal tension glaucoma: Looking beyond IOP

Purpose:To study the relationship between intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) in patients with POAG and NTG. The secondary objective was to identify other contributory ischemic factors.Methods:This was an observational cross-sectional study from a tertiary eye hospital in patients who underwent full-day diurnal variation of tension (DVT). Blood pressure (BP) and IOP measurements were done every 3 h over 24 h. Mean arterial pressure (MAP) and MOPP were calculated. The nocturnal dip in BP was assessed; patients were classified as non-dippers, dippers, and over-dippers. The circadian MOPP fluctuation (CMF) was calculated using the Kruskal–Wallis test, and its relationship with type and severity of visual field was assessed.Results:In total, 149 patients were evaluated; 109 were classified as NTG, and 40 were classified as POAG. A nocturnal dip in BP was noted in 20% of NTG and 17.5% of POAG. The MAP was found to be lower in patients with NTG than POAG. In the NTG subgroup, we found that 20% of patients were over-dippers, 32% were dippers, and 48% were non-dippers. The CMF showed a greater fluctuation for over-dippers (P = 0.004 for the RE and 0.003 for the LE) than dippers and non-dippers. A weak positive correlation of CMF with the severity of fields was found.Conclusion:A 24-h monitoring of IOP, BP, MOPP, and assessment of systemic risk factors for primary glaucoma acts as an invaluable tool for the comprehensive management of NTG despite the limitations posed by DVT and BP recording.     

Superiority of chlorhexidine 2%/alcohol 70% wipes in decontaminating ultrasound equipment

Ultrasound equipment is known to act as a reservoir for potentially pathogenic organisms. The aims of these studies were to establish current cleaning practices, to review the extent of bacterial contamination of ultrasound equipment in our hospital, to establish an effective cleaning regimen and to ensure that cleaning does not cause damage. A questionnaire was sent to all acute NHS hospitals in England to establish current cleaning practices. A review of our current practice was performed to establish the extent of bacterial contamination of ultrasound equipment currently in use. Laboratory studies compared cleaning the probes with soap and water with decontaminating with a chlorhexidine 2% and alcohol 70% wipe, including quantifying the residual effect. Accelerated aging was performed on the probe and staff surveyed to establish potential problems with using the wipes on the probe. The survey revealed that a variety of cleaning methods were used to decontaminate ultrasound probes; 57% of our ultrasound machines were contaminated with bacteria. The laboratory studies showed superiority of the chlorhexidine and alcohol wipes over soap and water due to a residual effect, both immediately after cleaning and after 24 hours. The staff survey demonstrated no apparent change in function of the probe after cleaning with the chlorhexidine wipes. Cleaning ultrasound probes with chlorhexidine and alcohol wipes is effective and provides additional protection against bacterial contamination due to its residual effect, and appears in the short term to have no detrimental effect on the probe.