MS 233 Guide to Phillip D. Robinson, MHA, LFACHE Papers (1993-1994)

This collection consists of materials relating to Phillip D. Robinson\u27s professional relationships and travels in Ukraine and Russia. The collection contains agreements, proposals, correspondence, reports, agendas, contact lists, and photographs. There are materials pertaining to the International Consortium for Research on the Health Effect of Radiation (ICRHER); the Ukrainian Research Center for Radiation Medicine; the International Consortium for Research of Radiation Induced Injury; the Methodist Hospital (Houston, Tex.); Institute of Experimental Radiology (Kiev, Ukraine); and the Ukrainian Research Center for Radiation Medicine. See more at MS 233

Unique Phosphorylation of Protein Kinase C-α in PC12 Cells Induces Resistance to Translocation and Down-regulation

Cell exposure to phorbol ester stimulates translocation and activation of protein kinase C (PKC), ultimately followed by its down-regulation. Upon activation, PKC-alpha, the best studied isotype of the PKC family, undergoes changes in its phosphorylation state. With a two-dimensional immunoblot procedure we have previously shown the existence in PC12 cells of several multiply phosphorylated forms of PKC-alpha, whose number increases in response to phorbol esters (Gatti, A., Wang, X., and Robinson, P. J. (1996) Biochim. Biophys. Acta 1313, 111-118). Using the same experimental system, here we report that besides the predominant pool of 80-kDa PKC-alpha forms that respond to phorbol ester by translocating to the cell membranes and down-regulating, there is a small pool of cytosolic 82-kDa PKC-alpha forms that are characterized by a more acidic pI and by an unique resistance to phorbol ester-mediated translocation and down-regulation. The appearance of similarly slower migrating and more acidic PKC-alpha forms is reproduced upon in vitro autophosphorylation in the presence of phosphatidylserine and phorbol ester, but not in the presence of calcium. These results suggest that site-specific transphosphorylation or autophosphorylation of this kinase may regulate its subcellular localization and susceptibility to down-regulation

Changing Trends in Total Knee Replacement

Introduction:  This study evaluates a possible change in the demographics and surgical practice observed in a large cohort of patients undergoing total knee replacement (TKR). Patients and methods:  We performed a retrospective analysis of a prospectively collected data on two groups of consecutive patients undergoing primary TKR. Group one consisted of patients who underwent surgery between 1994 and 1998. Group two consisted of patients who had surgery between 2009 and 2012. Results:  The mean age of group two was significantly greater than that of group one: 68.9 years (68.1–69.7 years) for group one versus 70.1 years (69.6–70.6 years) for group two (p = 0.009). The mean BMI of group two was significantly greater than that of group one: 29.5 kg/m2 (29.0–29.9 kg/m2) for group one versus 32.0 kg/m2 (31.7–32.3 kg/m2) for group two (p < 0.001). The mean pain component of the AKSS was significantly worse in group one than in group two: 28.6 (27.2–30.0) for group one versus 35.5 (34.6–36.4) for group two (p < 0.001). The mean function component of the AKSS was significantly worse in group one than in group two: 48.6 (47.3–49.9) for group one versus 51.5 (50.7–52.3) for group two (p < 0.001). Conclusion:  This study describes the change in demographics of patients undergoing TKR in our institution over the last two decades.Publisher PDFPeer reviewe

Tissue Penetration of Bipolar Electrosurgery at Different Power Settings

Introduction: Bipolar electro-surgery is used in all disciplines of surgery to aid in haemostasis. Although common sense dictates tissue penetration will be effected by power settings, no formal evaluation of this effect has been made. We performed an experiment to accurately measure the tissue penetration of bipolar diathermy at different strengths. Materials and Methods: Laboratory study using a porcine liver model. Different wattages (10–40 W) of bipolar electro-surgery were applied to deceased porcine liver, with and without fascial covering for a fixed duration. The tissue penetration was measured with a light microscope in two planes, horizontal and perpendicular. The data was compared with a Spearman Rank correlation coefficient calculation. Results: For both fascia and non fascia covered liver there was a statistically significant correlation between increasing power and superficial spread of tissue penetration (Non fascia rho=0.3604, p =0.05) (Fascia rho=0.893, p =0.0068). No such correlation was noted between burn depth and wattage (Non fascia rho=-0.75, p =0.93) (Fascia rho = 0.714, p = 0.0713). There was a statistically significant correlation between the diameter and depth of tissue penetration for fascia covered tissue (rho 0.893, p = 0.0068) but not for non fascia covered tissue (rho 0.3604, p =0.42). Discussion: There is a clear relationship between the power setting of electro surgery and superficial spread of tissue damage however the effects of power setting and deep tissue penetration are not so clear. Interestingly, maximum tissue effects were not encountered at the higher power settings but between 20 and 30 W

Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression

<p>Abstract</p> <p>Background</p> <p>The aim of both classical (e.g. taxol) and targeted anti-mitotic agents (e.g. Aurora kinase inhibitors) is to disrupt the mitotic spindle. Such compounds are currently used in the clinic and/or are being tested in clinical trials for cancer treatment. We recently reported a new class of targeted anti-mitotic compounds that do not disrupt the mitotic spindle, but exclusively block completion of cytokinesis. This new class includes MiTMAB and OcTMAB (MiTMABs), which are potent inhibitors of the endocytic protein, dynamin. Like other anti-mitotics, MiTMABs are highly cytotoxic and possess anti-proliferative properties, which appear to be selective for cancer cells. The cellular response following cytokinesis failure and the mechanistic pathway involved is unknown.</p> <p>Results</p> <p>We show that MiTMABs induce cell death specifically following cytokinesis failure via the intrinsic apoptotic pathway. This involves cleavage of caspase-8, -9, -3 and PARP, DNA fragmentation and membrane blebbing. Apoptosis was blocked by the pan-caspase inhibitor, ZVAD, and in HeLa cells stably expressing the anti-apoptotic protein, Bcl-2. This resulted in an accumulation of polyploid cells. Caspases were not cleaved in MiTMAB-treated cells that did not enter mitosis. This is consistent with the model that apoptosis induced by MiTMABs occurs exclusively following cytokinesis failure. Cytokinesis failure induced by cytochalasin B also resulted in apoptosis, suggesting that disruption of this process is generally toxic to cells.</p> <p>Conclusion</p> <p>Collectively, these data indicate that MiTMAB-induced apoptosis is dependent on both polyploidization and specific intracellular signalling components. This suggests that dynamin and potentially other cytokinesis factors are novel targets for development of cancer therapeutics.</p

One size doesn’t always fit all:professional perspectives of serious incident management systems in mental healthcare

PurposeThe need to develop effective approaches for responding to healthcare incidents for the purpose of learning and improving patient safety has been recognised in current national policy. However, research into this topic is limited. This study aims to explore the perspectives of professionals in mental health trusts in England about what works well and what could be done better when implementing serious incident management systems.Design/methodology/approachThis was a qualitative study using semi-structured interviews. In total, 15 participants were recruited, comprising patient safety managers, serious incident investigators and executive directors, from five mental health trusts in England. The interview data were analysed using a qualitative-descriptive approach to develop meaningful themes. Quotes were selected and presented based on their representation of the data.FindingsParticipants were dissatisfied with current systems to manage serious incidents, including the root cause analysis approach, which they felt were not adequate for assisting learning and improvement. They described concerns about the capability of serious incident investigators, which was felt to impact on the quality of investigations. Processes to support people adversely affected by serious incidents were felt to be an important part of incident management systems to maximise the learning impact of investigations.Originality/valueFindings of this study provide translatable implications for mental health trusts and policymakers, informed by insights into how current approaches for learning from healthcare incidents can be transformed. Further research will build a more comprehensive understanding of mechanisms for responding to healthcare incidents