Effects of thermal exposure on binding of heparin in vitro to the arterial wall and to clot and on the chronic angiographic luminal response to local application of a heparin film during angioplasty in an in vivo rabbit model

Experimentally, heparin inhibits mechanisms that promote fibrosis, neointimal cellular proliferation, and thombin bound to fibrin at the surface of intraluminal thrombus, but only in relatively high concentrations. A preliminary hypothesis was tested and confirmed in vitro that initial binding of ³H-heparin to mechanically injured porcine aorta is concentration-dependent over a 1,000–50,000 units/ml range (r = 0.9). The hypothesis was then tested in vitro that thermal exposure during contact of heparin to arterial tissue and to clot would enhance binding of the drug. ³H-heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatures > 70°C. Thermal exposure (80°C × 40 s) also enhanced tissue persistence of the drug within porcine aorta subjected to a shear rate of 1,100^?1in an annular Baumgartner chamber perfused with normal saline at 37°C for 48 h. Heparin in vitro anticoagulant activity persisted after thermal exposure and binding to tissues. A new method was developed for local application of a heparin film that provides a maximum concentration with a tolerable systemic dose during an angioplasty procedure. In an in vivo rabbit model of mural fibrosis after iliac artery angioplasty, the 1-month mean angiographic luminal diameter loss (23% compared to the acute postangioplasty result by computer image analysis) in response to conventional balloon angioplasty (BA) and laser balloon angioplasty (LBA) was the same (P > 0.05). Local application of a heparin film (3,000 units at a concentration > 100,000 units/g), however, reduced the mean % loss in diameter 1 month after LBA (12 %), but not after BA (29%), compared to arteries subjected to angioplasty without local heparin (P < .05). The results are consistent with the hypothesis that thermal energy enhances heparin binding to tissues and that local application of a heparin film favorably modulates arterial luminal responses to LBA, but not to BA, in this animal model. © 1994 Wiley-Liss, Inc.     

Permanent iodine-125 implants in postoperative radiotherapy for head and neck cancer with positive surgical margins

Background. Patients with head and neck cancer treated surgically have a high local recurrence rate, unless the surgeon is able to obtain adequate margins of resection. In patients with positive margins, tumor control is suboptimal despite postoperative radiotherapy. Methods. We treated 25 consecutive patients, who were at high risk for local recurrence by virtue of positive margins, by modest dose postoperative external-beam irradiation (median 60 Gy) followed by elective iodine 125 (I-125) implantation. Results. With a median follow-up of 1.5 years (range 1-5 years), there were no instances of necrosis, and only one (4%) instance of a local recurrence. Six patients (24%) developed distant metastases. Conclusions. These results indicate that elective 1-125 implantation as a part of postoperative radiotherapy is safe enough for a phase III study in patients with positive margins. © 1994 John Wiley & Sons, Inc.     

Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer

An ineffective tumor-specific immune response from inadequate/incompetent antigen presentation could contribute to the failure in tumor control and its dissemination. Dendritic cells (DCs) have been shown to present antigen from apoptotic cells. We hypothesized that Flt3-ligand (Flt3L) therapy, which expands DCs in vivo, in combination with local tumor radiotherapy (RT), should improve antigen presentation from dying, irradiated tumor cells. RT + Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcinoma and significantly improved survival in C57Bl/6 mice with established footpad tumors. Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT + Flt3L failed to impact survival in immunodeficient athymic mice, implicating the role of T cells in prolonging survival. These results support an attractive strategy of sequential RT and immunotherapy with Flt3L to enhance tumor antigen presentation, which may produce therapeutic responses against disseminated cancer and improvement in survival.     

Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation

Hepatic tumors often recur in the liver after surgical resection. Postoperative radiotherapy (RT) could improve survival, but curative RT may induce delayed life-threatening radiation-induced liver damage. Because RT inhibits liver regeneration, we hypothesized that unirradiated, transplanted hepatocytes would proliferate preferentially in a partially resected and irradiated liver, providing metabolic support. We subjected F344 rats to hepatic RT and partial hepatectomy with/without a single intrasplenic, syngeneic hepatocyte transplantation. Hepatocyte transplantation ameliorated radiation-induced liver damage and improved survival of rats receiving RT after partial hepatectomy. We further demonstrated that transplanted hepatocytes extensively repopulate and function in a heavily irradiated rat liver.     

Paper or plastic? Simulation based evaluation of two versions of a cognitive aid for managing pediatric peri-operative critical events by anesthesia trainees: evaluation of the society for pediatric anesthesia emergency checklist

Cognitive aids (CA), including emergency manuals and checklists, are tools designed to assist users in prioritizing and performing complex tasks during time sensitive, high stress situations (Marshall in Anesth Analgesia 117(5):1162–1171, 2013; Marshall and Mehra in Anaesthesia 69(7):669–677, 2014). The society for pediatric anesthesia (SPA) has developed a series of emergency checklists tailored for use by pediatric perioperative teams that cover a wide range of intraoperative critical events (Shaffner et al. in Anesth Analgesia 117(4):960–979, 2013). In this study, we evaluated user preferences for a CA (SPA checklist) using two different presentation formats, paper and electronic, during management of simulated critical events. Anesthesia trainees managed the simulated critical events under one of three randomized conditions: (1) memory alone, (2) with a paper version of the CA, (3) with an electronic version of the CA. Following participation in the simulated critical events, participants were asked to complete a survey regarding their experience using the different versions of the CA. The percentage of favorable responses for each format of the CA was compared using a mixed effects proportional odds model. There were 143 simulated events managed by 89 anesthesia trainees. Approximately one out of three trainees (electronic 29 %, paper 30 %) assigned to use the CA chose not to use it and completed the scenario from memory alone. The survey was completed by 68 % of participants, 58 % of trainees preferred the paper version and 35 % preferred the electronic version. All survey responses that reached statistical significance favored the paper version. In this study, anesthesia trainees had a favorable opinion of the content and perceived clinical relevance of both versions of the CA. In both quantitative and qualitative analysis, the paper version of the CA was preferred over the electronic version by participants. Despite overall favorable responses to the CA, a sizeable number of participants chose not to use either version the CA during the crisis.     

Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall

IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied—tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4–IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.