Performance and Consistency of Circulating Warm Water Blankets for Rodents

General anesthesia as used for rodent research can have adverse effects on physiologic mechanisms. Thermoregulation is often greatly inhibited, with resultant deleterious effects on cardiac and respiratory function. These potential effects can be mitigated by providing external heat support. The circulating warm water blanket and associated heat pump are often used in rodent procedures. The current study demonstrated that the heating pump and water blanket require quality control assessment to ensure adequate function. Our data showed that of the 6 pumps tested, 5 were able to achieve a temperature that met or exceeded the documented thermoneutral zone for mice. Pumps required 20 min of warming to reach their maximal attainable temperatures for the designated user setting. Although the pumps reached a temperature that was sufficient to provide external thermal support, only 1 of the 6 pumps reached the temperature that was set by the user during the trial. Surface temperatures across the water blanket were recorded to analyze whether a difference in heat support was influenced by animal placement along the water blanket; however, the location points did not yield statistically different results. Two pumps were eliminated from the study due to failure to pass the preparation phase of the trial. The results of this study support the need for facilities to establish quality control measures to ensure that heat support systems are functioning at a level required to maintain normothermia during anesthetic procedures.     

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch–German cross-border region, 2017 to 2018: the importance of healthcare structures

BackgroundAntimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.AimThe aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.MethodsBetween September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.ResultsA total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).ConclusionsThis first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.     

No evidence for tumorigenesis of AAV vectors in a large-scale study in mice.

Six hundred ninety-five mice received adeno-associated virus (AAV) vectors, mostly via portal vein injection. At necropsy, the livers were inspected for tumors, and tissue sections were prepared for histology. We observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. This tumor contained fewer vector genomes per total DNA than the surrounding liver tissue, as shown by quantitative PCR. In another mouse we found a macroscopically visible nodule containing lymphocytes. Immunohistochemistry revealed cells not of monoclonal origin, and they contained fewer AAV genomes than the surrounding hepatocytes. There were no macroscopic tumors in 226 control mice. Upon microscopic examination, lymphocytic infiltrates were found in 5% of livers of both control and vector-treated mice; no transgene expression was seen in those infiltrates in AAV-injected animals. Compared to an average frequency of spontaneous liver tumors in C57BL/6 mice (0-10%), and given the absence of high levels of vector DNA in the observed tumor, we conclude that AAV vectors do not predispose these target animals to the formation of liver tumors.     

Immunoadsorption with tryptophan columns: A therapeutic option for the treatment of rheumatoid arthritis with septic complications

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting multiple organs and tissues. Although there is a wide range of therapeutic applications, the coexistence of severe side effects and contraindications outlines the necessity of new therapeutic options in the treatment of severe RA. We report on the case of a 71‐year‐old patient with successful treatment of a complicated RA with tryptophan immunoadsorption combined with low‐dose steroids. Bacterial spondylitis developed in this patient during long‐term treatment with infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan columns resulted in continuous suppression of RA activity over a period of more than 5 months, as indicated by laboratory findings, the disease activity score, and the visual analog scale. This is the first report of successful treatment of a refractory and complicated RA using tryptophan immunoadsorption columns. In conclusion, immunoadsorption is a safe and effective therapeutic alternative, which should be considered to bridge infectious complications in patients with severe RA. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Modulation of matrix metalloproteinase and TIMP-1 expression by cytokines in human RPE cells

PURPOSE: The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) is crucial for homeostasis of ocular extracellular matrices. To assess altered MMP activity as a determinant in the migration of human retinal pigment epithelial (RPE) cells, expression characteristics of several MMPs and TIMP-1 in RPE cell cultures were investigated. METHODS: Expression studies were performed with RT-PCR, ELISA, and immunofluorescence analysis. Secretion of MMP-2 was demonstrated by zymography. Migration of cytokine-stimulated RPE cells was evaluated with microporous membranes of permeable chambers. RESULTS: MMP-1, -2, -3, and -9; MT2-MMP; and TIMP-1 were expressed in cultured RPE cells. MMP-2 was detected on the cell surface and in secreted inactive and active forms. TGF-beta(2), IL-1beta, and TNF-alpha enhanced secretion of MMP-1, -2, and -3. TGF-beta(2) also stimulated MT2-MMP cell surface expression and release of TIMP-1. The mRNA levels of MMP-1, -2, and -3 and TIMP-1 were markedly increased by TNF-alpha and TGF-beta(2). MMP-2 mRNA levels were also upregulated by PDGF-BB. Migration of RPE cells stimulated by TGF-beta(2) or PDGF-BB was inhibited in presence of a synthetic MMP inhibitor. CONCLUSIONS: Proinflammatory cytokines and TGF-beta(2) play an important role in the upregulation of expression of MMP-1, -2, and -3 in RPE cells and account for a directional shift in the balance between MMPs and TIMPs. Facilitation of RPE cell migration stimulated by cytokines (i.e., TGF-beta(2) or PDGF-BB) in ocular diseases may be due to increased release of MMPs, in the presence of comparatively lower levels of their inhibitors.