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  • Dahlqvist, Jenny Alenius, et al. (författare)
  • Heart Rate Variability in Children With Fontan Circulation: Lateral Tunnel and Extracardiac Conduit
  • 2012
  • Ingår i: Pediatric Cardiology. - Springer. - 0172-0643. ; 33:2, s. 307-315
  • Tidskriftsartikel (refereegranskat)abstract
    • The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT.
  • Gullbo, Joachim, et al. (författare)
  • Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.
  • 2004
  • Ingår i: Investigational new drugs. - 0167-6997. ; 22:4, s. 411-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.
  • Larsson, Rolf, et al. (författare)
  • På spaning efter ett ekonomisystem
  • 2009
  • Ingår i: Från barkbröd till ciabatta : kreativitet och kontroll inom ekonomistyrning: en generationsväxlingsbok tillägnad Lars-Göran Aidemark, Göran Andersson, Torbjörn Bredenlöw och Tomas Prenkert - kreativitet och kontroll inom ekonomistyrning: en generationsväxlingsbok tillägnad Lars-Göran Aidemark, Göran Andersson, Torbjörn Bredenlöw och Tomas Prenkert : kreativitet och kontroll inom ekonomistyrning: en generationsväxlingsbok tillägnad Lars-Göran Aidemark, Göran Andersson, Torbjörn Bredenlöw och Tomas Prenkert. - Växjö University Press. - 978-91-7636-667-7 ; s. 89-116
  • Bokkapitel (övrigt vetenskapligt)abstract
    • Begreppet ekonomisystem har en sedan länge gällande och väl etablerad definition innehållande delarna: redovisning, budgetering, kalkylering samt icke-finansiella nyckeltal. Trots detta har praxis för ekonomisystem inom både företag och förvaltning stora svårigheter att leva upp till definitionens krav på samordning av de fyra delarna
  • Cabric, Sanja, et al. (författare)
  • Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation
  • 2007
  • Ingår i: Diabetes. - American Diabetes Association Inc.. - 1939-327X. ; 56:8, s. 2008-2015
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective-In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface. Research design and methods-A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant. Results-Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets. Conclusions-This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.
  • Carlier, Charlotte, et al. (författare)
  • Preclinical activity of melflufen (J1) in ovarian cancer
  • 2016
  • Ingår i: OncoTarget. - 1949-2553 .- 1949-2553. ; 7:37, s. 59322-59335
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra-and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.</p>
  • Christensen, Kjeld, et al. (författare)
  • Effects on blood compatibility in vitro by combining a direct P2Y(12) receptor inhibitor and heparin coating of stents
  • 2006
  • Ingår i: Platelets. - 0953-7104 .- 1369-1635. ; 17:5, s. 318-327
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The effect of the direct platelet P2Y<sub>12</sub> receptor inhibitor, AR-C69931MX, on activation of blood induced by stents with and without heparin coating was investigated using a whole blood Chandler loop model in vitro . Stents were deployed in Chandler loops. Fresh human blood with heparin and AR-C69931MX was rotated for 1 h at 37°C and used for measurements of platelets, microparticles, thrombin-antithrombin complex (TAT), fibrinogen binding to platelets, P-selectin expression by platelets, CD11b, Prothrombin Fragment F<sub>1+2</sub>, FXIa-AT, FXIIa-AT, C3a, sC5b-9 and stent score. In the first experiment there were four study groups with unmodified stents: 1a, no AR-C69931MX; 1b, 250 nmol/L; 1c, 750 nmol/L; 1d, 2250 nmol/L of AR-C69931MX. In the second experiment the concentration of AR-C69931MX was 500 nmol/L: 2a; tubings without stent; 2b; tubings with heparin-coated stent; 2c; tubings with unmodified stents. Heparin-coated stents were used in the third experiment: 3a; no AR-C69931MX; 3b; 500 nmol/L of AR-C69931MX. In the first experiment there were significant differences in all parameters analysed except for C3a, and stent score when the group with no AR-C69931MX was compared to all the groups with AR-C69931MX. In the second experiment there were significant differences in platelet count, TAT, FXIa-AT, FXIIa-AT and stent score when unmodified stents were compared to loops with no stents and partly to loops with heparin-coated stents. In the third experiment there was a significant reduction in generation of TAT, stent score and better preservation of platelet number by combining the platelet inhibitor and heparin-coated stents as compared to heparin-coated stents alone. The conclusion is that the direct P2Y<sub>12</sub> receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents.</p>
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