UTOPI OG DANNELSE – DANNELSE I ET EKSISTENTIELT PERSPEKTIV

Dannelse risikerer at blive presset ud og forfalde i en tid, hvor den herskende evidensforståelse, der fokuserer på effektmåling, gør sig gældende i udviklings- og læringsoptikker. Med en evidensforståelse, der bygger på kausaliteten ‘metode – resultat’, risikerer beskæftigelsen med menneskets udvikling og dannelse at blive en beskæftigelse med metoder og koncepter og om “what works”– og netop ikke om menneske og levet liv, hvor etik, fællesskab og livsduelighed er det centrale. Dannelse – og dermed mennesket – reduceres til at blive et spørgsmål om instrumentaliseret kompetenceudmåling. I denne artikel anvendes begrebet utopi som greb til at fremskrive et eksistentialistisk dannelsesperspektiv, hvor væren og til-bliven træder frem som modtræk til den herskende evidensbaserede, effektivitets- og målrationelle dannelsestænknings ensidighed. Dannelse er et historisk begreb, der må forstås i tidslighed, hvor et eksistentialistisk dannelsesperspektiv tilbyder et vokabular, der gør det muligt at tænke dannelse i postmodernismens kontingente vilkår uden at forfalde til rent konstruktionistiske betragtninger eller evidensbaserede optikker. Dannelse skrives frem som et eksistensanliggende grundet i kontingens, hvor begreber som tidslighed, transcendens, undren, meningstilskrivelse og sandhedssøgen bliver centrale omdrejningspunkter. Dannelse er aldrig dannelse uden et dannelsesideal. I et eksistentialistisk perspektiv træder der idealer frem som evne til meningstilskrivelse, evne til undren og refleksion og evne til at skønne i en kontingent og kompleks verden – evner, der rummes i begrebet serendipitet, der er artiklens bud på et tidsligt, ontologisk dannelsesideal

Tourniquets do not increase the total blood loss or re-amputation risk in transtibial amputations

AIM: To investigate the total blood loss (TBL) and the safety with respect to the re-amputation rate after transtibial amputation (TTA) conducted with and without a tourniquet. METHODS: The study was a single-centre retrospective cohort study of patients with a primary TTA admitted between January 2013 and April 2015. All patients with a primary TTA were assessed for inclusion if the amputation was performed because of arteriosclerosis or diabetic complications. All patients underwent a standardized TTA procedure that was performed approximately 10 cm below the knee joint and performed with sagittal flaps. The pneumatic tourniquet, when used, was inflated around the femur to a pressure of 100 mmHg above the systolic blood pressure. The number of blood transfusions within the first four postoperative days was recorded. The intraoperative blood loss (OBL), which is defined as the volume of blood lost during surgery, was determined from the suction volume and by the weight difference of the surgical dressings. The trigger for a blood transfusion was set at a decrease in the Hgb level < 9.67 g/dL (6 mmol/L). Transfusions were performed with pooled red blood cells containing 245 mL per portion, which equals 55 g/L of haemoglobin. The TBL during the first four postoperative days was calculated based on the haemoglobin level and the estimated blood volume. The re-amputation rate was evaluated within 30 d. RESULTS: Seventy-four out of 86 consecutive patients who underwent TTA within the two-year study period were included in the analysis. Of these, 38 were operated on using a tourniquet and 36 were operated on without using a tourniquet. There were no significant preoperative differences between the groups. The patients in both groups had a postoperative decrease in their Hgb level compared with preoperative baseline values. The patients operated on using a tourniquet received approximately three millilitres less blood transfusion per kilogram body weight compared with patients operated on without a tourniquet. The duration of surgery was shorter and the OBL was less for the tourniquet group than the non-tourniquet group, whereas no significant difference was observed for the TBL. The TBL median was 859 mL (IQR: 383-1315) in the non-tourniquet group vs 737 mL (IQR: 331-1218) in the tourniquet group (P = 0.754). Within the 30-d follow-up period, 9 patients in the tourniquet group and 11 in the non-tourniquet group underwent a re-amputation at the trans-femoral level. The use of a tourniquet showed no statistically significant association with the 30-d re-amputation at the femur level in the multiple logistic regression model (P = 0.78). The only variable with a significant association with re-amputation was age (OR = 1.07; P = 0.02). CONCLUSION: The results indicate that tourniquets do not cause severe vascular damage with an increased postoperative bleeding or failure rate as the result

Protein Replacement Therapy Partially Corrects the Cholesterol-Storage Phenotype in a Mouse Model of Niemann-Pict Type C2 Disease

Niemann-Pick type C2 (NPC2) disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6-phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background. NPC2 was purified from bovine milk and its functional competence assured in NPC2-deficient fibroblasts using the specific cholesterol fluorescent probe filipin. For evaluation of phenotype correction in vivo, three-week-old NPC2−/− mice received two weekly intravenous injections of 5 mg/kg NPC2 until trial termination 66 days later. Whereas the saline treated NPC2−/− mice exhibited massive visceral cholesterol storage as compared to their wild-type littermates, administration of NPC2 caused a marked reduction in cholesterol build up. The histological findings, indicating an amelioration of the disease pathology in liver, spleen, and lungs, corroborated the biochemical results. Little or no difference in the overall cholesterol levels was observed in the kidneys, blood, cerebral cortex and hippocampus when comparing NPC2−/− and wild type mice. However, cerebellum cholesterol was increased about two fold in NPC2−/− mice compared with wild-type littermates. Weight gain performance was slightly improved as a result of the NPC2 treatment but significant motor coordination deficits were still observed. Accordingly, ultrastructural cerebellar abnormalities were detected in both saline treated and NPC2 treated NPC2−/− animals 87 days post partum. Our data indicate that protein replacement may be a beneficial therapeutic approach in the treatment of the visceral manifestations in NPC2 disease and further suggest that neurodegeneration is not secondary to visceral dysfunction