| 1. |
- Treusch, Sebastian, et al.
(författare)
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Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
- 2011
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Ingår i: Science. - Washington : American association of advancement in science. - 0036-8075 .- 1095-9203. ; 334:6060, s. 1241-1245
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Tidskriftsartikel (refereegranskat)abstract
- Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.
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| 2. |
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| 3. |
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| 4. |
- Bergqvist, D, et al.
(författare)
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Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis
- 1988
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 75:9, s. 888-891
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Tidskriftsartikel (refereegranskat)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a low molecular weight heparin fragment for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the heparin fragment was given the evening before surgery, and further doses were given thereafter every evening. There were 1002 analysable patients, 826 having received correct prophylaxis. Of these 1002 patients, 64 per cent were operated on for malignant disease. A total of 20 patients died, 10 in each group. The frequency of deep vein thrombosis was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2-5.0 per cent, P = 0.02) [corrected]. The frequency of bleeding was 6.7 per cent among the heparin fragment patients and 2.7 per cent among the patients given conventional heparin (P = 0.01), but all bleeds were of minor degree and there was no difference in the reoperation rate for bleeding, or in the transfusion requirements. Local pain at the injection site was reported significantly less often among patients given the heparin fragment.
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| 5. |
- Bergqvist, D, et al.
(författare)
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Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin
- 1990
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Ingår i: Seminars in Thrombosis and Hemostasis. - 1098-9064. ; 16:Suppl., s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There were 1002 analyzable patients, 826 having received correct prophylaxis. Sixty three percent of the patients were operated on for malignant diseases. The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2 to 5.0%, p = 0.02). In patients with malignancies the reduction was from 11.2 to 6.4% (p = 0.06). The frequency of bleeding was 6.7% among the heparin fragment patients and 2.7% among the patients given conventional heparin (p = 0.01). The corresponding frequencies for patients with malignancies were 3.2 and 2.8%, respectively (p = 0.28). All bleedings were minor and of no clinical significance. Local pain at the injection site was reported significantly less often among patients with the fragment. Twenty patients died, 13 with malignant disease, mortality being the same in the two groups. It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery, also when the histology shows malignancy. Thus, the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines, better thromboprophylactic effect, and less local pain at injection sites. A disadvantage is the slight increase in hemorrhagic side effects, all of minor clinical importance and not seen in patients undergoing surgery for malignancy.
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| 6. |
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| 7. |
- Eriksson, Anna, et al.
(författare)
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The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia
- 2012
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 2, s. e81-
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Tidskriftsartikel (refereegranskat)abstract
- Aberrantly expressed tyrosine kinases have emerged as promising targets for drug development in acute myeloid leukemia (AML). We report that AKN-028, a novel tyrosine kinase inhibitor (TKI), is a potent FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor (IC50=6 nM), causing dose-dependent inhibition of FLT3 autophosphorylation. Inhibition of KIT autophosphorylation was shown in a human megakaryoblastic leukemia cell line overexpressing KIT. In a panel of 17 cell lines, AKN-028 showed cytotoxic activity in all five AML cell lines included. AKN-028 triggered apoptosis in MV4-11 by activation of caspase 3. In primary AML samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean IC50 1 μM). However, no correlation between antileukemic activity and FLT3 mutation status, or to the quantitative expression of FLT3, was observed. Combination studies showed synergistic activity when cytarabine or daunorubicin was added simultaneously or 24 h before AKN-028. In mice, AKN-028 demonstrated high oral bioavailability and antileukemic effect in primary AML and MV4-11 cells, with no major toxicity observed in the experiment. In conclusion, AKN-028 is a novel TKI with significant preclinical antileukemic activity in AML. Possible sequence-dependent synergy with standard AML drugs and good oral bioavailability has made it a candidate drug for clinical trials (ongoing).
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| 8. |
- Jivegård, Lennart, 1950, et al.
(författare)
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Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.
- 2005
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Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 29:2, s. 190-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.
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| 9. |
- Kald, A, et al.
(författare)
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Reoperation as surrogate endpoint in hernia surgery. A three year follow-up of 1565 herniorrhaphies.
- 1998
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Ingår i: European Journal of Surgery. - : Oxford University Press (OUP). - 1102-4151 .- 1741-9271. ; 164:1, s. 45-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Analysis of reoperation and recurrence rates three years after repair of groin hernias.DESIGN: Prospective audit by questionnaire and selective follow-up.SETTING: Eight Swedish hospitals.SUBJECTS: All groin hernia operations done during 1992 on patients between the ages of 15 and 80 years.MAIN OUTCOME MEASURES: Postoperative complications, reoperation for recurrence, and recurrence.RESULTS: During 1992, 1565 hernia operations were done. The postoperative complication rate was 8% (125/1565). At 36 months postoperatively 108 recurrences had already been reoperated on, six patients with recurrences were on the waiting list for reoperation and a further 36 recurrences had been detected at follow-up. The interhospital variation in recurrence rate ranged from 3% to 20%. Postoperative complications, recurrent hernia, direct hernia and hospital catchment area over 100000 inhabitants were all factors associated with an increased relative risk of recurrence.CONCLUSIONS: The recurrence rate exceeded the reoperation rate for recurrence by almost 40% which should be taken into account if the reoperation rate is used as the endpoint after repairs of groin hernia. An audit scheme, based on prospective recording, reoperation rate, and (periodic) calculation of the recurrence rate may be used to identify risk factors for recurrence and areas in need of improvement.
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| 10. |
- Arnbjörnsson, E., et al.
(författare)
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Laparoscopy for nonpalpable testis in childhood : Is inguinal exploration necessary when vas and vessels are not seen?
- 1996
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Ingår i: European Journal of Pediatric Surgery. - : Georg Thieme Verlag KG. - 0939-7248 .- 1439-359X. ; 6:1, s. 7-9
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Tidskriftsartikel (refereegranskat)abstract
- A case of bilateral nonpalpable testes is described. Ultrasonography showed no testis. Laparoscopy revealed no intraabdominal testis, vas or vessels. Human chorionic gonadotrophine test suggested the presence of testicular tissue Computed tomography showed a testis present in each inguinal canal. Inguinal exploration confirmed the finding. This case stresses the importance of careful interpretation of the laparoscopic findings together with other diagnostic methods in localizing testicular tissue in patients with nonpalpable testes.
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