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Sökning: WFRF:(Braide M)

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1.
  • Wilking, N., et al. (författare)
  • Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
  • 2007
  • Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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2.
  • Ebrahimzadeh, P. R., et al. (författare)
  • A subpopulation analysis of f-MLP stimulated granulocytes migrating in filters
  • 1996
  • Ingår i: Biorheology. - : IOS Press. - 0006-355X .- 1878-5034. ; 33:3, s. 231-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Leukocyte migration in vitro has been studied extensively during many years without providing satisfactory theoretical models for the different migratory behaviors (chemotaxis and chemokinesis) of leukocyte populations. The present study utilized the fluid gradient chamber, which is a new method to study leukocyte migration in filters. Human neutrophils were applied between two stacked filters and migrated in all directions under the influence of constant concentrations or chemotactic gradients of f-MLP, maintained in fluid phase density gradients. The distributions of the granulocytes over filter depth were fitted to theoretical functions composed by 1-3 Gaussian distributions, representing subpopulations. The results showed that the neutrophils migrated as two discrete subpopulations during chemokinetic stimulation (a constant concentration of f-MLP). One of the subpopulations showed less active and passive (slow sedimentation under the influence of gravity) translocation. The most mobile subpopulation was divided into two new subpopulations when exposed to chemotactic stimulation (concentration gradient of f-MLP), one of which responded chemotactically and one of which migrated in random directions. The properties of the different subpopulations where characterized in terms of diffusion coefficient (random migration), convection velocity (chemotactic migration) and sedimentation coefficient (passive translocation).
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3.
  • Olsson-Strömberg, Ulla, et al. (författare)
  • Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase
  • 2006
  • Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. ; 47:9, s. 1768-73
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
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4.
  • Albrektsson, A., et al. (författare)
  • Peritoneal dialysis fluid-induced angiogenesis in rat mesentery is increased by lactate in the presence or absence of glucose
  • 2006
  • Ingår i: ASAIO journal (1992). - : Lippincott Williams & Wilkins. - 1058-2916 .- 1538-943X. ; 52:3, s. 276-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiogenesis may be an important mechanism behind the functional deterioration of the peritoneum leading to ultrafiltration failure in peritoneal dialysis. The present study was designed to compare the angiogenic properties of lactate-, bicarbonate-, and pyruvate-buffered fluids, evaluated separately with and without glucose. Five different fluids (lactate and bicarbonate with and without 2.5% glucose and pyruvate without glucose) were studied for 5 weeks of twice-daily injections in rats. The respective buffers (40 mmol/l) were adjusted to pH 7.2, and sodium, chloride, calcium, and magnesium were present at standard concentrations. The mesenteric window model, based on observation of the translucent peritoneal sections of the small intestine mesentery, was used for immunohistochemical imaging of microvessels (RECA-1 antigen) and macrophages (ED1 and ED2 antigens). All fluids induced angiogenesis as compared with untreated controls. The lactate-buffered fluids induced larger vascularized zones than did their bicarbonate- and pyruvate-buffered counterparts. Angiogenesis was accompanied by a local recruitment of ED1 macrophages from blood. Addition of glucose to the lactate- and bicarbonate-buffered fluids did not seem to alter their pro-angiogenic properties. In conclusion, intraperitoneal exposure to lactate buffer, compared with bicarbonate, stimulates angiogenesis in the presence or absence of glucose.
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5.
  • Bazargani, Farhan, 1969, et al. (författare)
  • Low molecular weight heparin improves peritoneal ultrafiltration and blocks complement and coagulation.
  • 2005
  • Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : Multimed Inc.. - 0896-8608 .- 1718-4304. ; 25:4, s. 394-404
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. DESIGN: Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. RESULTS: Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. CONCLUSIONS: The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.
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6.
  • Bazargani, Farhan, 1969-, et al. (författare)
  • The roles of complement factor C5a and CINC-1 in glucose transport, ultrafiltration, and neutrophil recruitment during peritoneal dialysis
  • 2006
  • Ingår i: Peritoneal Dialysis International. - : Sage Publications. - 0896-8608 .- 1718-4304. ; 26:6, s. 688-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In a recent experimental study, we showed that low molecular weight heparin improved ultrafiltration and blocked complement activation and coagulation in a single peritoneal dialysis (PD) dwell.Objective: The aim of the present study was to evaluate the possible contribution of the complement factor C5a and the potential interactions between C5a, the coagulation system, and cytokines of the interleukin (IL)-8 family (cytokine-induced neutrophil chemoattractant; CINC-1).Methods: Nonuremic rats were exposed through an in-dwelling catheter to a single dose of 20 mL glucose- (2.5%) based fifter-sterilized PD fluid, with or without the addition of anti-rat CS antibody. The dwell fluid was analyzed 2 and 4 hours later concerning activation of the coagulation cascades, neutrophil recruitment, ultrafiltration volume; CINC-1, glucose, urea, and histamine concentrations; and ex vivo intraperitoneal chemotactic activity. Results: The numbers of neutrophils and levels of thrombin-antithrombin complex (TAT) and CINC-1 increased significantly during the PD dwell. C5 blockade significantly reduced the levels of TAT and increased the ultrafiltration volumes at 2 hours. Glucose concentrations were significantly positively correlated to ultrafiltration volumes.Conclusions: Blockade of C5 Leads to an increase in ultrafiltration, probably by a mechanism that involves a reduction in glucose transport. This effect may form a basis for improving PD efficiency in situations where high glucose transport limits ultrafiltration. Mechanisms connected to complement activation during PD may involve coagulation. Further studies of the intraperitoneal cascade systems under conditions of PD are indicated.
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7.
  • Blomqvist, G, et al. (författare)
  • Differences in lodgement of tumour cells in muscle and liver
  • 1988
  • Ingår i: Clinical and Experimental Metastasis. - : Springer. - 1573-7276. ; 6:4, s. 285-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences in the lodgement of circulating tumour cells in various organs are considered an important factor in metastatic organ selection. The present vital microscopic studies show that the pattern of intravascular arrest of tumour cells in muscle after intra-arterial injection is similar to that observed earlier, in the liver, after intraportal injection. However, parallel isotope studies on the lodgement process (at 5 min and 3 h after injection) showed that the tumour cells trapped in the muscle microvasculature were destroyed at a higher rate than in the liver. Tumour cells kept in test tubes, and thus not being subjected to the shearing forces of the circulation, had a higher survival rate than cells trapped in the muscle. The results indicate that stronger retardation forces acting on the tumour cells in muscle (arterial dissemination) than in the liver (venous dissemination) may be one mechanism behind the increased tumour cell destruction in muscle.
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8.
  • Braide, M, et al. (författare)
  • Migration of human granulocytes in filters: effects of gravity and movable gradients of f-MLP
  • 1994
  • Ingår i: Biorheology. - : IOS Press. - 0006-355X. ; 31:6, s. 617-630
  • Tidskriftsartikel (refereegranskat)abstract
    • The Boyden chamber technique for chemotaxis uses a mesh filter that constitutes a matrix for cell locomotion and, at the same time, creates a local restriction for convective fluid movements that allows the establishment of a diffusive concentration gradient of chemotactic substance in the filter. In the present study, the Boyden chamber was modified by the introduction of a filter sandwich that allowed cell migration both upwards and downwards and by the use of a fluid density gradient controlling cell buoyancy and mechanically supporting a movable chemotactic gradient. This method was used to study chemotaxis and random migration of human granulocytes under the influence of gravitational forces and movable gradients of f-MLP. The results show that gravity affected cell motion significantly during random migration but not during chemotaxis. The rate of chemotactic migration was dependent on the steepness of the spatio-temporal f-MLP gradients. A stationary spatial gradient produced less migration than a gradient that was slowly moved through the filter sandwich in a direction opposite to that of the cell migration. The presence of f-MLP at constant concentration caused a minor, statistically insignificant, increase of the rate of random migration.
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9.
  • Braide, M, et al. (författare)
  • Optimized density gradient separation of leukocyte fractions from whole blood by adjustment of osmolarity
  • 1986
  • Ingår i: Journal of Immunological Methods. - : Elsevier. - 1872-7905. ; 93:2, s. 183-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Some of the compounds used for density gradient separation of blood cells have high osmolarities at the concentrations needed to create the required specific densities. Several mixed media use a combination of hyperosmolar shrinkage and red cell aggregation to improve cell separation. Due to the characteristics of Percoll density gradient medium the density and osmolarity of the gradient can be controlled separately. In the present study, Percoll gradients were used to determine the buoyant densities of different human blood cells at the osmolarities 300 mosM, 350 mosM and 400 mosM. Cell volumes were measured at the same osmolarities using a Coulter counter with channelyzer. As expected, the cell buoyant densities increased and the cell volumes decreased at the higher osmolarities used. There were, however, quantitative differences between the cells with respect to the effects of an increased osmolarity, making a 350 mosM density gradient the most effective in separating mononuclear leukocytes from polymorphonuclear leukocytes. A 400 mosM gradient offered the best possibilities to separate red blood cells from polymorphonuclear leukocytes. A one-step centrifugation procedure, based on these principles, is presented. This procedure makes possible the simultaneous purification of mononuclear leukocytes and polymorphonuclear leukocytes, suitable for functional assays.
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10.
  • Ebrahimzadeh, PR, et al. (författare)
  • MIGRATION OF HUMAN GRANULOCYTES IN FILTERS - EFFECTS OF GRAVITY AND MOVABLE GRADIENTS OF F-MLP
  • 1994
  • Ingår i: Biorheology. - THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB : PERGAMON-ELSEVIER SCIENCE LTD. - 0006-355X .- 1878-5034. ; 31:6, s. 617-630
  • Tidskriftsartikel (refereegranskat)abstract
    • The Boyden chamber technique for chemotaxis uses a mesh filter that constitutes a matrix for cell locomotion and, at the same time, creates a local restriction for convective fluid movements that allows the establishment of a diffusive concentration gradient of chemotactic substance in the filter. In the present study, the Boyden chamber was modified by the introduction of a filter sandwich that allowed cell migration both upwards and downwards and by the use of a fluid density gradient controlling cell buoyancy and mechanically supporting a movable chemotactic gradient, This method was used to study chemotaxis and random migration of human granulocytes under the influence of gravitational forces and movable gradients of f-MLP. The results show that gravity affected cell motion significantly during random migration but not during chemotaxis, The rate of chemotactic migration was dependent on the steepness of the spatio-temporal f-MLP gradients, A stationary spatial gradient produced less migration than a gradient that was slowly moved through the filter sandwich in a direction opposite to that of the The presence of f-MLP at constant concentration caused a minor, statistically insignificant, increase of the rate of random migration.
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