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2.
  • Biglarnia, Alireza, et al. (author)
  • Decentralized glomerular filtration rate (GFR) estimates in healthy kidney donors show poor correlation and demonstrate the need for improvement in quality and standardization of GFR measurements in Sweden
  • 2007
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 67:2, s. 227-235
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Glomerular filtration rate (GFR) is generally accepted as the best overall index of renal function. Thus, all potential live kidney donors are tested to ensure that they have a normal GFR before they are eligible for kidney transplantation. The choice of GFR test is very much dependent on local traditions and may include iohexol, 51Cr-EDTA, inulin, or creatinine clearance based on urine collection, and creatinine clearance calculated from the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) equation as well as cystatin C. The aim of this study was to compare the results of GFR measurements performed in all actual live kidney donors who have undergone live donor nephrectomy at the University Hospital in Uppsala, Sweden, between the years 2000 and 2004. MATERIAL AND METHODS: The patients were selected from all parts of Sweden and the measurements were performed at their local hospital. RESULTS: We found large discrepancies between repeated iohexol measurements in these presumably healthy individuals. There was also a poor correlation between iohexol clearance and calculated creatinine clearance using the Cockcroft-Gault (R2=0.046) or MDRD formula (R2=0.045). CONCLUSIONS: The study shows that the standardization and quality of GFR measurements in Sweden have to be improved.
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3.
  • Biglarnia, Ali-Reza, et al. (author)
  • Desensitization With Antigen-Specific Immunoadsorption Interferes With Complement in ABO-Incompatible Kidney Transplantation
  • 2012
  • In: Transplantation. - 0041-1337 .- 1534-6080. ; 93:1, s. 87-92
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation.METHODS:All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day -30 and postoperative day 30. C1q was measured on day -30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma.RESULTS:Patient and graft survival were 100% for a median follow-up of 40 months (range, 12-60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day -30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected.CONCLUSIONS:The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.
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4.
  • Biglarnia, Ali-Reza, 1973-, et al. (author)
  • Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy
  • 2011
  • In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:1, s. 93-100
  • Journal article (peer-reviewed)abstract
    • Morphine-based analgesia is effective but can compromise donor safety. We investigated whether continuous infusion of local anesthetics (CILA) can provide sufficient pain control and reduce morbidity related to opiate analgesics after hand-assisted retroperitoneoscopic (HARS) live donor nephrectomy. Forty consecutive live kidney donors underwent HARS and were treated with the ON-Q system providing CILA with 0.5% ropivacaine through two SilvaGard® catheters placed in the retroperitoneal cavity and the rectus sheath, respectively. The case control group consisted of 40 donors matched with regard to sex, age, BMI and surgical technique. All donors were maintained on standardized multimodal analgesia combining nurse-controlled oxycodone treatment and acetaminophen. CILA donors had lower median cumulative consumption of morphine equivalents (CCME) (7 mg [0-56] vs. 42 mg [15-127]; p < 0.0000001), lower incidence of nausea (18 [45%] vs. 35 [87.5%] donors; p < 0.001), shorter time in postoperative care unit (160 vs. 242.5 min; p < 0.001) and shorter hospital stay (4 [4-7] vs. 6 [4-11] days; p < 0.001). In 32.5% of CILA donors the CCME was 0 mg (0% in matched control group, p < 0.001). CILA with 0.5% ropivacaine provides effective postoperative pain relief, reduces the need for opioid treatment and promotes postoperative recovery. Continuous local infusion of ropivacaine provides sufficient analgesia and opioid-sparing effect as well as reduces the incidence of nausea and vomiting after hand-assisted retroperitoneoscopic live donor nephrectomy.
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5.
  • Biglarnia, Ali-Reza, 1973- (author)
  • Minimizing Risks and Morbidity in Live Kidney Donors
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Live kidney donors are healthy volunteers who are exposed to major surgical procedure and physical harms with no direct therapeutic benefits. Efforts to minimize their risks and morbidity are therefore of utmost importance. The current thesis describes studies on donor evaluation, surgical procedure and postoperative management of live kidney donors. The overall purpose is to evaluate and possibly improve routines and treatments in order to reduce risks and the overall morbidity of live kidney donors. In Study I, we evaluated the assessment of kidney function during donor evaluation and found that the accuracy of iohexol glomerular filtration rate (GFR) is compromised by large variations in repeated measurements in presumably healthy donors. We proposed that there is a need for improvement of GFR measurements and that the assessment of predonation kidney function should be more comprehensive, involving GFR, laboratory investigations, functional and morphological examinations and sound clinical judgment. In Study II, we addressed the risk of perioperative venous thromboembolism (VTE) and concluded that expanding the standard screening protocol for VTE to include perioperative venous duplex can potentially decrease the VTE-related morbidity. In studies III and IV, we investigated the impact of hand-assisted retroperitoneoscopic (HARS) nephrectomy on donor safety and perioperative morbidity. The HARS nephrectomy uses the hand-assisted approach, which enables immediate manual compression for hemostasis in case of sudden and severe bleeding. Additionally, the pure retroperitoneal access further increases the safety margin of laparoscopic donor nephrectomy by 1) minimizing the risk of intestinal injury, and 2) exposure of the retroperitoneal nerves, making HARS suitable for continuous infusion of local anesthetics (CILA). CILA effectively reduces the need for opioid consumption and has the potential to totally obviate opiate analgesics postoperatively. Consequently, CILA in combination with HARS reduces morphine-related morbidity and promotes postoperative recovery. In accordance with these data, we recommend improvement and modification of the donor evaluation process as well as a broad introduction of HARS nephrectomy in combination with CILA to increase the safety margin for live kidney donors.
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6.
  • Biglarnia, Ali-Reza, et al. (author)
  • Pulmonary Nocardiosis with Brain Abscess in a Sensitized Kidney Transplant Recipient with a History of Repeated Graft Loss and HLA-Antibody Depletion Treatment : A case report
  • 2008
  • In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 113:1, s. 111-116
  • Journal article (peer-reviewed)abstract
    • Nocardiosis is an opportunistic infection with unfavourable prognosis and is predominantly seen in immunocompromised patients. We here present a kidney transplant recipient with a history of two early graft losses who subsequently developed Human Leukocyte Antigen (HLA)-antibodies and underwent a desensitization treatment with plasmapheresis and monoclonal anti-CD20 antibody application. However, 3 months after a third HLA-identical kidney transplantation he developed Nocardiosis with pulmonary and asymptomatic brain manifestation. The present case report exemplifies this opportunistic infection and gives an overview of the literature.
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7.
  • Biglarnia, Alireza, et al. (author)
  • Venous thromboembolism in live kidney donors : a prospective study
  • 2008
  • In: Transplantation. - 0041-1337 .- 1534-6080. ; 86:5, s. 659-661
  • Journal article (peer-reviewed)abstract
    • AIM:The aim of this study was to evaluate risk factors for venous thromboembolism (VTE) and deep vein thrombosis after living donor nephrectomy in a center using extensive preoperative screening and perioperative venous duplex scan.MATERIAL AND METHODS: Thrombophilia screening and pre- and postoperative ultrasonographies were performed in 130 consecutive living kidney donors (laparoscopic 105, open 25). Donors were followed prospectively for at least 3 months. All donors received prophylaxis with the low molecular weight heparin enoxaparin and compression stockings. Donors with increased risk received a double dose of enoxaparin and the prophylaxis was continued for 6 weeks. Donors with venous thrombosis at discharge duplex also received prolonged prophylaxis.RESULTS:The frequency of thrombophilia was similar to what can be expected in the Swedish population (four with factor V Leiden and one each with protein S deficiency, prothrombin gene mutation, and anticardiolipin antibodies). Preoperative duplex was normal. Three donors had small postoperative deep vein thrombosis. Twelve donors (9.2%) received an intensified and prolonged prophylaxis. No further thromboembolic complications developed in 3 postoperative months.CONCLUSION:With the present protocol for preoperative evaluation, perioperative duplex screening, and prophylaxis, the risk of postoperative VTE is low after living donor nephrectomy. Given that 9.2% had risk factors or developed deep vein thrombosis, the extraordinary situation of an operation being performed on a healthy person who has no therapeutic benefit and the low incidence of VTE in the present study, we recommend the presented approach to be implemented more broadly and that further studies are performed in larger cohorts.
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8.
  • Björkman, Henrik, 1977- (author)
  • Alternative Methods for Assessment of Split Renal Function
  • 2008
  • Doctoral thesis (other academic/artistic)abstract
    • Living kidney donation is a clinical situation with unique features in the sense that healthy individuals voluntarily expose themselves to certain risks and inconveniences. Therefore, eliminating as much of the associated discomfort as possible is crucial. The primary aim of this study was to evaluate whether it is possible to use the examination with computed tomography (CT), which is essential to the investigation, also for determining the ratio of the two kidneys’ function – the split renal function. If possible, an examination with gamma camera renography could be excluded from the work-up. To investigate this possibility, 27 subjects who had underwent CT and renography as part of kidney donor investigation were studied retrospectively. The quantity of contrast material in each kidney was considered proportional to that kidney’s function, and measurement was made in each of the two available contrast phases. The results were compared to the results from renography. A similar analysis was conducted in 38 patients investigated for suspected renal artery stenosis with CT and renography, including a study of an automatized method for the acquisition of data from CT. For further scrutiny, a respiratory triggered dynamic contrast-enhanced magnetic resonance imaging (MRI) examination was investigated in 26 individuals. Results of split renal function were compared with renography and with CT in a subgroup. To study the possibility of facilitating the data analysis with CT, a formula for approximation of the contrast attenuation was studied in 64 subjects. An analysis of the significance of choice of contrast phase was also conducted in 43 subjects. Unsatisfactory agreement with renography resulted from the CT analysis of previous donors, partly due to technical shortcomings. However, the technique was recognized to have a potential value. In the subsequent material, the settings were improved, with beneficial effects on the agreement. Respiratory-triggered MRI generated high quality examinations of renal uptake and excretion, with results harmonizing well with renography and CT. The approximation formula applied to CT resulted in higher accuracy for renal volume assessment than with the automatic method, and an acceptable agreement of the split renal function estimate. From the presented results, a revision of the current donor investigation protocol is suggested. CT gives sufficient information to exclude renography as a routine examination. In cases of uncertainty, renography is recommended for secondary evaluation.
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  • Björkman, Henrik, et al. (author)
  • Split renal function in patients with suspected renal artery stenosis : a comparison between gamma camera renography and two methods of measurements with computed tomography
  • 2006
  • In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:1, s. 107-113
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To validate a method for calculating split renal function from computed tomography (CT) compared with gamma camera renography, and to test a new method for the measurement based on a volume-rendering technique. MATERIAL AND METHODS: Thirty-eight patients, aged 65.7 +/- 11.6 (range 37.8-82.1) years, who had undergone both CT angiography and gamma camera renography for a suspected renal artery stenosis were included in this study. Split renal function was calculated from the CT examinations by measuring area and mean attenuation in the image slices of the kidneys, and also by measuring volume and mean attenuation from a 3D reconstruction of the kidneys. Gamma camera renography with 99mTc-MAG3 with or without captopril enhancement was used as a reference. RESULTS: The 2D CT method had good correlation with renography (r=0.93). Mean difference was 4.7 +/- 3.6 (0-12) percentage points per kidney. There was also excellent correlation between the two CT methods (r=1.00). CONCLUSION: CT is equivalent to renography in determining split renal function, and the measurement from the CT examination can be made more quickly and equally accurately with a 3D technique.
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  • Dahlin, Lars B., et al. (author)
  • Handtransplantation snart verklighet i Sverige
  • 2017
  • In: Läkartidningen. - 0023-7205. ; 114:39, s. 1578-1578
  • Journal article (peer-reviewed)abstract
    • Some patients with a uni- or bilateral hand- or forearm amputation cannot use a hand prosthesis, although high-tech prostheses have been developed. A hand transplantation, particularly for those with bilateral amputations, may be an alternative solution. In a hand-transplanted patient, grip function, strength, sensibility and subsequent improved quality of life can be restored. Risks related to immunosuppression must be balanced by expected benefits, and thorough selection of patients has to be performed from both medical and psychological point of view. Therefore, a national network has been established in Sweden to achieve coordination with the needed competence.
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11.
  • Dahlin, Lars B., et al. (author)
  • Handtransplantation snart verklighet i Sverige : [Hand transplantation in Sweden - preparations under way]
  • 2017
  • In: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 114:39
  • Journal article (peer-reviewed)abstract
    • Some patients with a uni- or bilateral hand- or forearm amputation cannot use a hand prosthesis, although high-tech prostheses have been developed. A hand transplantation, particularly for those with bilateral amputations, may be an alternative solution. In a hand-transplanted patient, grip function, strength, sensibility and subsequent improved quality of life can be restored. Risks related to immunosuppression must be balanced by expected benefits, and thorough selection of patients has to be performed from both medical and psychological point of view. Therefore, a national network has been established in Sweden to achieve coordination with the needed competence.
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12.
  • Enbom, Malin, et al. (author)
  • Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden : variable frequencies found in a multicenter serological study
  • 2000
  • In: Journal of Medical Virology. - 0146-6615 .- 1096-9071. ; 62:4, s. 498-504
  • Journal article (peer-reviewed)abstract
    • Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.
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13.
  • Engstrand, Mats, et al. (author)
  • Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants
  • 2000
  • In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 69:11, s. 2243-2250
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects 50-90% of individuals in different populations. After primary infection, the virus persists latently in myeloid cells under the control of specific T-cells. Reactivation of CMV infection may cause lethal organ dysfunction and is frequently seen in immunosuppressed individuals. CD8+ cytotoxic T-cells (CTL) have a primary role in suppressing CMV reactivation, and the dominating CTL response is directed against pp65. METHODS: MHC tetramers, that is, complexes between HLA class I (or class II) molecules and antigenic peptides conjugated to fluorochromes allow the direct visualization of antigen-specific receptor-carrying T-cells using flow cytometry. We constructed a novel MHC tetramer for identification of CMVpp65-specific CD8+ T-cells using HLA-A2 molecules folded with the immunodominant NLVPMVATV peptide. RESULTS: The A2/pp65 tetramer specifically stained CMV-directed T-cell lines, and sorted cells showed CMV-specific cytotoxicity. High proportions (0.1-9%) of the CD8+ T-cells were A2/pp65 tetramer+ in healthy HLA-A2+ CMV carriers and in immunosuppressed kidney transplant patients with latent infection. Patients with reactivated CMV infection exhibited up to 15% A2/pp65 tetramer+ cells, which seemed to correlate with CMV load over time. A2/pp65 tetramer+ cells expressed T-cell activation markers. CONCLUSIONS: The construction of a novel A2/pp65 MHC tetramer enabled the design of a rapid and precise flow cytometric method allowing quantitative and qualitative analysis of CMV-specific T-cells. The number of A2/pp65 tetramer binding CTLs in blood may prove to be clinically relevant in assessing the immune response to CMV.
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15.
  • Hagen, Gaute, 1958- (author)
  • 3D Rotational Angiography of Transplanted Renal Arteries : A Clinical and Experimental Study
  • 2004
  • Doctoral thesis (other academic/artistic)abstract
    • Three-dimensional rotational angiography (3D-RA) is an established method within the field of interventional neuroradiology. The method has also a great potential in other areas with a complicated arterial anatomy. The purpose of this study was firstly to develop an investigative protocol for 3D-RA in renal transplanted patients with threatening allograft failure in diagnosing stenosis in the transplanted renal artery; secondly the protocol was evaluated and compared with a modified protocol including reduced contrast medium load. Furthermore, the advantages of the 3D reconstructions compared to the angiographic images were evaluated, likewise if an extended angle of rotation reduced the artifacts in the 3D reconstructions. The two protocols were compared with regard to image quality and acute nephrotoxicity. The accuracy of Doppler ultrasonography and the result of percutaneous transluminal angioplasty (PTA) were also assessed.3D-RA was consecutively performed in 57 renal transplanted patients with suspicion of renal artery stenosis. A significant stenosis was found in 49% of the patients. The 3D reconstructions profiled 43% of the transplant renal artery stenoses better than the angiographic images. An extended angle of rotation reduced the artifacts. There was no statistical difference regarding image quality between the two protocols, and the renal function was equally affected in both protocols. Doppler ultrasonography sensitivity was 100%; specificity was 48% and positive predictive value 67%. PTA had a technical success rate of 92% and a clinical success rate of 75% after 3 months.3D-RA is a helpful supplement in cases with complicated vascular anatomy, especially when PTA may be indicated. The 3D reconstructions profile the course of the artery more frequently than the angiographic images and support PTA. The 3D reconstructions are degraded of artifacts. Sampling artifacts can be diminished by increased C-arm rotation and increased number of projections. The distortions caused by beam hardening remain to be solved.
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17.
  • Hagen, Gaute, et al. (author)
  • Three-dimensional rotational angiography of transplanted renal arteries : influence of an extended angle of rotation on beam-hardening artifacts
  • 2005
  • In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 46:2, s. 170-176
  • Journal article (peer-reviewed)abstract
    • PURPOSE:To investigate whether three-dimensional rotational angiography (3D-RA) of the transplant renal artery performed with an extended angle of rotation can reduce beam-hardening artifacts in 3D reconstructed images without image quality being lost or side effects to the transplanted kidney being increased.MATERIAL AND METHODS:3D-RA with a C-arm rotation of 180 degrees was performed consecutively in 12 renal transplanted patients with suspicion of renal artery stenosis. A 1.7-mm balloon occlusion catheter was placed using the crossover technique and this was compared to a protocol with 160 degrees rotation and a traditional 1.4-mm catheter in 10 patients. The occurrence of beam-hardening artifacts was registered and the effects of the reduced contrast load on image quality and of arterial occlusion on renal function were assessed.RESULTS:The extended angle of rotation, from 160 degrees to 180 degrees, reduced the beam-hardening artifacts. Artifacts were observed in 4/11 patients (36%) in the study group and in all 10 (100%) of the controls. There was no statistical difference regarding image quality between the two protocols. Renal function was equally affected in both protocols.CONCLUSION:3D-RA with an extended C-arm rotation reduced the beam-hardening artifacts. Image quality was not reduced despite the reduced contrast medium load. The different protocols had no effect on patient outcome.
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18.
  • Hansson, Lars-Olof, et al. (author)
  • Dagens svenska metoder för att mäta njurfunktion måste bli bättre : Rutinformlerna ger osäker diagnostik - stor risk för feldosering av läkemedel
  • 2008
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 105:10, s. 731-734
  • Journal article (peer-reviewed)abstract
    • Njurfunktionsmätningar och främst måttet på glomerulär filtrationshastighet (GFR) tillhör våra mest använda laboratorieanalyser.Nuvarande metoder och ekvationer för beräkning av glomerulär filtration håller för låg diagnostisk kvalitet och innebär klara risker för felklassificering av njurpatienter och feldosering av läkemedel.Nuvarande svenska metoder för att mäta GFR måste förbättras.Vi måste förbättra kunskapen om skillnader mellan GFR beräknat i ml/min och i ml/min/ 1,73 m2.Det är viktigt att vi i sjukvården har ett enhetligt sätt att rapportera beräknat GFR.
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  • Mahdavi, Jafar, et al. (author)
  • Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation
  • 2002
  • In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 297:5581, s. 573-578
  • Journal article (peer-reviewed)abstract
    • Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
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27.
  • Tyden, Gunnar, et al. (author)
  • A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation
  • 2009
  • In: Transplantation. - 1534-6080 .- 0041-1337. ; 87:9, s. 1325-1329
  • Journal article (peer-reviewed)abstract
    • We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.
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28.
  • Tydén, Gunnar, et al. (author)
  • Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations
  • 2007
  • In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 7, s. 157-158
  • Journal article (peer-reviewed)abstract
    • Background. A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany. Methods. The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period. Results. Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala. Conclusions. The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.
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  • von Zur-Mühlen, Bengt, et al. (author)
  • Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time.
  • 2017
  • In: Annals of Transplantation. - 1425-9524 .- 2329-0358. ; 22, s. 773-779
  • Journal article (peer-reviewed)abstract
    • Background: We sought to study gender differences and differences over time with respect to demographics, relation to recipient,donor motives, and experiences of live kidney donation.Material/Methods: In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers wasanalyzed for gender differences and, where relevant, for changes over time.Results: In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and childto-parent donors (40%). No significant gender differences were seen in perceived information given before donation.For males, it was more common that the recipient took the initiative to donate. For females, the motivationfor donating was more frequently to help the recipient and because others wanted them to donate.For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference.Conclusions: Females donate more frequently than males, a difference that did not change over time. Only a few genderdifferences were seen in donor motives and the donation experience; however, these differences may be relevantto address the gender imbalance in kidney donations.
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  • Wadström, Jonas, et al. (author)
  • Comparison of Hand-Assisted Laparoscopy Versus Open and Laparoscopic Techniques in Urology Procedures : A Systematic Review and Meta-analysis
  • 2011
  • In: Journal of endourology. - : Mary Ann Liebert Inc. - 0892-7790 .- 1557-900X. ; 25:7, s. 1095-1104
  • Research review (peer-reviewed)abstract
    • Background and Purpose: Hand-assisted laparoscopic surgery (HALS) is an integral part of the urologist's armamentarium. We aimed to perform a comprehensive meta-analysis comparing HALS renal surgery with open and laparoscopic techniques. Methods: A systematic review and meta-analysis of HALS renal procedures (donor nephrectomy, nephrectomy, or nephroureterectomy) from 1996 to 2007 was performed. Results: Sixty-two studies of 30 donor nephrectomy, 21 radical nephrectomy, and 14 nephroureterectomy procedures in 5446 patients were included in the analysis. In donor nephrectomy, estimated blood loss (EBL) was statistically significant for HALS vs the open and laparoscopic cohorts, -69.0mL (95% confidence interval [CI], -129.7, -8.2) and -40.1mL (95% CI, -68.2, -12.0), respectively. Length of stay (LOS) was shorter compared with the open group, -1.7 days (95% CI, -2.3, -1.1). For nephroureterectomy, EBL (-29.9mL (95% CI, -242.3, 182.5)), and LOS (-1.5 d [95% CI, -2.8, -0.3]) again favored HALS vs open procedures. Operating room (OR) time and warm ischemia time (WIT) were statistically significant in favor of HALS donor nephrectomy vs the laparoscopic cohort; -36.8 minutes (95% CI, -61.3, -12.3) and -1.3 minutes (95% CI, -1.8, -0.7), respectively. For radical nephrectomy, both EBL -232.9mL (95% CI, -383.6, -82.2) and LOS -2.4 days (95% CI, -3.5, -1.3) were statistically significant, favoring HALS vs the open group. Conclusion: We report the largest meta-analysis of HALS renal surgery to date. When compared with open surgery, HALS allows for a significant decrease in EBL and LOS. Compared with laparoscopic donor nephrectomy, HALS resulted in a significant decrease in blood loss, OR time, and WIT.
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32.
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33.
  • Wadström, Jonas (author)
  • Hand-assisted retroperitoneoscopic live donor nephrectomy : experience from the first 75 consecutive cases
  • 2005
  • In: Transplantation. - 0041-1337 .- 1534-6080. ; 80:8, s. 1060-6
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The two major life-threatening complications associated with laparoscopic live donor nephrectomy are sudden severe bleeding and intestinal injury. A combined technique-hand-assisted and retroperitoneoscopic (HARS)-reduces the risk of these life-threatening complications. In this study, we report on our experience from the first 75 consecutive HARS operations. METHODS: The data has been collected prospectively according to intention to treat and includes all consecutive donors operated with the HARS technique. Warm ischemia time, operating time, and blood loss were recorded. Complications, convalescence, and allograft outcome were followed postoperatively with a mean follow-up of 701 (range 60-1438) days. RESULTS: The mean operating time was 138 (range 85-260) minutes and the mean warm ischemia time 175 (85-510) seconds. The operative time was significantly longer in male donors. The mean bleeding was 176 (50-700) ml. There were no conversions to open surgery. Major complications comprised one pulmonary embolus and one donor required 2 units of blood transfusion. One donor was reoperated due to suspicion of trocar hernia. Nine patients experienced minor complications (fever, n=4; urinary tract infection, n=2; chylous ascites, n=1; orchialgia, n=1; subcostal pain, n=1). All except two kidneys had immediate onset of function. Neither of these could, however, be attributed to the donor operation. One recipient experienced urinary leakage and one a stenosis. Recipient and graft survival were 99% and 96%, respectively. CONCLUSIONS: We conclude that HARS facilitates the procedure by enabling short operating times and at the same time significantly reducing the risks associated with endoscopic live donor nephrectomy.
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34.
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35.
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36.
  • Wadström, Jonas, et al. (author)
  • Introducing hand-assisted retroperitoneoscopic live donor nephrectomy : Learning curves and development based on 413 consecutive cases in four centers
  • 2011
  • In: Transplantation. - 0041-1337 .- 1534-6080. ; 91:4, s. 462-469
  • Journal article (peer-reviewed)abstract
    • Background: Hand-assisted and retroperitoneoscopic techniques reduce the risk of bleeding and intra-abdominal complications in live donor nephrectomy (LDN). This study reports on our four-centre experience, development and learning curves from the first 413 LDN using a hand-assisted retroperitoneoscopic technique (HARS). Methods: The first 413 consecutive donors operated on using HARS were included in the study. Donor demographics, peri- and postoperative data, complications, and recipient outcomes have been compiled. The data was analysed as a whole and separately for each centre, looking at centre differences and learning curves over time. Results: Significant differences were found in donor demographics between centres for the variables: age, BMI, number of arteries, and side of operation. Mean operating time was 170.2 minutes, with significant differences between centres. Operating time was also significantly influenced by learning curves, Sex/BMI, and side of operation. Warm ischemia time differed significantly between centres and was influenced by centre-wise learning and number of arteries. Overall conversion rate was 2.4% and differed significantly between centres. There was no mortality and no intra-abdominal complications. Apart from the conversions and one pulmonary embolism, there were no major intra- or postoperative complications. Overall 3-month graft survival was 99%, with 96% immediate onset of function and 1% ureteral complications. Conclusions: The HARS technique reduces the risk of intra-abdominal complications. It can be implemented with excellent donor and recipient outcomes despite different population demographics and centre/surgeon-related tradition and experience. Based on our experience, we recommend the technique in order to increase the safety margin of LDN.
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37.
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38.
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39.
  • Wadström, Jonas, et al. (author)
  • Laparoscopic nephropexy exposes a possible underlying pathogenic mechanism and allows successful treatment with tissue gluing of the kidney and fixation of the colon to the lateral abdominal wall
  • 2010
  • In: International Brazilian journal of urology : official journal of the Brazilian Society of Urology. - 1677-5538. ; 36:1, s. 10-17
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Surgical treatment of "Ren Mobilis" has historically been associated with poor results and fairly high morbidity. We have used a transperitoneal laparoscopic approach in order to minimize morbidity. The goal of this study was to evaluate the success rate and to discuss the possible pathogenic mechanism, which has implications for the surgical strategy. MATERIALS AND METHODS: Seven women with a right mobile kidney were examined by intravenous pyelogram and CT scans. Symptoms were judged to emanate from the mobile kidney. Transperitoneal laparoscopic nephropexy was performed. The surgical treatment consisted of fixing the kidney to the dorsal abdominal wall using tissue glue (Tisseel) after diathermy coagulation of the surfaces to induce fibrosis. The right colon was fixed with clips to the lateral abdominal wall, trapping the kidney in place. RESULTS: In 6 of the cases, there was an incomplete rotation of the ascending colon to the right side, allowing the kidney to move freely. In one case, the kidney moved into a retroperitoneal pocket of the mesocolon. The 6 cases with a lateral passage for the kidney were symptom-free at follow-up (30-80 months), but in the 7th case the patient's kidney quickly loosened and she underwent an open reoperation, after which she was symptom-free. CONCLUSION: Our series demonstrates that good results can be achieved with a transperitoneal laparoscopic approach, but also indicates that there is a common pathogenic mechanism with incomplete rotation of the ascending colon that can be corrected during surgery, which might contribute to the good results.
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40.
  • Wadström, Jonas, et al. (author)
  • Living Anonymous Renal Donors Do Not Regret: Intermediate and Long-Term Follow-Up with a Focus on Motives and Psychosocial Outcomes.
  • 2019
  • In: Annals of transplantation. - : INT SCIENTIFIC INFORMATION, INC. - 2329-0358 .- 1425-9524. ; 24, s. 234-241
  • Journal article (peer-reviewed)abstract
    • BACKGROUND Living anonymous donation (LAD) of kidneys was introduced in Sweden in 2004. This study reports on outcomes of Swedish LAD experiences from 2004 to 2016, focusing on donors' motives, the care they received, psychosocial aspects, and medical status at follow-up. MATERIAL AND METHODS Donor data were collected through a physician interview, medical check-up, review of medical charts, the Hospital Anxiety Depression Scale (HADS), and a routine national questionnaire. Of the 26 LADs during the study period, 1 donor died and 1 declined to participate, leaving a study population of 24. RESULTS Half of the donors were male, which is a higher proportion than for directed living donors. The major motive detected was altruism. Of the 24 LADs, 96% were very satisfied and would donate again if possible, 46% noted increased self-esteem, and a third were happier after the donation. Sixty-two percent received anonymous information about the recipient and 40% would have liked to meet the recipient. HADS scores were normal. Two donors had antidepressant treatment, 1 of whom had received treatment before donation. Half mentioned that the pre-donation assessment took too long. At follow-up, mean eGFR was 62±12 mL/min/1.73 m², of which 16 were in CKD II and 8 were in CKD III. Four donors had developed hypertension, 1 of whom also developed type 2 diabetes. CONCLUSIONS Swedish LADs are very satisfied and medical outcomes are acceptable. We propose that the transplant community and the National Board of Health and Welfare take a more active approach to informing the general public about LAD.
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41.
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42.
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43.
  • Westerberg, Per-Anton, et al. (author)
  • Fibroblast growth factor-23 and mineral metabolism after unilateral nephrectomy
  • 2010
  • In: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 25:12, s. 4068-4071
  • Journal article (peer-reviewed)abstract
    • Background. Fibroblast growth factor -23 (FGF-23) is a key regulator of mineral metabolism. It regulates renal phosphate (Pi) reabsorption and calcitriol synthesis, and has an inhibitory effect on parathyroid hormone (PTH) secretion. FGF-23 increases early in chronic kidney disease (CKD), but the regulation of FGF-23 in mild -to -moderate renal dysfunction is not fully understood. Methods. Nine healthy kidney donors underwent unilateral nephrectomy. Estimated glomerular filtration rate (eGFR) calculated from cystatin C and parameters of mineral metabolism: (Pi, ionized calcium, biointact PTH, intact FGF-23, calcitriol, and urinary excretion of calcium and Pi) were analysed before surgery, and one day, one week and three to six months after surgery. Results. On the first post-operative day, PTH increased due to a decrease in the calcium level. One week after nephrectomy, the FGF-23 level increased from 31.8 +/- 12.3 pg/mL to 55.8 +/- 15.1 pg/mL, while PTH, Pi and calcium levels were unchanged compared towith baseline. On follow-up, eGFR improved compared with its one-week value, and PTH and FGF-23 were unchanged compared towith baseline. The calcitriol level decreased but was in the normal range at all points in time. The total amount of Pi in urine did not change, while the calcium excretion decreased significantly. Conclusions. Pi homeostasis after nephrectomy is maintained by PTH on the first day. When serum calcium is stabilized and food intake resumed, FGF-23 rises, possibly in response to the Pi- load in relation to GFR.
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44.
  • Yamamoto, Shinji, et al. (author)
  • Factors influencing outcome of simultaneous kidney and pancreas transplantation : a 23-year single-center clinical experience
  • 2010
  • In: Transplantation Proceedings. - : Elsevier BV. - 0041-1345 .- 1873-2623. ; 42:10, s. 4197-4201
  • Journal article (peer-reviewed)abstract
    • Introduction:Simultaneous kidney and pancreas transplantation (SKPT) has become an effective treatment for patients who have diabetes mellitus type I with advanced nephropathy. This study assesses the progress of the SKPT program at Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft survival.Materials and MethodsBetween February 1986 and September 2009, we performed 113 SKPT. The immunosuppression protocols changed over time and are defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S); era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA, mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4, tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF, steroids and basiliximab induction (T/M/S/B). We analyzed donor/recipient/ operative and postoperative variables to assess their influence on pancreas graft and patient survivals.ResultsThe overall 1-, 5-, and 10-year patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10-year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-, and 10-year pancreas graft survivals in SKPT patients transplanted between October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%, 72.7%, and 63.1%, respectively, which was significantly better than those of patients transplanted between February 1986 and September 1997 (era, 1 through 3) (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF (eras 4 and 5) decreased the incidence of acute rejection episodes compared with eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate analysis revealed that donor age (younger than 40 years), immunosuppressive regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes independently affected pancreas graft survival.ConclusionsWe demonstrate a superiority of the quadruple protocol with T/M/S/B for graft and patient survival with a decreased incidence of CMV infection after SKPT.
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