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  • 1.
    Al Ahmadi, Ibrahim
    et al.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Abasi, Amira
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Syed, Raza
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Broering, Dieter-C.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, S58-S59 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.

  • 2. Baba, Hideo A.
    et al.
    Wohlschlaeger, Jeremias
    Schmitz, Klaus J.
    Nadalin, Silvio
    Lang, Hauke
    Benesch, Alexandra
    Gu, Yanli
    Biglarnia, Ali-Reza
    Sotiropoulos, Georgios C.
    Takeda, Atsushi
    Takeda, Nobuakira
    von Wnuck Lipinski, Karen
    Levkau, Bodo
    Survivin is upregulated during liver regeneration in rats and humans and is associated with hepatocyte proliferation2009In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 29, no 4, 585-592 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Survivin regulates cell division and inhibits apoptosis. Liver regeneration is a complex process involving both proliferation and apoptosis. The role of survivin is not well elucidated and no data exist in humans.

    METHODS:

    Seventy per cent liver resection was used to investigate liver regeneration in rats. Survivin was identified by means of reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Proliferation and apoptosis were quantified. Liver biopsies from 33 patients who underwent living donor liver transplantation were used to study survivin immuno-expression, proliferation and apoptosis within the first 17 days after transplantation. Seven healthy donors served as controls.

    RESULTS:

    Survivin transcript and protein were significantly upregulated in rat hepatocytes after 24-72 h during regeneration and showed a significant correlation with proliferation but not with apoptosis. In humans, survivin was nearly absent in donor and reperfused liver tissue but increased significantly 5-7 days after transplantation and correlated with proliferation but not with apoptosis.

    CONCLUSIONS:

    Survivin is upregulated in human and rodent liver regeneration and correlates with proliferation, suggesting an association of survivin and cell division.

  • 3.
    Berglund, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Berglund, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Screening of mortality in transplant patients using an assay for immune function2011In: Transplant Immunology, ISSN 0966-3274, E-ISSN 1878-5492, Vol. 24, no 4, 246-250 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: So far, the ImmuKnow Immune Cell Function Assay (Cylex, Inc., Columbia, MD, USA) has been used to assess risks of infection and rejection in transplant patients. We hypothesized that the ImmuKnow assay might be used for mortality screening in transplant patients overall. METHODS: In the period of February 2007 to December 2009, at the Uppsala University Hospital, 362 patients who received either kidney, kidney+pancreas, kidney+islet cells, liver or liver+kidney allografts were randomly screened using the ImmuKnow assay. All causes of mortality were compared between two groups: patients with at least one ImmuKnow assay below 175ng/mL and patients with all ImmuKnow assays from 175ng/mL and above. Subsequently, the frequency of rejection within thirty days of the ImmuKnow assay was compared between these two groups. RESULTS: The study included 1031 ImmuKnow assays obtained from the 362 patients. A total of 111 patients had at least one ImmuKnow below 175ng/mL and 251 patients had all their ImmuKnow assays from 175ng/mL and above. By January 31st 2010, 16 of 111 patients (14.4%) with at least one ImmuKnow assay below 175ng/mL were deceased, compared to 13 of 251 patients (5.2%) with all ImmuKnow assays from 175ng/mL and above (p=0.0053, Fisher's exact test). There was no difference in the frequency of rejection between the two groups (19.8% versus 17.5%, p=0.66). CONCLUSIONS: In addition to assessing relative risks of infection and rejection in transplant patients, the ImmuKnow assay may be used to identify patients with increased risk of short-term mortality. Transplant patients being highly overimmunosuppressed as assessed by the ImmuKnow assay do not seem to have a lower risk of short-term rejection.

  • 4.
    Berglund, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lundqvist, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Vascular reconstruction using allogeneic homografts in a renal transplant patient with pseudoaneurysm and infected vascular prosthesis2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 4, e15-e16 p.Article in journal (Refereed)
  • 5.
    Berglund, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Karlsson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Carlsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials2013In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 173, no 2, 310-322 p.Article in journal (Refereed)
    Abstract [en]

    Adoptive transfer of regulatory T cells (Tregs) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with Treg therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4+CD25highCD127low Tregs from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare Treg preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded Treg preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that Treg preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the Treg preparations. In particular, FACS-sorted Treg preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted Treg preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with Tregs from uraemic patients that may guide future efforts to produce clinical-grade Tregs for use in kidney transplantation.

  • 6.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Minimizing Risks and Morbidity in Live Kidney Donors2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

    List of papers
    1. 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
    Open this publication in new window or tab >>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 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 2, 227-235 p.Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keyword
    Creatinine, Glomerular filtration rate, Human, Iohexol, Kidney, Living donor evaluations
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-10994 (URN)10.1080/00365510600979154 (DOI)000244842400013 ()17366002 (PubMedID)
    Available from: 2007-05-09 Created: 2007-05-09 Last updated: 2017-12-11Bibliographically approved
    2. Venous thromboembolism in live kidney donors: a prospective study
    Open this publication in new window or tab >>Venous thromboembolism in live kidney donors: a prospective study
    2008 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 86, no 5, 659-661 p.Article in journal (Refereed) Published
    Abstract [en]

    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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-87433 (URN)10.1097/TP.0b013e3181817d36 (DOI)000259361700007 ()18791446 (PubMedID)
    Available from: 2008-12-18 Created: 2008-12-18 Last updated: 2017-12-14Bibliographically approved
    3. Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: Learning curves and development based on 413 consecutive cases in four centers
    Open this publication in new window or tab >>Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: Learning curves and development based on 413 consecutive cases in four centers
    Show others...
    2011 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 4, 462-469 p.Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keyword
    Hand assistance, Hand-assisted retroperitoneoscopic nephrectomy, Learning curve, Live donor nephrectomy, Living donors, Morbidity, Multicenter, Review, Safety
    National Category
    Surgery
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:uu:diva-134509 (URN)10.1097/TP.0b013e3182052baf (DOI)000287127600017 ()21169880 (PubMedID)
    Available from: 2010-11-27 Created: 2010-11-27 Last updated: 2017-12-12Bibliographically approved
    4. Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy
    Open this publication in new window or tab >>Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy
    Show others...
    2011 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 11, no 1, 93-100 p.Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keyword
    Continuous infusion of local anaesthetics, convalescence, donor safety, HARS, pain relief, ropivacaine
    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:uu:diva-134510 (URN)10.1111/j.1600-6143.2010.03358.x (DOI)000285783500015 ()21199350 (PubMedID)
    Available from: 2010-11-27 Created: 2010-11-27 Last updated: 2017-12-12Bibliographically approved
  • 7.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Retroperitoneoscopic Hand-Assisted Live Donor Nephrectomy - a Single Center Experience2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, S86-S90 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Hand-assisted retroperitoneoscopic live donor nephrectomy (HARS) increases the safety margin of live kidney donors by combining hand-assistance with pure retroperitoneal access to the kidney. Furthermore, HARS enables effective and safe non-morphine based analgesia with continuous infusion of local anesthetics (CILA), which potentially adds further safety advantage by reduction of morphine-related complications. This report emphasizes the impact of HARS on donor safety and presents a 12-years experience with the procedure at the University Hospital in Uppsala. MATERIAL AND METHODS : A literature review of relevant reports on HARS is presented. Furthermore, latest unpublished in-house data on HARS nephrectomy procedures from 2010 and 2012 are analyzed for operative characteristics, donor outcome as well as kidney function. RESULTS : Since 2000, HARS is the default donor nephrectomy procedure at our center. Within 12 years, 344 HARS nephrectomies were performed. The overall conversion rate to open surgery was 0.3% (1 out of 344). Between January 2010 and December 2012, 122 HARS and 1 open nephrectomy (anterior incision) were performed. Sixteen donors (13%) were right-sided HARS. After matching for sex, BMI and vascular anatomy, the mean operative time for right and left-sided HARS were 125 minutes (75-175) and 153 minutes (113-251), respectively. The overall mean operative time was 150 minutes (60-251). No donor presented early or late intra-abdominal complications, which is in consistent with our previous reports. The overall morbidity rate was 7.2%. All 122 HARS donors were treated with CILA. The overall mean total cumulative consumption of morphine equivalents (CCME) was 12.4 mg (0-240), while 107 donors (87%) received a total CCME of less than 20 mg. Thirty-four donors (28%) received no morphine equivalents during the hospitalization CONCLUSION : HARS is a safe procedure that virtually eliminates the risk for intra-abdominal complications. The intrinsic advantage for non-morphine based analgesia in combination with excellent donor outcome make this technique eligible for a broader implementation.

  • 8.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bennet, William
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation: Exemplification of the Surgical Technique and the Surveillance2014In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 260, no 2, e5-7 p.Article in journal (Refereed)
  • 9.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Johansson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Venous thromboembolism in live kidney donors: a prospective study2008In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 86, no 5, 659-661 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Emanuelsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Schneider, Mårten K. J.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    The free radical scavenger S-PBN significantly prolongs DSG-mediated graft survival in experimental xenotransplantation2012In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 19, no 3, 166-176 p.Article in journal (Refereed)
    Abstract [en]

    Background: Nitrones such as 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) are known to trap and stabilize free radicals and to reduce inflammation. Recently, S-PBN was shown to reduce infiltration of T lymphocytes and the expression of adhesion molecules on the endothelium in experimental traumatic brain injury. We hypothesized that S-PBN could reduce infiltration of T lymphocytes during cell-mediated xenograft rejection and thereby increase graft survival. The concordant mouse-to-rat heart transplantation model was used to test the hypothesis. In this model, grafts undergo acute humoral xenograft rejection (AHXR) almost invariably on day 3 and succumb to cell-mediated rejection on approximately day 8 if AHXR is inhibited by treatment with 15-deoxyspergualin (DSG). Material and methods: Hearts from Naval Medical Research Institute (NMRI) mice were transplanted to the neck vessels of Lewis rats. Recipients were treated with S-PBN (n = 9), DSG (n = 9), S-PBN and DSG in combination (n = 10) or left untreated (n = 9) for survival studies. S-PBN was given daily intraperitoneally at a dose of 150 mg/kg body weight (BW) on day -1 to 30, and DSG was given daily intraperitoneally at a dose of 10 mg/kg BW on day -1 to 4 and 5 mg/kg BW on day 5 to 21. Nine additional recipients were given S-PBN only on days -1 and 0 in combination with continuous DSG treatment. Grafts were monitored until they stopped beating. Additional recipients were treated with S-PBN (n = 5), DSG (n = 5), S-PBN and DSG in combination (n = 6) or left untreated (n = 5) for morphological, immunohistochemical and flow cytometry analyses on days 2 and 6 after transplantation. Results: S-PBN treatment in combination with DSG resulted in increased median graft survival compared to DSG treatment alone (14 vs. 7 days; P = 0.019). Lower number of T lymphocytes on day 6 (P = 0.019) was observed by ex vivo propagation and flow cytometry when combining S-PBN with DSG, whereas immunohistochemical analyses demonstrated a significant reduction in the number of infiltrated CD4+, but not TCR+, cells. S-PBN treatment alone had no impact on graft survival compared to untreated rats (3 vs. 3 days). No differences were seen in ICAM-1 and VCAM-1 expression or in morphology between the groups. Conclusion: The combination of S-PBN and DSG treatment increases xenograft survival. The main effect of S-PBN appears to be in direct connection with the transplantation. Because of its low toxicity, S-PBN could become useful in combination with other immunosuppressants to reduce cell-mediated xenograft rejection.

  • 11.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lee, Hyon-Soek
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tötsch, Martin
    Malagó, Massimo
    Liver regeneration is impaired by FK778 in partially hepatectomized rats, while supplemental uridine restores both liver growth and hepatocyte proliferation2009In: Hepatology Research, ISSN 1386-6346, E-ISSN 1872-034X, Vol. 39, no 1, 86-92 p.Article in journal (Refereed)
    Abstract [en]

    Aim:

    The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model.

    Methods:

    Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in combination with uridine (n = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage.

    Results:

    In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h (P < 0.05) after the PH. In addition, morphological analysis showed confluent central lobular necrosis at 72 h in four of seven animals. Uridine supplementation restored PI, LBR and the de Ritis ratio in FK778-treated animals and no confluent necroses were observed.

    Conclusion:

    FK778 is antihepatotrophic as well as antiproliferative during rat liver regeneration. Both liver growth and hepatocyte proliferation are completely restored by supplementation with uridine. In addition, supplemental uridine markedly reduces the severity of morphological abnormalities consistent with FK778 toxicity.

  • 12.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Desensitization With Antigen-Specific Immunoadsorption Interferes With Complement in ABO-Incompatible Kidney Transplantation2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 1, 87-92 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 13.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 8, e61-e66 p.Article in journal (Refereed)
    Abstract [en]

    We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.

  • 14.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Kristina Ekdahl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective2015In: IMMUNE RESPONSES TO BIOSURFACES: MECHANISMS AND THERAPEUTIC INTERVENTIONS, 2015, 211-233 p.Conference paper (Refereed)
    Abstract [en]

    The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool. Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

  • 15.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy2011In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 11, no 1, 93-100 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 16.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    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 Sweden2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 2, 227-235 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 17.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    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 report2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 1, 111-116 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 18. Biglarnia, Ali-Reza
    et al.
    Yamamoto, Shinji
    Gustafsson, Bengt I
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Wagner, Michael
    von Zur-Mühlen, Bengt
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Transplantation av pankreas botande alternativ vid typ 1-diabetes: [Transplantation of pancreas, a curative option for type 1 diabetes]2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39-40, 1754-1757 p.Article in journal (Refereed)
    Abstract [en]

    In the past decade, pancreas transplantation (PTx) has become increasingly attractive as a curative treatment in patients with labile diabetes and secondary complications. In the United Kingdom, the percentage of deceased-donors utilized for PTx increased 5-fold between 2003 and 2007. The trend towards a higher number of annual pancreas transplantations is also observed in Sweden. The increasing activity and the excellent outcome are consequences of meticulous surgery, effective immunsuppression and adequate follow-up. The present report descibes the current status of PTx and shows the short- and long-term results during the last decade in Sweden.

  • 19.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sund, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    von Zur-Muehlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S15-S15 p.Article in journal (Other academic)
  • 20.
    Biglarnia, AliReza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sund, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Impact Of Duodenal Cuff Inflammation On Outcome After Clinical Pancreas Transplantation - A Survey Of A Comprehensive Follow-Up Strategy Including Serial Protocol Biopsy Of The Duodenal Cuff.2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 11, S24-S24 p.Article in journal (Other academic)
  • 21. Bockhorn, Maximilian
    et al.
    Goralski, Michal
    Prokofiev, Dennis
    Dammann, Philipp
    Grünewald, Petra
    Trippler, Martin
    Biglarnia, Alireza
    Kamler, Markus
    Niehues, Eva M.
    Frilling, Andreja
    Broelsch, Christoph E.
    Schlaak, Jörg F.
    VEGF is important for early liver regeneration after partial hepatectomy2007In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 138, no 2, 291-299 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model.

    METHODS:

    To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR.

    RESULTS:

    In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF.

    CONCLUSIONS:

    VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified.

  • 22.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Selvaraju, Ram K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Jansson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 10, 3428-3437 p.Article in journal (Refereed)
    Abstract [en]

    In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.

  • 23.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Sjöberg, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Functional Imaging of the Pancreatic Graft by Positron Emission Tomography2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, S94-S94 p.Article in journal (Other academic)
  • 24.
    Hansson, Lars-Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Dagens svenska metoder för att mäta njurfunktion måste bli bättre: Rutinformlerna ger osäker diagnostik - stor risk för feldosering av läkemedel2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 10, 731-734 p.Article in journal (Refereed)
    Abstract [sv]

    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.

  • 25.
    Lorant, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eich, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Winstedt, Lena
    Hansa Med AB, Lund, Sweden..
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Kjellman, Christian
    Hansa Med AB, Lund, Sweden..
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Rapid Removal Of Anti-Hla Antibodies In Immunized Patients Awaiting Renal Transplantation - A Dose Finding Study Of The Igg Degrading Enzyme Ides2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, 73-73 p.Article in journal (Other academic)
  • 26.
    Lundqvist, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Andersson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Measurement of transplanted pancreatic volume using computed tomography: reliability by intra- and inter-observer variability2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 9, 966-972 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Unlike other solid organ transplants, pancreas allografts can undergo a substantial decrease in baseline volume after transplantation. This phenomenon has not been well characterized, as there are insufficient data on reliable and reproducible volume assessments. We hypothesized that characterization of pancreatic volume by means of computed tomography (CT) could be a useful method for clinical follow-up in pancreas transplant patients.

    Purpose

    To evaluate the feasibility and reliability of pancreatic volume assessment using CT scan in transplanted patients.

    Material and Methods

    CT examinations were performed on 21 consecutive patients undergoing pancreas transplantation. Volume measurements were carried out by two observers tracing the pancreatic contours in all slices. The observers performed the measurements twice for each patient. Differences in volume measurement were used to evaluate intra- and inter-observer variability.

    Results

    The intra-observer variability for the pancreatic volume measurements of Observers 1 and 2 was found to be in almost perfect agreement, with an intraclass correlation coefficient (ICC) of 0.90 (0.77-0.96) and 0.99 (0.98-1.0), respectively. Regarding inter-observer validity, the ICCs for the first and second measurements were 0.90 (range, 0.77-0.96) and 0.95 (range, 0.85-0.98), respectively.

    Conclusion

    CT volumetry is a reliable and reproducible method for measurement of transplanted pancreatic volume.

  • 27.
    Lundqvist, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ureteroperitoneostomy: a rare complication after kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 9, e75-e76 p.Article in journal (Refereed)
  • 28.
    Malm, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Hellström, Vivan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    von Zuhr-Muhlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Thomas
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    The Uppsala Experience of Switching from Cni:s to Belatacept after Kidney Transplantation2013In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 26, 92-93 p.Article in journal (Other academic)
  • 29. Mastellos, Dimitrios C.
    et al.
    Yancopoulou, Despina
    Kokkinos, Petros
    Huber-Lang, Markus
    Hajishengallis, George
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lupu, Florea
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Risitano, Antonio M.
    Ricklin, Daniel
    Lambris, John D.
    Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention2015In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 45, no 4, 423-440 p.Article, review/survey (Refereed)
    Abstract [en]

    There is a growing awareness that complement plays an integral role in human physiology and disease, transcending its traditional perception as an accessory system for pathogen clearance and opsonic cell killing. As the list of pathologies linked to dysregulated complement activation grows longer, it has become clear that targeted modulation of this innate immune system opens new windows of therapeutic opportunity for anti-inflammatory drug design. Indeed, the introduction of the first complement-targeting drugs has reignited a vibrant interest in the clinical translation of complement-based inhibitors. Compstatin was discovered as a cyclic peptide that inhibits complement activation by binding C3 and interfering with convertase formation and C3 cleavage. As the convergence point of all activation pathways and a molecular hub for crosstalk with multiple pathogenic pathways, C3 represents an attractive target for therapeutic modulation of the complement cascade. A multidisciplinary drug optimization effort encompassing rational wet' and in silico synthetic approaches and an array of biophysical, structural and analytical tools has culminated in an impressive structure-function refinement of compstatin, yielding a series of analogues that show promise for a wide spectrum of clinical applications. These new derivatives have improved inhibitory potency and pharmacokinetic profiles and show efficacy in clinically relevant primate models of disease. This review provides an up-to-date survey of the drug design effort placed on the compstatin family of C3 inhibitors, highlighting the most promising drug candidates. It also discusses translational challenges in complement drug discovery and peptide drug development and reviews concerns related to systemic C3 interception.

  • 30. Nadalin, Silvio
    et al.
    Biglarnia, Ali Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Testa, Giuliano
    Koppara, Tobias R.
    Schaffer, Randolph
    Johnson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Toetsch, Martin
    Broelsch, Christoph E.
    Malagó, Massimo
    Role and significance of plasma citrulline in the early phase after small bowel transplantation in pigs2007In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 20, no 5, 425-431 p.Article in journal (Refereed)
    Abstract [en]

    A reliable serological marker of acute cellular rejection (ACR) after small bowel transplantation (SBTx) is still missing. Plasma citrulline level (PCL) reflects the functional integrity of intestinal mucosa which is partially lost during ACR. The aim of our study was to investigate the role of PCL as marker of ACR after SBTx. Eighteen German landrace pigs were used and divided into three groups. Group 1 (G1), autologous SBTx (n = 4) as control; group 2 (G2), allogeneic SBTx without immunosuppression (IS) (n = 7) and group 3 (G3), allogeneic SBTx with IS (n = 7). IS consisted of tacrolimus and steroids without induction treatment. Observation period was 14 days. Mucosal biopsies were obtained intraoperatively and daily using a Thiry-Vella loop. ACR was differentiated into indeterminate, mild, moderate and severe using a standardized grading schema. PCL was measured daily. An ACR onset occurred generally from postoperative day 4 both in G2 and G3 as mild form and developed differently in the two groups: moderate to severe in G2 and indeterminate to mild in G3. A significant decline of PCL occurred only in cases of moderate and severe ACR, but not in cases of indeterminate and mild ACR. The PCL failed as a marker in the early diagnosis of ACR and became reliable only when advanced mucosal damage was present.

  • 31.
    Sedigh, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial experience with hypothermic machine perfusion of kidneys from deceased donors in the uppsala region in Sweden2013In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 45, no 3, 1168-71 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Simple cold storage (CS) is the gold standard for organ preservation. Recently, evidence has been presented suggesting compared with CS hypothermic machine perfusion (HMP) improves the quality and outcome of kidneys for transplantation. Uppsala has used the LifePort Kidney Transporter to preserve deceased donor kidneys. We evaluated our first single-center 52 cases retrospectively.

    METHODS: Deceased donor kidneys preserved with HMP between July 2010 and July 2012 (n = 52) were compared with a matched historical cohort of organs preserved by CS between January 2009 and July 2012 (n = 87). We evaluated delayed graft function (DGF), creatinine level at hospital discharge, length of hospital stay, incidence of acute rejection episodes during the first year after transplantation, and graft survival.

    RESULTS: Both groups included approximately 69% expanded criteria donors (ECD). Median cold ischemia time (CIT) was 12.8 hours in the HMP group and 11.7 hours in the CS group. The incidence of DGF was 11.5% with HMP and 20.7% with CS. Compared with CS, HMP significantly reduced the occurrence of DGF from 21.4% to 0% using standard criteria kidneys (P = .046), whereas the use of HMP did not impact the occurrence of DGF with ECD kidneys. The creatinine level at hospital discharge was lower after HMP than after CS (P = .047). No difference in graft survival was observed between the groups.

    CONCLUSIONS: Machine perfusion resulted in a lower occurrence of DGF using kidneys from standard criteria donors with a lower creatinine at hospital discharge among the cohort with reasonably low CIT. Using machine perfusion seems to be safe; no adverse surgical events occurred during the study period.

  • 32.
    Sjöberg, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Assessing the Viability of Human Pancreas Grafts using 31P MR Spectroscopy - a Pilot Study2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, S13-S13 p.Article in journal (Other academic)
  • 33. Tydén, G.
    et al.
    Nordén, G.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Björk, P.
    Blodgruppsinkompatibla njurar kan transplanteras2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39, 1738- p.Article in journal (Refereed)
  • 34.
    Wadström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Gjertsen, Henrik
    Sugitani, Atsushi
    Fronek, Jiri
    Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: Learning curves and development based on 413 consecutive cases in four centers2011In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 4, 462-469 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 35.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Univ Uppsala Hosp, Dept Surg, Div Transplantat, Uppsala, Sweden..
    Simultaneous Hand-Assisted Transperitoneal Bilateral Native Nephrectomy And Extracapsular Transplant Nephrectomy In A Patient With Polycystic Kidney Disease2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, 216-216 p.Article in journal (Other academic)
  • 36.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wahlberg, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Factors influencing outcome of simultaneous kidney and pancreas transplantation: a 23-year single-center clinical experience2010In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 42, no 10, 4197-4201 p.Article in journal (Refereed)
    Abstract [en]

    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 Methods

    Between 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.

    Results

    The 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.

    Conclusions

    We 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.

1 - 36 of 36
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