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Biomedical subjects

L Mjörnstedt

Publications and source records attributed to L Mjörnstedt.

At least 19 recordsLinked to original sources

Successful combined partial auxiliary liver and kidney transplantation in highly sensitized cross-match positive recipients.

Combined liver and renal transplantations can be performed against a positive cross-match, indicating that the liver protects the kidney from the harmful HLA antibodies. This led us to the hypothesis that a partial auxiliary liver graft may have a similar protective effect when performed together with the kidney in highly sensitized patients. Seven patients, with broadly reacting HLA antibodies and positive crossmatches, were transplanted with a partial liver and a kidney from the same donor. In one of the cases a living donor was used. We performed lymphocytotoxic and flow cross-matches before and after the transplantation. Cross-matches turned negative after grafting in five of seven cases. The kidney function was excellent, without rejections, during the follow-up (24-60 months) in these patients. In two cases the cross-match remained positive after transplantation, one with a never-functioning renal graft and the other with an early graft failure, probably due to humoral rejection. A simultaneous transplantation of a partial auxiliary liver graft from the same donor, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, can be performed successfully despite a positive cross-match and may thus be a new option of treatment for highly sensitized patients waiting for a kidney transplant.

Adult↗

Successful ABO-incompatible liver transplantation using A2 donors.

INTRODUCTION: The longer waiting time for a liver graft among patients with blood group O makes it necessary to expand the donor pool for these patients. We herein have reported our experience with ABO-incompatible liver transplantation using A(2) donors to blood group O recipients. PATIENTS AND METHODS: Between 1996 to 2005, 10 adult blood group O recipients received 10 A(2) cadaveric grafts. Mean recipient age was 52 +/- 7.7 years (mean +/- SD). The initial immunosuppression was induction with antithymocyte globulin (n = 2), interleukin-2-receptor antagonists (n = 3), or anti-CD20 antibody (rituximab, n = 1), followed by a tacrolimus-based protocol. No preoperative plasmapheresis, immunoadsorption, or splenectomies were performed. RESULTS: Patient and graft survival was 10/10 and 8/10, respectively, at 8.5 months median follow-up (range 10 days to 109 months). Two patients were retransplanted because of bacterial arteritis (n = 1) and portal vein thrombosis (n = 1). The six acute rejections, which occurred in four patients, were all reversed by steroids or increased tacrolimus dosages. The pretransplant anti-A titers against A(1) red blood cells were 1:128 (NaCl technique) and 1:8 to 1024 (IAT technique). The maximum postoperative titers were 1:64 to 4000 (NaCl) and 1:256 to 32000 (IAT). CONCLUSION: The favorable outcome of A(2) to O grafting, with a patient survival of 10/10 and graft survival of 8/10, makes it possible to consider this blood group combination also in nonurgent situations. There was no hyperacute rejection or increased rate of rejections. Anti-A/B titer changes seem to not play a significant role in the monitoring of A(2) to O liver transplantation.

ABO Blood-Group System↗

Pseudoaneurysm of the hepatic artery following liver transplantation.

We report 12 cases of pseudoaneurysm hepatic artery (PA) among 825 liver transplantations (OLT) performed between January 1985 and December 2005. In the early period (1985 to 1995), the incidence was 2.6% and in the later period (1996 to 2005), 0.9%. Median time to onset was 39.5 days post-OLT (range 14 days to 5 years). Six patients presented with rupture into the peritoneum (n = 4) or gastrointestinal tract (n = 2), while five patients presented with gastrointestinal bleed due arteriobiliary fistulation with hemobilia. The twelfth PA was found incidentally during retransplantation. PAs were detected with radiological imaging (n = 4), exploratory laparotomy (n = 6), at autopsy (n = 1) or at retransplantation (n = 1). We performed immediate revascularization, after surgical excision was performed in three and endovascular embolization in one patient. In six patients hepatic artery ligation without revascularization was inevitable with subsequent successful retransplantation in four patients. No PA-specific treatment was attempted in two cases due to the poor prognosis or diagnostic ambiguity. In 10 cases microbial pathogens were cultured in the blood, subhepatic abscesses, or from the wall of the hepatic artery. A hepaticojejunostomy was performed for biliary reconstruction in six patients and two had a hepaticojejunostomy conversion due to biliary leak. Survival in the early period (1985 to 1995) was 14%, whereas during the later period (1996 to 2005), the survival increased to 100% with a 4.2-year median follow-up (range 7.4 months to 6.9 years). Infrequently PA complicates OLT, becoming evident primarily after rupture with hemoperitoneum or a gastrointestinal bleed. Early recognition with angiography is important but acute hemorrhage often requires immediate exploration with ligation of the PA, although surgical or endovascular exclusion of the PA followed by revascularization provides a feasible treatment option.

Anastomosis, Surgical↗

Late mortality in 679 consecutive liver transplant recipients: the Gothenburg liver transplant experience.

PURPOSE: Liver transplantation (OLT) is an established treatment with excellent early outcome. However, the long-term results are hampered by side effects of immunosuppression, cardiovascular morbidity, recurrent disease, and chronic rejection. We analyzed causes of late death (>/=2 years post-OLT) in 679 consecutive primary recipients in our institution. MATERIALS AND METHODS: A total of 679 primary OLT recipients including those retransplanted within 3 months between January 1985 and August 2005 were identified; 460 (67.7%) patients survived >/=2 years. The indications were cholestatic disease (35.1%), postviral (11.4%), alcoholic (12.9%), fulminant hepatic failure (7.0%), cryptogenic (3.1%), autoimmune hepatitis (4.8%), malignancy (7.7%), and others (18.0%). Sixty three patients (9.3%) died >/=2 years post-OLT. For 51 patients, sufficient records were present to establish the cause of death. RESULTS: Four hundred sixty (67.7%) patients survived >/=2 years. Their median age was 58 years with, 43.7% older than 60 and 11.1% older than 70 years. Sixty three patients (9.3%) died at a median time of 69 +/- 4.8 months post-primary OLT; 49.1% died of malignancy and 13.7% of vascular complications and infectious complications respectively. CONCLUSIONS: Late mortality in our material is mainly due to malignant disease. Compared to other published reports on late mortality, the proportion of malignancy, especially recurrent, as cause of late death is higher. This might reflect a more generous approach toward accepting older patients and a higher proportion of patients with various malignant diseases accepted for OLT.

Aged↗

Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab.

In contrast to focal segmental glomerulosclerosis, which is well known to recur early in a renal graft, there are only few cases described with recurrence of immunoglobulin M (IgM) nephropathy after transplantation. We herein describe a patient with early recurrence of IgM nephropathy. A 15-year-old boy with nephrotic syndrome (IgM nephropathy) proceeding to end-stage renal disease was on dialysis before living related renal transplantation. Native kidneys were not removed. Standard immunosuppression including steroids, tacrolimus, and mycophenolate mofetil yielded initially good graft function with the s-creatinine falling to 73 micromol/L. Proteinuria was present on day 1, increasing to 20 g/L after 3 days. S-creatinine increased to 158 micromol/L and urine production diminished. A graft biopsy showed no rejection or glomerulopathy but protein vacuoles were seen within tubular cells indicating massive proteinuria. Treatment with plasma exchanges, immunoglobulin, and steroids was started. Hemodialysis was necessary. Proteinuria improved to 3.5 g/L, but s-creatinine continued to rise and a second graft biopsy showed vascular rejection (Banff type IIA). The patient was treated with antithymocyte globulin and further plasma exchanges. A single dose of rituximab was given. Five months after transplantation the s-creatinine was 67 micromol/L and there was no proteinuria. In this case early recurrence of nephrotic syndrome occurred on the first posttransplant day in combination with later occurring vascular rejection. Successful treatment included a combination of plasma exchanges, rituximab, immunoglobulin, and antithymocyte globulin.

Adolescent↗

Increase in organ donation rate in a Swedish region after implementing a new angle of approach.

In the Swedish Västra Götaland region (1.65 million inhabitants), we have implemented, as from January 1, 2006, a new concept to improve the organ donation rate, which in 2005 was 13.9 per million population (PMP). There are two cornerstones in the project: a new, active role for the transplant coordinators and the establishment of a uniform policy for the care of potential donors as well as criteria for the decision to offer intensive care in various critical conditions. The coordinator is now contacted at an early stage and is in place when the brain death diagnosis is underway or completed. The coordinator is thereafter a resource for all aspects of the care of the potential donor/donor, and also in the contact with the relatives. To date (May 2006) the donation rate has reached 23.6 PMP annually (a 70% increase).

Adolescent↗

[Liver transplantation--from experiment to routine care. Experiences from the first 500 liver transplantations in Gothenburg].

During a fifteen-year period, 500 liver transplantations have been performed at Sahlgrenska University Hospital in Göteborg. The results have improved, and factors influencing outcome are discussed. A one-year survival rate over 90% and a 5-year survival rate close to 80% can now be expected for most indications. Long-term complications as well as special problems occurring in different groups of recipients are discussed. New indications for liver transplantation such as liver metastasis of endocrine tumors are described. This article also describes our experience of in situ splitting and living-related liver transplantation as well as other innovations such as cavoportal hemitransposition and multivisceral transplantation.

Adult↗

Endoluminal laser-Doppler measurements of jejunal perfusion in patients undergoing liver transplantation.

Patients undergoing liver transplantation are at risk of developing the multiple organ dysfunction syndrome, and attention has been focused on the pathogenic role of decreased gastro-intestinal mucosal perfusion. The aim of this study was to investigate the use of laser-Doppler flowmetry for determination of jejunal perfusion. In 10 patients an endoluminal laser-Doppler catheter was positioned with the tip in the jejunum for continuous measurements of jejunal perfusion. The anhepatic phase was associated with a progressive decrease in jejunal perfusion to 49 (40/65)% (P < 0.01) of dissection phase value. At the end of surgery the jejunal perfusion had increased to 134 (103/158)% (P < 0.01) of dissection phase jejunal perfusion. The endoluminal laser-Doppler technique was found to be easily applicable for continuous monitoring of jejunal perfusion, and the technique could prove valuable in detecting gastro-intestinal hypoperfusion in patients undergoing liver transplantation.

Adult↗

Characterization of Forssman and other antigen/antibody systems in vascularized mouse heart to rat xenotransplantation.

In the present study, the nature of hyperacute xenograft rejection was closely studied in a vascularized mouse-to-rat transplantation model. Antibodies against mouse heart, erythrocytes and lymphocytes and against the Forssman antigen were raised in the rat. Upon heterotopic heart transplantation the respective antisera were intravenously (i.v.) injected. Passive transfer of antiheart, antierythrocyte or antilymphocyte serum resulted in hyperacute rejection of the transplanted mouse heart. Subfractionation of the antiheart serum showed that the capacity to induce hyperacute rejection was carried by the immunoglobulin (Ig)G fraction. When antierythrocyte serum adsorbed with mouse erythrocytes was administered the cardiac grafts remained beating. To the contrary, antilymphocyte serum adsorbed with erythrocytes still had the capacity to induce hyperacute rejection. None of the rats that had previously been challenged with the Forssman antigen rejected their grafts hyperacutely. Subsequent investigations by electron microscopy revealed that the Forssman antigen is expressed on dendritic cells (DC) adjacent to the vessels, but not on the vascular endothelium, thus explaining the inability of the anti-Forssman serum to induce hyperacute rejection. Taken together, we have demonstrated the existence of several xenoantigens that can be targets for antibody-mediated rejection, suggesting that more than one relevant xenoantigen exists also in more distantly related combinations, such as the pig-to-human combination.

Acute Disease↗

Decreasing ratios of phosphocreatine to beta-ATP correlates to progressive acute rejection in a concordant mouse heart to rat xenotransplantation model.

Biopsies are difficult to perform in rodent heart transplant models without compromising the graft function and therefore other means to evaluate the grafts repeatedly and noninvasively are warranted. The goal of the present study was to measure changes in ratios of high energy phosphorus containing metabolites detected with in vivo 31Phosphorous Magnetic Resonance Spectroscopy ((31)P MRS) in a xenotransplantation model and to investigate if these ratios correlated to histological signs of acute xenograft rejection. Thirty-five heart transplantations were performed (NMRI-mice to Lewis (RT1(1)) rats). Thirteen heart transplants underwent repeated daily in vivo (31)P MRS measurements and 22 grafts were measured on any of 4 postoperative days and thereafter sacrificed for histology. A modified scoring system based on Billingham's criteria was used to stage the rejection process. The median graft survival was 3.0 +/- 0.44 (median +/- SD) days (n = 17). Significant differences, both overall and interday, could be calculated for the phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) ratios and for the rejection score. The decreases in PCr/beta-ATP ratios correlated significantly to the progressive acute rejection process in the sacrificed grafts (P = 0.01). Further studies are indicated to establish the potential of (31)P MRS in immunosuppressed recipients of vascularized xenotransplants with prolonged graft survival.

Acute Disease↗

[Liver transplantation from a living donor is now possible. The first cases in Sweden completed with good results].

Liver transplantation is the sole treatment option for children with chronic liver failure, a patient category previously characterised by high mortality due to the lack of suitable organs. The introduction of new surgical techniques used in 'in situ splitting' of a donor liver, and in living related donor transplants has enabled mortality to be reduced. The article consists gives an account of the first five procedures where the in situ split technique was used in cadaveric livers, and of the first living related liver transplant performed in Sweden. The technique will improve the outcome of liver transplantation in children, and reduce the risk of death due to long waiting lists.

Adult↗

Increasing prevalence of cardiovascular disease in kidney transplant patients with Type 1 diabetes.

Type 1 diabetes was evaluated as a risk factor in kidney transplantation with respect to cardiovascular disease and with focus on changes over time. From 1985 to 1993, 159 Type 1 diabetic patients received first kidney transplants in Göteborg. Actual 5 year-survival of diabetic patients was 75% compared to 94% for matched controls, P < 0.0001, and survival of grafts was 60% compared to 75%. In the diabetic group, high age and preexisting coronary heart disease were additional, independent risk factors. When patients were divided into three groups according to time of transplantation, survival was found to improve initially but then declined, P = 0.03. Patients in the last group were older and 39% had pre existing vascular disease. The fact that Type 1 diabetic patients now reach end-stage renal failure at a higher age and with more established vascular disease calls for careful evaluation of a larger proportion of the transplant candidates.

Adolescent↗

Antithymocyte globulin and cyclosporin A are synergistic in an experimental transplantation tolerance model in the rat.

The aim of the present investigation was to study the possible synergistic effect between cyclosporin A (CsA) and antithymocyte globulin (ATG), using the potent immunostimulator, Linomide. DA rats were transplanted with a PVG/c heart to the neck vessels, and the recipients were treated for 10 days with oral CsA (10mg/kg), oral Linomide (160mg/kg) and/or ATG, which was given as a single dose of either 0.02 ml, 0.1 ml or 0.2 ml prior to transplantation. Rats given a combination of ATG and Linomide or CsA and Linomide were used as controls. Synergism between CsA and ATG was tested using the two immunosuppressive drugs given in combination in order to override the challenge of Linomide. CsA or ATG treatment alone resulted in rats with long-term surviving grafts. Addition of Linomide to CsA-treated recipients was followed by early graft rejection. Similarily, Linomide triggered rejection in rats given a low dose of ATG and in recipients given a high dose of ATG if Linomide treatment was prolonged to 21 days. The combination of ATG, CsA and 21 days of Linomide resulted in a significantly prolonged graft survival compared with either ATG + Linomide or CsA + Linomide. These findings demonstrate the synergistic capacity of ATG and CsA in combined immunosuppressive therapy.

Adjuvants, Immunologic↗