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Biomedical subjects

L Rydberg

Publications and source records attributed to L Rydberg.

At least 19 recordsLinked to original sources
PubMed2007

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↗
PubMed2006

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↗
PubMed2005

Characterization of the humoral immune response in two paediatric patients transplanted with split livers from ABO-incompatible living-related donors: appearance of cytomegalovirus-induced ABO antibodies.

Two blood group O paediatric patients, 12 and 6 months old, were transplanted with liver segments from their blood group A2Le (a(-)b+) Se and blood group A1Le (a(-)b+) Se fathers, respectively. Recipient anti-A antibody titres were reduced prior to transplantation by blood exchange. Both patients had rejection episodes in the post-transplant period that were reversed by anti-rejection therapy. No anti-A antibody titre rise occurred concomitant with these rejections. Postoperatively both patients had cytomegalovirus (CMV) infections, and simultaneous with these infections, a strong increase in anti-A antibody titres was seen, but no rejection occurred. The anti-A antibody titre increase seemed to be specific for A antigens, because the anti-B and anti-alphaGal (anti-pig) antibody titres did not show any changes. CMV infection is a serious cause of morbidity and mortality in immunosuppressed patients, and the virus can influence glycosylation of infected cells. Whether this can explain the importance of the infection in relation to the increase in titre remains to be elucidated.

ABO Blood-Group System↗
PubMed2005

Novel glycolipid variations revealed by monoclonal antibody immunochemical analysis of weak ABO subgroups of A.

BACKGROUND AND OBJECTIVES: The chemical basis of the subgroups of A is largely unknown. We used thin-layer chromatography immunochemical staining techniques together with a range of characterized monoclonal reagents to analyse glycolipids isolated from a variety of weak subgroups. MATERIALS AND METHODS: Glycolipids isolated from red cells collected from nine genetically defined individuals of the rare subgroups of A, including a novel A(3) allele (A(2) 539G>A) not described previously, were subjected to a highly sensitive thin-layer chromatographic immunochemical analysis. RESULTS: Semicharacterized monoclonal antibodies revealed that, in addition to the expected quantitative differences between common phenotypes and the weak subgroups, qualitative glycolipid differences (or at least an apparent qualitative basis), caused by major changes in the ratios of different structures exist. Specifically it was found that the weakest A-expressing samples (A(el) phenotype) appeared to express an unusual A structure in the 8-12 sugar region. Variable expression of several structures in one of the A weak samples were suggestive of novel blood group A structures. CONCLUSIONS: Although no structural characterization could be undertaken, the results are clearly indicative that the variant glycosyltransferases of the rare ABO subgroups are not only inefficient, but they may potentially synthesize novel ABO structures.

ABO Blood-Group System↗
PubMed2004

Complement activation in prestorage leucocyte-filtered plasma.

Complement activation and generation of pro-inflammatory cytokines occur during storage of blood components. Prestorage leucocyte filtration of platelet concentrates and red cells diminishes the accumulation of leucocyte-derived cytokines during storage, however, transfusion reactions are not eliminated. We investigated inflammatory mediator release during storage of plasma and whole blood and the effect of prestorage leucocyte filtration of plasma. Twenty-four blood units were collected from healthy blood donors and stored for 35 days. Eight units were stored as whole blood, eight units as plasma and eight units as prestorage filtered plasma. Samples were collected weekly for analyses of potassium, leucocytes, free plasma haemoglobin, complement activation (C3a and SC5b-9) and pro-inflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha]. Elevated levels of C3a and SC5b-9 were registered in filtered plasma, from the beginning of storage. C3a levels increased during storage. There was a higher rate of change during storage in C3a (P < 0.01) and SC5b-9 (P < 0.05) in plasma compared with filtered plasma. Interleukin (IL)-8 is released in whole blood. The cytokine levels generated in plasma and filtered plasma were low. Complement activation is present in whole blood, plasma and filtered plasma during storage. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation.

Blood↗
PubMed2001

ABO-incompatibility in solid organ transplantation.

The most important transplantation antigen system in solid organ transplantation is the ABO histo-blood group system. Crossing the ABO barrier in solid organ transplantation is usually not done except for emergency liver transplantations. Early experiences of crossing the ABO barrier in renal transplantation were very disappointing. In the 1970s, clinical trials were started transplanting kidneys of subgroup A2 into blood group O recipients. The tissues of the A2 subgroup expresses reduced amount of A antigens compared to subgroup A1 and the recipients had no special pretreatment and standard immunosuppression. A number of early graft losses were experienced but the trial also resulted in several long time surviving grafts. A few centres have adapted the concept of A2 to non A kidney transplantations with successful results, when the recipient anti-A titres are low or reduced prior to transplantation. In the early 1980s one group successfully transplanted A1 and B kidneys from living related donors across the ABO-barrier using an immunosuppressive protocol consisting of quadruple drugs and splenectomy and this protocol was adapted by a few other groups. In Japan, where cadaver donors are available in very limited number, the largest number of ABO-incompatible transplantations have been performed. Altogether more than 300 ABO-incompatible kidney transplantations have been performed in more than 40 centres since 1989. ABO-incompatible liver transplantations have been performed mainly in emergency cases and the results have generally been inferior to ABO-compatible grafts. In children below the age of three years, liver transplantations across the ABO-barrier have been quite successful especially with living related donors. Very few ABO-incompatible heart/heart-lung/lung-transplantations have been reported with a few successful cases, but the majority have been failures. Recently a series of ABO-incompatible heart transplants performed in small children have been reported with a high success rate.

ABO Blood-Group System↗
PubMed2001

Histo-blood group A antigen expression in pig kidneys--implication for ABO incompatible pig-to-human xenotransplantation.

OBJECTIVE: There is a relative shortage of donor organs for clinical transplantation, and the use of animal organs is being considered. A clinical trial was performed connecting pig kidneys to the circulation of a dialysis patient. MATERIAL AND METHODS: A pig kidney was, after plasmapheresis, extracorporeally connected to the circulation of a volunteer dialysis patient. The patient was of blood group B and the pig of blood group A. RESULTS: The experiment gave rise to a strong humoral immune response where the xenoantibodies were shown to be of immunoglobulin G (IgG), IgM and IgA immunoglobulin classes, recognizing mainly the Gal alpha1-3Gal epitope and the anti-A antibodies was exclusively of IgM type, recognizing the blood group A trisaccharide. Immunohistological examinations of blood group A pig kidneys revealed that blood group A antigens are located in the distal tubules, thin and thick tubules of Henle and the epithelium of the collecting ducts but absent in proximal tubules, glomeruli, large vessels and capillaries. In the perfused kidney, a patchy destruction of tubular cells was found and these segments stained positive for blood group A antigens and had a codeposition of human IgM antibodies and complement components. Tubular segments which were apparently normal were all negative for blood group A antigens but strongly expressed the Gal alpha1-xenoantigen. CONCLUSION: In this patient, challenged simultaneously with carbohydrate antigen epitopes representing both the ABO and the xenobarrier, the humoral immune response differed concerning the immunoglobulin classes induced. The low remaining anti-A titre after plasmapheresis was probably sufficient to cause destruction of A antigen-positive tubular cells, while the corresponding Gal alpha1-xenoantigen-positive cells were structurally intact. This case confirms that in future xenotransplantation, matching for the ABO system has to be undertaken in the same way as in human allotransplantation.

ABO Blood-Group System↗
PubMed2000

Blocking of human anti-pig xenoantibodies by soluble GAL alpha 1-3Gal and Gal alpha 1-2Gal disaccharides; studies in a pig kidney in vitro perfusion model.

Depletion of anti-pig xenoantibodies reduces cell cytotoxicity of human serum to pig endothelial cells and lymphocytes. The aim of this study was to test, in a pig kidney xenoperfusion model, the ability of soluble alpha Gal terminated disaccharides to prevent the hyperacute rejection process in an organ. Porcine kidneys were perfused with whole human blood lacking saccharide and blood supplemented with Gal alpha 1-3GAL, Gal alpha 1-2Gal and lactose. Parameters evaluated were, urine production, renal blood flow, vascular resistance, renal clearance, blood cell counts, xenoantibody titers, complement activation and histopathology. The blood flow was higher in the Gal alpha 1-3Gal (155 +/- 31 ml/min x 100 g-1 kidney tissue) group compared to Gal alpha 1-2Gal (138 +/- 16), lactose (92 +/- 78) and controls (69 +/- 16), When calculated as percent of the blood flow value at 1 min, the blood flow at 30 min was 157% for the Gal alpha 1-3Gal and for 187% the Gal alpha 1-2Gal. The corresponding values for the lactose and control groups were 102% and 74%, respectively. Urine production in the lactose/control groups was lower (0.7 ml/min x 100 g-1 kidney tissue) compared to Gal alpha 1-3Gal (3.0) and Gal alpha 1-2Gal (3.7). Urine sodium excretion was reduced in the lactose/control groups, compared to the Gal alpha alpha 1-groups during the perfusions. An increase in urine potassium excretion was found in the Gal alpha alpha 1-groups while a reduction occurred in the lactose/control experiments. An initial 40-50% reduction in platelet count was observed in all groups while the leukocyte count showed a continuous decrease. Immunohistochemistry revealed less deposition of IgM, IgG, C3 and C1 q in the Gal alpha alpha 1-saccharide groups compared to the lactose/control groups. Soluble Gal alpha a1-disaccharides improved both functional and histological parameters. However, significant pathological changes were still present indicating that this approach to inhibit HAR must be used in combination with additional therapeutic approaches such as solid phase xenoantibody immunoadsorption and blocking of complement activation.

Animals↗
PubMed2000

Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history.

The significance of non-alphagalactosyl antigens remains unclear in pig-to-primate xenotransplantation. Hanganutziu-Deicher (H-D) antigens with terminal N-glycolylneuraminic acid (NeuGc) are widely expressed on endothelial cells of mammalian species, with the exception of humans. As baboons and monkeys also express H-D antigens, a pig-to-non-human primate experimental model cannot resolve the question of whether H-D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to elucidate the clinical significance of H-D antigens by examining the sera from patients who have been previously exposed to porcine tissue. After the digestion of porcine aortic endothelial cells (PAEC) by neuraminidase, NeuGc and N-acetylneuraminic acid (NeuAc) were quantitated by HPLC. IgG and IgM antibody levels against H-D antigens were measured by NeuGc-GM3-coated ELISA plates in the sera of patients who had undergone ex vivo kidney perfusion 1 to 3 weeks and 2 years previously (n=2) or had been injected with fetal porcine islets 2 months previously (n= 10). HPLC determined that 9.7x 10(7) NeuAc and 6.3x 10(7) NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7x 10(7) NeuAc and an undetectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuGc-GM3 was observed in sera from patients with a history of porcine exposure. Considering the active production of antibody against the foreign galactosyl antigens after pig-to-human xenotransplantation, some production of antibodies against the equally foreign H-D antigens would be expected, because large amounts of NeuGc terminated saccharides are present in the pig endothelial cell surface. However, no production of antibodies directed to H-D antigens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H-D antigens do not elicit a significant antibody production.

Animals↗
PubMed2000

Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases. METHODS: In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Adult↗
PubMed2000

Characteristics of secondary oesophageal peristalsis in operated and non-operated patients with chronic gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: Secondary oesophageal peristalsis contributes to oesophageal volume clearance and may be impaired in a significant proportion of patients with chronic gastro-oesophageal reflux disease (GORD). This study aimed to investigate the triggering of secondary peristalsis in chronic GORD patients compared to those previously operated on with anti-reflux surgery. PATIENTS AND METHODS: Healthy volunteers, chronic GORD patients with proven oesophagitis and patients successfully operated on with anti-reflux surgery (> 3 years ago) were investigated. Secondary peristalsis was elicited by oesophageal distension by a bolus of air (10 ml) injected rapidly into the mid-portion of the oesophagus. The peristaltic characteristics in the distal oesophagus were assessed by use of stationary manometry. RESULTS: The primary peristaltic amplitude in the distal third of the oesophagus was significantly higher (P < 0.002) in the non-operated GORD cases than in those recruited for surgery. Furthermore, a difference in the frequency of failed primary peristalsis was revealed (2.1 versus 8.4%) between the non-operated and operated patients. Secondary peristalsis occurred in 65 +/- 13.2% (mean +/- SE) of the healthy subjects on stimulation, which was a higher figure than in the GORD patients. In patients investigated after successful anti-reflux surgery, a secondary peristaltic wave was elicited in only 26 +/- 7.2% of the attempts, which was significantly lower than the 46 +/- 7.7% seen in non-operated GORD patients (P < 0.05). A direct comparison between motor characteristics of primary and secondary peristalsis revealed that the latter amplitudes were significantly lower both in the non-operated and in the operated cases (P < 0.005). CONCLUSIONS: The triggering of secondary peristalsis seems to be impaired in chronic GORD patients. Investigating similar patients > 3 years after successful anti-reflux surgery revealed an even lower prevalence of secondary peristaltic waves, implying persistence of the abnormality after surgery and consistent with other evidence that GORD is associated with a primary defect in oesophageal motor function.

Adult↗
PubMed1999

alpha-Gal epitopes in animal tissue glycoproteins and glycolipids.

alpha-Gal terminated saccharides are present on the cell surface both as glycolipids and glycoproteins in all mammals except Old World monkeys and humans. The structural diversity among identified saccharides terminated by this epitope in animal tissues is steadily increasing. The majority of these saccharides have the alpha-Gal linked to lactosamine but other core saccharides exist. The alpha-Gal terminated saccharides are recognized by the immune system as a specific antigen and antibodies directed to the alpha-Gal, which do not cross-react with the classic blood group B trisaccharide, are found in man and Old World monkeys. Similar to other complex carbohydrate cell surface antigens, the alpha-Gal epitope is heterogeneously distributed in different organs and in different cells within an organ. It is present on the vascular endothelium and it is the primary target for human naturally occurring antibodies following pig to primate/man xenotransplantation leading to hyperacute rejection of the graft. Important for the future will be to further structurally characterize this antigen system, its cellular/subcellular distribution, and to identify possible of additional glycosyltransferases, related to the already described alpha 1,3galactosyltransferase that may explain the structural diversity. Such information will be of importance in the studies of, for example, the pathogenesis of autoimmune diseases and for the production of genetically modified pigs to prevent xenograft rejection.

Animals↗
PubMed1999

Tailoring antireflux surgery: A randomized clinical trial.

A hypothesis has been formulated that mandates the adjustment of antireflux surgery to either a total or a partial wrap depending on the motor function of the esophagus to avoid dysphagia and other obstructive complaints. This hypothesis has been tested in a randomized, clinical trial where 106 chronic gastroesophageal reflux patients were allocated to either a total Nissen-Rossetti (n = 53) or a Toupet partial posterior (n = 53) fundoplication, irrespective of their preoperative esophageal motor function. All patients were followed at least 3 years, during which time none had a relapse of moderate to severe reflux symptoms. Motor dysfunctions defined as peristaltic amplitude </= 30 mmHg in the distal third and failed primary peristalsis with or without > 20% simultaneous contractions were noted in 67 patients preoperatively, but these patients did not have a specific symptom profile (e.g., dominated by obstructive symptoms) nor did seven patients with "aperistaltic esophagus." The incidence of dysphagia decreased from 20% preoperatively to 8% (mild) at 3 years after the operation with no difference between the surgical procedures. We were unable to demonstrate a relation between preoperative manometric findings and postoperative symptoms when assessed in the total group or when subdivided by the type of fundoplication (r < 0.3). Flatulence occurred more frequently among those with a total fundic wrap (p < 0.01). When patients representing motor dysfunction (see above) were specifically analyzed, we again observed no difference in outcome between those having a total or a partial fundic wrap. In conclusion, the concept of tailoring antireflux surgery based on the preoperative motor function of the esophagus in patients with chronic gastroesophageal reflux disease was not supported by the results of this clinical trial.

Adult↗
PubMed1999

Mechanism of action of antireflux procedures.

BACKGROUND: To define the clinical role of antireflux surgical procedures a proper understanding of their mode of action is required. The aim of this study was to investigate the impact of total or posterior partial fundoplication on the function of the lower oesophageal sphincter (LOS) in the basal state as well as during stimulation. METHODS: Patients with chronic reflux (n = 24) were randomized either to a total fundic wrap or to a posterior partial (Toupet) fundoplication. Basal LOS function was investigated as well as the response to inhibitory stimuli 4 years after operation. Inhibitory stimulation was elicited by water swallows and by gas distension (750 ml air insufflation into the stomach). RESULTS: Basal LOS tone was substantially higher (P = 0.01) after a total than a partial wrap, as was the nadir pressure after water swallows (10.1 versus 3.4 mmHg). Body position did not affect this difference. Transient LOS relaxations occurred only occasionally in the basal state. The frequency of transient LOS relaxation increased somewhat during the first 10 min of stomach distension with more occurring in patients who underwent a Toupet procedure. Common oesophagogastric cavities were more often seen in this latter group of patients after gas distension of the stomach. CONCLUSION: These physiological observations on the LOS after total and posterior partial fundoplication explain the observed clinical differences in favour of the latter operation. The partial fundoplication seems to restore the physiology of the gastro-oesophageal junction more adequately, allowing air to be vented from the stomach without jeopardizing the antireflux barrier.

Adult↗