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Biomedical subjects

G Tufveson

Publications and source records attributed to G Tufveson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Intestinal distribution of hyaluronan in small bowel allografting in the rat.

Hyaluronan (hyaluronic acid; HA) was demonstrated and quantified in small bowel tissue at different times after small bowel transplantation. Semiallogeneic or semisyngeneic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease (GVHD). In normal rat small bowel, HA was present in the villous lamina propria and around medium-sized vessels in the interstitium of the crypt area. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt area where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection, and on day 6 there was a threefold increase compared to the values in syngeneic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. In specimens from animals suffering from GVHD, no significant changes in water or HA content and distribution were observed until day 12. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value in differentiating between graft rejection and GVHD.

Animals↗
PubMed1993

Recovery of hyaluronan during perfusion of small bowel transplantation reflects rejection.

Rejection seen after small bowel transplantation (SBT) in the rat is associated with an accumulation of hyaluronan (HA) in the lamina propria of the graft. In this study the intestinal intraluminal content of this connective tissue component was measured in order to determine if HA could be used as an index of rejection following SBT. Syngeneically and semiallogeneically transplanted rats were investigated by perfusion of a 4-cm segment of the intestinal graft on days 2, 4, and 6 posttransplantation. The amounts of HA recovered during perfusion were analyzed using a radiometric assay. In rejecting grafts the recovered HA amounts increased 15 times from day 2 to day 6, although after syngeneic transplantation there was only a minor increase from day 2 to day 4 and no further increase on day 6. Thus, the recovery of HA during perfusion of transplanted small bowel grafts has the potential value to reflect rejection.

Animals↗
PubMed1993

Increased hyaluronan in acutely rejecting human kidney grafts.

The glycosaminoglycan hyaluronan is not only involved in cellular differentiation and migration but may also play a role in several inflammatory diseases. We have previously demonstrated an increased local production of hyaluronan in chronically rejected kidneys and the correspondingly affected renal vessels. In this report, we demonstrate the presence of hyaluronan in acutely rejecting kidneys. A total of 77 biopsies classified as either acute rejection or nonrejecting were analyzed using a biotin-labeled hyaluronan-binding protein in conjunction with an avidin-biotin peroxidase detection system and graded using an arbitrary scale from 0 to 3. Those biopsies classified as nonrejecting did not contain any peritubular hyaluronan in the cortex, with hyaluronan being localized only in the medulla. In contrast, those biopsies exhibiting acute rejection had an increase of hyaluronan both in the cortex and in the medulla. This increase was significantly different (P = 0.0001) and correlated with edema and interstitial inflammation. The detection of the local hyaluronan production may be a useful marker to measure acute rejection episodes.

Acute Disease↗
PubMed1993

The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens.

To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poorer in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 45-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejection were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-match, young recipient age, disease of diabetes mellitus, and HLA-DR mismatching. In LD recipients, the corresponding risk factors were treatment schedule, young recipient, HLA mismatching, and transplantation from parent to child. Thus, the study has demonstrated some factors of importance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graft survival and renal function. These results suggest that a primary aim of future treatment strategies should be to reduce the incidence of these episodes.

Adolescent↗
PubMed1993

The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation.

Lipoprotein patterns were investigated before and after renal transplantation in a prospective study including 151 patients. Kidney graft losses during the first 6 months were associated with higher total cholesterol (P = 0.03), LDL cholesterol (P = 0.003) and LDL triglyceride levels (P = 0.01) before transplantation. Patients with serum cholesterol > or = 6.9 mmol l-1 before transplantation had more acute rejections (1.7 vs. 0.9), a worse graft function and more vascular intimal hyperplasia and glomerular mesangial changes in transplant biopsies at 6 months. Patients with serum creatinine levels exceeding 160 mumol l-1 at 6 months had more severe lipid disorders already before transplantation. Serum creatinine at 6 months was influenced by the number of acute rejection episodes (P = 0.0001) and the age of the donor (P = 0.009) while the number of acute rejections was found to be related to pretransplant total cholesterol levels (P = 0.0086) and the age of the recipient (P = 0.025). In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progression of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction.

Adolescent↗
PubMed1993

Organ transplantation in Göteborg with particular reference to kidney transplantation.

The limiting factor in organ transplantation is the availability of organs. Continuing work to improve the public's willingness to donate organs and inspire hospital staff to collaborate in organ procurement is essential. Identification of patients who will not benefit from transplantation can also increase the availability of organs. Grafts may also be saved by identification and appropriate treatment of recurrent renal disease. Xenotransplantation may eventually solve the problem, but major obstacles remain. Meanwhile, work in this field may help to clarify mechanisms of rejection. New immunosuppressive drugs may improve graft survival and reduce the incidence and progression of chronic rejection.

ABO Blood-Group System↗
PubMed1993

Factors influencing anaemia in dialysis patients. A special survey by the EDTA-ERA Registry.

The European Dialysis and Transplantation Association-European Renal Association (EDTA-ERA) Registry conducted a special study on anaemia in dialysis patients because it seemed important to elucidate the various factors that influence the degree of anaemia and the use of regular transfusions in dialysis patients before the introduction of recombinant human erythropoietin (rHuEpo) for larger groups of patients. In a 20% sample of all patients recorded to have been dialysed throughout 1987, statistically significant associations could be found by multifactorial analysis between haemoglobin (Hb) concentration and age, sex, primary renal disease, type of treatment, hours of dialysis per week, and number of years on renal replacement therapy. The type of dialyser membrane did not seem to play a role (although there was weak evidence of an effect of the dialyser). Mean Hb concentration for dialysis patients differed between countries as did the transfusion policy. In view of the high costs of the rHuEpo treatment and potential side-effects, factors such as method of dialysis and hours of haemodialysis per week should be taken into consideration in the treatment of anaemia in dialysis patients.

Adolescent↗
PubMed1992

Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats.

The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.

Adjuvants, Immunologic↗
PubMed1992

Hyaluronic acid accumulation; the mechanism behind graft rejection edema.

Hyaluronic acid (HA) is an important stabilizing consistuent of the loose connective tissue and regulates water homeostasis. Thus, excessive accumulation of HA in interstitial tissue immobilizes water and may thereby contribute to interstitial tissue edema. By the use of biotin labelled core protein and an avidin-enzyme system, we visualized HA in grafted rat kidney, rat heart, rat small bowel and also in human kidneys. By an extraction procedure the tissue amounts of HA were measured in the experimental grafts. Simple techniques for measuring water content were also employed. The extracellular amounts of HA increased between 100% and 350% in rejecting tissues as compared to syngeneic controls. The relative water content also increased and correlated well with the HA accumulation. The clinical value of these experimental observations was confirmed in human transplantation where rejecting kidney allografts demonstrated a highly significant increase in HA staining in the interstitium as compared to non-rejecting biopsy specimens. We therefore concluded that transplantation edema--a key features of graft rejection--is regulated by the accumulation of HA not only under experimental conditions but also in the clinical setting.

Animals↗
PubMed1992

Is repeated mismatching at regrafting deleterious?

We reviewed our clinical experience of allowing kidney regrafting with a repeated HLA mismatch. We also permitted a weakly positive B-cell cross-match. All patients who received a second or subsequent renal graft (n = 92) between January 1985 and June 1990 were analysed for graft survival. The overall 1-year graft survival was 70%. A repeated mismatch occurred in 29 of the patients at at least one HLA locus and their 1-year graft survival was 66%. The balance of the regrafts (63) were performed without a repeated mismatch, and their 1-year graft survival was 70%. Even a weakly positive B-cell cross-match was deleterious; when a grafting with a repeated mismatch was performed only one out of five grafts survived. Our results indicate that retransplantation of renal grafts with a repeated mismatch in the HLA A or B locus can be performed without a negative influence on transplant outcome provided that both the T- and B-cell cross-matches are negative.

Graft Survival↗
PubMed1992

Enhancement of the effect of low-dose cyclosporin A by sulphasalazine in prevention of cardiac allograft rejection in the rat.

Sulphasalazine (SASP) is an immunomodulatory compound with disease-modifying activity in ulcerative colitis and in other autoimmune disorders. SASP was previously shown to prolong the survival of heart allografts in rats treated with cyclosporin A (CyA) for 9 days after transplantation. We have now evaluated whether SASP also exerts a beneficial effect under continuous treatment with CyA, when CyA is discontinued after 14 days, or alone if given 10 days prior to transplantation. Cardiac grafts were transplanted from PVG donors to Wistar/Kyoto recipients using an accessory cervical heart transplantation technique. Rejection was defined as the absence of palpable contractions and occurred in the control group in a very reproducible manner on day 8 or 9. SASP alone was given orally (100 mg/kg body weight) starting 10 days before transplantation and resulted in a minor prolongation of graft survival. When SASP was given in addition to oral CyA (1 mg/kg or 2 mg/kg from day 0 to rejection) there was a significant prolongation in graft survival [from medians of 8 (range 6-11) and 9 (range 8-11) days, respectively, to medians of 10 (range 8-15) and 12 (range 11-15) days, respectively]. When SASP was given from day 0 to rejection, in addition to a schedule of oral CyA (10 mg/kg) for 15 days, there was no prolongation of graft survival [median of 30 (range 26-42) days vs median of 32 (26-38) days]. The data show that SASP acts as a weak immunosuppressive agent which enhances the effect of CyA given at a low dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗