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Biomedical subjects

M Olausson

Publications and source records attributed to M Olausson.

At least 91 records · Page 5Linked to original sources

Mycophenolate mofetil, azathioprine and cyclophosphamide enhanced efficacy combined with cyclosporine in rat cardiac transplantation.

Anti-proliferative drugs have been used for immunosuppression since the introduction of clinical transplantation. Most transplant centres include azathioprine (Aza) and cyclosporine (CyA) in their standard regimens, despite several controlled studies having failed to confirm the benefit of this combination. Aza is still the most commonly used anti-proliferative drug, although no major differences in immunosuppressive or toxic effects have been shown between Aza and cyclophosphamide (Cph). Cph as an adjunct to CyA has never been tested in a randomized study. Recently, mycophenolate mofetil (MMF) has been developed as the most selective inhibitor of T- and B-cell proliferation and promoted as an adjunct to CyA treatment. In the present study, the additive or synergistic effects of these three anti-proliferative agents in combined treatment with CyA have been investigated using a rat cardiac transplantation model in which the immunomodulator linomide (Lin) was included as a potentiator of rejection. As single drug treatment, CyA, Cph and MMF, but not Aza, exerted a beneficial effect on graft survival. This prolongation of graft survival was abrogated when any one drug was administered together with Lin. The addition of MMF, Aza or Cph to CyA plus Lin treatment improved the graft survival significantly, thus demonstrating each of the anti-proliferative drugs to exert additive or synergistic effects in conjunction with cyclosporine. MMF seemed to be the most effective and least toxic of the drugs tested.

Adjuvants, Immunologic↗

Rejection rates in kidney transplant patients with and without IgA nephropathy.

BACKGROUND: Based on graft survival rates it has been claimed that patients with IgA nephropathy have a reduced risk of rejection after kidney transplantation. We wanted to evaluate this hypothesis. METHODS: Certified IgA nephropathy was the original disease in 70 of 874 consecutive kidney transplant patients (8.0%). Eighty per cent of the patients were men. Median age was 37 years, range 9-64. Fifty-three per cent had living donors and 20% of the transplantations were pre-emptive. Non-diabetic patients matched for age, sex, type of donor, and transplant number served as controls. Median follow-up time was 68 months. Duration of treatment for rejection during the first year post-transplant and graft loss due to rejection was recorded. RESULTS: The fraction of patients treated for rejection during the first year was 53% versus 54% of controls and the number of days when any antirejection treatment was given was 5.0 +/- 7.5 versus 5.5 +/- 7.4. Actual 3-year graft survival was 81% versus 80% and the number of grafts lost due to rejection was 9 versus 11. CONCLUSIONS: Rejection rates were not reduced in patients with IgA nephropathy and survival of grafts and patients not better than for matched controls.

Adolescent↗

Steroid-resistant rejection in kidney-transplanted patients: is ATG treatment for three or ten days preferable?

We carried out a randomized prospective trial to compare a 3-day with a 10-day course of antithymocyte globulin (ATG)-(Fresenius) for treatment of steroid-resistant rejection after renal transplantation. The aim was to study whether a short 3-day course was as safe and effective as the longer 10-day treatment. Thirty patients over a 3-year period were included. Patients that did not respond to treatment after 3 days received additional ATG from day 5 to day 10. The graft survival and the proportion of rejections reversed with the treatment were compared. Fifty percent responded promptly in the 3-day group and a further 29% after additional treatment. In the 10-day group, 62% responded to the treatment. There was no significant difference between the groups. We, therefore, suggest that the standard antirejection treatment with ATG could be shortened without an increased risk of graft failure.

Adrenal Cortex Hormones↗

In situ splitting of cadaveric livers. The ultimate expansion of a limited donor pool.

OBJECTIVE: The authors evaluate the safety, applicability, and effectiveness of a new technique for split-liver transplantation. SUMMARY BACKGROUND DATA: Split-liver transplantation offers an attractive way to increase the donor pool for cadaveric liver transplantation. The application of this concept has been hampered by inferior patient and graft survivals and higher complication rates. Without supportive data, the concern about increasing biliary leakage and poor initial graft function persisted. The authors focused on the causes of these complications by presenting a new technique to eliminate these problems. METHODS: Liver splitting was performed in the heart-beating cadaveric organ donor, using the technique described for procurement of the left lateral lobe of a live donor. A detailed description of the technique is presented. A retrospective review of the first 14 transplantations resulting from 7 in situ splitting procedures was collected. The results were compared with 19 conventional split-liver transplants performed during the same period. RESULTS: Six-month patient and graft survivals after in situ split-liver transplantation were 92.8% and 85.7%, respectively. Biliary complications were absent. Postoperative courses were mostly uneventful and characterized by lower peak transaminase levels compared with standard techniques. Early graft function of extrahepatic organs procured simultaneously was excellent. CONCLUSIONS: In situ split-liver transplantation provides superior results, related mainly to reduction of cold ischemic damage of the grafts and avoidance of biliary complications. In situ split-liver transplantation renders graft reduction alone obsolete and opens a donor pool for adults to receive right lobes safely. It allows for long-distance sharing between pediatric and adult liver transplant units because the procedure abolishes ex situ benching and prolonged ischemia time and provides two anatomically perfect grafts with hemostasis accomplished.

Adult↗

Glomerular ultrastructure in kidneys transplanted simultaneously with a segmental pancreas to patients with type 1 diabetes.

BACKGROUND: Pancreas transplantation has been reported to prevent development and progression of diabetic glomerulopathy. STUDY DESIGN: Kidneys transplanted to type 1 diabetic patients were investigated for signs of diabetic glomerulopathy. Biopsies were obtained from 11 patients 2-4 years after simultaneous pancreas and kidney transplantation and from six patients 2-6 years after kidney transplantation alone. During follow-up, glycaemic control was monitored as glycated haemoglobin and, in the pancreas transplant patients, as i.v. glucose tolerance. RESULTS: Measures of glycaemic control were consistently normal in only two pancreas transplant patients. Four had mean k values <1.0. In kidney biopsies from the pancreas transplant patients, thickness of the glomerular basement membrane was 395 (0.13) nm (mean, coefficient of variation), which is higher than normal (324 (0.13) nm, P=0.01) and not different from diabetic patients with kidney transplants alone, 418 (0.15) nm. The mean calculated annual increase in thickness did not differ between patients with and without a pancreas transplant, 26 (0.77) versus 29 (0.54) nm/year. Estimates of the mesangium and mesangial matrix were in the normal range in both groups while the interstitial volume fraction was increased and to a similar extent. CONCLUSION: The increase in thickness of the glomerular basement membrane in kidneys transplanted simultaneously with a segmental pancreas is probably an expression of diabetic glomerulopathy caused by the modest impairment in glucose metabolism present in most patients.

Adult↗

Localization of fibrinolytic activators and inhibitors in normal and atherosclerotic vessels.

UNLABELLED: Local fibrinolytic changes in atherosclerotic arteries have been suggested to influence plaque growth and promote mural thrombosis on ruptured or ulcerated plaques. Increased levels of plasminogen activator inhibitor (PAI-1) have been found in atherosclerotic arteries. In this study tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and PAI-1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemistry. The expression of fibrinolytic regulators was related to the distribution of endothelial cells (EC) and macrophages. RESULTS: t-PA was expressed in vasa vasorum. PAI-1 was positive in endothelial cells, in the media and in the adventitia. Increased expression of t-PA, u-PA and PAI-1 was found in atherosclerotic vessels. t-PA, u-PA, PAI-1 and macrophages were co-localized in plaques. These results support the concept that macrophages can be important in the local regulation of fibrinolysis in atherosclerotic vessels.

Adult↗

Alterations of the post transplant blood lymphocyte phenotype subsets as a marker of rejection in renal allograft recipients.

The postoperative alterations of absolute levels of lymphocyte phenotype subsets in peripheral blood were studied in recipients of living donor renal allografts and in kidney donors. The results were expressed as per cent changes of the preoperative values. The lymphocyte subsets, CD3, CD4 and CD8 cells, decreased to approximately 50% following the surgical trauma, with rapid recovery to preoperative levels within 1 week in kidney donors and in recipients without rejection episodes. In contrast, the T-cell levels in recipients with rejection episodes remained low after 1 week, before clinical signs of rejection, and was predictive for the later occurrence of acute rejection episodes. The T-cell levels in the recipients with rejection episodes remained low during the first 6 weeks, maybe due to the rejection treatments given during this period. The B-lymphocytes were not affected in any of the recipient groups. The alterations observed were not explained by CMV infections, which occurred mainly after the observation period of 6 weeks. In conclusion, the operation per se induced alterations in circulating T-lymphocyte subsets and low T-cell levels after 1 week were predictive of rejection episodes.

Adult↗

Original renal disease in a kidney-transplant population.

Classification of the underlying renal disorder in kidney transplant patients involves some uncertainties. To allow evaluation of the risk of recurrence of renal disease in the transplanted kidney and other characteristics and risks inherent to the specific renal disorder we have investigated the basis for and reevaluated the diagnosis of 1000 consecutive patients who received transplants in Göteborg 1985-1993. In the original registry, 36% of patients had been given the diagnosis chronic glomerulonephritis but the diagnosis was confirmed by biopsy in only half of them, 18% of the total population. Systemic vasculitides and hereditary disorders other than adult polycystic kidney disease which constituted 3% and 6%, respectively, had frequently been overlooked. The term chronic pyelonephritis (15%) covered a variety of conditions including toxic tubulointerstitial disease, but was dominated by those caused by congenital urinary tract formations. Diabetic nephropathy (21%) was the consequence of Type 1 diabetes in 18% and Type 2 or other forms of diabetes in 3%. The proportion of patients with unknown cause of renal failure was 20%. The registry allows identification of small, distinct entities, which may be characterised as regards prerequisites for and consequences of kidney transplantation.

Aged↗