Evaluation of various immunosuppressive regimes in second renal transplants.
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Acute Disease↗
Biomedical subjects
F Perner
Publications and source records attributed to F Perner.
Effect of cyclosporine withdrawal on mycophenolic acid pharmacokinetics in kidney transplant recipients with deteriorating renal function: preliminary report.
Mycophenolic acid (MPA) concentrations are lower in transplant recipients receiving mycophenolate mofetil (MMF) and cyclosporine compared with MMF with tacrolimus. It is not clear whether this is due to an effect of cyclosporin or tacrolimus on MPA pharmacokinetics. To study this effect, kidney transplant recipients with deteriorating renal function (n = 5) receiving cyclosporin and steroids were given mycophenolate mofetil over 4 weeks during a run-in phase (1 g/d in week 1, 1.5 g/d in week 2, 2 g/d starting from week 3). From week 5 the cyclosporin dose was reduced, and it was completely withdrawn at week 10. Creatinine, MPA, and MPA glucuronide metabolites (MPAG, AcMPAG) were determined before (week 4) and after (week 11 and week 32) cyclosporin was withdrawn. Cyclosporin withdrawal was associated with increased MPA areas under the curve (AUCs) and predose concentrations in four of the five patients. In contrast, MPAG and AcMPAG AUCs as well as predose MPAG concentrations significantly decreased. Six months after cyclosporin withdrawal, MPA AUC and predose values tended to return to initial values, whereas metabolite concentrations remained low. Cyclosporin discontinuation caused an acute increase in MPA exposure and a concomitant reduction in metabolite concentrations. The results are consistent with the hypothesis that cyclosporin attenuates the enterohepatic recirculation of MPAG/MPA.
Adult↗
Optimization of hepatocyte spheroid formation for hepatic tissue engineering on three-dimensional biodegradable polymer within a flow bioreactor prior to implantation.
We hypothesize that in vitro conditioning of hepatocytes within biodegradable poly-L-lactic acid (PLLA) polymer matrices prior to implantation may increase hepatocyte survival and function after transplantation. The purpose of this study was to optimize the culture conditions of hepatocytes in a pulsatile flow bioreactor. PLLA discs were seeded with rat hepatocytes in a concentration of 2.5, 5, 10, 20 and 40 x 10(6) cells/ml. Seeded discs were exposed to recirculated perpendicular flow of 0, 7, 15, 24, 32, 52 ml/min of supplemented Williams' Medium E and harvested after 6 days in flow culture. Only under flow conditions the hepatocytes formed spheroidal aggregates (SphA) of 50-260 microm in diameter with a liver-like morphology and active metabolic function. The number of SphA was examined by phase contrast microscopy and the reductive enzyme function of the hepatocytes was tested using MTT. Hematoxylin and eosin histology showed vital hepatocytes within the SphA less than 200 microm in diameter but central necrosis in the SphA exceeding this size. Immunohistochemical staining confirmed albumin production of hepatocytes within the SphA. The optimal cell seeding concentration was 10 x 10(6) cells/ml with a flow speed of 24 ml/min. SphA of hepatocytes cultured with this flow bioreactor method may prove useful as a functional unit for tissue engineering of an in vivo liver substitute.
Albumins↗
Prediction of early renal graft function by the measurement of donor urinary glutathione S-transferases.
BACKGROUND: We have investigated the possibility of urinary alpha- and pi class glutathione S-transferases (GST-a; GST-pi) serving as a valuable parameter to predict early graft function after transplantation. METHOD: Urinary GST concentrations of 61 donors (DON) and recipients (REC) were analyzed at preoperative, intraoperative, and postoperative periods. We grouped recipients according to the early postoperative graft recovery days. RESULTS: The donor graft function, represented by the donor urinary GST concentration (GST-pi:17,1+/-12 microg/l mmol creatinine (crea); GST-a:14,3+/-10 microg/mmol crea), sustained a loss in comparison to the healthy controls (GST-a; pi< or =1 microg/mmol crea). According to statistical analysis, the donor GST-pi level showed a strong correlation with graft recovery days-pi (r = 0.84; P<0.001). The early graft function cannot be predicted by means of cold ischemia time (22.8+/-3.4 hr), nor handling time (42.4+/-11.1 min), nor even the intraoperative enzyme concentrations. The GST-pi cut off level (12.55 microg/mmol crea) might predict the possible posttransplant graft dysfunction. The discriminative analysis showed that using only DON GST-pi alone could discriminate well between the groups among all grafts in 68%. CONCLUSION: Prognosis is poorer if the donor GST-pi concentration is above 12.55 microg/mmol crea. On the basis of the determination of GST-pi concentration in the donor urine, we can predict graft viability before the surgical procedure with a reliability of 68%.
Adult↗
[Current diagnostic method, prognosis estimation and therapy of papillary thyroid cancer: recommendations of the medical universities and the National Oncologic Institute of Budapest].
Physical examination, cervical ultrasonography (US) and aspiration cytology are the mainstays of the preoperative diagnostics of papillary thyroid carcinoma. For the staging of suspected malignant cases, cervical and mediastinal CT (MRI for inconclusive results) is indicated before any surgery. The end-result of primary treatment is assessed by total-body iodine scintigraphy and the serum human thyroglobulin (hTG) level. For long-term follow-up, physical examination and the serum hTG level are the most reliable tools (6-monthly), supplemented by cervical US and chest X-ray (yearly), and total-body iodine scintigraphy (2-yearly). If these furnish positive results, further examinations may be indicated. In suspected relapses of hTG non-producing and iodine non-accumulating papillary carcinomas, 201thallium chloride or 99mTc-sesta-MIBI (methoxy-isobutyl-isonitrile) scintigraphy, and positron emission tomography with 18fluoro-deoxyglucose or 11C-methionine may be of help. For estimation of the prognosis (cause-specific survival) of the patients, the MACIS score system of the Mayo Clinic is widely accepted, the patients being divided into low-risk and intermediate/high-risk categories. The recommended standard surgical intervention is near-total thyroidectomy (2-4 g residual glandular tissue left at the upper pole of the less-involved lobe), with a central cervical lymph node dissection for diagnostic purposes. In cases of lymph node dissemination, dissection (radical, modified radical, selective or microdissection) of any of the involved compartments (central, right or left cervical, or upper mediastinal) is indicated for therapeutic reasons, the method of which is depending on the extent of the metastatic involvement. Following adequate surgical intervention, no adjuvant radioiodine therapy is indicated for low-risk cases with a tumour of less than 1 cm diameter. For other low-risk or intermediate/high-risk patients, radioiodine ablation (R0N0M0) or a therapeutic radioiodine dosage (R2N1M1) is indicated. In cases at high-risk of local/regional relapse and in radioiodine non-accumulating tumorous cases, external radiotherapy may be applied. Thyroid hormone medication in a TSH suppressive dose is indicated during the first 5 postsurgical years: the goal is to achieve a TSH level below 0.1 (determined by a 3rd generation assay). If no relapse occurs or the case is a low-risk one, following the 5 years, it is enough to maintain the TSH level in a subnormal range (0.1-0.3).
Carcinoma, Papillary↗
Papillary microcarcinoma of the thyroid gland in renal transplant patients.
Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31st of August 1999 1709 cadaver renal allograft transplantations were performed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature papillary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieved even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.
Brain Neoplasms↗
Liver transplantation in Eastern Europe.
The aim of this report is to evaluate the development of liver transplantation in eastern Europe until mid-1998. Representatives of gastroenterological and hepatological societies of the respective countries answered a questionnaire about the most descriptive items of the issue of liver transplantation. The Baltic countries, together with 6 southern Balkan countries, Moldovia, and Belarus, have not developed a program of liver transplantation. In Ukraine, 7 transplantations were performed, with 3 early deaths. In Russia, 31 liver transplantations were performed, with 8 of the last 12 patients surviving short term. In Slovenia, 1 of 2 patients, and in Yugoslavia, 8 of 9 patients survived. In Croatia and Slovakia, 2 patients each died immediately after surgery. The number of liver transplantations is increasing in both Hungary and Poland. In Hungary, 63 transplantations were performed, with a 1-year survival rate reaching 85%; in Poland, 55 adults and 29 children underwent transplantation, with an actuarial 1-year survival rate of 70%. In former East Germany, 4 centers developed their programs since 1992. A total of 196 transplantations were performed, with 1-year survival rates varying from 80% to 89%. The total spectrum of indications for transplantation was standard, with a greater proportion of hepatocellular cancer compared with Eurotransplant statistics. In the Czech Republic, the first liver transplantation was performed in 1983, but it was not until 1994 that the number of procedures increased steeply. Until mid-1998, a total of 182 transplantations were performed. At the Prague Institute for Clinical and Experimental Medicine, we performed 94 transplantations, with a 1-year patient survival rate of 90.6%. There has been rapid development over the last 3 years in the 3 countries of Central Europe. The progress is influenced by the sweeping political and economic changes.
Adult↗
Experimental autologous substitute vascular graft for transplantation surgery.
Vascular complications in liver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs. The patency was followed by palpation and Doppler ultrasound. The grafts were removed after one month. Five grafts remained patent. The Doppler showed good, relatively increased flow (median flow rate: 383 cm/sec) after one month in all of the cases. Slight increase in diameter was present in all cases. By microscopy the five patent grafts showed viable morphology, fibroblasts, smooth muscle cells and thin fibrin layer in the wall. The grafts were lined partially with a neoendothelial monolayer and a thin fibrin layer. In conclusion, this graft presents an acceptable patency rate and low thrombogenicity, and could be useful in transplantation. Further investigations are needed to study the effect of immunosuppression and rejection on long-term morphology and patency of the grafts.
Animals↗
[Ret-protooncogene mutation, verified by molecular genetic methods, in a Hungarian MEN Type 2a family].
Multiple endocrine neoplasia Type 2 (MEN2) is a hereditary tumour syndrome characterized by the association of medullary thyroid cancer, phaeochromocytoma and hyperparathyroidism. It is inherited as an autosomal dominant trait. During the past few years the cloning of the gene responsible for the syndrome, the ret protooncogene, made the molecular genetic diagnosis of the disease possible. In this study we demonstrate the results of the MEN2 mutation analysis performed in three members of a Hungarian MEN2A family. The mutation analysis was carried out according to the method of Dr. W. Hoppner's Laboratory (Hamburg) that is the main centre for MEN2 genetic diagnosis in Germany. Two Members of the family are affected, one suffered from both medullary thyroid cancer and phaeochromocytoma, the other (the first patient's daughter) had only medullary thyroid cancer. We found a ret exon 11 codon 634 mutation, that resulted in the change of TGC to TAC, a cysteine-tyrosine amino acid exchange. We found no mutation in the youngest member of the family. This result is of great clinical significance, because the carrier status of this individual can thus be excluded and, therefore, there is no need for prophylactic thyroidectomy and further clinical screening tests. As molecular genetic diagnosis of MEN2 becomes possible, the uncertain clinical examinations used for MEN2 diagnosis seems to be less important.
Adult↗
Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence.
Dipeptidyl peptidase IV (CD26) is a membrane-associated enzyme that is expressed on the surface of T cells and on the hepatocyte brush border. In a soluble form it is present in serum. CD26 has been implicated in the regulation of T cell activation and in the metabolism of hormones and cytokines. Dipeptidyl peptidase (DPP) activity is elevated in the urine and serum of patients with biliary atresia (BA). To clarify the role of cholestasis in the development of increased serum and urinary DPP/CD26 activity, we studied the mechanism of activity increase in experimentally induced cholestasis of CD26-deficient and wild-type rats. The clinical utility of serum and urinary DPP/CD26 activity measurements was tested in adult and pediatric patients with hepatobiliary diseases and in liver transplant recipients. The results establish CD26-associated serum DPP activity as a novel, clinically useful marker of cholestasis and demonstrate that in contrast with alkaline phosphatase levels, DPP levels do not change in metastatic bone disease. Additionally, DPP activity is useful as a urinary test of cholestasis in infants who are not receiving nephrotoxic medication.
Alkaline Phosphatase↗
Prevention of apoptosis reperfusion renal injury by calcium channel blockers.
Apoptosis has been shown in the literature to be the form of cell death occurring in renal tubular epithelial cells during the reperfusion phase after brief periods of renal ischaemia. In the present study apoptosis was examined in the rat kidney in the first 24 hours after 30 min ischaemia and apoptosis was influenced by administration of the Ca channel blockers Verapamil, Bepridil, Nifedipin and Sensit. Apoptosis was observed in the renal tubular cells two hours after the start of reperfusion and reached in maximum at hour 6. All above mentioned Ca channel blockers decreased the occurrence and degree of apoptosis.
Animals↗
Primary hepatic carcinoid in a renal transplant patient.
There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases were malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression.
Carcinoid Tumor↗
[Importance of endocrine imaging methods in multiple endocrine neoplasia type 2A proved by mutation analysis].
Multiple endocrine neoplasias are rare, inherited disorders. The authors describe a case history of a patient with multiple endocrine neoplasia type 2A, who presented with unusual clinical manifestations. The diagnosis of phaeochromocytoma, which was the first manifestation of the disorder, was greatly facilitated with radiologic imaging methods. The authors review, on the basis of recent data from the literature, the importance of radiologic methods, which improved due to methodological advance. Finally, the authors emphasize the importance of follow-up for early diagnosis.
Diagnostic Imaging↗
[Diagnostic value of glutathione-S-transferase].
The authors evaluated the diagnostic value of the glutathione-S-transferase (GST) enzyme in the medical practice. The GST is widely distributed in human tissues, the majority of the enzyme protein is present in the cytoplasm. GST plays a pivotal protective role against the environmental damages. It can be made a conclusion from the quantity, the localization of the enzyme expression and enzyme forms to the degree of chemical insult suffered by the organism. The increase of alpha GST izoenzyme can reflect the degree of the hepatocellular and renal proximal tubular epithelium damage. The overexpression of pi-class GST represents the injury of bile epithelium and renal distal tubules. Overexpression of GST is associated with tumor appearances and with resistance to cytostatic agents. It was possible to took the enzyme izoenzymes apart, to identify them--hereby to explore their origin--and to detect their quantity with the development of the separation techniques, the immunological and genetical methods. Since the enzyme expression is in direct proportion to the magnitude organs and tissues damage or/and the presence of specific izoenzymes suspects tumor formation, for this reason the monitoring of the GST expression could give a help for the physicians in creating the diagnosis.
Glutathione Transferase↗
Comparative analysis of kidneys retrieved from the same donor and transplanted into different recipients.
We have reviewed the outcome of kidney transplantations where both kidneys retrieved from the same donor were transplanted at our Department and the factors which might be decisive in the outcome. Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. In 360 cases, both kidneys retrieved from the same donor were transplanted at our Department. We evaluated only first transplant cases who were treated with a combination of cyclosporin and prednisolon. After this selection, 248 pairs of kidneys were left for analysis. We divided them into three groups. The first comprised immediately functioning kidneys (135 pairs), the second, no immediate graft function in any of the recipients (29 pairs). The third group was mixed: the kidneys retrieved from the same donor were functioning in one recipient and not in the other, so this group was omitted from the analysis. We therefore analysed the donor factors of age, sex and cause of death. We found no significant difference between the groups relating to the cause of donor death. There was, however a significant difference in the age of donors: those kidneys functioning well in both recipients derived from a younger donor group (16-40 years), 18/58 versus 136/270, P < 0.01, chi 2 = 7.17. There were significantly fewer older donors (41-65 years) in the immediately functioning group than in the other, 38/58 versus 110/ 270, P < 0.001, chi 2 = 11.84. We investigated the number of HLA mismatches, ischaemic time, cytotoxicity index and the type and duration of pretransplantation dialysis. It appears from this analysis that the age of the donor is a significant factor in the short-term outcome of transplanted kidneys. Recipient factors as HLA match, ischaemic time and cytotoxicity index seems to be less important.
Adolescent↗
Evaluation of the state of health of living related kidney transplantation donors.
Renal transplantation is the optimal mode of therapy for patients with end-stage renal disease; the results are even better with living related donors. This procedure, therefore, favours the recipients, but what are the consequences for the donor? At our Department, between 1973 and 1996, 1325 kidney transplantations were performed, 78 from living, related donors (5.89%). We decided to follow up these patients and investigate the function of the remaining kidney and also their current general health status. Thirty donors (38.4%) were investigated. Of these, 25 of had normal blood pressure and 5 were hypertensive, needing antihypertensive treatment. The average age was higher in the hypertensive group (60.2/53.25 years). The time interval since transplantation was longer in the hypertensive group than in the normal one. We carried out a scintigraphy of the kidney with Tc-99mMAG-3. The mean value of the glomerular filtration rate calculated from the MAG clearance was 98.1 ml/min and this value is higher than half of the normal isotope clearance value, i.e. higher then the expected value for a single kidney. We conclude that no impairment of renal function is observed in the living, related kidney donors. In 16.66% a mild hypertension developed. With isotope investigation we found hypertrophy of the remaining kidney. Thus, after a correct preoperative assessment, unilateral nephrectomy has no long-term consequences in healthy donors.
Adult↗
Effect of diet and fluvastatin treatment on the serum lipid profile of kidney transplant, diabetic recipients: a 1-year follow up.
The effect of a cholesterol-lowering diet and subsequent fluvastatin treatment (Lescol, Novartis; 20 mg/day) on serum lipids and lipoproteins was investigated in 21 diabetic patients (eight women, 13 men, age range 31-63 years, BMI 25.9 +/- 4.5 kg/m2) who had undergone successful kidney transplantation. A cholesterol-lowering diet followed for 8 weeks had apparently no effect on serum lipid concentrations. Fluvastatin applied afterwards for 12 months significantly decreased the total cholesterol, triglyceride and LDL cholesterol levels from 7.7 +/- 0.94, 2.84 +/- 0.85 and 4.87 +/- 1.05 mmol/l to 6.40 +/- 0.74, 2.64 +/- 0.86 and 3.52 +/- 0.69 mmol/l, P < 0.001, < 0.05 and < 0.001, respectively, while the level of HDL cholesterol increased from 1.12 +/- 0.28 to 1.52 +/- 0.39 mmol/l, P < 0.001. Serum concentration of lipoprotein(a) remained unchanged. The serum level of apolipoprotein-A1 increased from 1.52 +/- 0.28 to 1.83 +/- 0.29 mmol/l (P < 0.01) and that of lipoprotein-B decreased from 1.37 +/- 0.20 to 1.20 +/- 0.36 mmol/l (P < 0.05). These maximum changes were achieved by the 12th week of fluvastatin treatment, and no further significant change was observed in the remaining part of the year. The other parameters that could have influenced lipid metabolism (doses of diuretics and steroid, daily dose and serum level of cyclosporin, kidney function, degree of proteinuria, HbA1c, etc.) remained unchanged throughout the study. Thus, the improvement in lipid concentrations can be ascribed exclusively to fluvastatin. No side effects were observed during the 1-year follow up. Liver enzymes and CPK remained within the normal reference limits. Fluvastatin proved to be an effective and safe drug for treating the dyslipidaemia of transplanted patients receiving steroid cyclosporin immunosuppression.
Adult↗
Long-term related kidney graft survival in high-risk patients after monitored donor-specific transfusion protocol.
Altogether 57 patients were included in the related kidney transplantation program. Forty-four recipients were mixed lymphocyte culture (MLC) negative or slightly positive (SI < 7) against their mother/father donor, and most of them showed Fc gamma RII [erythrocyte antibody inhibition (EAI)] blocking antibody in their sera as the consequence of previous random transfusion. Thirteen patients showed significantly high MLC reactivity against their prospective parent donor (SI > 7) and had no EAI blocking antibody in their sera. The latter group was immunized either by buffy coat or purified platelets obtained from their donor in general two or three times at biweekly intervals. The indication for transplantation of donor-specific transfusion (DST)-treated patients was based on the appearance of EAI antibody and a significant reduction in the MLC reactivity (9 patients). DST patients had 100% kidney graft survival for 5 years and the DST untreated ones 75%. Suggested responsible factors for this observation are the haploidentity in HLA and the induction of suppressive immune regulation by DST.
Adult↗