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Biomedical subjects

J Lácha

Publications and source records attributed to J Lácha.

At least 37 records · Page 2Linked to original sources
PubMed2000

Withdrawal of steroids from triple-drug therapy in kidney transplant patients.

BACKGROUND: In renal transplant patients with stable graft function, triple-drug immunosuppression may not be necessary, while withdrawal of steroids may eliminate side effects. The primary aim of this study was to assess the risk of rejection after steroid withdrawal. METHODS: A total of 88 patients with stable graft function and serum creatinine <160 micromol/l, treated with cyclosporin A, azathioprine and prednisone were randomized into group A (n=46) with a gradual prednisone reduction to zero in the course of 6 months, and group B (n=42) on triple-drug therapy without change. At the time of randomization, fine-needle aspiration biopsy (FNAB) was carried out in all of the patients. After stopping steroids, the patients were followed up for a period of 12 months. RESULTS: Four patients failed to complete steroid withdrawal, three due to rejection, and one due to leukopenia. The proportion of rejection in three patients in group A (6.6%) was not significantly different from rejection in two patients in group B (4.8%). The mean value of serum creatinine was not significantly different in both groups in the course of follow-up. A finding of some degree of immunological activity in FNAB was made in four patients in each group, but none of these patients developed rejection. Compared with group B, significant decreases in serum cholesterol and blood leukocytes were observed in group A. Prednisone withdrawal did not have any influence on hypertension and serum triglycerides. CONCLUSIONS: Gradual withdrawal of steroids is not associated with a higher risk for rejection and has a beneficial effect on serum total cholesterol levels. FNAB was not a useful tool for predicting rejection.

Adult↗
PubMed1999

Serum procalcitonin concentrations in transplant patients with acute rejection and bacterial infections.

Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections. PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome. The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response. PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples. Normal serum levels were in the range of 0.08-0.6 ng/ml. Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients. Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods. Good response to antibiotic therapy was associated with a decline in serum PCT concentrations. Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels. Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max. 7 ng/ml). We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation.

Bacterial Infections↗
PubMed1999

[A negative interference effect of pathologic levels of bilirubin on the determination of serum creatinine].

BACKGROUND: Negative interference of bilirubin with assessment of creatinine concentration is generally known from the biochemical aspect. The objective of the presented work was to find the bilirubin level and creatinine concentration where this phenomenon has actually a clinical impact. METHODS AND RESULTS: In 200 samples selected at random the bilirubin and creatinine levels were examined by the classical Jaffé method and a method where the effect of bilirubin is suppressed. After dividing the group into 8 sub-groups by bilirubin and creatinine concentrations it was revealed that the interference plays a statistically significant role (p < 0.01) already at total bilirubin concentrations above 70 mumol.l-1. In abnormal creatinine levels the interference is manifested only at bilirubin concentrations above 150 mumol.l-1 (p < 0.001). The degree of interference in the whole group is directly proportional to the bilirubin level (r = 0.5497, p < 0.001). CONCLUSIONS: At bilirubin levels above 70 to 150 mumol.l-1 its interference with assessment of the creatinine concentration can be so significant that it must be taken into account when evaluating the patient's renal function.

Bilirubin↗
PubMed1999

Ultrastructure of rat aortic grafts.

This study compares the ultrastructure of three syngeneic and three allogeneic grafts of rat abdominal aorta (Lewis to Lewis and BN to Lewis, respectively); the tissue was sampled three months after transplantation (TPL). The endothelial plate was preserved and mononuclear cell adherence was absent. In syngeneic grafts the intima and media remained close to normal with well-preserved smooth muscle cells (SMC). The thickened allograft neointima consisted of elongated spindle cells and rich intercellular matrix. The cells were typical SMC without apparent signs of dystrophy or degeneration. On the other hand, most SMC of the media showed complete disruption and disorganization of membrane and organelles suggestive of accomplished necrosis. However, the framework of elastic lamellae was preserved, without apparent ruptures or lytic changes. Intraintimal migration of medial SMC was not recorded while some cytoplasmic strips were seen to extend across the outer elastic lamella (possible rudimentary outgrowth of SMC?). Lymphocytes and histiomonocytic cells (macrophages) were found in the adventitia but not in the destroyed media. Thus electron microscopy elucidated the histological picture of "anuclear allograft media" and confirmed the predominance of SMC in the thickened neointima. However, signs of the mediointimal SMC invasion were not apparent three months post TPL.

Animals↗
PubMed1999

Morphology and immunohistochemistry of rat aortic grafts.

Allotransplantation (TPL) of the abdominal aortic segments of BN donors was performed in 32 Lewis recipients with or without cyclosporin A (CyA) immunosuppression, and the vascular changes were compared to those of 10 syngeneic grafts (Lewis-->Lewis) and to the autologous rat aortae. The vessels were examined 2, 3, 4 and 5 months post TPL by light microscopy, the thickness of intima and media was measured morphometrically and the cell infiltration of adventitia and intima was assessed semiquantitatively. Thirty-six aortae were examined by three-step enzyme immunohistochemistry (proof of selected differentiation, proliferation, cytoskeletal and connective tissue matrix antigens). The adventitia displayed an intense focal and scattered mononuclear cell infiltration; it was more discrete and focal in the intima. This cellularity persisted in the allografts but disappeared from the intima and was reduced in the adventitia of the isografts after four and five months. Disseminated ED1+ activated macrophages were the most prominent population of infiltrates whereas modest numbers of adventitial ED2+ tissue macrophages remained constant throughout the intervals examined. CD4+ cells (focal and scattered) outnumbered (roughly twice) the scattered CD8+ lymphocytes; both these types were rare in the intima. Leukocyte invasion of the media was lacking (except for scarce isolated CD8+ cells in some allografts). In syngeneic grafts the smooth muscle cells (SMC) of media remained intact and the intimal thickening was slight to absent (about 5 microns) four and five months post TPL. On the other hand, the allograft media underwent severe destructive changes (karyolysis, depletion of alpha-SMC actin, focal calcification and general thinning without rupture or aneurysm). The prominent allograft intimal thickening (70-80 microns) was due to the proliferation of longitudinally oriented myointimal cells (alpha-SMC actin, FD2, PCNA and Ki67+) and an increase in matrix substance (strong metachromasia and positivity of chondroitin-sulfate proteoglycan). The deposition of lipids remained discrete, without atheromatous plaques and mural thrombosis. All changes were comparable in CyA-treated and untreated animals. Thus the main lesions of the allografts were (i) persistent mononuclear infiltration chiefly in adventitia, (ii) destruction of medial SMC, and (iii) intimal thickening by proliferation of myointimal cells. At the postTPL intervals examined the proliferation and intimal migration of medial SMC were not apparent and a morphological correlate of significant anti-medial-SMC cytotoxic attack was lacking.

Animals↗
PubMed1999

[Pregnancy after kidney transplantation].

In the period 1966-1997 renal allografting was performed in 1746 recipients, 244 of whom were women in fertile age. In 32 of them 45 pregnancies were registered. 29 of them (64%) resulted in abortion, which was spontaneous in 4 and medically advised in 25. There were 16 labours, 4 of them free of any complications; of the latter, hypertension was the most frequent one (8). Of the former, 13 were solved by caesarean section and 3 were vaginal deliveries. Of 15 live babies 7 were immature (one died 1.5 year later of renal failure due to microcystic kidneys). No unfavourable effect of pregnancy on prognosis and on long-term graft function was found.

Adult↗
PubMed1999

[Conversion from Consupren sol. to Consupren S capsules in kidney transplant patients].

In a group of patients after transplantation of the kidney with stabilized graft function treated by Consupren sol. combined with prednisone and azathioprin in 20 patients (group A) Consupren sol. was replaced by Consupren S capsules, in 17 patients (group B) Consupren sol. therapy proceeded without any change. To maintain the cyclosporin blood concentration within the therapeutic range it was necessary after the change of drug form in group A to adjust the dosage of the drug in 12 patients of group A while in group B only in one patient (p<0.01). The mean doses and levels of Cy-A however did not change significantly during the three-month investigation period in the two groups and and the bioequivalence of the two preparations was evident. Conversion from Consupren sol. to Consupren S capsules is not associated with the risk of rejection or undesirable effects. It can be implemented at a ratio of 1:1 or 1: the closest dose divisible by 25 (the smallest capsules are 25 mg) and after conversion a check-up or possible modification of the dose is necessary.

Administration, Oral↗
PubMed1998

[Repeat kidney transplantation].

BACKGROUND: The objective of the study was an analysis of results of repeated kidney transplantations (Tx2, Tx3) implemented during the first 29 years of activities of the Transplantation Centre of the Institute of the Clinical and Experimental Medicine in subjects with a different maintenance immunosuppression. METHODS AND RESULTS: The retrospective study pertains to 134 Tx2 and 17 Tx3 in 134 non-diabetic subjects: 43 of them had during Tx1 and Tx2 (1966-1981 and 1966-1985 resp.) immunosuppression on the basis of azathioprin (Aza, sub-group AA), 42 during Tx1 (1972-85), Aza, while during Tx2 (1984-85) immunosuppression on the basis of cyclosporin (CyA, subgroup AC) and 49 both during Tx1 and Tx2 (1985-93 and 1986-95 resp.) CyA (subgroup CC). Compared was survival of grafts by the actuarial method (with regard to all losses regardless of cause) by the end of the 4th year inside the subgroups (Tx2, vs. Tx1 and Tx3 vs. Tx2 in the same subjects) and between subgroups (Tx1 vs. Tx1 and Tx2 vs. Tx2 in different subjects). Moreover in paired investigations the survival of recipients and grafts after Tx2 was compared after immunosuppression on the basis of CyA with the same parameters after Tx1 in different subjects with the same immunosuppression, operated at approximately the same time (n = 81) and survival of subjects with Tx1 + Tx2 on the CC regime regardless whether the second grafts functioned at the time of the last examination, with survival of subjects after Tx1 where after graft failure Tx2 was not performed (n = 34). Prophylaxis with antilymphocyte globulins was not used. Survival of second and first grafts did not differ in any of the subgroups, third grafts survived at the end of the third year more frequently than second grafts (66 vs. 18%, p < 0.01). Second grafts in CC survived more than in AA (55 vs. 28%, p < 0.01). In the paired study Tx2 vs. Tx1 the survival of grafts and recipients was the same (88 vs. 89%, N.S. and 47 vs. 62% resp.), in the paired study Tx1 + Tx2 vs. Tx1 more subjects with Tx1 + Tx2 survived 10 years after Tx1 than subjects who did not have Tx2 (82 vs. 49%, p < 0.05). CONCLUSIONS: A further transplantation of the kidney after functional loss of the first graft is the method of choice: the mortality is low, the probability of several years' function is considerable and the prognosis as regards quality and length of life better than with regular dialysis treatment.

Adult↗
PubMed1998

Flow cytometry cross-match before kidney transplantation in relation to early postransplant rejection.

The aim of this study was to compare flow cytometry cross match (FCXM) results in patients before first kidney transplantation with the incidence of rejection episodes and kidney graft survival after transplantation. Sera of 51 patients obtained immediately before transplantation were tested on spleen cells of respective kidney donors. We found no correlation between a positive FCXM result before transplantation and the occurrence of immunological complications after transplantation.

Czech Republic↗
PubMed1997

[Conversion of cyclosporin A therapy to conventional treatment with diagnostic use of aspiration biopsy in kidney transplantation].

BACKGROUND: Withdrawal of cyclosporin-A from maintenance immunosuppressive therapy involves risk of rejection. The aim of the study was to reduce the risk of rejection and to evaluate the fine-needle aspiration biopsy in predicting rejection. METHODS AND RESULTS: In 41 patients 14.4 +/- 2.6 months after the first transplantation of a cadaveric graft with good and stabilized function, cyclosporine was withdrawn from triple-drug therapy while the doses of azathioprine and prednisone were increased. Prior to the change fine-needle aspiration biopsy (FNAB) was performed and methylprednisolone 500-250-250 mg administered in 3 days. FNAB was repeated after 2 weeks. 39 patients fulfilling inclusion criteria but ineligible for the switch for different reasons served as a control group. Both groups were comparable in demographic and immunological parameters. Within 3 months after conversion, rejection was observed in 3 patients (7%) vs 2 patients (5%) of the control group over a comparable period of time: and within 6 months in 6 patients (15%) and 3 patients (8%) respectively (NS). No relationship between rejections before and after conversion was found. FNAB appeared to have some predictive value for rejection. In all of the 3 patients experiencing rejection, a rejection pattern was present in the 2nd biopsy. CONCLUSIONS: Incorporation of methylprednisolone into conversion therapeutic regime decreased the risk of rejection to 7%. The rejection pattern in the second FNAB after methylprednisolone administration may be predictive for further rejection development.

Biopsy, Needle↗
PubMed1997

Prophylaxis of acute gastroduodenal bleeding after renal transplantation.

Severe gastroduodenal bleeding after renal transplantation is effectively prevented by H2 receptor blockers. New drugs for prophylaxis include proton pump inhibitors. The aim of the present study was to compare the effects of prophylaxis with the H2 blocker ranitidine and with the proton pump inhibitor omeprazole. One hundred seventy-seven consecutive patients were included in a controlled, prospective, randomized study after cadaveric renal transplantation. In one case, ranitidine failed to prevent exsanguination due to duodenal peptic ulcer bleeding. No bleeding was noted in the omeprazole group. There were no significant differences between the groups in hospitalization time, development of renal function, amount of cyclosporin A, prednisone, azathioprine, or methylprednisoline ingested, or laboratory biochemical parameters. We conclude that prophylaxis of severe gastroduodenal bleeding after renal transplantation with omeprazole is effective. Omeprazole is certainly as good as ranitidine; its advantages are a prolonged effect and a simple dosage, independent of graft function development.

Acute Disease↗
PubMed1997

[A single-center controlled clinical study with Sandimmune Neoral after kidney transplantation].

The authors compared in a controlled clinical study two groups of patients after a first renal transplantation treated by triple drug immunosuppressive therapy. In a group of 31 patients the triple combination comprised Sandimmune Neoral. In the control group there were 30 patients who received Sandimmune. No differences were found between the two groups as regards the effectiveness of this treatment and the authors did not confirm a lower incidence of rejections described in patients treated with Sandimmune Neoral. They confirmed, however, a lower interindividual variability of Cy-A levels assessed specifically in patients treated with Sandimmune Neoral.

Cyclosporine↗
PubMed1994

[Early changes in vascular graft rejection in transplanted kidneys: the past and the present].

BACKGROUND: With maintenance azathioprine+prednisone and in biopsies performed exceptionally earlier than in the 4th week (1966-1984, 476 cadaveric kidney transplantations), prevalence of obliterative arteriopathy (OA, transmural arteritis, 4/III/v3 Banff classif.) was 22.1%, with graft loss by rejection within 6 mos. in 89.4%. The aim of this analysis was to study prevalence and prognostic importance of the former and of further early vascular lesions in subjects with maintenance cyclosporin A using biopsies performed as early as in the 1st week. METHODS AND RESULTS: In a retrospective study on 449 transplantation (1987-92, cyclosporin A+prednisone+azathioprine, 64.7% grafts histologically--mostly repeatedly--examined), prevalence and prognostic classification (A-good, B-uncertain, C-poor prognosis) in recipients with OA, with cellular arteriopathy (CA, intimal arteritis, 4/II-III/v2-v3 Banff classif.) and with minimal arterial lesions (MZ) were assessed. Prevalence of OA was found to be 7.1% transplantations, with graft loss by rejection within 6 mos. in 71.9%, and with A:C proportion 25.0%: 62.5%. CA was found in 5.1% and showed A:C proportion 34.7%: 34.7%; in 6/13 cases with repeated histology, OA was later encountered, which is a strong point against its humoral pathogenesis. Prevalence of MZ was 10.9%, with A:C proportion 40.8: 4.1%. CONCLUSIONS: Both OA and CA are related to rejection, while the etiology of MZ remains to be clarified. With cyclosporine, prevalence of OA markedly decreased and its prognosis somewhat improved; secondary prevention is possible when an early diagnosis (early and repeated biopsies) is done and immediate treatment (antilymphocyte globulins) started.

Graft Rejection↗
PubMed1994

[Kidney transplantation and tumors].

BACKGROUND: In conjunction with organ transplantation and subsequent treatment there is a number of influences which potentiate the development and possibly the growth of tumours. This applies naturally also to transplantations of the kidneys. The objective of the present study was to assess the frequency and type of tumours in patients after renal transplantation and compare these results with data of the at present most extensive worldwide register in Cincinnati (CTTR). METHODS AND RESULTS: The authors analyzed a group of 879 patients where within the period between March 21, 1966 and Sept. 29, 1992 a total of 989 renal transplantations were performed from dead relations-934 or from living relations (55); in 38 patients combined transplantations of kidney and pancreas were performed. The group comprised 59% men and 41% women. In the course of years the pattern of prophylactic immunosuppression changed: up to 1984 the basic drug was azathioprin combined with prednisone, during the same year cyclosporin A was introduced as a rule in a triple combination with azathioprin and prednisone; less frequent was the combination of cyclosporin A and prednisone. For antirejection treatment corticoids were used, later supplemented with polyclonal or monoclonal antibodies. During the period 1966-1992 tumourous diseases were diagnosed in 32 patients (3.64%); in two of these patients; combined transplantation of the kidney and pancreas was performed (5.3%). There was no difference in the frequency of tumours in patients with immunosuppressive medication (azathioprin with prednisone-3.80%) and cyclosporin A (3.51%). The mean age of the patients at the time of diagnosis of the tumour was 50.2 years, the interval after transplantation was 42.2 months (in patients treated with azathioprin 57 months, in the group treated with cyclosporin A 29.2 months). As far as the location of tumours is concerned, tumours of the skin predominated 25% (as compared with CTTR where it was 30%), tumours of the patient's own kidneys 21.9% and of the urinary pathways 15.6%, tumours of the gastrointestinal tract 12.5%, lymphomas in 9% (as compared with 15-20% in CTTR), tumours of the lungs 6.25% and other localizations also 6.25%. Some tumours frequently encountered in the population (lung cancer, cancer of the prostate, breast, colorectal carcinoma) are less frequent in patients after transplantation (CTTR); however, this fact was not confirmed by the authors. In renal tumours and tumours of the efferent urinary pathways data on analgetic nephropathy were encountered very frequently. CONCLUSIONS: The prevalence of tumours of various organs in patients after transplantations of the kidneys are not a frequent but a very serious complication. Its causes are multifactorial. The group after renal transplantations in the Czech Repubic has some deviations as compared with CTTR as regards affection of organs.

Female↗