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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chemical Physics Letters 90 (1982), S. 17-21 
    ISSN: 0009-2614
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 93 (1998), S. s051 
    ISSN: 1435-1803
    Keywords: Key words Anti-hypertensive treatment – AT1 receptor blocker – candesartan cilexetil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The main goal of the treatment of hypertension is to decrease cardiovascular morbidity and mortality. Since this has been demonstrated for betablocker and diuretics only, other antihypertensive agents should be recommended for initial single-drug therapy only if they demonstrate that their antihypertensive potency, and their tolerability is at least comparable to that of the other established drug classes. From this latter perspective AT1 blockers should become one of the most favored anti-hypertensive drugs, since it can be shown that their efficacy is comparable to all other classes of antihypertensive drugs and their tolerability is undoubtedly better. Candesartan seems to be the most efficient AT1 blocker with regard to molar potency. Moreover, it has been shown that Candesartan achieves an impressively long duration of action presumably due to its special receptor binding properties with a peak through ratio of more than 0.9. An other advantage of this special AT1 blocker may be its dose response curve which demonstrates a continuous increase of efficacy between 2 and 16 mg daily.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Key words Cyclosporin A ; Drug monitoring; liver dysfunction ; transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Apparent cyclosporin A (CSA) blood levels, as determined by fluorescence polarization immunoassay (FPIA) and enzyme-multiplied immunoassay technique (EMIT), were compared in CSA-treated patients with various degrees of liver dysfunction. Methods: FPIA and EMIT were performed in parallel according to test manufacturer instructions in blood from kidney (n=82), liver (n=96) and heart transplant (n=20) patients. Results: The precision of both techniques was greatest in patients with the highest blood levels, and at each blood level greater for the FPIA than for the EMIT. Apparent CSA blood levels, as determined by EMIT, were typically approximately 70% of those determined by FPIA, indicating greater cross-reaction of the antibody in the FPIA with CSA metabolites. However, the ratio of values determined with EMIT and FPIA was very similar in kidney, liver and heart transplant patients. Among liver transplant patients it was also very similar in those without major alterations of hepatic function and in those with impaired excretory (increased bilirubin and γGT) or synthetic (i.e., reduced thromboplastin time) function. Extended storage of blood samples for up to 10 days did not affect apparent CSA blood level estimates by EMIT in a clinically relevant manner. Conclusions: We conclude that the greater specificity of the antibody in the EMIT for the CSA parent compound does not translate into a clinically relevant advantage for CSA monitoring.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2277
    Keywords: Key words Renal transplantation ; Hyperlipidemia ; Cyclosporine ; Tacrolimus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As more than 90 % of renal grafts retain their function 1 year after renal transplantation, side effects of immunosuppressive therapy gain more and more importance. In a randomised prospective study, we investigated the effects of conversion from cyclosporine A to tacrolimus due to hyperlipidemia in recipients of renal allografts. Fifty-seven patients with stable graft function treated with cyclosporine were randomly assigned to conversion to tacrolimus or continuation of their current therapy and followed for 1 year. Twenty-seven patients were switched and 30 patients remained on cyclosporine A. Cholesterol levels decreased significantly in the tacrolimus group as compared to controls in the intent to treat analysis. When only those patients were evaluated who received cyclosporine or tacrolimus during the whole study, statistical significance was even more pronounced. Triglyceride levels decreased in the tacrolimus group, whereas they increased in controls. Creatinine levels remained stable and no acute rejection was observed. A switch to tacrolimus is a safe alternative in cases of hyperlipidemia after renal transplantation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2277
    Keywords: Key words Kidney transplantation ; diverticulosis ; polycystic kidney disease ; Polycystic kidney disease ; diverticulosis ; kidney transplantation ; Diverticulosis ; polycystic kidney disease ; kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sigmoid perforation due to diverticulitis is a life-threatening complication in the postoperative course of allogenic kidney transplantation. The incidence of diverticulosis is especially high among patients with autosomal dominant polycystic kidney disease (ADPKD). Thus, those who undergo allogenic kidney transplantation represent a high-risk group. The aim of this study was to evaluate the prevalence of diverticulosis in ADPKD patients awaiting renal transplantation and the incidence of bowel perforation following allogenic kidney transplantation due to ADPKD. Within the group of 1128 patients who underwent transplantation between January 1974 and January 1990, there were 46 patients (4.07 %) whose indication for transplantation was ADPKD. There was one patient who developed a sigmoid perforation under postoperative immunosuppression. Surgical treatment was a discontinuity resection of the sigmoid (Hartmann's procedure). The postoperative course was favorable, the bowel continuity has already been restored, and the graft is still functioning well. Fifteen of the 28 (53.5 %) ADPKD patients awaiting transplantation had colon diverticulosis (12 male and 3 female patients). No case of bowel perforation has thus far been observed in 15 of these patients who have undergone transplantation. A sigmoid resection was necessary in one patient due to diverticulitis without perforation. We did not find a higher prevalence of diverticulosis in patients with ADPKD, nor did we see a higher incidence of sigmoid perforation during post-transplant immunosuppression in this study.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2277
    Keywords: Key words Chronic rejection ; lymphocytes ; Lymphocytes ; migration ; chronic rejection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Histological analyses have identified lymphocytes and macrophages as the predominant leukocyte populations that infiltrate organs undergoing chronic rejection. In order to define the time frame of this infiltration, we investigated the in vivo migration pattern of lymphocytes in a well-established rat model of chronic kidney allograft rejection. F344 kidneys were orthotopically transplanted into bilaterally nephrectomized Lewis rats. Recipients were treated with cyclosporin A (1.5 mg/kg/per day) for the first 10 days. After anti-CD18 or vehicle pretreatment, peripheral blood lymphocytes obtained from naive Lewis rats and labeled with 3H-uridine were injected into transplanted rats 12 and 16 weeks after transplantation. Organs were harvested 4, 8, and 12 h thereafter. After 12 weeks, proteinuria developed, accompanied by all signs of chronic rejection including glomerular sclerosis. Labeled lymphocytes rapidly infiltrated grafted kidneys 4 h after injection. Even more lymphocytes had accumulated in the grafts 12 h after injection. After 16 weeks, few lymphocytes had emigrated into the graft at 4 h, while infiltration was most pronounced by 12 h. Pretreatment with anti-CD18 inhibited the influx of lymphocytes. There was no difference between the patterns of lymphocytes derived from naive and transplanted rats. Our results emphasize the importance of endothelial cells in chronically rejecting kidneys for the control of leukocyte influx. β2-integrins may play a central role in determining the transendothelial migration during this process.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2277
    Keywords: Key words Tacrolimus ; Cyclosporine ; Kidney transplantation ; High risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens were compared in a prospectively defined subgroup of kidney transplant recipients from the European, open, multicentre, 2 : 1 randomised, parallel group study. Patients were stratified as high risk for immunological events if they had a panel-reactive antibodies grade greater than 80 % and/or a previous transplant functional for less than 1 year. The primary efficacy variables evaluated were the incidence of acute rejection, steroid usage and patient and graft survival. Safety was assessed based on adverse events and laboratory evaluations. At 1 year, the tacrolimus group (n = 22) had a lower incidence of biopsy-proven acute rejection (31.8 %) and a higher graft survival (86.0 %) than the 11 patients in the cyclosporine group (54.5 % and 72.0 %, respectively). The frequencies of adverse events were similar between the two groups. The tacrolimus regimen appears more beneficial for high risk patients than cyclosporine.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2277
    Keywords: Key words Kidney transplantation ; Hypertension ; Chronic rejection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK → SHR) or an SHR (SHR → SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR → SHR developed a significantly higher blood pressure than BBOK → SHR. Blood pressure in BBOK → BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK → SHR) and SHR → SHR kidneys as compared with the BBOK → BBOK kidneys (P 〈 0.05). Infiltration of ED-1+ monocyte/macrophages and OX19 pan-T-cells was most pronounced in allografts (BBOK → SHR) and was also increased in SHR → SHR as compared with BBOK → BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependentfactors are of greater important.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2277
    Keywords: Key words Cystatin C ; Diagnostic test ; Glomerular filtration rate ; Kidney transplantation ; ROC curve ; Sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The performance of serum cystatin C as a screening marker of reduced creatinine clearance in renal transplantation was evaluated and compared to serum creatinine. In addition we studied whether cystatin C accurately reflects creatinine clearance over the entire range of transplant function. Serum cystatin C, serum creatinine, and creatinine clearance were measured in 110 adult renal transplant recipients. Cystatin C detected reduced creatinine clearance with the high sensitivity of 95 %. Serum cystatin C and serum creatinine did not differ regarding 90 and 95 % sensitivity, derived from the receiver-operating characteristics plot. We demonstrated a strong correlation and linear association between 1/cystatin C and creatinine clearance over the entire range of transplant function, equivalent to that of 1/creatinine. In summary, serum cystatin C accurately reflects creatinine clearance over the entire range of transplant function and is as efficacious as serum creatinine to detect reduced creatinine clearance in renal transplant recipients.
    Type of Medium: Electronic Resource
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