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Biomedical subjects

Manfred Wiesel

Publications and source records attributed to Manfred Wiesel.

14 recordsLinked to original sources
PubMed2003

Psychological consultation before living kidney donation: finding out and handling problem cases.

BACKGROUND: Since 1996, a team of medical psychologists, nephrologists, and urologists at Heidelberg University Hospital has developed a family-oriented consultation procedure for donors, recipients, and family members before living kidney transplantation. Qualitative content analyses of these consultations and their follow-up histories are presented, with particular focus on "problem cases." METHODS: Sixty-seven consultation interviews were explored by rating family interaction, consultee-consultant interaction, decision-making process, and intervention strategies in problem cases. Subsequently, 33 catamnestic interviews 1 year or more after living donation were explored by qualitative content analysis for donor and recipient quality of life, quality of relationships, and health status. RESULTS: Generally, donors show themselves to be eager; recipients appear more reluctant. Expectations focus on spontaneity and a "normal life." Fears are usually expressed not about oneself but about the partner involved. Types of confrontation with possible complications are anxious avoidance, active consideration, and optimistic fatalism. Past family experiences of medical traumata may influence content and level of anxiety. Problem cases are characterized by unilaterally dependent close relationships, unrealistic expectations, anxious avoidance of problem confrontation, and negative experiences with the medical system. At follow-up, the majority are in good medical and psychological health. Few donors and recipients are suffering from disappointed expectations or unexpected treatment side effects. CONCLUSIONS: The Heidelberg consultation setting has proven useful for allowing open discussion about critical issues. In problem cases, prescribing a moratorium instead of rejecting donation helps to relax consultation anxiety. Psychological support after transplantation seems to be indicated for a minority with typical first-year problems.

Attitude to Health↗
PubMed2003

High urine sIL-6R as a predictor of late graft failure in renal transplant recipients.

BACKGROUND: Chronic allograft nephropathy is an important cause of late renal transplant failure. Although numerous studies on cytokines have been carried out, the pathogenetic role of cytokines in chronic renal allograft nephropathy remains unclear. METHODS: In a retrospective study, the authors compared posttransplant plasma and urine cytokine levels (interleukin [IL]-1alpha, IL-1beta, soluble [s] IL-1 receptor [R] antagonist [A], IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta2, and interferon-gamma) in 34 matched pairs of patients with or without late graft failure and in 50 matched pairs with either normal or increased serum creatinine levels and continued stable graft function. RESULTS: Twelve and 6 months before late graft failure, urine levels of sIL-6R were significantly increased (P=0.003 and P=0.01, respectively). Serum creatinine levels were not associated with increased urine sIL-6R. CONCLUSION: High urine sIL-6R appears to be predictive of late graft failure in renal transplant recipients.

Adult↗
PubMed2003

Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients.

BACKGROUND: It has been suggested that increased monocyte responses might play a role in chronic allograft rejection. METHODS: We investigated in vitro monokine responses in 112 patients with long-term stable kidney graft function (ST patients; n=80, non-mycophenolate mofetil [MMF]; n=32, MMF) and 25 patients with chronic renal transplant rejection (CR patients; non-MMF). Interleukin 10 and tumor necrosis factor (TNF)-alpha promoter gene polymorphisms were tested by polymerase chain reaction and sequence-specific primers; antigen-presenting capacity (AC) of monocytes was tested by incubation with staphylococcal superantigens (SEA, SEE, SED). RESULTS: Although non-MMF-based immunosuppression in ST patients did not result in compromised AC or lipopolysaccharide (LPS)-stimulated monokine responses compared with healthy controls, we found MMF therapy to be associated with significantly reduced TNF-R1 expression on monocytes (P<0.001), suppressed AC (P<0.02, SED), and suppressed LPS-stimulated IL-1 beta, IL-10, and TNF-alpha secretion (P<0.01). Coinciding with a significantly higher steroid dosage in CR patients, IL-6 receptor and TNF-R1 expression on monocytes were down-regulated (P< or =0.02) and AC was suppressed in CR compared with ST (non-MMF) patients (P<0.01, SED; P<0.05, SEE). However, LPS-stimulated monokine secretion was not decreased or even enhanced (IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF]; P<0.05). Enhanced in vitro IL-10 responses (>500 pg/mL) were found predominantly in non-MMF-treated patients with the IL-10 genotype GCC (GCC: 23/62 [37%], non-GCC: 2/27 [7%], P<0.005; GCC and non-MMF: 22/47 [47%], GCC and MMF: 1/15 [7%], P<0.005]. CONCLUSION: Steroids and azathioprine did not sufficiently suppress monokine responses, whereas MMF treatment might inhibit chronic graft rejection because of suppression of TNF-R1 expression and vigorous inhibition of monokine secretion. MMF treatment may especially be indicated in patients with the IL-10 "high-producer" genotype GCC.

Adult↗
PubMed2003

Assessment of renal graft function by perioperative monitoring of cortical microcirculation in kidney transplantation.

BACKGROUND: We evaluated the significance of perioperative cortical microperfusion for graft function and long-term prognosis after renal allotransplantation. Thermodiffusion technology was clinically applied for the first time, after previous validation for perfusion monitoring of the renal cortex in pigs. METHODS: A thermodiffusion probe was inserted into the renal cortex in 30 transplant recipients after graft reperfusion. Real-time measurements were recorded until the end of the operation. In 14 patients perfusion was measured daily until postoperative day 7. Microcirculation was correlated to serum creatinine level, scintigraphic findings, and long-term outcome. RESULTS: In primary graft function, intraoperative perfusion was 85+/-7 mL/100 g per min compared with significantly lower values in cases with subsequent graft dysfunction. The best discrimination was defined for a level of 70 mL/100 g per min with a positive predictive value of 88% for detection of good graft function and 86% for nonfunction. Intraoperative perfusion was significantly different in patients with normal grafts, delayed function, and graft loss. Postoperatively, lower perfusion was found in acute tubular necrosis; a significant correlation could be noted between microcirculation and perfusion index measured by nuclear scanning (r=0.78, P<0.01). Living-related grafts were characterized by higher intraoperative perfusion and superior graft quality. CONCLUSION: Thermodiffusion could be clinically applicable for the perioperative monitoring of renal graft perfusion. Intraoperative reduction of cortical microcirculation has a high predictive value with respect to detection of delayed renal function. Postoperatively, impaired renal microperfusion is associated with acute tubular necrosis. Living-related donor grafts show less microcirculatory alteration than cadaveric kidneys.

Adolescent↗
PubMed2003

Pediatric renal transplantation with mycophenolate mofetil-based immunosuppression without induction: results after three years.

BACKGROUND: Mycophenolate mofetil (MMF)-based immunosuppression has reduced the acute rejection rate in adults and in children in the early posttransplantation period. Three-year posttransplantation results have been reported for adults but not for children thus far. In the present open-labeled study, patients 18 years old and younger were evaluated prospectively for up to 3 years after renal transplantation (RTX). METHODS: Eighty-six patients receiving MMF in combination with cyclosporine and prednisone without induction were evaluated for patient survival, transplant survival, renal function, arterial blood pressure, adverse events, and opportunistic infections. These patients were compared with a historic control group (n=54) receiving azathioprine (AZA) instead of MMF. RESULTS: Patient survival after 3 years was 98.8% in the MMF group and 94.4% in the AZA group (NS). Intent-to-treat analysis of graft survival demonstrated superiority for MMF (98% vs. 80%; P<0.001). Cumulative acute rejection episodes occurred in 47% of patients in the MMF group versus 61% in the AZA group (P<0.05). Renal function was not significantly different, neither after 3 years nor in the long-term calculation. Antihypertensive medication was administered to 73% to 84% of patients, similar in both groups. Opportunistic infections were recorded only for MMF. Infection rates were comparable to those reported in adults. CONCLUSIONS: These results suggest that MMF is safe and beneficial as a longer term maintenance immunosuppressive drug in children and adolescents.

Acute Disease↗
PubMed2003

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

BACKGROUND: Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. METHODS: We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. RESULTS: Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). CONCLUSIONS: sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

Acute Disease↗
PubMed2003

The effect of ATG on cytokine and cytotoxic T-lymphocyte gene expression in renal allograft recipients during the early post-transplant period.

BACKGROUND: Despite the long history of ATG use, the exact in vivo mechanism of action remains unclear. In the present study, we analyzed the effect of ATG-induction therapy on expression of 10 immunologically relevant genes in the early post-transplant period. METHODS: Eight renal allograft recipients received post-transplant prophylactic ATG treatment on 10 consecutive days and an additional three patients received treatment on 5, 6, or 7 consecutive days, respectively. Gene expression was measured at the beginning and the end of therapy and normalized to a control gene using Taqman real-time PCR methodology. Results were compared with those of matched control patients. No patients were diagnosed with rejection. RESULTS: ATG-treated patients showed decreases in the expression of cytotoxic T cell genes perforin (-56%, p = 0.03) and granzyme B (-45%, p = 0.01) and cytokine gene IFN-gamma (-75%, p = 0.005), and significant increases in the expression of cytokine genes IL-7 (550%, p = 0.04), IL-10 (275%, p = 0.01), IL-15 (417%, p = 0.03), TNF-alpha (615%, p = 0.01), and TGF-beta (235%, p = 0.02). No significant changes were observed in the control group, with the exception of a decrease in IL-10 expression (-42%, p = 0.01). There were no significant changes in IL-12 or Fas-L expression in either group. CONCLUSION: ATG-induced decreases in the expression of IFN-gamma, perforin, and granzyme B and increases in IL-10 and TGF-beta might be considered beneficial to the recipient, whereas increases in the expression of IL-7, IL-15, and TNF-alpha genes might be involved in immunological processes not effected by ATG that may harm the transplant in the long term.

Adult↗
PubMed2003

Serial peripheral blood perforin and granzyme B gene expression measurements for prediction of acute rejection in kidney graft recipients.

In the present study we investigated whether peripheral blood gene expression measurements may serve as an early and non-invasive tool to predict renal allograft rejection. Peripheral blood was collected twice weekly after transplantation and gene expression was measured using real-time polymerase chain reaction (PCR). Recipients with acute rejection (n = 17) had higher levels of perforin and granzyme B transcript on days 5-7, 8-10, 11-13, 17-19, 20-22, and 26-29, as compared to patients without rejection (n = 50, p < 0.05 in all cases). Rejection diagnosis using gene expression criteria, determined with receiver operating characteristic (ROC) curves, was possible 2-30 days before traditional diagnosis (median 11 days). The best diagnostic result was obtained from samples taken on days 8-10, with a specificity of 90% and a sensitivity of 82% for perforin, and a specificity of 87% and sensitivity of 72% for granzyme B. Decreases in perforin (p < 0.01) and granzyme B expression (p < 0.05) were observed after initiation of anti-rejection therapy. Our data indicate that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy.

Biomarkers↗
PubMed2002

Diameter of the infrarenal aorta and the iliac arteries in children: ultrasound measurements.

BACKGROUND: In adults, the diameters of the infrarenal abdominal aorta and the iliac vessels on ultrasound (US) are known. Similar values have not yet been reported in children. The purpose of this study was to establish a nomogram for these diameters in children. Therefore, the aim is to delineate another factor to limit intraoperative graft lost. METHODS: Studies were performed in 176 healthy children from 1 to 16 years of age. The diameters of the aorta and iliac arteries were measured by B-mode ultrasound at predefined sites. A correlation of the vessel diameter, age, gender, weight, height, body mass index, and body surface area (BSA) was performed. RESULTS: At all measured points, vessel diameters were significantly (P<0.0001) larger in boys than in girls. There was a significant (P<0.0001) increase of all the vessel diameters over age in both sexes. Vessel diameters correlate positively with age, gender, weight, height, and BSA. The highest correlation was found to be with BSA (r > or = 0.8, P<0.0001). Nomograms for each arterial diameter could be established for males and females separately. CONCLUSION: Normal US values of the diameter of the infrarenal aorta and the iliac vessels have been determined for children. The change in diameter strongly correlates with BSA. The nomograms can be of great help in the pretransplantation assessment of these vessels.

Adolescent↗
PubMed2002

Soluble CD30 as a predictor of kidney graft outcome.

BACKGROUND: In the present study, we investigated whether the soluble form of CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is increased in sera of potential kidney graft recipients. We also investigated whether the pretransplantation serum sCD30 content is related to kidney graft survival. METHODS: Pretransplantation sera of 844 cadaver kidney recipients from three transplant centers in Germany were tested for serum sCD30 content using a commercially available ELISA kit. RESULTS: Kidney graft recipients showed a significantly higher serum sCD30 content than healthy controls (P<0.0001). High sCD30 serum content was associated with graft rejection. The 2-year graft survival rate in recipients with a high pretransplantation serum sCD30 was 68+/-6%, significantly lower than the 86+/-1% rate in recipients with a low sCD30 (P<0.0001). Importantly, high sCD30 was indicative of an increased risk of graft loss even in recipients without lymphocytotoxic alloantibodies. CONCLUSION: These data show that an elevated pretransplantation serum sCD30 reflects an immune state that is detrimental for kidney graft survival.

Adult↗
PubMed2002

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.

Adenocarcinoma↗
PubMed2002

Malignancy after renal transplantation.

Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression.

Adolescent↗
PubMed2002

Functional and morphologic evaluation of congenital urinary tract dilatation by using combined static-dynamic MR urography: findings in kidneys with a single collecting system.

PURPOSE: To assess combined static-dynamic magnetic resonance (MR) urography in the evaluation of congenital urinary tract dilatation in infants and children. MATERIALS AND METHODS: Sixty-two patients with urinary tract dilatation underwent prospective examination with combined static-dynamic MR urography. A combination examination involved use of a static T2-weighted three-dimensional inversion-recovery fast spin-echo sequence and a dynamic T1-weighted two-dimensional fast field-echo sequence with gadopentetate dimeglumine-DTPA and furosemide application. Twelve additional patients underwent examination with only static MR urography. Thus, both image quality and morphologic features were assessed in 74 patients with the use of MR urography. The results were compared with those of ultrasonography and, when available, conventional urography or surgery. In 62 patients, the dynamic sequence was used to calculate split renal function from renograms generated from parenchymal regions of interest and to assess urinary excretion from whole-kidney renograms. Results were compared with those of diuretic renal scintigraphy (DRS) for split function (Spearman rank correlation coefficient) and urinary excretion (kappa coefficient). RESULTS: Stenoses at the ureteropelvic (n = 33) and ureterovesical (n = 31) junctions and within the ureter (n = 3) and nonstenotic dilatation (n = 23) were clearly depicted, while the normal urinary tract (n = 51) was depicted in its entirety in 47 of 51 examinations. Image quality was considered good or excellent in 95% of the kidney-ureter units. For split renal function, dynamic MR urography and DRS showed significant correlation (r = 0.92, P <.001). For urinary excretion, MR urography and DRS showed strong agreement (kappa = 0.67), with concordant classification of urinary excretion in 59 (81%) of 73 abnormal kidney-ureter units and in all 47 (100%) normal kidney-ureter units. CONCLUSION: Combined static-dynamic MR urography provides high-quality depiction of the urinary tract in infants and children, while allowing accurate determination of single-kidney function and reliable evaluation of urinary excretion.

Child↗