Improvement of liver function in a paediatric patient with biliary cirrhosis after triple immunosuppression with Mycophenolate following renal transplantation.
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Child↗
Biomedical subjects
G Kirste
Publications and source records attributed to G Kirste.
Unusual cause of early graft dysfunction after kidney transplantation.
BACKGROUND/AIMS: Transplant renal artery stenosis usually develops in the later period after renal transplantation and is usually due to atherosclerosis and fibrosis at the anastomosis. A kinking renal artery stenosis, however, is a rare cause of early graft dysfunction. METHODS: In a 34-year-old-man early graft failure developed within 1 week after kidney transplantation. In the presence of histologically proven ischemic damage an arterial kinking stenosis was diagnosed by color Doppler sonography. Selective arteriography confirmed the sharp kinking of the transplant renal artery; however, a significant stenosis could not be visualized by arteriography. RESULTS: Due to progressive loss of renal function surgical resection of scar tissue in the kink of the transplant artery and nephropexy was performed. Immediately thereafter graft function and blood pressure significantly improved so that the successful clinical outcome of this unusual case of early graft failure confirmed the relevance of the arterial kinking stenosis. CONCLUSIONS: In this unusual case of early graft dysfunction relevant kinking renal artery stenosis could not be adequately visualized by arteriography, although color Doppler sonography clearly demonstrated the stenosis. Therefore, both methods should be considered if parenchymal causes of graft dysfunction are excluded by biopsy and a kinking renal artery stenosis is suspected.
Adult↗
Glycoprotein B genotype correlates with cell tropism in vivo of human cytomegalovirus infection.
Human cytomegalovirus (HCMV) strains can be classified into four genotypes of the glycoprotein B (gB). In a previous study, the gB genotype 1 was found more frequently in bone marrow transplant recipients with nonfatal HCMV infection than in patients who died from HCMV disease [Fries et al. (1994): Journal of Infectious Diseases 169:769-774]. The distribution and cell tropism of different gB types in vivo were investigated. The gB type of HCMV was determined in blood or urine specimen from 76 organ and 47 bone marrow transplant recipients using PCR and restriction fragment length polymorphism (RFLP). The leukocyte populations (polymorphonuclear leukocytes, monocytes, T lymphocytes, non-T lymphocytes) of 20 viremic patients were purified by a fluorescence-activated cell sorter (FACS) and examined for HCMV infection by PCR. Sequence analysis of four randomly selected strains showed that gB types were similar to published sequences and no atypical gB types were found. Within the compartments blood and urine, the gB types were almost equally distributed, whereas the gB type 1, in contrast to gB types 2 and 3, did not infect T lymphocytes in vivo. These data show that the gB type correlates with viral tropism in vivo and thus provides further evidence that the gB variation may indeed influence the virulence of HCMV.
Bone Marrow Transplantation↗
Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.
BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.
Blood Transfusion↗
Flow cytometry cross-match: a method for predicting graft rejection.
Long-term graft survival is mainly influenced by early graft rejection and posttransplant graft function. The ability of both complement-dependent cytotoxicity cross-match (CDC) and flow cytometry cross-match (FCXM) to predict acute rejection episodes has been evaluated by cross-matching 40 patients who received cadaveric kidney transplants, before (current serum) and after transplantation (on days 1, 7, 14, 21, 28, 60, and 90). Of the 40 patients, all of whom had a negative CDC before transplant, seven patients had a positive FCXM before transplant: five of them (5/7=71.4%) experienced severe rejection within 2 months after transplantation. In patients with a negative FCXM before transplant, the incidence of acute rejection was lower (25.8%). Pre-transplant FCXM recipients who had a positive FCXM after transplant, experienced more frequent rejection (38.5%) than those pre-transplant FCXM recipients who never had a positive FCXM (15.8%). With respect to the incidence of acute graft rejection, no difference was found between patients who had a positive CDC after transplant and those who had a negative CDC after transplant. Patients who had a positive FCXM before transplant had significantly higher creatinine levels within the first month after transplant. Immediate onset of function and accelerated lowering of the creatinine level were found to be more frequent in patients who had a negative FCXM before transplant. As early graft rejection is the largest contributing factor for the development of chronic rejection and, therefore, of graft loss, we regard FCXM as a sensitive method for predicting long-term prognosis and graft survival, due to its competence in predicting both restricted graft function and early acute rejection, in particular.
Complement System Proteins↗
Determinants of intrarenal Doppler indices in stable renal allografts.
Color Doppler sonography has been introduced for graft monitoring after renal transplantation. Little is known, however, about independent factors that have an impact on intrarenal Doppler indices as indicators for transplant dysfunction. Therefore, in this study, potential determinants of the resistive index (RI) and of the pulsatility index (PI) in 110 patients with stable renal allografts were studied. The mean RI and PI were 0.70 +/- 0.07 (range, 0.53 to 0.88) and 1.36 +/- 0.21 (range, 0.91 to 1.98), respectively. In multivariate regression analysis, RI and PI correlated significantly with age and arterial pulse pressure of the recipient. There was no correlation with donor age, heart rate, mean arterial blood pressure, and cyclosporine trough levels. Furthermore, parameters of kidney function, such as serum creatinine concentration, creatinine clearance rate, 51Cr-ethylenediaminetetraacetate clearance rate, and proteinuria, showed no significant correlation with the Doppler indices. The data indicate that intrarenal Doppler indices of the grafts are hemodynamic indices, primarily depending on the recipient-related vascular compliance rather than on the function of the graft. Therefore, only intraindividual comparison of the Doppler indices may be useful to detect potential changes of graft resistance during long-term follow-up.
Adolescent↗
Human cytomegalovirus glycoprotein B genotypes in renal transplant recipients.
Based on sequence variation of the glycoprotein B (gB) gene, human cytomegalovirus (HCMV) strains can be classified into four gB genotypes. In a previous study of bone marrow transplant recipients, infection with the gB type 1 correlated with a more favorable clinical outcome than infection with the gB types 2, 3, or 4. The gB type was determined in 60 renal transplant and in 47 bone marrow transplant recipients using PCR and restriction analysis. All HCMV variants in patient specimens could be assigned to one of the four previously described gB types. Two or more specimens obtained from 39 patients were analysed; in 31 of these patients the gB type was the same in all samples. The gB type did not correlate with the clinical outcome or the level of viremia in renal transplant recipients.
Bone Marrow Transplantation↗
Immunosuppressive therapy and hepatitis C virus infection: the clinical course of liver disease.
In a retrospective long-term follow-up study the clinical course of liver disease was examined in renal allograft recipients with hepatitis C virus (HCV) infection and negative hepatitis B surface antigen under immunosuppressive therapy. We compared 42 anti-HCV antibody (anti-HCV) positive patients (study group) to 213 anti-HCV negative patients (control group). All patients received immunosuppressive therapy. Measurements were made of the following: aminotransferases, bilirubin, albumin, gammaglobulins, ascites, spleen diameter, HCV RNA, and anti-HCV antibody. We found all but four anti-HCV positive patients to be HCV RNA positive prior to transplantation. There were no differences in overall mortality or mortality secondary to liver disease or sepsis. Normal liver enzymes were found in 13 (31%) anti-HCV positive and in 137 (64%) anti-HCV negative patients during the whole mean observation period of 65 months (range 10-215). Aminotransferase activity decreased in anti-HCV positive and negative patients during the observation period. Liver function with regard to synthesis and excretion was normal in anti-HCV negative and anti-HCV positive patients. No signs of portal hypertension were observed in the anti-HCV positive group. Neither the different immunosuppressive regimens nor the antirejection therapy led to differences between anti-HCV positive and negative groups with respect to liver function and did not alter the clinical course. We conclude that HCV infection in patients under immunosuppressive therapy causes only a mild liver disease, as determined by clinicochemical and clinical parameters, and that mortality rate is not increased.
Adolescent↗
Results of en bloc kidney transplantation with a new technique.
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Adult↗
Bone mineral density after kidney transplantation. A cross-sectional study in 190 graft recipients up to 20 years after transplantation.
Kidney transplant recipients are exposed to multiple factors that lead to osteoporosis after kidney transplantation. Recent short-term longitudinal studies revealed a strong decline of bone mineral density (BMD) within 1 year after transplantation. The long-term course of BMD after transplantation is still unknown. Therefore, we performed a cross-sectional study to determine BMD in 190 renal graft recipients (mean age 44 years, range 20-71 years) by dual-energy x-ray absorptiometry at various time intervals up to 20 years after transplantation (range 0-237 months). Mean BMD of graft recipients was lower than BMD values of an age- and sex-matched European reference collective at every time of measurement after renal transplantation (P < 0.01). Lowest mean BMD values were measured 12-24 months after transplantation. No loss of BMD occurred after the second posttransplant year beyond the normal age- and sex-dependent decline of BMD. Mean daily prednisone dosage was significantly higher within the first 2 posttransplant years compared with the later posttransplant period (13.1 +/- 6.2 vs. 6.7 +/- 3.4 mg/day). Other drugs or metabolic causes, including daily dosage of CsA, AZA, parathormone level, and graft function, did not show additional important differences before and after the second posttransplant year. Interpreting the results of a cross-sectional study in light of a time-dependent process, we suggest that the preexisting low BMD of kidney transplant recipients at the time of transplantation is further strongly reduced within the initial 2 posttransplant years, probably due mainly to the effect of prednisone therapy. After that time, when prednisone dosage is below a threshold of 7.5 mg/day, only a moderate, normal loss of BMD is apparent, even in patients up to 20 years after transplantation.
Adult↗
Human cytomegalovirus immediate early and late transcripts in peripheral blood leukocytes: diagnostic value in renal transplant recipients.
Peripheral blood leukocytes of renal transplant recipients were investigated to compare the following markers of human cytomegalovirus (HCMV) infection: pp65 antigen by indirect immunofluorescence, viral DNA by nested polymerase chain reaction (PCR), and immediate early (IE) and late (pp150) mRNA by nested PCR following reverse transcription. Sixty-five patients were monitored weekly for 20 weeks after transplantation. In 76 samples from 20 patients positive for HCMV DNA by PCR, HCMV mRNA was detected. Detectable amounts of IE and pp150 mRNA were positively correlated with high numbers of pp65 antigen-positive cells and confirmed the significance of pp65 antigen as a marker for active viral replication. However, with respect to the early diagnosis of HCMV-related disease and monitoring of antiviral therapy, the test for viral mRNA was not superior to the pp65 antigen test.
Base Sequence↗
Human cytomegalovirus immediate early and late transcripts are expressed in all major leukocyte populations in vivo.
Leukocyte populations were purified by fluorescence-activated cell sorter and analyzed for human cytomegalovirus (HCMV) DNA and mRNA using polymerase chain reaction (PCR) and cDNA PCR, respectively. Twenty-two blood samples from 17 patients with active HCMV infection were studied. HCMV DNA was detected most frequently in granulocytes and monocytes but was also found in CD4+, CD8+, and CD19+ lymphocytes. Viral immediate early and late mRNA was found in ficoll-enriched mononuclear cells and polymorphonuclear leukocytes. In 11 samples from 9 patients with active HCMV infection, immediate early mRNA was detected in 8 lymphocyte, 6 monocyte, and 8 granulocyte fractions. Late mRNA was detected in 7 lymphocyte, 7 monocyte, and 9 granulocyte fractions. The presence of viral late mRNA provides strong evidence for infection of these leukocyte populations with HCMV in vivo.
Base Sequence↗
Increase of islet yields obtained from human pancreas donor following change of pH value in collagenase digestion medium.
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Adult↗
Bone fracture and osteodensitometry with dual energy X-ray absorptiometry in kidney transplant recipients.
Kidney transplant recipients have multiple factors leading to osteoporosis. The purpose of this study was to determine the fracture rate after kidney transplantation and the significance of osteodensitometry with dual energy x-ray absorptiometry (DXA) in identifying the risk patients. Bone mineral density (BMD) was measured with DXA in 100 graft recipients (mean interval 63 +/- 53 months after transplantation) and correlated with the incidence of fractures. Fracture rate of peripheral bones increased from 0.009 before transplantation and 0.012 on hemodialysis to 0.032 fractures per patient and year after transplantation. Seventeen fractures of peripheral bones occurred in 11% of the patients within a mean of 103 +/- 59 months after transplantation. Three additional patients had fractures of the lumbar spine. Patients with fractures were characterized by low or low-normal BMD (0.93 +/- 0.23 versus 1.04 +/- 0.17 g/cm2 at lumbar spine), a frequent history of parathyroidectomy (21% versus 6%), and a longer transplant interval (103 +/- 59 versus 57 +/- 49 months). Fractures occurred in patients with low and normal BMD. DXA at the femoral neck proved to be of no value to define patients at risk of fractures. DXA at the lumbar spine also proved to be of limited value for this question. Therefore, alternatively, more sensitive methods of BMD and of bone architecture measurements are necessary for identifying the kidney transplant recipients at risk of fracture.
Absorptiometry, Photon↗
Incidence, diagnosis, and treatment of ureteric stenosis in 1298 renal transplant patients.
Of 1130 patients who had undergone a total of 1298 kidney transplantations, 40 developed a stenosis of the ureter (3.1%). In all of the transplants, the anastomosis between the ureter and the urinary bladder was established as extravesical ureteroneocystostomy. Up until 1984, in cases where an obstruction in the urinary tract was suspected, the diagnosis was made by an i.v. pyelogram or by nuclear scans of the transplant. Thereafter, in 28 patients, in cases of sonographically suspected stenosis of the ureter, the diagnosis was established by means of a simplified Whitaker test. Nearly one-half of the stenoses of the ureter developed within the first 3 months after transplantation. In five patients (12.5%) the stenosis developed significantly later, 3-10 years after kidney transplantation. Seventy percent of the stenoses were localized in the distal third of the ureter. About 75% of the surgically explored stenoses could be corrected by resection and reimplantation of the ureter. During the post-operative follow-up, restenosis occurred in three patients. At present, 62% of all patients whose ureteric stenoses were corrected have well-functioning kidney transplants.
Adolescent↗
Progressive proliferative diabetic retinopathy after transplantation of the pancreas. A case and a review of the topic.
The unusual case history of the development of a progressive diabetic retinopathy despite normal blood glucose after transplantation of the pancreas and despite panretinal laser coagulations is described. A 26-year-old male with diabetic background retinopathy underwent a segmental transplantation of the pancreas in 1988. One year after surgery, a progressive proliferative retinopathy despite normoglycemia was found, which required an intensive panretinal photocoagulation during the following months. However, despite massive retinal coagulations, vitreous hemorrhages and retinal neovascularizations continuously occurred, thus requiring two vitrectomies. After these procedures, visual acuity recovered distinctly. It is suggested that the 'point of no return' for the development of proliferative changes in the retina had been passed at a time when a background retinopathy was still present. The effect of normoglycemia during follow-up of patients with diabetic retinopathy, described in the literature, is compared to this unusual case history.
Adult↗
A new operative technique of paratopic positioning of pediatric en bloc kidneys for transplantation.
Technical difficulties and insufficient renal mass have been reasons not to use en bloc-removed kidneys from organ donors under the age of 3 years. We developed a new technique of paratopic positioning of en bloc-removed kidneys with a prolonging interpositional graft of donor aorta and vena cava. With transperitoneal approach, anastomosis directly to the recipient's aorta and vena cava can be performed. Using this technique, 7 patients have been transplanted so far. They were chosen out of a list of possible recipients according to HLA-match, body weight and blood pressure. All patients had primary function. Anastomosis and renal vessels were controlled by color duplex ultrasound imaging and angiography. Patients developed a stable kidney function. There were no surgical complications except a thrombosed kidney in 1 patient. With the new technique described, transplantation of en bloc-removed kidneys from donors under the age of 3 years can be performed with a low rate of technical complications. Donors of this age should be considered not only as potential liver donors but as kidney donors as well.
Adult↗
Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease.
BACKGROUND: Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance--multiple endocrine neoplasia type 2 (MEN-2) (with medullary thyroid carcinoma and hyperparathyroidism) and von Hippel-Lindau disease (with angioma of the retina, hemangioblastoma of the central nervous system, renal-cell carcinoma, pancreatic cysts, and epididymal cystadenoma). The frequency of these syndromes in patients with pheochromocytoma is not known. METHODS: In an unselected group of patients with pheochromocytoma, we performed pentagastrin tests, parathyroid hormone assays, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, ophthalmoscopy, CT imaging of the abdomen, and ultrasonography of the testes. We also screened members of families with MEN-2 or von Hippel-Lindau disease for pheochromocytoma by measuring plasma and urine catecholamines and plasma chromogranin A and by performing abdominal ultrasonography, CT and MRI, and metaiodobenzylguanidine scintigraphy. RESULTS: Nineteen of 82 unselected patients with pheochromocytomas (23 percent) were carriers of familial disorders; 19 percent had von Hippel-Lindau disease and 4 percent had MEN-2. Prospectively, in 36 of 79 subjects at risk for pheochromocytoma (46 percent), 42 unsuspected pheochromocytomas were found. Overall, there were 130 patients with 185 pheochromocytomas; 43 had von Hippel-Lindau disease, 24 had MEN-2, and 63 had sporadic tumors. The patients with familial and those with sporadic pheochromocytomas differed in mean age at diagnosis (32 vs. 46 years, P < 0.001), multifocal localization (55 vs. 8 percent, P < 0.001), and cancer (0 vs. 11 percent, P = 0.005); but not in the frequency of extraadrenal tumors (24 vs. 16 percent). Thirty-eight percent of carriers of von Hippel-Lindau disease and 24 percent of carriers of MEN-2 had pheochromocytoma as the only manifestation of their syndrome. CONCLUSIONS: All patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. All patients in families with MEN-2 or von Hippel-Lindau disease should be screened for pheochromocytoma, even if they are asymptomatic.
Adolescent↗