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J Pratschke

Publications and source records attributed to J Pratschke.

At least 19 recordsLinked to original sources
PubMed2000

Activation of the heart by donor brain death accelerates acute rejection after transplantation.

BACKGROUND: Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. METHODS AND RESULTS: Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean+/-SD, 9. 3+/-0.6 days) by their (Lewis) recipients than hearts from living donor controls (11.6+/-0.7 days, P=0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls. CONCLUSIONS: Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.

Animals↗
PubMed2000

Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial.

BACKGROUND: Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation. However, it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation. Therefore, we designed a prospective, randomized study to compare the immunosuppressive efficacy of dual (tacrolimus and prednisolone) and quadruple (tacrolimus, azathioprine, ALG Merieux and prednisolone) induction after liver transplantation. METHODS: After randomization, 120 consecutive patients of primary liver transplants were divided into the dual group (n=59) and the quadruple group (n=61) and followed for a minimum of 3 years. RESULTS: Patient survival at 3 years was 88.2% in the dual versus 94.9% in the quadruple group. Overall 25 patients in each group (41 and 42%, respectively) developed acute rejection. There was no difference in the number and severity of rejections. In each group only four patients required OKT3-therapy, however, although three of four patients in the quadruple group responded to OKT3 and cleared rejection, none of the four patients in the dual group were treated successfully with OKT3 (P<0.02). Rejection in these patients resolved only after additional treatment with mycophenolate mofetil. Adverse events and infections were equally distributed in both groups. Asymptomatic Cytomegalovirus infections were more common in the quadruple group (P<0.02). As of today, only one patient developed posttransplant lymphoproliferative disease (dual group). CONCLUSIONS: The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation.

Adult↗
PubMed2000

Activation of inflammatory mediators in rat renal isografts by donor brain death.

BACKGROUND: Brain death (BD) has been thought to influence the early course of transplanted organs by triggering a series of nonspecific inflammatory events that in turn may increase the kinetics and intensity of the immunological host responses. In this study early nonspecific, cellular, and molecular changes occurring in kidney isografts from BD donors are compared with those from normal anesthetized, ventilated controls. METHODS: After induction of brain death, the animals were mechanically ventilated for 6 hr before organ removal. Only rats with stable blood pressure (mean arterial pressure >80 mmHg) were included. Serum creatinines were measured daily. Representative grafts were harvested 6 hr after brain death and between 1 hr and 5 days after engraftment for morphology, immunohistology, and reverse transcriptase-polymerase chain reaction. The presence of serum cytokines was assessed by enzyme linked immunoabsorbant assay. RESULTS: Serum creatinine levels rose slightly in recipients from BD donors. Serum interleukin-1beta levels increased within 6 hr versus controls (P<0.05). mRNA levels of interleukin-1beta and macrophage inhibitory protein-1 in the kidneys were up-regulated transiently before engraftment (6 hr after BD) and 1 hr after revascularization (P<0.05). By immunohistology, numbers of infiltrating polymorphonuclear leukocytes peaked at 24 hr in parallel with intragraft induction of P- and E-selectin, complement, and other proinflammatory chemokines and cytokines. At 5 days, the isografts from BD donors were highly infiltrated by host leukocyte populations associated with intense up-regulation of their products. In contrast, those from control donors remained relatively normal through this initial follow-up period. CONCLUSIONS: The intense nonimmune inflammation produced in isografts after donor BD may represent the initial stages of a continuum between an initial nonspecific and later immune reactivity, when placed in the context of allotransplantation.

Animals↗
PubMed2000

A model of gradual onset brain death for transplant-associated studies in rats.

BACKGROUND: The relatively few studies that have examined the systemic events after brain death have primarily involved large animals. For more precise definition of the physiology of this central catastrophe and its influence on peripheral organs, we have established a reproduceable model of gradual onset brain death in rats. METHODS: The central injury is induced by graded inflation of a Fogarty catheter placed intracranially under EEG and blood pressure monitoring. The rats were mechanically ventilated for 6 hr before removal of their kidneys. Complications and mortality are discussed. RESULTS: The majority (83%) of the 100 experimental animals could be used as organ donors. After a transient period of autonomic storm, the mean arterial blood pressure remained consistently between 80-100 mmHg, not appreciably different from controls. Despite normotension, the transplanted kidneys from brain dead donors showed a significantly longer interval to regain uniform cortical color and turgor than kidneys from control animals. CONCLUSIONS: We describe a controlled model of gradual onset brain death in the rat in which normotension can be sustained for several hours before the kidneys are removed for transplantation. Despite stable donor blood pressure, ischemia of peripheral organs may explain in part the increased incidence of delayed graft function of cadaver kidneys compared with those from living donors. This model is suitable for transplant-related studies involving organs from donors with irreversible central injury.

Animals↗
PubMed2000

Accelerated rejection of renal allografts from brain-dead donors.

OBJECTIVE: To define the potential influences of donor brain death on organs used for transplantation. SUMMARY BACKGROUND DATA: Donor brain death causes prompt upregulation of inflammatory mediators on peripheral organs. It is hypothesized that this antigen-independent insult may influence the rate and intensity of host alloresponsiveness after engraftment. METHODS: The rates of survival of unmodified Lew recipients sustained by kidney allografts from brain-dead, normal anesthetized, and anesthetized ventilated F344 donors were compared. Brain death was induced by gradually increasing intracranial pressure under electroencephalographic control. Tracheotomized brain-dead animals and anesthetized controls were mechanically ventilated for 6 hours before transplant nephrectomy. The rate and intensity of the acute rejection event were examined by histology, immunohistology, and reverse transcriptase-polymerase chain reaction. RESULTS: Animals bearing kidneys from brain-dead donors died of renal failure secondary to acute rejection at a significantly faster rate than those from anesthetized living controls or anesthetized animals ventilated for 6 hours. Within 3 hours after placement and reperfusion of brain-dead donor grafts, significant neutrophil infiltration was observed, followed by increasing numbers of macrophages and T cells. mRNA of proinflammatory mediators detected in kidneys within 6 hours of brain death and upregulated even before transplantation increased thereafter and appeared to accelerate and amplify host alloresponsiveness, as manifested by the rapid expression of chemokines, cytokines, adhesion molecules, and major histocompatibility complex class II antigens in the engrafted organ. The process evolved in the controls less intensely and at a slower rate. CONCLUSIONS: Donor brain death is a significant risk factor for peripheral organs used for transplantation. The activated state of such organs appears to trigger host immune mechanisms that accelerate the process of acute rejection. The effects of this central injury may explain in part the less satisfactory performance of cadaver organs in human transplantation compared with those from living sources.

Animals↗
PubMed1999

[Lymphoepithelial carcinoma of the extrahepatic bile duct].

A 36-year-old female patient was transferred to our unit for surgical treatment of a biliary tract obstruction. ERC disclosed an obliteration of the common hepatic duct involving the hepatic bifurcation. Primary sclerotic cholangitis and carcinoma of the bile duct could not be confirmed histologically in the biopsy specimens. Tumor markers and autoimmune antibodies were normal. Histological examination of the ductus choledochus during the operation was not conclusive and a malignant lymphoma was considered. The macroscopic appearance comprised obliterative alterations extending to the right hepatic duct. Therefore, resection of the extrahepatic bile duct, right hemihepatectomy and hepaticojejunostomy were performed. The final histological statement revealed a lymphoepithelial carcinoma. The postoperative course of the patient was uneventful, and the patient is in good condition without any signs of recurrent disease 12 months after the operation. This tumor has been described as occurring as a neoplasm of the stomach and salivary glands exclusively and as being of low-grade malignancy. Additional histological evaluations confirmed the diagnosis of lymphoepithelial carcinoma.

Adult↗
PubMed1998

Prompt treatment of initial acute rejection episodes may improve long-term graft outcome.

Acute rejection episodes have been cited as a major immunological risk factor for the development of chronic rejection. To examine the influence of a single rejection event on ultimate graft outcome, acutely rejection rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time Early structural changes (days 3 and 4) were completely reversible, while signs of chronic rejection did become obvious during the long-term follow up. More advanced deteriorated grafts (days 5 and 7) were irreversibly damaged and the rats died shortly after retransplantation. Those results indicate the critical impact of acute rejection episodes on chronic graft rejection. Immediate and aggressive treatment of acute rejection episodes may remove this event as a risk factor for late deteriorating changes.

Acute Disease↗
PubMed1998

Contribution of early acute rejection episodes to chronic rejection in a rat kidney retransplantation model.

Chronic graft rejection represents the single most important risk factor for unsatisfactory long-term results after organ transplantation. In addition to various alloantigen dependent and independent factors, acute rejection episodes have been cited as a major immunological risk factor. However, the effects of acute rejection episodes on long-term graft outcome remains unknown. To examine the influence of a single early rejection event on ultimate graft outcome, acutely rejecting rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. LEWxBNF1 kidney allografts and LEW isografts were removed from their LEW recipients after three, four, five and seven days (N = 12/group/time period) and retransplanted into donor strain hosts. The grafts were followed functionally and harvested four, eight, and 32 weeks later. Urinary protein excretion was measured weekly. Kidneys were examined morphologically and immunohistologically using monoclonal antibodies (mAbs) against macrophages (ED-1), T cells and their subsets (CD5, CD4, CD8), MHC class II expression (OX3) and adhesion molecules (ICAM-1 and LFA-1alpha). The mean standard time +/- SD of non-retransplanted allografts was 14.5 +/- two days; isografts functioned indefinitely. At five and seven days, acutely rejecting allografts showed massive cellular infiltrates associated with extensive necrosis. These changes could not be reversed by retransplantation and the syngeneic recipients later died of renal failure. In contrast, most allografts retransplanted earlier in the process recovered completely when retransplanted after three (12 of 12 allografts) and four (7 of 12 allografts) days. During the subsequent follow-up period, urinary protein excretion was comparable in retransplanted allografts and isografts. The increased mononuclear cell infiltration in non-retransplanted allografts seen at three and four days was only occasionally observed during the follow-up period after retransplantation. Only a few sclerosed glomeruli (approximately 15%), mild arterial changes and minimal cellular infiltrates were observed by 32 weeks, which were similar to that seen in retransplanted isografts. A single acute rejection episode was completely reversible and did not progress to chronic rejection if retransplanted into syngeneic donors when the inflammatory changes are still early. Those results demonstrate the critical effect of alloantigen-dependent events on chronic graft deterioration, and indicate that prompt and aggressive treatment of initial acute rejection episodes are beneficial to protect against late deleterious changes in the graft.

Animals↗
PubMed1998

Orthotopic liver transplantation for hepatic associated metabolic disorders.

Hepatic associated metabolic disorders represent 5% of the indications for orthotopic liver transplantation (OLTX) according to the European Liver Transplant Registry. We studied the outcome of this group at our institution after OLTX and combined liver/kidney transplantation. Between September 1988 and January 1997, 837 OLTXs were performed in 735 patients. Patient survival and graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr, range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7), hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n = 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1), ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering from primary hyperoxaluria type I received combined liver/kidney grafts. Survival rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant lymphoma 5 months after transplantation. One patient required retransplantation 2 months after OLTX following arterial thrombosis and ischemic type biliary lesion. One year after OLTX, all patients demonstrated good graft function, liver grafts (ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/- 15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX, respectively combined OLTX/NTX, represent a successful therapy for hepatic associated metabolic disorders. Survival rates and graft function are similar to those in liver graft recipients for established indications at our institution. OLTX seems to be an excellent treatment for hepatic based therapy resistant neurological disorders.

Adolescent↗
PubMed1997

Treatment of cyclosporine-related adverse effects by conversion to tacrolimus after liver transplantation.

BACKGROUND: Cyclosporine (CsA)-associated side effects include nephrotoxicity, hypertension, neurological disorders, and hyperlipidemia. A considerable share of early and long-term posttransplant morbidity is likely to be drug related. METHODS: In 31 patients with stable graft function, conversion from CsA to tacrolimus was implemented due to nephrotoxicity (n=19), hypertension (n=9), and neurological disorders (n=8). RESULTS: Three months after conversion, a response was evident in 26 patients (84%), whereas 5 patients (16%) were nonresponsive. In 13 of 19 patients (68%) suffering from nephrotoxicity, serum creatinine levels decreased significantly from 2.0+/-0.5 mg/dl to 1.5+/-0.4 mg/dl (P<0.005), whereas in 6 of 19 patients (32%) no improvement was observed. Antihypertensive therapy was reduced in six of nine patients and neurological disorders improved in six of eight patients. When analyzing all patients, average levels of cholesterol and triglycerides were significantly lower after conversion when compared with at the time of conversion (P<0.05) CONCLUSIONS: Conversion to tacrolimus reduced drug-related side effects in the majority of patients, while graft function remained stable. Conversion to tacrolimus may be considered for CsA-related side effects as a potential beneficial approach.

Adult↗