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A Pascher

Publications and source records attributed to A Pascher.

At least 19 recordsLinked to original sources
PubMed2006

Rat cytomegalovirus infection interferes with anti-CD4 mAb-(RIB 5/2) mediated tolerance and induces chronic allograft damage.

In order to assess the role of heterologous immunity on tolerance induction (TI) by signal 1 modification, the influence of rat cytomegalovirus infection (RCMVI) on TI by a non-depleting monoclonal anti-CD4 mAb (monoclonal antibody) (RIB 5/2) in a rat kidney transplant (KTx) model was investigated. Orthotopic rat KTx (Dark Agouty (DA)-->Lewis (LEW)) was performed after TI with RIB 5/2 [10 mg/kg body weight (BW); day -1, 0, 1, 2, 3; i.p. (intraperitoneal route)]. RCMVI (5x10E5 Plaque forming units [PFU] i.p.) was simultaneously conducted to KTx, 50 days after KTx, and 14 days before and after KTx. RIB 5/2 induced robust allograft tolerance even across the high-responder strain barrier. RCMVI broke RIB 5/2-induced tolerance regardless of the time of RCMVI but did not induce acute graft failure during the 120 days follow-up. RCMVI induced a significant chronic deterioration of allograft function (p<0.01) and enhanced morphological signs of chronic allograft damage (p<0.05). Cellular infiltrates and major histo-compatibility complex (MHC)-expression were more pronounced (p<0.05) in the infected groups. RCMVI induced not only RCMV-specific T-cell response but also enhanced the frequency of alloreactive T cells. RCMV interferes with anti-CD4 mAb-induced tolerance and leads to chronic allograft damage. The data we presented suggest a potentially important role of viral infections and their prophylaxis in clinical TI protocols.

Animals↗
PubMed2006

[Intensive care treatment following transplant surgery].

Transplant-related intensive care treatment after transplantation of visceral organs, in Germany traditionally headed by transplant surgeons, is an integral part of postoperative therapy after liver, pancreas, intestinal, and combined organ transplantation, i.e. pancreas-kidney, liver-kidney, and multivisceral transplantation. Apart from adjustment and monitoring of immunosuppressive therapy, as well as common intensive care issues such as cardiopulmonary disease and complications, the avoidance, early detection, and rigorous treatment of transplant-related problems are the focus of surgical intensive care treatment of transplant patients. In the following article, its role after visceral organ transplantation is described regarding the most frequent transplant-related complications such as technical failure, various kinds of infection, and graft failure with different etiologies.

Critical Care↗
PubMed2006

Improved long-term graft survival after HO-1 induction in brain-dead donors.

Brain death (BD) of the donor, a risk factor uniquely relevant for organs derived from cadaver donors, influences organ quality by induction of various inflammatory events. Consequently ischemia/reperfusion injury is deteriorated and acute and chronic rejections accelerated. Donor treatment might be an approach to improve the quality of the graft. The induction of heme oxygenase 1 (HO-1) has been shown to exert beneficial effects in living-donor transplantation models. Therefore, we examined the impact of donor treatment with the selective inducer of HO-1, cobalt protoporphyrin (CoPP), on organ quality and transplant outcome in a standardized BD model in a F344-->LEW kidney transplant rat model. Immediately after BD induction, donor animals were administered a single dose of CoPP (5 mg/kg) and in control groups, HO-1 activity was blocked with zinc protoporphyrin (ZnPP, 20 mg/kg). Recipients of organs from brain-dead donors treated with CoPP survived significantly better than those from untreated brain-dead donors (p < 0.05) and intra-graft analysis showed improved histology (p < 0.05). Blockade of HO-1 with ZnPP decreased the survival rates (p < 0.05) comparable to untreated brain-dead donors. Our results demonstrate that HO-1 induction by one single treatment of CoPP in brain-dead donors leads to enhanced allograft survival.

Animals↗
PubMed2006

Current concepts in gene therapy of the musculoskeletal system.

The purpose of this article is to review the remarkable progress in the field of musculoskeletal system gene therapy. Since the introduction of this concept 15 years much of the preclinical and clinical data have emerged. The original target, rheumatoid arthritis, has been subjected to clinical phase II efficacy protocol, and osteoarthritis gene therapy efficacy is being thoroughly investigated in various animal models. The most promising area of research in this field however, is the tissue repair, because it doesn't require prolonged period of gene expression, local delivery is reasonably simple and it avoids substantial risk associated with systemic delivery, and levels of gene expression don't need to be so finely regulated. Gene transfer is successfully being used to aid the repair and regeneration of bone, cartilage, ligament tendon, meniscus and intervertebral disc. Other potential applications of gene therapy in musculoskeletal system include osteoporosis, aseptic loosening, genetic diseases and tumors. Highly encouraging data gained from these studies have confirmed that gene therapy is a promising therapeutic solution to treat various musculoskeletal system disorders.

Genetic Therapy↗
PubMed2005

[Psychological and somatic aspects of living liver donors: preoperative assessment and postoperative course].

BACKGROUND AND OBJECTIVE: Living donor liver transplantation (LDLT) has been gaining importance in the treatment of end-stage liver disease in adults as a partial solution to the growing organ shortage. Thus far, only few empirical studies have been published on the situation of donors who are faced with the risk of medical complications after resection of the right hepatic lobe. PATIENTS AND METHODS: 87 potential donors were preoperatively assessed in the years 2000 and 2001 at the Charité Berlin. 41 potential donors were excluded, 46 donors (31 women, 15 men, mean age 41 [19 - 67] years) underwent liver surgery and were re-assessed 6 months after the operation. The frequency of postoperative complications and the course of psychosocial parameters were investigated. Donors' moods were analysed with the Berlin Mood Questionnaire, the physical complaints were assessed with the Giessen Complaint Questionnaire. The preoperative interviews of 20 potential donors were analysed according the current social qualitative research methods. RESULTS: In 11 % (n = 10) of potential donors transplantation was not recommended for psychosocial reasons because they showed a marked ambivalence towards the operation. After operation, 22 % (n = 12) of donors had postoperative complications. Most relevant single causes of severe impairment were temporary and reversible biliary leakages from the cutting edge. There were no long- term complications. 26 % (n = 10) of donors showed postoperative high values for anxious depression and physical complaints. CONCLUSIONS: The resection of the right hepatic lobe holds promise of a good psychosocial outcome for most donors, irrespective of donation-related complications. The psychosocial impairment and physical complaints of some donors after transplantation are yet not clearly understood. Further psychosocial studies will be necessary to develop criteria for an evidence based medical care of living donors.

Adult↗
PubMed2005

[Clinical results of intestinal and multivisceral transplantation at the Charité, Berlin. A case series].

BACKGROUND AND OBJECTIVE: Intestinal transplantation (ITx) is the only causal therapy of short bowel syndrome (SBS). Long-term survival after ITx has been improved significantly during the last years. The experience with ITx at the Charite, Campus Virchow Klinikum, are described and discussed. PATIENTS AND METHODS: Twelve isolated ITx and one multivisceral transplantation (including stomach, pancreatodudenal complex, small intestine, liver, ascending colon, right kidney, and adrenal gland) were performed. Mean recipient age was 37.7+/-10.6 yrs (median: 35 yrs; range: 27 - 58 yrs; M:F = 8:5). All patients had irreversible SBS (0 - 30 cm residual bowel length; mean: 11.8+/-11.4 cm; median: 13 cm). RESULTS: 6-months and 1-year patient and graft survival were 85 % (11/13) and 77 % (10/13), respectively. Reasons for graft loss and patient death were necrotizing enterocolitis, severe, muromonab-resistent, acute rejection, and graft ischemia due to complex coagulopathy. All other patients had good long-term outcome. They received enteral nutrition at six hours after operation and were persistently off total parenteral nutrition (TPN) by week two after ITx. CONCLUSION: ITx as established in our centre, with 1-year-patient and graft survival rates of 77 %, reflects current international standard. ITx is complementary to conservative and other operative methods of treating SBS. Referral and indication criteria need wider dissemination to prevent life-threatening complications of TPN.

Adolescent↗
PubMed2005

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation.

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.

Acute Disease↗
PubMed2005

Immunohistochemical analysis of desmoid tumours.

BACKGROUND/AIMS: Although the standard treatment for desmoid tumours is complete surgical resection with wide margins, the optimal adjuvant treatment for recurrent or inoperable disease is unclear, often being based on sporadic immunohistochemical reports with a low number of cases. Therefore, a large immunohistochemical study was performed, to provide a theoretical basis for adjuvant treatment regimens. METHODS: One hundred and sixteen tissue samples from 80 patients (49 female, 31 male; mean age, 34 years; range, 0-83) with desmoid tumours (46 extra-abdominal, 21 abdominal, 13 intra-abdominal) were tested for oestrogen receptors alpha and beta, progesterone and androgen receptors, and somatostatin, in addition to HER2, cathepsin D, Ki-67, and c-KIT by immunohistochemistry. RESULTS: All samples were negative for oestrogen receptor alpha, HER2, and the progesterone receptor. Positive staining for the androgen receptor was found in six extra-abdominal cases. Staining for oestrogen receptor beta was positive in four extra-abdominal, two abdominal, and one intra-abdominal case. Staining for somatostatin was positive in six extra-abdominal, two abdominal, and one intra-abdominal case, and staining for cathepsin D was positive in all cases. Positive staining for Ki-67 was found in 14 extra-abdominal, three abdominal, and three intra-abdominal cases. C-KIT was detectable in one abdominal case only. CONCLUSIONS: The data from this immunohistochemical study show that the published effects of antioestrogens and imatinib mesylate in the treatment of aggressive fibromatoses may not be attributable to oestrogen receptor alpha or c-KIT expression.

Abdominal Neoplasms↗
PubMed2005

Liver transplantation as ultimate tool to treat portal hypertension.

Portal hypertension is a complication of liver cirrhosis that may itself cause complications such as variceal bleeding, ascites and hepatorenal syndrome. There are several options for symptomatic treatment including drug therapy, endoscopy, transjugular intrahepatic portosystemic shunt (TIPS), and various surgical procedures, notably liver transplantation, the only causal treatment. The indication for liver transplantation has to be defined carefully. Progression of the primary disease, evaluation of comorbidity and overall prognosis have to be considered. Conservative symptomatic treatment is used for bridging purposes until liver transplantation can be provided to cure portal hypertension and the underlying primary disease. Careful timing of the transplantation is necessary as well as reorganization of the waiting lists by introducing new priority systems as the Model for End-Stage Liver Disease (MELD) in order to reduce mortality. Furthermore, living donor liver transplantation and split liver transplantation are methods to enlarge the donor pool, and thus accessibility of transplantation to a greater number of patients. This review evaluates the indication of liver transplantation in the treatment of portal hypertension.

Comorbidity↗
PubMed2004

Immunosuppression following intestinal transplantation.

Acute rejection is still the main risk factor following intestinal transplantation. Potent immunosuppression decreases rejection frequency, but may increase immunosuppression-related complications. Isolated small intestinal transplantation was performed in 14 adult patients with short bowel syndromes. Immunosuppression included tacrolimus and rapamycin in combination with steroids for 6 months after ATG or daclizumab induction therapy. In addition to protocol biopsies, cellular immune status and soluble immune parameters were used to guide immunosuppression. CMV and EBV markers were determined on a routine basis. Ten of 14 patients (71%) survived for 1 to 38 months (median 26 months). Eight patients are at home, in good physical condition, completely on enteral nutrition. Among the 5 patients (36%) who developed acute rejection, 2 patients with early postoperative events underwent graft removal and 1 patient died due to multiple organ failure. Two patients developed severe acute rejection episodes at 10 and 24 months following transplantation. Both patients recovered following OKT3 rescue therapy and increased baseline immunosuppression with repeated methylprednisolone and infliximab treatment. Infections included peritonitis (n = 3), pneumonia (n = 3), central line infection (n = 5), urinary tract (n = 2), CMV (n = 2), and EBV (n = 4). Two patients developed anastomotic leaks at the esophageal and coloanal anastomosis. In conclusion, acute rejection episodes can be controlled by potent immunosuppression using tacrolimus in combination with rapamycin. Immunosuppression-associated complications, including infections, were in an acceptable range. However, even late after transplantation, reduction in immunosuppression may lead to severe rejection without major clinical symptoms.

Adult↗
PubMed2004

Isolated adult intestinal transplantation using portal venous drainage.

There is some evidence that portal venous drainage may offer immunologic and metabolic advantages in small bowel transplantation. Isolated small bowel transplantation was performed in 14 adult patients. In all cases, the donor pancreas was transplanted into another patient. During the donor procedure, the superior mesenteric artery and vein were separated below the division of the inferior pancreaticoduodenal artery and below the veins of the pancreatic head. An arterial interposition graft was used in all cases. One donor mesenteric artery was reconstructed in 6 patients; two arteries in 5 patients; and three arteries in 3 patients. Proximal arteries of the graft were ligated and the upper part of the jejunum resected. In 10 patients, a direct anastomosis was performed in an end-to side fashion between donor superior mesenteric vein (SMV) and recipient inferior mesenteric vein (IMV). In 2 patients, a branch of the superior mesenteric vein was used and 2 patients required a venous interposition graft to confluence using the donor iliac vein. Patency of the venous anastomosis was documented by magnetic resonance imaging (MRI) angiography after 6 months. No vascular complications have been observed to date. Portal venous drainage is technically feasible in most cases. An anastomosis to the recipient IMV offers the advantage of being direct despite the short donor vein segment. Furthermore, donor and recipient vessels are well matched for size. Using microsurgical techniques, vascular complications may be avoided.

Adult↗
PubMed2004

CMV, EBV, HHV6, and HHV7 infections after intestinal transplantation without specific antiviral prophylaxis.

PURPOSE: To analyze the incidence and relevance of viral infections after intestinal transplantation (ITx) without specific antiviral prophylaxis. METHODS: Eleven patients (median age 34 years; range 26 to 58 years) who underwent ITx received no CMV/EBV prophylaxis but rather preemptive treatment. Viral monitoring for CMV or EBV polymerase chain reactions (PCR) in peripheral blood and graft biopsies, for HHV6-, and HHV7-PCR; for adeno-/rotavirus antigen and serology was performed based on clinical indications. RESULTS: Median time under risk was 19 months (range 2 to 39). CMV: The donor (D)-to-recipient (R) status prior to ITx was: D+/R+ (4); D+/R- (3); D-/R- (2); D-/R+ (2). Eight patients showed no positive CMV-PCR. Three episodes of tissue invasive CMV disease occurred in two patients. There were two asymptomatic CMV infections but no episodes of CMV disease. None of the R(-) recipients developed CMV infection or enteritis irrespective of the donor status. EBV: Four patients experienced six episodes of transient significant EBV-viremia. Two patients developed EBV enteritis concurrently with CMV enteritis during acute rejection. There were no PTLD. CMV and EBV enteritis only occurred during or immediately after steroid and OKT3 therapy. None of the patients developed significant HHV6 and HHV7 infection or viremia. There was one episode of adeno- and rotavirus enteritis. CONCLUSIONS: Despite witholding specific antiviral prophylaxis against CMV and EBV, we observed no such infections in 60% to 80% of patients. Donor-recipient matching regarding CMV was not predictive for the occurrence of CMV-related complications. HHV6 and HHV7 have not contributed to posttransplant morbidity.

Adult↗
PubMed2004

Gene delivery to cartilage defects using coagulated bone marrow aspirate.

The long-term goal of the present study is to develop a clinically applicable approach to enhance natural repair mechanisms within cartilage lesions by targeting bone marrow-derived cells for genetic modification. To determine if bone marrow-derived cells infiltrating osteochondral defects could be transduced in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with adenoviral vectors containing various marker genes into lesions surgically generated in rabbit femoral condyles. Analysis of the recovered implants showed transgenic expression up to 21 days; however, a considerable portion was found in the synovial lining, indicating leakage of the vector and/or transduced cells from the matrix. As an alternative medium for gene delivery, we investigated the feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral suspension with the fluid phase of freshly aspirated bone marrow resulted in uniform dispersion of the vector throughout, and levels of transgenic expression in direct proportion to the density of nucleated cells in the ensuing clot. Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex vivo with recombinant adenovirus, were readily incorporated into the coagulate when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow clots were found to maintain their structural integrity following extensive culture and maintained transgenic expression in this manner for several weeks. When used in place of the CG matrix as a gene delivery vehicle in vivo, genetically modified bone marrow clots were able to generate similarly high levels of transgenic expression in osteochondral defects with better containment of the vector within the defect. Our results suggest that coagulates formed from aspirated bone marrow may be useful as a means of gene delivery to cartilage and perhaps other musculoskeletal tissues. Cells within the fluid can be readily modified with an adenoviral vector, and the matrix formed from the clot is completely natural, native to the host and is the fundamental platform on which healing and repair of mesenchymal tissues is based.

Adenoviridae↗
PubMed2003

Quality of life of living donors before and after living donor liver transplantation.

Living donor liver transplantation (LDLT) is becoming an established method for treatment of terminal liver disease in adults. After resection of the right hepatic lobe, postoperative complications can arise in healthy donors, and even individual cases of death have been recorded. There remains, however, little research on the psychosocial aspects in living donors before and after LDLT. Using the WHOQOL questionnaire, this prospective study investigates the quality of life (QoL) in a sample of 28 living donors, including the relationship between postoperative complications and QoL before and 6 months after donation. Before LDLT, the donor QoL is high, above that of the general healthy population. After LDLT, a significant reduction in the QoL appears in the areas of "physical health" and "living conditions." Nevertheless, the QoL remains above the level of the general population. Only two donors showed general QoL values below those of the general population. The postoperative complications had no significant influence on the QoL after transplantation. The high QoL of donors following LDLT indicates a positive psychosocial outcome for the majority of donors, irrespective of donation-related complications. Additional psychosocial studies will be necessary to disclose predictors for an unfavorable psychosocial outcome following LDLT.

Adult↗
PubMed2003

Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation.

From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end-to-end microanastomosis of the donor right hepatic duct with the recipient's bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux-en-Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end-to-end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T-tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end-to-end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.

Adolescent↗
PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗