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1.
BMC Complement Altern Med ; 17(1): 440, 2017 Sep 04.
Article in English | MEDLINE | ID: mdl-28870250

ABSTRACT

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.


Subject(s)
Kidney Diseases/psychology , Kidney Diseases/surgery , Kidney Transplantation/psychology , Living Donors/psychology , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Moon , Prospective Studies , Retrospective Studies , Time Factors , Young Adult
2.
Infection ; 44(3): 365-70, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26498284

ABSTRACT

Because of global mobility and migration resulting in a growing diversity of the donor pool, the risk for donor-derived tuberculosis in solid organ transplant recipients becomes more and more relevant, even in countries with a low overall tuberculosis incidence. Here, we describe a case series of donor-derived tuberculosis in 2 of 3 solid organ transplant recipients and one medical staff member in Germany resulting in the death of one recipient. This case series highlights the relevance of this topic to clinicians. It advocates for a better communication between organ procurement organizations and transplant centers regarding donor information and transplant recipient outcome. Furthermore, it underpins the necessity for a standardized critical incident reporting system in the german transplant system to improve short- and long-term recipient's safety, health and survival.


Subject(s)
Organ Transplantation/adverse effects , Tissue Donors , Transplant Recipients , Transplants/microbiology , Tuberculosis , Aged , Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Female , Health Personnel , Humans , Male , Middle Aged , Tuberculosis/drug therapy , Tuberculosis/microbiology , Tuberculosis/transmission
3.
Anaesthesist ; 65(5): 363-5, 2016 May.
Article in English | MEDLINE | ID: mdl-27129535

ABSTRACT

We report a case of a 27-year-old anesthetist who acquired tuberculosis (TB) while performing general anesthesia in a renal transplant (RTX) patient who had donor-derived contagious TB. The anesthetist developed pleural TB 6 months after exposure. Contact investigations (CIs) did not include health care workers (HCWs) of the Department of Anesthesiology, thereby missing the opportunity for the early diagnosis and treatment of TB. Genomic fingerprinting revealed identical Mycobacterium tuberculosis (MT) isolates in the anesthetist and in the RTX patient. The recipient had acquired disseminated TB from the harvested renal graft. The donor (liver and kidneys), a 67-year-old immigrant, had died from brain death by cerebral herniation after a stroke. She had been treated for tuberculosis with a pneumectomy 40 years ago. Since that time, she had been suffering from latent tuberculous infection (TBI), but had been considered to have been cured.


Subject(s)
Infectious Disease Transmission, Patient-to-Professional , Kidney Transplantation/adverse effects , Tuberculosis, Pulmonary/etiology , Tuberculosis, Pulmonary/transmission , Adult , Aged , Anesthetists , Antibiotics, Antitubercular/therapeutic use , Female , Humans , Liver Transplantation/adverse effects , Mycobacterium tuberculosis , Tissue Donors , Tuberculosis, Pulmonary/therapy
4.
Langenbecks Arch Surg ; 400(8): 979-83, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26566989

ABSTRACT

INTRODUCTION: Ascites is a common complication of liver cirrhosis and represents the main cause of hospitalization among patients with cirrhosis. First-line therapy for those patients is the use of diuretics and dietary sodium restriction. However, 10 % of patients per year become therapy refractory to diuretic treatment with the need of repeated high-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS). For these patients, an automated pump system (Alfapump/Sequana Medical) was developed. Here, we describe our single-center experience of ten consecutively implanted pump systems. PATIENTS AND METHODS: Between 08/13 and 11/14, ten Alfapump systems were implanted in patients with refractory ascites all suffering from liver cirrhosis. Those patients were treated as a bridge to transplant (4/10) or as an end-stage therapy (6/10). Median follow-up was 165 days (23-379 days). RESULTS: Postimplant, the need of paracentesis could be markedly reduced to a mean of 0.45 (0-4/month) per month. In eight patients, paracentesis was not needed after implantation of the pump system. The median daily output volume was 1000 ml/day (450-2000 ml/day). Prerenal insufficiency was a recurrent complication in the postoperative period. DISCUSSION: The Alfapump system is a useful system in the treatment of patients suffering from therapy refractory ascites. However, due to the high level of comorbidities, careful patient selection and postoperative monitoring are required.


Subject(s)
Ascites/etiology , Ascites/therapy , Liver Cirrhosis/complications , Prostheses and Implants , Female , Humans , Kidney Function Tests , Length of Stay/statistics & numerical data , Liver Function Tests , Male , Operative Time , Paracentesis , Patient Selection , Portasystemic Shunt, Transjugular Intrahepatic , Postoperative Complications/epidemiology , Treatment Outcome
5.
Zentralbl Chir ; 139(3): 271-5, 2014 Jun.
Article in German | MEDLINE | ID: mdl-24258630

ABSTRACT

Currently, there is no structured training plan to become a transplant surgeon in Germany. Similar to the Anglo-Saxonian educational system we have implemented a 3-year fellowship in transplant and hepatic-, pancreatic-, biliary (HPB) surgery. The educational curriculum is based on the guidelines of the European Board of Surgery (EBS) for transplant and HPB surgery. Here, we describe the underlying thoughts, the selection process, structure and curriculum for this fellowship. Furthermore, we critically compare our programme to the established international training standards. So far, our programme has proven valuable. We believe a fellowship for transplant and HPB surgery is a reasonable approach to ensure a high quality training of the following generations of surgeons in this field.


Subject(s)
Biliary Tract Surgical Procedures/education , Education, Medical, Graduate , Fellowships and Scholarships , General Surgery/education , Liver/surgery , Pancreas/surgery , Transplantation/education , Curriculum , Germany , Humans , Pilot Projects
6.
Transpl Infect Dis ; 15(3): 306-13, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23489913

ABSTRACT

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.


Subject(s)
Biliary Tract Diseases/etiology , Hepacivirus/isolation & purification , Hepatitis C/virology , Liver Transplantation/adverse effects , Viral Load , Adolescent , Adult , Aged , Biliary Tract Diseases/surgery , Cohort Studies , Female , Graft Rejection , Graft Survival , Hepacivirus/genetics , Hepatitis C/diagnosis , Humans , Male , Middle Aged , RNA, Viral/blood , Retrospective Studies , Risk Factors , Treatment Outcome , Young Adult
7.
Clin Exp Immunol ; 170(2): 238-47, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23039895

ABSTRACT

Approximately 60% of transplanted islets undergo apoptosis within the first week post-transplantation into the liver attributed to poor engraftment, immune rejection and toxicity of immunosuppressive drugs. Understanding how extracellular matrix (ECM) components, immunosuppressive drugs and proinflammatory cytokines affect insulin secretion will contribute to an improved clinical outcome of islet transplantations. In this study, functional activity of isolated murine islets was measured by glucose-stimulated insulin secretion (GSIS) and by electrophysiological measurements using patch-clamp. Cultivating islets with soluble fibronectin or laminin, as opposed to with coated laminin, markedly increased GSIS. Addition of cyclosporin A reduced GSIS and suppressed glucose-induced spike activity. Tacrolimus affected neither GSIS nor spike activity, indicating a different mechanism. To evaluate the influence of proinflammatory cytokines, islets were incubated with interleukin (IL)-1ß, tumour necrosis factor (TNF)-α or with supernatants from cultured Kupffer cells, the main mediators of inflammation in the hepatic sinusoids. IL-1ß exerted a bimodal effect on insulin secretion, stimulating below 2 ng/ml and suppressing above 10 ng/ml. Soluble laminin in combination with a stimulatory IL-1ß concentration further increased insulin secretion by 20% compared to IL-1ß alone, while with high IL-1ß concentrations soluble laminin slightly attenuated GSIS inhibition. TNF-α alone did not affect GSIS, but with stimulatory IL-1ß concentrations completely abolished it. Similarly, supernatants derived from Kupffer cells exerted a bimodal effect on GSIS. Our data suggest that improved insulin secretion of transplanted islets could be achieved by including soluble laminin and low IL-1ß concentrations in the islet cultivation medium, and by a simultaneous inhibition of cytokine secretion from Kupffer cells.


Subject(s)
Extracellular Matrix/metabolism , Immunosuppressive Agents/pharmacology , Insulin/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/physiology , Animals , Apoptosis/drug effects , Cyclosporine/pharmacology , Extracellular Matrix/drug effects , Extracellular Matrix/physiology , Fibronectins/pharmacology , Glucose/metabolism , Humans , Inflammation/metabolism , Insulin Secretion , Interleukin-1beta/pharmacology , Islets of Langerhans/metabolism , Islets of Langerhans Transplantation , Kupffer Cells/metabolism , Laminin/pharmacology , Mice , Mice, Inbred C57BL , Tacrolimus/pharmacology , Tumor Necrosis Factor-alpha/metabolism
9.
Eur Surg Res ; 43(2): 245-51, 2009.
Article in English | MEDLINE | ID: mdl-19590217

ABSTRACT

BACKGROUND: For experimental basic research, standardized transplantation models reflecting technical and immunologic aspects are necessary. This article describes an experimental model of combined pancreas/kidney transplantation (PKTx) in detail. MATERIALS AND METHODS: Donor rats underwent en bloc pancreatectomy and nephrectomy. Revascularization was performed using the aorta with the superior mesenteric artery and the inferior vena cava with the portal vein. Exocrine drainage of the pancreas took place over a segment of the duodenum which was transplanted side-to-side to the jejunum. The kidney vessels were transplanted end-to-side. The ureter was anastomosed by patch technique. Postoperatively, serum parameters were monitored daily. Biopsies for histopathology were taken on days 5, 8 and 12. RESULTS: All 12 recipients survived the combined PKTx without serious surgical complications. One thrombosis of the portal vein led to organ failure. Blood glucose levels were normal by the 3rd postoperative day. The transplanted duodenal segment showed slight villous atrophy, and the kidneys were well perfused without vascular complications. The anastomosis between ureter and bladder was leakproof. CONCLUSIONS: Excellent graft function and survival rates can be achieved due to simplified operation technique and short operation time. It may thus have high clinical relevance to immunologic issues within the scope of basic research.


Subject(s)
Kidney Transplantation/methods , Microsurgery/methods , Pancreas Transplantation/methods , Animals , Graft Survival/immunology , Graft Survival/physiology , Humans , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Kidney Transplantation/physiology , Male , Models, Animal , Pancreas Transplantation/immunology , Pancreas Transplantation/pathology , Pancreas Transplantation/physiology , Rats , Rats, Inbred Lew , Transplantation, Isogeneic
10.
Transplant Proc ; 40(4): 921-2, 2008 May.
Article in English | MEDLINE | ID: mdl-18555079

ABSTRACT

The increasing prevalence of obesity among patients with end-stage renal disease accompanies more common renal transplantation from living donors. Since several studies have shown a negative impact of recipient obesity on renal transplantation outcomes, we investigated the influence of recipient-weight and donor-recipient-weight ratio on the outcome of living related renal transplantations. From October 2000 until December 2004, we performed 81 living donor renal transplantation with 30.8% (n = 25) of recipients with a body mass index >25 donor. In this group 6 patients lost their grafts (1-year survival rate, =76%). Among 56 recipients of normal body weight only 3 patients lost their graft (1-year graft survival rate, 94.6%; P < .001). Upon multivariate analysis body mass index was an independent risk factor for graft loss within the first year. When the body weights of the donor and recipient were analyzed in detail the quotient (body weight recipient(2)/ body weight donor) was also an independent risk factor. This study confirmed the results of larger analyses suggesting that body weight matching could significantly improve the outcomes in living donor renal transplantation. As a result of this study, in our institutional policy has changed; recipients of living donor grafts are only accepted when their body mass index is <25.


Subject(s)
Kidney Transplantation/physiology , Obesity/physiopathology , Adult , Body Mass Index , Body Weight , Graft Survival , Humans , Kidney Transplantation/mortality , Living Donors , Middle Aged , Obesity/complications , Obesity/epidemiology , Obesity/mortality , Prevalence , Risk Factors , Survival Rate , Treatment Outcome
11.
Transplant Proc ; 40(4): 915-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18555077

ABSTRACT

BACKGROUND: Immunosuppressive therapy increases the incidence of posttransplantation cancer. Primary renal cell carcinoma (RCC) represents 4.6% of all cancers in transplant recipients. The treatment options for RCC in a renal allograft include radical nephrectomy or nephron-sparing surgery. We report the case of a patient who underwent percutaneous radiofrequency ablation (RFA) of a RCC in the grafted kidney. PATIENT AND METHODS: Twelve years after undergoing heterotopic, allogenic kidney transplantation, a de novo lesion was diagnosed in the upper pole of the kidney graft in a 77-year-old patient during routine duplex ultrasonography. The magnetic resonance image showed a spherical lesion of 17 mm in diameter, which undoubtedly showed radiological signs of a RCC. After adequately informing the patient about alternative treatment strategies and the associated risks, we made an interdisciplinary decision for a percutaneous RFA of the lesion. RESULTS: After the intervention, graft function remained unchanged and is still good at 6 months with no signs of local recurrence on follow-up MRI. A small coagulation defect at the site of the former lesion was the only morphological change. There was also no evidence of distant tumor spread. CONCLUSION: Percutaneous RFA seems an acceptable, allograft-preserving treatment option associated with low morbidity and mortality for RCC in a renal allograft considering the significant risks associated with open partial nephrectomy in a kidney graft.


Subject(s)
Carcinoma, Renal Cell/therapy , Catheter Ablation , Kidney Neoplasms/therapy , Kidney Transplantation/adverse effects , Aged , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Postoperative Complications/therapy , Time Factors , Transplantation, Homologous , Treatment Outcome
12.
Transplant Proc ; 40(4): 971-3, 2008 May.
Article in English | MEDLINE | ID: mdl-18555092

ABSTRACT

BACKGROUND: It is generally accepted that nitric oxide (NO) plays a crucial role in acute rejection caused by inflammatory responses. Therefore, the purpose of this study was to investigate the effect on survival following arterialized orthotopic rat liver transplantations (o-RLTx) of NO inhibition and consequent blockade of platelet aggregation by application of Aspisol. MATERIALS AND METHODS: Inbred LEWIS-(RT(1)) rats underwent arterialized o-RLTx under ether anesthesia with DA-(RT1av1) rats as organ donors. After liver transplantation, serum parameters were determined and hepatic biopsy specimens were sampled on postoperative days 5, 8, 10, 30, and 90. Sixty-one rats were divided into 5 groups: syngenic controls (group I, n = 12); allogenic controls (group II, n = 11); allogenic with FK506 immunosuppression (group III, n = 12); allogenic with AGH-treatment (group IV, n = 13); and allogenic with AGH/low- dose Aspisol treatment for 5 days after liver transplantation (group V, n = 13) (Bayer, Leverkusen, Germany). RESULTS: Rats of group V with AGH/low-dose Aspisol treatment showed significantly longer graft survival (18.2 days +/- 1.8 days) compared with group II rats with untreated grafts (11.3 days +/- 1.7 days) the allogenic group IV with AGH treatment (11.2 days +/- 1.8 days; P < .05). Histological examination revealed moderate graft rejection among the AGH-treated group IV; however, marked platelet aggregation in sinusoids was present, which was not observed in the AGH/low-dose Aspisol-treated animals (group V). CONCLUSION: Our data suggested that simultaneous treatment with AGH/low-dose Aspisol leads to a significant increase in survival and inhibition of platelet aggregation in the graft after orthotopic liver transplantation.


Subject(s)
Aspirin/analogs & derivatives , Graft Survival/drug effects , Liver Transplantation/physiology , Lysine/analogs & derivatives , Nitric Oxide/antagonists & inhibitors , Animals , Aspirin/pharmacology , Biopsy , Immunosuppressive Agents/therapeutic use , Liver Transplantation/pathology , Lysine/pharmacology , Models, Animal , Nitric Oxide Synthase Type II/antagonists & inhibitors , Rats , Rats, Inbred Lew , Tacrolimus/therapeutic use , Transplantation, Homologous , Transplantation, Isogeneic
13.
Transplant Proc ; 40(4): 983-5, 2008 May.
Article in English | MEDLINE | ID: mdl-18555096

ABSTRACT

BACKGROUND: Activity levels of cytochrome P450 (CYP) provide markers for liver function and graft rejection episodes after orthotopic liver transplantation (OLT). Some in vitro studies have shown decreased CYP activation of inducible nitric oxide synthase (iNOS) in rejecting liver grafts. The aim of this study was to evaluate CYP isoenzyme activity changes in vivo and to examine histopathologic aspects during inhibition of iNOS after treatment with aminoguanidine (AG) using OLT in the rat. MATERIALS AND METHODS: Thirty DA-(RT1av1) rats that served as donors and LEWIS-(RT(1)) rats as recipients were divided into three groups: group I (controls, syngeneic rats; n = 6), group II (allogeneic rats without immunosupression; n = 11), and group III (allogeneic rats with AG treatment; n = 13). On postoperative days 5, 8, and 10 we performed laboratory investigations and liver biopsies for histopathologic investigations. RESULTS: On postoperative day 5, activities of CYP-1A1 and -3A4 were significantly lower (P = .022) in group III and the activity of CYP-1A2 higher (P < .05) compared with group II. At postoperative days 8 and 10, the activities of all CYP isoenzymes were significant higher in AG-treated rats (group III) in contrast with group II after allogeneic OLT without immunosuppression. Histopathologic findings revealed less distinct rejection signs in group III specimens after AG treatment compared with group II. CONCLUSION: Summarizing our results, we concluded that AG treatment led to increased CYP activity and less distinction of graft rejection after OLT in rats.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Liver Transplantation/physiology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Biomarkers/metabolism , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP3A/metabolism , Enzyme Activation , Guanidines/pharmacology , Kinetics , Models, Animal , Nitric Oxide Synthase Type II/metabolism , Rats
14.
Transplant Proc ; 40(9): 3191-3, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19010230

ABSTRACT

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Liver Transplantation/physiology , Germany , Hospital Mortality , Humans , Liver Transplantation/mortality , Retrospective Studies , Survival Rate , Survivors , Time Factors
15.
Transplant Proc ; 39(2): 505-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362768

ABSTRACT

There is only limited information about recipient risk factors for graft survival in living- donor kidney transplantation. This study aimed to investigate prognostic factors and their impact on living-related and unrelated renal transplant recipients. From October 2000 until October 2004, 81 adult living-related renal transplantations were performed at our institution. Using multivariate analysis, the association of the following variables with kidney graft outcome was studied: ages of donors and recipients, gender and body mass index, cold and warm ischemia, HLA mismatches, identity and compatibility of blood group, duration of dialysis, cytomegalovirus (CMV) status, recipient original disease, surgical and general complications, and status of retransplantation. Multivariate analysis revealed significant reduction of graft function and graft survival in recipients with retransplantation, more than 4 mismatches, and a high body mass index. Thus, living-donor kidney transplantation can be regarded as a safe and standardized operation relating to surgical technique, but further consideration of the recipient body mass index and the number of mismatches are recommended during the preparation for transplantation.


Subject(s)
Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Living Donors , Adult , Blood Group Incompatibility/epidemiology , Female , Histocompatibility Testing , Humans , Kidney Transplantation/immunology , Male , Middle Aged , Postoperative Complications/epidemiology , Reoperation/statistics & numerical data , Risk Assessment , Treatment Failure , Treatment Outcome
16.
Transplantation ; 65(5): 737-40, 1998 Mar 15.
Article in English | MEDLINE | ID: mdl-9521212

ABSTRACT

BACKGROUND: The impact of antibody adsorption by immunoapheresis on liver damage, complement activation, and hepatic perfusion was evaluated against the background of an application in extracorporeal pig liver perfusion for hepatic coma. METHODS: Eighteen pig livers were ex vivo perfused close to physiological conditions with fresh human blood for 4 hr. The influence of the perfusion circuit was investigated by perfusions of the circuit in the absence of livers (group 1 [G1]; n=5). Livers were xenoperfused without modifications in group 2 (G2; n=6). In group 3 (G3; n=6), pure Sepharose columns were used prior to liver perfusion. Immunoapheresis with Ig-Therasorb 100 columns was used in group 4 (G4; n=6). RESULTS: IgG was reduced by 95%, IgM by 72%, and IgA by 82% in G4, but only by about 30% in G3 (P<0.05). C4d, Bb fragment, and C3a levels were significantly lower in G4 than in G3 and G2 (P<0.05) after 180 min. Immunoadsorption diminished antibody and complement deposition as well as hepatocellular damage in G4. Portal angiographies demonstrated improved hepatic perfusion in G4. CONCLUSION: Immunoapheresis reduced organ damage as well as complement activation and improved hepatic perfusion during xenogeneic pig liver perfusion.


Subject(s)
Complement Activation , Complement System Proteins/metabolism , Liver/blood supply , Acute Disease , Animals , Antibodies/metabolism , Extracorporeal Circulation , Graft Rejection , Humans , Immunosorbent Techniques , Liver/immunology , Perfusion , Swine
17.
Transplantation ; 47(3): 424-7, 1989 Mar.
Article in English | MEDLINE | ID: mdl-2784239

ABSTRACT

Small-bowel allografts are replete with lymphocytes, which may be the main stimulus for the recipient's immune system, thereby inducing rejection. Since most of the lymphoid tissue is located in the ileum, one would expect ileal grafts to be rejected more rapidly than are jejunal grafts. To test this theory, we transplanted a jejunal (n = 13) or an ileal segment (n = 9) or the entire small bowel (n = 6) orthotopically in the BN----LEW rat strain combination. Jejunal grafts included a short segment of the mesentery, whereas ileal and whole small-bowel grafts included the entire mesentery with its lymph nodes. Segmental as well as entire-bowel grafts induced peak anti-BN titers on the 6th to 7th postoperative day. In rats with entire-bowel grafts, rejection culminated in the recipient's death after an average of 9.5 +/- 1 days from graft necrosis and peritonitis; the rejection of jejunal (13.1 +/- 2.1 days) and ileal grafts (12.9 +/- 1.3 days) was less rapid. Segmental grafts were often encapsulated, and the causes of death were inanition and intestinal obstruction. Thus, despite their high lymphocyte content, ileal grafts were not rejected more quickly than were jejunal grafts; they should, therefore, be preferred because of their greater specialized absorptive capacity. Histologically, entire-bowel grafts were found to be rejected as rapidly as were segmental grafts; however, the toxic effects of the larger grafts that are undergoing rejection lead to earlier death of the recipient.


Subject(s)
Ileum/transplantation , Jejunum/transplantation , Animals , Graft Rejection , Graft Survival , Hemagglutination Tests , Male , Rats , Rats, Inbred BN , Rats, Inbred Lew , Transplantation, Homologous
18.
Transplantation ; 63(6): 867-75, 1997 Mar 27.
Article in English | MEDLINE | ID: mdl-9089228

ABSTRACT

BACKGROUND: Extracorporeal liver perfusion in hepatic coma, used to eliminate toxic metabolites causing hepatic encephalopathy, is limited by the antibody (Ab) and complement-mediated hyperacute rejection of discordant xenografts. Thus, the efficacy of highly selective immunoadsorption columns to deplete xenoreactive human anti-porcine antibodies before ex vivo liver perfusion was examined in this study. METHODS: Eighteen domestic pigs were hepatectomized according to standard techniques. The livers were ex vivo perfused for 4 hr. The perfusion protocol closely followed the physiological conditions of a human liver. Parameters of liver function and damage were analyzed. Three groups were formed differing in the treatment of the perfusate. As basic control, livers were perfused with heparinized human blood (group 1; n=6). Immunoapheresis was applied in group 3 (n=6). Immunoapheresis was performed using Ig Therasorb columns consisting of sheep-anti-human IgG Abs covalently coupled to Sepharose CL-4B. Additionally, the effect of pure Sepharose CL-4B without immobilized Ab was tested in group 2 (n=6). RESULTS: The use of Ig Therasorb 100 columns in group 3 resulted in a reduction of IgG, IgM, and IgA in the order of 95.0%, 72.3%, and 81.5%, respectively. In group 2, IgG, IgM, and IgA were lowered by 30% to 39%. Determination of liver-specific enzymes and tolerance tests revealed a significant reduction of cellular damage and functional restrictions in group 3 compared with the control groups. CONCLUSIONS: Immunoapheresis conducted according to this protocol appears to be an effective approach for delaying antibody-mediated hyperacute xenogeneic rejection.


Subject(s)
Antibodies, Heterophile/isolation & purification , Blood Component Removal/methods , Extracorporeal Circulation , Graft Rejection/prevention & control , Hepatic Encephalopathy/therapy , Liver , Transplantation, Heterologous , Acute Disease , Ammonia/blood , Animals , Complement C3/analysis , Complement C4/analysis , Enzyme-Linked Immunosorbent Assay , Enzymes/blood , Galactose/analysis , Galactosemias , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lactates/blood , Liver Function Tests , Perfusion , Sheep , Swine
19.
Transplantation ; 52(3): 399-405, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1897008

ABSTRACT

This study was undertaken to investigate under which circumstances graft versus host disease occurs following fully allogenic small bowel transplantation in the rat. To facilitate the development of GVHD, Brown-Norway donors were specifically sensitized against the Lewis hosts prior to transplantation. Additionally, the Lewis recipients were immunocompromised before transplantation using splenectomy, cyclosporine, and antilymphocyte serum. No further immunosuppressive therapy was administered after transplantation. When all pretreatment regimens were used, acute lethal GVHD arose in two of nine animals (22%), whereas in two animals (22%) signs of acute GVHD and rejection were observed concurrently. When recipients of sensitized grafts were pretreated with CsA alone, one of eight animals (12.5%) showed signs of GVHD and rejection. All other animals died of acute rejection without clinical signs of acute GVHD. However, histological signs of GVHD were observed frequently in hosts grafted with a sensitized small bowel transplant. These data show that acute lethal GVHD can occur when an immunocompromised host is grafted with a sensitized intestinal transplant.


Subject(s)
Graft Rejection , Graft vs Host Disease/etiology , Immunization , Intestine, Small/transplantation , Animals , Cyclosporins/therapeutic use , Immunosuppression Therapy , Male , Rats , Rats, Inbred BN , Rats, Inbred Lew , Transplantation, Homologous
20.
Transplantation ; 66(1): 44-9, 1998 Jul 15.
Article in English | MEDLINE | ID: mdl-9679820

ABSTRACT

BACKGROUND: The currently used macrolide immunosuppressants, i.e., cyclosporine and tacrolimus, exert considerable nephrotoxicity. We aimed to avoid the nephrotoxic effects by applying a cyclosporine-free regimen for the induction as well as for the maintenance treatment of renal allograft recipients using mycophenolate mofetil (MMF) as the primary immunosuppressant. METHODS: Thirteen patients were converted from cyclosporine (CsA) to MMF monotherapy. For 4 weeks, MMF (2 g/day) was added to the CsA treatment, before CsA was tapered by weekly steps of 25 mg/day and without "safeguard treatment" with additional immunosuppressants. In a second approach, 12 patients older than 50 years, and receiving a renal graft from a donor older than 50 years, were treated primarily with MMF combined with steroids and an induction therapy using antithymocyte globulin, and without the addition of CsA. RESULTS: Thirteen long-term renal transplant patients could be converted from CsA to MMF monotherapy. Conversion resulted in an immediate and long-lasting improvement of their median creatinine values by 20%. No serious adverse events occurred. In the second cohort of 12 patients, MMF was used as the primary immunosuppressant. All patients are alive and no grafts were lost after 4 months (n= 12) and after 6 months (n=7). The median creatinine values achieved after 4 and 6 months were 1.16+/-0.25 and 1.30+/-0.21 mg/dl, respectively. One patient was converted to CsA because of a reversible rejection episode (8.3%), and another patient was converted because of cytomegalovirus disease. Major complications consisted of wound-healing disturbances (16.6%) and cytomegalovirus infections (41.6%). CONCLUSION: MMF monotherapy can be safely applied as long-term maintenance immunosuppression with improvement of renal function. Steroids are not required as an adjunct to MMF. MMF monotherapy, in the absence of drug-related nephrotoxicity, is particularly beneficial for grafts derived from marginal donors, such as donors of advanced age.


Subject(s)
Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Acute Disease , Adult , Cyclosporine/therapeutic use , Female , Graft Rejection/therapy , Humans , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Retreatment
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