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Biomedical subjects

S Schneeberger

Publications and source records attributed to S Schneeberger.

11 recordsLinked to original sources
PubMed2006

Non-invasive monitoring of kidney allograft rejection through IDO metabolism evaluation.

The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma (IFN-gamma) and via tryptophan depletion, suppresses adaptive T cell-mediated immunity in inflammation, host immune defense, and maternal tolerance. Its role in solid organ transplantation is still unclear. Therefore, we investigated the usefulness of IDO-mediated tryptophan catabolism in the evaluation of kidney allograft rejection. Blood, urine, and tissue samples were collected from 34 renal transplant patients without rejection and from nine patients with biopsy-confirmed episodes of acute rejection (n=12). Concentrations of kynurenine and tryptophan in serum and urine were analyzed by high-pressure liquid chromatography. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO activity. Immunostaining for IDO was performed on renal biopsies. Neopterin was assessed using radioimmunoassay. Kyn/trp and neopterin were detectable at low levels in serum of healthy volunteers and were increased in non-rejecting allograft recipients. Serum levels of kyn/trp were higher in recipients with rejection compared to non-rejectors as early as by day 1 post-surgery. Rejection episodes occurring within 13+/-5.9 days after transplantation were accompanied by elevated kyn/trp in serum (114+/-44.5 micromol/mmol, P=0.001) and urine (126+/-65.9 micromol/mmol, P=0.02) compared to levels during stable graft function. Kyn/trp correlated significantly with neopterin suggesting an IFN-gamma-induced increase in IDO activity. Immunostaining showed upregulation of IDO in rejection biopsies, localized in tubular-epithelial cells. Non-rejected grafts displayed no IDO expression. Acute rejection is associated with simultaneously increased serum and urinary kyn/trp in patients after kidney transplantation. Thus, IDO activity might offer a novel non-invasive means of immunomonitoring of renal allografts.

Acute Disease↗
PubMed2006

Hand transplantation: the state-of-the-art.

The feasibility of hand transplantation has been demonstrated, both surgically and immunologically. Levels of immunosuppression comparable to regimens used in solid organ transplantation are proving sufficient to prevent graft loss. Many patients have achieved discriminative sensibility and recovery of intrinsic muscle function. In addition to restoration of function, hand transplantation offers considerable psychological benefits. The recipient's pre-operative psychological status, his motivation and his compliance with the intense rehabilitation programme are key issues. While the induction of graft specific tolerance represents a hope for the future, immunosuppression currently remains necessary and carries significant risks. Hand transplantation should, therefore, only be considered a therapeutic option for a carefully selected group of patients.

Feasibility Studies↗
PubMed2006

Status 5 years after bilateral hand transplantation.

Graft survival and function early after hand transplantation is good. It remains unknown, however, whether long-term survival is limited by chronic rejection. We here describe the clinical course and the status 5 years after bilateral hand transplantation with emphasis on immunosuppression (IS), function, morphology and graft vascular changes. Clinical observation, evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, CT angiography, electrophysiologic studies including compound motor and sensory action potentials (CMAP, CSAP) and somatosensory evoked potentials were performed and results recorded at regular intervals. Following reduction of IS one mild (grade II) rejection episode occurred at 4 years. Subsequently, skin histology remained normal and without signs of chronic rejection. Hand function continuously improved during the first 3 years and remained stable with minor improvement thereafter. CMAP and CSAP progressively increased during the observation period. Latencies of the cortical responses were prolonged but amplitudes were within normal range. Investigation of hand vessels revealed no signs of occlusion but showed revascularization of a primarily occluded right radialis artery. Motor and sensory function improved profoundly between years 1 and 5 after hand transplantation. No signs whatsoever of chronic rejection have been observed.

Angiography↗
PubMed2006

Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation.

In this study we investigated the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, on ischemia-reperfusion injury (IRI) following murine pancreas transplantation. Pancreatic grafts were exposed to prolonged cold ischemia times (CIT) and different treatment regimens: normal saline (S), S + 16 h CIT, BH4 50 mg/kg + 16 h CIT. Nontransplanted animals served as controls. Graft microcirculation was analyzed by means of functional capillary density (FCD) and capillary diameters (CD) after 2 h reperfusion using intravital microscopy. Quantification of inflammatory responses (mononuclear infiltration) and endothelial disintegration (edema formation) was done by histology (hematoxylin and eosin), and peroxynitrite formation assessed by nitrotyrosine immunostaining. FCD was significantly reduced after prolonged CIT, paralleled by increased peroxynitrite formation as compared with controls (all p < 0.05). Microcirculatory changes correlated significantly with intragraft peroxynitrite generation (Spearman: r = -0.56; p < 0.01). Pancreatic grafts treated with BH4 displayed markedly higher FCD values (p < 0.01) and abrogated nitrotyrosine staining (p = 0.03). CD were not significantly different in any group. Histology showed increased inflammation, interstitial edema, hemorrhage, acinar vacuolization and focal areas of necrosis after 16 h CIT, which was diminished by BH4 administration (p < 0.01). BH4 treatment significantly reduces post-ischemic deterioration of microcirculation as well as histologic damage and might be a promising novel strategy in attenuating IRI following pancreas transplantation.

Animals↗
PubMed2005

Excellent results with calcineurin inhibitor-free initial immunosuppression in old recipients of old kidneys.

The ever increasing demand for donor organs has forced transplant surgeons to liberalize selection criteria. To avoid initial nephrotoxicity to kidneys from donors over 65 years of age, immunosuppression was begun with an IL-2 receptor antibody, mycophenolate mofetil, and steroids in a total of 38 recipients over 65 years. Calcineurin inhibitors (CI) were added after sufficient graft function was reached. After a mean cold ischemia time of 14:01 hours and a delayed function rate of 31%, patient survival, graft survival, and serum creatinine were 97.4%, 94.7%, and 1.5 mg/dL at 1 and 92.1%, 92.1%, and 1.7 mg/dL at 2 years, respectively. Thus, excellent results can be achieved in old recipients of old donor kidneys with CI-free initial immunosuppression.

Adrenal Cortex Hormones↗
PubMed2002

A double-hand transplant can be worth the effort!

BACKGROUND: Composite-tissue transplantation offers a new therapeutic option for patients with loss of a hand. Little is known, however, about the long-term outcome after such a transplant with regard to graft function and immunosuppression and its side effects. We here report on our experience with a double-hand transplant performed more than 18 months ago. METHODS: Both distal forearms and hands of an age-, gender-, and size-matched cadaveric donor were transplanted to a 47-year-old policeman 6 years after loss of both hands. He received antithymocyte globulin as induction therapy and tacrolimus, mycophenolate mofetil, and prednisone as maintenance immunosuppression. Ganciclovir and co-trimoxazole were given prophylactically for cytomegalovirus and Pneumocystis carinii infection. A special rehabilitation program based mainly on cognitive therapy was designed and continued for 1 year. RESULTS: Apart from a small area of skin that became necrotic early and some arteriovenous fistulas in the left forearm, which required ligation 6 months after transplantation, there were no surgical complications. One acute rejection episode occurred on day 55 and resolved completely after high-dose steroids and topical tacrolimus. Despite ganciclovir prophylaxis, virus replication was observed. The patient became negative for cytomegalovirus only after additional treatment with foscarnet (Foscavir) and cidofovir. At the end of 18 months, graft function with regard to motility is overall 60% of normal and enables the patient to pursue activities he could not with his myoelectric prostheses. CONCLUSIONS: Excellent long-term results can be achieved with double-hand transplantation. Prerequisites are an appropriate surgical technique, careful immunosuppression, and an extensive rehabilitation program.

Anti-Inflammatory Agents↗
PubMed2002

[Bilateral hand transplantation].

In March 2000 we performed a bilateral hand transplantation on a 47-year-old policeman who had lost both hands in a bomb accident. Although he was fitted with myoelectric prostheses, he kept investigating the possibility of hand transplantation. The ethical, surgical, medical, legal and human aspects of this special kind of reconstruction was discussed in a symposium in Vienna, and it was decided to go ahead with it if a suitable candidate presented. The operation was successful, the immunosuppressive regimen well-planned and carried out, the post-operative course without any remarkable events. Under intensive physical therapy, the patient gradually but steadily regained sensory and motor functions in his hands. Now, two years after the operation, the patient is practically independent in the activities of daily living and is able to work at his job.

Activities of Daily Living↗
PubMed1997

Expression of FGF5 in choroidal neovascular membranes associated with ARMD.

PURPOSE: The fibroblast growth factors (FGFs) are a family of 9 heparin binding proteins which have been proposed to play key roles in angiogenesis. Basic FGF (bFGF), acidic FGF (aFGF) and FGF5 have previously been demonstrated to be expressed in the normal retina and RPE. In this study, the expression of FGF5 was explored in choroidal neovascular membranes removed from patients with age-related macular degeneration (ARMD). METHOD: Three membranes were surgically removed from patients with ARMD, and were fixed, embedded and sectioned for immunohistochemistry. The membranes were immunostained with an affinity purified rabbit polyclonal antibody raised against the amino acid sequence for residues 175 to 185 of human FGF5 and visualized with the silver enhanced colloidal gold method for light microscopy. RESULTS: FGF5 was expressed in membranes arising from ARMD, and was found primarily in blood vessels and the surrounding extracellular matrix. CONCLUSIONS: These results suggest that FGF5 may have a functional role in the pathophysiology of ARMD.

Choroid↗
PubMedDate not supplied

Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems.

BACKGROUND: Extended hepatectomy is a valid model for the study of acute liver failure. Since the porcine liver is comparable in size, morphology and anatomy to the human liver, we describe a technique employing hepatic ischemia and extended liver resection to induce acute liver failure in a porcine model as a means of studying bioartificial liver support. METHOD: A subtotal (75-80% resection) extended left hepatectomy was performed in 7 pigs after 60 min warm ischemia of the future remnant liver. After resection, the animals were given the best supportive care and observed until death. RESULTS: All animals died within 18-48 h, none as a result of surgical complications. Gross appearance of the liver showed severe steatosis of the right lateral lobe, and histology revealed severe coagulative necrosis of the whole lobule. CONCLUSION: This technique of extended liver resection after hepatic ischemia in the porcine model may be useful for studies of potentially reversible acute liver failure and experimental bioartificial support.

Animals↗