PubMed Health⌕ Search

Biomedical subjects

A Pascher

Publications and source records attributed to A Pascher.

51 records · Page 3Linked to original sources

Transsection of the peroneal nerve complicating knee arthroscopy: case report and cadaver study.

We report the case of a 36-year-old male patient who sustained a hyperextension trauma of the left knee. After performing diagnostic arthroscopy (partial tear of the anterior cruciate ligament) and partial resection of the anterior cruciate ligament, the patient experienced a complete paralysis of the peroneal nerve. One year after the first surgical procedure, a reconstructive repair of the peroneal nerve and a transfer of the anterior tibial muscle was performed. This complication is reported for the first time in literature.

Adult↗

Immunopathological observations after xenogeneic liver perfusions using donor pigs transgenic for human decay-accelerating factor.

BACKGROUND: Donor pigs transgenic for human decay-accelerating factor (hDAF) were used in a xenogeneic ex vivo liver perfusion model to study the effect of this modification on the development of hyperacute rejection. METHODS: Three transgenic pigs were hepatectomized after hypothermic portal and transaortal gravity perfusion. Livers from six nontransgenic pigs served as controls. All livers were perfused for 3 hr with human blood from two donors diluted to a hematocrit of 30%. Particular importance was placed on the use of an optimal perfusion technique incorporating the floating suspension of the organs in a waterbath and intermittent external pressurization. Biochemical, physiological, and immunological parameters were assessed. Tissue specimens taken before and after perfusion were analyzed using routine histology, electron microscopy, and immunohistology. RESULTS: Complement activation was more pronounced in the control group. AP50 and CH50 values fell to about 60% of the initial levels in control experiments, whereas they remained at 80% of the initial levels during perfusion of hDAF livers. After 180 min, pig tumor necrosis factor alpha levels were 7862+/-1645 pg/ml for unmodified livers and 2830+/-734 pg/ml in the hDAF group. Human tumor necrosis factor alpha levels were similar in both groups. Control livers showed marked morphological alterations and distinct deposition of complement factors, whereas livers expressing hDAF showed no signs of hepatocellular necrosis and almost no complement deposition beyond C3 activation. CONCLUSIONS: These results confirm that the transgenic expression of the human complement regulatory protein hDAF reduces complement activation and prevents hyperacute rejection in a xenogeneic liver perfusion model over the 3-hr evaluation period used in this study.

Animals↗

Application of immunoapheresis for delaying hyperacute rejection during isolated xenogeneic pig liver perfusion.

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.

Acute Disease↗

Expression of human decay accelerating factor (hDAF) in transgenic pigs regulates complement activation during ex vivo liver perfusion--immunopathological findings.

Ex vivo perfusions of human decay accelerating factor-expressing transgenic (n = 3), and nontransgenic (n = 6) porcine livers with human blood revealed a higher degree of organ damage in non-transgenic pig livers. Transgenic livers were protected from immunohistologically detectable complement deposition, despite corresponding IgM and IgG deposits in both groups. Complement activation and consumption of C3 and C4 turned out to be lower in transgenic pig livers. In contrast to livers of normal landrace pigs, livers from genetically manipulated pigs showed no morphological alterations after perfusion.

Animals↗

The function of transgenic human DAF-expressing porcine livers during hemoperfusion with human blood.

Extracorporal pig liver perfusion could bridge the deadly problem of acute human liver failure. However, preformed natural antibodies and complement activation (CA) are the predominant mechanisms of hyperacute xenogeneic rejection. The blockade of both pathways of CA in the xenograft, using transgenic livers expressing human decay accelerating factor on the endothelial surface results in prolonged graft survival and lower release of mediators.

Animals↗

Induction of carbon monoxide in the donor reduces graft immunogenicity and chronic graft deterioration.

Chronic allograft dysfunction remains the major obstacle for long-term successful transplantation. To date there is no effective treatment. Overexpression of protective genes has provided increased graft function and survival. This mechanism has been implicated in the process of graft accommodation. One of these genes that has been shown to mediate protective effects decodes the enzyme heme oxygenase-1 (HO-1), and an HO-1 downstream product, carbon monoxide (CO). Using an established model of kidney chronic allograft rejection in the rat, we investigated the impact of methylene chloride (MC), a CO donor, as a therapeutic tool to reduce chronic graft deterioration. We showed that donor and long-term recipient treatment with MC improved graft function and reduced histological signs of chronic rejection. Carbon monoxide may be a promising agent to improve graft quality and long-term graft function.

Animals↗

Induction of heme oxygenase-1 in the donor reduces graft immunogenicity.

There is increasing evidence that the induction of the enzyme heme oxygenase-1 (HO-1) improves both graft function and survival. Although it has been shown that HO-1 promotes graft protection, it remains unknown whether it reduces graft immunogenicity by modulating dendritic cells. In the current experiment, we investigated the impact of HO-1 induction on frequencies and trafficking of donor-derived dendritic cells (DCs). Kidneys from DA rats were transplanted into untreated Lewis recipients. Donor animals were treated with cobalt protoporphyrin (CoPP; 5 mg/kg IP) 24 hours prior to organ harvesting to induce HO-1. Controls remained untreated or received zinc protoporphyrin (ZnPP; 20 mg/kg, IP) to block HO-1 induction. Analyses of grafts, spleens, lymph nodes and blood of Lewis recipients were performed at days 1 and 3 posttransplantation. Donor-specific DCs were determined by flow cytometry using haplotype-specific mAb against RT1(ab) and mAb against OX62(+) antigens. Cell markers (CD4/CD8(+) T cells, ED1(+) monocytes, MHC class II(+) CD86(+) DC) were measured by immunohistochemical staining. T-cell alloreactivity of recipient splenocytes was measured by ELISPOT. Induction of HO-1 reduced frequencies of donor-derived DCs in the graft and recipient compartments, which was associated with reduced frequencies of CD4(+) T cells and CD8(+) T cells and alloreactivity. Expression of costimulatory molecule CD86 and MHC class II antigens were also reduced, although not significantly. Thus, induction of HO-1 reduced graft immunogenicity. These mechanisms may explain the protective effects of HO-1 induction.

Animals↗

Grafts from elderly donors elicit a stronger immune response in the early period posttransplantation: a study in a rat model.

With a growing demand for transplants, grafts from older donors are increasingly used. However, altered immune responses associated with increasing donor age may influence graft survival. We dissected the effects of donor age on the immune response in an experimental model. Kidneys from young and old F-344 donors (3 and 18 months) transplanted into young Lewis recipients (3 months) were followed for 6 months. Renal function, structural changes, and immune activation were tested at serial time intervals. Splenocytes and peripheral blood mononuclear cells were examined by flow cytometry; alloantigen-specific intracellular IFN-gamma secretion was evaluated by ELISPOT. Grafts from both young and old donors survived the observation period. The ratio of structural changes (6/1 months) increased twofold in old vs young grafts. In parallel, the ratio of renal function declined by fivefold in recipients of old donor kidneys. Most interestingly, elderly grafts produced a modified immune response: the numbers of T/B cells and alloreactive T cells increased early following the transplantation of old grafts (P < .05). However, by 6 months, the amounts of T and B cells as well as alloantigen-specific immune responses were comparable in recipients of old versus young grafts. Older grafts elicit a stronger immune response during the early period posttransplantation. This process is associated with an increased immunogenicity in older grafts. Clinical immunosuppressive protocols need to consider these effects.

Aging↗

[Analysis of two different techniques of osteosynthesis in high tibial osteotomy].

AIM: High tibial osteotomy is an accepted method for varus osteoarthritis. This study intended to compare the technique of plate osteosynthesis with the technique of staple osteosynthesis, as a less invasive procedure. METHOD: 61 patients (65 knees) were included in this retrospective study evaluating the HSS score, patient's satisfaction, non weight bearing period, radiological stage of osteoarthritis, bone healing and complications after a follow up period of 5.7 (5 - 9) years. 26 patients (27 knees) were treated with plates and 37 patients (38 knees) with staples after osteotomy. RESULTS: Patients treated with plates showed 62.2 % excellent and good, 27.8 % moderate and poor results in the HSS score, 77.8 % were very satisfied and satisfied, 22.2 % less or not satisfied. Patients who received staple osteosynthesis showed 80.8% excellent and good, 19.2 % moderate and poor results in the HSS score and were very satisfied and satisfied in 86.9 %, less and nor satisfied in 13.1 %. The periods of non weight bearing and bone healing were slightly longer for patients treated with staples. There was no significant difference in complications. CONCLUSION: The data of the present study suggest that staples as a less invasive osteosynthesis after high tibial osteotomy seem to be justified compared to plate osteosynthesis having no significant difference in clinical results.

Aged↗