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Biomedical subjects

J Pratschke

Publications and source records attributed to J Pratschke.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intravenous or intramuscular anti-HBs immunoglobulin for the prevention of hepatitis B reinfection after orthotopic liver transplantation.

To prevent reinfection with hepatitis B virus after orthotopic liver transplantation, patients receive long-term intravenous anti-HBs immunoprophylaxis. We compared the pharmacokinetics of intravenously and intramuscularly administered commercially available hepatitis B virus immunoglobulins. The study group consisted of 12 patients on immunoprophylaxis after orthotopic liver transplantation, who were Hbs antigen negative; 11 were anti-HBe positive and one was HBe positive. The patients first received intravenous immunoglobulin, and six of them were then transferred to intramuscular immunoglobulin. Our findings show that with fortnightly intramuscular application of 1000 IU of anti-HBs, reproducible and stable antibody titers above 100 IU of anti-HBs can be achieved. Side effects of intramuscular immunoprophylaxis are minimal and the method is safe. The switch from intravenous (1500 IU of anti-HBs) to intramuscular (1000 IU of anti-HBs) reduced the cost of immunoprophylaxis by more than 50%.

Adult↗
PubMed1997

Mycophenolate mofetil added to immunosuppression after liver transplantation--first results.

Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive agent after kidney and heart transplantation, but experience with MMF after liver transplantation is still limited. Between August 1995 and January 1996, we treated 20 patients with MMF after orthotopic liver transplantation in an open, prospective study. Five out of eight patients with acute rejection and one patient with early chronic rejection showed a complete response after MMF was added to the immunosuppression. Three patients with chronic rejection did not improve, one died, and two have stable graft function at present. In eight patients who suffered from toxicity, a reduction in the dosage of tacrolimus was attempted with simultaneous MMF therapy. One patient died due to multiple organ failure. Liver function improved completely in one other patient, and partially in three patients after adding MMF. In the remaining three patients, a reduced dosage of tacrolimus or cyclosporin, together with MMF, reduced toxicity, not significantly. In conclusion, MMF appears to be a safe and potentially useful adjuvant immunosuppressive agent for rescue and maintenance therapy.

Acute Disease↗
PubMed1992

Allogeneic heart transplantation following xenogeneic bridging.

Xenografting seems to be a solution to bridge the time intervals when an essential allograft cannot be obtained. A subsequent allograft was never tried. Eight dogs (20-24 kg) of 2 years of age underwent right cervical heart transplantation. Donors were silver foxes (3-4 kg). The animals were treated by triple drug therapy consisting of cyclosporin A, methylprednisolone and azathioprine in clinical dosages. For control, six recipients received allogeneic heart transplantation (AHTP) and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed to the same right cervical vessels. Routine histology and immunohistology were performed. Thromboxane B2 and 6-keto-prostaglandin Fla were determined daily in peripheral blood. After final rejection sensitization of the recipient was controlled by haemagglutination tests. Survival times of the xenografts were 9.6 +/- 1.2. The subsequent hearts under the same therapy beat for 4.5 +/- 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However 6-keto-prostaglandin Fla showed no significant differences between long-time survivors and hyperacute rejecting hearts. After xenogeneic transplantation all recipients showed haemagglutinating titres between 1:4 and 1:16. Allogeneic grafts have different kinetics of rejection following xenogeneic heart transplantation (XHTP) compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection. This type of rejection is not associated with a change in 6-keto-prostaglandin Fla levels. These results indicate, that xenogeneic bridging under a common immunosuppressive regimen could lead to accelerated rejection of the following allograft. Under this condition clinical bridging is not advisable.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor.

INTRODUCTION: Experimental studies suggest that brain death in the donor has a significant impact on graft quality; however, there are no data correlating organ-specific cytokine expression and the corresponding serum protein levels in human organ donors. Furthermore, it is unknown whether donor treatment can reduce the up-regulation of proinflammatory cytokines and thereby optimize organ quality. METHODS: We investigated the expression pattern of cytokines comparing serum (n = 53) and tissue expression (n = 25) in brain-dead human donors. The controls were living donors (n = 25). Additionally 41 deceased donors were treated with steroids before organ harvest (250 mg initial, afterward 100 mg/h until laparotomy). Hepatic tissue samples were obtained immediately after donor laparotomy to assess transcription rates of tissue cytokines (IL-6, IL-10, CD3, TGFb, TNFa, BAG, HO-1, Mipla) by RT-PCR. Serum samples were obtained after declaration of brain death and before laparotomy. RESULTS: Transcription of proinflammatory cytokines was significantly increased in brain-dead compared to living donor grafts (P < .005). Donor treatment with steroids led to significantly decreased tissue and serum expression of proinflammatory cytokines (P < .01), which were comparable to living donors. Tissue levels of cytokines (IL-6, IL-10) correlated strongly with serum levels of the corresponding proteins. CONCLUSIONS: Serum protein levels of proinflammatory cytokines proffer a valuable, easy accessible marker to define the immunological status of a graft. Our data suggest a beneficial effect of anti-inflammatory treatment of brain-dead organ donors.

Brain Death↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗