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Biomedical subjects

H Obertop

Publications and source records attributed to H Obertop.

At least 235 records · Page 13Linked to original sources

The effect of cyclosporin A and blood transfusions on cardiac allograft survival in rats.

Blood transfusions may have a beneficial or deleterious effect on graft survival. The purpose of the present study was to see whether cyclosporin A (CyA) could overcome the sensitizing effect of pretransplant blood transfusions and whether it would alter the beneficial effect of blood transfusions. Therefore, the effect of CyA was studied in transfused and nontransfused recipients by use of a rat cardiac allograft model. The BN/Ro and Wag/Ro strains were used. Each strain rejects a heart allograft from the other in 8 to 9 days when nontransfused recipients are involved. After conditioning with one donor-specific pretransplant blood transfusion, accelerated rejection is seen in the Wag/Ro to BN/Ro combination, whereas indefinite survival occurs in the reverse combination. CyA treatment results in indefinite graft survival in nonsensitized recipients of both strains but at a lower dosage in the BN/Ro to Wag/Ro combination. In transfused BN/Ro recipients, CyA prolongs heart allograft survival indefinitely, although higher doses are required (15 mg/kg) than in nonsensitized recipients; in the reverse combination, CyA does not interfere with the beneficial blood transfusion effect. The findings that CyA can prevent accelerated rejection in the Wag/Ro to BN/Ro combination and that it does not alter the beneficial effect in the reverse combination might mean that CyA is a useful drug even in sensitized recipients.

Animals↗

Expression of beneficial blood transfusion effect in dogs is dependent upon immunosuppressants used.

To achieve the beneficial blood transfusion effect, postoperative immunosuppression with Aza/Pred is mandatory. When CY-A is used for immunosuppression during a limited time, the transfusion effect is not manifested; however CY-A does not lessen the effect in animals given Aza/Pred. In nontransfused recipients, the combination of Aza/Pred and CY-A did not give better graft survival than CY-A alone.

Animals↗

Haemodynamics and renal function in patients undergoing surgery for abdominal aortic aneurysm.

Haemodynamics and renal function were studied in patients undergoing surgery for abdominal aortic aneurysm, before, during and after infrarenal aortic clamping, in order to establish base-line criteria. The mean arterial pressure (MAP) remained practically unchanged during aortic clamping. A significant decrease in cardiac index (CI) was found. The significant decrease in pulmonary artery wedge pressure (PAWP), despite a significant rise in the systemic vascular resistance (SVRI), probably reflects relative preoperative dehydration and venous pooling in the lower part of the body. Brief suggestions are made concerning the management of this condition. No irreversible loss of renal function was seen.

Aged↗

Pretransplant blood transfusions can harm matched kidneys in dogs.

The effect of pretransplant blood transfusion (PBT) and histocompatibility matching on kidney allograft survival was studied in immunosuppressed dogs. PBT was found to be beneficial for related and unrelated mismatched kidney grafts. In contrast, after withdrawal of the immunosuppressants, transfused recipients of related and unrelated matched grafts rejected the kidney significantly more often than non-transfused dogs. Crossimmunisation for minor histocompatibility antigens may be responsible for this adverse effect, but could not be demonstrated in vitro by serology or mixed lymphocyte reactions. The possible deleterious effect of PBT in this model argues against the routine use of pretransplant blood transfusions in man.

Animals↗

Genetics of kidney allograft survival in dogs. III. Relevance of histocompatibility matching in immunosuppressed recipients.

The relevance of matching for the serologically defined (SD) and lymphocyte-defined (LD) antigens of the major histocompatibility complex (MHC) for renal allograft survival was evaluated in a dog model. Kidney recipients were treated with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney function remained normal for the period of 150 days during which immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function deteriorated during immunosuppressive therapy, and most of the recipients died eventually from graft rejection. Thus, it seems that, in moderately immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause rejection, whereas DLA incompatibilities almost always do so. The data differ from those obtained in a previous study in nonimmunosuppressed dogs, in which non-DLA incompatibilities seemed to be as strong as DLA incompatibilities in this respect. Differences in minor histocompatibility antigens can apparently be overcome more easily by immunosuppressive drug therapy than differences in major histocompatibility antigens. After the gradual complete withdrawal of immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs survived for another 150 days or more, implying that some kind of unresponsiveness was induced in those dogs.

Animals↗

Clinical experience with the medical anti-shock trousers (MAST) treatment of hemorrhage, especially from compound pelvic fracture.

The experience and results of treatment with external counterpressure for uncontrollable bleeding in 11 patients with compound pelvic fractures and 7 other patients with various subdiaphragmatic bleeding sites are reported. In 11 cases (61%) the bleeding could be arrested with medical anti-shock trousers (MAST). 9 patients died: 5 due to hemorrhagic shock and 4 of related disorders. Treatment with MAST was unsuccessful in 7 cases of major arterial tears. In patients with compound pelvic fractures the acute blood loss may necessitate further treatment by either arterial embolization, an operation for concomitant traumata, or both. Complications of the use of MAST were minor. The (clinical) use of this garment can therefore be strongly advised in patients with otherwise intractable bleeding.

Adolescent↗

Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy.

The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.

Animals↗

Prolongation of renal allograft survival in DLA-tissue typed beagles after third-party leucocyte and erythrocyte transfusion.

In a dog model, both transfusion of leucocytes and of erythrocytes induced lymphocytotoxic antibodies. The results, obtained in DLA identical littermate and DLA nonidentical nonrelated beagle recipient pairs, suggest a correlation between DLA-type and lymphocytotoxic immune response. Two weeks after the last of three transfusions from different blood donors, kidneys from unrelated DLA-mismatched donrs were transplanted to the beagle recipients. A standard postoperative immunosuppressive regimen was given. No correlation between erythrocyte or leucocyte induced immune response was observed, but both erythrocyte as well as leucocyte transfusions significantly prolonged renal allograft survival as compared with nontransfused controls.

Animals↗

Effect of prior third-party blood transfusions on canine renal allograft survival.

The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed. Genetic control of this reactivity or a linkage of this property to DLA, sex, or red blood cell markers inheritance was not apparent in the four beagle families studied. The two recipients with the lowest immune reactivity scores were also found to be the longest survivors after a DLA-mismatched kidney graft. Seven other recipients with higher scores rejected their DLA-mismatched kidneys as rapidly as did untransfused animals. Kidney graft survival was decreased in some recipients of DLA-identical kidneys (n = 5), presumably through sensitization for minor histocompatibility antigens. A normal or an increased survival time of DLA-identical kidneys was found in the remaining animals (n = 6). The majority of these recipients appeared to have a higher than average reactivity in two-stage microcytotoxicity testing. This might have been attributable to the presence of enhancing antibodies. Further studies in preclinical animal models are needed to define the optimal transfusion policy for human patients awaiting a kidney graft.

Animals↗

Prolongation of renal allograft survival in DLA tissue-typed beagles after third-party blood transfusions and immunosuppressive treatment.

Significant prolongation of survival of nonrelated DLA-mismatched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.

Animals↗

Effect of prior parental blood transfusions on the survival of renal allografts from a DLA-identical sibling.

Renal allografting was performed between DLA-identical beagle littermates without immunosuppressive treatment. One transfusion of 200 ml of parental blood donor to induce the formation of antibodies against non-DLA antigens that might enhance renal graft survival. Kidney graft survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of DLA-identical nontransfused littermates. Blood transfusions did not have a significant influence on the median graft survival time. Antibodies against the kidney donor lymphocytes were not demonstrated after blood transfusion. However, antibodies were induced in three of the six animals tested as shown by the reactivity of the sera of these animals against a lymphocyte panel. Antibodies occurred in animals with long-term as well as short-term surviving grafts.

Animals↗

Lost mass and excretion as stimuli to parabiotic compensatory renal hypertrophy.

To help determine the roles of lost renal mass and lost excretory ability in producing renoprival hypertrophy, observations were made in otherwise normal rats cross-circulated for 24 h with rats prepared in one of the following ways: bilateral nephrectomy, bilateral ureteral ligation, or bilateral nephrectomy with 24 h of uremia. Bilateral nephrectomy produced parabiotic increases in renal mass and in the average cellular concentration of RNA: bilateral ureteral ligation did not. Uremia did not potentiate the effects of bilateral nephrectomy. Lost mass is the determinant of compensatory renal hypertrophy.

Animals↗

Onset of cell proliferation in the shortened gut. Colonic hyperplasia after ileal resection.

Cytokinetics in colonic mucosa were studied after ileal resection in young female rats. The RNA content of the transverse colon was increased 32% after 7 days; after 14 days the increase was present throughout the colon. The DNA content of the ascending colon increased 29% after 10 days. Specific activity of DNA labeled with [3H-methyl]thymidine was elevated 29% in the ascending colon and elevated 49% in the descending colon on the 7th postoperative day. Colonic cell proliferation is stimulated within 1 week of ileal resection.

Animals↗