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Biomedical subjects

K Reemtsma

Publications and source records attributed to K Reemtsma.

At least 91 records · Page 5Linked to original sources

Elevated pulmonary vascular resistance and cardiac transplantation.

Severe elevation of pulmonary vascular resistance has been considered a contraindication to cardiac transplantation. Most centers exclude patients with pulmonary vascular resistance greater than 6 Wood units. Wood units, however, do not correct for variations in body size and therefore may not be the best measure for use in comparison of patients. We performed a retrospective analysis of 82 cardiac transplant recipients and compared preoperative pulmonary vascular resistance (PVR) calculated in two ways to the incidence of right ventricular failure and death. Our data show that the PVR index unit (PVRI) identifies those patients that are at risk for right heart failure better than the Wood unit, which does not correct for body size. Four patients died of right heart failure with resistance less than 6 Wood units, but had PVRI greater than 6 units. High resistance is not an absolute contraindication to cardiac transplantation; 28 of 33 patients operated on with a PVRI greater than 6 survived. The degree of elevation of PVR did not correlate with survival. Ten of 12 patients with a PVRI greater than 9 survived. Testing with nitroprusside at cardiac catheterization was helpful in determining reversibility of pulmonary vascular obstruction. No patients with a PVRI less than 6 developed right heart failure.

Adolescent↗

Cardiac xenotransplantation in primates.

Successful cardiac xenotransplantation would alleviate the severe shortage of donor organs that presently limits the availability of cardiac transplantation. Early attempts at human xenotransplantation achieved minimal success. However, the effectiveness of cyclosporine in nonhuman xenotransplant models has received little experimental investigation. We have therefore studied the effect of cyclosporine-based immunosuppression in primate cardiac xenograft models using cynomolgus monkey donors and baboon recipients. Donor hearts were transplanted heterotopically into the necks of recipients or in the orthotopic position. Recipients were treated with no immunosuppression (controls), cyclosporine and steroids, or cyclosporine, steroids, azathioprine, and antithymocyte globulin. Statistically significant prolongation of graft survival compared to the control group was observed in the heterotopic groups. Mean survival time of the cyclosporine-treated and steroid-treated heterotopic grafts was 61 days compared to 6 days for grafts in the control group (p = 0.01); the addition of azathioprine and antithymocyte globulin yielded a mean survival of 84 days (p less than 0.01). No significant increase in graft survival was noted in the orthotopic groups treated with either immunosuppressive regimen. Although long-term use of human xenografts as an alternative for heart replacement is not supported by these data, further investigation of the orthotopic model is clearly justified.

Animals↗

Reversal of cardiac transplant rejection without massive immunosuppression.

Although cyclosporine has decreased the severity of acute cardiac transplant rejection, most centers have continued to use high-dose intravenous steroids to treat acute rejection. To minimize the morbidity of antirejection therapy, acute rejection episodes in 37 cardiac transplant recipients were treated prospectively with only a boost of oral prednisone. Cyclosporine was continued at the same maintenance dose while oral prednisone was increased to 100 mg/day for 3 days, then rapidly tapered over 1 week to the maintenance dose. Seventy-six of 85 acute rejection episodes (90%) showed histologic resolution of mycocyte necrosis on repeat biopsy. Three acute rejection episodes (3.5%) resolved only after "rescue therapy" with intravenous steroid, and an additional three episodes (3.5%) required the combination of intravenous steroid and rabbit antithymocyte globulin to effect resolution. In addition, three acute rejection episodes (3.5%) resulted in graft loss. This was fatal in two patients and one patient underwent successful retransplantation. Oral steroid therapy alone is adequate therapy for most acute rejection episodes in cyclosporine-treated heart transplant recipients, and low infectious morbidity and mortality has been associated with this antirejection protocol.

Adolescent↗

Hemostatic effectiveness of fibrin glue derived from single-donor fresh frozen plasma.

Fibrin glue derived from pooled human blood is an effective sealant for high-porosity vascular grafts and a valuable topical hemostatic agent in heparinized patients. Use of this agent in the United States is prohibited because of potential transmission of hepatitis B, acquired immunodeficiency syndrome, and other serologically transmitted illnesses. We have developed a cryoprecipitation technique that allows preparation of fibrin glue from single-donor fresh frozen plasma. Use of this agent presumably entails no greater risk of disease transmission than intravenous administration of single-unit fresh frozen plasma. This report describes our early clinical experience with this material. Fibrin glue was used as a sealant for porous woven Dacron tubular prostheses and cardiovascular patches in 19 patients. The fibrin glue sealant has also been employed to control bleeding from needle holes and small anastomotic tears in 22 patients. No patient in this series had a bleeding complication from a suture line or graft treated with fibrin glue. This experience indicates that like fibrin glue from pooled blood, fibrin glue from single-donor plasma is effective as a graft sealant and topical hemostatic agent. Preparation of fibrin glue from single-donor plasma is simple and economical, and may provide cardiothoracic surgeons in the United States with a widely available, valuable hemostatic adjunct.

Blood Donors↗

Cardiac transplantation. Changing patterns in evaluation and treatment.

This study reports the authors' experience with 66 heart transplants in 64 patients done over an 8-year period (1977-1985). In the early series, a high frequency of complications involving serious infections was noted. In April 1983, the immunosuppressive regimen was changed to cyclosporine and low-dose steroids. Patients were monitored with frequent myocardial biopsies and determinations of serum cyclosporine levels. Although this is not a controlled study, the authors believe that the improved results, including reduced frequency and severity of infections, are related to altered immune suppression. They speculate that patients with successful cardiac grafts develop a form of specific unresponsiveness and now are studying the mechanisms of this adaptation.

Azathioprine↗

Selective lymphoid irradiation. VI. Effect of palladium-109-labeled lymphocytes on rat cardiac allograft survival.

We have previously shown that pretransplant treatment with palladium-109 hematoporphyrin (Pd-H) and two small doses of antilymphocyte globulin (ALG) leads to donor-specific permanent acceptance of cardiac allografts in weakly histoincompatible rat combinations and significant prolongation of hearts in the ACI-to-Lewis strains. Pd-H also concentrates in nonlymphoid organs to a significant degree that is undesirable, so we have examined, in the present study, the efficacy of Pd-109 attached to lymphocytes in producing selective lymphoid irradiation and compared it with the immunosuppressive effect of Pd-H. Adoptive transfer of syngeneic lymphocytes labeled with palladium-109 (Pd-L) led to significant concentration of radioactivity in the peripheral lymphoid organs relative to the bone marrow (BM), intestine, thymus, and endocrine organs. The concentration of radioactivity in the spleen relative to BM and intestinal mucosa was 23:1 and 58:1, respectively. The immunosuppressive efficacy of a suboptimal dose of 3 mCi (one-third of the dose used in our earlier reports with Pd-H) administered via Pd-L (6 X 10(9) cells) at 4 days combined with 5 mg ALG at 2 days and 1 day prior to transplantation was compared in its effect on cardiac allografts with a similar dose of Pd-H (3 mCi) combined with ALG. The mean survival time (MST) of 6.5 +/- 0.4 days in untreated recipients was moderately prolonged to 14.6 +/- 3.0 days by Pd-H and ALG, and was not significantly different from an MST of 14.1 +/- 0.3 days achieved with 2 doses of ALG alone. Pretransplant treatment of Lewis rats with Pd-L and ALG produced a significant prolongation of ACI heart allografts to 30.5 +/- 3.1 days (P less than 0.001). These results suggest that Pd-L is more effective in prolonging rat cardiac allografts than a similar dose of Pd-H, and thus it may be a new method of selective lymphoid irradiation prior to transplantation.

Animals↗

Presence of neuron-specific enolase and somatostatin in human parathyroid tissues.

The association of parathyroid abnormalities with apudomas prompted us to examine parathyroid tissues for the presence of neuron-specific enolase and somatostatin. Enolase was present in extracts of 29 out of 29 parathyroid specimens; tissue content was significantly higher in adenoma than in hyperplasia tissues (p less than 0.005). Somatostatin was present in 14 of 33 specimens. Immunoreactive somatostatin measured in tissue extracts' fluids coeluted on Sephacryl chromatography along with synthetic somatostatin-14 in studies of two parathyroid carcinoma specimens. Since neuron-specific enolase has been found only in neural and neuroendocrine cells, our results suggest that human parathyroid glands may contain neuroendocrine elements. The differential content of neuron-specific enolase in adenoma versus hyperplasia specimens may be diagnostically useful in selected cases. The significance of the presence of somatostatin in some but not all parathyroid tumors requires further investigation. Taken together with our prior findings of gastrin and pancreatic polypeptide in some human parathyroid glands, we postulate that human parathyroid tumors contain neural crest elements.

Adenoma↗

Preparation of fibrin glue from single-donor fresh-frozen plasma.

Fibrin glue is used widely in Europe as a tissue sealant and hemostatic agent. The European glue is prepared commercially from pooled human blood. It is not available in this country because of the risk of transmission of hepatitis B, acquired immune deficiency syndrome, and other blood-transmitted diseases. We describe a cryoprecipitation technique for preparation of fibrin glue from single-donor fresh-frozen plasma. This technique enables the glue to be made in large quantities with no greater risk of disease transmission than with that from the transfusion of single-unit fresh-frozen plasma. We have found that the glue is a useful tool in surgery. By helping to control difficult bleeding, its use can decrease the need for blood transfusions and shorten operating room time. It also is effective as a means to pretreat highly porous vascular prostheses that currently are used infrequently because of bleeding. These porous grafts offer potential advantages in handling, suturing, and long-term patency. This new technique of fibrin glue preparation may make this useful surgical adjunct as readily available in this country as it is in Europe.

Chemical Precipitation↗

Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats.

Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression.

Animals↗

Reduced infection in cardiac transplant recipients.

Despite the introduction of cyclosporine immunosuppression, infectious morbidity and mortality in cardiac transplant recipients has remained high. To decrease infectious complications, lower doses of cyclosporine and oral prednisone than previously reported were used for maintenance immunosuppression in 22 operative survivors of orthotopic cardiac transplantation. Twelve infections occurred in 10 patients followed 8 +/- 5 months. Fifty-five percent of patients had no infectious complications. There were no deaths. Seven infections required hospitalization for a mean of 12 days. Infection rate per patient for the first 3 months after transplantation was 0.23 compared with a range of 0.82 to 1.06 in series previously reported in which higher doses of steroids were used. Lowered doses of steroid can be used for maintenance immunosuppression and treatment of rejection with acceptable short-term results. With such a protocol, a low incidence of controllable infectious complications with no deaths has been observed.

Adolescent↗