Biomedical subjects
K Reemtsma
Publications and source records attributed to K Reemtsma.
Mercurial diuretic protection of the ischemic kidney in the rat.
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Colon interposition for esophageal obstruction.
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Vascular (humoral) rejection in human cardiac allograft biopsies: relation to circulating anti-HLA antibodies.
Vascular or humoral rejection (as defined by linear deposits of immunoglobulin and complement in myocardial capillaries) and the presence of circulating lymphocytotoxic anti-HLA antibodies are each associated with reduced long-term graft or patient survival. The relationship between these two factors has not been determined. We used immunofluorescent techniques to study 46 cardiac biopsy specimens in 16 patients from 15 to 412 days after transplantation. Biopsy specimens were selected from the first 2 months, and at approximately 6 and 12 months after transplantation and did not include episodes of acute cellular rejection. Each specimen studied was compared to a serum sample drawn an average of 1.8 days (range, 0 to 9 days) from the time of biopsy to assay for circulating anti-HLA antibodies. Of the specimens obtained at or near a positive anti-HLA antibody test, 90% (27 of 30) were found to have linear deposits of immunoglobulin (not necessarily with complement) versus 75% (12 of 16) of specimens obtained at the time of a negative test. Twenty-one cases of vascular rejection were documented. Both immunoglobulin M and immunoglobulin G were deposited along with complement in 13 instances; immunoglobulin M and complement were deposited in eight cases; no case had only immunoglobulin G and complement. The presence of circulating anti-HLA antibody in the serum was associated with 14 of the 21 cases of vascular rejection. Linear deposits of immunoglobulin in the capillaries of myocardium were frequently observed when anti-HLA antibodies were present in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Prolonged cardiac xenograft survival: a favorable comparison with allografts in primates.
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Effect of simultaneous lung transplantation on heart transplant survival in rats.
Clinical observations in humans reveal that heart-lung transplant recipients suffer significantly less cardiac rejection than those receiving only heart transplants. A heterotopic combined heart-lung model in rats was used to test the hypothesis that the presence of the lung in this combination increases survival of the heart transplant. Cardiac survival was compared between en bloc heart-lung transplants and heart transplants. Low dosages of cyclosporine were used to prolong but not prevent the rejection process. Heart graft survival in the cyclosporine, 1 mg/kg/day, groups was significantly prolonged in heart-lung allografts. Histologic studies also demonstrated more advanced rejection of the heart in the heart-only transplant groups as compared with the heart-lung transplant groups. This study shows that the presence of the lungs in heart-lung allografts provides for prolongation of cardiac survival.
Femorofemoral bypass for unilateral iliac artery occlusion in the presence of bilateral superficial femoral artery occlusions.
The femorofemoral bypass has become a popular technique of reconstruction for unilateral iliac artery occlusion because of low morbidity and excellent long-term patency. A "steal phenomenon" is infrequently seen, but even in relatively sedentary patients with limb-threatening ischemia femorofemoral grafting has been associated with severe donor limb ischemia in occasional instances. This report describes five high risk elderly patients who underwent femorofemoral bypass for limb-threatening ischemia due to unilateral iliac artery occlusion in association with bilateral superficial femoral artery occlusions. All patients underwent successful bypass as judged by relief of rest pain and healing of ulcerations. Despite a pre-operative resting donor limb mean ankle/brachial index of .45, there was no deterioration of donor limb perfusion when patients were followed for a mean of 15.6 months. It is concluded that femorofemoral bypass is the procedure of choice for limb salvage in poor risk patients with adequate donor limb inflow regardless of the degree of outflow occlusive disease.
Present status of human cardiac allografts and prospects for xenografts.
Cardiac allotransplantation is no longer experimental. It is the standard by which all other methods of cardiac replacement must be judged. The dramatic improvement in survival and the quality of life of cardiac transplant recipients reflects many factors including refined criteria for patient and donor selection, as well as the clinical introduction of cyclosporine. Current contraindications to the procedure include: 1) age greater than 65 years, 2) active infection, 3) active malignant neoplastic disease, 4) recent pulmonary embolus or infarction, 5) irreversible renal or hepatic failure, and 6) fixed elevation of pulmonary vascular resistance. The introduction of cyclosporine has been accompanied by an increase in the 1 year survival. While the use of cyclosporine has not decreased the incidence of rejection episodes, it has dramatically decreased their severity. In addition, the incidence and severity of infectious complications, as well as the length of hospitalization, have been decreased with the introduction of cyclosporine. Despite the progress made, several problems remain in the management of transplant recipients. Chronic cyclosporine therapy has been associated with a disturbingly high incidence of hypertension and renal impairment, and a low, yet significant, incidence of malignant neoplasms. However, the most significant obstacle to successful clinical cardiac transplantation is the scarcity of donor organs. Many centers now report that the mortality rate for patients awaiting transplantation exceeds the mortality associated with the procedure itself. Donor scarcity has led to renewed interest in the development of mechanical cardiac devices and investigation into cross-species transplantation (xenotransplantation).
Role of the carrier solution in cyclosporine pharmacokinetics in the baboon.
Although numerous investigational models have demonstrated the potent immunosuppressive properties of cyclosporine, the effectiveness of any given dosage may vary with the metabolism of the animal, the route of administration, and the carrier solution of the drug. We investigated the pharmacokinetics of intramuscular cyclosporine administration in the baboon using three carriers: polyoxethylated castor oil (Cremophor), a mixture of octanoic and decanoic acids (Miglyol), and olive oil. Cyclosporine prepared in Cremophor, Miglyol, or olive oil was injected intramuscularly into the hindlegs of baboons. Specimens for cyclosporine assay were obtained 2, 4, 6, 12, 18, and 24 hours after single intramuscular injection of 10 mg/kg or 15 mg/kg. In addition, weekly, then monthly, levels were obtained on animals receiving daily intramuscular injections following heterotopic heart xenografts. Attempts at oral administration proved unreliable and were discontinued. Cyclosporine assay was performed on stored serum using the RIA-KIT (Sandoz Pharmaceuticals Corporation, East Hanover, N.J.). Cremophor provides a more bioavailable form of cyclosporine than Miglyol when administered intramuscularly. (Area under curve = 7776 +/- 1437 for Cremophor 15 mg/kg vs 1837 +/- 726 for Miglyol 15 mg/kg; 2579 +/- 694 for Cremophor 10 vs 1123 +/- 393 for Miglyol 10.) Long-term daily intramuscular administration of Cremophor provides a sustained drug serum trough level with wide variability between individual animals (80 to 825 ng/ml). Toxicity was limited to injection site inflammation. There was no biochemical evidence of renal toxicity; however, some animals did demonstrate early histologic changes of cyclosporine effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Pretransplant blood transfusion in a primate cardiac xenograft model.
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Cyclosporine increases rat heart weight in heterotopic transplants.
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High-density seeding of cultured endothelial cells leads to rapid coverage of polytetrafluoroethylene grafts.
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Efficacy of percutaneous angioplasty in lower extremity arterial occlusive disease.
One hundred and twenty four percutaneous transluminal angioplasties performed over a 5 year period for lower extremity arterial occlusive disease were reviewed to evaluate clinical efficacy and define parameters of success. Technical success was achieved in 82%, clinical success in 71%. The important predictive variables were severity of disease, anatomic site and length of diseased vessel segment. Best results (94% success rate) were obtained in the proximal single segment lesion with lesser initial disease as reflected by flow study, calf vessel runoff and claudication as the indication for treatment. The poorest results (33% success rate) were obtained in distal vessels with multisegmental disease where limb salvage was the indication for intervention. Stenosing or recently occluded bypass grafts were successfully dilated in 7 of 8 patients. With a complication rate of 3%, percutaneous angioplasty is clearly a highly effective treatment for lower extremity arterial insufficiency in the properly selected patient judged by immediate and relatively short term follow-up observations.
Counterpulsation with a new pulsatile assist device (PAD) in open-heart surgery.
A new pulsatile assist device that converts roller pump flow to pulsatile flow has been developed and proven effective through clinical testing. The PAD is also a hemodynamically effective arterial counterpulsator both before and after cardiopulmonary bypass. The PAD has been found to be an important adjunct to the care of critically ill patients undergoing open-heart surgery. In addition, in selected patients, the PAD is a reasonable alternative to the elective use of intra-aortic balloon pumping.
Hemodynamic alterations with a reversed unidirectional intra-aortic balloon.
The hemodynamic effects of dual-chambered unidirectional balloon pumping in alternate directions were studied in 44 trials conducted on 8 dogs. Results indicate an increase in cardiac output in normal dogs with downstream pumping by unidirectional intra-aortic balloon, which may have important implications for the treatment of low output cardiac failure.