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K Reemtsma

Publications and source records attributed to K Reemtsma.

At least 19 recordsLinked to original sources

Supporting future surgical innovation. Lung transplantation as a case study.

OBJECTIVE: Using lung transplantation as a case study, this article addressed the problem of supporting innovative clinical surgery in an era of increasing pressures for cost containment. SUMMARY BACKGROUND DATA: After sporadic attempts at lung transplantation during the 1960s and 1970s, its clinical development began in earnest during the early 1980s. As a result of a wide range of incremental advances, the results have improved significantly. The Health Care Financing Administration, however, has not yet issued a national policy covering lung transplants and has left the coverage decision to the discretion of its regional contractors. METHODS: The authors surveyed the major commercial insurers, the Blue Cross Blue Shield Association, and a sample of Medicare intermediaries to evaluate the coverage of lung transplantation. They also interviewed the National Heart, Lung, and Blood Institute and industrial firms about their support for clinical research. RESULTS: Government and industry funding were limited, and the development and assessment of lung transplants have been financed predominantly by academic institutions through cross-subsidization from patient care and teaching funds. The major private payers and Blue Cross Blue Shield decided to cover this procedure in the early 1990s. Coverage decisions by Medicare intermediaries, however, revealed considerable variability. Moreover, the absence of a specific diagnosis-related group for lung transplants had considerable consequences for institutions in all-payer states, in which payments appeared to be considerably lower than the mean costs of a transplant procedure (about $110,000). CONCLUSIONS: This analysis indicated that there was a growing disparity between the increasing demand for outcomes data about new procedures and the limited resources available for supporting the development and assessment of new operations. It this disparity is not addressed, the rate of surgical innovation may be jeopardized, and timely outcomes data may not be acquired. It was concluded that provisional coverage within a predetermined research protocol may be a promising mechanism to remedy this situation, providing timely assessment of new procedures before widespread application.

Centers for Medicare and Medicaid Services, U.S.

Sixteen years of cardiac transplantation: the Columbia Presbyterian Medical Center experience 1977 to 1993.

Cardiac transplantation is currently recognized as the best therapy available for the treatment of endstage heart disease. Since 1977, more than 650 cardiac transplants have been performed at CPMC, with a one-year survival rate currently approaching 85% and a 5-year survival rate approaching 65%. Throughout the 16-year experience with cardiac transplantation at CPMC, the criteria of eligibility for both donor and recipient candidates have been expanded to include older patients. In addition, pediatric patients requiring complex arterial or venous reconstruction and patients with elevated, but reversible pulmonary vascular resistance have been transplanted with excellent results. With the evolution of prolonged posttransplant survival has come a new group of complications associated with chronic long-term immunosuppressive therapy. These, and issues relating to cardiac retransplantation, continue to increase, largely because of the critical lack of organ donors. Continued efforts are being developed to optimize and reduce the total amount of immunosuppression administered postoperatively. Currently, research interests at CPMC include therapy for transplant coronary artery disease, left ventricular assist devices, and xenotransplantation. Ongoing investigations in these and other areas of transplantation have been established to encourage continued growth both within the field and at CPMC through the 21st century.

Academic Medical Centers

Xenografts.

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Animals

Evaluation of surgical procedures. Changing patterns of patient selection and costs in heart transplantation.

During the past 4 years we have observed a marked increase in costs of heart transplantation in our center. This trend coincides with a shift in our recipient population toward the more severely ill patients. The percentage of patients bound for the intensive care unit has doubled. In analyzing the components of cost, we find that the length of stay, both in special care and regular nursing units, accounts for most of the cost increase. In our study of outcomes we find no significant difference in survival, at 1 month and 1 year, between recipients operated on from the intensive care unit and those not in intensive care. We find that at 1 year after transplantation, approximately 80% of patients are rehabilitated, which we define as the ability to work or to go to school. Only 20% of patients are off disability rolls, however, primarily because of problems related to insurance and the cost of continuing care, including drugs. We conclude that the comprehensive evaluation of surgical procedures requires an approach that balances costs with results on a continuing and long-term basis.

Costs and Cost Analysis

Management of peripheral vascular problems in recipients of cardiac allografts.

Five hundred and twenty consecutive heart transplant cases (458 adult, 62 pediatric) were reviewed to assess the impact of peripheral vascular problems. Peritransplant interventions requiring vascular cannulation (e.g., intraaortic balloon pump procedures, catheterization of the right and left sides of the heart, femoral bypass) resulted in 10 complications that necessitated nine surgical procedures. Five aortic aneurysms (three infrarenal and two suprarenal) were resected. There was one death unrelated to the aneurysm resection. Sixteen patients had evidence of peripheral vascular disease (PVD). There were three deaths in this group, none directly related to the PVD. Three patients required vascular reconstruction (axillobifemoral, bilateral femoral distal and popliteal endarterectomy) in the posttransplant period, all for advanced ischemic symptoms. Except for one patient in whom ischemia-related ulcers developed on the heels, all patients had improved or stable symptoms that did not require intervention. There were no limb losses or vascular infections. We conclude that despite the rigors of posttransplant immunosuppression, patients with stable manifestations of PVD may successfully undergo heart transplantation and subsequent vascular reconstruction, when indicated, without prohibitive risk.

Adolescent

Effect of recipient gender and race on heart and kidney allograft survival.

Study of long-term survival of heart allografts shows that AA males and females have lower graft survival rates than those observed in NAC recipients. Primary kidney allografts in AA males, but not females, also display lower 5-year survival rates compared to those observed in the corresponding populations of NAC. Comparison of graft survival in the overall population of male and female recipients of kidney allografts shows that females have higher graft survival rates, probably as a result of better HLA matching. The level of alloantibody activity in posttransplantation sera is similar in the two populations, suggesting that factors other than HLA mismatching may contribute to the higher degree of graft failure in AA recipients.

Actuarial Analysis

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Animals

Immunomodulation of kidney and heart transplants by anti-idiotypic antibodies.

To explore the possibility that circulating HLA antigens from the graft and anti-anti-HLA (anti-idiotypic) antibodies influence the long-term survival of renal and cardiac allografts, analysis of 330 renal allograft recipients and 174 recipients of cardiac allografts was conducted. Anti-donor-HLA antibodies (Ab1) present before or after transplantation are associated with graft failure, whereas irrelevant anti-HLA antibodies had no impact on actuarial graft survival. Ab1 may be uncovered by dissociation of immune complexes and depletion of soluble antigens with monoclonal antibody-coated magnetic beads. Of the 421 sera tested from 65 heart recipients, 97 showed Ab1 before depletion and 178 after depletion; similar rise in positive sera was seen in 39 renal transplant recipients. Three distinct patterns of appearance of Ab1 and Ab2 (anti-Ab1 antibody) were recognized. Patients with cyclic variations of Ab1 in association with Ab2 had 100% graft survival, whereas patients with cyclic variations of Ab1 but no detectable Ab2 had 2-year graft survival of 36% for kidneys and 71% for hearts. Presence of Ab1 in all sera after transplantation led to 47% and 56% 2-year renal and heart allograft survival, respectively.

Actuarial Analysis

The role of anti-HLA antibodies in heart transplantation.

The major threat to long-term survival of heart allograft recipients is the development of graft atherosclerosis, which seems to be a manifestation of chronic rejection. To assess the role of anti-HLA antibodies in heart allograft rejection we studied 107 patients and compared the survival of recipients who formed anti-HLA antibodies with the survival of recipients who developed no antibodies. At 4 years the actuarial survival was 90% in the nonproducer group and 38% in antibody-producers (P = 0.038). We further explored the possibility that HLA antigens from the injured graft are released into the circulation and can be found in the serum either free or complexed with anti-HLA antibodies. This hypothesis was confirmed by the finding that the frequency of sera containing soluble HLA antigens from the graft or immune complexes of HLA alloantigens with anti-HLA antibodies was significantly higher in patients who rejected compared with patients with successful heart allografts (P less than 0.05). Following depletion of soluble HLA antigens, anti-HLA antibodies became detectable in 53% and 74% sera obtained during the first and second year posttransplantation, respectively, from patients undergoing chronic rejection. Long-term survivors showed a significantly lower (P less than 0.001) frequency of anti-HLA antibodies in sera depleted of HLA antigens. Lastly, studies of anti-anti-HLA-A2 and A3 antibodies in recipient sera suggest that quiescence is maintained by antiidiotypic antibodies.

Antigen-Antibody Complex

The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms.

As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution. A prospective clinical study was undertaken to assess the validity of this policy. One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989. All patients underwent CT scanning as an initial evaluation. Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease. During this period 19 patients (19%) underwent both CT scanning and angiography. The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4). Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation. No patient was adversely affected by elimination of angiographic evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated.

Aged

Immunomodulation of vascular endothelium. 1. Ultrastructural changes following ultraviolet B irradiation of peripheral veins.

Immunologic function of endothelial cells is especially important in consideration of vein allografting for arterial reconstruction and in organ allotransplantation. Ultraviolet B radiation (UVB) has previously been shown to modulate graft immunogenicity, and to alter cell surface receptor function. In this study, superficial epigastric veins were UVB irradiated with 10, 24, 40, 80, and 150 mJ/cm2 while control veins were not irradiated; all specimens were examined for endothelial ultrastructural changes. Veins were perfuse-fixed at 1, 3, 7, 14, and 28 days after irradiation, and were evaluated by transmission electron microscopy and scanning electron microscopy. Control veins had a normal appearing endothelial lining, composed of elongated, attenuated endothelial cells. Veins irradiated with more than 24 mJ/cm2 displayed injured endothelial cells characterized by altered microvilli, defects in the cell surface, and a change in cell shape. The degree of cell damage correlated closely with increasing UVB dose. At doses of 80 mJ/cm2 or greater there was moderate to severe endothelial cell separation from the underlying basement membrane and an increase in cellular lysosomes. The effects of UVB were maximal at 3 days with virtual recovery in resurfacing of all specimens with endothelium 28 days after irradiation. These data suggest that UVB has a dose-dependent effect on venous endothelium that is morphologically reversible with time. Cell membrane changes seen following exposure to UVB may contribute to altered cell surface receptor function.

Animals

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice.

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.

Animals