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Biomedical subjects

E A Rose

Publications and source records attributed to E A Rose.

At least 145 records · Page 8Linked to original sources
PubMed1993

Posttransplantation lymphoproliferative disorders treated with cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy.

BACKGROUND: Posttransplantation lymphoproliferative disorders after solid organ transplantation are a serious complication occurring in 1-10% of patients. Different therapies have been used, but the optimal treatment is unknown. There is relatively little information in the literature on the experience with cytotoxic chemotherapy. METHODS: The disease stage of patients with biopsy-documented posttransplantation lymphoproliferative was determined with standard methods to establish the extent of the disease. Patients in whom the disease failed to regress after initial management, which included reduction in immunosuppression, were treated with a combination chemotherapy regimen consisting of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Response to therapy was determined by following previously defined sites of disease with appropriate tests. Patients were maintained on a reduced dose of immunosuppressants. RESULTS: In the four patients studied, lymphoproliferative disorders developed after heart (three cases) or lung (one case) transplantation, which did not regress after immunosuppression was reduced. All four experienced a complete remission with CHOP chemotherapy, which continued at 3, 13+, 20 and 30+ months after completion of treatment. One patient died of sepsis after completing therapy at a point when his leukocyte count was normal, and no evidence of posttransplantation lymphoproliferative disorder was found at autopsy. A second patient died of liver failure with no clinical evidence of lymphoproliferative disorder. CONCLUSION: Although this is a small series, it demonstrates that patients with posttransplantation lymphoproliferative disorders may respond to cytotoxic chemotherapy. The duration of response is undetermined.

Adult↗
PubMed1993

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients.

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. Analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p < 0.004). Patients carrying the DR2 alleles, DRB1*1501, *1502 or *1601 were at a lower risk of producing anti-donor HLA antibodies.

Alleles↗
PubMed1993

Management of lymphoproliferative disorders after cardiac transplantation.

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.

Adult↗
PubMed1993

Use of a sensitive fluorescent intercalating dye to detect PCR products of low copy number and high molecular weight.

The ability to routinely and specifically amplify and detect PCR products ranging in size from < 1 to > 10 kb, regardless of target template sequence or structure, would facilitate several tasks in human genome research. Generation of a wide size range of PCR products would potentially expedite isolation of uncloned DNA (gaps) represented in physical maps and provide a means for maintaining order and orientation of closely linked loci during analysis. Long-range PCR offers an alternative to isolation of genomic or cDNA clones from tissues or species where appropriate libraries are unavailable. This methodology also provides a powerful strategy to pursue directed transposon-based mapping and sequencing of templates of 100 kb or greater. Further development of basic PCR technology has been necessary in order to make it feasible to use large DNA targets as primary templates for genome analysis. Application of these extended PCR capacities would potentially save time, materials, and cost.

Bacteriophage lambda↗
PubMed1993

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↗
PubMed1993

Decreasing incidence of coronary disease in pediatric cardiac transplant recipients using increased immunosuppression.

BACKGROUND: Coronary artery disease (CAD) is a limiting factor to long-term survival in cardiac transplant recipients, affecting from 30% to 50% of patients by 4 years after surgery. Can the incidence of CAD be lowered with augmentation of immunosuppression? METHODS AND RESULTS: We compared the incidence of CAD in our pediatric transplant population with nine potential risk factors, including immunosuppressive regimen. The study group consisted of 55 patients who survived more than 1 year (or to first angiogram) or had autopsies. Coronary angiograms were performed yearly and compared sequentially. The mean follow-up of 55 patients was 36 months. Mean age was 10.3 +/- 6 years (range, 4 months to 18 years). Thirteen patients received double immunosuppression with cyclosporine and prednisone, and 42 received triple therapy with cyclosporine, prednisone, and azathioprine. Significant CAD occurred in 10 grafts (6 deaths and 3 retransplants). Cause for graft loss in 6 patients with CAD was acute rejection. CAD was detected by angiogram in only 2 patients. Nine of 10 patients received double therapy (P < .001). There was no difference in mean follow-up between immunosuppression groups. There was a higher rejection frequency for double therapy (0.19 +/- 0.16 rejections per patient month) compared with triple therapy (0.07 +/- 0.11). Ten patients were rejection free in the triple therapy group. CONCLUSIONS: We experienced a significant decrease in the incidence of CAD in our pediatric cardiac transplant recipients using increased immunosuppressive therapy. Type of immunosuppressive regimen (double) and rejection frequency were independent predictors for CAD by multivariate analysis.

Azathioprine↗
PubMed1993

Clinical experience with cardiac retransplantation.

Although more than 560 patients worldwide have undergone cardiac retransplantation, few studies of this population have been reported. To evaluate the risk of cardiac retransplantation and to better establish selection criteria, we reviewed the records of all patients who underwent retransplantation at the Columbia-Presbyterian Medical Center. Of 431 patients who underwent transplantation between February 1977 and March 1991, 408 underwent the procedure in the era of cyclosporine-based immunosuppression. Thirteen of these 408 patients underwent retransplantation (including one patient who received a third graft). Indications for the 14 retransplantations included transplant coronary artery disease (n = 8), rejection (n = 5), and intraoperative graft failure (n = 1). Immunosuppression and follow-up protocols used in this cohort were similar to those in the primary transplantation population. No significant differences were found in either actuarial survival between primary transplant recipients (75.1% +/- 2.2% at 1 year and 71.3% +/- 2.4% at 2 years) and patients who underwent retransplantation (71.4% +/- 12.1% at 1 year and 59.5% +/- 14.8% at 2 years) or in linearized rates of rejection and actuarial freedom from rejection between the two groups. No differences between these groups were found with regard to age, sex, race, origin of end-stage heart disease, or early (< 30 day) mortality. The origin of primary graft failure did not correlate with survival outcome in the retransplantation cohort. Follow-up time for patients having primary transplantation ranged from 0 to 8 years (mean 24 months) with a cumulative patient follow-up of 830 patient-years; follow-up time for patients who underwent retransplantation ranged from 0 to 3 years (mean 8.1 months) with a cumulative patient follow-up of 9.5 patient-years. Approximately 50% of patients in both groups had at least one rejection episode by 3 months. Within the limited time period studied after retransplantation, only one patient had transplant coronary artery disease, approximately 27 months after her first retransplantation procedure for acute rejection. These results indicate that the prognosis for patients undergoing cardiac retransplantation is good for patients for whom the indication for retransplantation is identified more than 30 days after initial transplantation.

Adolescent↗
PubMed1993

Effect of anti-HLA antibodies on the long-term survival of heart and kidney allografts.

Study of anti-HLA antibodies in a population of 238 primary renal and 199 primary heart allograft recipients showed significant association between development of anti-HLA antibodies and that of chronic allograft rejection. The 5-year renal allograft survival was 70% in recipients without antibodies and 53% in recipients who developed anti-HLA alloantibodies during the first year following transplantation. Heart allograft survival at 5 years was 91% in patients without and 78% in patients with antibodies during the first 12 months posttransplantation. Development of antibodies is associated with acute rejection episodes and probably with the release of soluble HLA antigens.

Antibodies, Anti-Idiotypic↗
PubMed1992

Acquired coarctation of the aorta.

Coarctation of the aorta is usually caused by a congenital narrowing of the aorta. This report describes two children who developed hypertension secondary to an acquired coarctation of the aorta. In one patient the coarctation was temporally related to umbilical artery catheterization and was associated with thrombosis and aneurysmal dilatation of the aorta. In the second patient, the coarctation occurred after surgical aortotomy during the removal of an intrathoracic neuroblastoma. Patients who have interventional damage to the aorta should be periodically examined for the appearance of a coarctation. Although an acquired coarctation of the aorta is an infrequent complication of invasive or surgical procedures, it should be identified since it represents a remediable cause of hypertension in children.

Aortic Coarctation↗
PubMed1992

Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device.

The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty-five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thromboembolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No device-related thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients (p greater than 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage cardiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology.

Adolescent↗
PubMed1992

Recurrent intravenous leiomyomatosis with cardiac extension.

A case of recurrent intravenous leiomyomatosis with cardiac extension and a temporally extended presentation is described. Complete excision was achieved employing simultaneous sternotomy and laparotomy and deep hypothermia with circulatory arrest. Coronary revascularization was performed concomitantly with complete tumor resection. Diagnostic, operative, and pathologic considerations are reviewed and a preferred surgical approach discussed.

Female↗
PubMed1992

Effect of complete cardiac denervation on atrial natriuretic factor release in baboons.

We investigated the influence of cardiac innervation on atrial natriuretic factor (ANF) release in baboons. For this purpose, plasma ANF levels were measured in control conditions and in response to head-down (-45 degrees) and head-up tilt (+45 degrees) in six anesthetized baboons before and after complete cardiac denervation obtained by orthotopic autotransplantation of the heart. Cardiac denervation did not modify baseline plasma ANF levels (60.4 +/- 17 pg/ml before and 63.1 +/- 16 pg/ml after heart autotransplantation). In contrast the significant ANF responses to changes in central venous pressure (CVP) induced by postural maneuvers (-45 degrees, + 16.2 +/- 4 pg/ml; +45 degrees, -18.5 +/- 4 pg/ml) were markedly altered after cardiac denervation (-45 degrees, +5.8 +/- 2 pg/ml; +45 degrees, -7.6 +/- 1 pg/ml). The changes in CVP and systemic blood pressure evoked by the postural challenges were comparable before and after cardiac denervation. These results demonstrate that cardiac nerves play a role in the control of ANF release.

Animals↗
PubMed1992

Optimization of long-distance PCR using a transposon-based model system.

The ability to amplify routinely long PCR products (5-25 kb) with high specificity and fidelity, regardless of target template sequence or structure, would provide significant benefits to genome mapping and sequencing endeavors. Although occasional reports have described the generation of long PCR products, such results have been difficult to replicate and have frequently utilized probe hybridization to identify the specific product from nonspecific amplified DNA. Production of specific PCR products has generally been limited to target templates of less than 3 kb. To extend the effective range of standard PCR amplification, it may be necessary to utilize alternative reaction conditions and/or components, such as novel thermostable DNA polymerases or accessory proteins. We describe the use of a model system to evaluate systematically methodological changes that might enable efficient long-range PCR. Specifically, the transposon Tn5supF has been used to introduce randomly identical, known primer binding sites within separate isolates of phage clones carrying identical inserts. Transposon-based PCR allows us to study amplification of DNA fragments that vary in size and sequence using only a single set of primers. In the present studies, we describe conditions that enable PCR amplification of specific DNA templates ranging in size up to 9 kb. Some of the key features of our methodology include the use of recombinant Thermus thermophilus (rTth) DNA polymerase, the addition of gelatin to the reaction mixture, the use of wax-mediated "hot starts" and, lastly, the use of auto-segment extension thermocycling. These results also provide insights into additional approaches that might further enhance our ability to perform long-distance PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

The implantable defibrillator: an electronic bridge to cardiac transplantation.

BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation.

Anti-Arrhythmia Agents↗