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Biomedical subjects

E A Rose

Publications and source records attributed to E A Rose.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.

Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.

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

Long-term survival of heart and kidney allografts is threatened by the development of chronic rejection. Analysis of the relationship between reversible acute rejection episodes and actuarial survival at 5 years showed an inverse correlation suggesting that early cellular events may trigger antibody-mediated chronic rejection. In both heart and kidney allograft recipients producing anti-HLA antibodies we found a significant decrease in the 5-year graft survival rate. However, there was heterogeneity among anti-HLA antibody producers with respect to the development of anti-idiotypic antibodies. The actuarial 5-year graft survival was significantly higher in patients with Ab2 compared to patients without.

Actuarial Analysis

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

Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution.

We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation.

Adenosine

Permanent pacing following cardiac transplantation.

Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing.

Adolescent

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

Adenosine