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Biomedical subjects

C C Marboe

Publications and source records attributed to C C Marboe.

At least 37 records · Page 2Linked to original sources
PubMed1993

Characterization of anti-HLA class II monoclonal antibody LGII-612.14 reacting with formalin fixed tissues.

mAb LGII-612.14 derived from a BALB/c mouse immunized with interferon-gamma (IFN-gamma) treated cultured human B lymphoid cells LG-2 has been shown with serological and immunochemical assays to recognize a monomorphic determinant expressed on the beta chain of HLA-DR, -DQ and -DP antigens. The linear nature of the determinant, which is likely to be formed by residues 19-25, is indicated by the reactivity of mAb LGII-612.14 with HLA-DR, -DQ and -DP beta chains purified by electrophoresis in presence of SDS. An unusual characteristic of mAb LGII-612.14 is its reactivity with fixed tissue sections. The intensity of staining is affected by the incubation temperature, the incubation time and the fixative used. Maximal intensity of staining of formalin fixed, paraffin embedded tissue sections required an incubation time of 16 h. The intensity of staining of paraffin embedded tissues initially fixed with Bouin's solution, formalin or ethanol was similar to that of frozen tissue sections and stronger than that of tissues fixed with B5 solution. No staining was detected of paraffin embedded tissues fixed with glutaraldehyde or Zenker's solution. Comparison of the staining patterns with mAb LGII-612.14 of frozen and fixed tissue sections showed that the latter substrates provide a superior detail of tissue architecture and cellular morphology without significant loss of sensitivity. Furthermore, comparison of the characteristics of mAb LGII-612.14 with the few previously published anti-HLA class II mAb reacting with fixed tissues indicates that mAb LGII-612.14 stains formalin fixed, paraffin embedded tissues, while mAb 910D7 and TAL-1B5 stain tissues fixed with less commonly used fixatives. Furthermore, mAb LGII-612.14 is likely to yield more sensitive staining results than anti-HLA-DR, -DQ and -DP mAb KUL/05. The present results indicate that mAb LGII-612.14 represents a useful probe to apply immunohistochemical techniques to the analysis of the distribution of HLA class II antigens in fixed tissues. This will greatly facilitate the use of readily available collections of fixed tissue specimens in retrospective studies to assess the clinical significance of changes in HLA class II antigen expression which occur in various disease states.

Animals↗
PubMed1993

Prevention of acute regional ischemia with endocardial laser channels.

Laser myocardial revascularization has been shown to reduce mortality and infarct size after left anterior descending coronary artery (LAD) ligation in dogs. It has not been shown to improve myocardial contractility in acute ischemia. In this study a holmium-yttrium-aluminum garnet laser (wavelength, 2.14 microns) was used to create nontransmural myocardial channels from the endocardial surface in the ischemic regions of the canine left ventricle. Twelve mongrel dogs (6 controls, 6 laser myocardial revascularizations) underwent 90 minutes of LAD ligation followed by 6 hours of reperfusion. The ischemic region was determined by methylene blue injection during brief LAD occlusion. Laser myocardial revascularization averaged three channels per square centimeter in the ischemic region created using 12 J/channel (600 mJ/pulse, 10 Hz) before LAD ligation. Contractility was assessed from regional preload recruitable stroke work (RPRSW), using pairs of segment length ultrasonic transducers in the ischemic and the nonischemic regions. Two-dimensional echocardiography corroborated with segmental length findings. In control dogs, the ischemic region was dyskinetic during LAD ligation and reperfusion. Dyskinesis of the ischemic region during systole produced negative values for regional stroke work, and RPRSW was considered zero. In 4 of 6 laser-revascularized dogs, RPRSW remained positive in the ischemic region. Two dogs had intermittent dyskinesis. The difference between laser-revascularized and control dogs in ischemic region RPRSW was significant (p < 0.01 by Fischer's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Novel preservation solution permits 24-hour preservation in rat and baboon cardiac transplant models.

BACKGROUND: Cardiac preservation for transplantation disrupts normal vascular homeostatic mechanisms. Hypoxia and reoxygenation increase endothelial cell permeability, induce procoagulant activity, and alter endothelial cell/leukocyte interactions, with a parallel reduction in endothelial cAMP and nitric oxide levels. Because hypoxia/reoxygenation simulates a significant component of the global ischemia/reperfusion of cardiac transplantation, we hypothesized that preservation failure may be related to these perturbations. This work focuses on repleting the intercellular/intracellular second messengers nitric oxide/cGMP and cAMP in the donor heart to enhance cardiac preservation for transplantation. METHODS AND RESULTS: A heterotopic rat heart transplant model was used to compare lactated Ringer's (LR) and University of Wisconsin (UW) solutions to a novel storage solution (Columbia University solution, CU), which contains a cAMP analogue (dibutyryl cAMP) and nitroglycerin (to enhance nitric oxide-related mechanisms). By 24 to 28 hours of preservation, no LR hearts survived (n = 9), 35% of UW hearts survived (n = 20), and 88% of CU-preserved hearts survived (n = 8; P < .05) versus LR or UW). The viability of preserved hearts was explored by determining whether CU preservation enabled myocytes to maintain resting membrane potentials and preserve their ability to generate an action potential in response to a field stimulus. Of 24 sites explored with a microelectrode in UW-preserved hearts, only 4% were able to generate an action potential, compared with 75% of 36 sites in CU-preserved hearts (P < .001), with corresponding preservation of resting membrane potential in the CU-preserved hearts (-13 mV for UW versus -54 mV for CU, P < .001). Orthotopic baboon cardiac transplantation performed after 24-hour simple hypothermic preservation demonstrated that no UW-preserved heart (n = 4) survived the perioperative period; in contrast, four of five hearts stored for 24 hours in CU solution sustained the recipient with minimal inotropic support, and two animals survived long-term. CONCLUSIONS: Sustaining higher levels of intercellular/intracellular second messengers cAMP and nitric oxide/cGMP provides a new approach to enhancing cardiac preservation.

Adenosine↗
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

Normal bronchial healing without bronchial wrapping in canine lung transplantation.

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.

Anastomosis, Surgical↗
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

Intersegmental (intersublobar) septum of the lower lobe in relation to the pulmonary ligament: anatomic, histologic, and CT correlations.

A thin horizontal linear area of hyperattenuation that extends laterally from the mediastinal surface of the lung within the area between the inferior pulmonary vein and the diaphragm is a common observation on computed tomographic (CT) scans of the chest. To determine the anatomic basis for this structure, the authors examined four normal human lungs (two right and two left lungs) fixed in an inflated state at pathologic and histologic examination and at CT. The structure in question was identified in one right and two left lungs. The linear area of hyperattenuation seen at CT is a septum of thin, loose intraparenchymal connective tissue that is bounded medially by the base of the pulmonary ligament, where the two sleeves of the visceral pleura appose one another, and laterally by a vertically oriented vein. The septum was identified in 39 of 50 (78%) normal chest CT scans. The pulmonary ligament often appeared to look like a beak at the mediastinal side of the lung. The septum, when visible (n = 39), was bounded medially by the beak in 28 CT scans (72%) and laterally by a vein in 24 scans (62%).

Connective Tissue↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Binding of preformed xenoantibodies to porcine bioprosthetic valves.

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.

Animals↗
PubMed1991

Ultrasonic angioplasty in totally occluded peripheral arteries. Initial clinical, histological, and angiographic results.

BACKGROUND: Ultrasonic angioplasty was recently shown to ablate thrombi and atherosclerotic plaques in vitro and to recanalize occluded arteries in experimental animal models. The goal of the present study was to examine the clinical feasibility of ultrasonic angioplasty. METHODS AND RESULTS: Intraoperative ultrasonic angioplasty was performed in vivo on totally occluded peripheral arteries (n = 7). The ultrasonic angioplasty device consists of a 1.6-mm diameter flexible wire attached to a piezoelectric crystal generating ultrasound at 20 kHz. The controls, totally occluded human atherosclerotic femoral arterial segments (n = 6), were crossed mechanically with the ultrasound wire ex vivo but without application of ultrasonic energy. Ultrasonic angioplasty achieved successful recanalization without perforation in all vessels. Angiograms of the treated arteries showed an average lumen patency of 82.5%. Histological examination of the recanalized arteries revealed that the recanalization had taken place through intima diffusely involved with complicated plaque. The treated arteries, compared with the controls, had greater area of recanalized lumen (5.9 +/- 1.8 versus 1.7 +/- 0.4 mm2, p less than 0.05) and more flow (49.3 +/- 16.0 versus 11.8 +/- 4.9 ml/min, p less than 0.03). The damage in treated and control arteries was similar. Size-distribution analysis of the plaque debris from the treated arteries showed that 41 +/- 5% of the debris was 0.2-8 microns, 48 +/- 8% was 8-30 microns, and the remainder was 30-100 microns. In the mechanically crossed arteries, there was a shift in the distribution to larger size debris with 47 +/- 1% greater than 100 microns (p less than 0.001). CONCLUSIONS: Ultrasonic angioplasty may be a useful clinical method for recanalization of total occlusions in patients with peripheral vascular disease. Ultrasonic energy appears to cause controlled injury to the atherosclerotic intima by selectively disrupting the ultrasound-sensitive occlusion.

Aged↗
PubMed1990

Tissue soldering by use of indocyanine green dye-enhanced fibrinogen with the near infrared diode laser.

Anastomoses welded by laser have been strengthened by applying a solder of fibrinogen combined with a laser energy absorbing dye (indocyanine green, maximum absorbance 805 nm) to the anastomotic site before continuous-wave diode laser exposure (808 +/- 1 nm, 4.8 W/cm2). Immediately after creation, the bursting pressures of welds created without fibrinogen (262 +/- 29 mm Hg, n = 11) were significantly less than repairs with fibrinogen (330 +/- 75 mm Hg, n = 11) (p less than 0.05). When repairs performed with fibrinogen were exposed to urokinase (25,000 IU) the bursting pressures were not significantly different from baseline (290 +/- 74 mm Hg, n = 5). Aortotomies closed by suture did not burst but leaked at pressures significantly below those of vessels closed by laser (165 +/- 9 mm Hg, n = 11) (p less than 0.01). Twenty-two repairs soldered with fibrinogen were incorporated into survival studies in rabbits and examined from 1 to 90 days after operation. No anastomotic ruptures, thromboses, or aneurysms were identified. Soldered sites rapidly regenerated a new intimal surface and healed by myofibroblast proliferation. No significant foreign body response was identified; the fibrinogen was resorbed. Laser soldering with exogenous fibrinogen is feasible without topical administration of additional clotting agents, significantly improves the bursting strength of primary laser welded anastomoses, and appears to result from urokinase-resistant fibrinogen cross-linking.

Anastomosis, Surgical↗
PubMed1989

Primate cardiac allo-and xenotransplantation: modulation of the immune response with photochemotherapy.

Survival of heterotopic allo- and xenografts was studied in a primate cardiac transplantation model. Initially, animals were presensitized to donor xenoantigens by blood transfusion and treated with strategies designed to elicit pretransplant immunosuppression. These animals underwent rapid rejection whether treated with ciclosporin and conventional immunosuppression, autologous sera, sensitized lymphocytes, or photochemotherapy. In a nonsensitized xenograft study, xenografts were maintained for prolonged periods with a combination of ciclosporin and photochemotherapy. All animals treated with photochemotherapy demonstrated periodic suppression of the mixed leukocyte culture response to their donor. Inhibition of lymphocytotoxic antibody was achieved only in animals treated with both ciclosporin and photochemotherapy. Xenosensitized animals were secondarily exposed to donor alloantigens. These animals were successfully allografted. Ciclosporin therapy was terminated and the animals maintained by photochemotherapy alone. This preliminary trial indicates that a combination of ciclosporin and photochemotherapy may be of value in maintaining concordant xenografts and preventing antibody mediated rejection.

Animals↗
PubMed1989

Long-term function of human cardiac allografts assessed by two-dimensional echocardiography.

Previous studies from our laboratory demonstrated increasing left ventricular mass in cyclosporine-treated cardiac allograft recipients over 30 days after transplantation, but the long-term evolution of this process and possible effects on allograft function are unknown. Accordingly, quantitative two-dimensional echocardiography was performed 2 and 23 days and 15 months postoperatively in 14 recipients treated with cyclosporine and prednisone. Changes in left ventricular ejection fraction, end-diastolic volume, mass, and end-systolic wall stress were analyzed. Comparison of studies at 2 and 23 days revealed significant (p less than 0.01) increases in ejection fraction (54% +/- 8% [standard deviation] to 62% +/- 4%), end-diastolic volume (84% +/- 32 ml to 96 +/- 31 ml), and left ventricular mass (118 +/- 45 gm to 136 +/- 41 gm). Comparison of studies at 23 days and 15 months revealed no significant change in end-diastolic volume or left ventricular mass, whereas ejection fraction decreased slightly (62% +/- 4% to 57% +/- 4%, p less than 0.01). End-systolic wall stress decreased when data at 2 days and 15 months were compared (83 +/- 24 gm/cm2 versus 66 +/- 18 gm/cm2, p less than 0.05), but no change in contractility was apparent from the ejection fraction/end-systolic stress relation. We conclude that left ventricular mass and end-diastolic volume increase early after transplantation in cyclosporine-treated cardiac allograft recipients, but these changes are not predictive of long-term results, which are characterized by no significant late variation in left ventricular mass, end-diastolic volume, or contractility.

Adolescent↗
PubMed1989

Relation between survival and development of coronary artery disease and anti-HLA antibodies after cardiac transplantation.

The importance of chronic humoral rejection in cardiac transplant patients has not been studied extensively. In an attempt to determine whether lymphocytotoxic antibodies are related to heart allograft survival, we evaluated 123 patients whose sera were monitored for cytotoxic antibodies against HLA antigens after transplantation. Patients underwent serial sampling of peripheral blood at the time of right-heart catheterization and endomyocardial biopsy. Patients with three or more sera containing lymphocytotoxic antibodies were considered alloantibody producers (81 of 123 patients). With similar follow-up, mortality was greater for antibody producers (27 of 81 patients) than for nonproducers (three of 42 patients, p less than 0.01). Among antibody producers, the mortality rate was higher when multiple samples obtained during the first 6 months after transplantation contained anti-HLA class I or class II antibodies. Coronary artery disease was documented in 12 of 81 antibody producers and only one of 42 nonproducers (p = 0.05). The presence of anti-HLA antibodies in the serum showed no association with the presence of lymphocytic infiltrates in myocardial biopsies or with hemodynamic abnormalities. However, histologic rejection was present in 14 of 19 antibody producers who died. Thus, the presence of anti-HLA antibodies was associated with increased mortality and the development of coronary artery disease and was a major correlate of the clinical course after cardiac transplantation. High- and low-risk groups can be differentiated within the first 6 months after transplantation.

Coronary Disease↗