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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)

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.

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.

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.

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

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.

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.

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)

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.

These studies demonstrate that photochemotherapy can be successfully evaluated in animal models. The therapy mediates specific suppression of immune responses and appears to operate at the level of the effector T cells. Future studies will focus on isolation and characterization of the host response to photochemotherapy. The extention of this form of therapy to conditions mediated by dysfunctional regulation of effector T cells is already in progress in clinical trials of cardiac allograft transplantation and autoimmune disease. The results of these trials will provide more evidence on the role of this form of therapy in autoregulation of the immune response.

Although in vitro and primate orthotopic transplant experiments have suggested the superiority of University of Wisconsin solution (UWS) compared with crystalloid cardioplegia and saline solution storage for hypothermic heart preservation, concerns about the viscosity and the high potassium concentration of UWS have precluded its use in human cardiac transplantation. To test the safety and efficacy of UWS, 16 patients received hearts arrested with, flushed with, and stored in UWS at 4 degrees C for a mean ischemic time of 153.3 +/- 30.7 minutes. After reperfusion, the hearts contracted vigorously and attained a stable sinus rhythm within 4.0 +/- 2.4 minutes, and the patients were weaned from bypass in 24.5 +/- 8.0 minutes. There was no evidence of acute or chronic ischemic myocardial injury by enzymatic analysis, electrocardiography, or biopsy specimen histology. The results suggest UWS can be safely used, within currently accepted limits of donor ischemic time, to arrest and preserve human hearts for transplantation. Further studies of preservation are required to compare UWS with crystalloid cardioplegia and saline solution storage and to test the ability of UWS to prolong the period of safe donor hypothermic ischemia in clinical heart transplantation.

We tested the ability of University of Wisconsin solution (UWS) to extend hypothermic nonperfused heart preservation in baboons and then proceeded to human transplantation. Orthotopic transplantation was performed in five baboons (UWS cardioplegia and storage [4 degrees C]; preservation time 10.3 +/- 0.6 hours). Four survivors were immunosuppressed for 45 days and killed. One animal died from disruption of the aortic anastomosis due to technical error. Preservation did not alter histology under light and electron microscopy or heart weight (at harvest, 51.4 +/- 11.6 g; before implant, 52.5 +/- 11.1 g). Animals were weaned from bypass (mean, 23 +/- 12 minutes) and returned to their cages without intravenous support within 3.6 +/- 0.6 hours. Weekly biopsy, electrocardiogram, enzyme analysis, echocardiogram, and right heart catheterization demonstrated excellent cardiac function. Following success in baboons, UWS was applied to human transplantation (n = 2, UWS cardioplegia and storage [4 degrees C]; preservation time 4.2 and 2.1 hours). The hearts returned to sinus rhythm within 4 minutes of reperfusion without defibrillation, and enzymatic and hemodynamic data reveal excellent heart preservation. Preliminary data suggest the ability of UWS to prolong heart preservation in baboons and be used safely in humans. Further studies are required to compare UWS with crystalloid cardioplegia and saline storage and to prolong donor heart preservation in humans.

We studied the relationship between immunologic rejection and changes in contractility of isolated perfused papillary muscle, using heterotopically transplanted rat hearts. Rejection assessed by mononuclear cell infiltration was associated with depressed twitch amplitude and lower rates of tension development and relaxation. The relationship between maximum developed tension and [Ca2+]o was attenuated in muscle from the rejecting allografted heart, as compared with muscle of normal or isografted hearts. To determine the effects of rejection on ventricular electrophysiologic properties, we recorded transmembrane action potentials in isolated ventricular myocardium. We found that in rejecting allografted hearts the resting potential, action potential amplitude, and maximum upstroke velocity of phase zero were significantly reduced compared with normal and isografted hearts. The attenuation in the mechanical and electrophysiologic properties was largely prevented by treating the transplanted rat with anti-lymphocyte-globulin on days 0, 1, and 2 after transplantation. In summary, the present study demonstrates that immunologic rejection of the heterotopically allotransplanted rat heart is associated with marked attenuation of both mechanical and electrophysiologic properties of the ventricular myocardium.

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.

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.

The thulium-holmium-chromium:yttrium-aluminum-garnet (THC:YAG) laser has a tissue effect similar to that of the CO2 laser, with the advantage of transmissibility through flexible fibers. The authors used a human-rabbit xenograft model to evaluate the thrombotic and healing responses of atherosclerotic vessels subjected to laser energy. Occluded atherosclerotic human coronary artery segments were recanalized in vitro by use of the THC:YAG laser. Destruction of plaque by the laser was achieved with minimal collateral thermal damage. These vascular segments were then transplanted into the rabbit abdominal aorta. The authors observed that the luminal surface of the lased vessels was more thrombogenic than that of the nonlased control vessels. However, occlusion of the lased vessels did not occur. Repair of laser-treated tissue progressed until a mature, nonthrombogenic fibrin-platelet aggregate was adherent to the luminal wall. Overall, the lased vessels behaved in a fashion similar to the nonlased control vessels. On the basis of these results, the authors believe that the THC:YAG laser may have use in human angioplasty.

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.

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.

Chronic erosive gastritis is a gastric mucosal lesion characterized by multiple, small, sessile elevations with central erosions. Symptoms typically resemble those in peptic ulcer disease. The elevations may persist and appear as sessile polyps after the erosions heal and symptoms resolve with therapy. Adenomatous transformation is reported in a patient with chronic erosive gastritis who had serial gastroscopies. This report suggests a possible association between chronic erosive gastritis and gastric neoplasia.

A 17-year-old woman with rheumatic carditis underwent endomyocardial biopsy both prior to and following treatment with prednisone and aspirin. Frozen sections from the endomyocardial biopsy specimens were studied with monoclonal antibodies by an indirect immunofluorescence technique to define the composition of the inflammatory infiltrate in the myocardium and to determine whether the composition of the infiltrate is distinctive and diagnostically useful. The specimen from the initial biopsy contained a heterogeneous infiltrate composed of T lymphocytes, macrophages, B lymphocytes, and mast cells. T lymphocytes predominated, and the ratio of T-helper to T-cytotoxic/suppressor cells was 2.0. Following treatment the overall cellularity of the infiltrate was diminished, but the infiltrate remained heterogeneous; T cells predominated, and the T-helper to T-cytotoxic/suppressor ratio was reversed, to 0.59. The composition of the inflammatory infiltrate in this case of rheumatic carditis distinguishes it immunologically from other "idiopathic," presumably virus-associated, forms of myocarditis.

A hybridoma-derived monoclonal antibody, produced by immunization with the Burkitt's tumor-derived B-lymphoblastoid cell line, B35M, was previously shown to detect a 68,000 dalton surface membrane protein, BL2, on the surface of peripheral blood B cells, which is absent from thymocytes, T cells, and granulocytes. In this study, we investigated the expression and distribution of BL2 on benign and malignant human lymphoid cells. Indirect immunofluorescent assay with this monoclonal antibody demonstrated that BL2 is expressed by cells within the fetal liver and by a variable proportion of lymph node, tonsil, and spleen B cells, but not by T cells. The neoplastic cells isolated from 18 T-cell malignancies were BL2- . BL2 was was heterogeneously expressed by a variable proportion of the malignant cells in 29/32 cases of B-chronic lymphocytic leukemia and 33/38 cases of B-cell lymphomas, but appeared to be lost in the terminal stages of B-cell differentiation, as myeloma plasma cells were BL2- . BL2 expression was not limited to B cells of a particular surface immunoglobulin isotype. Immunofluorescent staining for BL2 in cryostat tissue sections demonstrated that the majority, but not all, germinal center and interfollicular Ia+ (non-T) cells are BL2+. These findings suggest that BL2 is a B-cell lineage-specific differentiation marker that may be useful in the study of B-cell ontogeny and in defining subgroups of the B-cell malignancies.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

We have recognized nine patients with gastric mucosal lesions which were characterized by an erosion with surrounding mucosal elevation. This lesions has previously been called chronic erosive or varioliform gastritis. Patients were investigated because of upper gastrointestinal symptoms (n = 7), weight loss (n = 2), and/or bleeding (n = 3). Radiologically the appearance was of typical target lesions. Pathological features included pseudopyloric metaplasia, pyloric gland hyperplasia, acute and chronic inflammation, edema, and fibrosis. Atypia was present in biopsies from four patients and in one was incorrectly interpreted as representing intramucosal carcinoma. The remaining patients were treated with antacids and/or cimetidine with resolution of symptoms and in five patients repeat endoscopy demonstrated resolution of the lesions. Chronic erosive gastritis may cause upper gastrointestinal symptoms indistinguishable from peptic ulceration. Greater numbers of patients will have to be treated in a controlled fashion to determine the natural history of the disease and the most efficacious treatment.

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.

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.

About 6% of perinatal mortality in Addis Ababa, Ethiopia, is associated with congenital syphilis. We report on 65 autopsies and the accompanying maternal examinations and interviews. Congenital syphilis was most common in unwanted pregnancies, in women with previous stillborns, in those who had multiple sexual partners, and in those who did not seek antenatal medical care. Congenital syphilis causes enlargement of liver, spleen, and placenta; premature labor; and increased perinatal mortality. It is recognizable even in severely macerated stillborns.

Between 1940 and 1978, 150 major pancreatic resections--92 pancreatoduodenal resections (PDRs) and 58 total pancreatectomies (TPs)--were performed for benign and malignant disease. The majority of resections were for pancreatic cancer (70 patients) and ampullary cancer (40 patients). The overall operative mortality rate for PDR was 14%; it was 26% for TP. After resection for adenocarcinoma of the head of the pancreas, the operative mortality rate was 28% for TP and 15% for PDR. The number of 5-year survivors after resection for cancer of the head of the pancreas was four (5.7%). Three survived after PDR and one after TP. Of the 42 adenocarcinomas resected by TP, one of the patients had multicentric cancer and two others had carcinoma in situ. TP appears to have no advantage over PDR for cancers of the head of the pancreas from a theoretical or practical standpoint.

Amniotic fluid infections were the most common cause of perinatal death in Addis Ababa, Ethiopia (21.8/1,000 live births). Most such infections appear to originate in the fetal membranes near the cervical os. The high rate of spread of these local infections into the amniotic fluid in Addis Ababa appears related to a lack of antimicrobial activity in amniotic fluids. Factors that adversely affected nutrition in the gravid woman, lack of prenatal medical care, and low water usage were associated with the high rate of fatal infections.

Monoclonal antibodies OKB1, OKB2, OKB4 and OKB7 have been previously shown to detect distinctive antigens displayed on B, but not on T, lymphocytes. Benign and malignant lymphoid cells were investigated for their reactivity with these antibodies in cell suspension by indirect immunofluorescence and in cryostat tissue sections by the avidin-biotin complex immunoperoxidase technique. Fetal liver pre-B cells and pre-B and common type acute lymphoblastic leukemia cells isolated from 15 patients were OKB1-OKB2+OKB4-OKB7-. All mature lymphoid tissue B cells and the neoplastic cell surface immunoglobulin-positive (SIg+) B cells isolated from each of 47 B cell neoplasms were OKB2+. OKB1 and OKB7 were expressed by interfollicular, follicular center, and many, but not all, mantle zone B cells. OKB4 was expressed by follicular center cells, but not by mantle zone or interfollicular B cells. The neoplastic SIg+ B cells isolated from 45 of 47 B cell malignancies were OKB1+OKB4+, and those isolated from 45 of 46 B cell malignancies were OKB7+. The neoplastic B cells of one mantle zone lymphoma were OKB1-, of one small lymphocytic cell lymphoma were OKB7-, of one large cell lymphoma were OKB4-, and of one small lymphocytic cell lymphoma with a monoclonal gammopathy were OKB1-OKB4-. Normal and myeloma plasma cells were OKB-. The malignant T cells isolated from 12 T cell neoplasms were OKB2-OKB4-, but were OKB1+ and/or OKB7+ in 3 cases. Thus, the OKB antibodies appear to detect distinctive antigens that may be expressed at different stages of B cell differentiation. In addition, OKB4 reacted with selected renal and respiratory epithelium, and OKB2 reacted with a wide range of epithelial tissues. The OKB antibodies should prove useful in the investigation of B cell differentiation and may aid in the identification and characterization of lymphoproliferative malignancies with significant therapeutic and prognostic differences not identifiable by conventional histopathologic and immunologic methods.

A case of human sympathetic ophthalmia, enucleated after surgical trauma, was studied by means of hybridoma-derived monoclonal antibodies, histochemistry, and transmission electron microscopy. The choroidal infiltrate was composed predominantly of T-lymphocytes of the suppressor/cytotoxic subset (OKT8+); only 5% of the cells were immunoglobulin-producing B-lymphocytes (kappa or lambda light chain positive), thereby explaining the well-known paucity of plasma cells in the infiltrate. The epithelioid cells and phagocytic histiocytes in the choroid were la+ and OKM1+, antigenic determinants specific for bone marrow-derived monocytes, and their cytoplasms exhibited histochemical reactivity for alpha-1-antichymotrypsin and lysozyme. Ultrastructurally, the choroidal epithelioid cells contained single melanin granules in the cytoplasm, but these were membrane-bound and frequently associated with lysosomal material, features militating against these cells being transformed choroidal melanocytes. By means of immunologic and ultrastructural analysis, the Dalen-Fuchs nodules were found to be composed of a mixture of histiocytes (la+ and OKM1+) and depigmented retinal pigment epithelial cells (la- and OKM1-); the latter cells focally formed desmosomes and displayed inclusions of lipofuscin. Scattered within the Dalen-Fuchs nodules were small numbers of T-lymphocytes of the suppressor/cytotoxic subset. We have concluded that the uveitis and retinal pigment epithelial changes are mediated by a T-cell, delayed hypersensitivity pathogenetic mechanism (cell-mediated immunity), possibly directed at surface membrane antigens that may be shared by photoreceptors, retinal pigment epithelial cells, and choroidal melanocytes.

A capillary hemangioma in the renal pelvis of a twelve-year-old child is presented. The diagnosis and management of renal pelvic tumors in childhood is reviewed. We believe this pathologic entity should be included in the differential diagnosis of hematuria and ureteropelvic junction obstruction in a child.