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Biomedical subjects

R M Bolman

Publications and source records attributed to R M Bolman.

At least 55 records · Page 3Linked to original sources

Antibody removal by column immunoabsorption prevents tissue injury in an ex vivo model of pig-to-human xenograft hyperacute rejection.

Hyperacute rejection of a pig-to-primate organ xenograft is triggered by binding of anti-pig endothelial cell antibodies to the vascular endothelium of the xenograft and complement activation. Xenograft survival can be prolonged by pretransplant depletion of antibody with plasmapheresis or organ perfusion. However, these techniques have disadvantages for use immediately pretransplant or in the post-transplant period, including a marked reduction in coagulation proteins. To remove IgM and IgG from human plasma we employed a reusable Ig-binding column containing polyclonal anti-human IgG (heavy chain- and light chain-specific) conjugated to Sepharose beads (Therasorb, Baxter Corp.). Human blood was separated into plasma and cell fractions. Column absorption of plasma followed by recombination of plasma and cell fractions in the perfusion system resulted in 90.5 and 86.0% reduction in total IgG and IgM, respectively, and in a 47.0 and 69.4% reduction in IgG and IgM anti-pig endothelial cell antibodies, respectively. When the cellular fraction was recombined with untreated plasma and used to perfuse pig hearts in an ex vivo perfusion system, there was rapid cessation of normal cardiac rhythm (25.2 +/- 5.6 min) and intense deposition of Igs, complement proteins, and fibrin in the tissues. In contrast, perfusion with blood containing column-absorbed plasma was able to sustain cardiac function, with normal sinus rhythm maintained for 258 +/- 48.1 min, without tissue deposition of IgM or complement proteins and minimal deposition of IgG. We conclude that column absorption can be used effectively to deplete plasma of anti-pig endothelial cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Suicide right ventricle after lung transplantation for Eisenmenger syndrome.

Right ventricular outflow tract obstruction, or "suicide right ventricle," rarely has been observed after single or bilateral single-lung transplantation for the treatment of Eisenmenger syndrome. We describe our experience in 2 patients with Eisenmenger syndrome in whom right ventricular outflow tract obstruction developed, in 1 after single-lung transplantation and ventricular septal defect repair and in the other after bilateral single-lung transplantation. Both patients suffered progressive deterioration and hemodynamic instability that was unresponsive to aggressive medical therapy. Diagnosis was confirmed in both patients by transesophageal echocardiography. Operative intervention was undertaken 72 and 24 hours after transplantation, and consisted of myectomy and outflow tract patching. One patient survived; the other died intraoperatively. The index of suspicion for this problem should be high during the intraoperative performance of transesophageal echocardiography, as well as during direct gradient measurement, with consideration of immediate management of severe right ventricular outflow tract obstruction at the time of transplantation.

Adult↗

Deep venous thrombosis and pulmonary embolism after lung transplantation.

The incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung (n = 87) or heart-lung (n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted.

Adult↗

Long-term health status and quality of life outcomes of lung transplant recipients.

STUDY OBJECTIVE: Health status and quality of life (QOL) in lung transplant candidates and recipients were compared to determine the impact of transplantation, and whether recipients experience continued improvements in the years after transplant surgery. DESIGN: Two patient groups, adult lung transplant candidates (n = 44) and adult lung transplant recipients (n = 54), completed self-report QOL questionnaires. Eighteen of the 54 recipients completed QOL questionnaires on two occasions, about 18 months apart, after lung transplant. The questionnaire included the Medical Outcome Study Health Survey (MOS 20) that assesses six dimensions of health-related QOL: physical, role and social function, mental health, health perceptions and bodily pain, as well as a self-report Karnofsky Index and other indicators of QOL. SETTING: University medical center transplant service. RESULTS: Compared with candidates, recipients reported higher levels of happiness and more satisfaction with their life and their health. They also reported better function on the Karnofsky Index and in every MOS 20 dimension (p < 0.0001), except pain. No significant differences were found in comparisons among recipients, grouped by the time since their transplant. Eighteen recipients completed two QOL questionnaires after transplant. No significant differences were found between the earlier (median, 11 months) and later (median, 29 months) QOL responses for this group overall. However, recipients (n = 5) who developed obliterative bronchiolitis between assessments showed decrements in their health-related QOL. Dimensions particularly affected were physical and social functioning and bodily pain. CONCLUSIONS: Dramatic improvements in health status and QOL occur after successful lung transplant and remain stable over time. Obliterative bronchiolitis results in notable QOL reductions.

Activities of Daily Living↗

Allogeneic microchimerism and donor antigen-specific hyporeactivity in lung transplant recipients.

The identification of peripheral donor cells in solid organ transplant recipients has led to speculation as to the tolerogenic role of circulating donor cells. Also being debated is the possible significance of persistent donor alloantigen-presenting cells in inducing and maintaining an alloantigen-specific unresponsive state. Previously, we showed that donor antigen-specific hyporeactivity is a useful marker for identifying kidney, lung, or heart recipients at low risk for immunologic complications; we found donor antigen-specific hyporeactivity in 25% of kidney, 35% of lung, and 22% of heart recipients. All 3 hyporeactive subgroups experienced fewer late (> 3 months) rejection episodes and a lower incidence of chronic rejection. The purpose of the current study was to determine whether peripheral blood microchimerism correlates with the development of donor antigen-specific hyporeactivity and affects clinical outcome. We correlated the detection of microchimerism with in vitro proliferative response to donor antigen in 19 lung recipients who were > or = 12 months posttransplant. Allogeneic peripheral blood microchimerism was studied with a PCR-based limiting detection assay using HLA-DR sequence-specific primers. We detected microchimerism in 47% (9 of 19) of the lung recipients tested. All recipients who were donor antigen-specific hyporesponsive had microchimerism, and all recipients without detectable microchimerism were responsive to donor antigen. However, not all recipients with microchimerism developed donor antigen-specific hyporeactivity. Further, none of the hyporesponsive recipients has been diagnosed with obliterative bronchiolitis (OB). In contrast, 2 of the 4 with microchimerism who were responsive to donor antigen have been diagnosed with OB, as have 5 of the 10 who were negative for both hyporeactivity and microchimerism. Thus, long-term graft outcome may correlate more closely with donor antigen-specific hyporeactivity than with microchimerism.

Antigen-Presenting Cells↗

Liberalization of donor criteria in lung and heart-lung transplantation.

Since March 1986, we have performed 26 heart-lung transplantations, 42 single-lung transplantations, 9 bilateral single-lung transplantations, and 1 double-lung transplantation. The original lung donor requirements were as follows: age less than 40 years, no smoking history; no gram-negative rods or fungus on sputum Gram stain; arterial oxygen tension greater than 140 mm Hg on an inspired oxygen fraction of 0.40; no infiltrate or pneumothorax on the chest radiograph; and donor height within 15 cm (6 inches) of recipient height. As the number of potential recipients increased, so did the waiting time. To counter this delay, during the past year we have liberalized our donor criteria. We now accept lung donors up to age 60 years. Any kind of smoking history is acceptable unless there is chronic obstructive pulmonary disease or pulmonary fibrosis on the chest radiograph. Sputum must be free from fungus, but gram-negative rods are treated with appropriate antibiotics. The arterial oxygen tension on an inspired oxygen fraction of 0.40 should be greater than 100 mm Hg, and a small pulmonary infiltrate is not worrisome. This liberalization of the donor pool for lung and heart-lung transplantation has not adversely affected early outcome.

Adult↗

Experimental large-animal model of obliterative bronchiolitis after lung transplantation.

Obliterative bronchiolitis is a major cause of long-term morbidity after lung transplantation. It is characterized by small-airway inflammation and occlusion by fibrous tissue. The pathogenesis is uncertain. To study this disease, we developed a model of posttransplantation obliterative bronchiolitis using genetically defined miniature swine. Group 1 (n = 2) received a left lung autograft; group 2 (n = 7), a left lung allograft. Group 2 recipients were given cyclosporine, prednisone, and azathioprine for 3 months, then immunosuppression was tapered and discontinued over 1 month. The animals were observed for an additional 2 months, then sacrificed. Lung grafts in both groups were monitored with serial bronchoalveolar lavages and transbronchial biopsies for 6 months. After sacrifice, lung grafts underwent histopathologic and immunohistochemical examination. No allograft had histologic evidence of acute rejection or peribronchiolar infiltrate during the first 3 months of immunosuppression. During the tapering period, airway changes characterized by severe peribronchiolar lymphocytic infiltrates were seen. Bronchoalveolar lavages of allografts showed significantly increased lymphocyte counts with CD8+ cells predominating. After the discontinuation of immunosuppression, transbronchial biopsy and autopsy specimens showed progressive fibrous inflammatory occlusion of bronchioles. Immunohistochemical staining demonstrated increased expression of MCH class II antigen on the bronchiolar epithelium and increased dendritic cells and CD4+ lymphocytes. None of these changes were seen in group 1. Our findings suggest obliterative bronchiolitis is an immunologically mediated phenomenon related to chronic graft rejection after lung transplantation. This model will allow systematic study of the pathogenesis of obliterative bronchiolitis and possible therapeutic intervention.

Animals↗

Cytomegalovirus colitis in a pediatric heart transplant patient.

Cytomegalovirus colitis is one of the sequelae of cytomegalovirus infection in transplant patients and can be associated with severe consequences. This case details the clinical, radiographic, and laboratory features of this infection in a child after heart transplantation where early recognition and treatment resulted in complete resolution of the disease.

Child, Preschool↗

Chest trauma. Assessment, diagnosis, and management.

In the United States, trauma is the leading cause of death in people under 40 years of age. Chest trauma is a relatively common but potentially lethal injury and requires a high level of suspicion, rapid diagnosis, and appropriate therapy. Methods for the assessment, diagnosis, and treatment of chest trauma are discussed in this article.

Chest Tubes↗

Early results after pediatric cardiac transplantation with triple immunosuppression therapy.

Pediatric heart transplant recipients were previously reported to have higher early mortality and morbidity than do adult patients treated with triple immunosuppression therapy (steroids, azathioprine and cyclosporine). Nineteen patients (11 infants and 8 older children) underwent orthotopic transplantation using triple immunosuppression therapy. Surveillance for cellular rejection and coronary arteriopathy was performed with endomyocardial biopsy and selective coronary angiography in all patients, with continuous monitoring for hypertension and serious infection. Seventeen of 19 patients (89%; 10 infants and 7 older children) are current survivors, with a median follow-up of 29 months (range 17 to 94). There were 5 and 7 episodes of rejection in the first 12 months after transplantation in the infant and older groups, respectively, for actuarial freedom-from-rejection rates of 65% at 3 months and 54% at 12 months. Severe coronary arteriopathy was detected in 1 infant 11 months after transplantation. In the first 12 months after transplantation, there were 3 hospitalizations for infection, and 2 patients needed treatment for hypertension in the infant group, compared with 1 hospitalization for infection, and 4 patients on antihypertensives in the older group. An increased prevalence of noninfectious complications in the infant group led to significantly longer postoperative stays than in the older group (mean 27.3 vs 19.4 days; p < 0.05). The results indicate that cardiac transplantation using triple immunosuppression therapy in infants, children and adolescents is associated with a high survival rate, and low rates of rejection and serious infection.

Actuarial Analysis↗

Trends in patient selection for heart transplantation.

OBJECTIVES: The purpose of this study was to review specific outcomes of patient referrals and the utility of selection criteria for heart transplantation at a single transplant center and to assess important trends over a 5-year period. BACKGROUND: Although patient selection criteria are important for the clinical success of heart transplantation and the optimal utilization of the limited supply of donor organs, there are few data regarding actual outcomes and whether selection criteria are facilitating the identification of the most appropriate patients. METHODS: We retrospectively reviewed 511 consecutive referrals of adult patients with heart failure from January 1, 1987 to December 31, 1991. Patients were followed up to one of five end points: 1) acceptance onto the transplant waiting list, 2) rejection from the transplant waiting list, 3) death, 4) referral to another program, and 5) still pending evaluation. RESULTS: Of the 511 referred patients, 221 (43%) were accepted onto the waiting list, 222 (43%) were rejected, 39 (8%) died before the evaluation was completed, 15 (3%) were referred to another program and 14 (3%) are still pending evaluation. The rates for acceptance and rejection each year ranged between 30% and 51% and there were no consistent trends in the acceptance/rejection ratio from 1987 to 1991. Of the 221 patients accepted onto the waiting list, 115 (52%) underwent transplantation, 50 (22%) died, 12 (5%) were removed from the list because of clinical improvement, 9 (4%) were referred to another program and 35 (16%) are still on the waiting list. The continuing shortage of donor organs resulted in a marked increase in the size of the waiting list from 12.6 patients in 1987 to 36.5 in 1991, as well as a marked increase in the time on the waiting list before transplantation. Over 5 years, 50 patients were considered "too well" for transplantation (23% of all rejections). Of these 50 patients, 43 (86%) are alive and 7 were lost to follow-up during a mean period of 28.6 months (range 4 to 62). All 12 patients who were taken off the active transplant list because of improvement in symptoms, ejection fraction or peak exercise oxygen consumption are alive with a mean follow-up period of 27.7 months (range 11 to 61). CONCLUSIONS: These data confirm the fact that transplant referrals are a selected group of patients with a high mortality rate, as 8% died before the evaluation could be completed and 22% died while waiting for a suitable donor organ. Furthermore, patient selection criteria are able to identify a small subset of patients with a low mortality risk as patients who were rejected because they were too well or taken off the list for clinical improvement have a reasonably good prognosis.

Adult↗