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R M Bolman

Publications and source records attributed to R M Bolman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Technique of single-lung transplantation.

The technique of single-lung transplantation at our institution has evolved as our experience has increased over the past 3 1/2 years. This technique is described and illustrated. Surgical staples are used to perform recipient pneumonectomy and provide free access to the hilar structures for anastomoses. The modified, telescoped bronchial anastomosis allows healing while obviating the need for omentopexy as seen in our last 30 bronchial anastomoses.

Anesthesia↗
PubMed1993

Prolongation of cardiac xenograft survival by depletion of complement.

Complement (C) activation is thought to be critical for the hyperacute rejection of xenografts. We investigated the role of C in the rejection of discordant cardiac xenografts by studying outcome in recipients depleted of C, using a highly purified form of cobra venom factor (CVF) in both a small (guinea pig [GP]-to-rat) and large (pig-to-baboon) animal model. A single dose of 30 or 60 units CVF given i.v. to rats completely abrogated hemolytic C activity for up to 72 hr. The lack of hemolytic C activity correlated with nearly undetectable serum levels of C3. Doses of 30 U/kg daily or 60 U/kg every other day over a 7-day period sustained C depletion without morbidity or mortality. Rats receiving GP cardiac xenografts during CVF therapy had significantly prolonged xenograft survival (88 +/- 10 hr in CVF-treated rats vs. 18.6 +/- 7.2 min in control rats, P < 0.001). Rats that rejected GP xenografts at 4 days posttransplant had higher levels of anti-GP antibodies than control rats, without hemolytic C activity at rejection. This rise in xenoreactive Ig reflected an increase in circulating IgG and IgM against GP antigens recognized before transplantation. Histologic analysis of GP cardiac xenografts taken from CVF-treated rats revealed leukocyte and monocyte margination along blood vessels, beginning at 12 hr posttransplant. Progressive cell infiltration, interstitial hemorrhage, and necrosis were observed over the next 72 hr. Rejected GP xenografts showed diffuse deposition of IgM and fibrin within blood vessels but no evidence of C3 deposition. A nonspecific pattern of IgG deposition was noted. CVF was tested in baboons. Complete C depletion was achieved with a dose of 60 U/kg, and was not associated with any morbidity or mortality. Xenotransplantation of a pig heart was performed in one baboon receiving CVF, 60 U/kg/day, for 2 consecutive days. Xenograft survival was prolonged to 68 hr, compared with 90 +/- 30 min in control baboons. Lack of hemolytic activity was noted during engraftment and at rejection. Histology showed evidence of vascular rejection. Immunopathology showed diffuse deposition of IgM, fibrin, and C4, and absence of C3 or membrane attack complex. We conclude that highly purified CVF can achieve marked C depletion with minimal morbidity and no associated fatalities. CVF alone can significantly prolong discordant cardiac xenograft survival. In the GP-to-rat model, the improvement in graft survival achieved with CVF was better than with conventional immunosuppression or isolated acute antibody depletion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Are multiple immunopathogenetic events occurring during the development of obliterative bronchiolitis and acute rejection?

The primed lymphocyte test (PLT) has been used to detect donor antigen-specific reactivity of bronchoalveolar lavage (BAL) lymphocytes associated with acute lung rejection and obliterative bronchiolitis (OB). To identify more precisely the immunopathogenetic events related to these processes, we have determined the PLT alloreactivity of 162 BAL specimens from 40 recipients as being directed against individual class I or class II antigens. We used selected homozygous typing cells representing the specific HLA class I and II antigens expressed by the recipient and donor cells. Our previous studies demonstrated a predominant CD8+ cell population mediating class I donor antigen-specific reactivity, correlating with OB in 3 out of 3 recipients tested, and a predominant CD4+ cell population mediating class II donor antigen-specific reactivity, correlating with acute rejection episodes in 13 out of 15 recipients tested. The obstructive airway disease OB, which is frequently fatal, is identified histologically by the presence of small airway inflammation and fibrosis of the lamina propria and lumen, and is characterized clinically by rapidly progressive airflow obstruction. However, a subgroup of patients with histologically proven OB demonstrates stabilization or only minimal progression of airflow limitation after augmentation of their immunosuppressive regimen, usually with high-dose methylprednisolone. To further characterize this subgroup, we tested the BAL-derived lymphocytes from 4 of these patients and observed PLT reactivity that correlated with the class II antigens of the donor, in contrast to the predominant donor class I antigen-specific PLT reactivity of patients with progressive OB. The distinct patterns of PLT reactivity observed for the BAL-derived lymphocytes from patients with the progressive versus the less progressive form of OB suggest that more than one immune process or perhaps different cell targets are involved. Alternatively, these clinical and in vitro findings may represent different stages of the same disease process. Taken together, these results suggest that distinct immunopathogenetic events may be occurring during acute lung rejection and OB.

Acute Disease↗
PubMed1993

The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model.

The mechanisms underlying rejection by rats of vascularized guinea pig xenografts have been controversial. The aim of this study was to define, using sequential immunopathologic analysis, the contributions of xenoreactive antibody, complement, and effector cells to the rejection of guinea pig cardiac xenografts by Lewis rats. In untreated recipients, hyperacute rejection of guinea pig cardiac xenografts occurred in 20 +/- 10.2 min and was characterized by focal endothelial deposition of IgM and by diffuse deposition of C3. IgG was not localized to endothelial surfaces, but was present in the same locations as albumin, suggesting that the accumulation of IgG might reflect nonspecific leakage of plasma proteins from blood vessels. No polymorphonuclear or monocytic infiltrate was observed. Depletion from rats of xenoreactive antibody to undetectable levels prolonged the survival of guinea pig cardiac xenografts, but did not prevent hyperacute rejection; the rejected xenografts contained deposits of C3 along the microvasculature but no deposits of IgM or IgG. No cellular infiltrate was observed. Depletion of complement with cobra venom factor prolonged the survival of xenografts up to 96 hr. Xenograft tissues from complement-depleted animals had diffuse deposits of IgM along the microvasculature, but no detectable deposits of C3 or IgG were noted. Graft tissues obtained at various times after transplantation into complement-depleted animals revealed cellular infiltrates consisting of granulocytes, monocytes, and lymphocytes, but few cells bearing an NK cell phenotype. Our findings are consistent with the concept that complement activation is essential for the hyperacute rejection of discordant xenografts, and that in this particular model complement activation can proceed without the involvement of antibody. However, our findings also suggest that xenoreactive antibody contributes to hyperacute rejection and, along with effector cells, contributes to the later rejection of a xenograft when hyperacute rejection has been averted. Finally, we show that when hyperacute rejection is avoided, a form of vascular rejection occurs in which certain of the pathologic features--i.e., interstitial hemorrhage, interstitial edema, and thrombosis--are very similar to those observed in hyperacute rejection. Whether this form of rejection is a delayed form of the process that leads to hyperacute rejection or a novel pathologic process of graft rejection has yet to be determined.

Animals↗
PubMed1993

Pulmonary function after successful heart transplantation. One year follow-up.

Congestive heart failure (CHF) has been associated with the development of restrictive ventilatory abnormalities and decreased pulmonary diffusing capacity. Whether these physiologic changes reflect permanent alterations of lung anatomy or result solely from potentially reversible alterations of lung water is not known. To examine this issue, we reviewed the pulmonary function tests (PFTs) and cardiac catheterization data from recipients of successful heart transplants prior to and 1 year after transplantation. Thirty-eight patients met the inclusion criteria (median age, 52 years). The median duration of symptomatic CHF prior to transplantation was 22 months (range, 3 to 72 months). After transplantation, spirometry revealed an improvement in FEV1 from 75.8 +/- 3.5 to 99.1 +/- 2.8 percent of predicted and FVC from 81.3 +/- 3.7 to 101.6 +/- 3.0 percent of predicted (p < 0.001). The FEV1/FVC ratio remained unchanged at 80 percent. Nonsmokers and former smokers had similar improvements in spirometry after transplantation. The TLC improved from 91.1 +/- 3.3 to 105.5 +/- 2.9 percent of predicted (p < 0.001); this improvement was due to an increase in inspiratory capacity. Diffusing capacity for carbon monoxide was decreased before transplantation and showed a small decline after transplantation from 82.3 +/- 3.2 to 76.8 +/- 2.6 percent of predicted (p < 0.05). After correction of severe CHF by cardiac transplantation, normalization of FEV1, FVC, and TLC can be anticipated. Diffusing capacity, however, may actually decline after transplantation.

Adolescent↗
PubMed1992

Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor.

Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative bronchiolitis patients (patients, 104 +/- 26.9 pM; controls, 8.4 +/- 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative bronchiolitis.

Adult↗
PubMed1992

Factors influencing the development of hypercholesterolemia after cardiac transplantation.

Although hypercholesterolemia is a frequent complication in cardiac transplant recipients, the exact mechanisms contributing to its development are not known. Cholesterol levels in 151 thoracic transplant patients treated with cyclosporine, azathioprine and prednisone were retrospectively examined to evaluate the factors influencing the heterogeneity of changes after the first year after transplantation in patients on a standard 3-drug immunosuppression regimen. Three groups were compared including ischemic heart transplant (n = 72), nonischemic heart transplant (n = 64) and heart-lung/lung transplant (n = 15) recipients. After the first year, 64 patients (43%) developed consistent hypercholesterolemia (greater than 240 mg/dl) for which pharmacologic treatment was initiated. Forty-eight patients (67%) in the ischemic heart transplant group required treatment, significantly (p less than 0.001) greater than both the nonischemic (n = 14; 22%) and heart-lung/lung transplant (n = 2; 13%) group. Univariate and forward stepwise multivariate regression analysis identified 4 factors that were all significantly and independently correlated with follow-up cholesterol including prednisone dose (p less than 0.001), baseline cholesterol (p less than 0.001), glucose (p less than 0.001) and weight gain (p less than 0.01). Changes in triglycerides in the 3 groups of patients were similar to changes in cholesterol. Furthermore, the increase in cholesterol in patients requiring treatment was primarily due to an increase in low-density lipoprotein cholesterol. These data demonstrate that hypercholesterolemia is common in heart transplant recipients treated with standard 3-drug immunosuppression and generally develops within the first 2 years after transplantation. However, this complication is not uniform and appears to be most strongly related to previous coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Use of epicardial electrocardiograms for detecting cardiac allograft rejection.

Since the advent of cyclosporin A surface electrocardiograms have been unreliable for diagnosing cardiac allograft rejection. Although several noninvasive methods have been proposed, none have been sufficiently accurate to be considered for clinical use. We have studied the use of the QRS complex amplitude, the unipolar peak-to-peak amplitude, recorded from intramyocardial electrodes for detecting rejection. Ten adult mongrel dogs underwent placement of intramyocardial electrodes on each ventricle. After stabilization of signals the hearts were transplanted heterotopically into unmatched recipients receiving cyclosporin A, azathioprine and methylprednisolone. Endomyocardial biopsies were performed after stabilization of unipolar peak-to-peak amplitude, twice weekly thereafter, and when unipolar peak-to-peak amplitude fell significantly. This detected 13 of 14 episodes of rejection. There was one false-positive and one false-negative result. The false-negative study became positive the following day. Thus, analysis of unipolar peak-to-peak amplitude detected all episodes of rejection in a clinically relevant time frame and was able to detect mild forms of rejection and multiple episodes of rejection in the same heart even in the presence of therapeutic levels of cyclosporin A.

Animals↗
PubMed1992

Differentiation of class I- and class II-directed donor-specific alloreactivity in bronchoalveolar lavage lymphocytes from lung transplant recipients.

Previous studies have demonstrated that donor antigen-specific primed-lymphocyte-test (PLT) reactivity of bronchoalveolar lavage lymphocytes is strongly associated with acute pulmonary rejection and with obliterative bronchiolitis (OB); however, a systematic analysis of PLT reactivity as being class I-or II-directed has not been performed. To assess reactivity directed against individual class I or II antigens, we tested a total of 67 BAL-derived lymphocyte samples from 26 recipients for alloreactivity in the PLT, using a pool of allogeneic cells and selected homozygous typing cells (HTCs) representing the HLA class I and II antigens expressed by the recipient and donor cells. The results obtained by PLT were correlated with the clinical status of the recipient with regard to rejection, infection, and OB. In 9 of 10 cases where transbronchial biopsy results were consistent with rejection, donor antigen-specific allogeneic PLT reactivity was observed and, more specifically, could be determined to be directed toward donor class II antigen in 8 of these cases. For 3 of 4 recipients tested chronologically, positive donor antigen-specific PLT reactivity was observed at the time of and 2-3 1/2 months prior to the diagnosis of rejection by transbronchial biopsy. During periods of acute infection, donor antigen-specific PLT reactivity was not observed; instead, non-specific PLT reactivity of BAL-derived cells (i.e., reactivity that did not correlate with any defined HLA antigens) was observed as well as reactivity associated with the self-antigens expressed by the recipients' cells. The PLT reactivity of BAL-derived cells from a recipient diagnosed with OB correlated specifically with one of the disparate donor class I antigens (HLA-B44). In 23 cases, BAL cells were propagated in the presence of autologous cells and rIL-2, thereby allowing for sufficient numbers of cells to test with a panel of 29 HTCs and to analyze for cell surface phenotype. The cultured BAL cells from 4 recipients undergoing a rejection episode demonstrated a predominant CD4+ phenotype consistent with the class II-directed reactivity observed in PLT. However, these results did not demonstrate a phenotype distinctive from the 7 BAL results obtained from 4 quiescent recipients. In marked contrast, the cultured BAL cells obtained from 4 recipients diagnosed with OB demonstrated a predominant CD8+ phenotype, with 60-92% of the cultured cells being CD8+. These results are consistent with the class I-directed reactivity observed in PLT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Evidence that 15-deoxyspergualin inhibits natural antibody production but fails to prevent hyperacute rejection in a discordant xenograft model.

Preventing hyperacute rejection (HAR) is a difficult and unsolved problem in xenotransplantation. This may be due, in part, to a lack of therapies that can suppress production of natural antibodies (NA), which are thought to be critical mediators of HAR. This study examined the effect of 15-deoxyspergualin (DSPG) and splenectomy (Spx) on NA production and return of NA after plasma exchange (PE) in a discordant species combination (strain 2 guinea pig to Lewis rat). A dose of 5 mg/kg/day DSPG + Spx significantly reduced Lewis rat anti-guinea pig NA titer after one week of therapy. Antibody titer was not significantly reduced in rats treated with splenectomy alone. PE alone acutely depleted NA titers; however, complete rebound was seen in 48 hr. When PE was performed in rats treated with DSPG + Spx, an additional significant NA reduction occurred; no rebound 24-48 hr after PE was seen. Except for a 20% reduction in body weight, no serious complications occurred in DSPG + Spx recipients. Despite a profound NA titer reduction, treatment with DSPG, Spx, and PE did not prolong guinea pig cardiac xenograft survival in a clinically significant fashion. Immunopathological study of rejected cardiac xenografts revealed no antibody deposition but persistent complement deposition on vascular endothelium. We conclude that DSPG + Spx effectively inhibits synthesis of rat anti-guinea pig NA, that further NA titer reduction can be achieved with the addition of PE, and that DSPG + Spx prevents post-PE antibody rebound. We also conclude that the limited prolongation in cardiac xenograft survival achieved, despite marked suppression of NA, supports a complement-mediated mechanism of HAR in our animal model.

Animals↗
PubMed1992

Shifting pneumothorax after heart-lung transplantation.

Heart-lung transplantation involves the total replacement of two of the most complex organs of the thoracic cavity. This procedure is usually reserved for patients with failure of both systems, such as in primary pulmonary hypertension or chronic Eisenmenger physiology. The en bloc replacement of the heart and lungs leaves an open communication between the two sides of the thorax that may allow air or fluid to shift from one side to the other. To evaluate this possibility, the authors reviewed the chest radiographs of 25 heart-lung transplant recipients for signs of rapidly changing pneumothoraces that could not be explained by the conventional dynamics of pleural physiology. A series of postoperative radiographs showed unusual shifting or apparently rapid disappearance of pneumothoraces in eight patients. Decompression of a pneumothorax with a contralateral chest tube was a phenomenon observed in six of these patients.

Adolescent↗
PubMed1992

Correlation of endomyocardial biopsy findings with electrocardiogram voltage in pediatric cardiac allografts.

Endomyocardial biopsy is said to be the gold standard for the diagnosis of cardiac rejection. In the pediatric age group endomyocardial biopsy is more difficult, and technically may be unsatisfactory. It is therefore desirable to correlate the biopsy finding with non-invasive studies so that patients may be monitored meaningfully, and endomyocardial biopsy may be used in a more selective manner. Ten pediatric patients (age range 2-16 years, mean 11.1 yr) underwent endomyocardial biopsy and electrocardiography simultaneously during their post-transplant course (2-24 biopsies, mean 14 biopsies). All patients were treated with triple-drug therapy including cyclosporine, azathioprine and prednisone. Biopsies were classified according to the working formulation of the International Society for Heart Transplantation. The total electrocardiographic voltage (summation of leads 1, 2, 3, V1 and V6) and the limb lead voltage (summation of leads 1, 2, and 3) were calculated. The measurements were then converted into percentage of the highest voltage for each patient, and these values were then compared in the different biopsy groups by analysis of variance. Both the total voltage and the limb lead voltage were significantly lower in the group with grade 3 biopsies versus all other groups (p less than 0.0005). At a level of 10% decline in total voltage, changes in EKG voltage had low specificity (87%) and positive predictive value (51%) but high sensitivity (94%) and negative predictive value (99%). We conclude that, although strong correlation is present between rejection and low voltage, a decline in voltage is not specific for rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗