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R M Bolman

Publications and source records attributed to R M Bolman.

156 records · Page 9Linked to original sources

Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival.

Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation.

Animals↗

Single lung transplantation for severe emphysema.

UNLABELLED: Lung transplantation is effective therapy for patients with severe obstructive lung disease. We reviewed seven patients with severe emphysema (age, 48 +/- 5 years; forced expiratory volume in 1 second [FEV1] 0.76 +/- 0.26 liters) who received single-lung transplants (SLT) at our institution between August 1989 and September 1990. Studies to assess the adequacy of cardiac function before transplantation showed moderately reduced right ventricular function (by multiple gated acquisition, 34 +/- 6%), moderately elevated pulmonary artery pressure (25 +/- 3 mm Hg), and normal left ventricular function (by multiple gated acquisition 65% +/- 12%) and coronary arteriograms. Time on the waiting list before transplantation was reduced compared with heart-lung transplant (HLT) recipients (waiting time, 2.9 +/- 1.5 months for SLT, 9.6 +/- 10.2 months for HLT). Six of the SLT recipients are currently alive (after transplantation interval, 17 +/- 5 months); the remaining recipient died of pulmonary embolism 21 days after SLT. Number of ventilator days, intensive care unit days, and days to hospital discharge after transplantation did not differ significantly from HLT recipients. Cardiopulmonary bypass was necessary in four SLT recipients. Pulmonary function was markedly improved after SLT (FEV1, 1.78 +/- 0.73 L/min after SLT versus 0.75 +/- 0.3 L/min before SLT; p less than 0.01), and functional status is correspondingly improved. CONCLUSIONS: SLT constitutes effective therapy for patients with severe emphysema, including those with moderate reduction of right ventricular function; and SLT offers distinct advantages over HLT, including decreased waiting time before transplantation, improved donor organ utilization, and less frequent need for cardiopulmonary bypass.

Female↗

Safe and effective plasma exchange to remove antibodies prior to xenogeneic heart transplantation in small primates.

The ability of an on-line, rapid plasma exchange (PE) system to remove circulating antibodies in preparation for xenogeneic heart transplantation was studied. Plasma exchanges were performed 27 times on 13 rhesus monkeys weighing from 6.5 to 12.0 kg, using systemic heparinization, without untoward effects. Blood flow rates of 22-72 ml/min resulted in plasma collection rates of 7-22.5 ml/min. Serum immunoglobulin levels were decreased by more than 90%, and specific antiendothelial xenoreactive IgM was completely removed after two plasma exchanges. Transferrin levels were decreased 85-95%, and complement levels fell by greater than 80%. Platelets were partially conserved, with removal rates of 18-60%. All factors returned to normal ranges within 48 hours and no bleeding complications were encountered. When antiendothelial antibodies were removed in this manner, survival of a pig heart transplanted into a rhesus monkey was extended to 12 hours, from a baseline of 2 hours, without treatment.

Animals↗

Reduction of infectious complications following heart transplantation with triple-drug immunotherapy.

Infection remains the major cause of mortality and is a significant source of morbidity following heart transplantation. Between March 1978 and March 1986, 62 orthotopic heart transplants were performed at the University of Minnesota. There were 56 clinically significant infectious episodes in 31 of the 58 patients surviving the perioperative period. The era I (1978-1982) experience with antilymphocyte globulin, prednisone, and azathioprine and the era II (1982-1983) experience with high-dose cyclosporine and prednisone were associated with a high incidence of cytomegalovirus and fungal infections. The conversion to low-dose triple-drug immunosuppression with cyclosporine, prednisone, and azathioprine in 1983 (era III) has markedly reduced infectious deaths and altered the spectrum of clinical infection by decreasing serious fungal and cytomegalovirus infections. This protocol has also significantly reduced the incidence of rejection. The reduction of infection and rejection complications with triple-drug immunosuppression has led to improved patient survival of 94% at 1 year and 87% at 2 years.

Adolescent↗

Heart transplantation in patients requiring preoperative mechanical support.

Since January 1985, the members of the Heart Transplant Program at Washington University Medical Center, St. Louis, have performed 53 transplants in 50 patients. Thirteen patients have required preoperative mechanical support. These patients ranged in age from 32 to 58 years, with a mean of 47 years. Seven patients had undergone a total of 12 prior cardiac surgical procedures. Preoperative diagnosis was coronary artery disease in nine patients, cardiomyopathy in three, and valvular heart disease in one. Two patients had mechanical ventilatory support before operation. Five patients required preoperative intraaortic balloon counterpulsation (IABP). Five patients required left ventricular assistance with the Bio-Medicus centrifugal pump (Bio-Medicus Inc., Eden Prairie, Minnesota). Two of these patients had the left ventricular assist device (LVAD) inserted at the end of a failed cardiac procedure. One patient required the extracorporeal membrane oxygenator (ECMO) for right ventricular decompensation and cardiac arrest 4 hours after a seemingly successful orthotopic transplantation. Twelve of the 13 patients (92%) who required mechanical assistance of circulation and/or respiration before operation underwent a successful transplant. One patient who had IABP support perioperatively did not survive surgery. All patients who had a bridge to transplantation with the LVAD and the one patient with a bridge to transplant with ECMO are long-term survivors of transplantation. There has been one late death from cardiac causes in a patient who had IABP support before operation; the death was presumed to be from acute rejection, though this could not be documented at autopsy. Actuarial survival in this group is 82% at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Improved long-term graft outcome in lung transplant recipients who have donor antigen-specific hyporeactivity.

We have shown that in renal transplant recipients the development of in vitro donor antigen-specific hyporeactivity correlates with improved long-term graft outcome. Donor antigen-specific hyporeactivity is determined by in vitro mixed lymphocyte culture assays with recipient cells used as responder cells and homozygous typing cells as stimulator cells. Hyporeactivity is defined as a decreased response to stimulation by specific homozygous typing cells that define donor antigens, whereas response to homozygous typing cells defining third-party antigens remains unchanged. We tested 23 lung transplant recipients at least 1 year after transplantation to determine if donor antigen-specific hyporeactivity and the corresponding improved graft outcome were organ specific. Of these 23 recipients, eight had donor antigen-specific hyporeactivity; they demonstrated a trend toward a lower incidence of late acute rejection episodes (one rejection episode in one patient) versus the 15 recipients who remained responsive to donor antigens (11 rejection episodes in six patients). No recipients with donor antigen-specific hyporeactivity have been diagnosed with obliterative bronchiolitis, unlike six recipients who remained responsive to donor antigens (0% versus 40%; p = 0.058). We conclude that immune regulation, as evidenced by donor antigen-specific hyporeactivity, correlates with improved graft outcome for lung transplant recipients and may even provide immunologically based criteria for selecting candidates whose immunosuppression might be reduced successfully.

Adult↗

Abdominal complications after lung transplantation.

BACKGROUND: Serious abdominal complications after heart and heart-lung transplantation have been a well-documented source of morbidity and mortality in this patient population. This report reviews the incidence and spectrum of abdominal complications occurring in lung transplant recipients at a single institution. METHOD: Between January 1988 and July 1993, 75 patients underwent lung transplantation (58 single lung, 16 bilateral single lung, and 1 double lung) at the University of Minnesota. RESULTS: Twelve patients (16%) sustained 20 abdominal complications. There were 11 early abdominal complications (< or = 30 days after transplantation) including prolonged adynamic ileus (4), diaphragmatic hernia after omental wrap (3), ischemic bowel (2), colitis with hemorrhage (1), and splenic injury after colonoscopy (1). There were nine late abdominal complications (range, 32 days to 28 months after transplantation) including colonic perforation (4), cholelithiasis/choledocholithiasis (2), development of a mesenteric pseudoaneurysm (1), fungal hepatic abscess (1), and intraabdominal hemorrhage (1). Twenty-six procedures were performed for management of the abdominal complications including: colonoscopy (7), colectomy (5), repair of diaphragmatic hernia (3), colostomy takedown (4), small-bowel resection (2), open cholecystectomy with common bile duct exploration (1), open cholecystectomy (1), splenectomy (1), mesenteric arterial pseudoaneurysm embolization (1), and percutaneous liver biopsy (1). Four patients died of causes attributable to their abdominal complications. CONCLUSIONS: In each case in which a death occurred, there was a delay between the onset of symptoms and diagnosis and intervention of more than 6 days. Abdominal complications accounted for 22% of all deaths in our lung transplantation group. A high index of suspicion and early recognition and intervention will decrease the morbidity and mortality caused by abdominal complications in lung transplant patients.

Actuarial Analysis↗

Pediatric heart transplantation: results of 2- and 5-year follow-up.

Pediatric heart transplantation has become an accepted method of treatment for certain pediatric heart disease. From July 1986 to January 1993, we performed 25 orthotopic pediatric heart transplantations at the University of Minnesota Hospital and Clinics in 16 male patients and nine female patients. The average age was 8.5 years with a range from 7 days to 18 years. Three of the patients were younger than 1 year of age. The indications for transplantation included congenital heart disease in six patients and cardiomyopathy in 19 patients. Four of the patients with congenital heart disease had previously undergone a cardiac surgical procedure. Two patients with cardiomyopathy had mechanical assist devices in place at the time of transplantation. Donor age ranged from 2 months to 36 years. The donor organ ischemic time ranged from 60 minutes to 329 minutes, with an average of 191 minutes. Follow-up ranged from 6 to 84 months. Overall, there were seven deaths (28%) in the patients undergoing transplantation. Of the seven deaths, four (16%) were early (within 30 days) and three (14.3%) were late. The four early deaths were a result of donor organ failure, and the three late deaths a result of acute rejection. The 2-year survival for patients with a minimum 24-month evaluation was 79% (15 of 19). Of 12 patients available for 5-year assessment, 75% (9 of 12) were alive and doing well at the time this article was written. Pediatric heart transplantation can provide good intermediate and long-term survival for selected pediatric patients.

Cardiomyopathies↗

Outcome after referral for pediatric transplantation.

Although heart, heart-lung, or lung transplantation is performed in more than 200 children annually, the number of patients referred for such procedures is considerably greater, and little is known about the outcome of those referrals. To determine the outcome of pediatric transplant referrals we reviewed the follow-up of 31 patients evaluated at our institution for heart (24), heart-lung (three), or lung (four) transplantations between January 1991 and September 1992. Indications included hypoplastic left heart syndrome (seven patients), cardiomyopathy or myocarditis (seven patients), and postoperative congenital heart disease (10 patients) for heart transplantation; Eisenmenger's syndrome (three patients) for heart-lung transplantation; and primary pulmonary hypertension (two patients), broncho pulmonary dysplasia, and cystic fibrosis for lung transplantation. Only 14 of 31 referred patients were listed for transplantation; the remaining 17 patients either improved when medical therapy was maximized (nine patients), died within days of referral (three patients), refused (two patients), chose alternate surgery (one patient), were medically unacceptable (one patient), or are currently undecided (one patient). To date 7 of 14 patients listed have undergone successful heart transplantation; the remaining seven patients either improved and did not require transplantation (two patients), refused (one patient), died waiting (one patient), are currently awaiting a donor (one patient), or underwent Norwood procedure because of donor unavailability (two patients). Thus including patients who died before listing, only 14 of 31 referrals (45%) were deemed in need of a transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Successful treatment of Mycoplasma mediastinitis after heart-lung transplantation.

Mycoplasma hominis and Ureaplasma urealyticum are members of the Mycoplasma genus that can infect surgical wounds. These organisms are rarely cultured by conventional laboratory techniques, and they respond poorly to commonly used broad-spectrum antibiotics. Including this case, five cases of Mycoplasma mediastinitis have been reported, three of which followed heart-lung transplantation. Successful treatment of Mycoplasma mediastinitis after heart-lung transplantation was achieved in this patient with extensive debridement, muscle-flap coverage, and long-term antibiotics. Possible sources of this infection after heart-lung transplantation and treatment options are discussed.

Heart-Lung Transplantation↗