Lung transplantation is here to stay.
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Heart Diseases↗
Biomedical subjects
J Theodore
Publications and source records attributed to J Theodore.
Clinical significance of hyperbilirubinemia in patients with pulmonary hypertension undergoing heart-lung transplantation.
Hyperbilirubinemia is commonly observed in long-standing pulmonary hypertension and is thought to be the result of chronic right ventricular failure and subsequent liver congestion. To evaluate the clinical significance of preoperative hyperbilirubinemia, we reviewed the cases of 62 patients with pulmonary hypertension (31 primary and 31 Eisenmenger's syndrome) who underwent heart-lung transplantation between 1981 and 1990 at Stanford. Bilirubin levels higher than 1.0 mg/dl were noted in 58% of patients, and bilirubin levels higher than 2.0 mg/dl were noted in 23% of patients. Indirect hyperbilirubinemia accounted for 66% to 87% of the total bilirubin and tended to fluctuate with diuretic therapy. It was associated with polycythemia, reticulocytosis, and mild elevations of liver enzymes. Early postoperative mortality in patients with total bilirubin levels greater than 2.1 mg/dl, bilirubin levels greater than 1 mg/dl but less than 2.0 mg/dl, and levels less than 1 mg/dl was 58%, 27%, and 16%, respectively (p less than 0.05). In those with high bilirubin levels, four patients had severe hemorrhage as part of their terminal event. Cardiac cirrhosis was found at autopsy in 75% of the early deaths of patients with high bilirubin. We conclude that hyperbilirubinemia is a late manifestation of pulmonary hypertension. The mechanism of hyperbilirubinemia is probably the result of the combination of increased hemolysis and decreased uptake by the chronically congested liver. Patients with pulmonary hypertension and hyperbilirubinemia appear to be at greater surgical risk during heart-lung transplantation.
Adult↗
Quest--sociology by any other name.
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Curriculum↗
Dermatologic complications following heart transplantation.
A total of 107 consecutive heart transplant recipients at Stanford University Medical Center were prospectively screened for dermatologic disease as part of their routine postoperative evaluation over a 6-month period. The incidence of nonmelanotic skin tumors and premalignant lesions was approximately 25-fold greater than expected in a normal population. Skin infections were seen in 55% of the patients and dermatologic drug side effects were almost universal including xerosis, hypertrichosis, and steroid acne. Successful excision or cryotherapy of all neoplastic lesions was achieved with no evidence of recurrence to date, a mean of 11 months. The skin infections responded to appropriate antiviral, antibacterial, and antifungal agents and the xerotic and acneiform lesions were successfully treated with emollients and topical retinoic acid, respectively. In addition, patients were instructed in preventive measures including the use of sunscreen agents and protective clothing. We conclude that heart transplant recipients have a significantly increased incidence of neoplastic, infectious, and drug-induced skin diseases. Routine dermatologic screening resulted in early identification and successful treatment of these lesions. We suggest that dermatologic screening is both feasible and valuable in this setting.
Adult↗
The spectrum of cytomegalovirus infection following human heart-lung transplantation.
Data were analyzed from 19 long-term survivors of cardiopulmonary transplantation in this institution, including nine patients with normal pulmonary function and 10 recipients with posttransplant obliterative bronchiolitis. In all cases, donor cytomegalovirus titers (IgG), preoperative recipient titers (IgG), and serial postoperative recipient titers (IgM, IgG, and complement fixation) were available. In addition, surveillance cytomegalovirus cultures and pulmonary function tests were obtained prospectively after surgery in all 19 patients. A total of 12 patients developed active cytomegalovirus infection (serologic conversion confirmed by positive cultures) after transplantation, six of whom subsequently developed obliterative bronchiolitis. However, infection was clinically associated with pulmonary deterioration in only four of these patients, three of whom had cytomegalovirus pneumonitis. With the exception of obliterative bronchiolitis, no other permanent sequelae of cytomegalovirus infection were evident in this small group. Progressive obliterative bronchiolitis was also seen in four of the seven recipients who had no evidence of cytomegalovirus infection at any time. Although viral causes have been associated with obliterative bronchiolitis, the current data suggest that cytomegalovirus infection in the absence of pneumonitis does not appear to be a significant risk factor for obliterative bronchiolitis in cardiopulmonary transplant recipients. A larger group of patients will be required to ultimately establish the role of cytomegalovirus infection in this setting.
Antibodies, Viral↗
Kidney function in heart-lung transplant recipients: the effect of low-dosage cyclosporine therapy.
The indices of kidney function of all discharged heart-lung transplant survivors were examined before and after the introduction of a triple-drug immunosuppressive regimen comprised of low dosages of cyclosporine (to maintain a trough serum level of 75 to 100 ng/ml by radioimmunoassay), azathioprine (1 to 1.5 mg/kg/day), and prednisone. A comparison of survivors treated with either high dosages of cyclosporine (n = 19) or low dosages of cyclosporine (n = 8) revealed a lower early creatinine level postoperatively (1.84 versus 0.96 mg/dl), a higher creatinine clearance (46.33 versus 62.47 ml/min), and a lower cyclosporine level (337.96 versus 204.30 ng/ml) in the latter group. The findings from the outpatient period were similar to the above, and all findings were statistically significant (p less than or equal to 0.05). Another comparison of a subgroup of survivors (n = 11) before and after conversion to the low dosage cyclosporine triple-drug regimen demonstrated no significant difference in kidney function for nine patients and equivocal evidence of improvement in the other two patients for creatinine levels and creatinine clearance. Overall, despite the lower cyclosporine dosage used, we have not encountered an increased prevalence of acute heart or lung rejection. We conclude that early implementation of low dosages of cyclosporine, as part of a triple-drug immunosuppression regimen, is associated with preservation of kidney function while maintaining adequate immunosuppression. Patients with chronic azotemia from long-term cyclosporine therapy may still reap some benefit from this regimen.
Creatinine↗
The role of right ventricular endomyocardial biopsy in the long-term management of heart-lung transplant recipients.
Right ventricular endomyocardial biopsy remains the gold standard for the diagnosis of acute rejection of the heart allograft. Surveillance right ventricular endomyocardial biopsies are performed routinely at 3-month intervals in heart-lung transplant patients with uncomplicated conditions who have long-term follow-up. Recent observations of asynchronous heart and lung rejection, plus the impression that acute rejection was a rare phenomenon in long-term heart-lung transplant survivors, led us to analyze our experience with this technique to determine its clinical role. During the first 6 years of the heart-lung transplantation program at Stanford University Medical Center, only one episode of moderate acute rejection has occurred at greater than 4 months after heart-lung transplantation, despite greater than 160 surveillance right ventricular endomyocardial biopsies. This was in a patient who was recovering from a viral illness and had a subtherapeutic cyclosporine level of 38 ng/ml (as measured by radioimmunoassay). Fourteen patients (40%) have never had acute rejection, but freedom from acute rejection did not correlate with freedom from obliterative bronchiolitis or concentric coronary artery intimal hyperplasia. We conclude that in the long-term management phase (greater than 6 months after heart-lung transplantation), right ventricular endomyocardial biopsy should be performed for specific indications, rather than as a surveillance procedure.
Adult↗
Late airflow obstruction in heart-lung transplantation recipients.
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Adrenal Cortex Hormones↗
Long-term results of combined heart-lung transplantation: the Stanford experience.
We assessed the long-term results of our experience with 109 patients with end-stage cardiopulmonary disease who underwent primary combined heart-lung transplantation at Stanford University Medical Center between March 1981 and January 1994. Average recipient age was 31 +/- 10 years (mean +/- standard deviation) median, 31 years; range, 1 month to 52 years. Recipient diagnoses included primary pulmonary hypertension (31%), Eisenmenger's syndrome (39%), complex congenital heart disease (8%), cystic fibrosis (14%), bronchiectasis (2%), and emphysema (3%). Immunosuppression was with cyclosporine and a tapering regimen of corticosteroids. In 1986 azathioprine was added, and since 1987 induction therapy with OKT3 has been employed. Actuarial survival rates at 1, 5, and 10 years were 68% +/- 4.6%, 43% +/- 5.4%, and 23% +/- 8.1%, respectively (mean +/- 1 standard error of the mean). Fourteen deaths occurred in the hospital for an operative mortality rate of 12.8% +/- 3.3%, and 61 deaths occurred overall. Causes of death included hemorrhage (five patients), infection (21), rejection (one), nonspecific pulmonary failure (four), graft coronary artery disease (six), and obliterative bronchiolitis (eight). Infection, rejection, and obliterative bronchiolitis were the major complications. Only 20% +/- 3.9% of patients were free from any infection 3 months after transplantation. Heart and lung rejection commonly occurred asynchronously; actuarial estimates of freedom from isolated lung rejection at 1 and 5 years were 47% +/- 5.2% and 40% +/- 5.6%, respectively. For simultaneous heart and lung rejection these estimates were 87% +/- 3.5% and 86% +/- 3.8%, and for isolated heart rejection 63% +/- 5.1% and 51% +/- 6.4%, respectively. Although graft coronary artery disease developed less frequently than in patients after isolated heart transplantation (90% +/- 4.6% of patients were free of graft coronary artery disease at 5 years), obliterative bronchiolitis remains a major long-term complication and cause of morbidity and mortality. Actuarial estimates of freedom from obliterative bronchiolitis at 1, 5, and 10 years were 71% +/- 5.1%, 51% +/- 6.1%, and 42% +/- 7.8%, respectively. These results show satisfactory early and medium-term outcome after combined heart-lung transplantation but also underscore that much progress is needed in controlling infection, rejection, and obliterative bronchiolitis, all of which remain as major impediments to long-term survival.
Actuarial Analysis↗
The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy.
Obliterative bronchiolitis is the most significant long-term complication of lung and heart-lung transplantation characterized by the rapid development of obstructive airway disease. It is thought to be a manifestation of chronic rejection and has been treated, with limited success, with augmentation of immunosuppression. Early detection of obliterative bronchiolitis and prompt initiation of therapy may result in an improved outcome. The role of transbronchial biopsy has been reported in the diagnosis of acute rejection and infection but not for obliterative bronchiolitis. To study this problem we retrospectively reviewed the transbronchial biopsy results of patients with advanced clinical obliterative bronchiolitis, as defined physiologically. Between January 1, 1988, and December 31, 1991, 46 "sets" of adequate transbronchial biopsy specimens were obtained from 16 patients (15 heart-lung recipients and one double lung recipient). Seven sets of transbronchial biopsy specimens (15.2%) showed obliterative bronchiolitis by pathologic study. In four patients with severe clinical obliterative bronchiolitis, only one transbronchial biopsy specimen of seven (14.3%) showed obliterative bronchiolitis. The pathologic diagnosis of obliterative bronchiolitis was confirmed in three of these patients at the time of autopsy or retransplantation. Twelve patients were still alive at the end of the study period, and all experienced further deterioration of lung function typical for obliterative bronchiolitis. We conclude that the sensitivity of transbronchial biopsy for obliterative bronchiolitis is poor. Possible explanations for these results are explored.
Adolescent↗
The role of transbronchial biopsies in the management of lung transplant recipients.
We examined the utility of the transbronchial biopsy in the management of 53 lung transplant patients. One hundred thirty-three protocol biopsies were performed to ascertain the frequency and nature of abnormalities in clinically stable or asymptomatic patients; 128 diagnostic biopsies were performed in clinically ill patients to assess the morphologic abnormalities before the institution of therapy, and 105 biopsies were performed to assess the response to therapy. Histologic evidence of acute rejection was found in 24% of the protocol biopsies, and infection was found in 17%. Twenty-five patients with grade 1 or grade 2 perivascular infiltrates in protocol biopsies did not receive antirejection therapy. Follow-up biopsy in these patients showed spontaneous resolution of the infiltrates in 19% and increased infiltrates in 6. Only two of these patients became clinically ill, representing "progression" to clinical rejection in only 8% of the nontreated patients. Forty percent of the biopsies performed to rule out acute rejection or infection had histologic features of acute rejection, and another 23% had features of infection. Treatment of patients with clinical and histologic evidence of rejection was associated with rapid resolution of clinical symptoms in nearly 90% of the patients, but follow-up biopsies showed residual infiltrates compatible with ongoing or resolving rejection in 52%. Despite repeat antirejection therapy in some patients, these infiltrates persisted for an average of 30 days after the diagnostic biopsy. Follow-up biopsies also showed asymptomatic infection, usually cytomegalovirus pneumonitis, which often persisted for weeks despite the lack of symptoms. Perivascular infiltrates compatible with acute rejection were also found in 38% of biopsy specimens with evidence of infection. These perivascular infiltrates resolved with antibiotic treatment alone in nearly 50% of the patients with these features. Although perivascular mononuclear cell infiltrates are the cardinal histologic feature of acute rejection, similar infiltrates occur in patients who apparently have infection alone and other patients who have both infection and rejection; infiltrates compatible with minimal, mild, and moderate acute rejection also occur in clinically asymptomatic patients. These histologic findings are a challenge to both the pathologists' and the clinicians' skills in the management of the lung transplant patient.
Biopsy, Needle↗