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Biomedical subjects

V G Valentine

Publications and source records attributed to V G Valentine.

7 recordsLinked to original sources

Total lymphoid irradiation for refractory acute rejection in heart-lung and lung allografts.

Persistent or recurrent acute allograft rejection (AR) refractory to high-dose steroid therapy can adversely affect long-term outcomes of heart-lung (HLT), bilateral-lung (BLT), and single-lung (SLT) transplantations. The use of total lymphoid irradiation (TLI) for the management of refractory acute AR in six transplant recipients (two men, four women; mean age, 29.8 +/- 3.8 years) is detailed. There are two HLT (primary pulmonary hypertension [PPH], cystic fibrosis [CF]), 1 BLT (pulmonary hypertension postventricular septal defect repair), and 3 SLT (sarcoid, PPH, congenital heart disease with atrial septal defect) recipients. Refractory AR is defined as persistent rejection unresponsive to high-dose steroid therapy in all cases. The BLT and SLT recipients had at least two moderate and one mild AR events per patient. The HLT recipients had at least two moderate acute heart and one severe and one mild asynchronous acute lung rejection events per patient. A total of 800 cGy of total lymphoid irradiation (TLI) was administered over a 5-week period. Mild and transient leukopenia was the only observed side effect. The patient with PPH received TLI 313 days after HLT for recurrent AR at another institution and died of ARDS 4 weeks after completing TLI. The patient with CF received TLI 707 days after HLT and died 457 days after TLI of severe obliterative bronchiolitis (OB) with multiorgan failure. The patient with BLT received TLI 176 days after transplant and died 372 days after TLI of respiratory failure related to severe rejection. One patient with SLT received TLI 78 days after transplant and died 679 days after TLI of severe acute AR. The two remaining patients with SLTs have been free from acute AR for more than 4 years. The patient with sarcoidosis received TLI 37 days after SLT following a clinical rejection event and two severe acute AR events. He is alive with normal lung function 5 years later. The patient with PPH received TLI 108 days after SLT following three moderate acute AR events and is alive with stable OB 4 years later. These limited preliminary results suggest that TLI has merit for the treatment of intractable acute AR following HLT and lung transplantation.

Acute Disease↗

Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis is a progressive form of obstructive airway disease that threatens long-term survival in lung transplant recipients. Its incidence and the long-term survival of lung transplant recipients with obliterative bronchiolitis are unknown. METHODS: The results of 89 heart-lung and 13 bilateral sequential lung transplant survivors beyond 90 days of their operation were analyzed. The date of diagnosis for obliterative bronchiolitis was established histologically (presence of submucosal fibrosis) or physiologically by a persistent reduction in the forced vital capacity to less than 0.7 for greater than 6 weeks. There were 43 patients without obliterative bronchiolitis and 59 patients with obliterative bronchiolitis. RESULTS: No differences were found in the mean age and gender ratios between the two groups. The actuarial 1-, 5-, and 10-year percentage freedom from obliterative bronchiolitis was 72 +/- 4.6, 30 +/- 5.6, and 15 +/- 7.4, respectively, with a median onset of 689 days (range 55 to 3404 days). About half the patients with biopsy-proven obliterative bronchiolitis had a fall in their forced expiratory flow at 50% of forced vital capacity/forced vital capacity nearly 4 months before fulfilling the forced expiratory volume in 1 second criteria established by the Working Group on chronic lung dysfunction. The actuarial 1-, 5-, and 10-year percentage survival of obliterative bronchiolitis negative patients was 90 +/- 4.5, 74 +/- 8.4, and 66 +/- 10.6, respectively, versus 90 +/- 3.9, 49 +/- 6.9, and 27 +/- 10.0, respectively, for obliterative bronchiolitis positive patients (p = 0.38). The actuarial 1-, 3-, 5-, 8-, and 10-year percentage survival of lung transplant recipients after the diagnosis of obliterative bronchiolitis was 74 +/- 5.8, 50 +/- 7.5, 43 +/- 7.8, 23 +/- 8.7, and 11 +/- 9.1, respectively, with a median survival of 1084 days (range 0 to 3442 days). CONCLUSIONS: The forced expiratory flow at 50% of forced vital capacity/forced vital capacity is a more sensitive indicator for the early detection of obliterative bronchiolitis than the forced expiratory volume in 1 second after heart-lung or bilateral sequential lung transplantation. The obliterative bronchiolitis negative group survival tends to be better than the obliterative bronchiolitis positive group. The obliterative bronchiolitis positive lung transplant recipients have reasonable outcomes with a median survival time of nearly 3 years after the diagnosis of obliterative bronchiolitis. Earlier detection of obliterative bronchiolitis and refinements in management may further improve these results.

Actuarial Analysis↗

Pediatric heart-lung transplantation: intermediate-term results.

BACKGROUND: Adult heart-lung transplantation was initiated at Stanford in 1981 and the first pediatric heart-lung transplantation was done in 1986. Intermediate-term results of pediatric heart-lung transplantation at Stanford University are presented. METHODS: A retrospective review of the records of all pediatric heart-lung transplantations done since 1986 was conducted. RESULTS: Nineteen heart-lung transplantations were done in 17 patients. Ages ranged from 2 months to 18 years with a median age of 10 years. At the time of transplantation 5 patients were infants, 7 children, and 7 adolescents. The mean follow-up was 29 +/- 6.2 months (range 1 to 77, median 16) and follow-up was 100% complete. Diagnoses were congenital heart disease in 13, primary pulmonary hypertension in 2, and cystic fibrosis, cystic lymphangiectasia, viral pneumonia, and obliterative bronchiolitis in 1 each. Median wait on the heart-lung transplantation list was 91 days (range 2 to 707). All patients had New York Heart Association class III to IV symptoms, two were receiving ventilator support, and six were receiving oxygen. Fifteen of 19 transplant recipients were discharged from the hospital. The 30-day operative mortality rate was 5.2% (1 of 19). The actuarial survival at 1, 3, and 5 years for all patients was 67%, 51%, and 41%, respectively, and for hospital survivors was 82%, 62%, and 51%. The cause of death was obliterative bronchiolitis in 4, multisystem organ failure in 3, and graft coronary artery disease and chronic airway disease in 1 each. Three patients required retransplantation, 2 because of obliterative bronchiolitis and 1 because of viral pneumonia. Two patients underwent repeat heart-lung transplantation and 1 patient underwent single lung transplantation. Rejection was diagnosed in 73% of recipients, and obliterative bronchiolitis has developed in 32% of recipients. CONCLUSIONS: Survival in pediatric heart-lung transplantation approximates that in the adult procedure at 1, 3, and 5 years. Long-term survival has been achieved but the primary factors limiting further improved survival remain infection and obliterative bronchiolitis.

Adolescent↗

Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients.

BACKGROUND: Cytomegalovirus infection threatens pulmonary allograft survival and function. This retrospective study details the experience of ganciclovir prophylaxis against cytomegalovirus infection and its sequelae. METHODS: Eight-nine lung and heart-lung transplant recipients with positive cytomegalovirus serology were analyzed. The 37 recipients who underwent transplantation before September 1989 received no prophylaxis. The 52 subsequent recipients received ganciclovir prophylaxis. RESULTS: Thirty-six non-prophylaxed versus 42 prophylaxed patients had cytomegalovirus events with cumulative incidences of 100% and 86% (p < < 0.01), and median onsets of 37 +/- 21 versus 85 +/- 35 days, respectively (p < < 0.01); 22 non-prophylaxed versus 27 prophylaxed patients had cytomegalovirus pneumonitis with cumulative incidences of 60% and 55% (p < < 0.01), and median onsets of 34 +/- 14 and 84 +/- 26 days, respectively (p < < 0.01). Respiratory failure caused by cytomegalovirus pneumonitis developed in nine of the non-prophylaxed versus two of the prophylaxed patients (p < < 0.01). The significant estimated survival benefit in patients who received prophylaxis (p = 0.04) was not apparent when reanalysis was performed after exclusion of patients with respiratory failure (p = 0.36). Ganciclovir prophylaxis produced a significant delay in the development of obliterative bronchiolitis with a median time to onset of 1072 +/- 280 days versus 432 +/- 189 days for the non-prophylaxis cohort (p < < 0.01). CONCLUSIONS: Ganciclovir prophylaxis (1) improves recipient survival by reducing the severity of disease and essentially eliminating respiratory failure caused by cytomegalovirus pneumonitis, (2) reduces the incidence and delays the onset of cytomegalovirus events and pneumonitis, and (3) delays the onset of obliterative bronchiolitis.

Adolescent↗

Risk factors for the development of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. METHODS: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome. RESULTS: Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation. CONCLUSIONS: Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

Adolescent↗