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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 145 records · Page 8Linked to original sources
PubMed1994

Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts?

Acute cellular rejection (ACR) in the early posttransplant period is recognized as one predictor of the development of bronchiolitis obliterans in lung transplant recipients. Using an immunohistochemical panel of antibodies to CD3, L26, HLA-DR, collagenase IV, proliferating cell nuclear antigen (PCNA), KPI, and S100 antigens we analyzed cases of moderate ACR that did respond (n = 11) and that did not respond (n = 10) to bolus solumedrol therapy early in the postoperative period (< 100 days) to determine if we could identify predictors of histological response. Responders who had follow-up negative biopsies after therapy had biopsy specimens containing an average of 41.1% T cells (range, 15.1 to 69.8), 8.8% B cells (range, 0.6 to 20), 18.1% HLA-DR-positive cells (range, 3 to 29.6), 12.2% PCNA-positive cells (range, 2.7 to 22.6), 8.9% collagenase IV-positive cells (range, 0.7 to 20.9), and rare dendritic cells. Nonresponders who had follow-up biopsies that failed to show a significant change in rejection grade had biopsy specimens with the following average cell profiles: 35.8% T cells (range, 7 to 70.7), 21.6% B cells (range, 3.7 to 39.5), 14.2% HLA-DR-positive cells (range, 1.8 to 24.7), 11.4% PCNA-positive cells (range, 0.8 to 22), 12.6% collagenase IV-positive cells (range, 0.6 to 34.1), and occasional dendritic cells. Statistical analysis suggested that large numbers of B lymphocytes in early acute rejection predicts non-responsiveness to interventional immunosuppressive therapy and may indicate a significant role of humoral rejection in the behavior of early allograft rejection.

Antibodies, Monoclonal↗
PubMed1994

Mixed allogeneic chimerism in lung allograft recipients.

Microchimerism in lung allograft recipients was studied in the autopsies of nine female recipients of male lung grafts who had survived for more than 1 month after transplantation. Using a Y chromosome-specific probe tissues were studied for the presence of donor cells that had migrated beyond the graft itself. They were quantitated by cell counting to give absolute numbers of cells per organ volume. While donor cells were disseminated throughout the body, their numbers were small. These absolute numbers should be studied in a larger group of recipients to determine if they correlate with prognosis and the development of bronchiolitis obliterans.

Adult↗
PubMed1994

Psychosocial predictors of vulnerability to distress in the year following heart transplantation.

This study examines psychological symptomatology in a cohort of 72 heart transplant recipients followed longitudinally during their first year post-transplant. In keeping with research on other domains of life stressors and illnesses, a central study goal was to identify pre-transplant and perioperative psychosocial factors associated with increased vulnerability to, and maintenance of, elevated psychological distress levels post-transplant. Average anxiety and depression levels, but not anger-hostility symptoms, were substantially elevated in the early post-transplant period, relative to normative data. Average symptom levels improved significantly over time, although one-third of the sample continued to have high distress levels at all follow-up assessments. Recipients with any of seven psychosocial characteristics at initial interview were particularly susceptible to continued high average distress levels over time: a personal history of psychiatric disorder prior to transplant; younger age; lower social support from their primary family caregiver; exposure to recent major life events involving loss; poor self-esteem; a poor sense of mastery; and use of avoidance coping strategies to manage health problems. Recipients without such factors showed improvement in average distress levels across the assessment period. These effects were stronger for anxiety than depressive symptoms, with the exception of a sizeable relationship between loss events and subsequent depression. The findings suggest that clinical interventions designed to minimize prolonged emotional distress post-transplant need to be closely tailored to heart recipients' initial psychosocial assets and liabilities.

Adaptation, Psychological↗
PubMed1994

Optimization of quantitative culture assay for human immunodeficiency virus from plasma. Plasma Viremia Group Laboratories of the AIDS Clinical Trials Group (National Institute of Allergy and Infectious Diseases).

Experimental conditions essential to a simple, reproducible, quantitative human immunodeficiency virus plasma assay were determined. Five parameters were evaluated: length of culture, reproducibility, assay dilution schema, washing procedures, and anticoagulant usage. The recommended quantitative plasma assay utilizes undiluted citrated plasma cultured with peripheral blood mononuclear cells for 14 days with fivefold dilutions and a medium change on day 1 with no washing.

Blood↗
PubMed1994

A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.

In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents.

Acyclovir↗
PubMed1994

A new complication related to laser bronchoscopy in a single lung transplant recipient.

We report a nearly complete obstruction of the left mainstem bronchus by a fibrinomyxoid plaque about 12 h after laser resection of scar/granulation tissue at a left bronchial anastomosis 27 days after a left single lung transplant. The formation of this plaque was associated with respiratory failure. The plaque was removed by grasping the plaque with biopsy forceps inserted through a fiberoptic bronchoscopy that was placed into the left mainstem bronchus via an endotracheal tube while the patient was receiving manual ventilation under general anesthesia. The respiratory failure resolved with removal of the plaque. To our knowledge, this is a complication that has not been reported previously.

Adult↗
PubMed1994

Lung transplantation at the University of Pittsburgh: 1982 to 1994.

Lung transplantation is a growing modality of treatment for patients with end-stage lung disease. In our program, survival has improved significantly in recent experience. Progress in candidate and donor selection, allograft preservation technique, recipient surgery, and postoperative management combine to reduce recipient morbidity and mortality. Although the tailored antibiotic treatment has significantly reduced the risk of bacterial pneumonia within 2 weeks after operation, infection is still a major cause of death for long-term recipients. Extensive studies need to be continued to understand the pathogenesis of OB and to establish the treatment for OB.

Adolescent↗
PubMed1994

Neurologic infections of the fetus and newborn.

This article concentrates primarily on infections of viral origin, although numerous microorganisms can infect the fetal and newborn brain (see Tables 1 and 2). Intrauterine infections occur most often for HIV, CMV and rubella, whereas HSV is preferentially transmitted intrapartum. In the last decade, changes in the epidemiology of some of the neonatal infections have occurred largely because of the AIDS epidemic. Indeed, pediatric HIV is now the second most frequent viral infection of the newborn (see Table 1) and congenital syphilis has reemerged. Surprisingly, the AIDS epidemic appears to have had minimum impact on infections with other organisms such as Toxoplasma and CMV that commonly infect the brain of adults with AIDS. The recent availability of improved viral diagnostic methods and anti-viral drugs has aided in the identification and treatment of infected newborns.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Anastomotic pitfalls in lung transplantation.

Although airway, arterial, and venous connections required for lung transplantation appear simple, in practice we have encountered morbid early stenosis and obstructions, which are now avoided by technical modifications gradually made since 1985 in 134 cases (60 single lung and 74 double lung). Our initial eight double lung transplant procedures were done with tracheal anastomoses and omental wraps, but ischemic disruption, with a 75% (6 of 8) rate of complications, resulted in the subsequent use of bi-bronchial connections. A total of 192 bronchial anastomoses were reviewed (60 single lung, 66 double lung). Although all anastomoses were constructed between the donor trimmed to one to two rings above the upper lobe origin and the host divided at its emergence from the mediastinum, the suture technique has evolved. Nine (32%) of 28 cases with early bronchial anastomoses with end-to-end suture and intercostal muscle wrap had ischemic or stenotic complications, but the telescoping technique without wrap in 164 bronchial anastomoses reduced the problem to 12% (19 of 164). Twelve anastomoses required temporary intraluminal stenting. Vascular anastomotic obstructions occurred in five arterial (excessive length 2, short allograft artery 1, restrictive suture or clot 2) and two venous (excessive length 1, restrictive suture or clot 1) connections. Suspicion of arterial obstruction was prompted by persisting pulmonary hypertension and reduced flow to the allograft measured by postoperative nuclear scan and hypoxia. Venous obstructions were suggested by persisting radiographic and clinical pulmonary edema. Modifications of earlier techniques have improved our early success in lung transplantation and might be considered by others entering this demanding field.

Anastomosis, Surgical↗
PubMed1993

Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience.

The influence of preoperative transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) on early post-transplant mortality was evaluated in 425 orthotopic transplant recipients. The overall 30-day post-transplant mortality rate was 12.5%; the majority of the deaths (52.8%) were due to primary allograft failure. The 0- to 2-day mortality rate was threefold higher in patients with severe preoperative pulmonary hypertension (TPG > or = 15 mm Hg or PVR > or = 5 Wood units), whereas the 3- to 7-day and 8- to 30-day mortality rates were similar. Early post-transplant mortality (0 to 2 days and 8 to 30 days) was also significantly higher (15.9% vs 3.9% and 9.9% vs 2.8%, respectively; p < 0.05) in women compared with men. Women with severe preoperative pulmonary hypertension had higher (p < 0.05) 0- to 2-day post-transplant mortality than comparable men. According to univariate analysis, recipients with preoperative TPG > or = 15 mm Hg had a significantly higher 30-day postoperative mortality rate, irrespective of their level of PVR. Furthermore, patients with severe preoperative pulmonary hypertension who underwent transplantation between 1980 and 1987 had a higher 0- to 2-day post-transplant mortality rate compared with patients operated on after that time. Multiple logistic regression analysis identified female recipient sex and preoperative TPG but not preoperative PVR, era of transplantation, or recipient age as significant (p < 0.001 and p < 0.01, respectively) independent predictors of early post-transplant mortality.

Adolescent↗
PubMed1993

Benefits of posttransplantation monitoring of interleukin 6 in lung transplantation.

To determine the predictive diagnostic value of interleukin 6 (IL-6) monitoring in lung and heart-lung transplants, we measured posttransplantation serum IL-6 levels in 17 adult lung or heart-lung transplant recipients. Posttransplantation IL-6 elevation patterns were classified into 4 groups: serum IL-6 level remained negative throughout the monitoring period (group 1; n = 1; 6%); several sharp spikes with normal baseline (group 2; n = 9; 53%); persistently high level of serum IL-6 (group 3; n = 3; 18%); and several sharp spikes of serum IL-6 elevation with abnormally high baseline (group 4; n = 4; 24%). One patient without an elevation of IL-6 (group 1) did not experience any episodes of rejection or infection. Nine patients in group 2 had 19 IL-6 spikes, 13 of which were associated with histopathologically or clinically diagnosed rejection, 3 with acute bronchitis, and 1 with diffuse alveolar damage. Three patients in group 3 had persistent infections including cytomegalovirus infection, toxic megacolon, and repeated bacterial infection during the monitoring period, and 4 in group 4 died within 3 months after transplantation. From this study it appears that a spiked elevation of IL-6 could have a predictive value in diagnosing rejection, and persistently high levels of IL-6 indicate the presence of infection. Thus, IL-6 monitoring is beneficial for lung transplant recipients.

Adult↗
PubMed1993

A decade of lung transplantation.

OBJECTIVE: The experience accrued at the University of Pittsburgh between March 1982 and December 1992 in the various forms of lung transplantation, including heart-lung, double lung, and single lung, is discussed. SUMMARY BACKGROUND DATA: Heart-lung (n = 97) was the most commonly performed operation followed by double lung (n = 80) and single lung (n = 68). Major indications included primary pulmonary hypertension (n = 76), obstructive lung disease (n = 57), Eisenmenger's syndrome (n = 42), cystic fibrosis (n = 32), and retransplantation (n = 13). Since May 1991, 115 procedures have been performed and heart-lung transplantation has decreased from 61% to 15% of the cases with a corresponding doubling in double lung from 24% to 43% and single lung from 15% to 42%. RESULTS: The 1-, 2-, and 5-year survival rates in all 232 recipients were 61%, 55%, and 44%, respectively. The actuarial survival rate was significantly better for those 107 recent recipients compared to the 125 early recipients (70% vs. 61%). Overall, the 63 single (70%) and 74 double (65%) lung procedures were more successful than heart-lung transplantation (53%). Recently, however, lung transplantation has been associated with an improvement in the survival rate from 48% to 72%. The survival rate has also improved from 53% to 77% for single lung transplant recipients. The causes of death in 106 recipients included infection (n = 40), early allograft dysfunction (n = 23), obliterative bronchiolitis (n = 13), and inoperative bleeding (n = 10). Poor outcomes also included technical problems (n = 6), lymphoma (n = 4), acute rejection (n = 3), diaphragmatic paralysis (n = 2), multisystem organ failure (n = 2), stroke (n = 2), liver failure (n = 1), and airway dehiscence (n = 1). CONCLUSIONS: The long-term outlook for lung transplant recipients has improved. There appears to be significant conservation of organs with single lung and double lung transplantation, finding greater acceptance for diseases once exclusively treated by heart-lung transplantation alone. The improved long-term outlook will be dependent upon better treatment for chronic rejection of the airways that histologically is defined by obliterative bronchiolitis.

Adolescent↗
PubMed1993

Evaluation of bioprosthetic valve-associated thrombus in ventricular assist device patients.

BACKGROUND: Thromboembolic events may be related to thrombotic deposition on prosthetic valves. In a left ventricular assist device (LVAD) that contains two porcine pericardial bioprosthetic valves in addition to significant associated biomaterial placement, this may be particularly true. Thrombotic deposits on valves removed from LVADs at autopsy or heart transplantation were scored to determine (1) the nature and location of valvular deposition, (2) whether deposition was related to thromboembolic events, (3) correlations between deposition and patient hemodynamic and coagulation parameters, and (4) implant time dependency. METHODS AND RESULTS: Novacor LVADs were implanted in 23 patients as a bridge to transplantation for 1 to 303 days. Photographs of the concave (downstream) and convex (upstream) side of the inflow and outflow valve were made at explant and later scored for (1) total thrombus area (10 = equivalent of cusp area), (2) percent of cusp area occupied by solid thrombus, (3) thrombus color (10 = dark red, 0 = white), and (4) average percent of valve strut height involved with thrombus (from a side view). The inflow valve was shown to have heavier and redder deposition than the outflow valve. This was also true for the concave versus the convex side. Heaviest deposition was seen on the inflow valve concave side, which rests within the LVAD pumping sac and may be subject to poor convection. Patients with neurological thromboembolic events (8/23) during implantation had heavier deposition on the inflow valve concave side (5.7 +/- 2.7 versus 4.6 +/- 2.2, P < .05). Pump volumetric output was also found to negatively correlate with thrombus area on this valve and side (r = -.61, P = .002). Platelet release (platelet factor 4) was correlated with thrombus involvement on the upstream (convex) side of the inflow valve (r = .82, P = .002). No significant dependence of deposition on the implant time was found. CONCLUSIONS: Valve thrombus deposition was related to thromboembolic events. Pump volumetric output and platelet release were found to be related to deposition. These results may have implications for the role of hemodynamics and platelet activation in thromboembolism associated with prosthetic valve placement in general.

Bioprosthesis↗
PubMed1993

Recurrence of sarcoidosis in pulmonary allograft recipients.

Lung transplantation is a potentially curative therapy for the end-stage pulmonary sequelae of sarcoidosis. We reviewed the course of five lung allograft recipients with underlying sarcoidosis (S) at the University of Pittsburgh Medical Center and compared them with a control group (C) of 44 contemporaneous transplant recipients with other respiratory diseases. Sarcoid granulomata have developed in the allografts of 4 S, although these lesions have not yet been demonstrated to result in clinically significant abnormalities. In comparison with C, sarcoidosis patients had significantly greater mean grades of acute rejection during the first 3 months after transplantation (2.1 +/- 0.3 versus 1.6 +/- 0.1, S and C, respectively, p < 0.042) and larger proportions of lung biopsies showing more than mild acute rejection (40 versus 18%, p < 0.012) and lymphocytic bronchitis (30 versus 13%, p = 0.02), as well as a greater percentage of polymorphonuclear leukocytes in BAL returns (34.9 +/- 5.4 versus 19.0 +/- 1.6, p < 0.01). The two groups did not differ, however, in frequency of obliterative bronchiolitis, survival, or pulmonary function. We conclude that lung transplant recipients with underlying sarcoidosis are very likely to develop recurrent disease in the allograft and have more severe acute rejection responses, especially in the first weeks after transplantation. Pulmonary transplantation appears to be an efficacious therapy for end-stage sarcoidosis, but the long-term sequelae of the increased acute rejection and recurrent sarcoidosis in the allograft remain to be determined.

Adult↗