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Biomedical subjects

E C Lawrence

Publications and source records attributed to E C Lawrence.

At least 37 records · Page 2Linked to original sources
PubMed1991

Dynamics of soluble interleukin-2 receptor levels immediately after heart transplantation. Attenuation of increase by OKT3 therapy.

Quantification of T cell activation after cardiac transplant by measuring serum soluble interleukin 2 receptor levels daily may give insight into immunologic dynamics after cardiac allograft implantation. It was our hypothesis that this protein would demonstrate a characteristic rise after heart transplant not related to severe rejection that was distinct from a control group, and that this increase could be attenuated with OKT3 therapy. We measured soluble interleukin 2 receptor levels daily for two weeks in 26 patients undergoing orthotopic cardiac transplantation (19 receiving triple therapy immunosuppression with cyclosporine, azathioprine, and prednisone, and 7 with OKT3 added days 1 through 5). Interleukin-2 receptor levels for transplant patients were compared with 15 control subjects (14 undergoing bypass surgery and one valve replacement). Mean soluble interleukin-2 receptor level for the entire two-week period was higher for transplants versus controls; 839 +/- 31 U/ml vs. 504 +/- 20 U/ml (mean +/- SEM; P less than .05). Patients receiving OKT3 had a lower level (670 +/- 39 U/ml) than those not (902 +/- 36 U/ml, P less than .05) despite the fact that mean biopsy scores for the observation period were not significantly different. No significant rejection or infection episodes occurred in any patient. These results describe, for the first time, sequential changes in soluble interleukin 2 receptor levels early after heart transplant and demonstrate that the characteristic early rise can be attenuated with short-term OKT3 administration.

Adolescent↗
PubMed1990

Lymphocyte subset populations in bronchiolitis obliterans after heart-lung transplantation.

The long-term success of heart-lung transplantation is limited by the development of bronchiolitis obliterans, possibly as a form of chronic lung allograft rejection. In the present study, we have characterized by immunohistochemical staining the lymphocytes infiltrating the lesions of bronchiolitis obliterans in one patient following heart-lung transplantation. The finding that the preponderant cells expressed the CD8 (putative cytotoxic/suppressor) marker lends support to the notion that chronic rejection is at least one mechanism for the development of bronchiolotis obliterans following heart-lung transplantation.

Adult↗
PubMed1990

Pulmonary function after heart-lung transplantation using larger donor organs.

Restrictive pulmonary function after heart-lung transplantation (HLT) has been attributed to the use of smaller donor lungs and/or an inability to generate normal negative pleural pressures. Pleural pressure generation depends on both the size of the recipient thoracic cage and its neuromuscular integrity. To determine whether lung volumes after heart-lung transplantation are more dependent on donor lung size or on recipient chest wall characteristics, seven HLT recipients were evaluated before and after transplantation. Postoperative values initially (average, 2 months), 6, and 12 months after transplantation were compared with predicted lung volumes for the recipient and donor organs. TLC dropped from a mean of 5.2 +/- 0.5 L preoperatively to 3.7 +/- 0.3 L (p less than 0.05) 2 months after HLT, but it improved with time and ultimately was not different from preoperative values. The predicted TLC of the HLT donor organs were significantly larger than those of the recipient's predicted TLC, with a mean of 6.9 +/- 0.4 versus 5.3 +/- 0.3 L (p less than 0.05). DLCO, arterial PO2, and PCO2 did not change after surgery. Within limits, larger donor lungs appear to adapt to the constraints of the recipient chest and may be used with clinical success, without apparent adverse effects.

Adolescent↗
PubMed1990

Diagnosis and management of lung allograft rejection.

Improvements in our understanding of the mechanisms underlying the rejection coupled with the development of novel approaches to dealing with the rejection process have allowed successful lung and heart-lung transplantation. Nonetheless, successful lung transplantation is still limited by acute rejection. This article defines the rejection process and outlines current approaches to preventing and treating this major clinical problem.

Graft Rejection↗
PubMed1989

Bronchoalveolar lavage analysis, gallium-67 lung scanning and soluble interleukin-2 receptor levels in asbestos exposure.

This study examined different markers of lung immunologic and inflammatory responses to previous asbestos exposure. We performed bronchoalveolar lavage (BAL) and gallium-67 (67Ga) lung scans and measured serum and BAL soluble interleukin-2 receptor (IL-2R) and angiotensin-converting enzyme (SACE) levels in 32 subjects with a history of significant asbestos exposure, 14 without (EXP) and 18 with (ASB) radiographic evidence of asbestosis. BAL analysis revealed increases in neutrophils in both ASB and EXP when compared to controls (P less than 0.01), which persisted after adjustment for smoking category. Although significant abnormalities of macrophage and total lymphocyte profiles were not found in the study population, lymphocyte subpopulation analysis revealed elevation of BAL T4/T8 ratios in the entire study group (ASB + EXP) when compared to controls (P less than 0.05), independent of smoking category. 67Ga lung scan activity was increased in 56% of ASB and in 36% of EXP: no correlations between positive scans and different radiological and functional parameters could be found. There was no significant elevation of mean SACE, serum, or BAL IL-2R levels in any of the study categories. These data suggest that asbestos exposure may be associated with parenchymal inflammation, even in the absence of clinical criteria for asbestosis. Abnormalities of gallium uptake and of BAL analysis reflect the clinically inapparent inflammation. The increased BAL T4/T8 ratios observed suggest that abnormal local pulmonary immunoregulation may play a role in the pathogenesis of asbestos-related lung diseases.

Adult↗
PubMed1989

Dynamic changes in soluble interleukin-2 receptor levels after lung or heart-lung transplantation.

Activation of T-lymphocytes is accompanied by the release of interleukin-2 receptors (IL-2R) in a soluble form that can be measured as an index of the activation process. We performed a prospective, blinded study of the dynamic changes in soluble IL-2R levels in serum in 12 patients undergoing lung or heart-lung transplantation. The levels of soluble IL-2R were markedly elevated during episodes of rejection (geometric mean value X divided by SEM = 3,770 X divided by 1.06 versus 411 X divided by 1.08 U/ml for normal controls, p less than 0.0001). Levels of soluble IL-2R were 2,105 X divided by 1.16 U/ml with rejection episodes in single lung recipients versus 5,560 X divided by 1.30 in recipients of two lungs (p = 0.005). Soluble IL-2R levels were 1,468 X divided by 1.05 during episodes of nonbacterial infections, 1,879 X divided by 1.34 with bacterial infections, and 5,056 X divided by 1.08 with sepsis (p less than 0.001 for each category compared to normals). Levels of soluble IL-2R exceeded 6,750 U/ml only with rejection episodes and were greater than 4,100 U/ml either with rejection, clinical sepsis, or overwhelming bacterial infection. We conclude that marked elevations of soluble IL-2R are associated with rejection, intermediate elevations with either rejection or infection, and that low levels of soluble IL-2R exclude rejection.

Adult↗
PubMed1989

Factors contributing to mortality in lung transplant recipients: an autopsy study.

Despite improved surgical techniques and advances in immunosuppressive therapy, posttransplant mortality rates remain significantly high in lung transplant patients. Since 1985, 3 of 6 single lung recipients, 3 of 3 double lung recipients, and 4 of 7 heart-lung recipients have died and undergone autopsy. We reviewed the autopsy findings in these patients to determine the type and frequency of pathologic processes associated with mortality. One or more infectious processes was found in every patient at autopsy. Gram-negative bacterial pneumonia and sepsis, found in 7 and 8 of 10 autopsy cases, respectively, were by far the most frequent contributing factors to mortality. Epstein-Barr virus infection was demonstrated in one patient using polymerase chain reaction amplification. Acute transplant rejection was found in only 2 patients and therefore is a much less common factor in the death of lung transplant recipients. Diffuse alveolar damage occurred in 6 patients and bronchiolitis obliterans occurred in 3 patients. These latter two processes may have different etiologies in different patients.

Adolescent↗
PubMed1988

Amiodarone pulmonary toxicity: prospective evaluation of serial pulmonary function tests.

Pulmonary toxicity developed in 15 (17%) of 89 patients treated with amiodarone during a follow-up period of 2 weeks to 54 (mean 20 +/- 15) months. Prospective evaluation of serial pulmonary function tests in 67 patients demonstrated both a significant decrease from baseline in three of six variables in patients with toxicity at the time of diagnosis and a significant difference compared with the same variables in patients without toxicity. The most significant of these was the diffusing capacity for carbon monoxide (DLCO). An individual decrease in DLCO greater than or equal to 15% gave an optimal sensitivity of 100% and a specificity of 89% for the diagnosis of pulmonary toxicity. However, a decrease in DLCO greater than or equal to 15% did not alone warrant a change in therapy in asymptomatic patients. Although higher maintenance doses of amiodarone appeared to be related to the development of this complication, an abnormal baseline DLCO (less than 60% of predicted) with or without an initial abnormal chest roentgenogram did not predispose to pulmonary toxicity.

Aged↗
PubMed1988

Elevated concentrations of soluble interleukin-2 receptors in serum samples and bronchoalveolar lavage fluids in active sarcoidosis.

Sarcoidosis is a granulomatous disorder of unknown cause characterized by activation of T-lymphocytes. We here report the use of an enzyme-linked immunosorbent assay for the soluble interleukin-2 receptor (IL-2R) as a measure of T-cell activation in serum samples and bronchoalveolar lavage fluids in 15 patients with active sarcoidosis. The geometric mean (x divided by SEM) value for soluble IL-2R in serum samples from patients with sarcoidosis was 1,110 (x divided by 1.17) versus 224 (x divided by 1.08) U/ml for normal control subjects (p less than 0.001). Detectable levels of soluble IL-2R were present in bronchoalveolar lavage fluids from 10 of 15 patients with sarcoidosis versus only 2 of 36 normal control subjects (p less than 0.001). Levels of soluble IL-2R in serum samples from untreated patients with sarcoidosis correlated with 67gallium lung scanning scores (p less than 0.05) but not with serum angiotensin-converting enzyme concentrations or constituents of bronchoalveolar lavage. In 5 patients, the level of soluble IL-2R in serum samples fell from 1,499 (x divided by 1.20) to 476 (x divided by 1.58) U/ml (p less than 0.05) after 6 wk of successful treatment with corticosteroids, whereas the changes in soluble IL-2R in bronchoalveolar lavage fluids were more variable. These observations suggest that measurements of soluble IL-2R, particularly in serum samples, may reflect disease activity and be clinically useful in the management of patients with sarcoidosis.

Adrenal Cortex Hormones↗
PubMed1988

Xanthomatous bronchiolitis obliterans with cholesterol pneumonia.

Reported is an instance of bronchiolitis obliterans due to the accumulation of lipid-laden cells within bronchiolar walls and lumina. The bronchiolar lining had extensive squamous and goblet cell metaplasia with focal ulceration. Scattered foci of cholesterol pneumonia, composed of acicular crystals with an associated foamy lipid material and type II alveolar epithelial cell hyperplasia, were present. The patient had no history related to this unusual pulmonary disease, although preoperatively her serum cholesterol level was mildly elevated. She was treated with pulmonary and cardiac allotransplantation.

Adolescent↗
PubMed1987

Elevated serum levels of soluble interleukin-2 receptors in active pulmonary sarcoidosis: relative specificity and association with hypercalcemia.

We have previously reported serum elevations of the soluble form of the interleukin-2 receptor (IL-2R), a marker of T-cell activation, in sarcoidosis. In the present study, an enzyme-linked immunosorbent assay for soluble IL-2R was employed to compare sera from normal controls with those from patients with active sarcoidosis or idiopathic pulmonary fibrosis (IPF). Sera from patients with active sarcoidosis and parenchymal lung disease (radiographic Stages II or III) had geometric mean values for soluble IL-2R of 1975 units/ml compared to 640 units/ml for normal controls (p less than 0.001, Student's t-test). By contrast, soluble IL-2R levels were lower (989 units/ml, p less than 0.05 compared to normals) in patients with active sarcoidosis but no radiographic evidence for parenchymal disease (Stages 0 or I). Soluble IL-2R levels were not elevated in patients with inactive sarcoidosis. Three of the 4 sarcoidosis patients with the highest levels of soluble IL-2R also manifested hypercalcemia. While levels of soluble IL-2R were elevated for the group of patients with IPF (1171 units/ml, p less than 0.05 compared to normals), the striking elevations of soluble IL-2R noted in active sarcoidosis were not seen and there was greater overlap with normal values. We conclude that marked serum elevations of soluble IL-2R are more suggestive of active pulmonary sarcoidosis than IPF.

Adrenal Cortex Hormones↗
PubMed1987

Phagocytosis and killing of Haemophilus influenzae by alveolar macrophages: no difference between smokers and non-smokers.

The susceptibility of smokers to pneumonia caused by Haemophilus influenzae may result from impairment of phagocytic or bactericidal function of pulmonary alveolar macrophages (PAM). We compared ingestion and killing of non-typable H. influenzae and H. influenzae type B by alveolar macrophages from asymptomatic smokers and non-smokers. Three times as many cells were recovered from bronchoalveolar lavage of smokers. Non-typable H. influenzae (NTHI) were phagocytosed and killed readily by PAM from both groups of subjects, while H. influenzae type B were resistant to phagocytosis. No difference in uptake of bacteria was detected between PAM of smokers and non-smokers. PAM from smokers had a slightly greater bactericidal activity than PAM from non-smokers. These results suggest that other host factors, such as impaired tracheobronchial clearance or the presence of conditions that favor bacterial growth rather than damage to alveolar macrophages, are responsible for the susceptibility of smokers to Haemophilus infections.

Adult↗