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Biomedical subjects

I L Paradis

Publications and source records attributed to I L Paradis.

At least 55 records · Page 3Linked to original sources
PubMed1989

The clinical spectrum, pathology, and clonal analysis of Epstein-Barr virus-associated lymphoproliferative disorders in heart-lung transplant recipients.

This study presents the clinical and laboratory observations on posttransplant lymphoproliferative disorders (PTLDs) occurring in 5 of 53 heart-lung transplantation recipients. Cervical lymph nodes, tonsils, lungs, and gastrointestinal tract were the common sites of involvement by PTLDs. The histopathologic findings showed a spectrum of lymphoid and immunoblastic proliferation ranging from diffuse hyperplasia to malignant lymphoma, immunoblastic or large cell type. All cases were associated with a primary Epstein-Barr virus infection, and viral DNA was demonstrated within the lesional tissue in three cases. Immunohistochemical and immunoglobulin gene rearrangement studies revealed a B-cell proliferation that was monoclonal in three cases and polyclonal in two cases. Compared with PTLDs arising in other organ transplant recipients, this series is remarkable for a high incidence of PTLDs (9.4%), a short interval to tumor diagnosis (2.2 months, mean), involvement of the primary allograft in three cases (60%), and the frequent development of bronchiolitis obliterans. Possible reasons for this distinct clinicopathologic profile are discussed.

Adolescent↗
PubMed1989

Proteins of the respiratory tract after heart-lung transplantation.

Heart-lung transplant recipients represent a unique population who experience episodic lung injury caused by infection or rejection. We hypothesized that the proteins in the respiratory lining fluids of these patients might reflect and provide insights into the in vivo immunologic and inflammatory events that occur in the transplanted lung. Structural, inflammatory, and immune proteins were quantitated in 57 samples of BAL fluid recovered from 17 heart-lung recipients when infections, rejection, or neither was present. Protein levels were compared with those of normal subjects and between the clinical transplant groups. When neither infection nor rejection was present, levels of albumin, fibronectin, and immunoglobulins G, M, and A were all higher in the transplanted lungs as compared with the normal lungs. These findings suggest that a new steady state of these proteins is established in the transplanted lungs. When infection or rejection was present, there was a further significant increase in albumin, fibronectin, IgG, and especially C5a in the transplanted lungs. These findings suggest that at least some elements of host defense remain intact in the posttransplantation period despite the use of immunosuppressive drugs and a HLA-incompatible microenvironment. The profiles of recovered alveolar proteins did not, however, help to differentiate infection from rejection. This is disappointing because distinguishing between infection and rejection without examination of lung tissue remains an unresolved and important clinical problem. Nevertheless these data provide new insights into organ tolerance and defense of the newly transplanted lung from infection or rejection.

Adolescent↗
PubMed1989

Ventilation and breathing pattern during progressive hypercapnia and hypoxia after human heart-lung transplantation.

The effects of human pulmonary denervation on the ventilatory responses to progressive hyperoxic hypercapnia and isocapnic hypoxia as well as the effect on resting breathing pattern were evaluated in nine female heart-lung transplant (H-LT) recipients. The results were compared to those obtained from 10 normal women of comparable age and stature. Testing was performed 2 to 37 months after H-LT (median, 7.5 months). Cardiac function was normal in all H-LT recipients. None of the patients had spirometric evidence of airway obstruction, while six had a restrictive pattern with forced vital capacities less than 80% of predicted values. Resting minute ventilation (VE), tidal volume (VT), and ventilatory drive (VT/TI) in the H-LT recipients were not significantly different from those of the normal subjects. Inspiratory time (TI), however, was significantly shorter in the H-LT patients (1.64 +/- 0.2 versus 2.09 +/- 0.13 s, p = 0.035), and resting breathing frequency (F) tended to be greater in the H-LT recipients (16.27 +/- 2.04 versus 12.82 +/- 0.53 breaths/min, p = 0.052). The overall ventilatory response to hypercapnia was reduced after H-LT (0.91 +/- 0.17 versus 1.5 +/- 0.27 L/min/mm Hg CO2, p less than 0.043), as was the F response (0.2 +/- 0.09 versus 0.65 +/- 0.13 breaths/min/mm Hg CO2, p less than 0.01). The VT and VT/TI responses to hypercapnia did not differ between the H-LT recipients and normal subjects. There were no significant differences between the two groups with respect to the responses to progressive hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Breathing during wakefulness and sleep after human heart-lung transplantation.

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pulmonary capillary hemangiomatosis. A report of three cases and a review of the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. At present, only eleven cases have been reported. This report describes the clinical and pathologic findings in three additional cases who presented to the University of Pittsburgh for heart-lung transplantation and integrates the clinical features of all fourteen cases. Clinically, this disorder should be suspected in a patient who presents with pulmonary hypertension, hemoptysis, a reticulonodular infiltrate on chest radiograph, a lung scan showing inhomogeneously enhanced perfusion (particularly in the lower lobes), and pulmonary angiography showing increased peripheral vascularity corresponding to both the radiographic infiltrate and the areas of enhanced perfusion on lung scan. Histologic features consist of nodular proliferation of capillary-sized vessels that infiltrate the pulmonary interstitium, vascular walls, and lumens as well as the alveolar septa. The vascular invasion results in a secondary veno-occlusive phenomenon that explains the clinical confusion with pulmonary veno-occlusive disease.

Adult↗
PubMed1988

Evidence of an altered pattern of breathing during exercise in recipients of heart-lung transplants.

Recipients of heart-lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart-lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart-lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart-lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart-lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise.

Acid-Base Equilibrium↗
PubMed1988

Immunologically mediated disease of the airways after pulmonary transplantation.

Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.

Bronchiolitis Obliterans↗
PubMed1988

Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival.

Pneumonia due to Pneumocystis carinii (PCP) is regularly encountered in organ allograft recipients who are immunosuppressed to prevent rejection. Recipients of lung/heart allografts may be particularly prone to pulmonary infection due to systemic immunosuppression and the fact that defense mechanisms in the transplanted lung may be further impaired through tissue incompatibility and the effects of surgery. In this study, we monitored 16 lung transplant recipients for infection with Pneumocystis carinii using serial bronchoalveolar lavage (BAL) and found the prevalence of Pneumocystis infection of the lung to be 88%. Six episodes were associated with the usual symptoms of pneumonia, whereas 10 episodes were associated with minimal or no symptoms. In 3 of the 6 symptomatic episodes, a concurrent bacterial infection was also found. The total number of cells recovered from the lung by BAL, the proportion of T-lymphocytes, and the number of cytotoxic/suppressor and helper/inducer cells were elevated during infection with Pneumocystis compared to before and after. Spontaneous and interleukin-2-induced proliferation of BAL cells in vitro was also higher during infection, suggesting that there was an increased number of activated T-lymphocytes in the airspaces of the infected allograft. BAL cells cultured with irradiated spleen cells from the donor proliferated at higher levels when obtained after Pneumocystis infection than when obtained before or during infection even for subclinical infections. These results indicate that in the absence of prophylaxis, the prevalence of Pneumocystis infestation is very high after lung/heart transplantation. Impaired defense of the transplanted lung does not seem to stem from the inability of activated T-lymphocytes to accumulate in the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1988

Rapid detection of cytomegalovirus pneumonia from lung lavage cells.

Because cytomegalovirus (CMV) is a common cause of fatal pneumonia in the immunocompromised host, a rapid and reliable method to confirm this diagnosis is essential. Bronchoalveolar lavage (BAL) has proved to be a rapid, safe, and sensitive method for the diagnosis of several forms of pneumonia in these patients, but its efficacy for confirming CMV pneumonia remains to be established. In this study, we compared the sensitivity and specificity of conventional viral culture, immunocytochemical staining, and cytological examination performed on cells recovered by BAL for establishing CMV as the cause of pneumonia in 71 BAL specimens from 56 immunocompromised patients. Pneumonia due to CMV was confirmed by stated criteria in 14 of these patients. Virus was isolated by culture in BAL specimens from all patients with CMV pneumonia (sensitivity 100%), but also in 17 specimens from patients who did not have CMV pneumonia (specificity 70%). On cytologic examination, CMV inclusions were found in 3 of the 14 specimens from patients with CMV pneumonia (sensitivity 21%) and also in 1 patient at risk for pneumonia but who did not fulfill the criteria (specificity 98%). Thus, a positive culture and positive cytology virtually confirmed CMV pneumonia, whereas a negative culture excluded it. Immunocytochemistry proved to be particularly useful when the culture was positive and cytology was negative. In this situation, specific labeling of CMV antigen by monoclonal antibody was found in 9 of the 11 patients with CMV pneumonia (sensitivity 82%). Thus, the absence of specific staining in BAL cells tended to exclude CMV as a cause of pneumonia in patients with positive cultures and negative cytologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1988

Identification, cellular localization, isolation, and characterization of human Clara cell-specific 10 KD protein.

Human lung lavage proteins were fractionated by centrifugation and molecular sieving. An antiserum to the post-albumin fraction of the soluble proteins reacted with a 10 KD protein and this protein was isolated by conventional chromatography. The protein, which has a pI of 4.8, consists of two 5 KD polypeptides and is rich in glutamic acid, leucine, serine, and aspartic acid amino acids. The protein does not bind to concanavalin A, pancreatic elastase, leukocyte elastase, or trypsin, and lacks anti-protease activity. It constitutes about 0.15% of the soluble proteins in lung lavage. Antibodies to the 10 KD protein specifically and exclusively stain Clara cells in human, dog, and rat. Staining of granules of Clara cells was prominent in the distal bronchioles; however, the non-ciliated cells of respiratory bronchioles did not stain for the 10 KD protein. This 10 KD protein appears in fetal lungs at 21 weeks of gestation, and was present in about 10% of the primary pulmonary adenocarcinomas. As a specific marker for Clara cells, this protein could be useful in the study of development, regulation of secretion, and pathobiology of these cells.

Aged↗
PubMed1987

Heart-lung transplantation: lessons learned and future hopes.

Since March, 1982, 33 patients have undergone cardiopulmonary transplantation. Nineteen were discharged from the hospital following the operation, and 16 continue to do well. Eight patients have survived 1 year, 5 patients 2 years, and 1 patient 3 years. Often survival has been influenced most by the selection of candidates, as no patient who had undergone a previous sternotomy survived (3 of 3). All 7 early (between 30 and 72 days) and 3 late (145 to 466 days) deaths were related to infection. Methods for ex vivo preservation of the heart-lung bloc have included storage at 4 degrees C, cardiopulmonary bypass and profound hypothermia, and autoperfusion of the heart-lung bloc. The last technique is original and currently is preferred for distant procurement. Because dehiscence of the tracheal anastomosis has occurred in 3 patients, a sutured line is now encircled with a wrap of omentum. Isolated rejection of the lung is frequent in the first three weeks following operation and has been controlled with methylprednisolone. Late survivors have shown a mild restrictive lung disorder that has not progressed between 6 and 24 months. Bronchoalveolar lavage has been useful for diagnosing infection and providing insight into the immunobiology of the transplanted lung. Although mortality and morbidity have been high, the experiences gained through this series will likely result in an improved outlook for future recipients.

Adolescent↗
PubMed1986

Infections in heart-lung transplant recipients.

Infectious episodes were analyzed in 14 heart-lung transplant recipients who survived more than one week after transplantation. These patients had higher rates of infection than heart transplant recipients at our institution (P less than 0.01) and greater than 90% of all infections were potentially life-threatening. A total of 67% of all infections involved the lung or thoracic cavity as a primary site, and most of the rest were disseminated viral or fungal infections. Pneumocystis carinii infections occurred in six patients and were more common in this group than in patients who received heart transplants in the same period (P less than 0.005). Two patients followed more than one year developed a syndrome of chronic sputum production and bronchial colonization with Pseudomonas aeruginosa, which required recurrent treatment with i.v. antibiotics for symptomatic relief. The high rate of pulmonary infections in these patients presents a challenge to clinical management, and suggests that intensive and invasive monitoring for pulmonary infection is desirable.

Adult↗
PubMed1986

Lymphocyte phenotypes in bronchoalveolar lavage and lung tissue in sarcoidosis and idiopathic pulmonary fibrosis.

To determine whether the lymphocytes recovered by bronchoalveolar lavage (BAL) are representative of the cells found in lung tissue, we identified and enumerated lymphocyte phenotypes directly in lung tissue and lavage fluid with monoclonal antibodies (Leu 4-total T, Leu 3-helper T, Leu 2-suppressor/cytotoxic T cells) and an avidin-biotin peroxidase method in 6 patients with sarcoidosis and 6 patients with idiopathic pulmonary fibrosis (IPF). We found that the absolute numbers of each phenotype and the ratios of Leu 3/Leu 4, Leu 2/Leu 4, and Leu 3/Leu 2 in lavage fluid and tissue correlated well for both groups of patients. This supports the notion that the lymphocytes recovered by BAL are representative of the cells present in the lung. However, when cell recovery was expressed as the number per milliliter of recovered lavage fluid, there were no significant correlations between lavage fluid and tissue for any phenotype in the IPF group. The degree of restrictive impairment was significantly greater and the lavage fluid recovery was significantly lower in this group than in the sarcoid group. Thus, the lymphocytes recovered by BAL appear to mirror the types of cells found in lung tissue in these 2 forms of diffuse interstitial disease, but this relationship may not hold when there is a severe restrictive impairment and a low recovery of lavage fluid.

Humans↗