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Biomedical subjects

I Paradis

Publications and source records attributed to I Paradis.

6 recordsLinked to original sources

Acute rejection of lung allografts with various immunosuppressive protocols.

Between February 1990 and December 1991, 69 patients who survived for a minimum of 5 days after single-lung (27), double-lung (32), or heart-lung transplantation (10) were studied to learn the incidence and severity of acute rejection and the possible effects of various immunosuppressive protocols on this rejection. Acute rejection was less common (2.1 versus 3.1 episodes/patient) after transplantation in those 30 candidates who received rabbit antithymocyte globulin for the first 5 postoperative days versus the 28 who were maintained on cyclosporine, azathioprine, and prednisone alone (p < 0.05), but no patient escaped at least one episode. Patients given cyclosporine received more 3-day courses of methylprednisolone (p < 0.02) than those given rabbit antithymocyte globulin (2.5 versus 1.7 courses). Although no disadvantage in terms of infectious morbidity was noted in the rabbit antithymocyte globulin group, no obvious intermediate advantage was noted in survival (85% at 12 months) or grade of rejection or airway flows. The most common histopathologic grades were mild (A2) and moderate (A3); the average grade was A2.3. FK 506 was tested in 11 patients, and early results are promising relative to low early and likely fewer late episodes of rejection. No differences were noted in the likelihood of rejection for any procedures.

Acute Disease

Proliferation of cytomegalovirus-primed lymphocytes in bronchoalveolar lavages from lung transplant patients.

Previous reports have described an association between cytomegalovirus infection and increased donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes in transplanted lungs and a higher risk of bronchiolitis obliterans due to chronic rejection. We have postulated that during infection, intragraft CMV-specific lymphocytes are activated and release lymphokines that augment cellular rejection. This study deals with an analysis of CMV antigen induced proliferation of 28 BAL lymphocyte and 27 peripheral blood lymphocytes samples from 17 lung transplant patients with or without CMV infection. Kinetic studies of lymphocyte proliferation have shown that CMV infection of the lung allograft is associated with an accelerated response of BAL lymphocytes but not PBL, following in vitro exposure to CMV antigen. These findings indicate an accumulation of primed CMV-specific lymphocytes within the lung allograft during CMV infection. Evidence has also been obtained that primed CMV-specific lymphocytes may persist for months in BAL. We conclude that the CMV antigen induced proliferation assay is useful for studies of CMV infection in transplant patients.

Antigens, Viral

Life in the allogeneic environment after lung transplantation.

Because infection and rejection are the principal complications of any transplant procedure and because the alveolar macrophage is crucial to the defense of the lung from infection and may play a role in lung allograft rejection, we have begun to assess functions of this cell that are thought to be important in lung defense from infection and in transplant immunity. Antimicrobial functions include chemotaxis, which is a mechanism for recruiting macrophages to sites of inflammation and phagocytosis, and intracellular killing of microorganisms. As an accessory cell, the alveolar macrophage is necessary for an effective immune response to develop against either microorganisms or transplantation antigens. Our results indicate that the chemotactic, phagocytic but not the killing capability of alveolar macrophages from lung recipients is impaired. Alveolar macrophages and blood monocytes from lung recipients are also significantly impaired in their support for mitogen and antigen presentation to lymphocytes. Thus, the generation of an effective immune response to a microorganism may be impaired. Alveolar macrophages from lung recipients, however, function as well as those from normal subjects in stimulating lymphocyte proliferation in response to donor antigens (primed lymphocyte test) or unrelated allogeneic antigens (mixed lymphocyte reaction), while their respective blood monocytes function poorly in this regard. Our conclusions are that the antimicrobial functions of the alveolar macrophages are impaired after lung transplantation and this may be one mechanism to explain the unusual susceptibility of the lung allograft to infection. Those functions related to transplant immunity, however, are preserved and indicate that the alveolar macrophage may play a role in allograft rejection.

Adolescent

HLA-class II antigen expression in human heart-lung allografts.

Long-term survival in heart-lung transplantation has ben hindered by the development of bronchiolitis obliterans (OB), which is believed to be a manifestation of chronic rejection of the lung. Since HLA-class II antigens are involved in the rejection response, the distribution of the class II products HLA-DR, HLA-DQ, and HLA-DP were studied in normal lung, and in transplanted lung with and without OB, utilizing frozen-section immunohistochemical techniques. All three allelic products are usually expressed on the epithelial, endothelial, and mesenchymal components of the lung. Sequential transbronchial biopsies from 4 recipients before and concurrent with the diagnosis of OB were stained with serial dilutions of monoclonal antibodies to assess the level of expression of the above class II products. Increased levels of HLA-DR and HLA-DP antigens may be seen on the bronchial and bronchiolar epithelium during OB, but the changes are subtle and complicated by many other variables. Additional studies are needed to confirm these preliminary results.

Bronchiolitis Obliterans