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Biomedical subjects

N Yonan

Publications and source records attributed to N Yonan.

At least 73 records · Page 4Linked to original sources
PubMed1996

Comparative study of three PCR assays with antigenaemia and serology for the diagnosis of HCMV infection in thoracic transplant recipients.

Three PCR assays were evaluated for the detection of human cytomegalovirus (HCMV) infection in heart and lung transplant recipients in comparison with HCMV antigenaemia and serology assay. Polymorphonuclear leucocyte (PMNL) samples taken at regular intervals after transplantation were tested for HCMV DNA using primer sets homologous to the glycoprotein B (gp58), major immediate early (IE1), and structural phosphoprotein (pp150) regions. The detection of HCMV infection at various times after transplantation showed all three primer sets to have a sensitivity of 100% and a specificity of 92.3% for the detection of HCMV infection although overall the gp58 primer set was found to be significantly more frequently associated with a positive PCR result than the IE1 (P = 0.0228) and pp150 (P = 0.0015) primer sets. The positive PCR result had a positive predictive value of 27.8% for HCMV disease. Detection of HCMV infection was first by the PCR assay, and significantly before the HCMV antigenaemia assay. Of nine patients who received antiviral therapy while PCR positive, only one patient cleared HCMV DNA from PMNLs during treatment but became positive again 17 days later. Quantitative PCR methodologies may improve the predictive value of PCR for HCMV disease and its value for monitoring antiviral therapy.

Antigens, Viral↗
PubMed1996

Pulmonary interstitial fibrosis and haemosiderin-laden macrophages: late following heart transplantation.

Impairment of pulmonary diffusion is recognized following heart transplantation. This study was undertaken to determine the histopathological basis for the defect in pulmonary physiology. Heart transplant recipients (HTR) entered into a prospective study of post-transplant pulmonary physiology were asked to undergo bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial biopsy (n = 18) in the presence of impaired gas transfer. Transbronchial biopsies were examined under light microscopy and demonstrated focal interstitial fibrosis in 12 patients, cytomegalovirus disease in four patients and Pneumocystis carinii pneumonia in three patients. Bronchoalveolar lavage differential counts were normal in HTR but BAL macrophages contained haemosiderin. The histological features of interstitial fibrosis may underlie the fall in gas transfer seen following heart transplantation. The presence of haemosiderin-laden macrophages late following heart transplantation suggests a capillary leak syndrome.

Bronchoalveolar Lavage↗
PubMed1996

Epstein-Barr virus associated graft failure following heart/lung transplantation.

A case is described of late pulmonary graft failure in a heart/lung transplant recipient. The major characteristics were alveolar fibrosis and a restrictive physiological deficit. Epstein-Barr virus was implicated as an aetiological agent using immunohistochemical analysis and by a response to treatment with ganciclovir.

Adult↗
PubMed1996

Allergic bronchopulmonary aspergillosis in lung allograft recipients.

Following lung transplantation for end-stage cystic fibrosis, two male patients presented with shortness of breath, peripheral blood eosinophilia and segmental lung collapse. At bronchoscopy, each had bronchial mucous plugging containing Aspergillus fumigatus. This finding was associated with a systemic eosinophilia and skin test positivity to Aspergillus. Augmented steroid therapy resulted in the successful resolution of the symptoms. We believe that these are the first reported cases of allergic bronchopulmonary aspergillosis in lung allograft recipients.

Adult↗
PubMed1996

Pulmonary diffusion impairment following heart transplantation: a prospective study.

The aim of this prospective study was to confirm whether and when a fall in gas transfer occurs following heart transplantation (HT); and to examine the potential relationship between gas transfer and haemodynamic change, immuno-suppression and cytomegalovirus (CMV) infection. The lung physiology of 34 heart transplant recipients (HTR) and 14 control patients undergoing coronary artery bypass grafting (CABG) were studied. The absolute and standardized residual values of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), residual volume (RV), forced residual volume (FRC), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO) were measured before and at 30, 60, 90, 120 and 150 days after HT. These data were compared to haemodynamic status, graft rejection, cyclosporin levels and episodes of CMV infection. Lung function was studied in a group of patients before and 4 weeks after CABG. There was a significant fall in mean KCO after HT (pre-HT = 1.29 and post-HT = 1.06 mmol.min-1.kPa.L-1) but not after CABG (pre-CABG = 1.49, post-CABG = 1.5 mmol.min-1.kPa.L-1. No relationship was observed between gas transfer and CMV. At the latest stage following HT (150 days) there was a positive correlation between TL,CO (absolute value and standardized residual) and mean cyclosporin level (r = 0.48 and r = 0.44, respectively) and also between the absolute KCO and actual (r = 0.56) and mean (r = 0.55) cyclosporin levels. Following HT, there is an early fall in gas transfer, which is independent of the effects of surgery and bypass, implicating early immunosuppression (e.g. antithymocyte globulin/cyclosporin).

Coronary Artery Bypass↗
PubMed1996

TNF alpha mRNA and protein in cardiac transplant biopsies: comparison with serum TNF alpha levels.

OBJECTIVES: To examine the role of TNF alpha (TNF alpha) in cardiac transplant rejection by simultaneous analysis of protein expression and its messenger RNA within serum and grafted tissue. METHODS: 54 endomyocardial biopsy specimens were taken from 19 patients at various times after transplantation. TNF alpha messenger RNA was localised using a digoxygenin labelled complementary DNA probe. An anti-TNF alpha antibody was used to immunohistochemically label the protein product. Serum TNF alpha levels at the time of biopsy were analysed using a specific enzyme-linked immunosorbent assay. RESULTS: TNF alpha mRNA was present in 22/34 endomyocardial biopsies. Eight also contained TNF alpha protein. None had protein alone. Expression did not relate to the grade of rejection in the present or subsequent biopsies. Serum TNF alpha was undetectable (assay sensitivity 30-330 pg/ml) for the majority of specimens. In the nine cases with elevated serum levels, eight samples were from cases within the first 30 days post transplant (r = -0.379; P < 0.05). CONCLUSIONS: Neither tissue TNF alpha mRNA, tissue protein, nor serum TNF alpha relate to the grade of rejection. Furthermore, TNF alpha expression within endomyocardial biopsies is not reflected in the serum. These findings argue against the use of serum analysis as an indicator of cytokine profiles within cardiac tissue allografts. The demonstration of a trend in the early expression of TNF alpha after transplantation suggests that its release may not be specific to the process of rejection.

Adult↗
PubMed1995

Antithymocyte globulin preparations after heart transplantation. Cytokine responses in vivo and in vitro.

It is accepted that antithymocyte globulin (ATG) preparations vary in their bioactivity and side effects. However, this is poorly documented in the literature. We compared the clinical course and cytokine response of heart transplant patients who had received either Merieux or Stanford ATG preparations. The serum cytokine response (interleukin [IL]-6, tumor necrosis factor [TNF]-alpha, IL-4, and IL-10) of 28 consecutive heart transplant recipients was measured for 14 days after surgery using ELISAs. The effect of various ATG preparations on cytokine stimulation of whole blood in vitro was also evaluated. There was a much greater in vivo IL-6 and TNF-alpha response to Merieux than to Stanford ATG (P < 0.0005). There was little IL-4 or IL-10 response with either preparation. No side effects could be attributed to either treatment. No significant difference was seen in the frequency of rejection at 30, 90, or 365 days. More infection episodes occurred in the group treated with Stanford ATG at 30 days (0.5 compared with 0.2 episodes/patient; P = 0.097), 90 days (1.2 compared with 0.5 episodes/patient; P = 0.17), and 365 days (2.8 compared with 1.8; P = 0.59), although none of these differences were statistically significant. When tested in vitro for cytokine stimulation, the in vivo pattern was confirmed, with Merieux ATG producing greater levels of TNF-alpha and IL-6 than Stanford ATG. The differences in cytokine stimulation may be reflected in different immunosuppressive activities. Further research to elucidate the important components of immunosuppressive activity while excluding potentially detrimental effects is important.

Adolescent↗
PubMed1995

Atrial arrhythmias and pacing after orthotopic heart transplantation: bicaval versus standard atrial anastomosis.

BACKGROUND: Right and left atrial configuration is more normal when the donor left atrium is anastomosed to a recipient left atrial cuff with direct anastomoses of the donor and recipient vena cavas on the right side. The right atrium and sinus node may be less disturbed by the technique of bicaval anastomosis than by the standard procedure. OBJECTIVE: To compare the incidence of atrial arrhythmias and pacing after bicaval and standard anastomoses. METHODS: 75 patients had heart transplants between January 1991 and December 1993. The notes were reviewed. Nine patients who died within the first 30 days were excluded from further analysis (seven patients with standard anastomoses, one with bicaval anastomosis, and one with a hybrid technique). RESULTS: 66 patients survived for more than 30 days. Thirty five patients had standard anastomoses and 31 bicaval anastomoses. Atrial tachyarrhythmias (atrial fibrillation, atrial flutter, atrial tachycardia, or supraventricular tachycardia) occurred on four days in three patients in the bicaval group compared with 27 days in 13 patients in the standard group (P = 0.009). The relative risk of atrial tachyarrhythmias with standard anastomosis was 5.52 (P = 0.015) compared with that of bicaval anastomosis. Atrial tachyarrhythmias requiring treatment occurred less often in the bicaval group (four episodes in three patients in the bicaval group and eight episodes in four patients in the standard group), and fewer patients with a bicaval anastomosis required temporary pacing (pacing on 20 days in 10 patients in the bicaval group, but pacing on 49 days in 16 patients in the standard group) and late permanent pacing (no patients in the bicaval group and three patients in the standard group), although these differences were not statistically significant. Patients in the bicaval group were discharged from hospital sooner than those in the standard group (mean 24.1 v 29.1 days, P = 0.024). CONCLUSIONS: The technique of bicaval anastomosis, in addition to theoretical advantages from maintaining a more normal atrial configuration, has a lower incidence of postoperative atrial tachyarrhythmias, may reduce the need for pacing, and allows earlier discharge from hospital.

Adult↗
PubMed1995

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Antigens, Viral↗
PubMed1995

Necrotic, ulcerative bronchitis, the presenting feature of lymphoproliferative disease following heart-lung transplantation.

Following heart-lung transplantation two of 21 patients who survived more than 100 days developed post-transplant lymphoproliferative disease. Both presented with localised ulcerative bronchitis documented at flexible bronchoscopy four months after transplantation. Histological examination showed necrosis with acute inflammation and ulceration. Case 2 demonstrated lymphoproliferative disease from biopsies subsequently taken at rigid bronchoscopy. Case 1 later developed lung nodules and a monoclonal high grade B cell non-Hodgkin's lymphoma was confirmed by an open lung biopsy. The bronchoscopic features described should alert clinicians to post-transplant lymphoproliferative disease as an underlying diagnosis and suggest that bronchus associated lymphoid tissue is the initial site for clonal proliferation in the disease.

Adult↗
PubMed1993

Pulmonary diffusion abnormalities in heart transplant recipients. Relationship to cytomegalovirus infection.

Lung function of patients with heart failure is characterized by a variety of changes proposed as being due to passive congestion, secondary pulmonary fibrosis, and/or recurrent pulmonary emboli. A diffusion impairment thought to be due to cyclosporine has also been noted in patients following heart transplantation. Similar changes of unclear origin have been observed in renal transplant recipients. The objective of this study was to determine the extent to which lung function changes are reversible by cardiac transplantation and relate changes to the status of the recipients lung in the presence of possible vascular, iatrogenic, immune, or infectious injury. We analyzed the data of 22 patients who underwent lung function testing before and after heart transplantation and correlated changes to hemodynamic change, episodes of rejection, concentration of cyclosporine, and cytomegalovirus infection. Despite excellent graft function, the carbon monoxide transfer factor deteriorated to a mean of 57 percent of predicted postoperatively. The fall in diffusion factor did not correlate with episodes of cardiac rejection, cyclosporine levels, or hemodynamic status. In those patients who had serologic evidence of cytomegalovirus infection, the reduction in transfer factor was greater compared to those without infection despite a normal chest radiograph. The effects of cardiopulmonary bypass were unlikely to have been responsible for the abnormalities as lung function was assessed at a mean of 14 months after surgery. In heart transplant recipients, a change in diffusion capacity may represent an additional marker for cytomegalovirus infection and reflect infectious/immune injury late following surgery.

Cyclosporine↗