WorldWideScience

Sample records for human lung transplant

  1. History of Lung Transplantation.

    Science.gov (United States)

    Dabak, Gül; Şenbaklavacı, Ömer

    2016-04-01

    History of lung transplantation in the world can be traced back to the early years of the 20 th century when experimental vascular anastomotic techniques were developed by Carrel and Guthrie, followed by transplantation of thoracic organs on animal models by Demikhov and finally it was James Hardy who did the first lung transplantation attempt on human. But it was not until the discovery of cyclosporine and development of better surgical techniques that success could be achieved in that field by the Toronto Lung Transplant Group led by Joel Cooper. Up to the present day, over 51.000 lung transplants were performed in the world at different centers. The start of lung transplantation in Turkey has been delayed for various reasons. From 1998 on, there were several attempts but the first successful lung transplant was performed at Sureyyapasa Hospital in 2009. Today there are four lung transplant centers in Turkey; two in Istanbul, one in Ankara and another one in Izmir. Three lung transplant centers from Istanbul which belong to private sector have newly applied for licence from the Ministry of Health.

  2. Long-term persistence of human donor alveolar macrophages in lung transplant recipients

    DEFF Research Database (Denmark)

    Eguíluz-Gracia, Ibon; Schultz, Hans Henrik Lawaetz; Sikkeland, Liv I. B.

    2016-01-01

    and life span of human AMFs is scarce. METHODS: To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100 weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation...... transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period...

  3. Endothelial cell chimerism associated with graft rejection after human lung transplantation.

    OpenAIRE

    Ratajczak , Philippe; Murata , Hideyuki; Meignin , Véronique; Groussard , Odile; Fournier , Michel; Socié , Gérard; Mal , Hervé; Janin , Anne

    2008-01-01

    International audience; Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD3...

  4. Ex vivo lung perfusion in clinical lung transplantation--state of the art.

    Science.gov (United States)

    Andreasson, Anders S I; Dark, John H; Fisher, Andrew J

    2014-11-01

    Ex vivo lung perfusion (EVLP) has emerged as a new technique for assessing and potentially reconditioning human donor lungs previously unacceptable for clinical transplantation with the potential to dramatically push the limits of organ acceptability. With the recent introduction of portable EVLP, a new era in lung preservation may be upon us with the opportunity to also limit organ ischaemic times and potentially improve the outcome of donor lungs already deemed acceptable for transplantation. It took over half a century for the technique to evolve from basic theory to semi-automated circuits fit for clinical use that are now rapidly being adopted in transplant centres across the globe. With this field in constant evolution and many unanswered questions remaining, our review serves as an update on the state of the art of EVLP in clinical lung transplantation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  5. Lung transplantation in children. Specific aspects.

    Science.gov (United States)

    Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio

    2013-12-01

    Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  6. Pulmonary rehabilitation in lung transplant candidates.

    Science.gov (United States)

    Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

    2013-06-01

    While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. [Lung transplantation: supply and demand in France].

    Science.gov (United States)

    Stern, M; Souilamas, R; Tixier, D; Mal, H

    2008-10-01

    For a decade lung transplantation has suffered from a lack of donor organs which aroused a national debate and led to planned action in collaboration with The French National Agency for Transplantation. Analysis of the stages of the process from potential donor to lung transplantation identified lung procurement as the main priority. An increase in the number of potential lung donors and revision of the acceptance criteria led to a doubling of the annual rate of lung transplantation in less than two years. In the near future we may solve the problem of donor family refusals and establish scientifically based criteria for lung acceptance to increase the rate of lung transplantation. Transplantation from non heart-beating donors and the reconditioning of ex vivo non acceptable lungs might supply additional organs to fulfill demand in the long term. The rate of lung transplantation activity in France doubled as the result of a dramatic increase of donor lung proposals. The current improvement in the results of lung transplantation might create new demands and generate future difficulties in the supply of donor lungs. New approaches, such as transplantation from non heart-beating donors and reconditioning ex vivo non acceptable lungs, should be examined in the near future.

  8. Antibody induction therapy for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Penninga, Ida Elisabeth Irene

    2013-01-01

    Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe and effect...... and effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation....

  9. Lung transplantation: overall approach regarding its major aspects

    Science.gov (United States)

    de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

  10. Waiting narratives of lung transplant candidates.

    Science.gov (United States)

    Yelle, Maria T; Stevens, Patricia E; Lanuza, Dorothy M

    2013-01-01

    Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives.

  11. Waiting Narratives of Lung Transplant Candidates

    Directory of Open Access Journals (Sweden)

    Maria T. Yelle

    2013-01-01

    Full Text Available Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman’s concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients’ stories and hear what is most meaningful in their lives.

  12. Technology and outcomes assessment in lung transplantation.

    Science.gov (United States)

    Yusen, Roger D

    2009-01-15

    Lung transplantation offers the hope of prolonged survival and significant improvement in quality of life to patients that have advanced lung diseases. However, the medical literature lacks strong positive evidence and shows conflicting information regarding survival and quality of life outcomes related to lung transplantation. Decisions about the use of lung transplantation require an assessment of trade-offs: do the potential health and quality of life benefits outweigh the potential risks and harms? No amount of theoretical reasoning can resolve this question; empiric data are needed. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that affect survival and quality of life. Lung transplant systems and registries mainly focus outcomes assessment on patient survival on the waiting list and after transplantation. Improved analytic approaches allow comparisons of the survival effects of lung transplantation versus continued waiting. Lung transplant entities do not routinely collect quality of life data. However, the medical community and the public want to know how lung transplantation affects quality of life. Given the huge stakes for the patients, the providers, and the healthcare systems, key stakeholders need to further support quality of life assessment in patients with advanced lung disease that enter into the lung transplant systems. Studies of lung transplantation and its related technologies should assess patients with tools that integrate both survival and quality of life information. Higher quality information obtained will lead to improved knowledge and more informed decision making.

  13. Lung transplantation for chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Liou TG

    2013-07-01

    Full Text Available Theodore G Liou, Sanjeev M Raman, Barbara C CahillDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USAAbstract: Patients with end-stage chronic obstructive pulmonary disease (COPD comprise the largest single lung disease group undergoing transplantation. Selection of appropriate candidates requires consideration of specific clinical characteristics, prognosis in the absence of transplantation, and likely outcome of transplantation. Increased availability of alternatives to transplantation for end-stage patients and the many efforts to increase the supply of donor organs have complicated decision making for selecting transplant candidates. Many years of technical and clinical refinements in lung transplantation methods have improved survival and quality of life outcomes. Further advances will probably come from improved selection methods for the procedure. Because no prospective trial has been performed, and because of confounding and informative censoring bias inherent in the transplant selection process in studies of the existing experience, the survival effect of lung transplant in COPD patients remains undefined. There is a lack of conclusive data on the impact of lung transplantation on quality of life. For some patients with end-stage COPD, lung transplantation remains the only option for further treatment with a hope of improved survival and quality of life. A prospective trial of lung transplantation is needed to provide better guidance concerning survival benefit, resource utilization, and quality of life effects for patients with COPD.Keywords: outcomes, emphysema, COPD, alpha-1-antitrypsin deficiency, survival, single lung transplant, bilateral sequential single lung transplant, lung volume reduction, referral, guidelines, health related quality of life

  14. Lung Transplantation for Lymphangioleiomyomatosis in Japan

    Science.gov (United States)

    Ando, Katsutoshi; Okada, Yoshinori; Akiba, Miki; Kondo, Takashi; Kawamura, Tomohiro; Okumura, Meinoshin; Chen, Fengshi; Date, Hiroshi; Shiraishi, Takeshi; Iwasaki, Akinori; Yamasaki, Naoya; Nagayasu, Takeshi; Chida, Masayuki; Inoue, Yoshikazu; Hirai, Toyohiro; Seyama, Kuniaki; Mishima, Michiaki

    2016-01-01

    Background Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported. Methods In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network. Results Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053). Conclusions Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus. PMID:26771878

  15. Unilateral lung transplantation for pulmonary fibrosis.

    Science.gov (United States)

    1986-05-01

    Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

  16. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... introduction. MATERIAL AND METHODS: The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...

  17. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  18. Suicidal hanging donors for lung transplantation

    Science.gov (United States)

    Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

    2018-01-01

    Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

  19. Lung Cancer in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jozicic Mirela

    2016-06-01

    Full Text Available Introduction. Although the incidence of malignancy has increased after solid organ transplantation, data on lung cancer in this group of patients is scarce. The aim of this study was to determine clinical characteristics and outcome of patients who developed lung cancer after renal transplantation. Methods. Among a cohort of 1658 patients who received a transplant at our institution and were followedup between 1973 and 2014, five patients developed lung cancer. We analyzed risk factors, transplantation characteristics, treatment options and survival. Results. Lung cancer was diagnosed in 5 patients (0.3%. Time to diagnosis after the transplant procedure ranged from 26 to 156 months (mean 115 months. All of them had a smoking history. Tumors were classified as IIB (20%, IIIA (40%, and IV (40%. Histological types included adenocarcinoma (80% and there was one case of sarcomatoid carcinoma (20%. One patient had concomitant thyroid papillary carcinoma. Radiotherapy was applied in 2 patients, 2 underwent chemotherapy (erlotinib and combination of carboplatinum and etopozide in one patient each, and 2 died within one month after the diagnosis from disseminated malignant disease. Patients with stage IIIA survived 14 and 24 months after the diagnosis. The patient with sarcomatoid cancer underwent thoracotomy with a complete resection, lost his graft function and died 7 months after the diagnosis. Conclusion. Lung cancer is relatively rare malignancy in renal transplant recipients, but associated with high mortality. Smoking is a significant risk factor, thus smoking cessation should be promoted among renal transplant recipients, as well as regular screening for lung cancer.

  20. Spirometric assessment of lung transplant patients: one year follow-up

    Directory of Open Access Journals (Sweden)

    Paulo M. Pêgo-Fernandes

    2009-06-01

    Full Text Available OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation. INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections. METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed. RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1 and the forced vital capacity (FVC in comparison to the pre-transplant values (p <0.05. Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation. DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery. CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

  1. Early laparotomy after lung transplantation

    DEFF Research Database (Denmark)

    Bredahl, Pia; Zemtsovski, Mikhail; Perch, Michael

    2014-01-01

    BACKGROUND: Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal...... for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS: A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung...

  2. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

    Science.gov (United States)

    Sayah, David M; Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J; Lynch, Joseph P; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B; Christie, Jason D; Belperio, John A; Looney, Mark R

    2015-02-15

    Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. To study NETs in experimental models of PGD and in lung transplant patients. Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.

  3. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis.

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St; Wadowsky, Robert M; Paterson, David L; McCurry, Kenneth R; Reinhart, Todd A; Husain, Shahid; Rinaldo, Charles R

    2007-02-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.

  4. Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis▿

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St.; Wadowsky, Robert M.; Paterson, David L.; McCurry, Kenneth R.; Reinhart, Todd A.; Husain, Shahid; Rinaldo, Charles R.

    2007-01-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses. PMID:17065270

  5. Imaging in lung transplants: Checklist for the radiologist

    International Nuclear Information System (INIS)

    Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

    2014-01-01

    Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients

  6. Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

    2014-10-01

    It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

  7. Lung Transplant

    Science.gov (United States)

    ... Severity of the recipient's lung disease Recipient's overall health Likelihood that the transplant will be successful Immediately before ... will begin within days of your surgery. Your health care team will likely work with you to design an exercise program that's right for you. Your doctor may ...

  8. Physical activity levels early after lung transplantation.

    Science.gov (United States)

    Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

    2015-04-01

    Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise

  9. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died......% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...

  10. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

    Science.gov (United States)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

    2014-03-01

    The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.

  11. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  12. Role of gastroesophageal reflux disease in lung transplantation

    Science.gov (United States)

    Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit

    2017-01-01

    Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques. PMID:28507913

  13. Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Richard C Cook

    1998-01-01

    Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

  14. Fusarium Infection in Lung Transplant Patients

    Science.gov (United States)

    Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios

    2013-01-01

    Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens. Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment

  15. Pulmonary hypertension as a risk factor of mortality after lung transplantation

    DEFF Research Database (Denmark)

    Andersen, Kasper H; Schultz, Hans Henrik L; Nyholm, Benjamin

    2016-01-01

    PURPOSE: Pulmonary hypertension (PH) is recognized as a risk factor in lung transplantation as reflected in the lung allocation score (LAS). We examined the impact of PH on outcome after lung transplantation, with special emphasis on pre- and post-capillary PH. METHODS: Consecutive lung transplant...

  16. Lifetime costs of lung transplantation : Estimation of incremental costs

    NARCIS (Netherlands)

    VanEnckevort, PJ; Koopmanschap, MA; Tenvergert, EM; VanderBij, W; Rutten, FFH

    1997-01-01

    Despite an expanding number of centres which provide lung transplantation, information about the incremental costs of lung transplantation is scarce. From 1991 until 1995, in The Netherlands a technology assessment was performed which provided information about the incremental costs of lung

  17. Lung transplantation in the most critically-III: forging ahead.

    Science.gov (United States)

    Mulvihill, Michael S; Hartwig, Matthew G; Daneshmand, Mani A

    2017-09-01

    Lung transplantation is the gold standard therapy for patients with end-stage lung disease. The use of the lung allocation score (LAS) has permitted improved allocation of scarce pulmonary allografts. Recently, Crawford et al. examined the experience in the United States in lung transplantation in candidates with the highest LAS, demonstrating that outcomes for candidates with the highest LAS scores have improved significantly. This editorial places these data in the broader context of thoracic transplantation, and highlights the critical need for ongoing examination of this critically-ill patient population.

  18. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation.

    Science.gov (United States)

    Ware, L B; Golden, J A; Finkbeiner, W E; Matthay, M A

    1999-03-01

    Reperfusion lung injury is an important cause of morbidity and mortality after orthotopic lung transplantation. The purpose of this study was to investigate the function of the alveolar epithelium in the setting of reperfusion lung injury. Simultaneous samples of pulmonary edema fluid and plasma were collected from eight patients with severe post-transplantation reperfusion edema. The edema fluid to plasma protein ratio was measured, an indicator of alveolar-capillary barrier permeability. The initial edema fluid to plasma protein ratio was > 0.75 in six of eight patients, confirming the presence of increased permeability of the alveolar-capillary barrier. Graft ischemic time was positively correlated with the degree of permeability (r = 0.77, p mean +/- SD). Alveolar fluid clearance was calculated from serial samples in six patients. Intact alveolar fluid clearance correlated with less histologic injury, rapid resolution of hypoxemia, and more rapid resolution of radiographic infiltrates. The two patients with no net alveolar fluid clearance had persistent hypoxemia and more severe histologic injury. This study provides the first direct evidence that increased permeability to protein is the usual cause of reperfusion edema after lung transplantation, with longer ischemic times associated with greater permeability to protein in the transplanted lung. The high rates of alveolar fluid clearance indicate that the fluid transport capacity of the alveolar epithelium may be well preserved in the allograft despite reperfusion lung injury. The ability to reabsorb fluid from the alveolar space was a marker of less severe reperfusion injury, whereas the degree of alveolar-capillary barrier permeability to protein was not. Measurement of alveolar fluid clearance may be useful to assess the severity of reperfusion lung injury and to predict outcome when pulmonary edema develops after lung transplantation.

  19. Neurological complications following adult lung transplantation

    NARCIS (Netherlands)

    Mateen, F. J.; Dierkhising, R. A.; Rabinstein, A. A.; van de Beek, D.; Wijdicks, E. F. M.

    2010-01-01

    The full spectrum of neurologic complications and their impact on survival in lung recipients has not been reported. A retrospective cohort review of the Mayo Clinic Lung Transplant Registry (1988-2008) was performed to determine the range of neurologic complications in a cohort of adult lung

  20. Anesthesia for Pediatric Lung Transplantation: Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Premal M Trivedi

    2017-08-01

    Full Text Available The first pediatric lung transplant was performed in 1987 at the University of Toronto in a 15-year-old with familial pulmonary fibrosis. Since that time, over 2000 children have received lung transplants worldwide, with an annual number ranging between 99 and 137 over the past decade. For the anesthesiologist charged with managing these rare patients, an understanding of the indications that lead to transplantation, their pathophysiology, and the physiology of the transplanted lungs are critical. To provide a context for the anesthetic management of the child undergoing lung transplantation, we discuss the case of a 2-month-old who underwent bilateral lung transplantation for intractable respiratory failure. Both the unique aspects of this case and pediatric lung transplantation, in general, are presented. Then a review of the literature is discussed.

  1. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function

    DEFF Research Database (Denmark)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F

    2012-01-01

    procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found......Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation...

  2. Advanced pulmonary arterial hypertension: mechanical support and lung transplantation

    Directory of Open Access Journals (Sweden)

    Sonja Bartolome

    2017-12-01

    Full Text Available The development of targeted therapies has transformed the outlook for patients with pulmonary arterial hypertension (PAH; however, some patients fail to achieve an adequate clinical response despite receiving maximal treatment. For these patients, lung transplantation remains an important therapeutic option, and recommendations for transplantation are included in the current European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension. Although lung transplantation is not without risk, overall long-term survival rates are good and substantial improvements in quality of life have been reported for lung transplant recipients. In this review, we describe the important considerations prior to, during and after transplantation, including the role of mechanical support, in patients with advanced PAH.

  3. Significance of single lung transplantation in the current situation of severe donor shortage in Japan.

    Science.gov (United States)

    Miyoshi, Ryo; Chen-Yoshikawa, Toyofumi F; Hijiya, Kyoko; Motoyama, Hideki; Aoyama, Akihiro; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Date, Hiroshi

    2016-02-01

    Although bilateral lung transplantation is the procedure of choice internationally, single lung transplantation is preferred in Japan because of the severe donor shortage except in cases of contraindications to single lung transplantation. This study aimed to evaluate the clinical characteristics of single lung transplant recipients and outcomes of this procedure at one of the largest lung transplant centers in Japan. Between April 2002 and May 2015, 57 cadaveric lung transplantations (33 single and 24 bilateral) were performed in Kyoto University Hospital. The clinical characteristics of the lung transplant recipients and outcomes of these procedures, including overall survival and postoperative complications, were investigated. Overall, the 1-, 3-, and 5-year survival rates were 86, 77, and 72 %, respectively, with a median follow-up period of 1.9 years. There was no significant difference in survival between patients who underwent single lung transplantations and those who underwent bilateral lung transplantations (p = 0.92). The median waiting time was significantly shorter for single lung transplant patients than for bilateral lung transplant patients (p = 0.02). Native lung complications were seen in 14 out of 33 patients (42 %) who underwent single lung transplantation. There was no significant difference in survival between patients with and without postoperative native lung complications. Single lung transplantation has been performed with acceptable outcomes in our institution. In the current situation of severe donor shortage in Japan, single lung transplantation can remain the first choice of treatment except in cases of contraindications to single lung transplantation.

  4. Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation.

    Science.gov (United States)

    Chauhan, Dhaval; Karanam, Ashwin B; Merlo, Aurelie; Tom Bozzay, P A; Zucker, Mark J; Seethamraju, Harish; Shariati, Nazly; Russo, Mark J

    2016-05-01

    Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all ≥18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Discrepancy between severity of lung impairment and seniority on the lung transplantation list.

    Science.gov (United States)

    Travaline, J M; Cordova, F C; Furukawa, S; Criner, G J

    2004-12-01

    Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r=0.01; P=.94), VO2 max percentage predicted (r=0.07; P=.71), or 6MWD (r=0.15; P=.42). Many patients with functional impairments as indicated by low maximum VO2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than "should be" based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. Rank order for lung transplantation has no relationship with illness

  6. Transplantes cardiopulmonar e pulmonar com doador em localidade distante Distant donor procurement for heart-lung and lung transplantation

    Directory of Open Access Journals (Sweden)

    Luis Sérgio Fragomeni

    1988-12-01

    Full Text Available Em situações específicas, os transplantes clínicos cardiopulmonar e pulmonar são, hoje, formas estabelecidas de tratamento para estágio final de doença cardiopulmonar e pulmonar. A obtenção de doadores adequados permanece o maior problema e a remoção de órgãos em localidades distantes é, hoje, uma necessidade. Embora muitos métodos de preservação pulmonar possam ser empregados, para períodos isquémicos de até 5 horas, a hipotermia e o uso de solução cardioplégica com infusão da solução de Collins modificada no tronco pulmonar tem sido método simples e eficiente para preservação do bloco coração-pulmão. Descrevemos, aqui, o método corrente que empregamos, com o qual os transplantes cardiopulmonar e pulmonar combinados foram sucedidos de excelente função cárdio-respiratória.In special situations, clinical heart-lung and lung transplantation are today established methods of therapy for end stage cardiopulmonary and pulmonary disease. Adequate donor availability remains a major problem and distant organ procurement is today a necessity. Although many methods of lung preservation can be used, for periods of up to 5 hours, hypothermic storage with cardioplegic arrest and pulmonary artery flush with modified Collins solution has proven to be a simple and reliable method of heart-lung preservation. We here describe our current method of heart-lung block protection, in which heart-lung and double lung transplantation were performed followed by excelent cardiac and pulmonary function.

  7. State of the Art in Pediatric Lung Transplantation.

    Science.gov (United States)

    Lancaster, Timothy S; Eghtesady, Pirooz

    2018-04-24

    Pediatric lung transplantation is a highly specialized therapy for end stage pulmonary disease in children, performed in only a handful of transplant centers around the world. Advancement in the field has been made on many fronts in recent years, including in public policy and organ allocation strategies, donor selection and management, emerging technologies for donor lung rehabilitation and bridge-to-transplant support of listed candidates, and ongoing refinement of surgical techniques. Despite this progress, children continue to suffer discrepant waitlist mortality and longer waiting times than their adult counterparts, and face special challenges of donor availability and size matching. Here we review the current state of the art in pediatric lung transplantation, reviewing progress made to date and further opportunities to improve care for this unique group of patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

    2013-01-01

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

  9. Physiotherapeutic Intervention in the lung transplant

    International Nuclear Information System (INIS)

    Castro C, Carolyn; Gonzalez M Sonia

    2001-01-01

    The physical therapist just as other health professionals must know, how to detect and control the risk factors that affect the welfare of his patients, this is done by evaluation, education and assistance in order to benefit the biological, psychological, emotional, social and environmental conditions that contribute to their development as human beings. The physical therapist in the lung transplant area can create strategies to promotion, prevent and rehabilitate in the pre and post surgical phases of the intervention, to facilitate the required conditions that allow optimal adaptation of the receiver to the new organ

  10. Pulmonary thromboembolism as a complication of lung transplantation

    DEFF Research Database (Denmark)

    Kristensen, Anna Warncke; Mortensen, Jann; Berg, Ronan M G

    2017-01-01

    Post-transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE...

  11. Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation.

    Science.gov (United States)

    Zaki, Khawaja S; Aryan, Zahra; Mehta, Atul C; Akindipe, Olufemi; Budev, Marie

    2016-03-24

    Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation.

  12. Life after a lung transplant: a balance of joy and challenges.

    Science.gov (United States)

    Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene; Berg, Selina Kikkenborg

    2017-11-01

    To describe patients' experiences throughout the first four months post-lung transplant. Health professionals are familiar with the fact that patients' average survival after a lung transplant is about seven years and that 74% of these patients reject new organs within the first two years. By contrast, knowledge of these patients' perspectives after lung transplantation is scant. A qualitative study was conducted between May 2013-May 2014 in which 26 interviewees participated - four months post-transplant - based on a semistructured interview guide. The data were inductively analysed using a content thematic approach within a phenomenological and hermeneutic frame. The main findings in the study reveal that (1) having a lung transplant is an overwhelming experience, which for some patients includes (2) troubling physical and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow? Having a lung transplant is described as an overwhelming experience because of the improvement in the physical function of the body. Patients were grateful to family, friends and healthcare professionals for supporting them. The first four months post-transplantation were described as both physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. The patients are troubled by both physical and

  13. Lung transplantation in the rat. III. Functional studies in iso- and allografts

    International Nuclear Information System (INIS)

    Marck, K.W.; Prop, J.; Wildevuur, C.R.

    1983-01-01

    Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research

  14. What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

    Science.gov (United States)

    Daimiel Naranjo, I; Alonso Charterina, S

    2016-01-01

    Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    Science.gov (United States)

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  16. Abnormal extraosseous activity in both lungs and stomach in pre-transplant 99mTc-MDP bone scan disappearing after renal transplant

    International Nuclear Information System (INIS)

    Sonavane, Sunita Tarsarya; Marwah, Atul; Jaiswar, Rajnath; Shah, Hardik

    2013-01-01

    A chronic kidney disease male patient presenting with bone pains, fever, weakness, and clinically ascites was subjected to four technetium-99m-methylene diphosphonate ( 99m Tc-MDP) bone scans, two before renal transplant and two after renal transplants. Pretransplant bone scan revealed metabolic bone disease with focal insufficiency fractures. Marked extraosseous activity in both lungs and stomach was also visualized. On regular hemodialysis (HD) after 4 months, repeat pretransplant bone scan showed persistent uptake in lungs and stomach, representing altered calcium metabolism with microcalcifications. He underwent human leukocyte antigen (HLA) matched live donor renal transplantation, started on immune-suppression and steroids. Posttransplant bone scan at 20 days revealed no definite interval change, but bone scan performed approximately 17 months posttransplant showed resolving metabolic bone disease and the tracer uptake in the lungs and stomach was no more visualized. Patient clinically followed-up until the date (February 2013) is asymptomatic with serum creatinine of 1.5 mg/dl, no bone scan done. (author)

  17. Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

    Science.gov (United States)

    Motoyama, H; Chen, F; Ohsumi, A; Hijiya, K; Takahashi, M; Ohata, K; Yamada, T; Sato, M; Aoyama, A; Bando, T; Date, H

    2014-04-01

    Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Pulmonary rehabilitation programs in lung transplant: a literature review

    Directory of Open Access Journals (Sweden)

    Juliana Maria de Sousa Pinto

    2015-09-01

    Full Text Available Objective: To analyze, using a literature review, Pulmonary Rehabilitation (RP Programs in lung transplant. Methods: A literature review in July 2014 in Ebsco Host, Periódicos Capes, BVS and Science Direct data bases using descriptors in English (“lung transplantation”, “lung transplant” AND/OR “rehabilitation” and Portuguese (“reabilitação” AND/OR “transplante pulmonar”. The eligibility criterions were interventional studies of PR before and/or after lung transplant; participants who were candidates to lung transplant or lung transplant recipients; studies that applied any kind of PR program (hospital-based, homebased or outpatient and articles published in English, Spanish or Portuguese. Literature reviews, guidelines and case reports were excluded. The search process yielded 46 articles of which two were duplicated. After title and abstract screening 13 articles remained for full text reading. Six studies met the inclusion eligibility and were included in the review. Results: The studies involved patients with Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, Pulmonary Hypertension, Interstitial Lung Disease and Pulmonary Fibrosis. Pulmonary function, exercise capacity, quality of life (QoL and quadriceps force were evaluated. Most interventions were outpatient programs with three months duration, three times a week and session with at least one hour. Protocols included physical training, educational approach and just one included nutritional, psychiatric and social assistant follow-up. The studies presented significant change in the six-minute walking distance, QoL and quadriceps force after PR programs. Conclusion: This review showed the benefits of the PR in the QoL and exercise capacity contributing to the Health Promotion of the patients.

  19. Immunological risk stratification of the bronchiolitis obliterans syndrome after lung transplantation

    NARCIS (Netherlands)

    Kwakkel - van Erp, J.M.

    2011-01-01

    The development of chronic allograft rejection after lung transplantation (LTx) is the most common cause of poor long-term survival in lung transplant recipients. This rejection leads to obliteration of the bronchioli. Since this obliteration has a patchy distribution and normal lung tissue obtained

  20. Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

  1. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    Science.gov (United States)

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

  2. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    Science.gov (United States)

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  3. Life after a lung transplant

    DEFF Research Database (Denmark)

    Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene

    2017-01-01

    and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow...... and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy...... physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. RELEVANCE TO CLINICAL PRACTICE: The patients are troubled by both physical and psychological...

  4. Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

    Science.gov (United States)

    Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

    2018-03-10

    Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. [Short-term outcomes of lung transplant recipients using organs from brain death donors].

    Science.gov (United States)

    He, W X; Jiang, C; Liu, X G; Huang, W; Chen, C; Jiang, L; Yang, B; Wu, K; Chen, Q K; Yang, Y; Yu, Y M; Jiang, G N

    2016-12-01

    Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days ( M ( Q R )) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.

  6. Depressive Symptoms, Exercise Capacity, and Clinical Outcomes After Lung Transplantation.

    Science.gov (United States)

    Smith, Patrick J; Byrd, Rebecca; Lusby, Megan; Clausen, Emily; Snyder, Laurie D

    2018-05-01

    Depressive symptoms are common among lung transplant recipients and have been associated with worse clinical outcomes. However, few studies have examined the association between depressive symptoms assessed at multiple time points or behavioral mechanisms by which posttransplant depressive symptoms may confer greater clinical risk. We therefore examined the associations between depressive symptoms, exercise capacity, chronic lung allograft dysfunction (CLAD), and mortality prospectively in a large sample of lung transplant recipients. Between July 2009 and February 2016, 251 lung transplant recipients were assessed before transplantation and again approximately 3 weeks and 3 months after transplant. Depressive symptoms were assessed using the Centers for Epidemiologic Studies of Depression scale. Functional exercise capacity was assessed using the 6-minute walk test. Cox proportional hazards models were used to examine the associations between depressive symptoms, exercise capacity, CLAD, and mortality. During a median (range) follow-up of 4.5 (0.1 to 6.3) years, 53 participants (21%) died. Greater depressive symptoms (hazard ratio [HR] = 1.39 [95% CI = 1.05 to 1.84], p = .021) and poorer exercise capacity (HR = 0.58 [95% CI = 0.38 to 0.90], p = .021) assessed 3 months after transplant were both independently associated with mortality. Although greater depressive symptoms were associated with lower exercise capacity (β = -0.14, p = .039), exercise capacity did not mediate the association between depressive symptoms and mortality. In secondary analyses, depressive symptoms were independently predictive of CLAD (HR = 1.29 [95% CI = 1.01 to 1.65], p = .045) and the composite outcome of CLAD and mortality in a clustered event model (HR = 1.30 [1.09 to 1.56], p = .005). Depressive symptoms are associated with mortality and CLAD after lung transplantation, independent of exercise capacity.

  7. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was

  8. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  9. Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

    Science.gov (United States)

    El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

    2018-01-01

    Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

  10. Fungal infection by Mucorales order in lung transplantation: 4 case reports.

    Science.gov (United States)

    Neto, F M F D; Camargo, P C L B; Costa, A N; Teixeira, R H O B; Carraro, R M; Afonso, J E; Campos, S V; Samano, M N; Fernandes, L M; Abdalla, L G; Pêgo-Fernandes, P M

    2014-01-01

    Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donor's segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Treatment of distal bronchial stenosis after bilateral lung transplantation

    Directory of Open Access Journals (Sweden)

    S. V. Golovinskiy

    2017-01-01

    Full Text Available The effi ciency of lung transplantation is considerably limited by the complications associated with the bronchial pathologies. Despite the progress of the treatment methods, bronchial complications are still remaining as an actual problem in the postoperative period with frequency of occurrence from 7 to 29%. However, the bronchial stenosis are the most common bronchial complications after lung transplantation with mortality from 2 to 4%.Aim. To study an experience of our center of bronchial stenosis treatment in lung recipients. Materials and methods. 34 patients underwent lung transplantation from September 2014 to January 2017. 6 (16% of them had a stenosis of lobar or segmental bronchi from 84 to 494 postoperative day. 5 (83% of them have demonstrated multifocal lesions. In all of the cases there was performed an endoscopic bougienage, which involved a balloon dilatation and electrocoagulated incision of granular tissue under X-ray control. After that the patients were administrated by everolimus.Results. Restenosis was formed in 132,0 ± 94,2 postoperative day after primary treatment in all patients. In four cases (67% we used nitinol stent placement under X-ray control. There were no complications. In 3 cases stents were dislocated distally, so we needed to use repeated endoscopic bougienage to replace the stent. Using of everolimus has allowed to decrease the rate of restenosis, but it need future research.Conclusion. Distal bronchial stenosis after lung transplantation can be managed with endoscopic bougienage and stent placement. Adding everolimus has not signifi cantly affected the risk of frequency of restenosis.

  12. Computed tomography findings of postoperative complications in lung transplantation

    International Nuclear Information System (INIS)

    Hochhegger, Bruno; Irion, Klaus Loureiro; Marchiori, Edson; Bello, Rodrigo; Moreira, Jose; Camargo, Jose Jesus; Universidade Federal do Rio de Janeiro

    2009-01-01

    Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis. (author)

  13. Lung transplant curriculum in pulmonary/critical care fellowship training.

    Science.gov (United States)

    Hayes, Don; Diaz-Guzman, Enrique; Berger, Rolando; Hoopes, Charles W

    2013-01-01

    Lung transplantation is an evolving specialty with the number of transplants growing annually. A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.

  14. Quality of life in caregivers providing care for lung transplant candidates.

    Science.gov (United States)

    Lefaiver, Cheryl A; Keough, Vicki A; Letizia, Marijo; Lanuza, Dorothy M

    2009-06-01

    Caregivers are essential members of the health care team who provide care, valued at more than $250 billion each year, to millions of persons who require assistance with health and daily care. Patients with respiratory diseases who are waiting for a lung transplant are required to have an identified caregiver. The caregivers are rarely studied. To explore the relationships among the health status of caregivers of lung transplant candidates, caregivers' reaction to caregiving, and caregivers' perceived quality of life. This descriptive study examined the quality of life of lung transplant caregivers from a multidimensional perspective. Twenty-nine dyads of lung transplant candidates and their caregivers were recruited from a Midwestern medical center. Data were collected by self-report: caregivers completed the Quality of Life Index, SF-12 health survey, Profile of Mood States-Short Form, and the Caregiver Reaction Assessment. Caregivers reported favorable levels of quality of life, physical health, and mood during the pretransplant waiting phase. However, problem areas for caregivers during this time included fatigue, depression, and the financial impact of the transplant. Data analyses indicated that depression, caregiver general health, impact on finances, and lack of family support had the greatest effect on caregivers' quality of life. Nurses are urged to recognize the role of caregivers in the transplant process, ask about and listen to caregivers' needs, and include caregivers in the plan of care.

  15. Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation.

    Science.gov (United States)

    Courtwright, Andrew M; Fried, Sabrina; Villalba, Julian A; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H; Hunninghake, Gary M; Raby, Benjamin A; Agarwal, Suneet; Camp, Philip C; Rosas, Ivan O; Goldberg, Hilary J; El-Chemaly, Souheil

    2016-01-01

    Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12-2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50-2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings.

  16. Direct quantification of human cytomegalovirus immediate-early and late mRNA levels in blood of lung transplant recipients by competitive nucleic acid sequence-based amplification

    NARCIS (Netherlands)

    Greijer, AE; Verschuuren, EAM; Harmsen, MC; Dekkers, CAJ; Adriaanse, HMA; The, TH; Middeldorp, JM

    The dynamics of active human cytomegalovirus (HCMV) infection was monitored by competitive nucleic acid sequence-based amplification (NASBA) assays for quantification of IE1 (UL123) and pp67 (UL65) mRNA expression levels In the blood of patients after lung transplantation. RNA was isolated from 339

  17. Lung ultrasound for the diagnosis of post-operative complications after lung transplantation

    DEFF Research Database (Denmark)

    Rømhild Davidsen, Jesper; Lawaetz Schultz, Hans Henrik; Henriksen, Daniel Pilsgaard

    2017-01-01

    Lung ultrasound (LUS) has a high diagnostic accuracy for the identification of pleural effusion, pneumonia, and interstitial syndrome (IS), all of which are common complications in the early phase after lung transplantation (LTx), and may be associated with primary graft dysfunction, bleeding, or...... after LTx, and could be an alternative to conventional and more time-consuming thoracic imaging....

  18. Primary Graft Dysfunction and Long-Term Outcomes Following Lung Transplantation

    OpenAIRE

    DerHovanessian, Ariss

    2012-01-01

    Background: Primary graft dysfunction (PGD) is an early complication of lung transplantation associated with poor early outcomes, however less is known about its prolonged effects on morbidity and mortality. We hypothesized that PGD is associated with long-term mortality and chronic rejection in the form of bronchiolitis obliterans syndrome. Methods: A retrospective study of 279 adult lung transplant recipients between 2000 and 2007 was performed. PGD grade was determined both immediately ...

  19. [What the family doctor must know about lung transplant (Part 1)].

    Science.gov (United States)

    Zurbano, L; Zurbano, F

    2017-09-01

    Lung transplant is a therapeutic, medical-surgical procedure indicated for pulmonary diseases (except lung cancer), that are terminal and irreversible with current medical treatment. More than 3,500 lung transplants have been performed in Spain, with a rate of over 6 per million and increasing. In this review, an analysis is made of the types of transplants, their indications and contraindications, the procedures, immunosuppressive treatments, their side effects and medical interactions, current prophylaxis. A list of easily accessible literature references is also include, the majority being by national authors. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    Science.gov (United States)

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

  1. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    Science.gov (United States)

    Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

  2. Psychosocial and financial aspects of lung transplantation.

    Science.gov (United States)

    Smolin, T L; Aguiar, L J

    1996-09-01

    This article summarizes the many psychosocial phases a patient will encounter during his or her transplantation experience and the ways the social worker can assist during this time. These include supportive services such as facilitating support groups and orientation programs, counseling, and crisis intervention. Also of importance is the financing of lung transplantation and its many associated costs, such as immunosuppressive medications and temporary housing. With the rise in managed care, the role of the transplant financial coordinator is of increasing importance from both a fiscal perspective and customer service standpoint for both the patient and the institution.

  3. A novel patient-centered "intention-to-treat" metric of U.S. lung transplant center performance.

    Science.gov (United States)

    Maldonado, Dawn A; RoyChoudhury, Arindam; Lederer, David J

    2018-01-01

    Despite the importance of pretransplantation outcomes, 1-year posttransplantation survival is typically considered the primary metric of lung transplant center performance in the United States. We designed a novel lung transplant center performance metric that incorporates both pre- and posttransplantation survival time. We performed an ecologic study of 12 187 lung transplant candidates listed at 56 U.S. lung transplant centers between 2006 and 2012. We calculated an "intention-to-treat" survival (ITTS) metric as the percentage of waiting list candidates surviving at least 1 year after transplantation. The median center-level 1-year posttransplantation survival rate was 84.1%, and the median center-level ITTS was 66.9% (mean absolute difference 19.6%, 95% limits of agreement 4.3 to 35.1%). All but 10 centers had ITTS values that were significantly lower than 1-year posttransplantation survival rates. Observed ITTS was significantly lower than expected ITTS for 7 centers. These data show that one third of lung transplant candidates do not survive 1 year after transplantation, and that 12% of centers have lower than expected ITTS. An "intention-to-treat" survival metric may provide a more realistic expectation of patient outcomes at transplant centers and may be of value to transplant centers and policymakers. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. The roles of social support and psychological distress in lung transplant candidacy.

    Science.gov (United States)

    Phillips, Kristin M; Burker, Eileen J; White, Hayley C

    2011-09-01

    Social support appears to be an important component in lung transplantation. However, the relationship between social support, psychological distress, and listing status has not been evaluated in lung transplant candidates. To evaluate the relationships between depression, anxiety, and social support in patients with end-stage lung disease being evaluated for transplantation and determine (1) relationships between social support, depression, anxiety, and coping via seeking emotional and instrumental support; (2) whether social support explains a significant proportion of the variance in depression and anxiety; and (3) whether these factors were associated with whether a patient was listed for transplant. For this observational study, patients completed self-report questionnaires after their pretransplant evaluations. Listing status was subsequently obtained from medical records. Participants were patients with end-stage lung disease evaluated for transplantation at a major hospital. Medical Outcomes Study Social Support Survey, COPE Inventory, Beck Depression Inventory, and State-Trait Anxiety Inventory. Social support was associated with depression, anxiety, and seeking support (P values social support explained a significant proportion of the variance in depression (9%), state anxiety (8%), and trait anxiety (7%; all P values anxiety, trait anxiety, or availability of social support. Results highlight the important role that coping via seeking support plays in transplant candidacy.

  5. Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

    Science.gov (United States)

    Sugimoto, Seiichiro; Yamane, Masaomi; Otani, Shinji; Kurosaki, Takeshi; Okahara, Shuji; Hikasa, Yukiko; Toyooka, Shinichi; Kobayashi, Motomu; Oto, Takahiro

    2018-04-21

    Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

  6. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

    Science.gov (United States)

    Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

    2013-07-01

    Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Lung Transplantation in Patients with Pulmonary Hypertension

    Science.gov (United States)

    ... 00:00 Lung Transplantation in Patients with Pulmonary Hypertension Consensus Statements Issued by the Scientific Leadership Council ... a treatment option for selected patients with pulmonary hypertension (PH) when medical therapy is no longer effective. ...

  8. Cytomegalovirus infection in living-donor and cadaveric lung transplantations.

    Science.gov (United States)

    Ohata, Keiji; Chen-Yoshikawa, Toyofumi F; Takahashi, Koji; Aoyama, Akihiro; Motoyama, Hideki; Hijiya, Kyoko; Hamaji, Masatsugu; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Takakura, Shunji; Date, Hiroshi

    2017-11-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT. The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed. Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D- recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P CLT. We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Survival benefit of cardiopulmonary bypass support in bilateral lung transplantation for emphysema patients

    NARCIS (Netherlands)

    Hepkema, BG; Loef, BG; van der Bij, W; Verschuuren, EAM; Lems, SPM; Ebels, T

    2002-01-01

    Background. This study is designed to examine a possible association of cardiopulmonary bypass (CPB) support and outcome of lung transplantation in a well-balanced group of emphysema patients. Methods. We performed a retrospective analysis of 62 consecutive primary bilateral lung transplantations

  10. Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

    DEFF Research Database (Denmark)

    Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik

    2018-01-01

    BACKGROUND: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. METHODS: Bronchoscopi...

  11. When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation.

    Science.gov (United States)

    Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R; Popov, Aron-Frederik

    2015-10-12

    In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed.

  12. The value of ventilation scintigraphy after single lung transplantation

    NARCIS (Netherlands)

    Ouwens, JP; van der Bij, W; van der Mark, TW; Piers, DA; Koeter, GH

    Background: A decrease in forced expiratory volume in 1 second (FEV1) as a diagnostic criterion for bronchiolitis obliterans syndrome (BOS) after single lung transplantation may be influenced significantly by the presence of the native lung. To quantify and to discriminate between the relative

  13. Single-Lung Transplant Results in Position Dependent Changes in Regional Ventilation: An Observational Case Series Using Electrical Impedance Tomography

    Directory of Open Access Journals (Sweden)

    Kollengode Ramanathan

    2016-01-01

    Full Text Available Background. Lung transplantation is the optimal treatment for end stage lung disease. Donor shortage necessitates single-lung transplants (SLT, yet minimal data exists regarding regional ventilation in diseased versus transplanted lung measured by Electrical Impedance Tomography (EIT. Method. We aimed to determine regional ventilation in six SLT outpatients using EIT. We assessed end expiratory volume and tidal volumes. End expiratory lung impedance (EELI and Global Tidal Variation of Impedance were assessed in supine, right lateral, left lateral, sitting, and standing positions in transplanted and diseased lungs. A mixed model with random intercept per subject was used for statistical analysis. Results. EELI was significantly altered between diseased and transplanted lungs whilst lying on right and left side. One patient demonstrated pendelluft between lungs and was therefore excluded for further comparison of tidal variation. Tidal variation was significantly higher in the transplanted lung for the remaining five patients in all positions, except when lying on the right side. Conclusion. Ventilation to transplanted lung is better than diseased lung, especially in lateral positions. Positioning in patients with active unilateral lung pathologies will be implicated. This is the first study demonstrating changes in regional ventilation, associated with changes of position between transplanted and diseased lung.

  14. Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

    Science.gov (United States)

    Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P

    2015-12-01

    Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C

    2016-10-07

    Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

  16. Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

    Science.gov (United States)

    Wood, Richard K

    2015-12-01

    Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

  17. The prevalence and extent of gastroesophageal reflux disease correlates to the type of lung transplantation.

    Science.gov (United States)

    Fisichella, Piero Marco; Davis, Christopher S; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G; Kovacs, Elizabeth J; Joehl, Raymond J; Love, Robert B

    2012-02-01

    Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation.

  18. Donor Smoking and Older Age Increases Morbidity and Mortality After Lung Transplantation

    DEFF Research Database (Denmark)

    Schultz, H H; Møller, C H; Zemtsovski, M

    2017-01-01

    survival as well as CLAD-free survival was significantly lower with donors ≥55 years. CONCLUSIONS: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking......BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free...... of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking...

  19. Nontuberculous Mycobacterial Disease Is Not a Contraindication to Lung Transplantation in Patients With Cystic Fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tanja; Thomsen, V O

    2013-01-01

    of these died of non-NTM-related causes whereas two developed deep Mycobacterium abscessus wound infections and one was transiently culture negative until M abscessus was reactivated. One patient was subsequently cured; the other two remained on therapy with good performance status. The study supports...... infection poses a contraindication to lung transplantation. All CF patients with current or prior NTM who had undergone lung transplantation were identified. Out of 52 lung transplant patients with CF 9 (17%) had NTM disease. Five patients had known infection at the time of transplantation. Two...

  20. Quality of life before and after lung transplantation in patients with emphysema versus other indications

    NARCIS (Netherlands)

    TenVergert, EM; Vermeulen, KM; van Enckevort, PJ

    2001-01-01

    Whether lung transplantation improves Health-related Quality of Life in patients with emphysema and other end-stage lung diseases before and after lung transplantation was examined. Between 1992 and 1999, 23 patients with emphysema and 19 patients with other indications completed self-administered

  1. A longitudinal study of patients' symptoms before and during the first year after lung transplantation.

    Science.gov (United States)

    Lanuza, Dorothy M; Lefaiver, Cheryl A; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta

    2012-01-01

    Lung transplantation provides a viable option for survival of end-stage respiratory disease. In addition to prolonging survival, there is considerable interest in improving patient-related outcomes such as transplant recipients' symptom experiences. A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000 and 2005. The transplant symptom inventory was administered before and at one, three, six, nine, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. After lung transplantation, significant (p<0.05) improvements were reported for the most frequently occurring and most distressing pre-transplant symptoms (e.g., shortness of breath with activity). Marked increases in the frequency and distress of new symptoms such as tremors were also reported. Patterns of symptom frequency and distress varied with time since transplant. The findings provide data-based information that can be used to inform pre- and post-transplant patient education and also help caregivers anticipate a general time frame for symptom changes to prevent or minimize symptoms and their associated distress. In addition, symptoms are described, using an innovative method of illustration which shows "at-a-glance" change or lack of change in patients' symptoms from pre- to post-lung transplant. © 2012 John Wiley & Sons A/S.

  2. Pulmonary nodules and masses in lung transplant recipients: clinical and CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Morla, Olivier; Liberge, Renan; Arrigoni, Pierre Paul; Frampas, Eric [Service de Radiologie Centrale, C.H.U. Hotel Dieu, Nantes (France)

    2014-09-15

    The purpose of this study was to review the clinical and CT findings of pulmonary nodules and masses in lung transplant recipients and to determine distinguishing features among the various aetiologies. This retrospective study included 106 lung transplant recipients who had a chest CT performed over a 7-year period in a single institution. Twenty-four cases of pulmonary nodules and masses were observed on CT. Among the single lesions, three (50 %) were due to infections, one (17 %) to organizing pneumonia, and two (33 %) remained of undetermined origin. Among the multiple lesions, 14 (78 %) were due to infection, three to post-transplant lymphoproliferative disorder (17 %), and one to bronchogenic carcinoma (5 %). The two main microorganisms were P. aeruginosa and Aspergillus spp. Among 12 solid nodules > 1 cm, four (33 %) were due to malignancy: three post-transplant lymphoproliferative disorders (25 %), and one bronchogenic carcinoma (8 %). Among five cavitary nodules four (80 %) were due to aspergillosis. Infection is the most frequent aetiology of pulmonary nodules and masses in lung transplant recipients, but other causes such as post-transplant lymphoproliferative disorder, bronchogenic carcinoma, or organizing pneumonia should be considered. (orig.)

  3. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

    Science.gov (United States)

    Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

    2008-06-01

    Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

  4. Superficial herpes simplex virus wound infection following lung transplantation.

    Science.gov (United States)

    Karolak, Wojtek; Wojarski, Jacek; Zegleń, Sławomir; Ochman, Marek; Urlik, Maciej; Hudzik, Bartosz; Wozniak-Grygiel, Elzbieta; Maruszewski, Marcin

    2017-08-01

    Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Aortic homograft for pulmonary artery augmentation in single lung transplantation.

    Science.gov (United States)

    Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda

    2005-06-01

    We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.

  6. Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

    Science.gov (United States)

    Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

    2017-11-01

    Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status

  7. Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review.

    Science.gov (United States)

    Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

    2010-06-01

    Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

  8. A longitudinal study of patients’ symptoms before and during the first year after lung transplantation

    Science.gov (United States)

    Lanuza, Dorothy M.; Lefaiver, Cheryl A.; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta

    2012-01-01

    Background Lung transplantation provides a viable option for survival of end-stage respiratory disease. In addition to prolonging survival, there is considerable interest in improving patient-related outcomes such as transplant recipients’ symptom experiences. Methods A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000–2005. The Transplant Symptom Inventory (TSI) was administered before and at 1, 3, 6, 9, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. Results After lung transplantation, significant (p<.05) improvements were reported for the most frequently occurring and most distressing pre-transplant symptoms (e.g., shortness of breath with activity). Marked increases in the frequency and distress of new symptoms, such as tremors were also reported. Patterns of symptom frequency and distress varied with the time since transplant. Conclusion The findings provide data-based information that can be used to inform pre- and post-transplant patient education and also help caregivers anticipate a general time frame for symptom changes in order to prevent or minimize symptoms and their associated distress. In addition, symptoms are described, using an innovative method of illustration which shows “at-a-glance” changes or lack of changes in patients’ symptoms from pre- to post-lung transplant. PMID:22988999

  9. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients

    Energy Technology Data Exchange (ETDEWEB)

    Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, Jose da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno, E-mail: iraigiacomelli@gmail.com [Complexo Hospitalar Santa Casa de Porto Alegre, RS (Brazil)

    2017-07-15

    Objective: Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. Methods: From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. Results: We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. Conclusions: The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease. (author)

  10. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients.

    Science.gov (United States)

    Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, José da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno

    2017-01-01

    Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

  11. Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

    Science.gov (United States)

    Shafii, Alexis E; Mason, David P; Brown, Chase R; Vakil, Nakul; Johnston, Douglas R; McCurry, Kenneth R; Pettersson, Gosta B; Murthy, Sudish C

    2012-01-01

    Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

  12. Antibody Desensitization Therapy in Highly Sensitized Lung Transplant Candidates

    Science.gov (United States)

    Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.

    2015-01-01

    As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831

  13. Lung transplant recipients holding companion animals: impact on physical health and quality of life.

    Science.gov (United States)

    Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

    2006-02-01

    Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

  14. Removal of metallic tracheobronchial stents in lung transplantation with flexible bronchoscopy

    Directory of Open Access Journals (Sweden)

    Fruchter Oren

    2010-09-01

    Full Text Available Abstract Background Airway complications are among the most challenging problems after lung transplantation, and Self-Expandable Metallic Stents (SEMS are used to treat airway complications such as stenosis or malacia at the bronchial anastomosis sites. Several transplantation centers are reluctant to use SEMS since their removal is sometimes needed and usually requires the use of rigid bronchoscopy under general anesthesia. The objective of the current report is to describe our experience in SEMS retrieval by flexible bronchoscopy under conscious sedation. Methods A retrospective review was done of patients requiring tracheobronchial stent placement after lung transplantation in which the SEMS had to be removed. The retrieval procedure was done by flexible bronchoscopy on a day-care ambulatory basis. Results Between January 2004 and January 2010, out of 305 lung transplantation patients, 24 (7.8% underwent SEMS placement. Indications included bronchial stenosis in 20 and bronchomalacia in 4. In six patients (25% the SEMS had to be removed due to excessive granulation tissue formation and stent obstruction. The average time from SEMS placement to retrieval was 30 months (range 16-48 months. The stent was completely removed in five patients and partially removed in one patient; no major complications were encountered, and all patients were discharged within 3 hours of the procedure. In all procedures, new SEMS was successfully re-inserted thereafter. Conclusions The retrieval of SEMS in patients that underwent lung transplantation can be effectively and safely done under conscious sedation using flexible bronchoscopy on a day-care basis, this observation should encourage increasing usage of SEMS in highly selected patients.

  15. Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates.

    Science.gov (United States)

    Kim, Miae; Townsend, Keri R; Wood, Isabelle G; Boukedes, Steve; Guleria, Indira; Gabardi, Steven; El-Chemaly, Souheil; Camp, Phillip C; Chandraker, Anil K; Milford, Edgar L; Goldberg, Hilary J

    2014-05-15

    The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known. We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation. We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January 2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays. Among 224 patients, 34% had anti-HLA antibodies at mean fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to receive transplants than patients without any anti-HLA antibodies (group I) (45.5 vs. 67.7%, P = 0.005). Wait time to transplant was longer in group III than group I, although this difference did not meet statistical significance, and waitlist mortality was similar. Among transplant recipients, antibody-mediated rejection (AMR) was more frequent in group III than in group II (20% vs. 0%, P = 0.01) or group I (6.3%, P = 0.05). The presence of anti-HLA antibodies at the high MFI threshold (>3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients.

  16. An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

    NARCIS (Netherlands)

    Ruttens, David; Verleden, Stijn E.; Bijnens, Esmee M.; Winckelmans, Ellen; Gottlieb, Jens; Warnecke, Gregor; Meloni, Federica; Morosini, Monica; van der Bij, Wim; Verschuuren, Erik A.; Sommerwerck, Urte; Weinreich, Gerhard; Kamler, Markus; Roman, Antonio; Gomez-Olles, Susana; Berastegui, Cristina; Benden, Christian; Holm, AreMartin; Iversen, Martin; Schultz, Hans Henrik; Luijk, Bart; Oudijk, Erik-Jan; Erp, Johanna M. Kwakkel-van; Jaksch, Peter; Klepetko, Walter; Kneidinger, Nikolaus; Neurohr, Claus; Corris, Paul. A.; Fisher, Andrew J.; Lordan, James; Meachery, Gerard; Piloni, Davide; Vandermeulen, Elly; Bellon, Hannelore; Hoffmann, Barbara; Vienneau, Danielle; Hoek, Gerard; de Hoogh, Kees; Nemery, Benoit; Verleden, Geert M.; Vos, Robin; Nawrot, Tims.; Vanaudenaerde, Bart M.

    2017-01-01

    Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10

  17. Heart rate variability and baroreflex sensitivity in bilateral lung transplant recipients.

    Science.gov (United States)

    Fontolliet, Timothée; Gianella, Pietro; Pichot, Vincent; Barthélémy, Jean-Claude; Gasche-Soccal, Paola; Ferretti, Guido; Lador, Frédéric

    2018-01-09

    The effects of lung afferents denervation on cardiovascular regulation can be assessed on bilateral lung transplantation patients. The high-frequency component of heart rate variability is known to be synchronous with breathing frequency. Then, if heart beat is neurally modulated by breathing frequency, we may expect disappearance of high frequency of heart rate variability in bilateral lung transplantation patients. On 11 patients and 11 matching healthy controls, we measured R-R interval (electrocardiography), blood pressure (Portapres ® ) and breathing frequency (ultrasonic device) in supine rest, during 10-min free breathing, 10-min cadenced breathing (0·25 Hz) and 5-min handgrip. We analysed heart rate variability and spontaneous variability of arterial blood pressure, by power spectral analysis, and baroreflex sensitivity, by the sequence method. Concerning heart rate variability, with respect to controls, transplant recipients had lower total power and lower low- and high-frequency power. The low-frequency/high-frequency ratio was higher. Concerning systolic, diastolic and mean arterial pressure variability, transplant recipients had lower total power (only for cadenced breathing), low frequency and low-frequency/high-frequency ratio during free and cadenced breathing. Baroreflex sensitivity was decreased. Denervated lungs induced strong heart rate variability reduction. The higher low-frequency/high-frequency ratio suggested that the total power drop was mostly due to high frequency. These results support the hypothesis that neural modulation from lung afferents contributes to the high frequency of heart rate variability. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  18. A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation.

    Science.gov (United States)

    Chaddha, Udit; Patil, Pradnya D; Omar, Ashraf; Walia, Rajat; Panchabhai, Tanmay S

    2018-06-01

    A 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1 week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8 weeks earlier were normal. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

    Science.gov (United States)

    Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

    2017-03-01

    Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

    Directory of Open Access Journals (Sweden)

    Dromer Claire

    2009-11-01

    Full Text Available Abstract Background Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen. Case presentation A case of pulmonary infection with bacteremia due to Tsukamurella tyrosinosolvens in a 54-year old man who underwent a double lung transplantation four years previously is presented. Conclusion The identification by conventional biochemical assays was unsuccessful and hsp gene sequencing was used to identify Tsukamurella tyrosinosolvens.

  1. Computed tomography findings of postoperative complications in lung transplantation; Achados tomograficos nas complicacoes pos-operatorias do transplante pulmonar

    Energy Technology Data Exchange (ETDEWEB)

    Hochhegger, Bruno; Irion, Klaus Loureiro; Marchiori, Edson; Bello, Rodrigo; Moreira, Jose; Camargo, Jose Jesus [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Postgraduate Program in Respiratory Sciences; Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Postgraduate Program in Radiological Sciences], e-mail: brunorgs@mail.ufsm.br

    2009-03-15

    Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis. (author)

  2. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients

    Directory of Open Access Journals (Sweden)

    Irai Luis Giacomelli

    Full Text Available ABSTRACT Objective: Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. Methods: From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. Results: We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%; cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%; and mediastinal lymph node enlargement (in 15.7%. Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. Conclusions: The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

  3. Transplantation of hamster lung lesions induced by 239PuO2 or benz(a)pyrene

    International Nuclear Information System (INIS)

    McDonald, K.E.; Sanders, C.L.

    1980-01-01

    None(0%) of 1000 recipients of lung lesions for 239 PuO 2 -exposed hamsters that were transplanted into other hamsters' cheek pouches, developed tumors, whereas 90% of transplants from benz(a)pyrene-induced lung lesions were malignant

  4. Association Between Donor MBL Promoter Haplotype and Graft Survival and the Development of BOS After Lung Transplantation

    NARCIS (Netherlands)

    Munster, Janna M.; van der Bij, Wim; Breukink, Myrte B.; van der Steege, Gerrit; Zuurman, Mike W.; Hepkema, Bouke G.; Verschuuren, Erik A. M.; van Son, Willem J.; Seelen, Marc A. J.

    2008-01-01

    Background. Lung transplantation is a well accepted therapy for end-stage lung disease, despite high mortality rates. Mortality after transplantation is mainly caused by allograft failure in the first years after transplantation. Mannose binding lectin (MBL), a recognition molecule of innate

  5. A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

    Science.gov (United States)

    van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

    2017-10-01

    The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    Science.gov (United States)

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

  7. Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

    Science.gov (United States)

    Herrera, Sabina; Husain, Shahid

    2018-05-21

    The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

  8. Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

    Science.gov (United States)

    Markelić, I; Jakopović, M; Klepetko, W; Džubur, F; Hećimović, A; Makek, M J; Samaržija, M; Dugac, A V

    2017-01-01

    A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

  9. A simple technique can reduce cardiopulmonary bypass use during lung transplantation

    Directory of Open Access Journals (Sweden)

    Marcos N. Samano

    2016-04-01

    Full Text Available Cardiopulmonary bypass causes an inflammatory response and consumption of coagulation factors, increasing the risk of bleeding and neurological and renal complications. Its use during lung transplantation may be due to pulmonary hypertension or associated cardiac defects or just for better exposure of the pulmonary hilum. We describe a simple technique, or open pericardium retraction, to improve hilar exposure by lifting the heart by upward retraction of the pericardial sac. This technique permits lung transplantation without cardiopulmonary bypass when bypass use is recommended only for better exposure.

  10. Pulmão e transplante renal Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

  11. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Nathan C. Bahr

    2015-01-01

    Full Text Available Background. De novo and donor-derived invasive fungal infections (IFIs contribute to morbidity and mortality in solid organ transplant (SOT recipients. Reporting of donor-derived IFIs (DDIFIs to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

  12. Primary Nocardia Infection Causing a Fluorodeoxyglucose-Avid Right Renal Mass in a Redo Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Sreeja Biswas Roy

    2018-01-01

    Full Text Available Immunosuppression after lung transplantation may increase susceptibility to opportunistic infection and is associated with early and delayed deaths in lung transplant recipients. Factors that may predispose lung transplant recipients to opportunistic bacterial and fungal infections include prolonged corticosteroid use, renal impairment, treatment of acute rejection, and post-transplant diabetes mellitus. We present a unique case of a 63-year-old woman with diabetes mellitus who underwent redo lung transplantation. Three years after her right-sided single redo lung transplant, she presented with right-sided abdominal pain, nausea, and vomiting. Upon examination, computed tomography showed a 4.5 × 3.3 cm heterogeneous, enhancing right renal mass with a patent renal vein. Magnetic resonance imaging confirmed a T1/T2 hypointense, diffusion-restricting, right mid-renal mass that was fluorodeoxyglucose-avid on positron emission tomography. We initially suspected primary renal cell carcinoma. However, after a right nephrectomy, no evidence of neoplasia was observed; instead, a renal abscess containing filamentous bacteria was noted, raising suspicion for infection of the Nocardia species. Special stains confirmed a diagnosis of Nocardia renal abscess. Computed tomography of the chest and brain revealed no lesions consistent with infection. We initiated a long-term therapeutic regimen of anti-Nocardia therapy with imipenem and trimethoprim-sulfamethoxazole.

  13. Forma acelerada da fibrose pulmonar idiopática no pulmão nativo após transplante pulmonar unilateral Accelerated form of interstitial pulmonary fibrosis in the native lung after single lung transplantation

    Directory of Open Access Journals (Sweden)

    Rogério Rufino

    2007-12-01

    Full Text Available Relatamos o caso de um paciente de 56 anos submetido a transplante pulmonar unilateral esquerdo em decorrência de fibrose pulmonar idiopática (FPI. No pós-operatório imediato, sob intensa imunossupressão, houve progressão rápida da FPI no pulmão nativo direito, confirmada pela biópsia pulmonar videotoracoscópica, necessitando de ventilação mecânica durante 104 dias até a realização de outro transplante pulmonar à direita. Obteve alta hospitalar após o 26º dia do segundo pós-operatório.We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF. Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation (MV, the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.

  14. Clinical characteristics of cystic fibrosis patients prior to lung transplantation: An international comparison between Canada and the United States.

    Science.gov (United States)

    Quon, Bradley S; Sykes, Jenna; Stanojevic, Sanja; Marshall, Bruce C; Petren, Kristofer; Ostrenga, Josh; Fink, Aliza; Elbert, Alexander; Faro, Albert; Goss, Christopher H; Stephenson, Anne L

    2018-03-01

    Cystic fibrosis (CF) patients from Canada have better-reported post-lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. Population-based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post-transplant survival. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared...... the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung...... transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...

  16. Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia settings).

    Science.gov (United States)

    Rabanal, J M; Real, M I; Williams, M

    2014-10-01

    Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  17. Adherence to immunosuppression in adult lung transplant recipients : Prevalence and risk factors

    NARCIS (Netherlands)

    Bosma, Otto H.; Vermeulen, Karin M.; Verschuuren, Erik A.; Erasmus, Michiel E.; van der Bij, Wim

    2011-01-01

    BACKGROUND: Adherence to medication is a favourable with regard to survival after kidney, heart and liver transplantation. Little is known about adherence to medication in lung transplant recipients. To determine the prevalence of adherence and identify risk factors of non-adherence (NA) we

  18. High emergency organ allocation rule in lung transplantation: a simulation study.

    Science.gov (United States)

    Riou, Julien; Boëlle, Pierre-Yves; Christie, Jason D; Thabut, Gabriel

    2017-10-01

    The scarcity of suitable organ donors leads to protracted waiting times and mortality in patients awaiting lung transplantation. This study aims to assess the short- and long-term effects of a high emergency organ allocation policy on the outcome of lung transplantation. We developed a simulation model of lung transplantation waiting queues under two allocation strategies, based either on waiting time only or on additional criteria to prioritise the sickest patients. The model was informed by data from the United Network for Organ Sharing. We compared the impact of these strategies on waiting time, waiting list mortality and overall survival in various situations of organ scarcity. The impact of a high emergency allocation strategy depends largely on the organ supply. When organ supply is sufficient (>95 organs per 100 patients), it may prevent a small number of early deaths (1 year survival: 93.7% against 92.4% for waiting time only) without significant impact on waiting times or long-term survival. When the organ/recipient ratio is lower, the benefits in early mortality are larger but are counterbalanced by a dramatic increase of the size of the waiting list. Consequently, we observed a progressive increase of mortality on the waiting list (although still lower than with waiting time only), a deterioration of patients' condition at transplant and a decrease of post-transplant survival times. High emergency organ allocation is an effective strategy to reduce mortality on the waiting list, but causes a disruption of the list equilibrium that may have detrimental long-term effects in situations of significant organ scarcity.

  19. Use of telehealth technology for home spirometry after lung transplantation: a randomized controlled trial.

    Science.gov (United States)

    Sengpiel, Juliane; Fuehner, Thomas; Kugler, Christiane; Avsar, Murat; Bodmann, Isabelle; Boemke, Annelies; Simon, Andre; Welte, Tobias; Gottlieb, Jens

    2010-12-01

    Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry. To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients. Single-center prospective randomized controlled trial. Intervention-Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages. Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point. Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P = .73). Median time to first consultation (P = .60) and frequency of consultation (P = .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0-4.0) than in the home spirometry alone group (4.0; range, 2.0-6.0; P = .04). Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

  20. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease.

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; Boer, W.; Timens, W.; Middeldorp, J.M.; The, T.H.

    2003-01-01

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  1. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; de Boer, W; Timens, W; Middeldorp, J; The, TH

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  2. Recurrence of sarcoid granulomas in lung transplant recipients is common and does not affect overall survival

    DEFF Research Database (Denmark)

    Schultz, Hans Henrik Lawaetz; Andersen, Claus Bøgelund; Steinbrüchel, D

    2014-01-01

    Background: Sarcoidosis represents 2,5% of all indications for lung transplantation and criteria are generally assumed to be the same as for pulmonary fibrosis. Recurrence of granulomas in transplanted lungs has earlier been proved to derive from recipient immune cells, but its role in relation t...

  3. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    Science.gov (United States)

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. No survival benefit to gaining private health insurance coverage for post-lung transplant care in adults with cystic fibrosis.

    Science.gov (United States)

    Tumin, Dmitry; Foraker, Randi E; Tobias, Joseph D; Hayes, Don

    2016-03-01

    The use of public insurance is associated with diminished survival in patients with cystic fibrosis (CF) following lung transplantation. No data exist on benefits of gaining private health insurance for post-transplant care among such patients previously using public insurance. The United Network for Organ Sharing database was used to identify first-time lung transplant recipients participating in Medicare or Medicaid, diagnosed with CF, and transplanted between 2005 and 2015. Survival outcomes were compared between recipients gaining private insurance after transplantation and those maintaining public coverage throughout follow-up. Since implementation of the lung allocation score, 575 adults with CF received lung transplantation funded by Medicare or Medicaid and contributed data on insurance status post-transplant. There were 128 (22%) patients who gained private insurance. Multivariable analysis of time-varying insurance status found no survival benefit of gaining private insurance (HR = 0.822; 95% CI = 0.525, 1.286; p = 0.390). Further analysis demonstrated that resuming public insurance coverage was detrimental, relative to gaining and keeping private insurance (HR = 2.315; 95% CI = 1.020, 5.258; p = 0.045). Survival disadvantages of lung transplant recipients with CF who have public health insurance were not ameliorated by a switch to private coverage for post-transplant care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. N-acetylcysteine-pretreated human embryonic mesenchymal stem cell administration protects against bleomycin-induced lung injury.

    Science.gov (United States)

    Wang, Qiao; Zhu, Hong; Zhou, Wu-Gang; Guo, Xiao-Can; Wu, Min-Juan; Xu, Zhen-Yu; Jiang, Jun-feng; Shen, Ce; Liu, Hou-Qi

    2013-08-01

    The transplantation of mesenchymal stem cells (MSCs) has been reported to be a promising approach in the treatment of acute lung injury. However, the poor efficacy of transplanted MSCs is one of the serious handicaps in the progress of MSC-based therapy. Therefore, the purpose of this study was to investigate whether the pretreatment of human embryonic MSCs (hMSCs) with an antioxidant, namely N-acetylcysteine (NAC), can improve the efficacy of hMSC transplantation in lung injury. In vitro, the antioxidant capacity of NAC-pretreated hMSCs was assessed using intracellular reactive oxygen species (ROS) and glutathione assays and cell adhesion and spreading assays. In vivo, the therapeutic potential of NAC-pretreated hMSCs was assessed in a bleomycin-induced model of lung injury in nude mice. The pretreatment of hMSCs with NAC improved antioxidant capacity to defend against redox imbalances through the elimination of cellular ROS, increasing cellular glutathione levels, and the enhancement of cell adhesion and spreading when exposed to oxidative stresses in vitro. In addition, the administration of NAC-pretreated hMSCs to nude mice with bleomycin-induced lung injury decreased the pathological grade of lung inflammation and fibrosis, hydroxyproline content and numbers of neutrophils and inflammatory cytokines in bronchoalveolar lavage fluid and apoptotic cells, while enhancing the retention and proliferation of hMSCs in injured lung tissue and improving the survival rate of mice compared with results from untreated hMSCs. The pretreatment of hMSCs with NAC could be a promising therapeutic approach to improving cell transplantation and, therefore, the treatment of lung injury.

  6. Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.

    Directory of Open Access Journals (Sweden)

    Joshua M Diamond

    Full Text Available Primary graft dysfunction (PGD is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE.There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40% and 47 non-PGD subjects (59% received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF. Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03. The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02; there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD (p = 0.9.Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

  7. Biomarkers for the prediction of the bronchiolitis obliterans syndrome after lung transplantation

    NARCIS (Netherlands)

    Paantjens, A.W.M.

    2011-01-01

    The main limitation for overall survival after lung transplantation (LTx) is the development of chronic rejection, which is represented by the bronchiolitis obliterans syndrome (BOS). The diagnosis BOS is based on lung function testing, however, it is a surrogate marker. And because BOS is an

  8. Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

    Science.gov (United States)

    Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

    2016-01-01

    Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Effective Prolonged Therapy with Voriconazole in a Lung Transplant Recipient with Spondylodiscitis Induced by Scedosporium apiospermum

    OpenAIRE

    Luijk, B.; Ekkelenkamp, M. B.; De Jong, P. A.; Kwakkel-van Erp, J. M.; Grutters, J. C.; van Kessel, D. A.; van de Graaf, E. A.

    2011-01-01

    Scedosporium/Pseudallescheria species are frequently seen in cystic fibrosis patients. However, disseminated forms after lung transplantation in these patients are rarely seen, but often with poor outcome. In this case report we describe a lung transplant recipient with cystic fibrosis who developed a spondylodiscitis that was caused by Scedosporium apiospermu...

  10. Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

    Science.gov (United States)

    Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy

    2015-10-15

    Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

  11. Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

    Science.gov (United States)

    Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

    2016-01-01

    The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

    Science.gov (United States)

    Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

    2016-01-01

    Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

  13. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

    Directory of Open Access Journals (Sweden)

    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  14. Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation.

    Science.gov (United States)

    Baste, Jean-Marc; Gay, Arnaud; Smail, Hassiba; Noël, Romain; Bubenheim, Michael; Begueret, Hugues; Morin, Jean-Paul; Litzler, Pierre-Yves

    2015-01-01

    Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture. A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours). No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion. The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults.

  15. Ethical and equity issues in lung transplantation and lung volume reduction surgery.

    Science.gov (United States)

    Glanville, A R

    2006-01-01

    New medical and scientific disciplines are often developed in haste with rampant enthusiasm and scant regard for the balance between action and thoughtful deliberation. Driven by the desire to prolong life and provide a better quality of life for desperately sick individuals, the twin modalities of lung transplantation and lung volume reduction therapy have only just reached their majority. Both are invested with the capacity to help and to harm so it is right to consider carefully their ethical and equitable distribution. Much has been learned in the last 20 years to assist in these deliberations. First, how can we ensure equity of access to transplant services and equality of outcomes? How do we balance resource allocation of a precious and scarce resource with individual recipient needs? Does the concept of distributive justice prevail in our daily work in this field? How do we honour the donor and their family? How do we as practitioners avoid ethical dilemmas related to personal bias and justifiable reward for services rendered? Finally, how do we learn to incorporate ethical forethought and planning guided by experts in the area into everyday behaviour?

  16. Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

    Science.gov (United States)

    Posner, S; Zheng, J; Wood, R K; Shimpi, R A; Hartwig, M G; Chow, S-C; Leiman, D A

    2018-05-01

    Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

  17. Improved quality of life after lung transplantation in individuals with cystic fibrosis

    NARCIS (Netherlands)

    Vermeulen, KM; van der Bij, W; Erasmus, ME; Duiverman, EJ; Koeter, GH; TenVergert, EM

    The aim of the present study was to assess the effect of lung transplantation (LgTX) on health-related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non-CF). HRQL was assessed before transplantation in a group of 32 CIF patients

  18. Influence of early neurological complications on clinical outcome following lung transplant.

    Science.gov (United States)

    Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

    2017-01-01

    Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

  19. Interaction between Pseudomonas and CXC Chemokines Increases Risk of Bronchiolitis Obliterans Syndrome and Death in Lung Transplantation

    Science.gov (United States)

    Wang, Xiaoyan; Weigt, S. Sam; Palchevskiy, Vyacheslav; Lynch, Joseph P.; Ross, David J.; Kubak, Bernard M.; Saggar, Rajan; Fishbein, Michael C.; Ardehali, Abbas; Li, Gang; Elashoff, Robert; Belperio, John A.

    2013-01-01

    Rationale: Pseudomonas aeruginosa is the most commonly isolated gram-negative bacterium after lung transplantation and has been shown to up-regulate glutamic acid–leucine–arginine–positive (ELR+) CXC chemokines associated with bronchiolitis obliterans syndrome (BOS), but the effect of pseudomonas on BOS and death has not been well defined. Objectives: To determine if the influence of pseudomonas isolation and ELR+ CXC chemokines on the subsequent development of BOS and the occurrence of death is time dependent. Methods: A three-state model was developed to assess the likelihood of transitioning from lung transplant (state 1) to BOS (state 2), from transplant (state 1) to death (state 3), and from BOS (state 2) to death (state 3). This Cox semi-Markovian approach determines state survival rates and cause-specific hazards for movement from one state to another. Measurements and Main Results: The likelihood of transition from transplant to BOS was increased by acute rejection, CXCL5, and the interaction between pseudomonas and CXCL1. The pseudomonas effect in this transition was due to infection rather than colonization. Movement from transplant to death was facilitated by pseudomonas infection and single lung transplant. Transition from BOS to death was affected by the length of time in state 1 and by the interactions between any pseudomonas isolation and CXCL5 and aspergillus, either independently or in combination. Conclusions: Our model demonstrates that common post-transplantation events drive movement from one post-transplantation state to another and influence outcomes differently depending upon when after transplantation they occur. Pseudomonas and the ELR+ CXC chemokines may interact to negatively influence lung transplant outcomes. PMID:23328531

  20. 3He-MRI in follow-up of lung transplant recipients

    International Nuclear Information System (INIS)

    Gast, Klaus Kurt; Zaporozhan, Julia; Ley, Sebastian; Biedermann, Alexander; Knitz, Frank; Eberle, Balthasar; Schmiedeskamp, Joerg; Heussel, Claus-Peter; Mayer, Eckhard; Schreiber, Wolfgang Guenter; Thelen, Manfred; Kauczor, Hans-Ulrich

    2004-01-01

    The aim of this study was to evaluate the possible contribution of 3 He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up 3 He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At 3 He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and 3 He-MRI was good, although subjective evaluation of 3 He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The 3 He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by 3 He-MRI. In 2 of these 5 cases, 3 He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that 3 He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies. (orig.)

  1. Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

    Science.gov (United States)

    Verbeek, G L; Myles, P S; Westall, G P; Lin, E; Hastings, S L; Marasco, S F; Jaffar, J; Meehan, A C

    2017-08-01

    Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH 2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg -1 , one-lung ventilation 4 ml.kg -1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH 2 O with 10 cmH 2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO 2 /F I O 2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO 2 /F I O 2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO 2 /F I O 2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO 2 /F I O 2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable

  2. Patient-reported outcome 2 years after lung transplantation: does the underlying diagnosis matter?

    Directory of Open Access Journals (Sweden)

    Ghosh S

    2012-11-01

    Full Text Available Maria Jose Santana,1 David Feeny,2 Sunita Ghosh,3 Dale C Lien41Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; 2Kaiser Permanente Center for Health Research, Portland, OR, USA; 3Cross Cancer Center, University of Alberta, Edmonton, Alberta, Canada; 4University of Alberta Hospital, Edmonton, Alberta, CanadaPurpose: Transplantation has the potential to produce profound effects on survival and health-related quality of life (HRQL. The inclusion of the patient’s perspective may play an important role in the assessment of the effectiveness of lung transplantation. Patient perspectives are assessed by patient-reported outcome measures, including HRQL measures. We describe how patients’ HRQL among different diagnosis groups can be used by clinicians to monitor and evaluate the outcomes associated with transplantation.Methods: Consecutive lung transplant recipients attending the lung transplant outpatient clinic in a tertiary institution completed the 15-item Health Utilities Index (HUI questionnaire on a touchscreen computer. The results were available to clinicians at every patient visit. The HUI3 covers a range of severity and comorbidities in eight dimensions of health status. Overall HUI3 scores are on a scale in which dead = 0.00 and perfect health = 1.00; disability categories range from no disability = 1 to severe disability <0.70. Single-attribute and overall HUI3 scores were used to compare patients’ HRQL among different diagnosis groups. Random-effect models with time since transplant as a random variable and age, gender, underlying diagnoses, infections, and broncholitis obliterans syndrome as fixed variables were built to identify determinants of health status at 2-years posttransplantation.Results: Two hundred and fourteen lung transplant recipients of whom 61% were male with a mean age of 52 (19–75 years were included in the study. Chronic obstructive pulmonary disease and cystic fibrosis patients displayed

  3. Median sternotomy for double lung transplantation with cardiopulmonary bypass in seven consecutive patients

    DEFF Research Database (Denmark)

    Kohno, Mitsutomo; Steinbrüchel, Daniel A

    2012-01-01

    We describe our technique of using median sternotomy to perform double lung transplantations with cardiopulmonary bypass. By sparing the respiratory muscles, median sternotomy is probably less invasive and preserves lung function. Furthermore, it causes less long-term discomfort than intercostal...

  4. A human lung xenograft mouse model of Nipah virus infection.

    Directory of Open Access Journals (Sweden)

    Gustavo Valbuena

    2014-04-01

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

  5. SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Batenburg, JJ; Haagsman, HP; Oetomo, SB; Prop, J

    2002-01-01

    Background. The function of pulmonary surfactant is affected by lung transplantation, contributing to impaired lung transplant function. A decreased amount of surfactant protein-A (SP-A) after reperfusion is believed to contribute to the impaired surfactant function. Surfactant treatment has been

  6. Evaluation of 99Tcm nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model

    International Nuclear Information System (INIS)

    Larcos, G.; McLarty, A.J.; McGregor, C.G.A.; Brown, M.L.; Hung, J.C.; O'Connor, M.K.; Tazelaar, H.D.

    1993-01-01

    Acute rejection is an important cause of graft failure in single lung transplantation, however, current noninvasive tests are neither sensitive nor specific for this diagnosis. The aim of this study was to determine whether 99 Tc m -labelled human nonspecific polyclonal IgG ( 99 Tc m -IgG) may serve as a marker for acute pulmonary rejection following allotransplantation in a dog model. Seventeen mongrel dogs were studied, including four controls and thirteen dogs which underwent surgery [right autotransplant recipient right unmodified allotransplant recipient, and right immunosuppressed allotransplant recipient]. At 6 days following surgery, all dogs received 67 Ga-citrate and 99 Tc m -IgG. Two days later all dogs were sacrified. Post-mortem examination revealed acute lung rejection in nine animals. No significant difference was found in the percentage uptake of both 99 Tc m -IgG and 67 Ga-citrate per gram of tissue between rejecting and nonrejecting transplanted lungs. In cases of moderate to severe rejection, only 67 Ga-citrate showed a significant difference in uptake between rejecting and contralateral native lungs, respectively. We conclude that 99 Tc m -IgG does not accurately identify acute lung rejection in the early postoperative period. (author)

  7. Heart and lung organ offer acceptance practices of transplant programs are associated with waitlist mortality and organ yield.

    Science.gov (United States)

    Wey, Andrew; Valapour, Maryam; Skeans, Melissa A; Salkowski, Nicholas; Colvin, Monica; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-19

    Variation in heart and lung offer acceptance practices may affect numbers of transplanted organs and create variability in waitlist mortality. To investigate these issues, offer acceptance ratios, or adjusted odds ratios, for heart and lung transplant programs individually and for all programs within donation service areas (DSAs) were estimated using offers from donors recovered July 1, 2016-June 30, 2017. Logistic regressions estimated the association of DSA-level offer acceptance ratios with donor yield and local placement of organs recovered in the DSA. Competing risk methodology estimated the association of program-level offer acceptance ratios with incidence and rate of waitlist removals due to death or becoming too sick to undergo transplant. Higher DSA-level offer acceptance was associated with higher yield (odds ratios [ORs]: lung, 1.04 1.11 1.19 ; heart, 1.09 1.21 1.35 ) and more local placement of transplanted organs (ORs: lung, 1.01 1.12 1.24 ; heart, 1.47 1.69 1.93 ). Higher program-level offer acceptance was associated with lower incidence of waitlist removal due to death or becoming too sick to undergo transplant (hazard ratios [HRs]: heart, 0.80 0.86 0.93 ; lung, 0.67 0.75 0.83 ), but not with rate of waitlist removal (HRs: heart, 0.91 0.98 1.06 ; lung, 0.89 0.99 1.10 ). Heart and lung offer acceptance practices affected numbers of transplanted organs and contributed to program-level variability in the probability of waitlist mortality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Restrictive allograft syndrome after lung transplantation: new radiological insights

    Energy Technology Data Exchange (ETDEWEB)

    Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A.; Wever, Walter de [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Verleden, Stijn E.; Vos, Robin; Verleden, Geert M. [University Hospitals Leuven, Department of Pneumology, Leuven (Belgium)

    2017-07-15

    To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. (orig.)

  9. Optimal Route for Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation to Protect Against Neonatal Hyperoxic Lung Injury: Gene Expression Profiles and Histopathology.

    Directory of Open Access Journals (Sweden)

    Dong Kyung Sung

    Full Text Available The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t. versus intravenous (i.v. MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i.t. (5×10(5 or i.v. (2×10(6 route at postnatal day (P 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV, indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both i.t. and i.v. transplantations. However, i.t. administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to i.v. administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the i.t. group, but not in the i.v. group. Although the i.t. group received only one fourth of the number of MSCs that the i.v. group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the i.t. group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the i.t. group, but not in the i.v. group. Thus

  10. Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.

    Science.gov (United States)

    Glorion, M; Polard, V; Favereau, F; Hauet, T; Zal, F; Fadel, E; Sage, E

    2017-10-25

    We describe the results of adding a new biological agent HEMO 2 life ® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO 2 life ® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex ® ) was compared with Perfadex ® associated with HEMO 2 life ® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO 2 life ® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p preservation improves early graft function after prolonged cold ischemia in lung transplantation.

  11. Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

    Science.gov (United States)

    Cantu, Edward; Diamond, Joshua M; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J; Kawut, Steven M; Palmer, Scott M; Snyder, Laurie D; Hartwig, Matthew G; Lama, Vibha N; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B; Bellamy, Scarlett L; Christie, Jason D

    2018-01-15

    Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.

  12. Increased proximal acid reflux is associated with early readmission following lung transplantation.

    Science.gov (United States)

    Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

    2016-02-01

    Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

  13. Guardians of 'the gift': the emotional challenges of heart and lung transplant professionals in Denmark.

    Science.gov (United States)

    Jensen, Anja M B

    2017-04-01

    This paper deals with the emotional challenges encountered by doctors and nurses caring for heart and lung transplant patients. Organ transplantation enables body parts from the dead to become usable in patients with no other life-saving option. These exchanges are not possible without transplant professionals carefully selecting, guiding and interacting with organ recipients before, during and after the transplant. Based on anthropological fieldwork at a Danish heart and lung transplant unit, the paper explores how doctors and nurses experience and handle the emotional challenges of their working life. By focusing on the everyday life of the transplant unit which, contrary to public understanding of transplant miracles, is sometimes characterised by sad cases and devastation, this paper argues that transplant professionals operate in the presence of death. Medically and emotionally they are at risk. They must take the difficult decisions of whether to admit critically ill patients onto the organ waiting list; face the distress of post-transplant sufferings and deaths; and deal with organ recipients who do not behave according to post-transplant recommendations. Drawing on a familiar metaphor for donated organs, it is suggested that transplant doctors and nurses are 'guardians of the gift'. Attention to the emotional burdens and rewards of this particular position enables new understandings of the practices of transplant medicine, of gift exchange theory, and of the role of emotion in medical practice.

  14. Effects of early surfactant treatment persisting for one week after lung transplantation in rats

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Haagsman, HP; Oetomo, SB; Prop, J

    We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by

  15. Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study.

    Directory of Open Access Journals (Sweden)

    Onno M Mets

    Full Text Available Lung disease in cystic fibrosis (CF involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs.In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined.All CF patients showed emphysema on histological examination: 3/20 (15% showed mild, 15/20 (75% moderate and 2/20 (10% severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03 and visual emphysema score (p = 0.001. CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively.In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.

  16. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

    Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

  17. Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds.

    Science.gov (United States)

    Wu, Tsai-Jung; Tzeng, Yan-Kai; Chang, Wei-Wei; Cheng, Chi-An; Kuo, Yung; Chien, Chin-Hsiang; Chang, Huan-Cheng; Yu, John

    2013-09-01

    Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

  18. Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

    International Nuclear Information System (INIS)

    Gast, Klaus K.; Biedermann, Alexander; Herweling, Annette; Schreiber, Wolfgang G.; Schmiedeskamp, Joerg; Mayer, Eckhard; Heussel, Claus P.; Markstaller, Klaus; Eberle, Balthasar; Kauczor, Hans-Ulrich

    2008-01-01

    Oxygen-sensitive 3 He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO 2 ) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3 He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acquired on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3 He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO 2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3 He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3 He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients. (orig.)

  19. Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality.

    Science.gov (United States)

    Sher, Yelizaveta; Mooney, Joshua; Dhillon, Gundeep; Lee, Roy; Maldonado, José R

    2017-05-01

    Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized. The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, and one-year mortality. Thirty-six percent of patients developed early-onset, and 44% developed ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first postoperative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (P=.001), ICU LOS (Pdelirium was associated with longer ICU (Pdelirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55). Delirium is common after lung transplant surgery and associated with increased hospital resources. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings

    International Nuclear Information System (INIS)

    Diederich, S.; Scadeng, M.; Flower, C.D.R.; Dennis, C.; Stewart, S.

    1998-01-01

    The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a ''halo'' of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances. (orig.)

  1. Low-flow venovenous CO₂ removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

    Science.gov (United States)

    Ruberto, F; Bergantino, B; Testa, M C; D'Arena, C; Zullino, V; Congi, P; Paglialunga, S G; Diso, D; Venuta, F; Pugliese, F

    2013-09-01

    Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Thoracic organ transplantation.

    Science.gov (United States)

    Pierson, Richard N; Barr, Mark L; McCullough, Keith P; Egan, Thomas; Garrity, Edward; Jessup, Mariell; Murray, Susan

    2004-01-01

    This article presents an overview of factors associated with thoracic transplantation outcomes over the past decade and provides valuable information regarding the heart, lung, and heart-lung waiting lists and thoracic organ transplant recipients. Waiting list and post-transplant information is used to assess the importance of patient demographics, risk factors, and primary cardiopulmonary disease on outcomes. The time that the typical listed patient has been waiting for a heart, lung, or heart-lung transplant has markedly increased over the past decade, while the number of transplants performed has declined slightly and survival after transplant has plateaued. Waiting list mortality, however, appears to be declining for each organ and for most diseases and high-severity subgroups, perhaps in response to recent changes in organ allocation algorithms. Based on perceived inequity in organ access and in response to a mandate from Health Resources and Services Administration, the lung transplant community is developing a lung allocation system designed to minimize deaths on the waiting list while maximizing the benefit of transplant by incorporating post-transplant survival and quality of life into the algorithm. Areas where improved data collection could inform evolving organ allocation and candidate selection policies are emphasized.

  3. Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

    Science.gov (United States)

    Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

    2018-04-01

    In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

  4. Mycobacterium bovis hip bursitis in a lung transplant recipient.

    Science.gov (United States)

    Dan, J M; Crespo, M; Silveira, F P; Kaplan, R; Aslam, S

    2016-02-01

    We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico-US border, clinical characteristics, resistance profile, and treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Scintigraphic diagnosis of silent aspiration following double-sided lung transplantation

    International Nuclear Information System (INIS)

    Toenshoff, G.; Stock, U.; Bohuslavizki, K.H.; Brenner, W.; Costard-Jaeckle, A.; Cremer, J.; Clausen, M.

    1996-01-01

    We present a case of a 25 year old patient who underwent double-sided lung transplantation and suffered from recurrent pneumonia. Silent aspiration was suspected clinically. Aspiration was proved by scintigraphy enabling to discriminate between direct oro-pulmonal aspiration and aspiration after gastro-esophageal reflux. (orig.) [de

  6. Depression, social support, and clinical outcomes following lung transplantation: a single-center cohort study.

    Science.gov (United States)

    Smith, Patrick J; Snyder, Laurie D; Palmer, Scott M; Hoffman, Benson M; Stonerock, Gregory L; Ingle, Krista K; Saulino, Caroline K; Blumenthal, James A

    2018-05-01

    Depressive symptoms are common among lung transplant candidates and have been associated with poorer clinical outcomes in some studies. Previous studies have been plagued by methodologic problems, including small sample sizes, few clinical events, and uncontrolled confounders, particularly perioperative complications. In addition, few studies have examined social support as a potential protective factor. We therefore examined the association between pretransplant depressive symptoms, social support, and mortality in a large sample of lung transplant recipients. As a secondary aim, we also examined the associations between psychosocial factors, perioperative outcomes [indexed by hospital length of stay (LOS)], and mortality. We hypothesized that depression would be associated with longer LOS and that the association between depression, social support, and mortality would be moderated by LOS. Participants included lung transplant recipients, transplanted at Duke University Medical Center from January 2009 to December 2014. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI-II) and social support using the Perceived Social Support Scale (PSSS). Medical risk factors included forced vital capacity (FVC), partial pressure of carbon dioxide (PCO 2 ), donor age, acute rejection, and transplant type. Functional status was assessed using six-minute walk distance (6MWD). We also controlled for demographic factors, including age, gender, and native disease. Transplant hospitalization LOS was examined as a marker of perioperative clinical outcomes. Participants included 273 lung recipients (174 restrictive, 67 obstructive, 26 cystic fibrosis, and six "other"). Pretransplant depressive symptoms were common, with 56 participants (21%) exhibiting clinically elevated levels (BDI-II ≥ 14). Greater depressive symptoms were associated with longer LOS [adjusted b = 0.20 (2 days per 7-point higher BDI-II score), P social support (P social support were

  7. Early and mid-term results of lung transplantation with donors 60 years and older.

    Science.gov (United States)

    López, Iker; Zapata, Ricardo; Solé, Juan; Jaúregui, Alberto; Deu, María; Romero, Laura; Pérez, Javier; Bello, Irene; Wong, Manuel; Ribas, Montse; Masnou, Nuria; Rello, Jordi; Roman, Antonio; Canela, Mercedes

    2015-01-01

    There are doubts about the age limit for lung donors and the ideal donor has traditionally been considered to be one younger than 55 years. The objective of this study was to compare the outcomes in lung transplantation between organs from donors older and younger than 60 years. We performed a retrospective observational study comparing the group of patients receiving organs from donors 60 years or older (Group A) or younger than 60 years (Group B) between January 2007 and December 2011. Postoperative evolution and mortality rates, short-term and mid-term postoperative complications, and global survival rate were evaluated. We analysed a total of 230 lung transplants, of which 53 (23%) involved lungs from donors 60 years of age or older (Group A), and 177 (77%) were from donors younger than 60 years (Group B). Three (5.7%) patients from Group A and 14 patients (7.9%) from Group B died within 30 days (P = 0.58). The percentage of patients free from chronic lung allograft dysfunction at 1-3 years was 95.5, 74.3 and 69.3% for Group A, and 94.5, 84.8 and 73.3% for Group B, respectively (P = 0.47). There were no statistically significant differences between Groups A and B in terms of survival at 3 years, (69.4 vs 68.8%; P = 0.28). Our results support the idea that lungs from donors aged 60-70 years can be used safely for lung transplantation with comparable results to lungs from younger donors in terms of postoperative mortality and mid-term survival. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  8. Genetic Modification of the Lung Directed Toward Treatment of Human Disease.

    Science.gov (United States)

    Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G

    2017-01-01

    Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.

  9. Evaluation of Lung Function in Liver Transplant Candidates.

    Science.gov (United States)

    Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

    2018-04-01

    A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

  10. Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation

    Directory of Open Access Journals (Sweden)

    Parissis Haralabos

    2010-09-01

    Full Text Available Abstract Background To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS. Methods Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus. Results The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51. The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully. The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis. Conclusions There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.

  11. The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Annelieke W. M. Paantjens

    2011-01-01

    Full Text Available The production of IgG HLA antibodies after lung transplantation (LTx is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS. It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantation. Serum was collected from 49 patients once prior to transplantation and monthly for up to 1 year after lung transplantation was analyzed by Luminex to detect IgM and IgG antibodies against HLA and MICA. The presence of either IgM or IgG HLA and/or MICA antibodies prior to or after transplantation was not related to survival, gender, primary disease, or the development of BOS. Additionally, the production of IgG alloantibodies was not preceded by an increase in levels of IgM, and IgM levels were not followed by an increase in IgG. Under current immune suppressive regimen, although the presence of IgM antibodies does not correlate with BOS after LTx, IgM high IgG low HLA class I antibody titers were observed more in patients with BOS compared to patients without BOS.

  12. [Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

    Science.gov (United States)

    López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

    2014-04-01

    Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  13. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  14. Comparison of characteristics of human small cell carcinoma of the lung in patients, in vitro and transplanted into nude mice

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1986-01-01

    Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast-free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of t...

  15. The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

    OpenAIRE

    Paantjens, Annelieke W. M.; van de Graaf, Ed A.; Kwakkel-van Erp, Johanna M.; Hoefnagel, Tineke; van Ginkel, Walter G. J.; Fakhry, Farzia; van Kessel, Diana A.; van den Bosch, Jules M. M.; Otten, Henny G.

    2011-01-01

    The production of IgG HLA antibodies after lung transplantation (LTx) is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS). It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantati...

  16. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

  17. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    Directory of Open Access Journals (Sweden)

    Israel L. Medeiros

    2012-09-01

    Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  18. Predictive equations for lung volumes from computed tomography for size matching in pulmonary transplantation.

    Science.gov (United States)

    Konheim, Jeremy A; Kon, Zachary N; Pasrija, Chetan; Luo, Qingyang; Sanchez, Pablo G; Garcia, Jose P; Griffith, Bartley P; Jeudy, Jean

    2016-04-01

    Size matching for lung transplantation is widely accomplished using height comparisons between donors and recipients. This gross approximation allows for wide variation in lung size and, potentially, size mismatch. Three-dimensional computed tomography (3D-CT) volumetry comparisons could offer more accurate size matching. Although recipient CT scans are universally available, donor CT scans are rarely performed. Therefore, predicted donor lung volumes could be used for comparison to measured recipient lung volumes, but no such predictive equations exist. We aimed to use 3D-CT volumetry measurements from a normal patient population to generate equations for predicted total lung volume (pTLV), predicted right lung volume (pRLV), and predicted left lung volume (pLLV), for size-matching purposes. Chest CT scans of 400 normal patients were retrospectively evaluated. 3D-CT volumetry was performed to measure total lung volume, right lung volume, and left lung volume of each patient, and predictive equations were generated. The fitted model was tested in a separate group of 100 patients. The model was externally validated by comparison of total lung volume with total lung capacity from pulmonary function tests in a subset of those patients. Age, gender, height, and race were independent predictors of lung volume. In the test group, there were strong linear correlations between predicted and actual lung volumes measured by 3D-CT volumetry for pTLV (r = 0.72), pRLV (r = 0.72), and pLLV (r = 0.69). A strong linear correlation was also observed when comparing pTLV and total lung capacity (r = 0.82). We successfully created a predictive model for pTLV, pRLV, and pLLV. These may serve as reference standards and predict donor lung volume for size matching in lung transplantation. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

    Science.gov (United States)

    Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

    2016-04-01

    Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The construct validity of the health utilities index mark 3 in assessing health status in lung transplantation

    Directory of Open Access Journals (Sweden)

    Zuk Dalyce

    2010-09-01

    Full Text Available Abstract Purpose To assess the cross-sectional construct validity of the Health Utilities Index Mark 3 (HUI3 in lung transplantation. Methods Two hundred and thirteen patients (103 pre-transplant and 110 post-transplant with mean age 53 years old (SD 13 were recruited during a randomized controlled clinical trial at the out-patient clinic in a tertiary institution. At baseline, patients self-completed measures that included the HUI3, EuroQol EQ-5D, Hospital Anxiety and Depression Scale (HADS and socio-demographic questionnaire. Six-minute walk test scores and forced expiratory volume in 1 second data were collected from patient's medical records. A priori hypotheses were formulated by members of the transplant team about the expected degree of association between the measures. Correlation coefficients of Results Of the ninety predictions made, forty three were correct but in 31 the correlation was slightly lower than predicted and in 7 the correlations were much higher than predicted. In 48% of the cases, predicted and observed associations were in agreement. Predictions of associations were off by one category in 42% of the cases; in 10% of the cases the predictions were off by two categories. Conclusions This is the first study providing evidence of cross-sectional construct validity of HUI3 in lung transplantation. Results indicate that the HUI3 was able to capture the burden of lung disease before transplantation and that post-transplant patients enjoyed higher health-related quality of life than pre-transplant patients.

  1. Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

    Science.gov (United States)

    Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

    2017-02-01

    Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

  2. Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Latini, Paolo; Aristei, Cynthia; Checcaglini, Franco; Maranzano, Ernesto; Panizza, B.M.; Perrucci, Elisabetta (University and Hospital, Policlinico, Perugia (Italy). Radiation Oncology Service); Aversa, Franco; Martelli, M.F. (University and Hospital, Policlinico, Perugia (Italy). Department of Haematology); Raymondi, Carlo (University and Hospital, Policlinico, Perugia (Italy). Radiation Physics Service)

    1991-10-01

    From July 1985 to December 1989, 72 evaluable patients aged 6-51 (median age 27) suffering from hematological malignancies received allo-geneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce risks of graft-versus-host-disease (GvHD); 57 were matched and 15 mis-matched. Three different conditioning regiments were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mis-matched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in 3 doses/day, 5 h apart over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of inter-stitial pneumonia (IP) was 12.3 percent in matched and 46.7 in mis-matched patients. The results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in the matched patients. (author). 30 refs.; 5 figs.; 1 tab.

  3. Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

    International Nuclear Information System (INIS)

    Latini, Paolo; Aristei, Cynthia; Checcaglini, Franco; Maranzano, Ernesto; Panizza, B.M.; Perrucci, Elisabetta; Aversa, Franco; Martelli, M.F.; Raymondi, Carlo

    1991-01-01

    From July 1985 to December 1989, 72 evaluable patients aged 6-51 (median age 27) suffering from hematological malignancies received allo-geneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce risks of graft-versus-host-disease (GvHD); 57 were matched and 15 mis-matched. Three different conditioning regiments were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mis-matched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in 3 doses/day, 5 h apart over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of inter-stitial pneumonia (IP) was 12.3 percent in matched and 46.7 in mis-matched patients. The results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in the matched patients. (author). 30 refs.; 5 figs.; 1 tab

  4. Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life

    NARCIS (Netherlands)

    van den Berg, JWK; van der Bij, W; Koeter, GH; Postma, DS; ten Vergert, EM

    The present study was undertaken to assess the relationship between health-related quality of life (HRQOL) and bronchiolitis obliterans syndrome (BOS), as both represent important parameters of outcome after lung transplantation. HRQOL was measured both cross-sectionally and longitudinally by

  5. Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

    Science.gov (United States)

    Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

    2000-12-01

    We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

  6. Humoral immune-response against human cytomegalovirus (hcmv)-specific proteins after hcmv infection in lung transplantation as detected with recombinant and naturally-occurring proteins

    NARCIS (Netherlands)

    van Zanten, J; Harmsen, M. C.; van der Giessen, M.; van der Bij, W; Prop, J.; de Leij, L; The, T. Hauw

    The humoral immune response to four intracellularly located cytomegalovirus (CMV) proteins was studied in 15 lung transplant recipients experiencing active CMV infections. Five patients had primary infections, and 10 had secondary infections. Antibodies of the immunoglobulin M (IgM) and IgG classes

  7. Lobar lung transplantation from deceased donors: A systematic review.

    Science.gov (United States)

    Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias

    2017-02-24

    To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx ( n = 138) was associated with a lower one-year-survival compared to conventional-LTx ( n = 539) (65.1% vs 84.1%, P < 0.001). Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

  8. Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment.

    Directory of Open Access Journals (Sweden)

    Christine Bonnal

    Full Text Available Aspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention.To elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed.Forty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27% had transient aspergillus colonisation, occurring 1-13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6, A. niger (3, A. sydowii (1, A. calidoustus (1 and Aspergillus sp. (1. In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient's room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases, two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%.Taken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients.

  9. Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

    Science.gov (United States)

    Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

    2016-01-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

  10. Mycoplasma hominis periaortic abscess following heart-lung transplantation.

    Science.gov (United States)

    Hagiya, Hideharu; Yoshida, Hisao; Yamamoto, Norihisa; Kimura, Keigo; Ueda, Akiko; Nishi, Isao; Akeda, Yukihiro; Tomono, Kazunori

    2017-06-01

    We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. The Prevalence of Pneumocystis jiroveci in Bronchoalveolar Lavage Specimens of Lung Transplant Recipients Examined by the Nested PCR.

    Science.gov (United States)

    Izadi, Morteza; Jonaidi Jafari, Nematollah; Sadraei, Javid; Mahmoodzadeh Poornaki, Abbas; Rezavand, Babak; Zarrinfar, Hossein; Abdi, Jahangir; Mohammadi, Younes

    2014-12-01

    The use of immune suppressive drugs for organ transplant recipients predisposes them to opportunistic infections, especially by fungal agents. Pneumocystis jiroveci, as an opportunistic pathogen, endangers the patients' life in those with immune system disorders. Early detection of latent Pneumocystis infection in susceptible patients may help choose the optimal treatment for these patients. The aim of this study was to identify and determine the colonization of latent P. jiroveci infection among lung transplant recipients. This cross-sectional descriptive study was conducted on lung transplant recipients. Bronchoalveolar lavage (BAL) specimens were collected from 32 patients undergoing bronchoscopy. The samples were aseptically homogenized by 10 mM dithiothreitol, and their DNA was extracted. The mtLSUrRNA gene of P. jiroveci was amplified using nested PCR in two stages. Nested PCR was performed using external primers of pAZ-102-E and pAZ102-H followed by using the PCR product of the first stage and internal primers of pAZ-102-E and pAZ102-L2. The genome of P. jiroveci was revealed by a 346 bp PCR product in the initial amplification and a 120 bp product in the nested PCR. The results showed that seven BAL specimens (21.9%) from lung transplant recipients were positive for P. jiroveci. In molecular epidemiology studies, nested PCR has higher sensitivity than PCR. Results of this study support the colonization of P. jiroveci in patients receiving lung transplantation. Patients who are carriers of P. jiroveci are at a higher risk of P. jiroveci pneumonia.

  12. Evaluation of right ventricular function for lung transplantation. Role of electron flow scan

    International Nuclear Information System (INIS)

    Stern, M.; Joint-Lambert, O.; Tainturier, C.; Seigneur, F.; Caubarrere, I.; Hernigou, A.

    1994-01-01

    Several invasive or not invasive technics were used to evaluate right ventricular insufficiency associated to severe chronic pulmonary insufficiency. But none of them were very accurate and now the use of EBT appears as a real improvement. We performed a prospective study with 50 patients waiting for a lung transplantation and we compared the values of right ventricular function obtained by EBT to those obtained by nuclear medicine and catheterism. Accuracy of EBT for left ventricle evaluation has already been proved. Stroke volumes calculated by EBT in right and left ventricles are similar and this constitutes a good validation of the method for right ventricle evaluation. Correlations with hemodynamic measurements are poor and nuclear medicine technics underestimate the ejection fraction. So, EBT is recommended for right ventricular study before and after lung transplantation. (authors). 11 refs., 4 figs

  13. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  14. Lipid raft facilitated ligation of K-{alpha}1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Tiriveedhi, Venkataswarup; Angaswamy, Nataraju [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Weber, Joseph [Department of Medicine, Washington University School of Medicine, St. Louis, MO (United States); Mohanakumar, T., E-mail: kumart@wustl.edu [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States)

    2010-08-20

    Research highlights: {yields} Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. {yields} Cholesterol depletion causes down regulation of growth factor expression. {yields} Cholesterol depletion is accompanied by loss of membrane bound caveolin. {yields} Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-{alpha}1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 {+-} 1.1-, 3.2 {+-} 0.9-, and 3.4 {+-} 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of {beta}-methyl cyclodextran ({beta}MCD) had significantly reduced growth factor expression (1.3 {+-} 0.3, vs {beta}MCD untreated being 6.4 {+-} 1.1-fold

  15. Lipid raft facilitated ligation of K-α1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    International Nuclear Information System (INIS)

    Tiriveedhi, Venkataswarup; Angaswamy, Nataraju; Weber, Joseph; Mohanakumar, T.

    2010-01-01

    Research highlights: → Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. → Cholesterol depletion causes down regulation of growth factor expression. → Cholesterol depletion is accompanied by loss of membrane bound caveolin. → Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-α1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 ± 1.1-, 3.2 ± 0.9-, and 3.4 ± 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of β-methyl cyclodextran (βMCD) had significantly reduced growth factor expression (1.3 ± 0.3, vs βMCD untreated being 6.4 ± 1.1-fold increase) upon stimulation with KAT Abs. Depletion

  16. Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

    Science.gov (United States)

    Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

    2014-12-01

    A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

  17. Metalloproteinase Profiling in Lung Transplant Recipients With Good Outcome and Bronchiolitis Obliterans Syndrome

    NARCIS (Netherlands)

    Heijink, Irene H.; Rozeveld, Dennie; van der Heide, Sicco; Bij, van der Wim; Bischoff, Rainer; Oosterhout, van Antoon J,; van der Toorn, Marco

    Background. Bronchiolitis obliterans syndrome (BOS), the major cause of death on lung transplantation, is characterized by bronchiolar inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) have been implicated in these processes, although it is still unclear whether MMP activity and

  18. Rapid decline in 51Cr-EDTA measured renal function during the first weeks following lung transplantation

    DEFF Research Database (Denmark)

    Hornum, M.; Iversen, M.; Steffensen, I.

    2009-01-01

    We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis/bronchiect......We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis....../bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the (51)Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12...

  19. Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.

    Science.gov (United States)

    Forli, Liv; Bollerslev, Jens; Simonsen, Svein; Isaksen, Gunhild A; Kvamsdal, Kari E; Godang, Kristin; Gadeholt, Gaut; Pripp, Are H; Bjortuft, Oystein

    2010-02-27

    Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year. In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention.

  20. Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.

    Science.gov (United States)

    Bennett, David; Fossi, Antonella; Bargagli, Elena; Refini, Rosa Metella; Pieroni, Maria; Luzzi, Luca; Ghiribelli, Claudia; Paladini, Piero; Voltolini, Luca; Rottoli, Paola

    2015-10-01

    Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.

  1. Successful Recanalization of a Complete Lobar Bronchial Stenosis in a Lung Transplant Patient Using a Combined Percutaneous and Bronchoscopic Approach

    International Nuclear Information System (INIS)

    Miraglia, Roberto; Vitulo, Patrizio; Maruzzelli, Luigi; Burgio, Gaetano; Caruso, Settimo; Bertani, Alessandro; Callari, Adriana; Luca, Angelo

    2016-01-01

    Airway stenosis is a major complication after lung transplantation that is usually managed with a combination of interventional endoscopic techniques, including endobronchial debridement, balloon dilation, and stent placement. Herein, we report a successful case of recanalization of a complete stenosis of the right middle lobe bronchus in a lung transplant patient, by using a combined percutaneous–bronchoscopic approach after the failure of endobronchial debridement

  2. Successful Recanalization of a Complete Lobar Bronchial Stenosis in a Lung Transplant Patient Using a Combined Percutaneous and Bronchoscopic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Vitulo, Patrizio, E-mail: pvitulo@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Pulmonology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Maruzzelli, Luigi, E-mail: lmaruzzelli@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Burgio, Gaetano, E-mail: gburgio@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Operating Room Service, Department of Anesthesia and Intensive Care (Italy); Caruso, Settimo, E-mail: secaruso@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Bertani, Alessandro, E-mail: abertani@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Thoracic Surgery and Lung Transplantation Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Callari, Adriana, E-mail: acallari@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Pulmonology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Luca, Angelo, E-mail: aluca@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy)

    2016-03-15

    Airway stenosis is a major complication after lung transplantation that is usually managed with a combination of interventional endoscopic techniques, including endobronchial debridement, balloon dilation, and stent placement. Herein, we report a successful case of recanalization of a complete stenosis of the right middle lobe bronchus in a lung transplant patient, by using a combined percutaneous–bronchoscopic approach after the failure of endobronchial debridement.

  3. Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

    Science.gov (United States)

    Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

    2018-04-13

    Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

  4. Clinical Outcomes of Lung Transplantation in Patients with Telomerase Mutations

    Science.gov (United States)

    Tokman, Sofya; Singer, Jonathan P.; Devine, Megan S.; Westall, Glen P.; Aubert, John-David; Tamm, Michael; Snell, Gregory I.; Lee, Joyce S.; Goldberg, Hilary J.; Kukreja, Jasleen; Golden, Jeffrey A.; Leard, Lorriana E.; Garcia, Christine K.; Hays, Steven R.

    2017-01-01

    Background Successful lung transplantation (LT) for patients with pulmonary fibrosis from telomerase mutations is limited by systemic complications of telomerase dysfunction including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes among 14 LT recipients with telomerase mutations. Methods Subjects underwent LT between February 2005 and April 2014 at 5 LT centers. We abstracted data from medical records, focusing on outcomes reflecting post-LT treatment effects likely to be complicated by telomerase mutations. Results The median age of subjects was 60.5 years (IQR 52.0–62.0), 64.3% were male, and the mean post-LT observation time was 3.2 years (SD ±2.9). Eleven subjects had a mutation in telomerase reverse transcriptase, 2 in telomerase RNA component, and 1 had an uncharacterized mutation. Ten subjects were leukopenic post-LT; leukopenia prompted cessation of mycophenolate mofetil in 5 and treatment with filgrastim in 4. Six subjects had recurrent lower respiratory tract infections (LRTI), 7 had acute cellular rejection (ACR) (A1), and 4 developed chronic lung allograft dysfunction (CLAD). Ten LT recipients developed chronic renal insufficiency and 8 experienced acute, reversible renal failure. Three developed cancer, none had cirrhosis. Thirteen subjects were alive at data censorship. Conclusions The clinical course for LT recipients with telomerase mutations is complicated by renal disease, leukopenia prompting a change in the immunosuppressive regimen, and recurrent LTRI. In contrast, cirrhosis was absent, ACR was mild, and development of CLAD was comparable to other LT populations. While posing challenges, lung transplantation may be feasible for patients with pulmonary fibrosis due to telomerase mutations. PMID:26169663

  5. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    Science.gov (United States)

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  6. Extracorporeal life support as a bridge to lung transplantation-experience of a high-volume transplant center.

    Science.gov (United States)

    Hoetzenecker, Konrad; Donahoe, Laura; Yeung, Jonathan C; Azad, Sassan; Fan, Eddy; Ferguson, Niall D; Del Sorbo, Lorenzo; de Perrot, Marc; Pierre, Andrew; Yasufuku, Kazuhiro; Singer, Lianne; Waddell, Thomas K; Keshavjee, Shaf; Cypel, Marcelo

    2018-03-01

    Extracorporeal life support (ECLS) is increasingly used to bridge deteriorating patients awaiting lung transplantation (LTx), however, few systematic descriptions of this practice exist. We therefore aimed to review our institutional experience over the past 10 years. In this case series, we included all adults who received ECLS with the intent to bridge to LTx. Data were retrieved from patient charts and our institutional ECLS and transplant databases. Between January 2006 and September 2016, 1111 LTx were performed in our institution. ECLS was used in 71 adults with the intention to bridge to LTx; of these, 11 (16%) were bridged to retransplantation. The median duration of ECLS before LTx was 10 days (range, 0-95). We used a single dual-lumen venous cannula in 23 patients (32%). Nine of 13 patients (69%) with pulmonary hypertension were bridged by central pulmonary artery to left atrium Novalung. Twenty-five patients (35%) were extubated while on ECLS and 26 patients (37%) were mobilized. Sixty-three patients (89%) survived to LTx. Survival by intention to treat was 66% (1 year), 58% (3 years) and 48% (5 years). Survival was significantly shorter in patients undergoing ECLS bridge to retransplantation compared with first LTx (median survival, 15 months (95% CI, 0-31) versus 60 months (95% CI, 37-83); P = .041). In our center experience, ECLS bridge to first lung transplant leads to good short-term and long-term outcomes in carefully selected patients. In contrast, our data suggest that ECLS as a bridge to retransplantation should be used with caution. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

  7. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  8. Uterine transplantation: Review in human research.

    Science.gov (United States)

    Favre-Inhofer, A; Rafii, A; Carbonnel, M; Revaux, A; Ayoubi, J M

    2018-06-01

    Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation. Copyright © 2018. Published by Elsevier Masson SAS.

  9. Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation

    DEFF Research Database (Denmark)

    Müller, Catharina; Andersson-Sjöland, Annika; Schultz, Hans Henrik

    2017-01-01

    are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS. Methods: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen...... and immunohistochemistry. Results: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased...... in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months...

  10. Multiphoton microscopy based cryo-imaging of inflated frozen human lung sections at -60°C in healthy and COPD lungs

    Science.gov (United States)

    Abraham, Thomas; Kayra, Damian; Zhang, Angela; Suzuki, Masaru; McDonough, John; Elliott, W. M.; Cooper, Joel D.; Hogg, James C.

    2013-02-01

    Lung is a complex gas exchanger with interfacial area (where the gas exchange takes place) is about the size of a tennis court. Respiratory function is linked to the biomechanical stability of the gas exchange or alveolar regions which directly depends on the spatial distributions of the extracellular matrix fibers such fibrillar collagens and elastin fibers. It is very important to visualize and quantify these fibers at their native and inflated conditions to have correct morphometric information on differences between control and diseased states. This can be only achieved in the ex vivo states by imaging directly frozen lung specimens inflated to total lung capacity. Multiphoton microscopy, which uses ultra-short infrared laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from endogenously fluorescent proteins (e.g. elastin) and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens in fresh human lung tissues [J. Struct. Biol. (2010)171,189-196]. Here we report for the first time 3D image data obtained directly from thick frozen inflated lung specimens (~0.7- 1.0 millimeter thick) visualized at -60°C without prior fixation or staining in healthy and diseased states. Lung specimens donated for transplantation and released for research when no appropriate recipient was identified served as controls, and diseased lung specimens donated for research by patients receiving lung transplantation for very severe COPD (n=4) were prepared as previously described [N. Engl. J. Med. (2011) 201, 1567]. Lung slices evenly spaced between apex and base were examined using multiphoton microscopy while maintained at -60°C using a temperature controlled cold stage with a temperature resolution of 0.1°C. Infrared femto-second laser pulses tuned to 880nm, dry microscopic objectives, and non-de-scanned detectors/spectrophotometer located in the reflection geometry were

  11. First Report of Lung Transplantation in a Patient With Active Pulmonary Mycobacterium simiae Infection

    DEFF Research Database (Denmark)

    Qvist, T; Katzenstein, Terese Lea; Lillebaek, T

    2013-01-01

    bilateral lung transplantation for end-stage idiopathic bronchiectasis and chronic M simiae infection. The disease proved manageable on a regimen of clarithromycin, moxifloxacin, and cotrimoxazole with a successful outcome 1-year posttransplantation. There is increasing evidence that nontuberculous...

  12. [Lung transplantation in sporadic lymphangioleiomyomatosis: study of 7 cases].

    Science.gov (United States)

    Ansótegui Barrera, Emilio; Mancheño Franch, Nuria; Peñalver Cuesta, Juan Carlos; Vera-Sempere, Francisco; Padilla Alarcón, José

    2013-10-19

    Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM. We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival. The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence. LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Radiographic manifestations of reperfusion edema after transplantation

    International Nuclear Information System (INIS)

    Park, Se Young; Kim, Tae Hoon; Ryu, Young Hoon; Moon, Sung Wook; Kim, Hyung Joong; Ahn, Chul Min; Paik, Hyo Chae; Lee, Doo Yun; Kim, Sang Jin

    2003-01-01

    To elucidate the sequential radiologic manifestations of reperfusion edema after lung transplantation. The study group comprised five consecutive lung transplant recipients (M:F=3:2;mean age; 47.5 years) who between July 1996 and April 2002 underwent lung transplantation procedures (four, unilateral; one, bilateral) at our institution. We retrospectively reviewed the serial postoperative radiographs obtained and characterized the lung infiltrates. Lung infiltrates compatible with reperfusion edema were present in all patients (5/5). Reperfusion edema appeared on day 1 in four, and by day 2 in the other. In all transplanted lungs, infiltrates were found in the perihilar and basilar regions, and were scored as maximal on day 1 in one, day 3 in two, day 4 in one and day 5 in the other. The recognition of sequential radiological manifestations helps identify recognition of reperfusion edema after lung transplantation

  14. Performance of long-term CT monitoring in diagnosing bronchiolitis obliterans after lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Berstad, Audun E. [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway)]. E-mail: a.e.berstad@medisin.uio.no; Aalokken, Trond Mogens [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway); Kolbenstvedt, Alf [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway); Bjortuft, Oystein [Department of Thoracic Medicine, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway)

    2006-04-15

    Aim: The purpose of the study was to evaluate the ability of CT, including expiratory scans with minimum intensity projection in predicting the development of bronchiolitis obliterans syndrome after lung transplantation. Materials and methods: Forty consecutive patients, 29 bilateral and 11 single lung transplanted, were followed-up with regular scans for a median of 36 months. Air trapping was evaluated on expiratory scans constructed from two short spiral scans with minimum intensity projection-technique, one at the level of the carina and the other midway between the right diaphragm and the carina. Air trapping was scored on a 16-point scale. Bronchiolitis obliterans syndrome was diagnosed according to established clinical criteria and quantified spirometrically. Results: Bronchiolitis obliterans syndrome developed in 17 patients (43%) after a median of 12 months. Air trapping and bronchiectasis was seen before the diagnosis of bronchiolitis obliterans syndrome in only two and one patient, respectively. Interobserver agreement for air trapping score was good (kappa = 0.65). Air trapping scores performed significantly better than that achieved by chance alone in determining the presence of bronchiolitis obliterans syndrome (P = 0.0025). An air trapping score of 4 or more provided the best results with regard to sensitivity and specificity in diagnosing bronchiolitis obliterans syndrome. The sensitivity, specificity, positive and negative predictive values of an air trapping of 4 or more in the diagnosis of bronchiolitis obliterans syndrome were 77, 74, 68 and 81%, respectively. Conclusion: Expiratory CT scans with minimum intensity projection-reconstruction did not predict the development of bronchiolitis obliterans syndrome in most patients. The findings seriously limit the clinical usefulness of long-term CT monitoring for diagnosing bronchiolitis obliterans syndrome after lung transplantation.

  15. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    Science.gov (United States)

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  16. Pattern and Predictors of Hospital Readmission During the First Year After Lung Transplantation.

    Science.gov (United States)

    Alrawashdeh, M; Zomak, R; Dew, M A; Sereika, S; Song, M K; Pilewski, J M; DeVito Dabbs, A

    2017-05-01

    Hospital readmission after lung transplantation negatively affects quality of life and resource utilization. A secondary analysis of data collected prospectively was conducted to identify the pattern of (incidence, count, cumulative duration), reasons for and predictors of readmission for 201 lung transplant recipients (LTRs) assessed at 2, 6, and 12 mo after discharge. The majority of LTRs (83.6%) were readmitted, and 64.2% had multiple readmissions. The median cumulative readmission duration was 19 days. The main reasons for readmission were other than infection or rejection (55.5%), infection only (25.4%), rejection only (9.9%), and infection and rejection (0.7%). LTRs who required reintubation (odds ratio [OR] 1.92; p = 0.008) or were discharged to care facilities (OR 2.78; p = 0.008) were at higher risk for readmission, with a 95.7% cumulative incidence of readmission at 12 mo. Thirty-day readmission (40.8%) was not significantly predicted by baseline characteristics. Predictors of higher readmission count were lower capacity to engage in self-care (incidence rate ratio [IRR] 0.99; p = 0.03) and discharge to care facilities (IRR 1.45; p = 0.01). Predictors of longer cumulative readmission duration were older age (arithmetic mean ratio [AMR] 1.02; p = 0.009), return to the intensive care unit (AMR 2.00; p = 0.01) and lower capacity to engage in self-care (AMR 0.99; p = 0.03). Identifying LTRs at risk may assist in optimizing predischarge care, discharge planning and long-term follow-up. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

    Science.gov (United States)

    Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

    2013-08-01

    Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

  18. Epidemiology, risk factors, and outcome of Clostridium difficile infection in heart and heart-lung transplant recipients.

    Science.gov (United States)

    Bruminhent, Jackrapong; Cawcutt, Kelly A; Thongprayoon, Charat; Petterson, Tanya M; Kremers, Walter K; Razonable, Raymund R

    2017-06-01

    Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013). Cox proportional hazards regression was used to model the association of risk factors with time to CDI and survival with CDI following transplantation. There were 254 HT recipients, with a median age of 53 years (IQR, 45-60); 34% were female. During the median follow-up of 3.1 years (IQR, 1.3-6.1), 22 (8.7%) patients developed CDI. In multivariable analysis, risk factors for CDI were combined heart-lung transplant (HR 4.70; 95% CI, 1.30-17.01 [P=.02]) and retransplantation (HR 7.19; 95% CI, 1.61-32.12 [P=.01]). Acute cellular rejection was associated with a lower risk of CDI (HR 0.34; 95% CI, 0.11-0.94 [P=.04]). CDI was found to be an independent risk factor for mortality (HR 7.66; 95% CI, 3.41-17.21 [PClostridium difficile infection after HT is more common among patients with combined heart-lung and those undergoing retransplantation. CDI was associated with a higher risk of mortality in HT recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Contemporary Outcomes of Extracorporeal Membrane Oxygenation Used as Bridge to Lung Transplantation.

    Science.gov (United States)

    Hakim, Ali H; Ahmad, Usman; McCurry, Kenneth R; Johnston, Douglas R; Pettersson, Gosta B; Budev, Marie; Murthy, Sudish; Blackstone, Eugene H; Tong, Michael Z

    2018-07-01

    Extracorporeal membrane oxygenation (ECMO), when used as bridge to lung transplantation, (BTT) identifies high-risk candidates. Recent advances in cannula design and patient selection fosters "awake ambulatory ECMO" as a viable option for critically ill candidates in an attempt to retard deconditioning while awaiting allografts. From 2012 to 2015, 30 patients underwent ECMO as BTT. Candidacy for ECMO was determined before listing for transplant. A dual-lumen single cannula was used first in 13 of 30 patients (43%). Of the remaining 30 patients, 6 (20%) were supported with venoarterial ECMO and 11 (37%) with venovenous ECMO, with double-site cannulation in 11 (37%), and 6 of 11 converted to a dual-lumen single cannula. All ECMO patients were managed in a dedicated heart/lung failure intensive care unit, and early aggressive physical therapy, ambulation, and spontaneous breathing trials were emphasized. BTT was successful in 26 patients (87%). In the 19 patients with dual-lumen single cannula, 5 (26%) were successfully ambulated, and 6 (32%) achieved spontaneous ventilation. Median (25th, 75th percentile) lengths of stay in the intensive care unit and hospital were 33 days (20, 46 days) and 56 days (28, 78 days), respectively, and were 20 and 31 days, respectively, in patients successfully ambulated (intensive care unit: p = 0.5; hospital: p = 0.4). Among all patients who received a transplant, 30-day, 1-year, and 3-year survival were 92%, 85%, and 80%, respectively. Among patients undergoing primary transplants, 3-year survival was 91%. ECMO as BTT has led to encouraging perioperative outcomes and early survival. Careful patient selection and early use of ECMO seems to allow for preservation of vitality while these critically ill candidates await donor organs, which may improve outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Bronchiolitis obliterans syndrome: thin-section CT diagnosis of obstructive changes in infants and young children after lung transplantation.

    Science.gov (United States)

    Lau, D M; Siegel, M J; Hildebolt, C F; Cohen, A H

    1998-09-01

    To characterize the thin-section computed tomographic (CT) appearance of bronchiolitis fibrosa obliterans syndrome in infants and young children after lung transplantation. Thin-section CT studies in six patients with bronchiolitis obliterans syndrome (age range, 2 months to 5 1/2 years) and in 15 control patients without obstructive airway disease (age range, 2 months to 7 years) who underwent bilateral lung transplantation were retrospectively reviewed. The thin-section CT scans were obtained during quiet sleep at a median of 24 months (range, 6-36 months) after transplantation. The CT studies were evaluated for mosaic perfusion, bronchial dilatation, bronchial wall thickening, and mucous plugging Final diagnoses in all patients were based pulmonary function test results. Thin-section CT findings in the six patients with clinically proved bronchiolitis obliterans syndrome were mosaic perfusion in five (83%) bronchial dilation in three (50%), and bronchial wall thickening in one (17%). Of the 15 control patients with normal pulmonary function test results, six (40%) had mosaic perfusion; none had bronchial dilatation or bronchial wall thickening. Mucous plugging was not seen in either group. Only the association of bronchial dilatation with bronchiolitis obliterans syndrome was significant (P = .02). Infants and young children with bronchiolitis obliterans syndrome after lung transplantation are more likely to have CT abnormalities than those with normal pulmonary function test results.

  1. Successful Semi-Ambulatory Veno-Arterial Extracorporeal Membrane Oxygenation Bridge to Heart-Lung Transplantation in a Very Small Child.

    Science.gov (United States)

    Wong, J Y W; Buchholz, H; Ryerson, L; Conradi, A; Adatia, I; Dyck, J; Rebeyka, I; Lien, D; Mullen, J

    2015-08-01

    Lung transplantation (LTx) may be denied for children on extracorporeal membrane oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful LTx been reported in children over 10 years of age receiving awake or ambulatory veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA ECMO) in children has never been reported to our knowledge. We present the case of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and refractory right ventricular failure. She was successfully bridged to heart-lung transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with standard VA ECMO was converted to an ambulatory circuit using Berlin heart cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40 days. She received an HLTx from an oversized marginal lung donor. Despite a cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery without neurological deficits. She achieved 104% force expiratory volume in 1 s 33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx in our patient. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher M.; Carlsen, Jørn

    2010-01-01

    Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides, and...

  3. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis.

    Science.gov (United States)

    Brügger, Aurelia; Aubert, John-David; Piot-Ziegler, Chantal

    2014-07-01

    Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients). Categorical analysis focusing on emotion-related descriptions was organized into positive-negative-neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and) contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient's perspective.

  4. HDR brachytherapy. An option for preventing nonmalignant obstruction in patients after lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, A.; Karstens, J.H.; Christiansen, H. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Warszawski-Baumann, A.; Baumann, R. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Medical Practice for Radiotherapy and Radiation Oncology, Hannover (Germany); Gottlieb, J.; Welte, T. [Medical School Hannover (Germany). Dept. of Respiratory Medicine

    2012-12-15

    Purpose: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. Patients and methods: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. Results: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. Conclusions: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm. (orig.)

  5. HDR brachytherapy. An option for preventing nonmalignant obstruction in patients after lung transplantation

    International Nuclear Information System (INIS)

    Meyer, A.; Karstens, J.H.; Christiansen, H.; Gottlieb, J.; Welte, T.

    2012-01-01

    Purpose: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. Patients and methods: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. Results: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. Conclusions: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm. (orig.)

  6. Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

    Science.gov (United States)

    Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J

    2009-02-01

    Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

  7. Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

    Science.gov (United States)

    Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

    2015-03-01

    Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

  8. Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

    Science.gov (United States)

    Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

    2012-01-01

    Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of

  9. Unusual case of a vanishing bronchus of the left allograft in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Don Hayes

    2013-01-01

    Full Text Available We present an interesting case of a complete vanishing of the left main bronchus in a lung transplant recipient who had a successful outcome due to acute respiratory support with venovenous extracorporeal membrane oxygenation in order to perform airway dilation.

  10. Computed tomography findings of postoperative complications in lung transplantation Achados tomográficos nas complicações pós-operatórias do transplante pulmonar

    Directory of Open Access Journals (Sweden)

    Bruno Hochhegger

    2009-03-01

    Full Text Available Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post-transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis.Com o número cada vez maior e uma melhor sobrevida dos pacientes submetidos ao transplante pulmonar, os radiologistas devem estar cientes das diversas possibilidades de complicações associadas ao transplante de pulmão. O tratamento precoce das complicações é importante para a sobrevida a longo prazo dos receptores de transplante pulmonar. Com frequência, a TCAR desempenha um papel central na investigação de tais complicações. O reconhecimento precoce dos sinais de complicações proporciona um tratamento rápido e melhora a sobrevida. O objetivo desta revisão pictórica foi proporcionar uma visão sobre as complicações mais prevalentes na TC, tais como edema de reperfusão, rejeição aguda, infecção, tromboembolismo pulmonar, rejeição crônica, síndrome da bronquiolite obliterante, pneumonia em organização criptogênica, doença linfoproliferativa pós-transplante, deiscência brônquica e estenose brônquica.

  11. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle

    2015-01-01

    Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies...

  12. Prevalência de refluxo gastroesofágico em pacientes com doença pulmonar avançada candidatos a transplante pulmonar Prevalence of gastroesophageal reflux in lung transplant candidates with advanced lung disease

    Directory of Open Access Journals (Sweden)

    Gustavo Almeida Fortunato

    2008-10-01

    Full Text Available OBJETIVO: Avaliar o perfil funcional do esôfago e a prevalência de refluxo gastroesofágico (RGE em pacientes candidatos a transplante pulmonar. MÉTODOS: Foram analisados prospectivamente, entre junho de 2005 e novembro de 2006, 55 pacientes candidatos a transplante pulmonar da Santa Casa de Misericórdia de Porto Alegre. Os pacientes foram submetidos a esofagomanometria estacionária e pHmetria esofágica ambulatorial de 24 h de um e dois eletrodos antes de serem submetidos ao transplante pulmonar. RESULTADOS: A esofagomanometria foi anormal em 80% dos pacientes e a pHmetria revelou RGE ácido patológico em 24%. Os sintomas digestivos apresentaram sensibilidade de 50% e especificidade de 61% para RGE. Dos pacientes com doença pulmonar obstrutiva crônica, 94% apresentaram alteração à manometria, e 80% apresentaram hipotonia do esfíncter inferior, que foi o achado mais freqüente. Pacientes com bronquiectasias apresentaram a maior prevalência de RGE (50%. CONCLUSÕES: O achado freqüente em pacientes com doença pulmonar avançada é RGE. Na população examinada, a presença de sintomas digestivos de RGE não foi preditiva de refluxo ácido patológico. A contribuição do RGE na rejeição crônica deve ser considerada e requer estudos posteriores para seu esclarecimento.OBJECTIVE: To assess the esophageal function profile and the prevalence of gastro-esophageal reflux (GER in lung transplant candidates. METHODS: From July of 2005 to November of 2006, a prospective study was conducted involving 55 candidates for lung transplantation at the Santa Casa de Misericórdia Hospital in Porto Alegre, Brazil. Prior to transplantation, patients underwent outpatient stationary esophageal manometry and 24-h esophageal pH-metry using one and two electrodes. RESULTS: Abnormal esophageal manometry was documented in 80% of the patients, and 24% of the patients presented pathological acid reflux. Digestive symptoms presented sensitivity and

  13. Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

    Science.gov (United States)

    Welsch, C; Augustin, P; Allyn, J; Massias, L; Montravers, P; Allou, N

    2015-02-01

    Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis

    Directory of Open Access Journals (Sweden)

    Aurelia Brügger

    2014-12-01

    Full Text Available Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients. Categorical analysis focusing on emotion-related descriptions was organized into positive–negative–neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient’s perspective.

  15. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis

    Science.gov (United States)

    Brügger, Aurelia; Aubert, John-David

    2014-01-01

    Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients). Categorical analysis focusing on emotion-related descriptions was organized into positive–negative–neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and) contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient’s perspective. PMID:28070345

  16. PHENOMENON OF DEMIKHOV. "TRANSPLANTATION OF VITAL ORGANS IN EXPERIMENT" (1960. HOMOPLASTIC ORGAN TRANSPLANTATION: OF AN ISOLATED HEART, ISOLATED LUNG, KIDNEY, HEAD, HALF OF THE TRUNK, AND THE WHOLE TRUNK

    Directory of Open Access Journals (Sweden)

    S. P. Glyantsev

    2017-01-01

    Full Text Available The  article  (the third one of five presents the analysis of the final part  of the third chapter on homoplastic organ transplantation from V.P.  Demikhov's monograph "Transplantation of  vital  organs  in  experiment"  (MedGIz Publ., Moscow,  1960. The article covers the data presented by V.P. Demikhov on his creating the following animal models:  of the isolated  heart  and lung,  kidneys, head, half of the trunk, and the whole  trunk. The isolated  heart  models where  the heart  was positioned in place of the biological one were not successful. The longest  period  of the dog-recipient survival was  15 hours. The  dogs with transplanted lobes of  the  lung  survived up  to 6 days  (there  are no evidence of  a whole lung  transplant in the book; animal-recipients of kidneys survived up to 19 days.  V.P. Demikhov considered that  the graft deaths might be caused  by the biological  tissue  incompatibility between  the donor  and  recipient, and  he stressed the  need  for  its suppression and  the  importance of  choosing the  donor  and  recipient compatible by their  blood group for  successful homoplastic transplantation. By  transplanting the puppies' heads  onto  the cervical  vessels  of  the dogs, starting the experiments from 1954, V.P. Demikhov attempted to prove the role of the central nervous system in the organ engraftment, which was one of the targets  in those experiments. The integration of two bodies, combining their vascular systems, and mixing the blood had two goals: to create the conditions for overcoming the transplantation immunity and to make an animal model  of organ transplant in combination with retaining the organ neurohumoral links. The model of the cross circulation also allowed the formulation and implementation of the organ bank concept in the experiment.

  17. Characteristics and outcomes among patients with need for early dialysis after lung transplantation surgery.

    Science.gov (United States)

    Banga, Amit; Mohanka, Manish; Mullins, Jessica; Bollineni, Srinivas; Kaza, Vaidehi; Tanriover, Bekir; Torres, Fernando

    2017-11-01

    With the introduction of lung allocation score (LAS), increasingly sicker patients are undergoing lung transplantation (LT). This study was conducted to determine the time trends in need for dialysis after LT, identify variables independently associated with need for dialysis, and evaluate its association with 1- and 5-year mortality. We queried the United Network of Organ Sharing database for adult patients undergoing LT between 1994 and 2014. We excluded patients with simultaneous dual organ transplantation and where data regarding the need for dialysis were not available. Time trends in the yearly incidence of the need for dialysis showed a gradual increase (P = .012). In the post-LAS era, ethnicity, underlying diagnosis, estimated GFR 35 mm Hg, ventilator or extracorporeal membrane oxygenation support at LT, and >20% increase in serum creatinine between listing and match were independently associated with the need for dialysis. Patients with need for dialysis had significantly increased hazard of 1-year (n = 13 849; adjusted hazard ratio, 95% CI:7.23, 6.2-8.4, P need for early dialysis after LT, and these patients have significantly worse early and late survival. Several pre-transplant recipient characteristics are independently associated with the need for dialysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

    Science.gov (United States)

    Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

    2017-02-01

    Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Ten-Year Survival in Patients with Idiopathic Pulmonary Fibrosis After Lung Transplantation.

    Science.gov (United States)

    ten Klooster, Liesbeth; Nossent, George D; Kwakkel-van Erp, Johanna M; van Kessel, Diana A; Oudijk, Erik J; van de Graaf, Ed A; Luijk, Bart; Hoek, Rogier A; van den Blink, Bernt; van Hal, Peter Th; Verschuuren, Erik A; van der Bij, Wim; van Moorsel, Coline H; Grutters, Jan C

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.

  20. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid

    DEFF Research Database (Denmark)

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H

    2016-01-01

    report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony...

  1. Idiopathic pulmonary fibrosis patient supported with extracorporeal membrane oxygenation for 403 days while waiting for a lung transplant: A case report

    Directory of Open Access Journals (Sweden)

    Nao Umei, M.D.

    Full Text Available According to the Extracorporeal Life Support Organization, the average duration of veno-venous extracorporeal membrane oxygenation (V-V ECMO in adults with acute respiratory failure is 10.5–13.5 days. Some patients on V-V ECMO may not recover in such a short period of time, and recently, there have been more reports of prolonged V-V ECMO. However, we do not know how long it is feasible to wait for native lung recovery or lung transplant (LTx with the use of ECMO. We describe a patient with acute exacerbation of idiopathic pulmonary fibrosis supported by ECMO for 403 days while waiting for a LTx. In this case, we kept the patient awake, and he was communicating frequently with his family. We changed the membrane oxygenator 23 times and the cannula 10 times without complication. However, we terminated the treatment on day 403 of ECMO because there was no access site for cannula insertion due to blockage by a venous thrombotic occlusion, making it impossible to continue this bridge to lung transplantation. It has become possible to maintain patients on ECMO for extended periods of time, but it is difficult to manage ECMO for more than one year without the development of a more durable lung support system. Keywords: Lung transplantation, Extracorporeal membrane oxygenation, Idiopathic pulmonary fibrosis

  2. Survival in pediatric lung transplantation: The effect of center volume and expertise.

    Science.gov (United States)

    Khan, Muhammad S; Zhang, Wei; Taylor, Rachel A; Dean McKenzie, E; Mallory, George B; Schecter, Marc G; Morales, David L S; Heinle, Jeffrey S; Adachi, Iki

    2015-08-01

    Institutional operative volume has been shown to impact outcomes of various procedures including lung transplantation (LTx). We sought to determine whether this holds true with pediatric LTx by comparing outcomes of adult centers (with larger overall volume) to those of pediatric centers (with smaller volume but more pediatric-specific experience). A retrospective analysis of the Organ Procurement and Transplant Network data was performed. Centers were categorized as either adult (LTx volume predominantly in adult patients), high-volume pediatric (HVP, ≥4 LTxs/year), or low-volume pediatric (LVP, HVP 3 [5%], LVP 8 [13%]). Although adult centers had larger overall LTx volume, their pediatric experiences were severely limited (median 1/year). In younger children, HVP centers were significantly better than LVP centers for patient survival (half-life: 7.3 vs 2.9 years, p = 0.002). Similarly, in older children and adolescents, HVP centers were significantly better than adult centers for patient survival (half-life: 4.6 vs 2.5 years, p = 0.001). Of note, even LVP centers tended to have longer patient survival than adult centers (p = 0.064). Multivariable analysis identified adult centers as an independent risk factor for graft failure (hazard ratio: 1.5, p < 0.001) as with LVP (hazard ratio: 1.3, p = 0.0078). Despite larger overall clinical volume, outcomes among pediatric LTx recipients in adult centers are not superior to those of pediatric centers. Not only center volume but pediatric-specific experience has an impact on outcomes in pediatric LTx. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Review of the International Society for Heart and Lung Transplantation Practice guidelines for management of heart failure in children.

    Science.gov (United States)

    Colan, Steven D

    2015-08-01

    In 2004, practice guidelines for the management of heart failure in children by Rosenthal and colleagues were published in conjunction with the International Society for Heart and Lung Transplantation. These guidelines have not been updated or reviewed since that time. In general, there has been considerable controversy as to the utility and purpose of clinical practice guidelines, but there is general recognition that the relentless progress of medicine leads to the progressive irrelevance of clinical practice guidelines that do not undergo periodic review and updating. Paediatrics and paediatric cardiology, in particular, have had comparatively minimal participation in the clinical practice guidelines realm. As a result, most clinical practice guidelines either specifically exclude paediatrics from consideration, as has been the case for the guidelines related to cardiac failure in adults, or else involve clinical practice guidelines committees that include one or two paediatric cardiologists and produce guidelines that cannot reasonably be considered a consensus paediatric opinion. These circumstances raise a legitimate question as to whether the International Society for Heart and Lung Transplantation paediatric heart failure guidelines should be re-reviewed. The time, effort, and expense involved in producing clinical practice guidelines should be considered before recommending an update to the International Society for Heart and Lung Transplantation Paediatric Heart Failure guidelines. There are specific areas of rapid change in the evaluation and management of heart failure in children that are undoubtedly worthy of updating. These domains include areas such as use of serum and imaging biomarkers, wearable and implantable monitoring devices, and acute heart failure management and mechanical circulatory support. At the time the International Society for Heart and Lung Transplantation guidelines were published, echocardiographic tissue Doppler, 3 dimensional

  4. The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation.

    Directory of Open Access Journals (Sweden)

    Michael Y Shino

    Full Text Available Since the pathogenesis of chronic lung allograft dysfunction (CLAD remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk.All transbronchial biopsies (TBBX from patients who received lung transplantation between 2000 to 2010 were reviewed. BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11 were compared between episodes of OP and "healthy" biopsies using linear mixed-effects models. The association between CXCR3 ligand concentrations during OP and CLAD risk was evaluated using proportional hazards models with time-dependent covariates.There were 1894 bronchoscopies with TBBX evaluated from 441 lung transplant recipients with 169 (9% episodes of OP and 907 (49% non-OP histopathologic injuries. 62 (37% episodes of OP were observed during routine surveillance bronchoscopy. Eight hundred thirty-eight (44% TBBXs had no histopathology and were classified as "healthy" biopsies. There were marked elevations in BALF CXCR3 ligand concentrations during OP compared with "healthy" biopsies. In multivariable models adjusted for other injury patterns, OP did not significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations were not taken into account. However, OP with elevated CXCR3 ligands markedly increased CLAD risk in a dose-response manner. An episode of OP with CXCR3 concentrations greater than the 25th, 50th and 75th percentiles had HRs for CLAD of 1.5 (95% CI 1.0-2.3, 1.9 (95% CI 1.2-2.8 and 2.2 (95% CI 1.4-3.4, respectively.This study identifies OP, a relatively uncommon histopathologic finding after lung transplantation, as a major risk factor for CLAD

  5. Long-term survival despite early loss of graft function after single lung transplantation for pulmonary fibrosis

    NARCIS (Netherlands)

    Ouwens, JP; van den Berg, JWK; van der Bij, W; Koeter, GH

    We report a patient who received a single, left lung transplantation for idiopathic pulmonary fibrosis. The effect of the graft on pulmonary improvement was only temporary, because the patient developed obliterative bronchiolitis (OB), resulting in complete destruction of the graft. The patient,

  6. Efficacy of total lymphoid irradiation for chronic allograft rejection following double lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Trulock, Elbert M.; Lynch, John P.

    1997-01-01

    Purpose: The purpose of this study was to assess the safety and efficacy of total lymphoid irradiation in a series of patients experiencing chronic rejection following bilateral lung transplantation. Patients and Materials: Eleven patients (10 males, 1 female) received total lymphoid irradiation for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Treatment was delivered between March, 1995, and September, 1996. Mean patient age was 33 years (range 15-51). Indications for transplantation included cystic fibrosis (7 patients), alpha 1 anti-trypsin deficiency (2 patients), primary pulmonary hypertension (1 patient), and emphysema (1 patient). Radiation therapy was prescribed as 800 cGy delivered in ten 80 cGy fractions, 2 fractions per week, via AP/PA mantle and inverted-Y fields. Radiation was withheld for total wbc count 3 , absolute neutrophil count 3 , or platelets 3 . Serial pre- and post-radiation therapy pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements (use of methylprednisolone, azathioprine, mycophenolate mofetil, OKT3, and FK506) were monitored. Results: In the 3 months preceding total lymphoid irradiation, the average decrease in FEV 1 was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). At initiation of radiation therapy, the average FEV 1 was 1.4 liters (range 0.77-2.28). Only (4(11)) patients completed all 10 treatment fractions. Reasons for discontinuation included unabated rejection (4 patients), worsening pulmonary infection (2 patients), and persistent thrombocytopenia (1 patient). No treatment course was discontinued because of persistent neutropenia or leukopenia. Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related donor transplants. He is alive and well. Six patients died. Two of these deaths were due

  7. Patterns and correlates of adherence to self-monitoring in lung transplant recipients during the first 12 months after discharge from transplant.

    Science.gov (United States)

    Hu, Lu; DeVito Dabbs, Annette; Dew, Mary Amanda; Sereika, Susan M; Lingler, Jennifer H

    2017-08-01

    Self-monitoring of lung function, vital signs, and symptoms is crucial for lung transplant recipients (LTRs) to ensure early detection of complications and prompt intervention. This study sought to identify patterns and correlates of adherence to self-monitoring among LTRs over the first 12 months post-discharge from transplant. This study analyzed existing data from the usual care arm participants of a randomized clinical trial who tracked self-monitoring activities using paper-and-pencil logs. Adherence was calculated as the percent of days LTRs recorded any self-monitoring data per interval: hospital discharge-2 months, 3-6 months, and 7-12 months. The sample (N=91) was mostly white (87.9%), male (61.5%), with a mean age of 57.2±13.8 years. Group-based trajectory analyses revealed two groups: (i) moderately adherent with slow decline (n=29, 31.9%) and (ii) persistently nonadherent (n=62, 68.1%). Multivariate binary logistic regression revealed the following baseline factors increased the risk in the persistently nonadherent group: female (P=.035), higher anxiety (P=.008), and weaker sense of personal control over health (P=.005). Poorer physical health over 12 months were associated with increased risk in the persistently nonadherent group (P=.004). This study highlighted several modifiable factors for future interventions to target, including reducing post-transplant anxiety, and strengthening sense of personal control over health in LTRs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

    Science.gov (United States)

    Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

    2010-09-01

    Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, pvolume (0.75+/-0.10 and 0.79+/-0.07 litres) (pvolumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

  9. Neisseria lactamica Causing a Lung Cavity and Skin Rash in a Renal Transplant Patient: First Report from India

    Directory of Open Access Journals (Sweden)

    Khalid Hamid Changal

    2016-01-01

    Full Text Available Neisseria lactamica, a commensal, has been very rarely reported to cause diseases in immunocompromised hosts. In medical literature, there is only one report of a cavitatory lung lesion caused by it. The patient was a kidney transplant recipient. Neisseria lactamica was found to be the cause of his pulmonary cavity and a desquamating rash on feet. With the rapidly spreading medical advance, more and more patients are getting organ transplants, so the population of immunocompromised people is on the rise. We expect more sinister and less expected organisms to cause diseases in patients who have organ transplants.

  10. Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient.

    Science.gov (United States)

    Jain, Richa; Gupta, Kirti; Bhatia, Anmol; Bansal, Arun; Bansal, Deepak

    2017-09-15

    Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.

  11. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  12. Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis.

    Science.gov (United States)

    Hammond, S P; Martin, S T; Roberts, K; Gabardi, S; Fuhlbrigge, A L; Camp, P C; Goldberg, H J; Marty, F M; Baden, L R

    2013-04-01

    A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies. We retrospectively assessed incidence, cumulative probability, and predictors of CMV disease and viremia in LT recipients transplanted between July 2004 and December 2009 at our center, where antiviral CMV prophylaxis for 6-12 months is standard. Of 129 LT recipients, 94 were at risk for CMV infection based on donor CMV seropositivity (D+) or recipient seropositivity (R+); 14 developed CMV disease (14.9%): 11 with CMV syndrome, 2 with pneumonitis, and 1 with gastrointestinal disease by the end of follow-up (October 2010); 17 developed asymptomatic CMV viremia (18.1%). The cumulative probability of CMV disease was 17.4% 18 months after transplantation. CMV D+/R- recipients who routinely received 1 year of prophylaxis were more likely to develop CMV disease compared with D+/R+ or D-/R+ recipients, who routinely received 6 months of prophylaxis (12/45 vs. 2/25 vs. 0/24, P = 0.005). Recipients who stopped CMV prophylaxis before 12 months (in D+/R- recipients) and 6 months (in R+ recipients) tended to develop CMV disease more than those who did not (9/39 vs. 3/41, P = 0.06). On a 6-month CMV prophylaxis protocol, few R+ recipients developed CMV disease in this cohort. In contrast, despite a 12-month prophylaxis protocol, D+/R- LT recipients remained at highest risk for CMV disease. © 2012 John Wiley & Sons A/S.

  13. [Value of preoperative pulmonary artery diastolic pressure on predicting primary graft dysfunction after bilateral lung transplantation for patients with idiopathic pulmonary fibrosis].

    Science.gov (United States)

    Zhang, Feng; Xu, Hongyang; Jiang, Shuyun; Li, Jiaqiong; Lu, Shunmei; Wang, Dapeng; Zang, Zhidong; Pan, Hong; Chen, Jingyu

    2017-05-01

    To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF). A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation. Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGD group, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non

  14. Computed tomography of complications of lung transplantation

    International Nuclear Information System (INIS)

    Soyer, P.; Devine, N.; Frachon, I.; Vinatier, I.; Stern, M.; Le Normand, S.; Scherrer, A.

    1997-01-01

    In spite of improvements in single or double lung transplantation (LT) technique, complications after LT are not uncommon; the most frequent ale anastomotic complications, infections and rejection (acute or chronic). Early detection of complications of LT allows the optimal therapeutic option to be taken, yielding decreased morbidity and mortality. In some cases, CT plays a key role in early detection of several complications of LT that may not be depicted with other diagnostic modalities, so that knowledge of their CT features is important. In this pictorial review, the authors describe the spectrum of CT features of the complications of LT (including reimplantation response, mechanical problems, acute and chronic rejection, infection, lymphoproliferative disorders, recurrence of the initial disease and complications involving the pleura and the anastomotic sites). In addition, the authors analyze the value of CT compared to that of the other available modalities for the detection of complications of LT. (orig.). With 19 figs

  15. Impact of pulmonary rehabilitation on quality of life and functional capacity in patients on waiting lists for lung transplantation

    Directory of Open Access Journals (Sweden)

    Juliessa Florian

    2013-06-01

    Full Text Available OBJECTIVE: To investigate the impact of a pulmonary rehabilitation program on the functional capacity and on the quality of life of patients on waiting lists for lung transplantation. METHODS: Patients on lung transplant waiting lists were referred to a pulmonary rehabilitation program consisting of 36 sessions. Before and after the program, participating patients were evaluated with the six-minute walk test and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36. The pulmonary rehabilitation program involved muscle strengthening exercises, aerobic training, clinical evaluation, psychiatric evaluation, nutritional counseling, social assistance, and educational lectures. RESULTS: Of the 112 patients initially referred to the program, 58 completed it. The mean age of the participants was 46 ± 14 years, and females accounted for 52%. Of those 58 patients, 37 (47% had pulmonary fibrosis, 13 (22% had pulmonary emphysema, and 18 (31% had other types of advanced lung disease. The six-minute walk distance was significantly greater after the program than before (439 ± 114 m vs. 367 ± 136 m, p = 0.001, the mean increase being 72 m. There were significant point increases in the scores on the following SF-36 domains: physical functioning, up 22 (p = 0.001, role-physical, up 10 (p = 0.045; vitality, up 10 (p < 0.001; social functioning, up 15 (p = 0.001; and mental health, up 8 (p = 0.001. CONCLUSIONS: Pulmonary rehabilitation had a positive impact on exercise capacity and quality of life in patients on lung transplant waiting lists.

  16. Stress, psychological distress, and coping in patients on the waiting list for lung transplantation : an exploratory study

    NARCIS (Netherlands)

    Vermeulen, KM; Bosma, OH; van der Bij, W; Koeter, GH; TenVergert, EM

    Little information is available in literature on quality of life, stress and coping during the period patients are waiting for lung transplantation. This study explored potential stressful events that patients experience during the waiting period assessed the level of anxiety and depression and

  17. Pseudomembranous aspergillus bronchitis in a double-lung transplanted patient: unusual radiographic and CT features

    International Nuclear Information System (INIS)

    Ducreux, D.; Chevallier, P.; Raffaelli, C.; Padovani, B.; Perrin, C.; Jourdan, J.; Hofman, P.

    2000-01-01

    Pseudomembranous aspergillus bronchitis is considered as an early form of invasive pulmonary aspergillosis, a well-known airway infection in immunocompromised patients. Radiologic features concerning invasive aspergillosis of the airways have been reported. However, we describe here an unusual feature of invasive aspergillus bronchitis, never reported to date, observed in a double-lung transplanted patient. Chest radiograph and CT revealed significant peribronchial thickening without any parenchymal involvement. (orig.)

  18. Aspiration, Localized Pulmonary Inflammation, and Predictors of Early-Onset Bronchiolitis Obliterans Syndrome after Lung Transplantation

    Science.gov (United States)

    Fisichella, P Marco; Davis, Christopher S; Lowery, Erin; Ramirez, Luis; Gamelli, Richard L; Kovacs, Elizabeth J

    2014-01-01

    BACKGROUND We hypothesized that immune mediator concentrations in the bronchoalveolar fluid (BALF) are predictive of bronchiolitis obliterans syndrome (BOS) and demonstrate specific patterns of dysregulation, depending on the presence of acute cellular rejection, BOS, aspiration, and timing of lung transplantation. STUDY DESIGN We prospectively collected 257 BALF samples from 105 lung transplant recipients. The BALF samples were assessed for absolute and differential white blood cell counts and 34 proteins implicated in pulmonary immunity, inflammation, fibrosis, and aspiration. RESULTS There were elevated BALF concentrations of interleukin (IL)-15, IL-17, basic fibroblast growth factor, tumor necrosis factor–α, and myeloperoxidase, and reduced concentrations of α1-antitrypsin, which were predictive of early-onset BOS. Patients with BOS had an increased percentage of BALF lymphocytes and neutrophils, with a reduced percentage of macrophages (p < 0.05). The BALF concentrations of IL-1β; IL-8; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; neutrophil elastase; and pepsin were higher in patients with BOS (p < 0.05). Among those with BOS, BALF concentrations of IL-1RA; IL-8; eotaxin; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; myeloperoxidase; and neutrophil elastase were positively correlated with time since transplantation (p < 0.01). Those with worse grades of acute cellular rejection had an increased percentage of lymphocytes in their BALF (p < 0.0001) and reduced BALF concentrations of IL-1β, IL-7, IL-9, IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, and vascular endothelial growth factor (p ≤ 0.001). Patients with aspiration based on detectable pepsin had increased percentage of neutrophils (p < 0.001) and reduced BALF concentrations of IL-12 (p < 0.001). CONCLUSIONS The BALF levels

  19. High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells

    Directory of Open Access Journals (Sweden)

    Steven M. Garcia

    2018-03-01

    Full Text Available Summary: Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs. : Garcia and colleagues report methods for efficient purification of satellite cells from human skeletal muscle. They use their approaches to demonstrate stem cell functions of endogenous satellite cells and to make human satellite cells accessible for sharing among researchers. Keywords: human satellite cell purification, serial transplantation, satellite cell cryopreservation

  20. Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Winkler-Heil, R.; Hofmann, W. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Hussain, M. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Higher Education Commission of Pakistan, Islamabad (Pakistan)

    2015-05-15

    Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM{sup -1}. If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas. (orig.)

  1. New estimates for human lung dimensions

    International Nuclear Information System (INIS)

    Kennedy, Christine; Sidavasan, Sivalal; Kramer, Gary

    2008-01-01

    Full text: The currently used lung dimensions in dosimetry were originally estimated in the 1940s from Army recruits. This study provides new estimates of lung dimensions based on images acquired from a sample from the general population (varying age and sex). Building accurate models, called phantoms, of the human lung requires that the spatial dimensions (length, width, and depth) be quantified, in addition to volume. Errors in dose estimates may result from improperly sized lungs as the counting efficiency of externally mounted detectors (e.g., in a lung counter) is dependent on the position of internally deposited radioactive material (i.e., the size of the lung). This study investigates the spatial dimensions of human lungs. Lung phantoms have previously been made in one of two sizes. The Lawrence Livermore National Laboratory Torso Phantom (LLNL) has deep, short lungs whose dimensions do not comply well with the data published in Report 23 (Reference Man) issued by the International Commission on Radiological Protection (ICRP). The Japanese Atomic Energy Research Institute Torso Phantom(JAERI), has longer, shallower lungs that also deviate from the ICRP values. However, careful examination of the ICRP recommended values shows that they are soft. In fact, they have been dropped from the ICRP's Report 89 which updates Report 23. Literature surveys have revealed a wealth of information on lung volume, but very little data on the spatial dimensions of human lungs. Better lung phantoms need to be constructed to more accurately represent a person so that dose estimates may be quantified more accurately in view of the new, lower, dose limits for occupationally exposed workers and the general public. Retrospective chest images of 60 patients who underwent imaging of the chest- lungs as part of their healthy persons occupational screening for lung disease were chosen. The chosen normal lung images represent the general population). Ages, gender and weight of the

  2. How to optimize the lung donor.

    Science.gov (United States)

    Sales, Gabriele; Costamagna, Andrea; Fanelli, Vito; Boffini, Massimo; Pugliese, Francesco; Mascia, Luciana; Brazzi, Luca

    2018-02-01

    Over the last two decades, lung transplantation emerged as the standard of care for patients with advanced and terminal lung disease. Despite the increment in lung transplantation rates, in 2016 the overall mortality while on waiting list in Italy reached 10%, whereas only 39% of the wait-list patients were successfully transplanted. A number of approaches, including protective ventilatory strategy, accurate management of fluid balance, and administration of a hormonal resuscitation therapy, have been reported to improve lung donor performance before organ retrieval. These approaches, in conjunction with the use of ex-vivo lung perfusion technique contributed to expand the lung donor pool, without affecting the harvest of other organs and the outcomes of lung recipients. However, the efficacy of issues related to the ex-vivo lung perfusion technique, such as the optimal ventilation strategy, the ischemia-reperfusion induced lung injury management, the prophylaxis of germs transmission from donor to recipient and the application of targeted pharmacologic therapies to treat specific donor lung injuries are still to be explored. The main objective of the present review is to summarize the "state-of-art" strategies to optimize the donor lungs and to present the actual role of ex-vivo lung perfusion in the process of lung transplant. Moreover, different approaches about the technique reported in literature and several issues that are under investigation to treat specific donor lung injury will be discussed.

  3. Reliability of sternal instability scale (SIS) for transverse sternotomy in lung transplantation (LTX).

    Science.gov (United States)

    Fuller, Louise M; El-Ansary, Doa; Button, Brenda; Bondarenko, Janet; Marasco, Silvana; Snell, Greg; Holland, Anne E

    2018-01-25

    A surgical incision for bilateral sequential lung transplantation (BSLTX) is the "clam shell" (CSI) approach via bilateral anterior thoracotomies and a transverse sternotomy to allow for sequential replacement of the lungs. This can be associated with significant post-operative pain, bony overriding or sternal instability. The sternal instability scale (SIS) is a non-invasive manual assessment tool that can be used to detect early bony non-union or instability following CSI; however, its reliability is unknown. This prospective blinded reliability study aimed to assess intra-rater and inter-rater reliability of the SIS following lung transplantation. Participants post BSLTX aged older than 18 years underwent sternal assessment utilizing the SIS. Two assessors examined the sternum using a standardized protocol at two separate time points with a test-re-test time of 48 hours. The outcome measure was SIS tool using four categories from 0 (clinically stable) to 3 (separated sternum with overriding). In total, 20 participants (75% female) with a mean age of 48 years (SD 17) and mean pain score of 3 out of 10 were included, 60% having well healed wounds and 25% reporting symptoms of sternal clicking. The most painful self-reported painful activity was coughing. The SIS demonstrated excellent reliability with a kappa = 0.91 by different assessors on the same day, and kappa = 0.83 for assessments by the same assessor on different days. The SIS is a reliable manual assessment tool for evaluation of sternal instability after CSI following BSLTX and may facilitate the timely detection and management of sternal instability.

  4. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  5. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident......, identified as ATP-ase positive dendritic cells, have almost disappeared from the transplanted epithelium whereas at day 21 after transplantation such cells were abundant. It is suggested that the ATP-ase positive cells which reappear in the transplanted epithelium are of mouse origin....

  6. [Anesthetic care for fibrobronchoscopy in patients with chronic terminal respiratory insufficiency undergoing evaluation for isolated lung transplantation].

    Science.gov (United States)

    Solca, M; Elena, A; Croci, M; Damia, G

    1993-01-01

    During the first 18 month operation of the isolated lung transplantation program at or Institution, eight patients with terminal chronic respiratory failure underwent fiberoptic bronchoscopy and broncho-alveolar lavage as part of their evaluation for isolated lung transplantation. Four patients had severe obstructive, three restrictive, and one mixed, obstructive and restrictive, disease; all of them were on continuous supplemental oxygen. Procedures were performed under topical anaesthesia, with either light sedation or simple monitored anaesthesia care. Monitoring included non-invasive blood pressure measurement, pulse oximeter and precordial stethoscope. No adverse events were recorded, except in one case, when pulse oximeter reading precipitously dropped below 80%, to a minimum of 68-69%. The procedures was terminated short of its completion, and the patient was briefly assisted with manual bag ventilation on oxygen 100%. Pulse oximeter quickly returned to normal levels (above 90%), and the patient promptly recovered, without complications. The importance of monitored anaesthesia care during fiberoptic bronchoscopy (a usually benign procedure) in critically ill patients is greatly emphasized.

  7. Idiopathic pulmonary fibrosis with complication of severe respiratory failure, right heart failure, and steroid induced diabetes – qualification for lung transplantation as a matter of urgency

    Directory of Open Access Journals (Sweden)

    Beata P. Kraśnicka-Sokół

    2016-09-01

    Full Text Available A 62-year-old woman 146 cm tall and weighing 50 kg, due to idiopathic pulmonary fibrosis, was firstly approved for lung transplantation according to the planned mode. Due to the low height of the patient there were difficulties in the selection of the donor and prolonged waiting time for the surgery. Rapid progression of pulmonary hypertension and steroid-induced diabetes forced us to change the mode of the procedure to urgent. The description of the case shows the difficulties in therapy and choosing the appropriate time for lung transplantation. In this case, the collaboration of specialists from various fields in the decision on transplant is noteworthy.

  8. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Mark M.; Sheybani, Elizabeth F. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Campus Box 8131, St. Louis, MO (United States); Zhang, Lingxin [Washington University School of Medicine, Department of Pathology, St. Louis, MO (United States); Stoll, Janis M. [Washington University School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, St. Louis, MO (United States)

    2016-04-15

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  9. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    International Nuclear Information System (INIS)

    Hammer, Mark M.; Sheybani, Elizabeth F.; Zhang, Lingxin; Stoll, Janis M.

    2016-01-01

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  10. Do the lungs contribute to propofol elimination in patients during orthotopic liver transplantation without veno-venous bypass?

    Institute of Scientific and Technical Information of China (English)

    Yi-Zhong Chen; Sheng-Mei Zhu; Hui-Liang He; Jian-Hong Xu; Su-Qin Huang; Qing-Lian Chen

    2006-01-01

    BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol. METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate of 2 mg· kg-1·h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the ifrst hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed-phase, high-performance liquid chromatographic method with lfuorescence detection. RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose signiifcantly compared with T0 and T1 (P CONCLUSIONS:Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.

  11. Pulmonary Rehabilitation in Lung Transplant Candidates: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Stefanie Tonguino Rosero

    2013-09-01

    Full Text Available Pulmonary rehabilitation (PR aims to improve physical fitness and to decrease symptoms in patients with chronic lung disease; however there is not clear evidence regarding the benefits of PR in candidates for lung transplantation (LT. Objective. To determine the effectiveness of PR in LT candidates and also to find out how quality of life and exercise tolerance affects the survival of these patients. Methodology. Electronic databases (Medline, Cochrane, PEDro, Scient Direct and SciELO Search of articles in spanish, english or portuguese; controlled clinical trials and cohort studies published between 2000-2011 regarding PR in candidates for LT, the model of Cochrane systematic reviews was used. Results. The papers included were four cohort, two of which regarded of survival pre LT using the six minutes walking test (6MWT; a study of quality of life related to post LT survival and an exercise tolerance study. Controlled clinical trial was not found. Conclusions. The information found in the included studies had clinical and methodological heterogeneity therefore a meta-analysis could not been undertaken. The PR should be considered as an essential part to maintain the exercise tolerance and the patient’s survival. Research regarding this subject is important and should be carried out.

  12. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

    Science.gov (United States)

    Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

    2016-03-01

    Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

  13. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    Science.gov (United States)

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  14. Lung transplantation and survival outcomes in patients with oxygen-dependent COPD with regard to their alpha-1 antitrypsin deficiency status

    Directory of Open Access Journals (Sweden)

    Ekström M

    2017-11-01

    Full Text Available Magnus Ekström, Hanan Tanash Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden Background: Individuals with severe alpha-1 antitrypsin deficiency (AATD have an increased risk of developing COPD. However, outcomes during long-term oxygen therapy (LTOT in patients with severe AATD and hypoxemia are unknown.Patients and methods: This was a prospective, population-based, consecutive cohort study of patients on LTOT due to COPD in the period from January 1, 1987, to June 30, 2015, in the Swedish National Registry for Respiratory Failure (Swedevox. Severe AATD was identified using the Swedish AATD registry and confirmed by isoelectric focusing. Data on lung transplantation (LTx were obtained from the two lung transplantation centers in Sweden. Mortality and causes of death were assessed based on the National Causes of Death Registry and analyzed using multivariable Cox regression.Results: A total of 14,644 patients who started LTOT due to COPD were included in this study. No patient was lost to follow up. Patients with AATD were younger, included more males and more never smokers, and had fewer comorbidities. During a median follow-up of 1.6 years (interquartile range [IQR], 2.7 on LTOT, patients without severe AATD had a higher mortality, hazard ratio [HR] 1.53 (95% CI, 1.24–1.88, adjusting for age, sex, smoking status, body mass index, performance status, level of hypoxemia, and comorbidities. Cardiovascular deaths were increased. A higher proportion of AATD patients underwent LTx, 53 (19% vs 118 (1%. Survival after LTx was similar for AATD and non-AATD patients and was predicted by age.Conclusion: In oxygen-dependent COPD, patients with severe AATD have a longer survival time on LTOT, but they have a similar prognosis after lung transplantation compared with patients without AATD. Keywords: COPD, long-term oxygen therapy, lung transplantation, severe alpha-1 antitrypsin deficiency

  15. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    DEFF Research Database (Denmark)

    Loeve, Martine; Hop, Wim C. J.; de Bruijne, Marleen

    2012-01-01

    Rationale: Up to a third of cystic fibrosis (CF) patients awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). Objectives: This study investigated the association between...... CT and survival in CF patients screened for LTX. Methods: Clinical data and chest CTs of 411 CF patients screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) 4-category scoring system, including the components "infection....../inflammation" (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR) and bulla/cysts (BUL). The volume of each component was computed using semi-automated software. Survival analysis included Kaplan-Meier curves, and Cox-regression models. Measurements and main results: 366 (186 males) out of 411...

  16. High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients

    International Nuclear Information System (INIS)

    Gazzoni, Fernando Ferreira; Hochhegger, Bruno; Severo, Luiz Carlos; Marchiori, Edson; Pasqualotto, Alessandro; Sartori, Ana Paula Garcia; Schio, Sadi; Camargo, José

    2014-01-01

    Objective: The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection. Materials and methods: We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case. Conclusion: The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients

  17. Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

    Science.gov (United States)

    Zeriouh, Mohamed; Sabashnikov, Anton; Mohite, Prashant N; Zych, Bartlomiej; Patil, Nikhil P; García-Sáez, Diana; Koch, Achim; Weymann, Alexander; Soresi, Simona; Wippermann, Jens; Wahlers, Thorsten; De Robertis, Fabio; Popov, Aron-Frederik; Simon, André R

    2016-09-01

    Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further

  18. Colonic complications following human bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paulino Martínez Hernández-Magro

    2015-01-01

    Full Text Available Background: Human bone marrow transplantation (BMT becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. Objective: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD, and treatment of patients suffering with colonic complications of human bone marrow transplantation. Patients and methods: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. Results: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%; five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%; graft vs. host disease was present in 16 patients (20%; 13 patients (16.8% developed acute colonic GVHD, and 3 (3.8% chronic GVHD. Infection was identified in 9 patients (11.6%. Conclusions: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0–20 day chemotherapy toxicity, 20 and more GVHD, and infection could appear in any time of transplantation. Resumo: Experiência: O transplante de medula óssea humana (MOH passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. Objetivo: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto

  19. Some quantitative studies on the transplantation of human tissues into nude mice

    International Nuclear Information System (INIS)

    Zietman, A.; Suit, H.D.; Sedlacek, R.

    1987-01-01

    Quantitative cell transplantation assays (TD/sub 50/) were performed for human tumors xenografted into athymic NCr(nμ/nμ) nude mice. Transplantation assays for FaDu when transplanted into brain and when transplanted into subcutaneous tissues are compared. Effects of immunization are discussed and results are given

  20. Lung Allocation Score: A Single-Center Simulation.

    Science.gov (United States)

    Rosso, L; Palleschi, A; Tosi, D; Mendogni, P; Righi, I; Carrinola, R; Montoli, M; Damarco, F; Rossetti, V; Morlacchi, L C; Nosotti, M

    2016-03-01

    The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted. We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation. We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population. High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

    Science.gov (United States)

    Moser, Bernhard; Jaksch, Peter; Taghavi, Shahrokh; Muraközy, Gabriella; Lang, Georg; Hager, Helmut; Krenn, Claus; Roth, Georg; Faybik, Peter; Bacher, Andreas; Aigner, Clemens; Matilla, José R; Hoetzenecker, Konrad; Hacker, Philipp; Lang, Irene; Klepetko, Walter

    2018-01-01

    Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides

  2. Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.

    1985-01-01

    The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases

  3. The world's first human-to-human heart transplant at Groote Schuur ...

    African Journals Online (AJOL)

    The world's first human-to-human heart transplant at Groote Schuur Hospital: 50 years later. Johan Brink, Tim Pennel, Karen Seele, Peter Zilla. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO ...

  4. Downregulation of Lung Toll-Like Receptor 4 Could Effectively Attenuate Liver Transplantation-Induced Pulmonary Damage at the Early Stage of Reperfusion

    Directory of Open Access Journals (Sweden)

    Xinjin Chi

    2015-01-01

    Full Text Available Acute lung injury (ALI is a severe complication of orthotopic liver transplantation (OLT with unclear underline mechanism. Toll-like receptor 4 (TLR4 has been identified as a key receptor mediating inflammation. We hypothesized that TLR4-mediated pulmonary inflammation may contribute to development of ALI during OLT. Patients with or without ALI were observed for serum cytokines and expression of TLR4 on peripheral blood polymorphonuclear leukocytes (PMNs. Next, rats which underwent orthotopic autologous liver transplantation (OALT were divided into sham and model groups. Pulmonary function and the level of TLR4 expression and cytokines were analyzed. Furthermore, the role of TLR4 in OALT-mediated ALI was assessed in rats treated with TLR4-siRNA before OALT. The PMNs TLR4 expression and the serum TNF-α and IL-β level were higher in patients with ALI than those with non-ALI. Interestingly, lung TLR4 expression was significantly increased after 8 hours of OALT with increased levels of TNF-α and IL-β, which lead to lung pathological damage and an increase of lung myeloperoxidase content. Moreover, knockdown of TLR4 reduced lung cytokines release and reversed the above pathologic changes after OALT and finally improved rats’ survival rate. In conclusion, TLR4 overexpression, potentially by stimulating proinflammatory cytokine overproduction, contributes to the development of ALI after OLT.

  5. Effect of primarily cultured human lung cancer-associated fibroblasts on radiosensitivity of lung cancer cells

    International Nuclear Information System (INIS)

    Ji Xiaoqin; Ji Jiang; Chen Yongbing; Shan Fang; Lu Xueguan

    2014-01-01

    Objective: To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells. Methods: Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining. The CAF was placed in direct contact co-culture with lung cancer A 549 and H 1299 cells, and the effects of CAF on the radiosensitivity of A 549 and H 1299 cells were evaluated by colony-forming assay. Results: The human lung CAF obtained by adherent culture could stably grow and proliferate, and it had specific expression of α-smooth muscle actin, vimentin, and fibroblast activation protein,but without expression of cytokeratin-18. The plating efficiency (PE, %) of A 549 cells at 0 Gy irradiation was (20.0 ± 3.9)% when cultured alone versus (32.3 ± 5.5)% when co-cultured with CAF (t=3.16, P<0.05), and the PE of H 1299 cells at 0 Gy irradiation was (20.6 ± 3.1)% when cultured alone versus (35.2 ± 2.3)% when co-cultured with CAF (t=6.55, P<0.05). The cell survival rate at 2 Gy irradiation (SF 2 ) of A 549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t=0.88, P>0.05), and the SF 2 of H 1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t=2.08, P>0.05). The protection enhancement ratios of human lung CAF for A 549 cells and H 1299 cells were 1.29 and 1.25, respectively. Conclusions: Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them, and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells. (authors)

  6. Does donor arterial partial pressure of oxygen affect outcomes after lung transplantation? A review of more than 12,000 lung transplants.

    Science.gov (United States)

    Zafar, Farhan; Khan, Muhammad S; Heinle, Jeffrey S; Adachi, Iki; McKenzie, E Dean; Schecter, Marc G; Mallory, George B; Morales, David L S

    2012-04-01

    In lung transplantation (LTx), the arterial partial pressure of oxygen (PaO(2)) is traditionally regarded as critical information for assessment of donor lung function. Each center sets its own thresholds; by convention, a donor PaO(2) of less than 300 mm Hg has been considered disqualifying. Limited literature exists to support such a practice. We analyzed all LTxs performed in the United States over a 9-year period to assess the effect of donor PaO(2) on graft survival. The United Network for Organ Sharing (UNOS) database was queried for LTx (January 2000-November 2009). Of 12,545 LTx performed, 12,045 (96%) had donor PaO(2) data on a fraction of inspired oxygen of 1.0, recorded at the time of procurement. Mean donor PaO(2) was 407 ± 140 mm Hg. The majority of LTxs had a donor PaO(2) greater than 300 mm Hg (9593 (80%]) whereas PaO(2) was 200 mm Hg or less in 1830 (15%) and 201 to 300 in 582 (5%) donors. Use of donors with a PaO(2) of less than 200 increased over time from 5% (45) in 2000 to 21% (295) in 2009 (P = .002). Kaplan-Meier survival analysis showed no difference in graft survival with differing donor PaO(2)s, irrespective of whether patients had a single or double LTx. A Cox multivariable analysis of 21 donor characteristics demonstrated that donor PaO(2) had no association with graft survival. Donor PaO(2) levels did not affect graft survival. The use of donors with lower PaO(2)s could substantially increase the donor pool. We are not suggesting that donor PaO(2) is not important when assessing potential lung donors but its level of importance in regard to other criteria appears less than previously believed. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  7. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yina; Tang, Yemin; Peng, Ling

    2014-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An initial partial response to icotinib was achieved, and graft function remained good. However, the patient subsequently developed interstitial pneumonitis. The plasma concentrations of rapamycin and icotinib were within the normal ranges, which excluded the possibility of a pharmacokinetic drug interaction and indicated that the interstitial pneumonitis was likely to be associated with the side-effects of icotinib. Drug therapy was discontinued and the patient underwent a segmentectomy. Tacrolimus was administered for ongoing renal graft immunosuppression. To the best of our knowledge, this is the first report of the concomitant administration of icotinib and rapamycin in post-transplant de novo lung cancer. It is also the first report of interstitial pneumonitis associated with icotinib in a post-transplant patient.

  8. The Interplay of "Big Five" Personality Factors and Metaphorical Schemas: A Pilot Study with 20 Lung Transplant Recipients

    Science.gov (United States)

    Goetzmann, Lutz; Moser, Karin S.; Vetsch, Esther; Grieder, Erhard; Klaghofer, Richard; Naef, Rahel; Russi, Erich W.; Boehler, Annette; Buddeberg, Claus

    2007-01-01

    The aim of the present study was to investigate the interplay between personality factors and metaphorical schemas. The "Big Five" personality factors of 20 patients after lung transplantation were examined with the NEO-FFI. Patients were questioned about their social network, and self- and body-image. The interviews were assessed with metaphor…

  9. Radioimmunoimaging of nude mice bearing human lung adenocarcinoma xenografts after injecting 131I-McAbs

    International Nuclear Information System (INIS)

    Liu Liang

    1992-01-01

    Monoclonal antibodies (Lc86a-C5, Lc86a-H8) directed against human lung adenocarcinoma cell line LTEP-a-2 and normal BALB/c IgG were labelled with iodine-131 by chloramine T. The 131 I-McAbs and 131 I-IgG were respectively injected into the peritoneal cavities of nude mice bearing transplanted human lung adenocarcinoma cell line LTEP-a-2. After 72 h, the tumor tissue in nude mice injected with 131 I-McAbs was distinguishable from normal tissues as a very clear image obtained during gamma scintigraphy. No difference was found between tumor and normal tissues in the nude mice injected with 131 I-IgG. The tumor: blood ration was 3.1:1 in nude injected with 131 I McAb(H8) and 0.9:1 in nude mice injected with 131 I-IgG respectively. This indicates that the tumor tissue image was the result of specific binding of the 131 I-McAbs, which have high specificity and affinity both in vitro and in vivo, to tumor cells, and these monoclonal antibodies may serve as potential agents in tumor diagnosis and treatment

  10. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

    Science.gov (United States)

    Matsumura, Y; Marchevsky, A; Zuo, X J; Kass, R M; Matloff, J M; Jordan, S C

    1995-06-15

    Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day

  11. Effect of inpatient rehabilitation on quality of life and exercise capacity in long-term lung transplant survivors: a prospective, randomized study.

    Science.gov (United States)

    Ihle, Franziska; Neurohr, Claus; Huppmann, Patrick; Zimmermann, Gregor; Leuchte, Hanno; Baumgartner, Rainer; Kenn, Klaus; Sczepanski, Bernd; Hatz, Rudolf; Czerner, Stephan; Frey, Lorenz; Ueberfuhr, Peter; Bittmann, Iris; Behr, Jürgen

    2011-08-01

    The purpose of this study was to examine the effect of an inpatient rehabilitation program on health-related quality of life (HRQOL) and exercise capacity (EC) in long-term (>1 year after lung transplantation) survivors (LTSs) in comparison to a control group (CG). Sixty LTSs, 4.5 ± 3.2 years after lung transplantation (LTx), were randomly assigned to two equally sized groups that were stratified for gender and underlying disease. Thirty LTSs (age 49 ± 13 years, 13 male and 17 females, 19 double LTxs, 7 BOS Stage ≥ 1) attended an inpatient rehabilitation program (intervention group, IG) for 23 ± 5 days. The CG (age 50 ± 12 years, 13 males and 17 females, 20 double LTxs, 2 BOS Stage ≥ 1) received medical standard therapy (physiotherapy). Patients were evaluated by cardiopulmonary exercise testing, 6-minute walk test (6MWT), SF-36, SGRQ and the Quality of Life Profile for Chronic Diseases questionnaire before and after (18 ± 3 days) the program. The groups were statistically indistinguishable in terms of clinical data. Each treatment group significantly improved their sub-maximal EC (6MWT: IG, 493 ± 90 m vs 538 ± 90 m, p exercise tolerance in LTS. Our study results did not demonstrate a significant benefit of an inpatient over an outpatient exercise program. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. 99Tcm-N(NOEt2 Uptake Kinetics Difference among KMB17 Human Embryonic Lung Diploid Fibroblast and Different Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wei JIA

    2010-04-01

    Full Text Available Background and objective PET/CT imaging is expensive, so searching the tumor imaging agent for SPECT/CT is necessary. 99Tcm-N(NOEt2 [bis (N-ethoxy-N-ethyl dithiocarbamato nitrido99Tcm (V] can be uptaken by lung cancer cells and other cells alike. The aim of this study is to evaluate the distinctive value in lung tumor with 99Tcm-N(NOEt2, the difference in its uptake kinetics in human embryonic lung diploid fibroblasts KMB17 and several kinds of lung cancer cells lines. Methods Firstly, six different cell culture medium which contained YTMLC Gejiu human lung squamous carcinoma cell, SPC-A1 human lung adenocarcinoma cell, AGZY low metastatic human lung adenocarcinoma, 973 high metastatic human lung adenocarcinoma cell, GLC-82 Gejiu human lung adenocarcinoma cell, and KMB17 human embryonic lung diploid fibroblast, respectively with equal cell density of 1×106/mL and the same volume were prepared; secondly, the same radioactive dose of 99Tcm-N(NOEt2 was added into each sample and then 300 μL mixed sample was taken out respectively and cultured in 37 oC culture box; Finally, 5 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min after cultivation, centrifuged each cultured sample and determined the intracellular radiocounts of each sample, calculated each cell sample’s uptake rate of 99Tcm-N(NOEt2 at different time. Results Statistical difference was found among six cell samples, and the uptake rate sequence from high to low is 973 and SPC-A1>YTMLC>GLC-82>AGZY>KMB17 respectively; furthermore, 30 min-45 min after culture, the uptake rate reached stability, and the 45 min uptake rate of each sample was higher than its 96.7% uptake peak. Conclusion Based on the results above mentioned, it is supposed that there are discriminative clinical value when using 99Tcm-N(NOEt2 as a tumor targeting imaging agent, and 30 min or so after injection may be the best imaging time in the early imaging stage.

  13. Quality of recipient-caregiver relationship and psychological distress are correlates of self-care agency after lung transplantation.

    Science.gov (United States)

    DeVito Dabbs, Annette; Terhorst, Lauren; Song, Mi-Kyung; Shellmer, Diana A; Aubrecht, Jill; Connolly, Mary; Dew, Mary Amanda

    2013-01-01

    Self-care behaviors are crucial for following the complex regimen after lung transplantation, yet little is known about recipients' levels of self-care agency (the capability and willingness to engage in self-care behaviors) and its correlates. We examined levels of self-care agency and recipient characteristics (socio-demographics, psychological distress, quality of relationship with primary lay caregiver, and health locus of control) in 111 recipients. Based on Perceived Self-Care Agency scores, recipients were assigned to either the low- or high-self-care agency comparison group. Characteristics were compared between groups to identify characteristics likely to be associated with lower-self-care agency. Mean (SD) score for self-care agency (scale range, 53-265) was 223.02 (22.46). Recipients with lowest-self-care agency scores reported significantly poorer quality of caregiver relationships (p recipient-caregiver relationship remained significantly associated with self-care agency. Every one-point decrease in the quality of caregiver relationship increased the risk of low-self-care agency by 12%. Recipients with poorer caregiver relationships and greater psychological distress may need additional support to perform the self-care behaviors expected after lung transplantation. © 2012 John Wiley & Sons A/S.

  14. Incomplete quality of life data in lung transplant research : comparing cross sectional, repeated measures ANOVA, and multi-level analysis

    NARCIS (Netherlands)

    Vermeulen, KM; Post, WJ; Span, MM; van der Bij, W; Koeter, GH; ten Vergert, EM

    2005-01-01

    Background: In longitudinal studies on Health Related Quality of Life (HRQL) it frequently occurs that patients have one or more missing forms, which may cause bias, and reduce the sample size. Aims of the present study were to address the problem of missing data in the field of lung transplantation

  15. Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis

    Directory of Open Access Journals (Sweden)

    Rubes Jiri

    2011-04-01

    Full Text Available Abstract Background Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB. Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs. Methods A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E was assessed and the fluorescence in situ hybridization (FISH method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors. Results Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R = 0.610 - 0.671 and p R = 0.698 and p p p Conclusions In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

  16. Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient.

    Science.gov (United States)

    Veitch, David; Abioye, Abu; Morris-Jones, Stephen; McGregor, Alastair

    2015-12-16

    A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co-amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature. 2015 BMJ Publishing Group Ltd.

  17. Radiosensitivity and cell kinetics of the human solid cancer transplanted to nude mouse

    International Nuclear Information System (INIS)

    Ikeuchi, Shunji

    1983-01-01

    This study was undertaken to analyse the relationship between radiosensitivity and cell kinetics of human solid cancer in experimental nude mouse system. Four strains of tumors used for the experiment were poorly differentiated squamous cell carcinoma of the lung (Lu-9), oat cell carcinoma of the lung (Lu-24), well differentiated squamous cell carcinoma of the tongue (To-1) and moderately differentiated squamous cell carcinoma of the esophagus (Es-4) which were serially transplantable to BALB/c nude mice. Radiosensitivity was evaluated by tumor growth in terms of inhibition rate, histological change and host reaction after irradiation. Cell kinetics were studied by autoradiography with pulse administration of 3 H-thymidine to mice. Although Lu-24 was most radiosensitive, followed by To-1, Es-4 and Lu-9 in the order of sensitivity, it was suggested that they might be more radioresistant in nude mice without T-cell function than in human. Regarding squamous cell carcinomas, well differentiated type was more radiosensitive than poorly differentiated one. All of these tumors in nude mouse revealed distinct percent labeled mitosis curves with two clear peaks which were quite different from those in human body. Lu-24 showed a characteristic pattern with a long time lag before visible growth, short G 1 , and low growth fraction, compared to other three tumors. Three strains of squamous cell carcinoma demonstrated similar cell kinetic factors which were almost the same as those in human body reported previously. The differences in volume doubling time of tumor, growth fraction and cell loss factor were partially related to those of radiosensitivities among tumors except for Lu-24. The theoretical volume doubling time was proved to be most reliable for estimation of effectiveness of irradiation, but the labeling index was not a valuable indicator for it. (author)

  18. Influenza in solid organ transplant recipients.

    Science.gov (United States)

    Martin, Spencer T; Torabi, Mina J; Gabardi, Steven

    2012-02-01

    To review available data describing the epidemiology, outcomes, prevention, and treatment of influenza virus in the solid organ transplant population and to evaluate the strengths and limitations of the current literature, with a focus on literature reviewing annual influenza strains and the recent pandemic novel influenza A/H1N1 strain. A systematic literature search (July 1980-June 2011) was performed via PubMed using the following key words: influenza, human; influenza; novel influenza A H1/N1; transplantation; solid organ transplantation; kidney transplant; renal transplant; lung transplant; heart transplant; and liver transplant. Papers were excluded if they were not written in English or were animal studies or in vitro studies. Data from fully published studies and recent reports from international conferences were included. The influenza virus presents a constant challenge to immunocompromised patients and their health care providers. The annual influenza strain introduces a highly infectious and pathogenic risk to solid organ transplant recipients. In 2009, the World Health Organization declared a pandemic as a result of a novel influenza A/H1N1 strain. The pandemic introduced an additional viral threat to solid organ transplant patients at increased risk for infectious complications. The mainstay for prevention of influenza infection in all at-risk populations is appropriate vaccination. Antiviral therapies against influenza for chemoprophylaxis and treatment of infection are available; however, dosing strategies in the solid organ transplant population are not well defined. The solid organ transplant population is at an increased risk of severe complications from influenza infection. Identifying risks, preventing illness, and appropriately treating active infection is essential in this patient population.

  19. Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death.

    Science.gov (United States)

    Stone, Matthew L; Zhao, Yunge; Robert Smith, J; Weiss, Mark L; Kron, Irving L; Laubach, Victor E; Sharma, Ashish K

    2017-12-21

    Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs. C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs. Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix. These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of

  20. CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation

    International Nuclear Information System (INIS)

    Lee, J.Y.; Shank, B.; Bonfiglio, P.; Reid, A.

    1984-01-01

    Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung

  1. Design and validation of a clinical-scale bioreactor for long-term isolated lung culture.

    Science.gov (United States)

    Charest, Jonathan M; Okamoto, Tatsuya; Kitano, Kentaro; Yasuda, Atsushi; Gilpin, Sarah E; Mathisen, Douglas J; Ott, Harald C

    2015-06-01

    The primary treatment for end-stage lung disease is lung transplantation. However, donor organ shortage remains a major barrier for many patients. In recent years, techniques for maintaining lungs ex vivo for evaluation and short-term (advance to more complex interventions for lung repair and regeneration, the need for a long-term organ culture system becomes apparent. Herein we describe a novel clinical scale bioreactor capable of maintaining functional porcine and human lungs for at least 72 h in isolated lung culture (ILC). The fully automated, computer controlled, sterile, closed circuit system enables physiologic pulsatile perfusion and negative pressure ventilation, while gas exchange function, and metabolism can be evaluated. Creation of this stable, biomimetic long-term culture environment will enable advanced interventions in both donor lungs and engineered grafts of human scale. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Severity of Acute Kidney Injury in the Post-Lung Transplant Patient Is Associated With Higher Healthcare Resources and Cost.

    Science.gov (United States)

    Nguyen, Albert P; Gabriel, Rodney A; Golts, Eugene; Kistler, Erik B; Schmidt, Ulrich

    2017-08-01

    Perioperative risk factors and the clinical impact of acute kidney injury (AKI) and failure after lung transplantation are not well described. The incidences of AKI and acute renal failure (ARF), potential perioperative contributors to their development, and postdischarge healthcare needs were evaluated. Retrospective. University hospital. Patients undergoing lung transplantation between January 1, 2011 and December 31, 2015. The incidences of AKI and ARF, as defined using the Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria, were measured. Perioperative events were analyzed to identify risk factors for renal compromise. A comparison of ventilator days, intensive care unit (ICU) and hospital lengths of stay (LOS), 1-year readmissions, and emergency department visits was performed among AKI, ARF, and uninjured patients. Ninety-seven patients underwent lung transplantation; 22 patients developed AKI and 35 patients developed ARF. Patients with ARF had significantly longer ICU LOS (12 days v 4 days, p < 0.001); ventilator days (4.5 days v 1 day, p < 0.001); and hospital LOS (22.5 days v 14 days, p < 0.001) compared with uninjured patients. Patients with AKI also had significantly longer ICU and hospital LOS. Patients with ARF had significantly more emergency department visits and hospital readmissions (2 v 1 readmissions, p = 0.002) compared with uninjured patients. A univariable analysis suggested that prolonged surgical time, intraoperative vasopressor use, and cardiopulmonary bypass use were associated with the highest increased risk for AKI. Intraoperative vasopressor use and cardiopulmonary bypass mean arterial pressure <60 mmHg were identified as independent risk factors by multivariable analysis for AKI. The severity of AKI was associated with an increase in the use of healthcare resources after surgery and discharge. Certain risk factors appeared modifiable and may reduce the incidence of AKI and ARF. Copyright © 2017. Published by Elsevier Inc.

  3. Using non-human primates to benefit humans: research and organ transplantation.

    Science.gov (United States)

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

  4. Tiny plastic lung mimics human pulmonary function

    Science.gov (United States)

    Careers Inclusion & Diversity Work-Life Balance Career Resources Apply for a Job Postdocs Students Goals Recycling Green Purchasing Pollution Prevention Reusing Water Resources Environmental Management Releases - 2016 » April » Tiny plastic lung mimics human pulmonary function Tiny plastic lung mimics

  5. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Directory of Open Access Journals (Sweden)

    Hanbo Hu

    Full Text Available Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of

  6. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report

    OpenAIRE

    ZHAO, QIONG; WANG, YINA; TANG, YEMIN; PENG, LING

    2013-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An ...

  7. Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

    OpenAIRE

    Miller, Melissa B.; Hendren, Ryan; Gilligan, Peter H.

    2004-01-01

    A North Carolinian developed fatal coccidioidomycosis immediately after bilateral lung transplantation. The donor had previously traveled to Mexico, and the recipient had no travel history to an area where Coccidioides immitis is endemic. Immunosuppresive therapy of the transplant recipient likely reactivated latent Coccidioides infection in the donor lungs, leading to posttransplant coccidioidomycosis.

  8. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  9. Low-dose computed tomography volumetry for subtyping chronic lung allograft dysfunction.

    Science.gov (United States)

    Saito, Tomohito; Horie, Miho; Sato, Masaaki; Nakajima, Daisuke; Shoushtarizadeh, Hassan; Binnie, Matthew; Azad, Sassan; Hwang, David M; Machuca, Tiago N; Waddell, Thomas K; Singer, Lianne G; Cypel, Marcelo; Liu, Mingyao; Paul, Narinder S; Keshavjee, Shaf

    2016-01-01

    The long-term success of lung transplantation is challenged by the development of chronic lung allograft dysfunction (CLAD) and its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). However, the current diagnostic criteria for CLAD subtypes rely on total lung capacity (TLC), which is not always measured during routine post-transplant assessment. Our aim was to investigate the utility of low-dose 3-dimensional computed tomography (CT) lung volumetry for differentiating RAS from BOS. This study was a retrospective evaluation of 63 patients who had developed CLAD after bilateral lung or heart‒lung transplantation between 2006 and 2011, including 44 BOS and 19 RAS cases. Median post-transplant follow-up was 65 months in BOS and 27 months in RAS. The median interval between baseline and the disease-onset time-point for CT volumetry was 11 months in both BOS and RAS. Chronologic changes and diagnostic accuracy of CT lung volume (measured as percent of baseline) were investigated. RAS showed a significant decrease in CT lung volume at disease onset compared with baseline (mean 3,916 ml vs 3,055 ml when excluding opacities, p volumetry is a useful tool to differentiate patients who develop RAS from those who develop BOS. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Heart transplantation in adults with congenital heart disease.

    Science.gov (United States)

    Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

    2017-05-01

    With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes. Copyright © 2017. Published by Elsevier Masson SAS.

  11. A Multiphase Non-Linear Mixed Effects Model: An Application to Spirometry after Lung Transplantation

    Science.gov (United States)

    Rajeswaran, Jeevanantham; Blackstone, Eugene H.

    2014-01-01

    In medical sciences, we often encounter longitudinal temporal relationships that are non-linear in nature. The influence of risk factors may also change across longitudinal follow-up. A system of multiphase non-linear mixed effects model is presented to model temporal patterns of longitudinal continuous measurements, with temporal decomposition to identify the phases and risk factors within each phase. Application of this model is illustrated using spirometry data after lung transplantation using readily available statistical software. This application illustrates the usefulness of our flexible model when dealing with complex non-linear patterns and time varying coefficients. PMID:24919830

  12. Effect of increases in lung volume on clearance of aerosolized solute from human lungs

    Energy Technology Data Exchange (ETDEWEB)

    Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

    1985-10-01

    To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure (12 cmH2O continuous positive airway pressure (CPAP)) or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

  13. Effect of increases in lung volume on clearance of aerosolized solute from human lungs

    International Nuclear Information System (INIS)

    Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

    1985-01-01

    To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH 2 O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH 2 O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH 2 O; clearance and FRC were determined at CPAP of 12 cmH 2 O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method

  14. Intrapulmonary Human Cytomegalovirus Replication in Lung Transplant Recipients Is Associated With a Rise of CCL-18 and CCL-20 Chemokine Levels.

    Science.gov (United States)

    Weseslindtner, Lukas; Görzer, Irene; Roedl, Kevin; Küng, Erik; Jaksch, Peter; Klepetko, Walter; Puchhammer-Stöckl, Elisabeth

    2017-01-01

    In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNA detection in the bronchoalveolar lavage fluid (BALF) indicates HCMV replication in the pulmonary compartment. Such local HCMV replication episodes may remain asymptomatic or may lead to symptomatic HCMV disease. Here, we investigated LTRs with intrapulmonary HCMV replication for the chemokines CCL-18 and CCL-20. In particular, we analyzed whether these chemokines rise in the allograft and/or the blood and are associated with HCMV disease. CCL-18 and CCL-20 levels were quantitated by ELISA in BALF and serum samples from 60 LTRs. During the posttransplant follow-up, these LTRs displayed HCMV DNA detection in the BALF by PCR, whereas other infectious agents were undetectable. Furthermore, we investigated samples from 10 controls who did not display any HCMV replication episode during the follow-up. HCMV replication in the allograft was associated with a significant increase of CCL-18 and CCL-20 BALF levels (P Wilcoxon signed-rank test) and a significant rise of CCL-20 (P Wilcoxon signed-rank test) but not of CCL-18 in the blood. In controls, no such chemokine increase was observed. Furthermore, CCL-18 BALF levels were significantly higher in 8 LTRs who additionally developed HCMV disease, as compared with the other 52 patients in whom HCMV replication remained asymptomatic (P test). HCMV replication in the allograft causes an intrapulmonary increase of CCL-18 and CCL-20 and a systemic rise of CCL-20 serum levels. Strong intrapulmonary CCL-18 responses are associated with symptomatic HCMV disease, proposing that CCL-18 BALF levels could serve as a marker.

  15. Heart transplantation for Churg-Strauss syndrome.

    Science.gov (United States)

    Thomson, D; Chamsi-Pasha, H; Hasleton, P

    1989-01-01

    A patient with heart failure caused by Churg-Strauss syndrome was successfully treated with transplantation. The case was unusual because there was little evidence of Churg-Strauss syndrome in the lung. The patient remains well on standard transplant immunotherapy. Images Figure PMID:2590597

  16. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  17. Machine Learning Algorithms Utilizing Quantitative CT Features May Predict Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation.

    Science.gov (United States)

    Barbosa, Eduardo J Mortani; Lanclus, Maarten; Vos, Wim; Van Holsbeke, Cedric; De Backer, William; De Backer, Jan; Lee, James

    2018-02-19

    Long-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV 1 ) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS. Paired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV 1 of >10% compared to baseline FEV 1 post LTx. Multifactor analysis correlated declining FEV 1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS. The FEV 1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV 1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters. ML utilizing qCT could discern distinct mechanisms driving FEV 1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  18. [Lung transplantation in Reunion Island, current situation from January 2005 till May 2015].

    Science.gov (United States)

    Simon, C; Allou, N; Schlossmacher, P; Gendry, T; Delay, L; Gazaille, V

    2017-04-01

    Lung transplantation (LT) is a therapeutic option for patients with terminal respiratory failure and high risk of mortality in two years. Until now, this activity is not performed in Reunion Island. The candidate potential are thus directed to the metropolitan reference centres causing logistics and financials constraints. This work presents a current situation of the pulmonary transplantation in Reunion Island. This retrospective study includes patients from Reunion Island with respiratory insufficiency who have been transferred to metropolitan centres to apply to LT. The selection was made from January, 2005 till May, 2015. Twenty-nine patients included, aged from 14 to 64 years, were transferred to metropolitan France: 13 patients with cystic fibrosis, 13 patients with pulmonary fibrosis, 1 patients with bronchiectasis, 1 patient with chronic obstructive pulmonary disease (COPD) and 1 patient with pulmonary arterial hypertension. Fifteen patients underwent LT (4 live in Reunion Island, 5 live in metropolitan France and 6 are dead), 1 patient is alive on waiting list, 3 died on the waiting list, 7 patients were refused for transplantation and 3 patients are lost to follow-up. The number of patients transferred for LT increases over 10 years with a maximal incidence in 2013 of 7 repatriated patients including 3 transplanted patients. LT could be performed in half of our patients with possible come back and follow-up on Reunion Island. Indications follow the current trends except an under representation of COPD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    Science.gov (United States)

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  20. Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Lynch, John P.; Trulock, Elbert P.

    1998-01-01

    Purpose: To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT). Patients and Materials: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored. Results: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV 1 ) was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV 1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died

  1. Analytic Intermodel Consistent Modeling of Volumetric Human Lung Dynamics.

    Science.gov (United States)

    Ilegbusi, Olusegun; Seyfi, Behnaz; Neylon, John; Santhanam, Anand P

    2015-10-01

    Human lung undergoes breathing-induced deformation in the form of inhalation and exhalation. Modeling the dynamics is numerically complicated by the lack of information on lung elastic behavior and fluid-structure interactions between air and the tissue. A mathematical method is developed to integrate deformation results from a deformable image registration (DIR) and physics-based modeling approaches in order to represent consistent volumetric lung dynamics. The computational fluid dynamics (CFD) simulation assumes the lung is a poro-elastic medium with spatially distributed elastic property. Simulation is performed on a 3D lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of a human subject. The heterogeneous Young's modulus (YM) is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The deformation obtained from the CFD is then coupled with the displacement obtained from the 4D lung DIR by means of the Tikhonov regularization (TR) algorithm. The numerical results include 4DCT registration, CFD, and optimal displacement data which collectively provide consistent estimate of the volumetric lung dynamics. The fusion method is validated by comparing the optimal displacement with the results obtained from the 4DCT registration.

  2. Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

    Science.gov (United States)

    Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

    2014-07-01

    Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Repeatability of Computerized Tomography-Based Anthropomorphic Measurements of Frailty in Patients With Pulmonary Fibrosis Undergoing Lung Transplantation.

    Science.gov (United States)

    McClellan, Taylor; Allen, Brian C; Kappus, Matthew; Bhatti, Lubna; Dafalla, Randa A; Snyder, Laurie D; Bashir, Mustafa R

    To determine interreader and intrareader repeatability and correlations among measurements of computerized tomography-based anthropomorphic measurements in patients with pulmonary fibrosis undergoing lung transplantation. This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study of 23 randomly selected subjects (19 male and 4 female; median age = 69 years; range: 66-77 years) with idiopathic pulmonary fibrosis undergoing pulmonary transplantation, who had also undergone preoperative thoracoabdominal computerized tomography. Five readers of varying imaging experience independently performed the following cross-sectional area measurements at the inferior endplate of the L3 vertebral body: right and left psoas muscles, right and left paraspinal muscles, total abdominal musculature, and visceral and subcutaneous fat. The following measurements were obtained at the inferior endplate of T6: right and left paraspinal muscles with and without including the trapezius muscles and subcutaneous fat. Three readers repeated all measurements to assess intrareader repeatability. Intrareader repeatability was nearly perfect (interclass correlation coefficients = 0.99, P < 0.001). Interreader agreement was excellent across all 5 readers (interclass correlation coefficients: 0.71-0.99, P < 0.001). Coefficients of variance between measures ranged from 3.2%-6.8% for abdominal measurements, but were higher for thoracic measurements, up to 23.9%. Correlation between total paraspinal and total psoas muscle area was strong (r 2 = 0.67, P < 0.001). Thoracic and abdominal musculature had a weaker correlation (r 2 = 0.35-0.38, P < 0.001). Measures of thoracic and abdominal muscle and fat area are highly repeatable in patients with pulmonary fibrosis undergoing lung transplantation. Measures of muscle area are strongly correlated among abdominal locations, but inversely correlated between abdominal and thoracic locations

  4. Expression analysis of asthma candidate genes during human and murine lung development.

    Science.gov (United States)

    Melén, Erik; Kho, Alvin T; Sharma, Sunita; Gaedigk, Roger; Leeder, J Steven; Mariani, Thomas J; Carey, Vincent J; Weiss, Scott T; Tantisira, Kelan G

    2011-06-23

    Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function. To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma. Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6. In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development. Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.

  5. Graft downsizing during ex vivo lung perfusion: case report and technical notes.

    Science.gov (United States)

    Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

    2014-09-01

    Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Clinical-radiological, histological and genetic analyses in a lung transplant recipient with Mounier-Kuhn syndrome and end-stage chronic obstructive pulmonary disease.

    Science.gov (United States)

    Mitterbauer, Andreas; Hoetzenecker, Konrad; Birner, Peter; Mildner, Michael; Prosch, Helmut; Streubel, Berthold; Taghavi, Shahrokh; Klepetko, Walter; Ankersmit, Hendrik Jan

    2015-07-01

    The Mounier-Kuhn syndrome (MKS) is a rare disease characterized by a pathological dilation of the trachea and the bronchial system. The etiology of the disorder remains elusive, but genetic alterations and degradation of elastic fibers are thought to be involved in the pathogenesis. No causative treatment is available although transplantation is an option for end-stage disease. Here, we describe a patient suffering from MKS who received a double lung transplant at our department. Since a familial clustering of MKS is discussed in the literature, we performed a chromosomal analysis and an array-comparative genomic hybridization (CGH) to search for genetic abnormalities. At the time of transplantation, we collected samples from the bronchi and performed hematoxylin and eosin (HE), Elastic von-Gieson (EVG) and immunohistochemical stains of the explanted MKS bronchus, a control bronchus and of the inflammatory infiltrates. Specimens of main bronchi from the donor lung harvested for transplant served as control. Bronchial smears were taken from both main bronchi of the recipient for microbiological cultures. No genetic alterations could be found in chromosomal analysis and in array-CGH. Histological analysis revealed a strong reduction of elastic fibers in the submucosal connective tissue and a diffuse inflammatory infiltrate, mainly comprised of CD4+ cells. In addition, immunohistochemistry showed increased matrix metalloproteinases (MMPs) protein expression of MMP-1, 2, 3 and 9. Based on our findings, we hypothesize that MKS is a chronic inflammatory disease characterized by an MMP-mediated degradation of submucosal elastic fibers. © 2014 John Wiley & Sons Ltd.

  7. A New Composite Eyeball-Periorbital Transplantation Model in Humans: An Anatomical Study in Preparation for Eyeball Transplantation.

    Science.gov (United States)

    Siemionow, Maria; Bozkurt, Mehmet; Zor, Fatih; Kulahci, Yalcin; Uygur, Safak; Ozturk, Can; Djohan, Risal; Papay, Frank

    2018-04-01

    Vascularized composite allotransplantation offers a new hope for restoration of orbital content and perhaps vision. The aim of this study was to introduce a new composite eyeball-periorbital transplantation model in fresh cadavers in preparation for composite eyeball allotransplantation in humans. The composite eyeball-periorbital transplantation flap borders included the inferior border, outlined by the infraorbital rim; the medial border, created by the nasal dorsum; the lateral border, created by the lateral orbital rim; and the superior border, created by the superior part of the eyebrow. The pedicle of the flap included the facial artery, superficial temporal artery, and external jugular vein. The skin and subcutaneous tissues of the periorbital region were dissected and the bony tissue was reached. A coronal incision was performed and the frontal lobe of the brain was reached by means of frontal osteotomy. Ophthalmic and oculomotor nerves were also included in the flap. After a "box osteotomy" around the orbit, the dissection was completed. Methylene blue and indocyanine green injection (SPY Elite System) was performed to show the integrity of the vascular territories after facial flap harvest. Adequate venous return was observed within the flap after methylene blue dye injection. Laser-assisted indocyanine green angiography identified a well-defined vascular network within the entire composite eyeball-periorbital transplantation flap. For the first time, a novel composite eyeball-periorbital transplantation model in human cadavers was introduced. Good perfusion of the flap confirmed the feasibility of composite eyeball-periorbital transplantation in the clinical setting. Although harvesting of the flap is challenging, it introduces a new option for reconstruction of the periorbital region including the eyeball.

  8. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... as a standard, e.g. in therapeutic experiments. The course of tumor growth is independent of the size of the transplant, and whether tumors are transplanted in the right or left or both flanks of the recipient mice. Furthermore, the growth does not vary in a systematic way with the number of passages in nude...

  9. Ethical issues of transplanting organs from transgenic animals into human beings.

    Science.gov (United States)

    Behnam Manesh, Shima; Omani Samani, Reza; Behnam Manesh, Shayan

    2014-01-01

    One of the most important applications of transgenic animals for medical purposes is to transplant their organs into human's body, an issue which has caused a lot of ethical and scientific discussions. we can divide the ethical arguments to two comprehensive groups; the first group which is known as deontological critiques (related to the action itself regardless of any results pointing the human or animal) and the second group, called the consequentialist critiques (which are directly pointing the consequences of the action). The latter arguments also can be divided to two subgroups. In the first one which named anthropocentrism, just humankind has inherent value in the moral society, and it studies the problem just from a human-based point of view while in second named, biocentrism all the living organism have this value and it deals specially with the problem from the animal-based viewpoint. In this descriptive-analytic study, ethical issues were retrieved from books, papers, international guidelines, thesis, declarations and instructions, and even some weekly journals using keywords related to transgenic animals, organ, and transplantation. According to the precautionary principle with the strong legal and ethical background, due to lack of accepted scientific certainties about the safety of the procedure, in this phase, transplanting animal's organs into human beings have the potential harm and danger for both human and animals, and application of this procedure is unethical until the safety to human will be proven.

  10. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    Science.gov (United States)

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

  11. The Australian and New Zealand Cardiothoracic Organ Transplant Registry: first report 1984-1992.

    Science.gov (United States)

    Keogh, A M; Kaan, A

    1992-12-01

    This initial report of the Australian and New Zealand Cardiothoracic Organ Transplant Registry summarises the results of all cardiothoracic transplants performed between February 1984 and April 1992. A total of 549 first cardiothoracic transplant procedures and six cardiac retransplant operations were performed in five transplant units throughout Australia and New Zealand. There were 466 orthotopic cardiac transplants and one heterotopic transplant with overall survival 86% at one year and 80% at five years. Two of six patients who underwent cardiac retransplantation are alive. Fifty-three heart-lung transplants were performed with 72% one year and 42% five year survival. Twenty-nine single lung transplant procedures were undertaken, with actuarial survival 72% at 12 months. Factors influencing waiting period and post-transplant survival for each type of procedure are detailed. The relative lack of donors compared with recipient demand has produced increased waiting times for every type of cardiothoracic organ transplant.

  12. Acceptance and Use of Mobile Technology for Health Self-Monitoring in Lung Transplant Recipients during the First Year Post-Transplantation.

    Science.gov (United States)

    Jiang, Yun; Sereika, Susan M; Dabbs, Annette DeVito; Handler, Steven M; Schlenk, Elizabeth A

    2016-01-01

    To describe lung transplant recipients (LTRs') acceptance and use of mobile technology for health self-monitoring during the first year post-transplantation, and explore correlates of the use of technology in the 0 to 2, >2 to ≤6, >6 to ≤12, and 0 to 12 months. Secondary analysis of data from 96 LTR assigned to use Pocket PATH(®), a smartphone application, for daily health self-monitoring in a randomized controlled trial. Use of Pocket PATH was categorized as low, moderate, and high use. Proportional odds models for ordinal logistic regression were employed to explore correlates of use of technology. LTR reported high acceptance of Pocket PATH at baseline. However, acceptance was not associated with actual use over the 12 months (p=0.45~0.96). Actual use decreased across time intervals (ptechnology training (p=0.02) in the first 2 months. Higher use from >2 to ≤6 months was associated with greater satisfaction with technology training (OR=3.37, p=0.01) and shorter length of hospital stay (OR=0.98, p=0.02). Higher use from >6 to ≤12 months was associated with older age (OR=1.05, p=0.02), lower psychological distress (OR=0.43, p=0.02), and better physical functioning (OR=1.09, p=0.01). Higher use over 12 months was also associated with older age (OR=1.05, p=0.007), better physical functioning (OR=1.13, p=0.001), and greater satisfaction with technology training (OR=3.05, p=0.02). Correlates were different for short- and long-term use of mobile technology for health self-monitoring in the first year post-transplantation. It is important to follow up with LTR with longer hospital stay, poor physical functioning, and psychological distress, providing ongoing education to improve their long-term use of technology for health self-monitoring.

  13. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

    Science.gov (United States)

    Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

    2017-05-01

    Extracellular matrix (ECM) is crucial to many aspects of vascular morphogenesis and maintenance of vasculature function. Currently the recapitulation of angiogenic ECM microenvironment is still challenging, due mainly to its diverse components and complex organization. Here we investigate the angiogenic potential of human lung fibroblast-derived matrix (hFDM) in creating a three-dimensional (3D) vascular construct. hFDM was obtained via decellularization of in vitro cultured human lung fibroblasts and analyzed via immunofluorescence staining and ELISA, which detect multiple ECM macromolecules and angiogenic growth factors (GFs). Human umbilical vein endothelial cells (HUVECs) morphology was more elongated and better proliferative on hFDM than on gelatin-coated substrate. To prepare 3D construct, hFDM is collected, quantitatively analyzed, and incorporated in collagen hydrogel (Col) with HUVECs. Capillary-like structure (CLS) formation at 7day was significantly better with the groups containing higher doses of hFDM compared to the Col group (control). Moreover, the group (Col/hFDM/GFs) with both hFDM and angiogenic GFs (VEGF, bFGF, SDF-1) showed the synergistic activity on CLS formation and found much larger capillary lumen diameters with time. Further analysis of hFDM via angiogenesis antibody array kit reveals abundant biochemical cues, such as angiogenesis-related cytokines, GFs, and proteolytic enzymes. Significantly up-regulated expression of VE-cadherin and ECM-specific integrin subunits was also noticed in Col/hFDM/GFs. In addition, transplantation of Col/hFMD/GFs with HUVECs in skin wound model presents more effective re-epithelialization, many regenerated hair follicles, better transplanted cells viability, and advanced neovascularization. We believe that current system is a very promising platform for 3D vasculature construction in vitro and for cell delivery toward therapeutic applications in vivo. Functional 3D vasculature construction in vitro is still

  14. The detection, diagnosis and therapy of human lung cancer

    International Nuclear Information System (INIS)

    1978-01-01

    The Cancergram covers clinical aspects of cancers of the lung and tracheo-bronchial tree, i.e., the lower respiratory tract. This includes primary lung cancer in both early and advanced disease status. The topic includes clinically relevant aspects of the prevention, detection, diagnosis, evaluation, and therapy of lung cancer. Certain aspects of metastatic lung disease treatment or therapy which involve aspects of interest to primary lung cancer are included. With certain exceptions, general pre-clinical or animal studies not directly related to the primary human disease are excluded

  15. Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

    Science.gov (United States)

    Wagner, Cynthia E; Pope, Nicolas H; Charles, Eric J; Huerter, Mary E; Sharma, Ashish K; Salmon, Morgan D; Carter, Benjamin T; Stoler, Mark H; Lau, Christine L; Laubach, Victor E; Kron, Irving L

    2016-02-01

    Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation. Copyright

  16. Annual literature review of donor-specific HLA antibodies after organ transplantation.

    Science.gov (United States)

    Kaneku, Hugo

    2011-01-01

    The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

  17. National review of use of extracorporeal membrane oxygenation as respiratory support in thoracic surgery excluding lung transplantation.

    Science.gov (United States)

    Rinieri, Philippe; Peillon, Christophe; Bessou, Jean-Paul; Veber, Benoît; Falcoz, Pierre-Emmanuel; Melki, Jean; Baste, Jean-Marc

    2015-01-01

    Extracorporeal membrane oxygenation (ECMO) for respiratory support is increasingly used in intensive care units (ICU), but rarely during thoracic surgical procedures outside the transplantation setting. ECMO can be an alternative to cardiopulmonary bypass for major trachea-bronchial surgery and single-lung procedures without in-field ventilation. Our aim was to evaluate the intraoperative use of ECMO as respiratory support in thoracic surgery: benefits, indications and complications. This was a multicentre retrospective study (questionnaire) of use of ECMO as respiratory support during the thoracic surgical procedure. Lung transplantation and lung resection for tumour invading the great vessels and/or the left atrium were excluded, because they concern respiratory and circulatory support. From March 2009 to September 2012, 17 of the 34 centres in France applied ECMO within veno-venous (VV) (n=20) or veno-arterial (VA) (n=16) indications in 36 patients. Ten VA ECMO were performed with peripheral cannulation and 6 with central cannulation; all VV ECMO were achieved through peripheral cannulation. Group 1 (total respiratory support) was composed of 28 patients without mechanical ventilation, involving 23 tracheo-bronchial and 5 single-lung procedures. Group 2 (partial respiratory support) was made up of 5 patients with respiratory insufficiency. Group 3 was made up of 3 patients who underwent thoracic surgery in a setting of acute respiratory distress syndrome (ARDS) with preoperative ECMO. Mortality at 30 days in Groups 1, 2 and 3 was 7, 40 and 67%, respectively (P<0.05). In Group 1, ECMO was weaned intraoperatively or within 24 h in 75% of patients. In Group 2, ECMO was weaned in ICU over several days. In Group 1, 2 patients with VA support were converted to VV support for chronic respiratory indications. Bleeding was the major complication with 17% of patients requiring return to theatre for haemostasis. There were two cannulation-related complications (6%). VV or

  18. Genetically modified human bone marrow derived mesenchymal stem cells for improving the outcome of human islet transplantation.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mundra

    Full Text Available The objective of this study was to determine the potential of human bone marrow derived mesenchymal stem cells (hBMSCs as gene carriers for improving the outcome of human islet transplantation. hBMSCs were characterized for the expression of phenotypic markers and transduced with Adv-hVEGF-hIL-1Ra to overexpress human vascular endothelial growth factor (hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra. Human islets were co-cultured with hBMSCs overexpressing hVEGF and hIL-1Ra. Islet viability was determined by membrane fluorescent method and glucose stimulation test. Transduced hBMSCs and human islets were co-transplanted under the kidney capsule of NOD.Cg-Prkdc(scid Il2rg(tm1Wjl /SzJ (NSG diabetic mice and blood glucose levels were measured over time to demonstrate the efficacy of genetically modified hBMSCs. At the end of study, immunofluorescent staining of kidney section bearing islets was performed for insulin and von Willebrand Factor (vWF. hBMSCs were positive for the expression of CD73, CD90, CD105, CD146 and Stro-1 surface markers as determined by flow cytometry. Transduction of hBMSCs with adenovirus did not affect their stemness and differentiation potential as confirmed by mRNA levels of stem cell markers and adipogenic differentiation of transduced hBMSCs. hBMSCs were efficiently transduced with Adv-hVEGF-hIL-1Ra to overexpress hVEGF and hIL-1Ra. Live dead cell staining and glucose stimulation test have shown that transduced hBMSCs improved the viability of islets against cytokine cocktail. Co-transplantation of human islets with genetically modified hBMSCs improved the glycemic control of diabetic NSG mice as determined by mean blood glucose levels and intraperitoneal glucose tolerance test. Immunofluorescent staining of kidney sections was positive for human insulin and vWF. In conclusion, our results have demonstrated that hBMSCs may be used as gene carriers and nursing cells to improve the outcome of islet

  19. Post-transplantation Infections in Bolivia.

    Science.gov (United States)

    Arze, S; Arze, L; Abecia, C

    2016-03-01

    Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic

  20. Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung Procurement Rates.

    Science.gov (United States)

    Chang, Stephanie H; Kreisel, Daniel; Marklin, Gary F; Cook, Lindsey; Hachem, Ramsey; Kozower, Benjamin D; Balsara, Keki R; Bell, Jennifer M; Frederiksen, Christine; Meyers, Bryan F; Patterson, G Alexander; Puri, Varun

    2018-05-01

    Lung procurement for transplantation occurs in approximately 20% of brain dead donors and is a major impediment to wider application of lung transplantation. We investigated the effect of lung protective management at a specialized donor care facility on lung procurement rates from brain dead donors. Our local organ procurement organization instituted a protocol of lung protective management at a freestanding specialized donor care facility in 2008. Brain dead donors from 2001 to 2007 (early period) were compared with those from 2009 to 2016 (current period) for lung procurement rates and other solid-organ procurement rates using a prospectively maintained database. An overall increase occurred in the number of brain dead donors during the study period (early group, 791; late group, 1,333; p procurement rate (lung donors/all brain dead donors) improved markedly after the introduction of lung protective management (early group, 157 of 791 [19.8%]; current group, 452 of 1,333 [33.9%]; p procurement rate (total number of organs procured/donor) also increased during the study period (early group, 3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006). Lung protective management in brain dead donors at a specialized donor care facility is associated with higher lung utilization rates compared with conventional management. This strategy does not adversely affect the utilization of other organs in a multiorgan donor. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Inverted Lobes Have Satisfactory Functions Compared With Noninverted Lobes in Lung Transplantation.

    Science.gov (United States)

    Kayawake, Hidenao; Chen-Yoshikawa, Toyofumi F; Motoyama, Hideki; Hamaji, Masatsugu; Hijiya, Kyoko; Aoyama, Akihiro; Goda, Yasufumi; Oda, Hiromi; Ueda, Satoshi; Date, Hiroshi

    2018-04-01

    To overcome the problem of small-for-size grafts in standard living-donor lobar lung transplantation (LDLLT), we developed inverted LDLLT, in which a right lower lobe from 1 donor is implanted as a right graft and another right lower lobe from another donor is implanted as a left graft. We retrospectively analyzed the functions of inverted grafts vs noninverted grafts. Between 2008 and 2015, 64 LDLLTs were performed. Included were 35 LDLLTs whose recipients were adults and monitored for more than 6 months without developing chronic lung allograft dysfunction. Among them, 65 implanted lobes were eligible for this analysis. There were 31 right lower lobes implanted as right grafts (right-to-right group), 7 right lower lobes as inverted left grafts (right-to-left group), and 27 left lower lobes as left grafts (left-to-left group). We evaluated the graft forced vital capacity (G-FVC) and graft volume of the 65 lobes before and 6 months after LDLLT and compared them among the three groups. Preoperatively, G-FVC in the right-to-left group (1,050 mL) was comparable to that in the right-to-right group (1,177 mL) and better than that in the left-to-left group (791 mL, p satisfactory compared with those of noninverted grafts. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Functional significance of cardiac reinnervation in heart transplant recipients.

    Science.gov (United States)

    Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

    1999-09-01

    There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation

  3. Ethical Issues of Transplanting Organs from Transgenic Animals into Human Beings

    Science.gov (United States)

    Behnam Manesh, Shima; Omani Samani, Reza; Behnam Manesh, Shayan

    2014-01-01

    One of the most important applications of transgenic animals for medical purposes is to transplant their organs into human’s body, an issue which has caused a lot of ethical and scientific discussions. we can divide the ethical arguments to two comprehensive groups; the first group which is known as deontological critiques (related to the action itself regardless of any results pointing the human or animal) and the second group, called the consequentialist critiques (which are directly pointing the consequences of the action). The latter arguments also can be divided to two subgroups. In the first one which named anthropocentrism, just humankind has inherent value in the moral society, and it studies the problem just from a human-based point of view while in second named, biocentrism all the living organism have this value and it deals specially with the problem from the animal-based viewpoint. In this descriptive-analytic study, ethical issues were retrieved from books, papers, international guidelines, thesis, declarations and instructions, and even some weekly journals using keywords related to transgenic animals, organ, and transplantation. According to the precautionary principle with the strong legal and ethical background, due to lack of accepted scientific certainties about the safety of the procedure, in this phase, transplanting animal’s organs into human beings have the potential harm and danger for both human and animals, and application of this procedure is unethical until the safety to human will be proven. PMID:25383334

  4. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1990-01-01

    Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

  5. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  6. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    International Nuclear Information System (INIS)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

  7. Late non-infectious lung damage in children after allogeneic hematopoietic stem cells transplantation

    Directory of Open Access Journals (Sweden)

    Yu. V. Skvortsova

    2015-06-01

    Full Text Available Hematopoietic stem cells transplantation (HSCT technology currently allows curing a lot of malignant and non-malignant diseases in adults and children. However, HSCT is highly toxic treatment. HSCT complications include the possibility of prolonged immunodeficiency, alloand autoimmune reactions and various organs dysfunction. These conditions require careful monitoring by specialists, early diagnosis and appropriate treatment. This article discusses the clinical features, diagnosis and treatment options of such late complications as non-infectious lung disease. These conditions can lead to disability of patients. Relevance and importance of timely diagnosis of these pathological conditions, including the range of clinical tests available on a residence, with a view to effective treatment can improve the quality of life ofchildren with complications after HSCT. Theoretical issues are illustrated by case report.

  8. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Directory of Open Access Journals (Sweden)

    Chun-Nun Chao

    Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  9. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Science.gov (United States)

    Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

    2016-01-01

    Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  10. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

    2004-01-01

    BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

  11. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

    2004-01-01

    Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

  12. Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Angela Koutsokera

    2017-07-01

    Full Text Available BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS and restrictive allograft syndrome (RAS, are major causes of mortality after lung transplantation (LT. RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs. Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

  13. Imaging in transplantation

    International Nuclear Information System (INIS)

    Bankier, A.A.

    2008-01-01

    This book covers all topics related to the imaging of organ transplantation. An introductory section addresses such issues as organ procurement, patient selection, immune responses, and ethical and economic considerations. The main part of the book then offers in-depth coverage of heart, renal, liver, lung, bone marrow and pancreatic and intestinal transplantation. Each of these topics is discussed firstly in a clinical chapter and then in a radiological chapter. The clinical chapters detail the epidemiology, clinical background, and surgical procedures, as well as any clinically relevant issues of which the radiologist should be aware. The radiological chapters describe and depict the imaging manifestations of specific organ transplantations, document the normal radiological appearance of transplanted organs and consider both early and late complications. This is a unique, superbly illustrated volume that will be of great assistance to all who work in this field. (orig.)

  14. Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT.

    Science.gov (United States)

    Holm, A M; Riise, G C; Hansson, L; Brinch, L; Bjørtuft, O; Iversen, M; Simonsen, S; Fløisand, Y

    2013-05-01

    Chronic GVHD (cGVHD) associated bronchiolitis obliterans syndrome (BOS) is a serious complication after allo-SCT, and lung transplantation (LTx) may be the ultimate treatment option. To evaluate this treatment, data on all patients with LTx after allo-SCT ever performed in Sweden, Norway, Denmark and Finland were recorded and compared with survival data from the Scandiatransplant registry. In total, LTx after allo-SCT had been performed in 13 patients. Allo-SCT was done because of AML (n=6), CML (n=3), ALL (n=2), immunodeficiency (n=1) and aplastic anemia (n=1). All developed clinical cGVHD, with median interval from allo-SCT to LTx of 8.2 (0.7-16) years. Median age at LTx was 34 (16-55) years, and the median postoperative observation time was 4.2 (0.1-15) years. Two patients died, one due to septicemia, the other of relapsing leukemia, after 2 and 14 months, respectively. Four developed BOS, one of these was retransplanted. The survival did not significantly differ from the survival in matched LTx controls, being 90% 1 year and 75% 5 years after LTx compared with 85% and 68% in the controls. We therefore suggest that LTx may be considered in carefully selected patients with BOS due to cGVHD after allo-SCT.

  15. Utilização de endoprótese metálica no tratamento de estenose brônquica após transplante pulmonar Treatment of bronchial stenosis after lung transplantation using a self-expanding metal endobronchial stent

    Directory of Open Access Journals (Sweden)

    Marcos Naoyuki Samano

    2005-06-01

    Full Text Available As complicações decorrentes da anastomose brônquica nos transplantes pulmonares, embora tenham diminuído ao longo do tempo, ainda figuram como um dos principais fatores de morbi-mortalidade nesses pacientes. As formas de tratamento dessas complicações incluem dilatação por balão, fotocoagulação por laser, endopróteses de silicone e metálicas, e reoperação. Relata-se o caso de um paciente que apresentou estenose brônquica após transplante pulmonar unilateral esquerdo, cujo tratamento foi realizado com endoprótese metálica auto-expansível de nitinol (Ultraflex®. Embora seja um caso pioneiro no Brasil, a boa resposta clínica, concordante com os dados da literatura, sugere que esse tratamento seja uma boa alternativa nesses casos.Although the incidence of bronchial anastomosis as a complication of lung transplantation has decreased in recent years, it remains a significant cause of morbidity and mortality in these patients. Treatment options include balloon dilatation, laser photocoagulation, placement of a stent (silicone or metal, and performing a second operation. We report the case of a patient who presented bronchial stenosis after left lung transplantation and was treated with a self-expanding metal alloy (nitinol stent (Ultraflex®. Despite the fact that this was the first case of stenosis treated in this fashion in Brazil, the positive clinical response, in agreement with results reported in the literature, indicates that this treatment is a viable alternative in such cases.

  16. Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Peperhove, Matti; Vo Chieu, Van Dai; Gutberlet, Marcel; Hartung, Dagmar; Tewes, Susanne; Wacker, Frank; Hueper, Katja [Hannover Medical School, Diagnostic and Interventional Radiology, Hannover (Germany); Jang, Mi-Sun; Gwinner, Wilfried; Haller, Hermann; Gueler, Faikah [Nephrology, Hannover Medical School, Hannover (Germany); Warnecke, Gregor; Fegbeutel, Christiane; Haverich, Axel [Hannover Medical School, Cardiothoracic, Transplantation and Vascular Surgery, Hannover (Germany); Lehner, Frank [Hannover Medical School, General, Abdominal and Transplant Surgery, Hannover (Germany); Braesen, Jan Hinrich [Pathology, Hannover Medical School, Hannover (Germany)

    2018-01-15

    To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function. 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation. Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function. T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation. (orig.)

  17. Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation

    International Nuclear Information System (INIS)

    Peperhove, Matti; Vo Chieu, Van Dai; Gutberlet, Marcel; Hartung, Dagmar; Tewes, Susanne; Wacker, Frank; Hueper, Katja; Jang, Mi-Sun; Gwinner, Wilfried; Haller, Hermann; Gueler, Faikah; Warnecke, Gregor; Fegbeutel, Christiane; Haverich, Axel; Lehner, Frank; Braesen, Jan Hinrich

    2018-01-01

    To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function. 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation. Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function. T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation. (orig.)

  18. Inhibiting CXCL12 blocks fibrocyte migration and differentiation and attenuates bronchiolitis obliterans in a murine heterotopic tracheal transplant model.

    Science.gov (United States)

    Harris, David A; Zhao, Yunge; LaPar, Damien J; Emaminia, Abbas; Steidle, John F; Stoler, Mark; Linden, Joel; Kron, Irving L; Lau, Christine L

    2013-03-01

    Fibrocytes are integral in the development of fibroproliferative disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti-collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and differentiate into smooth muscle actin-producing (CD45+CXCR4+α-smooth muscle actin+) cells. We postulated that an antibody directed against CXCL12 would attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal transplant allografts. A total alloantigenic mismatch murine heterotopic tracheal transplant model of obliterative bronchiolitis was used. The mice were treated with either goat-anti-human CXCL12 F(ab')(2) or goat IgG F(ab')(2). Buffy coat, bone marrow, and trachea allografts were collected and analyzed using flow cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and Direct Red 80 collagen stain. Compared with the controls, the anti-CXCL12-treated mice showed a significant decrease in tracheal allograft fibrocyte populations at 7 and 21 days after transplantation. Bone marrow and buffy coat aspirates showed the same trend at 7 days. In the anti-CXCL12-treated mice, there was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated; interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen deposition at 21 and 28 days after transplantation (P = .042 and P = .012, respectively). Understanding the role of fibrocytes in airway fibrosis after lung transplantation could lead to a paradigm shift in treatment strategy. Anti-CXCL12 antibody afforded protection against infiltrating fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after lung transplantation, and the quantification of fibrocyte populations could provide clinicians with a biomarker of fibrosis, allowing individualized drug therapy. Copyright © 2013 The American Association for Thoracic Surgery. Published

  19. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    Science.gov (United States)

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  20. The immunologic considerations in human head transplantation.

    Science.gov (United States)

    Hardy, Mark A; Furr, Allen; Barret, Juan P; Barker, John H

    2017-05-01

    The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  1. Polyomavirus – an emergent pathogen in transplant recipients

    Directory of Open Access Journals (Sweden)

    Juliana de Moura Montagner

    2007-06-01

    Full Text Available Medical centers that work with transplants often face opportunisticinfections that demand specific tools to make diagnosis. Theprevalence of latent polyomavirus infections is high, and the mostcommon site of latency of the most prevalent polyomavirus in humans,BK virus (BKV, is the renal tissue. Hence, renal transplanted patientsare particularly vulnerable to the damage caused by viral reactivationduring immunosupression. In such patients BKV is associated toureteral stenosis and/or BKV nephropathy, leading to progressivedysfunction and graft loss, often diagnosed as rejection. In other organsrecipients (namely lung, liver, heart and pancreas, BKN is also the mostimportant clinical manifestation, whereas in bone marrow recipients themost common is hemorrhagic cystitis. This review presents the viralbiology and discusses the pathophysiology of polyomavirus diseasesand the diagnostic efficacy of the laboratory tests available, guidingto the best strategy for assessment and monitoring of patients at riskor under specific treatment.

  2. Desensitization strategies in adult heart transplantation-Will persistence pay off?

    Science.gov (United States)

    Chih, Sharon; Patel, Jignesh

    2016-08-01

    Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model.

    Science.gov (United States)

    Liljebäck, Hanna; Grapensparr, Liza; Olerud, Johan; Carlsson, Per-Ola

    2016-01-01

    Clinical islet transplantation is characterized by a progressive deterioration of islet graft function, which renders many patients once again dependent on exogenous insulin administration within a couple of years. In this study, we aimed to investigate possible engraftment factors limiting the survival and viability of experimentally transplanted human islets beyond the first day after their transplantation to the liver. Human islets were transplanted into the liver of nude mice and characterized 1 or 30 days after transplantation by immunohistochemistry. The factors assessed were endocrine mass, cellular death, hypoxia, vascular density and amyloid formation in the transplanted islets. One day posttransplantation, necrotic cells, as well as apoptotic cells, were commonly observed. In contrast to necrotic death, apoptosis rates remained high 1 month posttransplantation, and the total islet mass was reduced by more than 50% between 1 and 30 days posttransplantation. Islet mass at 30 days posttransplantation correlated negatively to apoptotic death. Vascular density within the transplanted islets remained less than 30% of that in native human islets up to 30 days posttransplantation and was associated with prevailing hypoxia. Amyloid formation was rarely observed in the 1-day-old transplants, but was commonly observed in the 30-day-old islet transplants. We conclude that substantial islet cell death occurs beyond the immediate posttransplantation phase, particularly through apoptotic events. Concomitant low vascularization with prevailing hypoxia and progressive amyloid development was observed in the human islet grafts. Strategies to improve engraftment at the intraportal site or change of implantation site in the clinical setting are needed.

  4. Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

    Science.gov (United States)

    Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

    2015-06-01

    Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

  5. Pulmonary function changes in long-term survivors of bone marrow transplantation

    International Nuclear Information System (INIS)

    Gore, Elizabeth M.; Lawton, Colleen A.; Ash, Robert C.; Lipchik, Randolph J.

    1996-01-01

    Purpose: This study was undertaken to evaluate long-term pulmonary function changes in patients undergoing bone marrow transplantation (BMT), to assess their clinical significance, and to identify factors influencing these changes. Methods and Materials: Pulmonary function tests (PFT) were evaluated before and after BMT in 111 adult patients undergoing BMT between 1985 and 1991. Forced expiratory volume at 1 s (FEV 1 ), forced vital capacity (FVC), diffusing capacity (DLCO), and total lung capacity (TLC) were evaluated. One hundred and three patients (92.8%) received total body irradiation (TBI) to a total dose of 14 Gy in nine equal fractions. The lung dose was restricted to 1 , FVC, and TLC were lower than pre transplant values (p 1 did not fall significantly in patients without acute or chronic GVHD and recovered earlier than in patients without post transplant pulmonary infection. Recovery of FVC, TLC, and DLCO was also delayed in patients with acute and chronic GVHD and post transplant pulmonary infection. Multiple regression analysis revealed an association between a higher radiation dose to the lungs, and decreased FVC at 2 years (p = 0.01). Progressive obstructive pulmonary disease was not observed. Conclusions: An initial decline in PFTs with subsequent recovery was observed. Factors associated with delayed recovery and incomplete recovery of PFTs were GVHD, post transplant pulmonary infection, and higher radiation dose to the lungs. The conditioning regimen used at Medical College of Wisconsin, including relatively high TBI doses with partial transmission pulmonary shielding, appears to be well tolerated by the lungs in long-term survivors. No progressive decline in PFTs or symptomatic decline in pulmonary function was observed during the time interval studied

  6. Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

    International Nuclear Information System (INIS)

    Varekamp, A.E.; de Vries, A.J.; Zurcher, C.; Hagenbeek, A.

    1987-01-01

    The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy

  7. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  8. Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

    2007-01-01

    One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

  9. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Tilahun Alelign

    2018-01-01

    Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

  10. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Science.gov (United States)

    Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

    2018-01-01

    Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

  11. Human papilloma virus infection in female kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Shirin Ghazizadeh

    2011-01-01

    Full Text Available The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years. Hypertension was the most common cause of renal insufficiency (34.4%, while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse was 16.2 years (range, 1-35. Coitus interruptus was the most common contraceptive method used (37.9%, followed by tubal ligation and condom (10.3% and 6.9%, respectively. All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%. There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

  12. Scintigraphic diagnosis of silent aspiration following double-sided lung transplantation; Szintigraphischer Nachweis einer stillen Aspiration nach beidseitiger Lungentransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Toenshoff, G. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin; Stock, U. [Kiel Univ. (Germany). Klinik fuer Herz- und Gefaesschirurgie; Bohuslavizki, K.H. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin; Brenner, W. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin; Costard-Jaeckle, A. [Kiel Univ. (Germany). Klinik fuer Herz- und Gefaesschirurgie; Cremer, J. [Kiel Univ. (Germany). Klinik fuer Herz- und Gefaesschirurgie; Clausen, M. [Kiel Univ. (Germany). Klinik fuer Nuklearmedizin

    1996-08-01

    We present a case of a 25 year old patient who underwent double-sided lung transplantation and suffered from recurrent pneumonia. Silent aspiration was suspected clinically. Aspiration was proved by scintigraphy enabling to discriminate between direct oro-pulmonal aspiration and aspiration after gastro-esophageal reflux. (orig.) [Deutsch] Vorgestellt wird der Fall einer 25jaehrigen Patientin nach beidseitiger Lungentransplantation und rezidivierenden Pneumonien. Klinisch bestand der Verdacht auf eine stille Aspiration. Szintigraphisch gelang sowohl der Aspirationsnachweis als auch eine Differenzierung hinsichtlich der Genese: Direkte oro-pulmonale Aspiration versus Aspiration nach gastrooesophagealem Reflux. (orig.)

  13. Esophageal motor disorders are frequent during pre and post lung transplantation. Can they influence lung rejection?

    Science.gov (United States)

    Ciriza de Los Ríos, Constanza; Canga Rodríguez-Valcárcel, Fernando; de Pablo Gafas, Alicia; Castel de Lucas, Isabel; Lora Pablos, David; Castellano Tortajada, Gregorio

    2018-06-01

    lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx. the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection. HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0. EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group. significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure.

  14. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

    Science.gov (United States)

    Gan, Lu; Duan, Hua; Xu, Qian; Tang, Yi-Qun; Li, Jin-Jiao; Sun, Fu-Qing; Wang, Sha

    2017-05-01

    Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  15. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

    Full Text Available Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI. The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

  16. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were......INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  17. First clinical evaluation of radioimmunoimaging using anti-human lung cancer monoclonal antibodies

    International Nuclear Information System (INIS)

    Zhou Qian

    1991-01-01

    Anti-human large cell lung cancer monoclonal antibodies (McAb) 2E3 and 6D1 were produced in the laboratory. Immunohistochemical studies and radiobinding assay showed these antibodies possessed high specificity against lung cancer cells. 28 patients with lung masses were investigated with 131 I-labeled McAb 6D1 and/or 2E3 scintigraphy. 19 of them were histologically proven and 13 were diagnosed primary lung carcinoma. Radioimmunoimaging visualized 10/13 of the primary lung cancers with a detection rate of 77%. Only 1 case of the non-cancer patients and a false localization, giving a true negative rate of 83%. Pathologically the squamous cell lung carcinoma had the highest localization and the small cell lung carcinoma next, but the detection rate was 100% for both. The adenocarcinoma of lung was less sensitive to these McAbs, with a detection rate of only 33% (1 of 3 cases). We conclude that radioimmunoimaging with anti-human large cell lung cancer McAbs is more specific and effective in detecting primary lung cancers and differentiating lung masses than with antibodies against other tumor associated antigens

  18. Diffusion on Networks and Diffusion Weighted NMR of the Human Lung

    DEFF Research Database (Denmark)

    Buhl, Niels

    2011-01-01

    of the diffusion propagator to general properties of the underlying graph. Diffusion weighted NMR of the human lung with hyperpolarized noble gases, which over the last decade has been demonstrated to be a very promising way of detecting and quantifying lung diseases like emphysema, represent an obvious...... application of the above mentioned theory, given that the human lung consists of a large network of bifurcating tube like airways. 90-95% of the gas in a human lung resides in the ~30000 pulmonary acini, each of these consists of ~500 airways, which are connected as the edges in a binary tree. We model...... diffusion in the pulmonary acini as diffusion on metric graphs with this structure. The metric graph for each individual pulmonary acinus is embedded in three dimensional space via line segments. By considering an isotropic distribution of acini and a symmetric branching geometry for the line segments...

  19. Detection of human leukocyte antigen compatibility and antibodies in liver transplantation in China

    Institute of Scientific and Technical Information of China (English)

    Xue-Qin Meng; Xuan Zhang; Jun Fan; Lin Zhou; Bing Hao; Xiao-Ming Chen; Wei-Hang Ma; Shu-Sen Zheng

    2009-01-01

    BACKGROUND: The exact roles of human leukocyte antigen (HLA) compatibility, HLA antibodies and underlying diseases in acute rejection of liver transplants are not clear. Moreover, cytomegalovirus (CMV) infection, one of the most common infections after transplantation, is related to HLA genotype and the incidence of acute rejection. METHODS: Since there are controversial reports, we analyzed the impact of HLA matching, HLA antibodies and underlying diseases in 38 liver transplant recipients in China, and assessed the association of CMV infection and HLA compatibility. RESULTS: The frequency of no HLA compatibility was high in patients without antigenemia (P=0.019). All 17 patients with HLA-A matching developed antigenemia (P0.05). In patients with acute rejection, no differences were found in the incidence of acute rejection in transplants for hepatitis B, tumors, or combined hepatitis B and tumors (P>0.05).CONCLUSIONS: There are fewer acute rejections in transplants with more HLA compatibilities. Speciifc investigations of underlying diseases and HLA typing may be necessary in liver transplantation. The mechanisms of CMV infection and HLA matching should be further studied. HLA before transplantation should be examined for the prevention of acute rejection and CMV infection.

  20. Thoracic organ transplantation: laboratory methods.

    Science.gov (United States)

    Patel, Jignesh K; Kobashigawa, Jon A

    2013-01-01

    Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques.

  1. Disseminated histoplasmosis presenting with ileal perforation in a renal transplant recipient.

    Science.gov (United States)

    Zainudin, B M; Kassim, F; Annuar, N M; Lim, C S; Ghazali, A K; Murad, Z

    1992-08-01

    A renal transplant patient presented with ileal perforation due to histoplasmosis 3 years after transplantation. Mesenteric lymph nodes and lungs were also affected by the disease. She was successfully treated with amphotericin B followed by ketoconazole.

  2. Surgical Thoracic Transplant Training: Super Fellowship-Is It Super?

    Science.gov (United States)

    Makdisi, George; Makdisi, Tony; Caldeira, Christiano C; Wang, I-Wen

    2017-10-11

    The quality of training provided to thoracic transplant fellows is a critical step in the care of complex patients undergoing transplant. The training varies since it is not an accreditation council for graduate medical education accredited fellowship. A total of 104 heart or lung transplant program directors throughout the United States were sent a survey of 24 questions focusing on key aspects of training, fellowship training content and thoracic transplant job satisfaction. Out of the 104 programs surveyed 45 surveys (43%) were returned. In total, 26 programs offering a transplant fellowship were included in the survey. Among these programs 69% currently have fellows of which 56% are American Board of Thoracic Surgery board eligible. According to the United Network for Organ Sharing (UNOS) requirements, 46% of the programs do not meet the requirements to be qualified as a primary heart transplant surgeon. A total of 23% of lung transplant programs also perform less than the UNOS minimum requirements. Only 24% have extra-surgical curriculum. Out of the participating programs, only 38% of fellows secured a job in a hospital setting for performing transplants. An astounding 77% of replies site an unpredictable work schedule as the main reason that makes thoracic transplant a less than favorable profession among new graduates. Long hours were also a complaint of 69% of graduates who agreed that their personal life is affected by excessive work hours. Annually, almost half of all thoracic transplant programs perform fewer than the UNOS requirements to be a primary thoracic surgeon. This results in a majority of transplant fellows not finding a suitable transplant career. The current and future needs for highly qualified thoracic transplant surgeons will not be met through our existing training mechanisms. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  3. A personal perspective: 100-year history of the humoral theory of transplantation.

    Science.gov (United States)

    Terasaki, Paul I

    2012-04-27

    The humoral theory states that antibodies cause the rejection of allografts. From 1917 to 1929, extensive efforts were made to produce antibodies against tumors. It was finally realized that the antibodies were produced against the transplant antigens present on transplantable tumors, not against the tumor-specific antigens. To get around this problem, inbred mouse strains were developed, leading to identification of the transplant antigens determined by the H-2 locus of mice. The antibodies were hemagglutinating and cytotoxic antibodies. The analogous human leukocyte antigen system was established by analysis of lymphocytotoxic alloantibodies that were made by pregnant women, directed against mismatched antigens of the fetus. The human leukocyte antigen antibodies were then found to cause hyperacute rejection, acute rejection, and chronic rejection of kidneys. Antibodies appeared in almost all patients after rejection of kidneys. With Luminex single antigen bead technology, donor-specific antibodies could be identified before rise in serum creatinine and graft failure. Antibodies were shown to be predictive of subsequent graft failure in kidney, heart, and lung transplants: patients without antibodies had superior 4-year graft survival compared with those who did have antibodies. New evidence that antibodies are also associated with chronic failure has appeared for liver and islet transplants. Four studies have now shown that removal or reduction of antibodies result in higher graft survival. If removal of antibodies prevents chronic graft failure, final validation of the humoral theory can be achieved.

  4. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  5. Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

    Science.gov (United States)

    Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

    2006-07-01

    Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

  6. Pulmonary complications in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jung Bin; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Lee, Seung Rho; Hahm, Chang Kok; Joo, Kyung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2003-04-01

    To evaluate the radiographic and CT findings of pulmonary complications other than pulmonary edema arising from renal transplantation. Among 393 patients who had undergone renal transplantation at our hospital during a previous ten-year period, 23 with pulmonary complications other than pulmonary edema were included in this study. The complications involved were infection caused by CMV (n=6), bacteria (n=4), fungus (n=4), tuberculosis (n=2), varicella (n=1) or chlamydia (n=1), and malignancy involving lung cancer (n=4) or Kaposi's sarcoma (n=1). Two chest radiologists reviewed all images. The complications manifesting mainly as pulmonary nodules were lung cancer (4/4), tuberculosis (1/2), and Kaposi's sarcoma (1/1). Pulmonary consolidation was a main feature in bacterial infection (4/4), fungal infection (3/4), tuberculosis (1/2), chlamydial infection (1/1), and varicellar pneumonia (1/1). Ground-glass attenuation was a main CT feature in CMV pneumonia (4/6), and increased interstitial making was a predominant radiographic feature in CMV pneumonia (2/6). The main radiologic features described above can be helpful for differential diagnosis of the pulmonary complications of renal transplantation.

  7. Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

    Directory of Open Access Journals (Sweden)

    Priya R. Prabhu

    2012-01-01

    Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

  8. The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration.

    Science.gov (United States)

    Reder, Nicholas P; Davis, Christopher S; Kovacs, Elizabeth J; Fisichella, P Marco

    2014-06-01

    Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that symptoms of GERD and detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplantation patients with GERD-induced aspiration. From November 2009 to November 2010, 85 lung transplantation patients undergoing surveillance bronchoscopy were prospectively enrolled. For these patients, self-reported symptoms of GERD were correlated with levels of pepsin and bile acids in BAL and EBC and with GERD status assessed by 24-h pH monitoring. The sensitivity and specificity of pepsin and bile acids in BAL and EBC also were compared with the presence of GERD in 24-h pH monitoring. The typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration. The atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in BAL. The sensitivity and specificity of pepsin in BAL compared with GERD by 24-h pH monitoring were respectively 60 and 45 %, whereas the sensitivity and specificity of bile acids in BAL were 67 and 80 %. These data indicate that the measurement of pepsin and bile acids in BAL can provide additional data for identifying lung transplantation patients at risk for GERD-induced aspiration compared with symptoms or 24-h pH monitoring alone. These results support a diagnostic role for detecting markers of aspiration in BAL, but this must be validated in larger studies.

  9. Isolation, culture and intraportal transplantation of rat marrow stromal cell

    International Nuclear Information System (INIS)

    Wang Ping; Wang Jianhua; Yan Zhiping; Li Wentao; Lin Genlai; Hu Meiyu; Wang Yanhong

    2004-01-01

    Objective: To observe the tracing and evolution of marrow stromal cell (MSC) after intraportal transplantation into the liver of homogenous rats, and to provide experimental data for MSC differentiation to hepatocyte in vivo. Methods: The MSC was isolated from the leg bone marrow of adult SD rats, and purified by culture-expanded in vitro. Before transplantation, MSC was labeled with DAPI. Then 10 5 MSC were intraportally transplanted into the homogenous rat liver. Rats were killed at 2 hours and 1, 2, 3 and 4 weeks after transplantation. The cryosection samples of liver and lung were observed under fluorescence microscopy. Results: MSC in vitro culture had high ability of proliferation. Except 4 rats were dead because of abdominal bleeding or infection, other recipients were healthy until sacrificed. The implantation cells were detected by identifying the DAPI labeled MSC in the host livers, but not in the host lungs. Conclusion: Intraportal transplanted MSC could immigrate and survive in the host livers at least for 4 weeks. They could immigrate from the small branches of portal veins to hepatic parenchyma

  10. Évaluation du risque d’embolie gazeuse durant les transplantations pulmonaires

    OpenAIRE

    Bezaz, Nadia

    2015-01-01

    Lung transplantation is the curatif treatment for terminal respiratory failure. Air embolism is one of its potential complications. As it is,this surgery implies an anastomosis of the pulmonary graft on the left atrium. The incomplete purge of the graft can consequently make one vulnerable to a systemic embolism. To our knowledge, no study has yet taken a cautious look at air embolism during lung transplantation. The main objective of this retrospective study is to evaluate the incidence of a...

  11. Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung.

    Science.gov (United States)

    Sava, Parid; Ramanathan, Anand; Dobronyi, Amelia; Peng, Xueyan; Sun, Huanxing; Ledesma-Mendoza, Adrian; Herzog, Erica L; Gonzalez, Anjelica L

    2017-12-21

    Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.

  12. Explant culture of human peripheral lung. I. Metabolism of benzo[alpha]pyrene

    DEFF Research Database (Denmark)

    Stoner, G.D.; Harris, C.C.; Autrup, Herman

    1978-01-01

    the predominant alveolar epithelial cell type. Lamellar inclusion bodies were released from the type 2 cells and accumulated in the alveolar spaces. The metabolism of benzo[alpha]pyrene (BP) in human lung explants cultured for up to 7 days was investigated. Human lung explants had measurable aryl hydrocarbon......Human lung explants have been maintained in vitro for a period of 25 days. Autoradiographic studies indicated that the broncholar epithelial cells, type 2 alveolar epithelial cells, and stromal fibroblasts incorporated 3H-thymidine during the culture. After 7 to 10 days, type 2 cells were...... hydroxylase activity and could metabolize BP into forms that were bound to cellular DNA and protein. Peripheral lung had significantly lower aryl hydrocarbon hydroxylase activity than cultured bronchus but both tissues had similar binding levels of BP to DNA. Radioautographic studies indicated that all cell...

  13. Commercialization of human organs for transplantation intervivos under the perspective of the social bioethics

    Directory of Open Access Journals (Sweden)

    Fernando Hellmann

    2012-12-01

    Full Text Available Buying and selling human organs for transplants from living donors has been discussed worldwide in the bioethical debate and it is becoming a public health problem. This essay discusses, in light of the Social Bioethics, arguments used to justify such practices, which are related to the common good, moral plurality, autonomy and individual freedom. Such justificatory aspects assume liberal and utilitarian characteristics. They present the possibility of double standard, do not consider social vulnerability, and harm dignity and human rights by evidencing an apology to the market laws. Thus, the justifications for buying and selling human organs for transplantations intervivos eventually turn the body, or part of it, into a commodity.

  14. Mycobacterium tuberculosis Invasion of the Human Lung: First Contact

    Directory of Open Access Journals (Sweden)

    Jeroen Maertzdorf

    2018-06-01

    Full Text Available Early immune responses to Mycobacterium tuberculosis (Mtb invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host–pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host–pathogen interactions, while animal models have their own limitations. In this study, we have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue-resident cell types. As first cell types confronted with pathogens invading the lung, alveolar macrophages, and epithelial cells displayed rapid proinflammatory chemokine and cytokine responses to Mtb infection. Other tissue-resident innate cells like gamma/delta T cells, mucosal associated invariant T cells, and natural killer cells showed partially similar but weaker responses, with a high degree of variability across different donors. Finally, we investigated the responses of tissue-resident innate lymphoid cells to the inflammatory milieu induced by Mtb infection. Our infection model provides a unique approach toward host–pathogen interactions at the natural port of Mtb entry and site of its implantation, i.e., the human lung. Our data provide a first detailed insight into the early responses of different relevant pulmonary cells in the alveolar microenvironment to contact with Mtb. These results can form the basis for the identification of host markers that orchestrate early host defense and provide resistance or susceptibility to stable Mtb infection.

  15. Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2015-09-01

    Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

  16. Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity

    International Nuclear Information System (INIS)

    Galton, J.E.; Xue, B.; Hochwald, G.M.; Thorbecke, G.J.

    1982-01-01

    Transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. Artificial metastases were seen in the stomach, pancreas, lungs, heart, and muscle, and occasionally in the kidneys and liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body ν-irradiation enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line

  17. Carbonyl Reduction of NNK by Recombinant Human Lung Enzymes. Identification of HSD17β12 as the Reductase important in (R)-NNAL formation in Human Lung.

    Science.gov (United States)

    Ashmore, Joseph H; Luo, Shaman; Watson, Christy J W; Lazarus, Philip

    2018-05-17

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most abundant and carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke. The major metabolic pathway for NNK is carbonyl reduction to form the (R) and (S) enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which, like NNK, is a potent lung carcinogen. The goal of the present study was to characterize NNAL enantiomer formation in human lung and identify the enzymes responsible for this activity. While (S)-NNAL was the major enantiomer of NNAL formed in incubations with NNK in lung cytosolic fractions, (R)-NNAL comprised ~60 and ~95% of the total NNAL formed in lung whole cell lysates and microsomes, respectively. In studies examining the role of individual recombinant reductase enzymes in lung NNAL enantiomer formation, AKR1C1, AKR1C2, AKR1C3, AKR1C4 and CBR1 all exhibited (S)-NNAL formation activity. To identify the microsomal enzymes responsible for (R)-NNAL formation, 28 microsomal reductase enzymes were screened for expression by real-time PCR in normal human lung. HSD17β6, HSD17β12, KDSR, NSDHL, RDH10, RDH11 and SDR16C5 were all expressed at levels >HSD11β1, the only previously reported microsomal reductase enzyme with NNK-reducing activity, with HSD17β12 the most highly expressed. Of these lung-expressing enzymes, only HSD17β12 exhibited activity against NNK, forming primarily (>95%) (R)-NNAL, a pattern consistent with that observed in lung microsomes. siRNA knockdown of HSD17β12 resulted in significant decreases in (R)-NNAL formation activity in HEK293 cells. These data suggest that both cytosolic and microsomal enzymes are active against NNK and that HSD17β12 is the major active microsomal reductase that contributes to (R)-NNAL formation in human lung.

  18. Imaging of Kaposi sarcoma in a transplanted liver: A rare case report

    Directory of Open Access Journals (Sweden)

    Saumya Gupta

    2015-06-01

    Full Text Available In post-transplant patients, de novo malignancies such as post-transplant lymphoproliferative disease (PTLD, lung carcinoma, renal cell carcinoma, cutaneous malignancies, and Kaposi sarcoma are now seen. The immunotherapy used to prevent graft failure indirectly increases their risk. We present a rare case of visceral Kaposi sarcoma in a patient with orthotopic liver transplant.

  19. Epidermal growth factor receptor in primary human lung cancer

    International Nuclear Information System (INIS)

    Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

    1996-01-01

    Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125 I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g -1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g -1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

  20. Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients.

    Science.gov (United States)

    Macesic, Nenad; Abbott, Iain J; Kaye, Matthew; Druce, Julian; Glanville, Allan R; Gow, Paul J; Hughes, Peter D; Korman, Tony M; Mulley, William R; O'Connell, Phillip J; Opdam, Helen; Paraskeva, Miranda; Pitman, Matthew C; Setyapranata, Stella; Rawlinson, William D; Johnson, Paul D R

    2017-10-01

    Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  2. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

    1998-01-01

    OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

  3. Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Amie L. Holmes

    2013-11-01

    Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

  4. Ureaplasma Transmitted From Donor Lungs Is Pathogenic After Lung Transplantation.

    Science.gov (United States)

    Fernandez, Ramiro; Ratliff, Amy; Crabb, Donna; Waites, Ken B; Bharat, Ankit

    2017-02-01

    Hyperammonemia is a highly fatal syndrome in lung recipients that is usually refractory to medical therapy. We recently reported that infection by a Mollicute, Ureaplasma, is causative for hyperammonemia and can be successfully treated with antimicrobial agents. However, it remains unknown whether the pathogenic strain of Ureaplasma is donor or recipient derived. Here we provide evidence that donor-derived Ureaplasma infection can be pathogenic. As such, we uncover a previously unknown lethal donor-derived opportunistic infection in lung recipients. Given the high mortality associated with hyperammonemia, strategies for routine donor screening or prophylaxis should be further evaluated in prospective studies. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Hiromichi Matsushita

    Full Text Available Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC or leukemia-initiating cells (LIC appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL, a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34(+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34- fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP from CD34(+/CD38(+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34(- APL cells may share the ability to maintain the tumor.

  6. [Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].

    Science.gov (United States)

    López, L M; Vicente, R; Ramos, F; Palacios, L; Calvo, A; Hernández, S; Borro, J M; Morales, P; Montero, R

    1996-03-01

    Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.

  7. Chest Fat Quantification via CT Based on Standardized Anatomy Space in Adult Lung Transplant Candidates.

    Directory of Open Access Journals (Sweden)

    Yubing Tong

    Full Text Available Overweight and underweight conditions are considered relative contraindications to lung transplantation due to their association with excess mortality. Yet, recent work suggests that body mass index (BMI does not accurately reflect adipose tissue mass in adults with advanced lung diseases. Alternative and more accurate measures of adiposity are needed. Chest fat estimation by routine computed tomography (CT imaging may therefore be important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification and quality assessment based on a recently formulated concept of standardized anatomic space (SAS is presented. The goal of the paper is to seek answers to several key questions related to chest fat quantity and quality assessment based on a single slice CT (whether in the chest, abdomen, or thigh versus a volumetric CT, which have not been addressed in the literature.Unenhanced chest CT image data sets from 40 adult lung transplant candidates (age 58 ± 12 yrs and BMI 26.4 ± 4.3 kg/m2, 16 with chronic obstructive pulmonary disease (COPD, 16 with idiopathic pulmonary fibrosis (IPF, and the remainder with other conditions were analyzed together with a single slice acquired for each patient at the L5 vertebral level and mid-thigh level. The thoracic body region and the interface between subcutaneous adipose tissue (SAT and visceral adipose tissue (VAT in the chest were consistently defined in all patients and delineated using Live Wire tools. The SAT and VAT components of chest were then segmented guided by this interface. The SAS approach was used to identify the corresponding anatomic slices in each chest CT study, and SAT and VAT areas in each slice as well as their whole volumes were quantified. Similarly, the SAT and VAT components were segmented in the abdomen and thigh slices. Key parameters of the attenuation (Hounsfield unit (HU distributions were determined from each chest slice and from the

  8. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    International Nuclear Information System (INIS)

    Rodrigues, L.P.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

    2011-01-01

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10 6 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10 6 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation

  9. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, L.P. [Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Iglesias, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Nicola, F.C. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Steffens, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Valentim, L.; Witczak, A.; Zanatta, G. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Achaval, M. [Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Pranke, P. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Netto, C.A. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2011-12-23

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10{sup 6} cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10{sup 6} cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  10. Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

    Directory of Open Access Journals (Sweden)

    Parikumar P

    2011-01-01

    Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

  11. Anaemia and fever in Kidney transplant. The role of human parvovirus B19.

    Science.gov (United States)

    Parodis López, Yanet; Santana Estupiñán, Raquel; Marrero Robayna, Silvia; Gallego Samper, Roberto; Henríquez Palop, Fernando; Rivero Vera, José Carlos; Camacho Galán, Rafael; Pena López, María José; Sablón González, Nery; González Cabrera, Fayna; Oliva Dámaso, Elena; Vega Díaz, Nicanor; Rodríguez Pérez, José Carlos

    Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice.

    Science.gov (United States)

    Dimomeletis, Ilias; Deindl, Elisabeth; Zaruba, Marc; Groebner, Michael; Zahler, Stefan; Laslo, Saskia M; David, Robert; Kostin, Sawa; Deutsch, Markus A; Assmann, Gerd; Mueller-Hoecker, Josef; Feuring-Buske, Michaela; Franz, Wolfgang M

    2010-11-01

    Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes. We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction. Human MAPCs were selected by negative depletion of CD45(+)/glycophorin(+) BM cells and plated on fibronectin-coated dishes. In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction. In vivo, we transplanted human MAPCs (5 × 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice. Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo. Heart tissues were analyzed immunohistochemically. Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency. In later passages, cardiac markers (Nkx2.5, GATA4, MLC-2v, MLC-2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22α) were expressed. Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%). Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC integrated in the peri-infarct region. The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor-sensitive SCID model. Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs. Lack of

  13. Food allergies developing after solid organ transplant.

    Science.gov (United States)

    Needham, J M; Nicholas, S K; Davis, C M

    2015-12-01

    The development of food allergy is an increasingly recognized form of morbidity after solid organ transplant. It occurs more commonly in liver transplant recipients, although it has also been reported in heart, lung, kidney, and intestinal transplants. Pediatric transplant recipients are more likely to develop symptoms compared to adults, and reports of frequency vary widely from 5% to 38% in pediatric liver transplant recipients. Multiple mechanisms have been proposed in the literature, although no single mechanism can yet account for all reported observations. As food allergy can have at worst potentially fatal consequences, and at best require lifestyle adjustment through food avoidance, it is important for recipients to be aware of the donor's food allergies and particularly in pediatrics, the possibility of completely de novo allergies. This review explores the recent reports surrounding food allergy after solid organ transplant, including epidemiology, proposed mechanisms, and implications for practice. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

    International Nuclear Information System (INIS)

    Koo, Hyun Jung; Do, Kyung-Hyun; Chae, Eun Jin; Kim, Hwa Jung; Song, Joon Seon; Jang, Se Jin; Hong, Sang-Bum; Huh, Jin Won; Lee, En; Hong, Soo-Jong

    2017-01-01

    To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O_2 saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. (orig.)

  15. Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Hyun Jung; Do, Kyung-Hyun; Chae, Eun Jin [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Kim, Hwa Jung [University of Ulsan College of Medicine, Cancer Center, Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul (Korea, Republic of); Song, Joon Seon; Jang, Se Jin [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Hong, Sang-Bum; Huh, Jin Won [University of Ulsan College of Medicine, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, En [Inje University Haundae Paik Hospital, Department of Pediatrics, Busan (Korea, Republic of); Hong, Soo-Jong [University of Ulsan College of Medicine, Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, Seoul (Korea, Republic of)

    2017-01-15

    To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O{sub 2} saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. (orig.)

  16. Cardiopulmonary transplantation service establishment in the 1990s: Australia--a developing country?

    Science.gov (United States)

    Esmore, D; Williams, T; Bergin, P; Rosenfeldt, F; Cochrane, A; Griffiths, A; Federman, J

    1992-10-01

    1. A National Transplantation Service has been established at the Alfred Hospital performing more than 50 transplants per year. 2. Increased access to transplantation technology has facilitated an improvement in national population servicing from 2.7 to 6.2 transplants per million population per year. National funding of A$4.062 million per year has been secured. 3. Basic research into organ preservation has facilitated transcontinental organ procurement. 4. An active lung transplantation program has been established synchronous with the cardiac transplant service activities. 5. MCS program establishment has paralleled clinical transplantation activities. 6. Budget management and cost containment has been achieved through rationalisation of management protocols.

  17. Experimental studies on lung carcinogenesis and their relationship to future research on radiation-induced lung cancer in humans

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-03-01

    The usefulness of experimental systems for studying human lung carcinogenesis lies in the ease of studying components of a total problem. As an example, the main thrust of attack on possible synergistic interactions between radiation, cigarette smoke, and other irritants must be by means of research on animals. Because animals can be serially sacrificed, a systematic search can be made for progressive lung changes, thereby improving our understanding of carcinogenesis. The mechanisms of radiation-induced carcinogenesis have not yet been delineated, but modern concepts of molecular and cellular biology and of radiation dosimetry are being increasingly applied to both in vivo and in vitro exposure to determine the mechanisms of radiation-induced carcinogenesis, to elucidate human data, and to aid in extrapolating experimental animal data to human exposures. In addition, biologically based mathematical models of carcinogenesis are being developed to describe the nature of the events leading to malignancy; they are also an essential part of a rational approach to quantitative cancer risk assessment. This paper summarizes recent experimental and modeling data on radon-induced lung cancer and includes the confounding effects of cigarette-smoke exposures. The applicability of these data to understanding human exposures is emphasized, and areas of future research on human radiation-induced carcinogenesis are discussed. 7 refs., 2 figs., 3 tabs

  18. 4-Methoxyestradiol-induced oxidative injuries in human lung epithelial cells

    International Nuclear Information System (INIS)

    Cheng Yahsin; Chang, Louis W.; Cheng Lichuan; Tsai, M.-H.; Lin Pinpin

    2007-01-01

    Epidemiological studies indicated that people exposed to dioxins were prone to the development of lung diseases including lung cancer. Animal studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased liver tumors and promoted lung metaplasia in females. Metabolic changes in 17β-estradiol (E 2 ) resulted from an interaction between TCDD and E 2 could be associated with gender difference. Previously, we reported that methoxylestradiols (MeOE 2 ), especially 4-MeOE 2 , accumulated in human lung cells (BEAS-2B) co-treated with TCDD and E 2 . In the present study, we demonstrate unique accumulation of 4-MeOE 2 , as a result of TCDD/E 2 interaction and revealed its bioactivity in human lung epithelial cell line (H1355). 4-Methoxyestradiol treatment significantly decreased cell growth and increased mitotic index. Elevation of ROS and SOD activity, with a concomitant decrease in the intracellular GSH/GSSG ratio, was also detected in 4-MeOE 2 -treated cells. Quantitative comet assay showed increased oxidative DNA damage in the 4-MeOE 2 -treated H1355 cells, which could be significantly reduced by the anti-oxidant N-acetylcysteine (NAC). However, inhibition of cell growth and increase in mitotic arrest induced by 4-MeOE 2 were unaffected by NAC. We concluded that 4-MeOE 2 accumulation resulting from TCDD and E 2 interaction would contribute to the higher vulnerability on lung pathogenesis in females when exposed to TCDD

  19. Comments on the rat lung as a human surrogate in inhalation studies

    International Nuclear Information System (INIS)

    Koblinger, L.

    1988-01-01

    The laboratory rat is often used as a surrogate to estimate the hazard to human health following inhalation exposure to ambient aerosols. Extrapolation of rat deposition data to humans depends, however, on the similarities and differences between the morphometric structures of the two airway systems. The main structural difference between the lungs of the two species, aside from dimensions per se, is their respective airway branching pattern : while the human lung is a rather symmetrically, dichotomously dividing system, the rat network is a more monopodial branching structure. In our stochastic modelling approach to defining suitable morphologies for human and rat lung, we utilise measured morphometric dimensions as the data base upon which a rigorous statistical analysis is performed, instead of forcing them into a formalised, average pathway scheme. This stochastic approach allows us, therefore, to account for structural irregularities, such as asymmetric branching, monopodial structure, and inter and intra-subject variability

  20. Non-heart-beating lung donation : How big is the pool?

    NARCIS (Netherlands)

    Nijkamp, Danielle M.; van der Bij, Wim; Verschuuren, Erik A. M.; Heemskerk, Martin B. A.; de Buijzer, Erwin; Erasmus, Michiel E.

    Lungs from non-heart-beating (NHB) donors are seldom used in The Netherlands despite the good quality of these organs. Based on a retrospective analysis of 162 NHB donor procedures we found that only 5% of the lungs were actually utilized, but that 30% of the lungs were suitable for transplantation.

  1. Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema.

    Science.gov (United States)

    Ng-Blichfeldt, John-Poul; Alçada, Joana; Montero, M Angeles; Dean, Charlotte H; Griesenbach, Uta; Griffiths, Mark J; Hind, Matthew

    2017-06-01

    Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

    2016-08-01

    Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

  3. Potent selective nonpeptidic inhibitors of human lung tryptase

    OpenAIRE

    Burgess, Laurence E.; Newhouse, Bradley J.; Ibrahim, Prabha; Rizzi, James; Kashem, Mohammed A.; Hartman, Ann; Brandhuber, Barbara J.; Wright, Clifford D.; Thomson, David S.; Vigers, Guy P. A.; Koch, Kevin

    1999-01-01

    Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting ...

  4. Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

    Directory of Open Access Journals (Sweden)

    Andrew R. Pepper

    2017-06-01

    Full Text Available Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC, with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

  5. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-01-01

    Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

  6. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-01-01

    Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

  7. Valor predicts the thyroid hormones in the evolution the transplant bony marrow

    International Nuclear Information System (INIS)

    Alonso, C.A.; Carnot, J.; De Castro, R.; Morera, M.L.; Garcia, I.

    1998-01-01

    In this work you values the valor I predict the thyroid hormones in the bony marrow transplant evolution as factors the metabolisms oxidative and the synthesis albumins. The patients received conditioning treatments to the transplant and in the postoperational. The received radiations were 1000 cGy lateral cube, with blocking lung, to those that were subjected 3 sessions irradiation, they are practiced a transplant marrow allogeneic

  8. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  9. Donor Lung Procurement by Surgical Fellow with an Expectation of High Rate of Lung Utilisation.

    Science.gov (United States)

    Smail, Hassiba; Saxena, Pankaj; Wallinder, Andreas; Lin, Enjarn; Snell, Gregory I; Hobson, Jamie; Zimmet, Adam D; Marasco, Silvana F; McGiffin, David C

    2017-12-22

    There is an ever increasing demand for donor lungs in patients waiting for transplantation. Lungs of many potential donors will be rejected if the standard criteria for donor assessment are followed. We have expanded our donor lung pool by accepting marginal donors and establishing a donation after circulatory death program. We have achieved comparable results using marginal donors and accepting donor lungs following donation after circulatory death. We present our assessment and technical guidelines on lung procurement taking into consideration an increasingly complex cohort of lung donors. These guidelines form the basis of the lung procurement training program involving surgical Fellows at the Alfred Hospital in Melbourne, Australia. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  10. Quantification of human lung structure and physiology using hyperpolarized 129Xe.

    Science.gov (United States)

    Chang, Yulin V; Quirk, James D; Ruset, Iulian C; Atkinson, Jeffrey J; Hersman, F William; Woods, Jason C

    2014-01-01

    To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality. Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model. The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm(-1) ; total septal wall thickness = 9.2 ± 6.5 μm; blood-air barrier thickness = 1.0 ± 0.3 μm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text. The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases. Copyright © 2013 Wiley Periodicals, Inc.

  11. Visual assessment of functional lungs parenchyma on HRCT and 3He-MRI in patients after single lung transplantation: comparison with quantitative volumetric results

    International Nuclear Information System (INIS)

    Zaporozhan, J.; Ley, S.; Gast, K.K.; Heussel, C.P.; Thelen, M.; Biedermann, A.; Eberle, B.; Mayer, E.; Kauczor, H.U.

    2005-01-01

    Purpose: Visual assessment of the ventilation using HRCT and 3 He-MRI in patients after single lung transplantation (SLTX). Analysis of specific ventilation defects found with 3 He-MRI and morphological changes found with HRCT. Materials and Methods: We evaluated 8 male patients (54±6 years) suffering from emphysema and six patients (3 males and 3 females, 58±9.5 years) suffering from idiopathic pulmonary fibrosis (IPF) after SLTX. The morphological changes at HRCT were classified and localized. In 3 He-MRI (2D FLASH), 10 to 14 slices (slice thickness 10 mm, gap 5 mm) were acquired in coronal orientation to cover the whole lung. Ventilation defects were localized and characterized. The visually estimated ventilation was recorded on a 5-point scoring system. A double threshold technique was applied to volumetric quantification in 3 He-MRI to serve as internal reference. Results: We found no correlation between morphological changes in HRCT and ventilation defects in 3 He-MRI. The visual assessment of ventilation in 3 He-MRI was sufficient in patients with emphysema, but this was not confirmed in patients with IPF. The visual assessment in HRCT did not correlate with the volumetric evaluation in both conditions. Conclusion: The various ventilation defects were not linked to specific morphological changes. For the visually assessed ventilation in patients with emphysema, 3 He-MRI is superior to HRCT. (orig.)

  12. Mutation and Expression of the DCC Gene in Human Lung Cancer

    Directory of Open Access Journals (Sweden)

    Takashi Kohno

    2000-07-01

    Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

  13. Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration

    Directory of Open Access Journals (Sweden)

    J. Behaegel

    2017-01-01

    Full Text Available Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and transplantation techniques. Culture procedures require the use of animal and/or human-derived products, which carry the potential of introducing toxic or infectious agents through contamination with known or unknown additives. Protocols vary widely, and the risks depend on the local institutional methods. Good manufacturing practice and xeno-free culture protocols could reduce potential health risks but are not yet a common practice worldwide. In this review, we focus on the safety of both autologous- and allogeneic-cultivated limbal stem cell transplantation, with respect to culture processes, surgical approaches, and postoperative strategies.

  14. IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation

    OpenAIRE

    Wójtowicz, Agnieszka; Gresnigt, Mark S.; Lecompte, Thanh; Bibert, Stephanie; Manuel, Oriol; Joosten, Leo A.B.; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans H.; Weisser, Maja; Mueller, Nicolas J.; Meylan, Pascal R.

    2017-01-01

    Background. Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Methods. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) fro...

  15. Discarded human fetal tissue and cell cultures for transplantation research

    International Nuclear Information System (INIS)

    Hay, R.J.; Phillips, T.; Thompson, A.; Vilner, L.; Cleland, M.; Tchaw-ren Chen; Zabrenetzky, V.

    1999-01-01

    A feasibility study has been performed to explore the utility of various tissues from discarded human abortuses for transplantation and related research. Specifically, aborted fetuses plus parental blood samples and all relevant clinical data were obtained through a local hospital complex. Whenever possible, pancreas, skin and skeletal muscle, heart, liver, kidney, cartilage and lung tissues were removed, dissociated and subfractionated for cryopreservation, characterization and cultivation trials in vitro. Existing protocols for these manipulations were compared and improved upon as required. Clonal culture, cell aggregate maintenance techniques and use of feeder cell populations have been utilized where appropriate to develop quantitative comparative data. Histological and biochemical assays were applied both to evaluate separation/cultivation methods and to identify optimal culture conditions for maintaining functional cells. Immunochemical and molecular biological procedures were applied to study expression of Major Histocompatibility Vomplex (MHC) class 1 and 11 molecules on cell lines derived. Tissue and cell culture populations were examined for infections with bacteria, ftingi, mycoplasma, HIV, CMV, hepatitis B and other viruses. Only 1% of the abortuses tested were virally infected. Cytogenetic analyses confin-ned the normal diploid status in the vast majority (>98%) of lines tested. A total of over 250 abortuses have been obtained and processed. Only 25 were found to be contaminated with bacteria or fungi and unsuitable for further cultivation trials. A total of over 200 cell populations were isolated, characterized and cryopreserved for further study. Included were kidney, lung, liver and epidermal epithelia: cartilage-derived cells from the spine and epiphyses plus myogenic myoblasts. Selected lines have been immortalized using HPV I 6E6/E7 sequences. Epithelia from the liver and pancreas and cardiac myocytes were the most problematic in that initial

  16. Radiation sensitivity of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

    1989-01-01

    X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

  17. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.

    Science.gov (United States)

    Hollander, Zsuzsanna; Chen, Virginia; Sidhu, Keerat; Lin, David; Ng, Raymond T; Balshaw, Robert; Cohen-Freue, Gabriela V; Ignaszewski, Andrew; Imai, Carol; Kaan, Annemarie; Tebbutt, Scott J; Wilson-McManus, Janet E; McMaster, Robert W; Keown, Paul A; McManus, Bruce M

    2013-02-01

    Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  19. Viral infections in transplant recipients.

    Science.gov (United States)

    Razonable, R R; Eid, A J

    2009-12-01

    Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

  20. High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

    Science.gov (United States)

    Raftopoulos, H; Ward, M; Bank, A

    1998-06-30

    Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

  1. In-vivo counting of 241Am in human lungs and tracheobronchial lymph nodes

    International Nuclear Information System (INIS)

    Northcutt, A.R.; Binney, S.E.; Palmer, H.E.

    1988-01-01

    A study was conducted of a human male who had inhaled a mixture of 241 Am and Pu. To distinguish 241 Am deposited in the subject's lungs from translocated activity deposited in the tracheobronchial lymph nodes (TBLN), two intrinsic Ge detectors were collimated with 0.3-cm Pb sheeting. A tissue-equivalent phantom containing either 22.9 kBq (620 nCi) of 241 Am in the lungs or a 81.4 kBq (2200 nCi) 241 Am point source in the TBLN was measured. Calibration curves observed from lateral differential scans on the phantom were compared to data obtained by the same detection system for a human male with a measured lung deposition of 89 Bq (2.4 nCi) of 241 Am. Comparison of the human data to the calibration curves indicated the activity was restricted primarily to the lungs. The calibration curves demonstrate that this method is useful in determining the distribution of inhaled radioactivity between the lungs and TBLN. The measured activity from the male subject generally supported the ICRP Publication 30 model translocation prediction for class Y compounds

  2. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Mina Jafarabadi

    2017-08-01

    Full Text Available Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN and matrix metalloproteinase 2 (MMP2 genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03. Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.

  3. Teaching basic lung isolation skills on human anatomy simulator: attainment and retention of lung isolation skills.

    Science.gov (United States)

    Latif, Rana K; VanHorne, Edgar M; Kandadai, Sunitha Kanchi; Bautista, Alexander F; Neamtu, Aurel; Wadhwa, Anupama; Carter, Mary B; Ziegler, Craig H; Memon, Mohammed Faisal; Akça, Ozan

    2016-01-20

    Lung isolation skills, such as correct insertion of double lumen endobronchial tube and bronchial blocker, are essential in anesthesia training; however, how to teach novices these skills is underexplored. Our aims were to determine (1) if novices can be trained to a basic proficiency level of lung isolation skills, (2) whether video-didactic and simulation-based trainings are comparable in teaching lung isolation basic skills, and (3) whether novice learners' lung isolation skills decay over time without practice. First, five board certified anesthesiologist with experience of more than 100 successful lung isolations were tested on Human Airway Anatomy Simulator (HAAS) to establish Expert proficiency skill level. Thirty senior medical students, who were naive to bronchoscopy and lung isolation techniques (Novice) were randomized to video-didactic and simulation-based trainings to learn lung isolation skills. Before and after training, Novices' performances were scored for correct placement using pass/fail scoring and a 5-point Global Rating Scale (GRS); and time of insertion was recorded. Fourteen novices were retested 2 months later to assess skill decay. Experts' and novices' double lumen endobronchial tube and bronchial blocker passing rates showed similar success rates after training (P >0.99). There were no differences between the video-didactic and simulation-based methods. Novices' time of insertion decayed within 2 months without practice. Novices could be trained to basic skill proficiency level of lung isolation. Video-didactic and simulation-based methods we utilized were found equally successful in training novices for lung isolation skills. Acquired skills partially decayed without practice.

  4. The effect of radiation sterilization on human transplantable bone

    International Nuclear Information System (INIS)

    Triantafyllou, N.; Karatzas, P.

    1974-11-01

    In order to study the effect of radiation sterilization on human transplantable bones, work was carried out on human and bovine bone tissue samples. Factors causing possible alterations in the mechanical structures of the preserved bone allografts were considered to be deep freezing (-35degC), lyophylization, irradiation, or a combination of lyophylization and irradiation. The latter could be shown to lower the mechanical strength of the bone. Crystal lattice of the bone did not show any alterations in x-ray diffraction pattern, following freeze drying and/or irradiation with doses up to 10 Mrad of gamma radiation. Deterioration in mechanical properties is probably due to damage to the organic phase of the bone matrix

  5. Potent selective nonpeptidic inhibitors of human lung tryptase

    Science.gov (United States)

    Burgess, Laurence E.; Newhouse, Bradley J.; Ibrahim, Prabha; Rizzi, James; Kashem, Mohammed A.; Hartman, Ann; Brandhuber, Barbara J.; Wright, Clifford D.; Thomson, David S.; Vigers, Guy P. A.; Koch, Kevin

    1999-01-01

    Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented. PMID:10411878

  6. Cardiothoracic Transplant Recipient Mycoplasma hominis: An Uncommon Infection with Probable Donor Transmission

    Directory of Open Access Journals (Sweden)

    Rahul Sampath

    2017-05-01

    Full Text Available The role of infection with Mycoplasma hominis following cardiothoracic organ transplantation and its source of transmission have not been well-defined. Here, we identify and describe infection with M. hominis in patients following cardiothoracic organ transplantation after reviewing all cardiothoracic transplantations performed at our center between 1998 and July 2015. We found seven previously unreported cases of M. hominis culture positive infection all of whom presented with pleuritis, surgical site infection, and/or mediastinitis. PCR was used to establish the diagnosis in four cases. In two instances, paired single lung transplant recipients manifested infection, and in one of these pairs, isolates were indistinguishable by multilocus sequence typing (MLST. To investigate the prevalence of M. hominis in the lower respiratory tract, we tested 178 bronchoalveolar lavage (BAL fluids collected from immunocompromised subjects for M. hominis by PCR; all were negative. Review of the literature revealed an additional 15 cases of M. hominis in lung transplant recipients, most with similar clinical presentations to our cases. We recommend that M. hominis should be considered in post-cardiothoracic transplant infections presenting with pleuritis, surgical site infection, or mediastinitis. M. hominis PCR may facilitate early diagnosis and prompt therapy. Evaluation for possible donor transmission should be considered.

  7. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

    1982-01-01

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

  8. JURIDICAL ANALYSIS OF LEGISLATION RELATED TO THE CRIME OF TRADE IN HUMAN ORGANS FOR THE BENEFIT OF THE KIDNEY ORGAN TRANSPLANT (Comparative Studies Between Indonesia with Philippines

    Directory of Open Access Journals (Sweden)

    Benny Situmorang

    2016-06-01

    Full Text Available In accordance with organ transplant’s evolve especially the kidneys it is necessary to rule out specific health legislation  in dealing with transplantation  of human body’s  organs  to prevent  human  trafficking  of human  organs.  The approaches used is the approach of legislation and comparisons to provide an overview of the regulation of transplantation of human body’s organs in Indonesia, and to know the comparison with other countries that have specific rules on transplants. The result is that the regulations in Indonesia does not have rules on organ transplants from living non-related organ donation and found no legal protection againts the donor. Keywords: Organ   transplant,   kidney   transplant,   human   trafficking,   health legislation.

  9. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Leah J.; Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Kandpal, Sanjeev Kumar; Mason, Michael D. [Department of Chemical and Biological Engineering, University of Maine, Orono, ME (United States); Zheng, Tongzhang [Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT (United States); Wise, John Pierce, E-mail: John.Wise@usm.maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States)

    2014-08-01

    Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.

  10. Cell Cycle Related Differentiation of Bone Marrow Cells into Lung Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dooner, Mark; Aliotta, Jason M.; Pimental, Jeffrey; Dooner, Gerri J.; Abedi, Mehrdad; Colvin, Gerald; Liu, Qin; Weier, Heinz-Ulli; Dooner, Mark S.; Quesenberry, Peter J.

    2007-12-31

    Green-fluorescent protein (GFP) labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit cell cycle by exposure to IL-3, IL-6, IL-11 and steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G1/S interface have a 3-fold increase in cells which assume a lung phenotype and that this increase is no longer seen in late S/G2. These cells have been characterized as GFP{sup +} CD45{sup -} and GFP{sup +} cytokeratin{sup +}. Thus marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine induced cell cycle transit. Previous studies have shown the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse cell cycle, leading to a continuum model of stem cell regulation. The present studies indicate that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.

  11. Scheduled transplantation of human umbilical cord blood to severe combined immunodeficient mice

    International Nuclear Information System (INIS)

    Wu Jianqiu; Yang Yunfang; Jin Zhijun; Cai Jianming; Yang Rujun; Xiang Yingsong

    2000-01-01

    Objective: To explore a new method for developing the efficiency of human umbilical cord blood (UCB) cells engraftment, and further understand the growth characteristic of hematopoietic stem cells (HSC) in vivo. Methods: Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted i.v. with UCB cells which had been cryo-preserved at -80 degree C. The human cells in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to the single transplantation, scheduled engraftment of similar numbers of UCB cells resulted in a proportionally obvious increase in the percentages of CD45 + , CD34 + cells produced in SCID mouse bone marrow (BM). When the donor cells were reduced to 20 percent, an identical reconstitution of both hematopoietic and part of immunologic functions was achieved. Conclusion: Scheduled engraftment improves the repopulating ability of HSC, which would provide a novel way for clinical cord blood engraftment in adult objects

  12. INFLUENCE OF INTERRUPTED PULMONARY LYMPH-DRAINAGE ON ANTIBODY-RESPONSES IN HILAR-STRIPPED LUNGS

    NARCIS (Netherlands)

    WANG, FZ; WINTER, JB; WILDEVUUR, CRH; PROP, J

    1992-01-01

    Lung transplantation interrupts hilar lymphatics. This may have an impact on immune responses to antigens entering the lung because the antigens cannot reach the lung-associated lymph nodes where the immune response is generated. We investigated the interruption and regeneration of lymphatics and

  13. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

    Directory of Open Access Journals (Sweden)

    Cyril Francioli

    Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

  14. LungMAP: The Molecular Atlas of Lung Development Program.

    Science.gov (United States)

    Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

    2017-11-01

    The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

  15. Histogram analysis for age change of human lung with computed tomography

    International Nuclear Information System (INIS)

    Shirabe, Ichiju

    1990-01-01

    In order to evaluate physiological changes of normal lung with aging by computed tomography (CT), the peak position (PP) and full width half maximum (FWHM) of CT-histogram were studied in 77 normal human lung. Above 30 years old, PP tended to be seen in the lower attenuation value with advancing ages, with the result that the follow equation was obtained. CT attenuation value of PP=-0.87 x age -815. The peak position shifted to the range of higher CT attenuation in 30's. FWHM did not change with advancing ages. There were no differences of peak value and FWHM among the upper, middle and lower lung field. In this study, physiological changes of lung were evaluated quantitatively. Furthermore, this study was considered to be useful for diagnosis and treatment in lung diseases. (author)

  16. Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival.

    Science.gov (United States)

    Gallagher, Harry M; Sarwar, Ghulam; Tse, Tracy; Sladden, Timothy M; Hii, Esmond; Yerkovich, Stephanie T; Hopkins, Peter M; Chambers, Daniel C

    2015-11-01

    Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation. We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died. Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005). Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  17. PHENOMENON OF DEMIKHOV. "Transplantation of vital organs In experiment" (1960. Transplantation immunity, artifi cial circulation in organ transplantation

    Directory of Open Access Journals (Sweden)

    S. P. Glyantsev

    2017-01-01

    Full Text Available The article (the fourth of five presents the analysis of the 4th and 5th chapters from V.P.Demikhov's monograph "Transplantation of vital organs in experiment" (MedGIz Publisher, Moscow, 1960, where he described his studies of transplantation immunity in originally created models and his use of artificial blood-circulation systems in experimental organ transplantation. It has been shown that V.P.Demikhov changed his views on the tissue biological incompatibility in homoplastic transplants and turned from the Michurin-Pavlov's concepts (1946–1953 to natural-scientific views (1959. Meanwhile, his multiple attempts to study both the morphological and humoral immunological response to transplanted organs did not give conclusive results because of lacking the experience of such studies even in the country's leading scientists and due the imperfection of their techniques. Realizing that the retrieval of a beating heart from a human would have created further problems for its subsequent transplantation, V.P. Demikhov attempted to reanimate human hearts in corpses by means of extracorporeal devices to provide artificial circulation. Methodologically, those devices were based on S.S.Bryukhonenko's research and his "auto-injector" pump modified by V.P.Demikhov. However, by 1960, those studies had not come beyond the experiments.

  18. Modeling of the Nitric Oxide Transport in the Human Lungs.

    Science.gov (United States)

    Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

    2016-01-01

    In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might

  19. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  20. [Effect of cisplatin on the expression of Pokemon gene: experiment with different human lung cancer cells].

    Science.gov (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Cong, De-Gang; Chang, Hao; Wang, Xue-Feng; Zhang, Tie-Wa; Zhang, Jian; Fu, Kai; Jiang, Jiu-Yang

    2008-04-29

    To investigate the correlation between Pokemon gene and cisplatin mechanism. Human lung adenocarcinoma cells of the lines A549 and AGZY83-a, human lung squamous carcinoma cells of the line HE-99, and human giant cell lung cancer cells of the line 95D were cultured and cisplatin was added into the medium. Other lung cancer cells of the above mentioned lines were cultured in the medium without cisplatin and were used as control groups. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Pokemon. Pokemon mRNA and protein were expressed highly in all the 4 cell lines. The Pokemon gene expression did not changed significantly after cisplatin treatment groups. There were not significant differences in the mRNA and protein expression of Pokemon among the 4 experiment groups and the control groups (all P > 0.05). Cisplatin has no effect on the Pokemon gene expression of the human lung cancer cells.

  1. Regulated gene expression in cultured type II cells of adult human lung

    OpenAIRE

    Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

    2010-01-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

  2. Nosocomial legionellosis in three heart-lung transplant patients

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Uldum, S; Jensen, J S

    1995-01-01

    Organ transplant recipients are at high risk of contracting Legionnaires' disease in a hospital environment contaminated with legionellae. This study describes the first cases of culture-verified Legionella infections with an established link to potable hospital water in Denmark; three patients...

  3. Pulmão e transplante renal

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge.Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease.Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months.Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed.Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.Rev Port Pneumol 2009; XV (6: 1073-1099 Palavras-chave: Pulmão, transplante renal, imunossupressão, Key-words: Lung, renal transplantation, immunosuppression

  4. Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis†.

    Science.gov (United States)

    Sabashnikov, Anton; Patil, Nikhil P; Popov, Aron-Frederik; Soresi, Simona; Zych, Bartlomiej; Weymann, Alexander; Mohite, Prashant N; García Sáez, Diana; Zeriouh, Mohamed; Wahlers, Thorsten; Choi, Yeong-Hoon; Wippermann, Jens; Wittwer, Thorsten; De Robertis, Fabio; Bahrami, Toufan; Amrani, Mohamed; Simon, André R

    2016-01-01

    Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  5. Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory.

    Science.gov (United States)

    Rheinheimer, Jakeline; Bauer, Andrea C; Silveiro, Sandra P; Estivalet, Aline A F; Bouças, Ana P; Rosa, Annelise R; Souza, Bianca M de; Oliveira, Fernanda S de; Cruz, Lavínia A; Brondani, Letícia A; Azevedo, Mirela J; Lemos, Natália E; Carlessi, Rodrigo; Assmann, Taís S; Gross, Jorge L; Leitão, Cristiane B; Crispim, Daisy

    2015-04-01

    Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.

  6. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  7. Anaemia and fever in kidney transplant. The role of human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Yanet Parodis López

    2017-03-01

    We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

  8. Heart Transplantation in Congenital Heart Disease: In Whom to Consider and When?

    Science.gov (United States)

    Attenhofer Jost, Christine H.; Schmidt, Dörthe; Huebler, Michael; Balmer, Christian; Noll, Georg; Caduff, Rosmarie; Greutmann, Matthias

    2013-01-01

    Due to impressive improvements in surgical repair options, even patients with complex congenital heart disease (CHD) may survive into adulthood and have a high risk of end-stage heart failure. Thus, the number of patients with CHD needing heart transplantation (HTx) has been increasing in the last decades. This paper summarizes the changing etiology of causes of death in heart failure in CHD. The main reasons, contraindications, and risks of heart transplantation in CHD are discussed and underlined with three case vignettes. Compared to HTx in acquired heart disease, HTx in CHD has an increased risk of perioperative death and rejection. However, outcome of HTx for complex CHD has improved over the past 20 years. Additionally, mechanical support options might decrease the waiting list mortality in the future. The number of patients needing heart-lung transplantation (especially for Eisenmenger's syndrome) has decreased in the last years. Lung transplantation with intracardiac repair of a cardiac defect is another possibility especially for patients with interatrial shunts. Overall, HTx will remain an important treatment option for CHD in the near future. PMID:23577237

  9. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  10. Profitability of our lung retrieval program from non heart beating donors.

    Science.gov (United States)

    Fernández, Elena; Calatayud, Joaquín; Jarabo, José Ramón; Hernando, Florentino; Rodríguez, Olga; Gómez, Ana María; Soria, Ana; Del Río, Francisco

    2009-02-01

    In 2002 the first lung transplant from non heart beating (NHB) donors took place in Madrid. The objective of this study was to analyse our Maastricht type I NHB lung donors retrieval program and to check out its profitability. Based on the NHB lung donors retrieval program carried out at Hospital Clínico San Carlos (Madrid) in association with Hospital Puerta de Hierro (Madrid), all lung donors from the beginning of the program from June 2002 to December 2006 have been analysed. When faced with a case of sudden death, advanced life support manoeuvres are initiated before 15 min. If the patient meets a given set of criteria, code 0/9 is activated. Arrival time to the hospital cannot exceed 90 min. Femoral artery and vein are cannulated, extracorporeal circulation is started and lungs are preserved. After the relatives' and judicial authorisation lungs are retrieved. Out of a total of 322 occurrences of code 0/9, 43 lung retrievals and 25 implants were reported. A total of 95% of donors were male, with an average age of 41 years and 91% with blood group A or O. 2004 saw the highest number of retrievals (14). January, May and December showed the highest number of retrievals. Incidence of sudden deaths was higher from 7 to 10 a.m. and from 7 to 10 p.m. Twenty-three implants at Hospital Puerta de Hierro and three more at Hospital Marqués de Valdecilla (Santander) were reported. A considerable amount of preserved lungs, valid for transplant, were not retrieved because of a lack of an appropriate recipient at the time. A total of 58.1% of preserved lungs were implanted. The ratio of obtained lungs was 11.4% of actual donors and 7.7% of total occurrences. However, this percentage could have been higher if we take into account the number of valid lungs that were not transplanted because of the lack of recipients.

  11. Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection.

    Science.gov (United States)

    Escaffre, Olivier; Saito, Tais B; Juelich, Terry L; Ikegami, Tetsuro; Smith, Jennifer K; Perez, David D; Atkins, Colm; Levine, Corri B; Huante, Matthew B; Nusbaum, Rebecca J; Endsley, Janice J; Freiberg, Alexander N; Rockx, Barry

    2017-08-01

    Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD-SCID/γ mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the bone marrow, liver, and thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections. Here, we characterized NiV Bangladesh strain (NiV-B) infection of human lung grafts from human immune system-reconstituted mice in order to identify the overall effect of immune cells on NiV pathogenesis of the lung. We show that NiV-B replicated to high titers in human lung grafts and caused similar cytopathic effects irrespective of the presence of human leukocytes in mice. However, the human immune system interfered with virus spread across lung grafts, responded to infection by leukocyte migration to small airways and alveoli of the lung grafts, and accelerated oxidative stress in lung grafts. In addition, the presence of human leukocytes increased the expression of cytokines and chemokines that regulate inflammatory influx to sites of infection and tissue damage. These results advance our understanding of how the immune system limits NiV dissemination and contributes to ALI and inform efforts to identify therapeutic targets. IMPORTANCE Nipah virus (NiV) is an emerging paramyxovirus that can cause a lethal respiratory and neurological disease in humans. Only limited data are available on NiV pathogenesis in the human lung, and the relative contribution of the innate immune response and NiV to acute lung injury (ALI) is still unknown. Using human lung grafts in a human immune system-reconstituted mouse model, we showed that the NiV Bangladesh

  12. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  13. Interplay between the lung microbiome and lung cancer.

    Science.gov (United States)

    Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

    2018-02-28

    The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  15. Islet transplantation: the quest for an ideal source

    International Nuclear Information System (INIS)

    Younes, Nidal A.; Nothias, J.; Garfinkel, Marc R.

    2008-01-01

    The progress of islet transplantation as a new therapy for patients with diabetes mellitus depends directly upon the development of efficient and practical immunoisolation methods for the supply of sufficient quantities of islet cells. Without these methods, large scale clinical application of this therapy would be impossible. Two eras of advances can be identified in the development of islet transplantation. The first was an era of experimental animal and human research that centered on islet isolation procedures and transplantation in different species as evidence that transplanted islets have the capability to reverse diabetes. The second was the era of Edmonton protocol, when the focus became the standardization of isolation procedures and introduction of new immunosuppressive drugs to maintain human allograft transplantation. The quest for an alternative source for islets (xenographs, stem cells and cell cultures) to overcome the shortage of human islets was an important issue during these eras. This paper reviews the history of islet transplantation and the current procedures in human allotransplantation, as well as different types of immunoisolation methods. It explores novel approaches to enhancing transplantation site vascularity and islet cell function, whereby future immunoisolation technology could offer additional therapeutic advantages to human islet allotransplantation. (author)

  16. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  17. Nocardia kroppenstedtii sp. nov., an actinomycete isolated from a lung transplant patient with a pulmonary infection.

    LENUS (Irish Health Repository)

    Jones, Amanda L

    2014-03-01

    A novel actinomycete, strain N1286(T), isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. Isolate N1286(T) was most closely related to Nocardia farcinica DSM 43665(T) (99.8% gene sequence similarity) but could be distinguished from the latter by the low level of DNA-DNA relatedness. These strains were also distinguishable on the basis of a broad range of phenotypic properties. It is concluded that strain N1286(T) represents a novel species of the genus Nocardia for which the name Nocardia kroppenstedtii sp. nov. is proposed. The type strain is N1286(T) ( = DSM 45810(T) = NCTC 13617(T)).

  18. A comparative study on the transplantation of different concentrations of human umbilical mesenchymal cells into diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Jia-Hui; Kong; Dan; Zheng; Song; Chen; Hong-Tao; Duan; Yue-Xin; Wang; Meng; Dong; Jian; Song

    2015-01-01

    AIM: To observe the effects of intravitreal injections of different concentrations of human umbilical mesenchymal stem cells on retinopathy in rats with diabetes mellitus.METHODS: Healthy and adult male Sprague-Dawley(SD) rats were randomly assigned to a normal control group(group A), a diabetic retinopathy(DR) blank control group(group B), a high-concentration transplantation group(group C), a low-concentration transplantation group(group D) and a placebo transplantation group(group E). The expression of nerve growth factor(NGF)protein in the retinal layers was detected by immunohistochemical staining at 2, 4, 6 and 8wk.RESULTS: The expression of NGF was positive in group A and most positive in the retinal ganglion cell layer. In groups B and E, the expression of NGF was positive 2wk after transplantation and showed an increase in all layers. However, the level of expression had decreased in all layers at 4wk and was significantly reduced at 8wk. In groups C and D, the expression of NGF had increased at 2wk and continued to increase up to 8wk. The level of expression in group C was much higher than that in group D.CONCLUSION: DR can be improved by intravitreal injection of human umbilical mesenchymal stem cells.High concentrations of human umbilical mesenchymal stem cells confer a better protective effect on DR than low concentrations.

  19. Post-transplant outcomes in pediatric ventricular assist device patients: A PediMACS-Pediatric Heart Transplant Study linkage analysis.

    Science.gov (United States)

    Sutcliffe, David L; Pruitt, Elizabeth; Cantor, Ryan S; Godown, Justin; Lane, John; Turrentine, Mark W; Law, Sabrina P; Lantz, Jodie L; Kirklin, James K; Bernstein, Daniel; Blume, Elizabeth D

    2017-12-13

    Pediatric ventricular assist device (VAD) support as bridge to transplant has improved waitlist survival, but the effects of pre-implant status and VAD-related events on post-transplant outcomes have not been assessed. This study is a linkage analysis between the PediMACS and Pediatric Heart Transplant Study databases to determine the effects of VAD course on post-transplant outcomes. Database linkage between October 1, 2012 and December 31, 2015 identified 147 transplanted VAD patients, the primary study group. The comparison cohort was composed of 630 PHTS patients without pre-transplant VAD support. The primary outcome was post-transplant survival, with secondary outcomes of post-transplant length of stay, freedom from infection and freedom from rejection. At implant, the VAD cohort was INTERMACS Profile 1 in 33 (23%), Profile 2 in 89 (63%) and Profile 3 in 14 (10%) patients. The VAD cohort was older, larger, and less likely to have congenital heart disease (p < 0.0001). However, they had greater requirements for inotrope and ventilator support and increased liver and renal dysfunction (p < 0.0001), both of which normalized at transplant after device support. Importantly, there were no differences in 1-year post-transplant survival (96% vs 93%, p = 0.3), freedom from infection (81% vs 79%, p = 0.9) or freedom from rejection (71% vs 74%, p = 0.87) between cohorts. Pediatric VAD patients have post-transplant outcomes equal to that of medically supported patients, despite greater pre-implant illness severity. Post-transplant survival, hospital length of stay, infection and rejection were not affected by patient acuity at VAD implantation or VAD-related complications. Therefore, VAD as bridge to transplant mitigates severity of illness in children. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Human dental pulp cell culture and cell transplantation with an alginate scaffold.

    Science.gov (United States)

    Kumabe, Shunji; Nakatsuka, Michiko; Kim, Gi-Seup; Jue, Seong-Suk; Aikawa, Fumiko; Shin, Je-Won; Iwai, Yasutomo

    2006-02-01

    Many studies on tissue stem cells have been conducted in the field of regenerative medicine, and some studies have indicated that cultured dental pulp mesenchymal cells secrete dentin matrix. In the present study we used alginate as a scaffold to transplant subcultured human dental pulp cells subcutaneously into the backs of nude mice. We found that when beta-glycerophosphate was added to the culture medium, dentin sialophosphoprotein mRNA coding dentin sialoprotein (DSP) was expressed. An increase in alkaline phosphatase, which is an early marker for odontoblast differentiation, was also demonstrated. At 6 weeks after implantation the subcutaneous formation of radio-opaque calcified bodies was observed in situ. Immunohistochemical and fine structure studies identified expression of type I collagen, type III collagen, and DSP in the mineralizing transplants. Isolated odontoblast-like cells initiated dentin-like hard tissue formation and scattered autolyzing apoptotic cells were also observed in the transplants. The study showed that subcultured dental pulp cells actively differentiate into odontoblast-like cells and induce calcification in an alginate scaffold.