Martin R Zamora

Publications (27)128.2 Total impact

• Article: Four Decades of Vascularized Heterotopic Cardiac Transplantation in the Mouse.

  Robert J Plenter, Martin R Zamora, Todd J Grazia
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  ABSTRACT: ABSTRACT Since the first clinical heart transplant in 1967, there has been a heightened need to understand immune and inflammatory responses to "foreign" tissues. Research efforts in those early days were based on species that would now be considered "large" and were typically out-bred individuals. While this closely mirrors the clinical scenario, where genetic mismatches of donors and recipients can only be minimized in the selection process, these were not ideal models for studying the complexities and nuances of the immune system. Even when the rat was considered the standard model those early endeavors were limited by a small number of rat strains. The mouse model has provided us with an overwhelming array of strains, knockouts, knockins and transgenics that allow us to investigate the many layers of the innate and adaptive immune systems leading to a much greater understanding of immune responses. Fully vascularized heterotopic cardiac transplantation in the mouse has now been with us for four decades; the original papers describing this technique being published by Corry in 1973. In the subsequent 40 years, this technique has been used by many laboratories, including our own, and has become a powerful tool for the investigation of transplant immunity and ischemia reperfusion injury. Given the modern availability of mouse strains and mouse-related reagents, our current understanding of transplant immunity undoubtedly would not exist without such a technique.
  Journal of Investigative Surgery 03/2013; · 1.09 Impact Factor
• Article: Respiratory viral infections. Preface.

  Adriana Weinberg, Martin R Zamora
  Seminars in Respiratory and Critical Care Medicine 08/2011; 32(4):371-2. · 2.43 Impact Factor
• Article: DNA viruses (CMV, EBV, and the herpesviruses).

  Martin R Zamora
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  ABSTRACT: The human Herpesviridae family consists of eight members: cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2 (HSV-1, -2), varicella-zoster virus (VZV), and human herpesvirus 6, 7, and 8 (HHV-6, -7, -8). Lifelong latency may develop in the host with reactivation during periods of relative immunosuppression that occurs in transplant recipients. These are pleiotropic viruses: in addition to their direct effects of tissue injury and clinical illness, they exhibit several indirect effects, including immunomodulation and effects on angiogenesis and tumorigenesis, which may result in long-term adverse sequelae in the lung allograft. CMV and HHV-6 and -7 are increasingly recognized as major causes of morbidity and mortality in lung transplant recipients. EBV and HHV-8 have proven oncogenic potential. HSV-1 and -2 and VZV are neurotropic, causing perioral fever blisters, genital ulcerations, and, rarely, encephalitis. This article discusses the individual pathogens, preventive strategies in the era of potent treatment regimens for established viral infection or disease and their potential impact on the indirect effects of these viruses on long-term allograft function, and the incidence, risk factors for, and impact of antiviral resistance.
  Seminars in Respiratory and Critical Care Medicine 08/2011; 32(4):454-70. · 2.43 Impact Factor
• Article: Update and review: state-of-the-art management of cytomegalovirus infection and disease following thoracic organ transplantation.

  David R Snydman, Ajit P Limaye, Luciano Potena, Martin R Zamora
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  ABSTRACT: Cytomegalovirus (CMV) is among the most important viral pathogens affecting solid organ recipients. The direct effects of CMV (eg, infection and its sequela; tissue invasive disease) are responsible for significant morbidity and mortality. In addition, CMV is associated with numerous indirect effects, including immunomodulatory effects, acute and chronic rejection, and opportunistic infections. Due to the potentially devastating effects of CMV, transplant surgeons and physicians have been challenged to fully understand this infectious complication and find the best ways to prevent and treat it to ensure optimal patient outcomes. Lung, heart, and heart-lung recipients are at considerably high risk of CMV infection. Both direct and indirect effects of CMV in these populations have potentially lethal consequences. The use of available treatment options depend on the level of risk of each patient population for CMV infection and disease. Those at the highest risk are CMV negative recipients of CMV positive organs (D+/R-), followed by D+/R+, and D-/R+. More than 1 guideline exists delineating prevention and treatment options for CMV, and new guidelines are being developed. It is hoped that new treatment algorithms will provide further guidance to the transplantation community. The first part describes the overall effects of CMV, both direct and indirect; risk factors for CMV infection and disease; methods of diagnosis; and currently available therapies for prevention and treatment. Part 2 similarly addresses antiviral-resistant CMV, summarizing incidence, risk factors, methods of diagnosis, and treatment options. Parts 3 and 4 present cases to illustrate issues surrounding CMV in heart and lung transplantation, respectively. Part 3 discusses the possible mechanisms by which CMV can cause damage to the coronary allograft and potential techniques of avoiding such damage, with emphasis on fostering strong CMV-specific immunity. Part 4 highlights the increased incidence of CMV infection and disease among lung transplant recipients and its detrimental effect on survival. The possible benefits of extended-duration anti-CMV prophylaxis are explored, as are those of combination prophylaxis with valganciclovir and CMVIG. Through improved utilization of information regarding optimized antiviral therapy for heart and lung transplant recipients to prevent and treat CMV infection and disease and through increased understanding of clinical strategies to assess, treat, and monitor patients at high risk for CMV recurrence and resistance, the health care team will be able to provide the coordinated effort needed to improve patient outcomes.
  Transplantation Proceedings 04/2011; 43(3 Suppl):S1-S17. · 1.00 Impact Factor
• Article: RNA interference therapy in lung transplant patients infected with respiratory syncytial virus.

  Martin R Zamora, Marie Budev, Mark Rolfe, Jens Gottlieb, Atul Humar, John Devincenzo, Akshay Vaishnaw, Jeffrey Cehelsky, Gary Albert, Sara Nochur, Jared A Gollob, Allan R Glanville
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  ABSTRACT: Lower respiratory tract infections due to respiratory syncytial virus (RSV) are associated with development of bronchiolitis obliterans syndrome in lung transplant (LTX) recipients. ALN-RSV01 is a small interfering RNA targeting RSV replication. To determine the safety and explore the efficacy of ALN-RSV01 in RSV infection. We performed a randomized, double-blind, placebo-controlled trial in LTX recipients with RSV respiratory tract infection. Patients were permitted to receive standard of care for RSV. Aerosolized ALN-RSV01 (0.6 mg/kg) or placebo was administered daily for 3 days. Viral load was determined by quantitative reverse transcriptase-polymerase chain reaction on serial nasal swabs. Patients completed symptom score cards twice daily. Lung function, including the incidence of new-onset or progressive bronchiolitis obliterans syndrome, was recorded at Day 90. We enrolled 24 patients (ALN-RSV01, n = 16; placebo, n = 8); randomization was stratified by ribavirin use. ALN-RSV01 was well tolerated, with no drug-related serious adverse events or post-inhalation perturbations in lung function. Interpretation of viral measures was confounded by baseline differences between the two groups in viral load and time from symptom onset to first dose. Mean daily symptom scores were lower in subjects receiving ALN-RSV01, and the mean cumulative daily total symptom score was significantly lower with ALN-RSV01 (114.7 ± 63.13 vs. 189.3 ± 99.59, P = 0.035). At Day 90, incidence of new or progressive bronchiolitis obliterans syndrome was significantly reduced in ALN-RSV01 recipients compared with placebo (6.3% vs. 50%, P = 0.027). ALN-RSV01 was safe and may have beneficial effects on long-term allograft function in LTX patients infected with RSV. Clinical trial registered with www.clinicaltrials.gov (NCT 00658086).
  American Journal of Respiratory and Critical Care Medicine 02/2011; 183(4):531-8. · 11.08 Impact Factor
• Article: Decreased neprilysin and pulmonary vascular remodeling in chronic obstructive pulmonary disease.

  Marilee J Wick, Erica J Buesing, Carol A Wehling, Zoe L Loomis, Carlyne D Cool, Martin R Zamora, York E Miller, Sean P Colgan, Louis B Hersh, Norbert F Voelkel, Edward C Dempsey
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  ABSTRACT: Studies with genetically engineered mice showed that decreased expression of the transmembrane peptidase neprilysin (NEP) increases susceptibility to hypoxic pulmonary vascular remodeling and hypertension; in hypoxic wild-type mice, expression is decreased early in distal pulmonary arteries, where prominent vascular remodeling occurs. Therefore, in humans with smoke- and hypoxia-induced vascular remodeling, as in chronic obstructive pulmonary disease (COPD), pulmonary activity/expression of NEP may likewise be decreased. To test whether NEP activity and expression are reduced in COPD lungs and pulmonary arterial smooth muscle cells (SMCs) exposed to cigarette smoke extract or hypoxia and begin to investigate mechanisms involved. Control and advanced COPD lung lysates (n = 13-14) were analyzed for NEP activity and protein and mRNA expression. As a control, dipeptidyl peptidase IV activity was analyzed. Lung sections were assessed for vascular remodeling and oxidant damage. Human pulmonary arterial SMCs were exposed to cigarette smoke extract, hypoxia, or H₂O₂, and incubated with antioxidants or lysosomal/proteasomal inhibitors. COPD lungs demonstrated areas of vascular rarification, distal muscularization, and variable intimal and prominent medial/adventitial thickening. NEP activity was reduced by 76%; NEP protein expression was decreased in alveolar walls and distal vessels; mRNA expression was also decreased. In SMCs exposed to cigarette smoke extract, hypoxia, and H₂O₂, NEP activity and expression were also reduced. Reactive oxygen species inactivated NEP activity; NEP protein degradation appeared to be substantially induced. Mechanisms responsible for reduced NEP activity and protein expression include oxidative reactions and protein degradation. Maintaining or increasing lung NEP may protect against pulmonary vascular remodeling in response to chronic smoke and hypoxia.
  American Journal of Respiratory and Critical Care Medicine 02/2011; 183(3):330-40. · 11.08 Impact Factor
• Source

  Available from: Mark R Nicolls

  Article: Bronchial blood supply after lung transplantation without bronchial artery revascularization.

  Mark R Nicolls, Martin R Zamora
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  ABSTRACT: This review discusses how the bronchial artery circulation is interrupted following lung transplantation and what may be the long-term complications of compromising systemic blood flow to allograft airways. Preclinical and clinical studies have shown that the loss of airway microcirculations is highly associated with the development of airway hypoxia and an increased susceptibility to chronic rejection. The bronchial artery circulation has been highly conserved through evolution. Current evidence suggests that the failure to routinely perform bronchial artery revascularization at the time of lung transplantation may predispose patients to develop the bronchiolitis obliterans syndrome.
  Current opinion in organ transplantation 10/2010; 15(5):563-7. · 1.22 Impact Factor
• Source

  Available from: Mark R Nicolls

  Article: Lung transplant airway hypoxia: a diathesis to fibrosis?

  Gundeep S Dhillon, Martin R Zamora, Justus E Roos, Deirdre Sheahan, Ramachandra R Sista, Pieter Van der Starre, David Weill, Mark R Nicolls
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  ABSTRACT: Chronic rejection, manifested pathologically as airway fibrosis, is the major problem limiting long-term survival in lung transplant recipients. Airway hypoxia and ischemia, resulting from a failure to restore the bronchial artery (BA) circulation at the time of transplantation, may predispose patients to chronic rejection. To address this possibility, clinical information is needed describing the status of lung perfusion and airway oxygenation after transplantation. To determine the relative pulmonary arterial blood flow, airway tissue oxygenation and BA anatomy in the transplanted lung was compared with the contralateral native lung in lung allograft recipients. Routine perfusion scans were evaluated at 3 and 12 months after transplantation in 15 single transplant recipients. Next, airway tissue oximetry was performed in 12 patients during surveillance bronchoscopies in the first year after transplant and in 4 control subjects. Finally, computed tomography (CT)-angiography studies on 11 recipients were reconstructed to evaluate the post-transplant anatomy of the BAs. By 3 months after transplantation, deoxygenated pulmonary arterial blood is shunted away from the native lung to the transplanted lung. In the first year, healthy lung transplant recipients exhibit significant airway hypoxia distal to the graft anastomosis. CT-angiography studies demonstrate that BAs are abbreviated, generally stopping at or before the anastomosis, in transplant airways. Despite pulmonary artery blood being shunted to transplanted lungs after transplantation, grafts are hypoxic compared with both native (diseased) and control airways. Airway hypoxia may be due to the lack of radiologically demonstrable BAs after lung transplantation.
  American Journal of Respiratory and Critical Care Medicine 03/2010; 182(2):230-6. · 11.08 Impact Factor
• Source

  Available from: Robert J Plenter

  Article: Acute cardiac allograft rejection by directly cytotoxic CD4 T cells: parallel requirements for Fas and perforin.

  Todd J Grazia, Robert J Plenter, Sarah M Weber, Helen M Lepper, Francisco Victorino, Martin R Zamora, Biagio A Pietra, Ronald G Gill
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  ABSTRACT: CD4 T cells can suffice as effector cells to mediate primary acute cardiac allograft rejection. Although CD4 T cells can readily kill appropriate target cells in vitro, the corresponding role of such cytolytic activity for mediating allograft rejection in vivo is unknown. Therefore, we determined whether the cytolytic effector molecules perforin (PFP) and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection in vivo. Wild-type C3H(H-2) or Fas (CD95)-deficient C3Hlpr (H-2) hearts were transplanted into immune-deficient C57B6rag (H-2) mice. Then, recipients were reconstituted with naïve purified CD4 T cells from wild-type, PFP-deficient, or FasL (gld)-deficient T-cell donors. In vitro, alloreactive CD4 T cells were competent to lyse donor major histocompatibility complex class II+ target cells, largely by a Fas-dependent mechanism. In vivo, the individual disruption of donor Fas expression (lpr) or CD4 T-cell-derived PFP had no significant impact on acute rejection. However, FasL-deficient (gld) CD4 T cells demonstrated delayed allograft rejection. Importantly, the simultaneous removal of both donor Fas expression and CD4 T-cell PFP completely abrogated acute rejection, despite the persistence of CD4 T cells within the graft. Results demonstrate that the direct rejection of cardiac allografts by CD4 effector T cells requires the alternative contribution of graft Fas expression and T cell PFP expression. To our knowledge, this is the first demonstration that cytolytic activity by CD4 T cells can play an obligate role for primary acute allograft rejection in vivo.
  Transplantation 01/2010; 89(1):33-9. · 4.00 Impact Factor
• Article: Medical complications of lung transplantation.

  Dennis M Lyu, Martin R Zamora
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  ABSTRACT: As short- and long-term survival rates for lung transplantation continue to improve, and as more lung transplantations are occurring with each year, a multitude of medical complications are encountered by the clinician. This article reviews the long-term non-pulmonary noninfectious medical complications that arise beyond the postoperative period in patients who have undergone lung transplantation. This article reviews the development of renal failure, diabetes, cardiovascular complications of hypertension and atherosclerosis, osteoporosis and avascular necrosis, hematologic complications, thromboembolic disease, gastrointestinial complications, neurologic complications, and malignancy, including post-transplant lymphoproliferative disorder.
  Proceedings of the American Thoracic Society 02/2009; 6(1):101-7.
• Article: Functional microcirculation is lost in early airway fibrosis.

  Ashok N Babu, Tomohiro Murakawa, Norbert F Voelkel, Martin R Zamora, Peter M Henson, Mark R Nicolls
  Proceedings of the American Thoracic Society 05/2008; 5(3):371.
• Article: Native lung volume reduction surgery relieves functional graft compression after single-lung transplantation for chronic obstructive pulmonary disease.

  T Brett Reece, John D Mitchell, Martin R Zamora, David A Fullerton, Joseph C Cleveland, Marvin Pomerantz, Dennis M Lyu, Frederick L Grover, Michael J Weyant
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  ABSTRACT: Single-lung transplantation is an accepted treatment for end-stage lung disease caused by chronic obstructive pulmonary disease. A complication unique to single-lung transplantation for chronic obstructive pulmonary disease is graft dysfunction due to compression caused by native lung hyperinflation. We hypothesized that patients with functional compromise from native lung hyperinflation would benefit from native lung volume reduction surgery. The charts of all patients undergoing single-lung transplantation for chronic obstructive pulmonary disease were reviewed for lung volume reduction surgery of their native lung. Data regarding length of stay, surgical morbidity and mortality, overall survival, type of lung volume reduction surgery, and pulmonary function were recorded to evaluate the effect of lung volume reduction surgery. Between February 1992 and May 2007, 206 single-lung transplantations were performed for chronic obstructive pulmonary disease. Ten (5%) patients had clinically significant graft compression from native lung hyperinflation. After excluding other causes for functional decline, these patients underwent a modified lung volume reduction surgery between 12 and 142 months after single-lung transplantation (mean, 50 months). Lung volume reduction surgery consisted of anatomic resection. Two (20%) of 10 patients died during their hospitalization. Of the remaining 8 patients, 7 (87.5%) have demonstrated functional improvement on the basis of forced expiratory volume in 1 second improving from 12% to 200% (mean improvement, 57%). Within 6 months of lung volume reduction surgery, mean 6-minute walk values improved significantly (866 to 1055 feet), whereas desaturation with exertion decreased significantly. Lung volume reduction surgery by means of formal lobectomy in patients with native lung hyperinflation undergoing single-lung transplantation and significant graft compression appears feasible. Additionally, improvements in forced expiratory volume in 1 second can be accomplished in nearly all properly selected patients. Lung volume reduction surgery should be considered in patients with decreasing graft function caused by graft compression from native lung hyperinflation.
  The Journal of thoracic and cardiovascular surgery 05/2008; 135(4):931-7. · 3.41 Impact Factor
• Source

  Available from: Mark R Nicolls

  Article: Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis.

  Ashok N Babu, Tomohiro Murakawa, Joshua M Thurman, Edmund J Miller, Peter M Henson, Martin R Zamora, Norbert F Voelkel, Mark R Nicolls
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  ABSTRACT: Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle to long-term survival following lung transplantation. Here, we show the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to rejection and for the first time, relate allograft microvascular injury and loss of tissue perfusion to immunotherapy-resistant rejection. To explore the role of alloimmune rejection and airway ischemia in the development of fibroproliferation, we used a murine orthotopic tracheal transplant model. We determined that transplants were reperfused by connection of recipient vessels to donor vessels at the surgical anastomosis site. Microcirculation through the newly formed vascular anastomoses appeared partially dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the microvasculature in rejecting allografts exhibited vascular complement deposition, diminished endothelial CD31 expression, and absent perfusion prior to the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell injury were refractory to immunotherapy. After early microvascular loss, neovascularization was eventually observed in the membranous trachea, indicating a reestablishment of graft perfusion in established fibrosis. One implication of this study is that bronchial artery revascularization at the time of lung transplantation may decrease the risk of subsequent airway fibrosis.
  Journal of Clinical Investigation 01/2008; 117(12):3774-85. · 15.39 Impact Factor
• Article: Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.

  Susan Stewart, Michael C Fishbein, Gregory I Snell, Gerald J Berry, Annette Boehler, Margaret M Burke, Alan Glanville, F Kate Gould, Cynthia Magro, Charles C Marboe, [......], Elaine F Reed, Nancy L Reinsmoen, John P Scott, Sean M Studer, Henry D Tazelaar, John L Wallwork, Glen Westall, Martin R Zamora, Adriana Zeevi, Samuel A Yousem
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  ABSTRACT: In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.
  The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2008; 26(12):1229-42. · 3.54 Impact Factor
• Article: Eleven years on: a clinical update of key areas of the 1996 lung allograft rejection working formulation.

  Gregory I Snell, Annette Boehler, Allan R Glanville, Keith McNeil, John P Scott, Sean M Studer, John Wallwork, Glen Westall, Martin R Zamora, Susan Stewart
  The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 06/2007; 26(5):423-30. · 3.54 Impact Factor
• Article: Functional and genomic changes induced by alveolar transmigration in human neutrophils.

  Christopher D Coldren, Jerry A Nick, Katie R Poch, Malcolm D Woolum, Brian W Fouty, James M O'Brien, Michael P Gruber, Martin R Zamora, Daiva Svetkauskaite, Don A Richter, Qianbin He, Jong Sung Park, Katherine H Overdier, Edward Abraham, Mark W Geraci
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  ABSTRACT: Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: approximately 15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.
  AJP Lung Cellular and Molecular Physiology 01/2007; 291(6):L1267-76. · 3.66 Impact Factor
• Article: Impact of viral infections on lung transplant outcomes

  Martin R Zamora
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  ABSTRACT: Purpose of review: Viruses are increasingly recognized as significant pathogens after lung transplantation. An update is presented on recognized or emerging pathogens, therapy with potent antiviral agents, molecular techniques for the detection of infection and response to therapy, the emergence of resistant isolates, and the role of viruses in chronic allograft rejection. Recent findings: Recognized pathogens include herpesviruses, community-acquired respiratory viruses, and new or emerging viruses such as human metapneumovirus, West Nile virus, or severe acute respiratory syndrome coronavirus. The efficacy of potent oral antiviral agents for prophylaxis and treatment of infections has been established for cytomegalovirus. Molecular monitoring techniques have proved useful for the detection of infections and their response to therapy. The emergence of cytomegalovirus isolates with antiviral resistance has had significant impacts on the approach to these patients. Increasing evidence suggests that, in addition to the direct effects of tissue injury and clinical illness, some viruses have indirect effects, leading to long-term adverse sequelae in the lung allograft, resulting in bronchiolitis obliterans or chronic rejection. Summary: Understanding the pleiotropic effects of viruses, the role of new antiviral agents, and molecular monitoring techniques is important for the development of comprehensive management strategies for viral infections after lung transplantation.
  Current Opinion in Organ Transplantation 09/2006; 11(5):475-482. · 2.97 Impact Factor
• Article: Pulmonary capillaritis in lung transplant recipients: treatment and effect on allograft function.

  Todd L Astor, David Weill, Carlyne Cool, Isaac Teitelbaum, Marvin I Schwarz, Martin R Zamora
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  ABSTRACT: The clinical outcomes of lung transplant recipients presenting with post-transplant pulmonary capillaritis have not been well described. We retrospectively reviewed 40 cases of biopsy-proven pulmonary capillaritis in lung transplant recipients. Patients presented with a clinical syndrome characterized by dyspnea, hypoxemia, abnormal chest X-ray, and a decrease in forced expiratory volume in 1 second (FEV1); 25% presented with hemoptysis, and 18% with fulminant respiratory failure. Therapy with intravenous corticosteroids resulted in clinical improvement in 17 cases (43%). A response to plasmapheresis was seen in 12 (67%) of 18 cases refractory to corticosteroids. There were 5 deaths within 3 months of diagnosis. Nine (82%) of 11 lung transplant recipients who presented with capillaritis within 4 weeks post-transplant were alive at 1 year; all but 1 patient achieved expected percent predicted FEV1 values. Only 3 (14%) of 21 who presented with capillaritis > 1 month after transplant had a >20% decrease in the FEV1 after 12 months. These results suggest that post-transplant pulmonary capillaritis is (1) likely a form of acute allograft rejection clinically and histologically distinct from typical acute rejection, (2) less responsive to corticosteroid therapy than typical acute rejection, and (3) not associated with long-term adverse effects on allograft function.
  The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2006; 24(12):2091-7. · 3.54 Impact Factor
• Article: Management of cytomegalovirus infection in lung transplant recipients: evidence-based recommendations.

  Martin R Zamora, R Duane Davis, Colm Leonard
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  ABSTRACT: Cytomegalovirus (CMV) continues to cause significant morbidity and mortality in lung transplant recipients. This article presents recommendations based on available evidence for the optimal management of CMV in lung transplant recipients, which have been developed by an expert committee of transplant physicians-surgeons and infectious disease specialists.
  Transplantation 08/2005; 80(2):157-63. · 4.00 Impact Factor
• Article: BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus.

  Jo Ann Lindenfeld, Shakar F Simon, Martin R Zamora, Carlyne D Cool, Eugene E Wolfel, Brian D Lowes, Nancy Ireland, Karin Keller, Rhonda Frisk, Linda Stepien, Joseph C Cleveland, Ronald Zolty
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  ABSTRACT: While bronchiolitis obliterans organizing pneumonia (BOOP) has been associated with the use of sirolimus (SIR), the incidence in a consecutive group of patients given SIR to replace a calcineurin-inhibitor (CI) is unknown. Twenty-nine consecutive cardiac transplant recipients were switched from a CI to SIR to ameliorate CI-associated nephropathy or coronary graft atherosclerosis. Seven patients (24%) developed BOOP. The clinical characteristics and biopsy results of these patients are presented. The clinical course and response to withdrawal of SIR in all and steroids in four of seven patients suggested the diagnosis of BOOP. Chest X-rays and CT scans showed typical findings of BOOP in all seven patients. Infection was excluded in all patients. Biopsy results were characteristic of BOOP in six of seven patients. Six patients recovered and one died. BOOP is a common and potentially serious adverse event in cardiac transplant patients switched from a CI to SIR, especially when SIR is started late post-transplantation.
  American Journal of Transplantation 07/2005; 5(6):1392-6. · 6.39 Impact Factor