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John M. Armitage

Bio: John M. Armitage is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Transplantation & Heart transplantation. The author has an hindex of 44, co-authored 110 publications receiving 5869 citations. Previous affiliations of John M. Armitage include Cardinal Glennon Children's Hospital & University of Southampton.


Papers
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Journal ArticleDOI
TL;DR: Recipients with obliterative bronchiolitis detected in the preclinical stage were significantly more likely to be in remission than recipients who had clinical disease at the time of diagnosis and results indicate that acute rejection is the most significant risk factor for development of obliteration and that obliteration responds to treatment with augmented immunosuppression when it is detected early by surveillance transbronchial biopsy.

412 citations

Journal Article
TL;DR: Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989 and no correlation with immunoprophylaxis or maintenance immunosuppression is found.
Abstract: Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.

358 citations

Journal ArticleDOI
TL;DR: Despite improvements in operative techniques and methods of myocardial protection, postoperative left ventricular dysfunction continues to be common in patients undergoing cardiopulmonary bypass surgery.

317 citations

Journal ArticleDOI
TL;DR: Patients with severe preoperative pulmonary hypertension who underwent transplantation between 1980 and 1987 had a higher 0- to 2-day post-transplant mortality rate compared with patients operated on after that time, and female recipient sex and preoperative TPG but not preoperative PVR, era of transplantation, or recipient age were identified as significant independent predictors of early post-Transplant mortality.

197 citations

01 Dec 1991
TL;DR: FK 506 appears to not only decrease the absolute incidence of rejection episodes, and allows for marked reduction in steroid doses, but makes the treatment of rejection much simpler.
Abstract: Cyclosporine (CyA)-based immunosuppression significantly enhanced both patient and graft survival in all solid organ transplants. when compared to the era of azathioprine and steroids. The widespread use of CyA has spawned a growing body of experience delineating the side effects of CyA use, which was apparent in the first reports on human patients.1 Prior to the utilization of monitoring techniques, renal dysfunction was often used as a guideline to effective CyA dosing.2 More recently, monitoring of CyA trough levels has been used to guide CyA dosing,3 although some patients manifest toxicity at “therapeutic levels.” while others do not manifest any side effects at levels considered “excessive”.4 This has held true, regardless of the development of a number of different assay systems monitoring either parent CyA drug or its metabolites. Nephrotoxicity remains the principle limiting side effect of CyA, and has been reported to occur in more than 50% of patients. Unfortunately, the mechanism(s) of CyA nephrotoxicity have not been clearly defined. Hypertension (40% to 60%), hyperkalemia, hirsutism (60% to 80%), gingival hypertrophy, hepatotoxicity (40% to 60%), and tremors are relatively common side effects of CyA (reviewed by Thiru5). Malignant complications include a higher incidence of posttransplant lymphoproliferative disease (PTLD), as well as a variety of skin cancers, including Kaposi’s sarcoma. PTLD is an abnormality of lymphocyte proliferation in a setting of an immunosuppressed patient. The spectrum of PTLD can range from a benign lymphoid proliferation, such as a mononucleosis syndrome, to a frankly malignant lymphoid tumor. PTLD has been associated with all types of immunosuppressive therapy. The incidence of PTLD in the CyA era is generally estimated between 2% and 4%.7 Most (90% to 95%) of PTLD are B cell in origin, and most are associated with integration of Epstein-Barr virus (EBV) DNA into the genome of the B cell. A smaller number of PTLD are T cell in origin. Because of the relatively high percentages of patients developing rejection on CyA therapy (estimated at 50% to 70%), multiple drug combinations have been utilized to prevent rejection, while minimizing toxicities. The sequelae of overimmunosuppression in attempts to treat rejection, such as use of excessive steroids, antilymphocyte preparations, are fraught with a high incidence of infectious complications and metabolic sequelae, such as diabetogenesis and ulcerogenesis. In addition, each component of the “cocktail”, has its inherent limitations. It stands to reason that a baseline immunosuppressive agent which allows for less incidence of rejection, and easier treatment of rejection, would decrease both graft and patient loss. FK 506 is a recent addition to the armamentarium of immunosuppressive agents. FK 506 shares some pharmacologic similarities with CyA, such as bioavailability, lipophilicity, and hepatic metabolism.8 Both drugs bind to proteins having a peptidyl-prolyl cis-trans isomerase activity, although the binding proteins for CyA and FK 506 are unique.9 A wealth of animal data1–12 and human experience13–16 suggest that FK 506 is effective in both the prevention and treatment of rejection. FK 506 appears to not only decrease the absolute incidence of rejection episodes, and allows for marked reduction in steroid doses, but makes the treatment of rejection much simpler. Nevertheless, a delineation of the side effects of FK 506 therapy is important in the comparison of two effective immunosuppressive agents. FK 506 and CyA share some of the same side effects, although they differ significantly in other important aspects. The purpose of this study was to examine the adverse effects associated with FK 506 therapy. Adverse reactions requiring treatment or adjustment of FK 506 doses can be categorized into four primary areas: (1) alterations in kidney function; (2) alterations in glucose metabolism; (3) neurotoxicity; and (4) susceptibility to infection or malignancy.

187 citations


Cited by
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01 Jan 2009
TL;DR: Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients and Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients.
Abstract: OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002

3,716 citations

Journal ArticleDOI
TL;DR: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.
Abstract: Background Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. Methods We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). Results Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P<0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P<0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated pat...

2,495 citations

Journal ArticleDOI
TL;DR: The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) 2005 Guideline Update for Percutaneous Coronary Intervention (PCI) contains changes in the recommendations, along with supporting text.
Abstract: The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) 2005 Guideline Update for Percutaneous Coronary Intervention (PCI) contains changes in the recommendations, along with supporting text. For the purpose of comparison

2,243 citations

Journal ArticleDOI
TL;DR: The molecular and biochemical characterization of HOs is reviewed, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress, to lay a foundation for potential future clinical applications of these systems.
Abstract: The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

2,111 citations

01 Jan 2011
TL;DR: This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations, including evidence-based recommendations supported by studies and experienced opinions based upon infection-control and engineering practices.
Abstract: The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.

1,478 citations