DOCSLIB.ORG

Twenty Years of Clinical Islet Transplantation at the Diabetes Research Institute – University of Miami

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Twenty Years of Clinical Islet Transplantation at the Diabetes Research Institute – University of Miami 1 CHAPTER Twenty Years of Clinical Islet Transplantation at the Diabetes Research Institute – University of Miami A. Pileggi, C. Ricordi, N.S. Kenyon, T. Froud, D.A. Baidal, A. Kahn, G. Selvaggi, and R. Alejandro Clinical Islet Transplant Program and Cell Transplant Center, Diabetes Research Institute, University of Miami - Leonard Miller School of Medicine, Miami, Florida Intensive insulin therapy with the goal of maintain- lowing pancreatectomy due to pain associated with ing blood glucose concentrations close to the normal chronic pancreatitis, benign neoplasm, or trauma)(9-15). range can delay or prevent the onset of diabetes compli- Transplantation of allogeneic islets is mainly performed cations in patients with type 1 diabetes mellitus in patients with T1DM: allogeneic islets have been trans- (T1DM)(1). This goal is difficult to achieve in the major- planted in patients with end-stage renal disease (ESRD) ity of patients and is associated with a three-fold increase together with the kidney (simultaneous islet and kidney; in severe hypoglycemia. Transplantation of pancreatic SIK) and in patients with a stable kidney allograft (islet islets in patients with T1DM can restore β–cell function after kidney; IAK)(16-22). In recent years, transplanta- and provide a more physiological glycemic control than tion of allogeneic islets has also been performed as islet ISLETS - MIAMI, FLORIDA exogenous insulin administration (2). transplantation alone (ITA) in patients with brittle diabe- Steady progress in the field of β–cell replacement tes characterized by hypoglycemia unawareness and has been observed in recent years (2, 3), starting from progressive diabetes complications for which the risk of the seminal work by Lacy, et al (4, 5) in the late 1960s life-threatening hypoglycemia overweighed those of the demonstrating reversal of hyperglycemia by islet trans- transplantation procedure and chronic immunosuppres- plantation in diabetic rodents. Numerous challenges sion (23-31). In a smaller number of cases, transplanta- have been overcome, while many still remain unsolved tion of allogeneic islets has also been performed for dis- (2, 3). Technological advances in organ procurement eases of the exocrine pancreas in patients with pancre- and preservation techniques together with improvements atectomy-induced diabetes (32-38), metabolic disorders in pancreatic islet isolation, purification and culture have such as cystic fibrosis, hemochromatosis, and liver cir- allowed for the increasing success rate of islet transplan- rhosis (39-44) in combination with lung or liver transplan- tation worldwide. Implementation of safer transplanta- tation, respectively, and in few patients with type 2 DM tion procedures has also contributed to the increasing (T2DM) (45, 46). numbers of transplants performed in the recent years. A It has been twenty years since the first islet trans- total of 493 allogeneic islet transplants (including histori- plant was performed by the Clinical Islet Transplant Pro- cal cases) and 240 autologous grafts from 51 centers gram (CITP) at the Diabetes Research Institute / Univer- (18 North American, 30 European, and 6 elsewhere) were sity of Miami School of Medicine. One hundred-one islet published by the International Islet Transplant Registry infusions have been performed in 73 patients during this in 2001 (6). In light of the increasing number of centers period. Here we present an overview of the activity of performing islet transplantation, the National Institute of our CITP and of the progress in the islet transplantation Health sponsored a North American Collaborative Islet field in recent years. Transplant Registry (CITR) that was established in 2001 METHODS (7, 8). Transplantation of autologous islets is currently a Human Cell Processing Facility. The Diabetes Re- therapeutic option for a number of diseases of the exo- search Institute - University of Miami School of Medicine crine pancreas leading to DM (iatrogenic diabetes fol- was the first academic research center to house a cur- Clinical Transplants 2004, Cecka and Terasaki, Eds. UCLA Immunogenetics Center, Los Angeles, California 2 PILEGGI, RICORDI, KENYON, ET AL rent Good Manufacturing Practice (cGMP) facility dedi- gies, National Disease Research Interchange, Interna- cated exclusively to human islet cell isolation. This facil- tional Bioresearch Solutions, and International Institute ity operates following cGMP and Food and Drug Admin- for the Advancement of Medicine. istration regulations to ensure the highest standards of Organ harvesting is performed using standard tech- quality, purity, potency and safety for medical products niques by the surgical team (either local or distant), gen- destined for human use (47, 48). In addition to the isola- erally consisting of the removal of the gland along with tion of human islets for research or clinical trials, the duodenum and spleen (49). The pancreas is collected cGMP facility is also utilized for manufacturing human and stored in University of Wisconsin (UW) solution bone marrow cells (BMC). The Cell Processing and Dis- (DuPont-Pharma; Wilmington, Delaware) on ice and tribution Center of our cGMP facility currently provides shipped to our processing facility within 12 hours. In the human islets, as well as other cells, to more than 50 col- 2000’s, the use of oxygen carrier moieties laborating scientists worldwide. The cGMP facility in- (Perfluorodecalin; FluoroMEd, L.P.) was introduced in cludes clean room suites, and various laboratory sup- order to reduce ischemic injury during preservation (50, port areas over approximately 16,000 square feet. The 51). Briefly, the gland is immersed in preservation solu- access to the facility is restricted to authorized cGMP tion and maintained at the interface between oxygen- personnel only. The clean room suites meet ISO Class ated perfluorocarbon and UW (the two-layer method; 7 (ISO 14644) requirements with HEPA-filtered air con- TLM), as described by Kuroda, et al (52), and transported ditioning. Procedures pertaining to required dirty/clean to the cell processing laboratory within 24 hours. The flow patterns and directions are enforced by standard TLM is currently utilized in most of the pancreata ob- operating procedures, training, management and facility tained at our center, allowing us to improve islet yields design. All procedures, processes and equipment are even from marginal donors (51), and therefore improv- periodically validated, and testing ensures that they op- ing the utilization of islet preparations processed for trans- erate according to the pre-established performance plantation. specifications. Islet Isolation. Islets are obtained using the auto- Pancreas Procurement and Preservation. Human mated method (53) consisting of a mechanically-en- pancreatic glands are obtained from multi-organ cadav- hanced enzymatic digestion of the pancreas. Briefly, the eric donors through the University of Miami Organ Pro- pancreatic gland is dissected-free from surrounding tis- curement Organization (OPO) part of UNOS Region 3. sue. After dividing the pancreas through its neck, retro- Other OPO’s offering pancreata for clinical and research grade injection of dissociation buffer in the pancreatic to our facility include: Gift of Life, LifeGift, LifeQuest, duct is performed. Since the 1990’s, we use the en- LifePoint, The Sharing Network, LifeNet, Arkansas Re- zyme blend Liberase HI ® (Boehringer Mannheim-Roche) gional Organ Recovery Agency, Center for Donation and characterized by reduced endotoxin contamination and Transplantation, Translife, Washington Regional Trans- higher reproducibility, when compared to other collage- plant Consortium, Life Connection of Ohio, LifeSource, nase blends; this has significantly contributed to improved LifeCenter NorthWest, SouthWest Transplant Alliance, islet yields from human pancreata (54-57). New Mexico Organ Donor Network, New England Or- After distension, the pancreatic gland is divided into gan Bank, Hawaii, Life Legacy, Carolina Donor Services, 9-11 pieces and placed into the dissociation chamber. and other organizations like Tissue Transfer Technolo- The chamber (Fig. 1A) consists of two portions divided Figure 1. Human islet isolation. The dissociation chamber (A) is a key element of the isolation process. It allows the efficient dissociation of the pancreatic tissue and enhances the effects of the enzymatic digestion. A peristaltic pump permits the circula- tion of the enzyme through the chamber via a circuit of tubes (B). Agitation of the dissociation chamber enhances the enzyme action, and the automated mechanical shaker (C) allows one to standardize the force applied to the chamber. After digestion, the pancreatic slurry is collected (D) and concentrated by centrifugation. Close monitor- ing of multiple variables may be of assistance to improve the outcome of the isolation (E). Samples of the pancreatic digest are collected (F) in order to assess islet number and appearance (G). Islets can be easily identified by the means of dithizone staining that confers red color to endocrine cells. Purification of 3 ISLETS - MIAMI, FLORIDA the islets from the non-endocrine pancreatic tissue is performed using a computerized COBE centrifuge (H) by sedimentation on continuous or discontinuous gradients (I). The purified fractions are collected and assessed for purity and counted (J-K) before being cultured (L). All procedures are performed under cGMP standard following SOP and maintaining documentation (M). 4 PILEGGI,
Load more

Recommended publications
  • Surgical Advances in Heart and Lung Transplantation
    Anesthesiology Clin N Am 22 (2004) 789–807 Surgical advances in heart and lung transplantation Eric E. Roselli, MD*, Nicholas G. Smedira, MD Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Desk F25, 9500 Euclid Avenue, Cleveland, OH 44195, USA The first heart transplants were performed in dogs by Alexis Carrel and Charles Guthrie in 1905, but it was not until the 1950s that attempts at human orthotopic heart transplant were reported. Several obstacles, including a clear definition of brain death, adequate organ preservation, control of rejection, and an easily reproducible method of implantation, slowed progress. Eventually, the first successful human to human orthotopic heart transplant was performed by Christian Barnard in South Africa in 1967 [1]. Poor healing of bronchial anastomoses hindered early progress in lung transplantation, first reported in 1963 [2]. The first successful transplant of heart and both lungs was accomplished at Stanford University School of Medicine (Stanford, CA) in 1981 [3]. The introduction of cyclosporine to immunosuppres- sion protocols, with lower doses of steroids, led to the first successful isolated lung transplant, performed at Toronto General Hospital in 1983 [4]. Since these early successes at thoracic transplantation, great progress has been made in the care of patients with end-stage heart and lung disease. Although only minor changes have occurred in surgical technique for heart and lung transplantation, the greatest changes have been in liberalizing donor criteria to expand the donor pool. This article focuses on more recent surgical advances in donor selection and management, procurement and implantation, and the impact these advances have had on patient outcome.
    [Show full text]
  • Medical Policy
    Medical Policy Joint Medical Policies are a source for BCBSM and BCN medical policy information only. These documents are not to be used to determine benefits or reimbursement. Please reference the appropriate certificate or contract for benefit information. This policy may be updated and is therefore subject to change. *Current Policy Effective Date: 5/1/21 (See policy history boxes for previous effective dates) Title: Composite Tissue Allotransplantation Description/Background Composite tissue allotransplantation refers to the transplantation of histologically different tissue that may include skin, connective tissue, blood vessels, muscle, bone, and nerve tissue. The procedure is also known as reconstructive transplantation. To date, primary applications of this type of transplantation have been of the hand and face (partial and full), although there are also reported cases of several other composite tissue allotransplantations, including that of the larynx, knee, and abdominal wall. The first successful partial face transplant was performed in France in 2005, and the first complete facial transplant was performed in Spain in 2010. In the United States, the first facial transplant was done in 2008 at the Cleveland Clinic; this was a near-total face transplant and included the midface, nose, and bone. The first hand transplant with short-term success occurred in 1998 in France. However, the patient failed to follow the immunosuppressive regimen, which led to graft failure and removal of the hand 29 months after transplantation. The
    [Show full text]
  • Clinical Policy: Lung Transplantation Reference Number: CP.MP.57 Coding Implications Last Review Date: 05/20 Revision Log
    Clinical Policy: Lung Transplantation Reference Number: CP.MP.57 Coding Implications Last Review Date: 05/20 Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Medical necessity criteria for the review of lung transplantation requests. Policy/Criteria I. It is the policy of health plans affiliated with Centene Corporation® that lung transplant for members with chronic, end-stage lung disease who have failed maximal medical therapy is medically necessary when all of the following criteria are met: A. High (> 50%) risk of death from lung disease within 2 years if lung transplantation is not performed. B. High (> 80%) likelihood of surviving at least 90 days after lung transplantation. C. High (> 80%) likelihood of 5-year post-transplant survival from a general medical perspective provided that there is adequate graft function. D. Does not have ANY of the following absolute contraindications: 1. Malignancy, except for non-melanoma localized skin cancer that has been treated appropriately, low grade prostate cancer, a malignancy that has been completely resected, or a treated malignancy determined to have a small likelihood of recurrence and acceptable future risks; 2. Untreatable significant dysfunction of another major organ system unless combined organ transplantation can be performed; 3. Uncorrected atherosclerotic disease with suspected or confirmed end-organ ischemia or dysfunction and/or coronary artery disease not amenable to revascularization; 4. Acute medical instability, including, but not limited to, acute sepsis, acute viral respiratory infection, myocardial infarction, and liver failure; 5. Uncorrectable bleeding diathesis; 6. Chronic infection with highly virulent and/or resistant microbes that are poorly controlled pre-transplant; 7.
    [Show full text]
  • Lung Transplantation with the OCS (Organ Care System)
    Lung Transplantation with the OCSTM (Organ Care System) Lung System Bringing Breathing Lung Preservation to Transplant Patients A Guide for You and Your Family DRAFT ABOUT THIS BOOKLET This booklet was created for patients like you who have been diagnosed with end-stage lung failure and are candidates for a lung transplant. It contains information that will help you and your family learn about options available to you for a transplant. This booklet includes information on your lungs, how they function, and respiratory failure. In addition, you will learn about a new way to preserve lungs before transplantation, called breathing lung preservation. Your doctor is the best person to explain your treatment options and their risks and to help you decide which option is right for you. The booklet explains: • Breathing lung preservation with the OCS™ Lung System • How the OCS™ Lung System works • Who is eligible for the OCS™ Lung System • Lung transplant complications • How the lungs function • What is respiratory failure and the treatment options • What to expect during your treatment • Summary of clinical data for the OCS™ Lung System • Contact Information Please read this booklet carefully and share it with your family and caregivers. For your convenience, a glossary is provided in the front of this booklet. Terms in the text in bold italics are explained in the glossary. If you have questions about the OCS™ Lung System that are not answered in this booklet, please ask your physician. This booklet is intended for general information only. It is not intended to tell you everything you need to know about a lung transplant.
    [Show full text]
  • Rapidly Growing Epstein-Barr Virus-Associated Pulmonary Lymphoma After Heart Transplantation
    Eur Respir J., 1994, 7, 612–616 Copyright ERS Journals Ltd 1994 DOI: 10.1183/09031936.94.07030612 European Respiratory Journal Printed in UK - all rights reserved ISSN 0903 - 1936 CASE REPORT Rapidly growing Epstein-Barr virus-associated pulmonary lymphoma after heart transplantation M. Schwend*, M. Tiemann**, H.H. Kreipe**, M.R. Parwaresch**, E.G. Kraatz+, G. Herrmann++, R.P. Spielmann$, J. Barth* Rapidly growing Epstein-Barr virus-associated pulmonary lymphoma after heart trans- Dept of *Internal Medicine, **Hemato- plantation. M. Schwend, M. Tiemann, H.H. Kreipe, M.R. Parwaresch, E.G. Kraatz, G. pathology, +Cardiovascular Surgery, Herrmann, R.P. Spielmann, J. Barth. ERS Journals Ltd 1994. ++Cardiology, and $Radiographic Diagnostics, ABSTRACT: There is strong evidence to show an association of Epstein-Barr virus Christian-Albrechts-University of Kiel, Kiel, Germany. (EBV) infection with the development of post-transplant lymphoproliferative dis- ease. We report the rapid development of a malignant lymphoma in a heart trans- Correspondence: J. Barth plant recipient, which occurred within less than eight weeks. I. Medizinische Universitätsklinik The diagnosis of this malignant high grade B-cell lymphoma was established by Schittenhelmstr. 12 open lung biopsy, and classified as centroblastic lymphoma of polymorphic subtype. D-24105 Kiel Immunohistochemically, the lymphoma showed reactivity with the B-cell markers Germany L-26 (CD20) and Ki-B5 and with the activation marker Ber-H2 (CD30). Furthermore, an expression of the bcl-2 oncoprotein was detected. Monoclonal JH gene rearrange- Keywords: Epstein-Barr virus ment was demonstrated by polymerase chain reaction (PCR), indicating monoclonal heart transplantation pulmonary lymphoma proliferation of B-blasts.
    [Show full text]
  • Chronic Lung Allograft Dysfunction Post Lung Transplantation: a Review of Computed Tomography Quantitative Methods for Detection and Follow-Up
    Journal of Clinical Medicine Review Chronic Lung Allograft Dysfunction Post Lung Transplantation: A Review of Computed Tomography Quantitative Methods for Detection and Follow-Up Trieu-Nghi Hoang-Thi 1,2,3 , Guillaume Chassagnon 1, Thong Hua-Huy 3, Veronique Boussaud 4, Anh-Tuan Dinh-Xuan 3 and Marie-Pierre Revel 1,* 1 AP-HP.Centre, Hôpital Cochin, Department of Radiology, Université de Paris, 75014 Paris, France; [email protected] (T.-N.H.-T.); [email protected] (G.C.) 2 Department of Diagnostic Imaging, Vinmec Central Park Hospital, Ho Chi Minh City 70000, Vietnam 3 AP-HP.Centre, Hôpital Cochin, Department of Respiratory Physiology, Université de Paris, 75014 Paris, France; [email protected] (T.H.-H.); [email protected] (A.-T.D.-X.) 4 AP-HP.Centre, Hôpital Cochin, Department of Pneumology, Université de Paris, 75014 Paris, France; [email protected] * Correspondence: [email protected]; Tel.: +33-1-5841-2471 Abstract: Chronic lung allograft dysfunction (CLAD) remains the leading cause of morbidity and mortality after lung transplantation. The term encompasses both obstructive and restrictive pheno- types, as well as mixed and undefined phenotypes. Imaging, in addition to pulmonary function tests, plays a major role in identifying the CLAD phenotype and is essential for follow-up after Citation: Hoang-Thi, T.-N.; lung transplantation. Quantitative imaging allows for the performing of reader-independent precise Chassagnon, G.; Hua-Huy, T.; Boussaud, V.; Dinh-Xuan, A.-T.; evaluation of CT examinations. In this review article, we will discuss the role of quantitative imaging Revel, M.-P.
    [Show full text]
  • MSBCBS Prior Authorization List: Codes to Be Deleted 9/27/10
    MSBCBS Prior Authorization List: Codes to be Deleted 9/27/10 FOREHEAD FLAP WITH PRESERVATION OF VASCULAR PEDICLE (EG, AXIAL PATTERN 1 15731 FLAP) ABLATION, CRYOSURGICAL, OF FIBROADENOMA, INCLUDING ULTRASOUND 2 19105 GUIDANCE, EACH FIBROADENOMA COMPUTER-ASSISTED SURGICAL NAVIGATIONAL PROCEDURE FOR MUSCULOSKELETAL PROCEDURES, IMAGE-LESS (LIST SEPARATELY IN ADDITION TO CODE FOR PRIMARY 3 20985 PROCEDURE) 4 21125 AUGMENTATION, MANDIBULAR BODY OR ANGLE; PROSTHETIC MATERIAL AUGMENTATION, MANDIBULAR BODY OR ANGLE; WITH BONE GRAFT, ONLAY OR 5 21127 INTERPOSITIONAL (INCLUDES OBTAINING AUTOGRAFT) 6 21137 REDUCTION FOREHEAD; CONTOURING ONLY REDUCTION FOREHEAD; CONTOURING AND APPLICATION OF PROSTHETIC MATERIAL 7 21138 OR BONE GRAFT (INCLUDES OBTAINING AUTOGRAFT) REDUCTION FOREHEAD; CONTOURING AND SETBACK OF ANTERIOR FRONTAL SINUS 8 21139 WALL 9 21210 GRAFT, BONE; NASAL, MAXILLARY AND MALAR AREAS (INCLUDES OBTAINING GRAFT) 10 21215 GRAFT, BONE; MANDIBLE (INCLUDES OBTAINING GRAFT) ARTHROPLASTY, TEMPOROMANDIBULAR JOINT, WITH OR WITHOUT AUTOGRAFT 11 21240 (INCLUDES OBTAINING GRAFT) 12 21740 RECONSTRUCTIVE REPAIR OF PECTUS EXCAVATUM OR CARINATUM; OPEN RECONSTRUCTION REPAIR OF PECTUS EXCAVATUM OR CARINATUM; MINIMALLY 13 21742 INVASIVE APPROACH (NUSS PROCEDURE), WITHOUT THORACOSCOPY RECONSTRUCTIVE REPAIR OF PECTUS EXCAVATUM OR CARINATUM; MINIMALLY 14 21743 INVASIVE APPROACH (NUSS PROCEDURE), WITH THORACOSCOPY EXTRACORPOREAL SHOCK WAVE, HIGH ENERGY, PERFORMED BY A PHYSICIAN, REQUIRING ANESTHESIA OTHER THAN LOCAL, INCLUDING ULTRASOUND GUIDANCE, 15 28890 INVOLVING
    [Show full text]
  • CIBMTR Scientific Working Committee Research Portfolio July 1, 2018
    CIBMTR Scientific July 1, Working Committee 2018 Research Portfolio Milwaukee Campus Minneapolis Campus Medical College of Wisconsin National Marrow Donor Program/ 9200 W Wisconsin Ave, Suite Be The Match – 500 N 5th St C5500 Minneapolis, MN 55401-9959 USA Milwaukee, WI 53226 USA (763) 406-5800 (414) 805-0700 cibmtr.org CIBMTR Scientific Working Committee Research Portfolio: July 1, 2018 TABLE OF CONTENTS 1.0 OVERVIEW .................................................................................................................................................................. 1 1.1 Membership ........................................................................................................................................................... 2 1.2 Leadership .............................................................................................................................................................. 2 1.3 Productivity ............................................................................................................................................................ 3 1.4 How to Get Involved ............................................................................................................................................ 3 2.0 ACUTE LEUKEMIA WORKING COMMITTEE .................................................................................................. 6 2.1 Leadership .............................................................................................................................................................
    [Show full text]
  • Value of Donor–Specific Anti–HLA Antibody Monitoring And
    CLINICAL RESEARCH www.jasn.org Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft Loss † †‡ | Denis Viglietti,* Alexandre Loupy, Dewi Vernerey,§ Carol Bentlejewski, Clément Gosset,¶ † † †‡ Olivier Aubert, Jean-Paul Duong van Huyen,** Xavier Jouven, Christophe Legendre, † | † Denis Glotz,* Adriana Zeevi, and Carmen Lefaucheur* Departments of *Nephrology and Kidney Transplantation and ¶Pathology, Saint Louis Hospital and Departments of ‡Kidney Transplantation and **Pathology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; †Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, UMR-S970, Paris, France; §Methodology Unit (EA 3181) CHRU de Besançon, France; and |University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania ABSTRACT The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor– specific anti–HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic moni- toring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post– transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post–transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post- transplant screening identified 186 (21.9%) DSA-positive patients. Post–transplant DSA monitoring im- proved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statisticfrom0.67;95%confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77).
    [Show full text]
  • Islet Interleukin-1Β Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to Β-Cell Failure
    Diabetes Care 1 Islet Interleukin-1b Rebecca L. Hull,1 Ronald L. Gibson,2 Sharon McNamara,2 Gail H. Deutsch,3 Immunoreactivity Is an Early Corinne L. Fligner,3 Charles W. Frevert,1,4 Bonnie W. Ramsey,2 and Srinath Sanda5,6 Feature of Cystic Fibrosis That May Contribute to b-Cell Failure https://doi.org/10.2337/dc17-1387 OBJECTIVE Cystic fibrosis–related diabetes (CFRD) is a common complication of cystic fibrosis (CF), increasing patient morbidity and mortality. Poor understanding of CFRD path- ogenesis limits the development of targeted therapies to treat and/or prevent the disease. The aim of this study was to evaluate islet pathology, specifically, inflam- mation, amyloid deposition, and endocrine cell composition in subjects with CF with diabetes and with CF without diabetes. RESEARCH DESIGN AND METHODS A retrospective analysis of archived pancreas tissue collected at autopsy was con- ducted using pancreas tissue from subjects with CF and diabetes (CFRD) (n = 18) and PATHOPHYSIOLOGY/COMPLICATIONS CF without diabetes (CF-no DM) (n = 17). Two cohorts of control non-CF subjects were identified, each matched to CFRD and CF-no DM subjects for age, sex, and BMI (non-CF older, n = 20, and non-CF younger, n = 20), respectively. Immunohistochem- istry was performed to assess IL-1b and islet hormone (insulin, glucagon, somato- statin, and pancreatic polypeptide) immunoreactivity; histochemistry was performed 1Department of Medicine, University of Wash- to quantify amyloid deposition. ington, Seattle, WA 2Department of Pediatrics, University of Wash- RESULTS ington, Seattle, WA 3Department of Pathology, University of Wash- Islet IL-1b immunoreactivity was substantially increased in both CFRD and CF-no DM ington, Seattle, WA subjects compared with non-CF subjects and was common in young subjects with CF 4Department of Comparative Medicine, Univer- (£10 years of age).
    [Show full text]
  • Comprehensive Review of the Role of Rituximab in Pediatric Cardiac Transplantation
    Central Journal of Pharmacology & Clinical Toxicology Review Research *Corresponding author Alfred Asante-Korang, Division of Cardiology, Johns Hopkins All Children’s Hospital, 601 5th Street South, Saint Comprehensive Review of the Petersburg, Florida 33701, Tel: 1-727-767-4772; Email: [email protected] Submitted: 22 June 2020 Role of Rituximab in Pediatric Accepted: 07 July 2020 Published: 10 July 2020 Cardiac Transplantation ISSN: 2333-7079 Copyright Amy L. Kiskaddon1 and Alfred-Asante Korang2* © 2020 Kiskaddon AL, et al. 1Department of Pharmacy, Johns Hopkins All Children’s Hospital, USA OPEN ACCESS 2Division of Cardiology, Johns Hopkins All Children’s Hospital, USA Keywords • Rituximab Abstract • Pediatric cardiac transplantation Rituximab is a chimeric anti-CD20 monoclonal antibody approved for the treatment of CD20 positive B cell malignancies. In the transplant context, rituximab has been used to prevent and treat antibody-mediated allograft rejection, minimize systemic toxicities secondary to chemotherapy, treat autoimmune anemias, and as a strategy for managing post-transplant lymphoproliferative disorders (PTLD). However, information in the pediatric cardiac transplant patient population is limited. This review summarizes the use of rituximab in the pediatric cardiac transplant population. ABBREVIATIONS polyangiitis, and pemphigus vulgaris. Generally, a rituximab dose of 375 mg/m2 weekly, depending on the indication it is utilized ADCC: Antibody-Dependent Cell Mediated Cytotoxicity; AIC: for, and has minimal reported side effects
    [Show full text]
  • Airway Versus Transbronchial Biopsy and BAL in Lung Transplant Recipients: Different but Complementary
    Eur Respir J 1997; 10: 2876–2880 Copyright ERS Journals Ltd 1997 DOI: 10.1183/09031936.97.10122876 European Respiratory Journal Printed in UK - all rights reserved ISSN 0903 - 1936 Airway versus transbronchial biopsy and BAL in lung transplant recipients: different but complementary C. Ward, G.I. Snell, B. Orsida, L. Zheng, T.J. Williams, E.H. Walters Airway versus transbronchial biopsy and BAL in lung transplant recipients: different Dept of Respiratory Medicine, Alfred but complementary. C. Ward, G.I. Snell, B. Orsida, L. Zheng, T.J. Williams, E.H. Walters. Hospital and Monash University Medical ©ERS Journals Ltd 1997. School, Melbourne, Australia. ABSTRACT: Lung transplantation is now an established therapeutic intervention Correspondence: E.H Walters for end-stage cardiopulmonary disease in humans. Chronic rejection, in the form Dept of Respiratory Medicine of bronchiolitis obliterans syndrome (BOS), remains the commonest cause of mor- Alfred Hospital bidity and mortality in those surviving more than 3 months. The pathology of BOS Prahran involves airway changes. We have evaluated the potential for endobronchial biop- Melbourne sies (EBB) to complement existing sampling methods used in allograft monitoring Victoria 3181 and have compared the results of EBB findings with those of bronchoalveolar Australia lavage (BAL) and transbronchial biopsy (TBB) in 18 clinically stable patients. Keywords: Bronchoalveolar lavage We found that all the EBB had inflammatory cells present but that only five endobronchial biopsy TBB specimens had evidence of inflammation, with airway material being present lung transplant in 78% of the TBB. Paired BAL and EBB yielded different results, with no cor- transbronchial biopsy relations between total macrophages, lymphocytes, CD4+ cells or CD8+ cells.
    [Show full text]