DOCSLIB.ORG

University of London Thesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
University of London Thesis 2808987859 REFERENCE ONLY UNIVERSITY OF LONDON THESIS Degree IM . P Year '^ o O ^ Name of Author f \ fcCG C O P YR IG H T This is a thesis accepted for a Higher Degree of the University of London. It is an unpublished typescript and the copyright is held by the author. All persons consulting the thesis must read and abide by the Copyright Declaration below. COPYRIGHT DECLARATION I recognise that the copyright of the above-described thesis rests with the author and that no quotation from it or information derived from it may be published without the prior written consent of the author. LOAN Theses may not be lent to individuals, but the University Library may lend a copy to approved libraries within the United Kingdom, for consultation solely on the premises of those libraries. Application should be made to: The Theses Section, University of London Library, Senate House, Malet Street, London WC1E 7HU. REPRODUCTION University of London theses may not be reproduced without explicit written permission from the University of London Library. Enquiries should be addressed to. the Theses Section of the Library. Regulations concerning reproduction vary according to the date of acceptance of the thesis and are listed below as guidelines. A. Before 1962. Permission granted only upon the prior written consent of the author. (The University Library will provide addresses where possible). B. 1962- 1974. In many cases the author has agreed to permit copying upon completion of a Copyright Declaration. C. 1975 - 1988. Most theses may be copied upon completion of a Copyright Declaration. D. 1989 onwards. Most theses may be copied. This thesis comes within category D. This copy has been deposited in the Library of_____________ —•_______ This copy has been deposited in the University of London Library, Senate House, Malet Street, London WC1E 7HU. OCULAR MONITORING IN IMMUNOSUPPRESSED PATIENTS AND QUANTIFICATION OF IMMUNOSUPPRESSION BY ASSESSMENT OF INTRACELLULAR CYTOKINES A thesis presentedfor the degree o f Doctor o f Medicine, Faculty of Medicine, University o f London By OLATOKUMBOH FOLAWUYO AKERELE BSc, MBBS, FRCOphth Clinical Ophthalmology, Institute of Ophthalmology University College London University of London 1 UMI Number: U591699 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U591699 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Although laboratory indices, such as drug levels, are in routine use for monitoring immunosuppression, these do not always correlate well with an individual’s risk of toxicity. In practice individual organs are monitored for toxicity with a combination of laboratory and clinical methods. These methods are limited by the fact that one has to await compromise before making therapeutic changes and there are often idiosyncrasies in the way individuals respond. Ocular complications can be sight threatening and many have proposed routine ocular monitoring in immunosuppressed patients. This study prospectively monitored a cohort of patients receiving high levels of immunosuppression for the prevention of rejection of heart, lung and heart-lung transplants for the development of ocular complications and to assess ocular morbidity. Specific surrogate markers that gave more information about the level of immunosuppression in a particular patient would improve patient care. Cytokines have the advantage of being directly generated by the immune response and offer promise as surrogate markers. Various, and not always consistent, cytokine profiles have been described for a number of conditions. Flow cytometry with intracellular cytokine staining allows quantification of the amount of cytokine present. These studies used this technique to describe the cytokine profile and changes in cytokine profile seen in patients during treatment for autoimmune uveitis and in patients with human immunodeficiency virus (HIV) receiving combination anti-retroviral therapy (ART). These studies emphasized the importance of prompt and careful clinical examination in the presence of clinical symptoms but did not support routine screening of patients on high levels of immunosuppression. Accurate measurements of interleukin-2 (IL-2) and interferon-gamma (IFNy) in patients with uveitis did not correlate well with disease activity. In contrast patients with different HIV profiles did show measurably different Thl cytokine expression providing information on the T cell deficits that persist despite treatment with ART. 2 TABLE OF CONTENTS HYPOTHESES....................................................................................................................14 OBJECTIVES...................................................................................................................... 14 1 CHAPTER 1: Clinical Monitoring: Ocular Complications Following Heart, Lung and Heart-Lung Transplantation ........................................................................................... 16 1.1 INTRODUCTION..................................................................................................... 17 1.1.1 Opportunistic Infections .................................................................................... 17 1.1.2 Other Complications Associated with Infection .............................................39 1.1.3 Noninfectious Ocular Complications Secondary to Drug Toxicity ..............42 1.2 AIMS........................................................................................................................... 51 1.3 METHODS................................................................................................................. 51 1.3.1 Patient Selection ..................................................................................................51 1.3.2 Data Collected ..................................................................................................... 51 1.4 RESULTS...................................................................................................................52 1.4.1 Heart Transplant Recipients ...............................................................................52 1.4.2 Heart-Lung Transplant Recipients ....................................................................58 1.4.3 Lung Transplant Recipients ...............................................................................60 1.5 SUMMARY............................................................................................................... 65 1.6 DISCUSSION ............................................................................................................ 67 2 CHAPTER 2: Quantification Of Immunosuppression by Flow Cytometric Assessment Of Intracellular Cytokines .................................................................................70 2.1 Overview of the Induction of the Immune Response ............................................ 71 2.1.1 Cells of the Immune System ..............................................................................71 2.1.2 Induction of an Immune response .....................................................................74 2.2 Cytokines .....................................................................................................................81 2.2.1 T Helper Subsets .................................................................................................82 3 2.2.2 Interleukin-2 (IL-2) and the Interleukin-2 Receptor (IL-2R) ........................84 2.2.3 Pro-inflammatory Cytokines ............................................................................. 84 2.2.4 Cytokines with Predominant Immunoregulatory Functions ..........................85 2.2.5 Clinical Correlations ...........................................................................................86 2.2.6 Measurement of Cytokines ................................................................................87 2.3 Laboratory Techniques Used In These Studies .......................................................91 3 CHAPTER 3: Assessment of Cytokine Production In Autoimmune Uveitis Patients On Systemic Immunosuppression ..........................................................................95 3.1 INTRODUCTION.....................................................................................................96 3.1.1 Definition of Uveitis ...........................................................................................96 3.1.2 Pathology of Posterior Uveitis and Effect on Cytokine Profile .....................97 3.1.3 Treatment of Posterior Uveitis .........................................................................102 3.1.4 Medical Suppression of the Inflammatory Response ....................................104 3.2 AIMS..........................................................................................................................I ll 3.3 METHODS................................................................................................................I ll
Load more

Recommended publications
  • 214622Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 214622Orig1s000 MULTI-DISCIPLINE REVIEW Summary Review Office Director Cross Discipline Team Leader Review Clinical Review Non-Clinical Review Statistical Review Clinical Pharmacology Review NDA214622 Multi‐disciplinary Review and Evaluation Infigratinib (Truseltiq) NDA/BLA Multi‐disciplinary Review and Evaluation FDA review was conducted in conjunction with other regulatory authorities under a regular ORBIS. While the application review is completed by the FDA, the application is still under review at the other regulatory agencies (Health Canada and Therapeutic Goods Administration). Disclaimer: In this document, the sections labeled as “Data” and “The Applicant’s Position” are completed by the Applicant, which do not necessarily reflect the positions of the FDA. Application Type NDA Application Number(s) 214622 Priority or Standard Priority Submit Date(s) September 29, 2020 Received Date(s) September 29, 2020 PDUFA Goal Date May 29, 2021 Division/Office OOD/DO3 Review Completion Date Please check electronic date stamp Established Name Infigratinib Trade Name Truseltiq Pharmacologic Class FGFR Inhibitor Code name BGJ398 Applicant QED Therapeutics, Inc. Formulation(s) Oral capsule Dosing Regimen 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28‐day cycles Applicant Proposed The treatment of adult patients with previously treated, Indication(s)/Population(s) unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangement as detected by an FDA approved test. Recommendation on Approval Regulatory Action Recommended For the treatment of adults with previously treated, Indication(s)/Population(s) unresectable locally advanced or metastatic (if applicable) cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA‐approved test.
    [Show full text]
  • Read PDF Edition
    REVIEW OF OPTOMETRY EARN 2 CE CREDITS: Positive Visual Phenomena—Etiologies Beyond the Eye, PAGE 58 ■ VOL. 155 NO. 1 January 15, 2018 www.reviewofoptometry.comwww.reviewofoptometry.com ■ ANNUAL CORNEA REPORT JANUARY 15, 2018 ■ CXL ■ EPITHELIAL DEFECTS How to Heal Persistent Epithelial Defects PAGE 38 ■ TRANSPLANTS Corneal Transplants: The OD’s Role PAGE 44 ■ INFILTRATES Diagnosing Corneal Infiltrative Disease PAGE 50 ■ POSITIVE VISUAL PHENOMENA CXL: Your Top 12 Questions —Answered! PAGE 30 001_ro0118_fc.indd 1 1/5/18 4:34 PM ĊčĞĉėĆęĊĉĆĒēĎĔęĎĈĒĊĒćėĆēĊċĔėĎēǦĔċċĎĈĊĕėĔĈĊĉĚėĊĘ ĊđĎĊċĎēĘĎČčę ċċĊĈęĎěĊ Ȉ 1 Ȉ 1 ĊđđǦęĔđĊėĆęĊĉ Ȉ Ȉ ĎĒĕđĊĎēǦĔċċĎĈĊĕėĔĈĊĉĚėĊ Ȉ Ȉ ĔēěĊēĎĊēę Ȉ͝ Ȉ Ȉ Ƭ 1 ǡ ǡǡǤ͚͙͘͜Ǥ Ȁ Ǥ ͚͙͘͜ǣ͘͘ǣ͘͘͘Ǧ͘͘͘ ĕĕđĎĈĆęĎĔēĘ Ȉ Ȉ Ȉ Ȉ Ȉ čĊĚėĎĔē̾ėĔĈĊĘĘ Ȉ Ȉ Katena — Your completecomplete resource forfor amniotic membrane pprocedurerocedure pproducts:roducts: Single use speculums Single use spears ͙͘͘ǡ͘͘͘ήĊĞĊĘęėĊĆęĊĉ Forceps ® ,#"EWB3FW XXXLBUFOBDPNr RO0118_Katena.indd 1 1/2/18 10:34 AM News Review VOL. 155 NO. 1 ■ JANUARY 15, 2018 IN THE NEWS Accelerated CXL Shows The FDA recently approved Luxturna (voretigene neparvovec-rzyl, Spark Promise—and Caution Therapeutics), a directly administered gene therapy that targets biallelic This new technology is already advancing, but not without RPE65 mutation-associated retinal dystrophy. The therapy is designed to some bumps in the road. deliver a normal copy of the gene to By Rebecca Hepp, Managing Editor retinal cells to restore vision loss. While the approval provides hope for patients, wo new studies highlight the resulted in infection—while tradi- the $425,000 per eye price tag stands as pros and cons of accelerated tional C-CXL has a reported inci- a signifi cant hurdle.
    [Show full text]
  • Neuro-Ophthalmic Side Effects of Molecularly Targeted Cancer Drugs
    Eye (2018) 32, 287–301 © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-222X/18 www.nature.com/eye 1,2,3 4 Neuro-ophthalmic side MT Bhatti and AKS Salama REVIEW effects of molecularly targeted cancer drugs Abstract The past two decades has been an amazing time culminated in indescribable violence and in the advancement of cancer treatment. Mole- unspeakable death. However, amazingly within cularly targeted therapy is a concept in which the confines of war have risen some of the specific cellular molecules (overexpressed, greatest advancements in medicine. It is within mutationally activated, or selectively expressed this setting—in particular World War II with the proteins) are manipulated in an advantageous study of mustard gas—that the annals of cancer manner to decrease the transformation, prolif- chemotherapy began touching the lives of eration, and/or survival of cancer cells. In millions of people. It is estimated that in 2016, addition, increased knowledge of the role of the over 1.6 million people in the United States will immune system in carcinogenesis has led to the be diagnosed with cancer and over a half a development of immune checkpoint inhibitors million will die.1 The amount of money being to restore and enhance cellular-mediated anti- spent on research and development of new tumor immunity. The United States Food and cancer therapies is staggering with a record $43 Drug Administration approval of the chimeric billion dollars spent in 2014. Nearly 30% of all monoclonal antibody (mAb) rituximab in 1997 registered clinical trials on the clinicaltrials.gov 1Department of for the treatment of B cell non-Hodgkin lym- website pertain to cancer drugs.
    [Show full text]
  • Eyelash-Enhancing Products: a Review Bishr Al Dabagh, MD; Julie Woodward, MD
    Review Eyelash-Enhancing Products: A Review Bishr Al Dabagh, MD; Julie Woodward, MD Long prominent eyelashes draw attention to the eyes and are considered a sign of beauty. Women strive to achieve ideal lashes through various modalities, including cosmetics, cosmeceuticals, and pharmaceu- ticals. The booming beauty industry has introduced many cosmetic and cosmeceutical products with claims of enhancing eyelash growth; however, many of these products have not been tested for efficacy or safety and are promoted solely with company- and/or consumer-based claims. The only pharmaceu- tical approved by the US Food and Drug Administration for eyelash growth is bimatoprost ophthalmic solution 0.03% (Latisse, Allergan, Inc). In this article, eyelash physiology, causes of genetic and acquired trichomegaly, and pharmaceutical and cosmeceutical products that claim eyelash-enhancing effects are reviewed. COS DERMCosmet Dermatol. 2012;25:134-143. yelashes decorate the eyes and crystallize cosmeceuticals contain active ingredients that are intended the beauty of the face.1 Long and lush eye- to produce beneficial physiologic effects through medicinal Dolashes in particular Notare considered a sign properties. Copy3,4 Cosmeceuticals fall in the gray area between of beauty. Women strive to achieve more inert cosmetics and pharmaceuticals. Drugs are defined pronounced eyelashes using a variety of tech- by the FDA as “articles intended for use in the diagnosis, niques.E Cosmetics are the mainstay of eyelash enhance- cure, mitigation, treatment, or prevention
    [Show full text]
  • Ocular Side Effects of Novel Anti-Cancer Biological Therapies
    www.nature.com/scientificreports OPEN Ocular side efects of novel anti‑cancer biological therapies Vicktoria Vishnevskia‑Dai1*, Lihi Rozner1, Raanan Berger2,3, Ziv Jaron1, Sivan Elyashiv1, Gal Markel2,3 & Ofra Zloto1 To examine the ocular side efects of selected biological anti‑cancer therapies and the ocular and systemic prognosis of patients receiving them. We retrospectively reviewed all medical records of patients who received biological anti‑cancer treatment from 1/2012 to 12/2017 and who were treated at our ocular oncology service. The following data was retrieved: primary malignancy, metastasis, type of biological therapy, ocular side efects, ophthalmic treatment, non‑ocular side efects, and ocular and systemic disease prognoses. Twenty‑two patients received biological therapies and reported ocular side efects. Eighteen patients (81.8%) had bilateral ocular side efects, including uveitis (40.9%), dry eye (22.7%), and central serous retinopathy (22.7%). One patient (4.5%) had central retinal artery occlusion (CRAO), and one patient (4.5%) had branch retinal vein occlusion (BRVO). At the end of follow‑up, 6 patients (27.27%) had resolution of the ocular disease, 13 patients (59.09%) had stable ocular disease, and 3 patients (13.64%) had progression of the ocular disease. Visual acuity improved signifcantly at the end of follow‑up compared to initial values. Eighteen patients (81.8%) were alive at study closure. Biological therapies can cause a wide range of ocular side efects ranging from dry eye symptoms to severe pathologies that may cause ocular morbidity and vision loss, such as uveitis, CRAO and BRVO. All patients receiving biological treatments should be screened by ophthalmologists before treatment, re‑screened every 4–6 months during treatment, and again at the end of treatment.
    [Show full text]
  • Chapter 129: Paraneoplastic Syndromes
    CHAPTER 129 – REFERENCES 1. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis 33. Kalia J, Swartz KJ. Elucidating the molecular basis of action of a classic drug: and treatment. Mayo Clin Proc 2010;85:838–854. guanidine compounds as inhibitors of voltage-gated potassium channels. 2. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous sys- Mol Pharmacol 2011;80:1085–1095. tem. N Engl J Med 2003;349:1543–1554. 34. Sanders DB, Massey JM, Sanders LL, et al. A randomized trial of 3. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J 3,4- diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology Rare Dis 2007;2:22. 2000;54:603–607. 4. de Beukelaar JW, Sillevis Smitt PA. Managing paraneoplastic neurological 35. McEvoy KM, Windebank AJ, Daube JR, et al. 3,4-Diaminopyridine in the disorders. Oncologist 2006;11:292–305. treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med 1989;321: 5. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies 1567–1571. to synaptic and neuronal cell surface proteins. Neurology 2011;77:179–189. 36. Low PA. Autonomic neuropathies. Curr Opin Neurol 2002;15:605–609. 6. Albert ML, Austin LM, Darnell RB. Detection and treatment of activated 37. Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar treatment. Am J Med 2007;120:841–847. degeneration. Ann Neurol 2000;47:9–17. 38. Calvet X, Martinez JM, Martinez M. Repeated neostigmine dosage as pal- 7. Antoine JC, Camdessanche JP.
    [Show full text]
  • A Review of Adverse Cutaneous Drug Reactions Resulting from the Use of Interferon and Ribavirin
    REVIEW A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin Nisha Mistry BSc MD1*, Jonathan Shapero BSc MD1*, Richard I Crawford MD FRCPC FAAD1,2 N Mistry, J Shapero, RI Crawford. A review of adverse Une analyse des réactions médicamenteuses cutaneous drug reactions resulting from the use of interferon and ribavirin. Can J Gastroenterol 2009;23(10):677-683. cutanées indésirables résultant de l’utilisation d’interféron et de ribavirine Drug-induced cutaneous eruptions are named among the most com- mon side effects of many medications. Thus, cutaneous drug eruptions Les éruptions cutanées induites par les médicaments font partie des are a common cause of morbidity and mortality, especially in hospital principaux effets secondaires de nombreux médicaments. C’est pour- settings. The present article reviews different presentations of drug- quoi elles sont souvent responsables de morbidité et de mortalité, induced cutaneous eruptions, with a focus on eruptions reported sec- notamment en milieu hospitalier. Le présent article analyse diverses ondary to the use of interferon and ribavirin. Presentations include présentations d’éruptions cutanées médicamenteuses et s’attarde aux injection site reactions, psoriasis, eczematous drug reactions, alopecia, éruptions déclarées après l’utilisation d’interféron et de ribavirine. Les sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and présentations incluaient des réactions au foyer d’injection, un psoria- lichenoid eruptions. Also reviewed are findings regarding life-threat- sis, des réactions eczémateuses médicamenteuses, une alopécie, une ening systemic drug reactions. sarcoïdose, un lupus, une éruption fixe d’origine médicamenteuse, des modifications pigmentaires et des éruptions lichénoïdes. On y analyse Key Words: Cutaneous; Drug; Eruption; Interferon; Ribavirin également les constatations portant sur les réactions médicamenteuses systémiques mettant la vie en danger.
    [Show full text]
  • Novel Therapeutic Options for Eyebrows and Eyelashes
    Alvin G, et al., J Clinic Exper Cosme Derma 4: 013 Journal of Clinical, Experimental and Cosmetic Dermatology Review Article Novel Therapeutic Options for Eyebrows and Eyelashes Enhancement Glen Alvin1* and Mike Chan2,3 1Jesselton Medical Centre, Kota Kinabalu, Malaysia 2EW Villa Medica, Eden Koben, Germany 3FCTI Research & Development GmbH, Germany Abstract The eyelash and eyebrow are equally important as anatomical *Corresponding author: Glen Alvin, Jesselton Medical Centre, Kota Kinabalu, structures with protective function and aesthetic value. Improvement Malaysia, E-mail: [email protected] to both the eyelash and eyebrow has galvanized the cosmetic industry to search for the perfect eyelash and brow. Current techniques and Received Date: March 23, 2021 apparatus utilized are beneficial but have their limitation. Novel therapies are gaining momentum to discover the perfect yet safe Accepted Date: March 30, 2021 eyelash and brow. Published Date: April 06, 2021 Keywords: Eyebrows; Eyelash; Therapy Citation: Alvin G, Chan M (2021) Novel Therapeutic Options for Eyebrows and Eye- Introduction lashes Enhancement. J Clinic Exper Cosme Derma 4: 013. Copyright: © 2021 Alvin G, et al. This is an open-access article distributed under the Facial aesthetics have been described, evaluated, and debated terms of the Creative Commons Attribution License, which permits unrestricted use, since the Renaissance era [1]. The eyelashes and eyebrows are among distribution, and reproduction in any medium, provided the original author and source the most important facial attributes that are the object of feminine are credited. aesthetical desires [2]. They are also important anatomical structures that protect the eye from particulate matter and water and wind Anatomy & Physiology [3].
    [Show full text]
  • Targeted Therapy: What Does the Internist Really Need to Know? Jonathan E
    Targeted therapy: What does the internist really need to know? Jonathan E. Dowell, MD Professor of Internal Medicine University of Texas Southwestern Medical Center This to acknowledge that Jonathan E. Dowell, MD has disclosed that he does have financial interests or other relationships with commercial concerns related directly or indirectly to this program. Dr. Dowell will be discussing off-label uses in his presentation. Biographical information: Dr. Dowell is a Professor of Internal Medicine in the Division of Hematology/Oncology at UT Southwestern, and he also serves as the Chief of the Section of Hematology/Oncology at the Dallas VA Medical Center. His primary research and clinical interest is thoracic malignancies. In addition, he has an interest in graduate medical education and serves as an Associate Program Director for the Hematology/Oncology Fellowship, the ACGME Subspecialty Education Coordinator for Hematology/Oncology for the IM residency, and the Division of Hematology/Oncology Education Director. Purpose/Educational Objectives: The purpose of this presentation is to familiarize the audience with the typical toxicities and drug interactions associated with the commonly used molecularly targeted agents in oncology. At the conclusion of this lecture, the listener should be able to: 1) Recognize the common and serious side effects of the VEGF inhibitors 2) Recognize the common and serious side effects of the EGFR inhibitors 3) Understand the cardiac risk of HER-2 directed therapy 4) Understand the cardiovascular risks of the ABL1 TKI’s 5) Recognize potential autoimmune toxicities associated with the immune checkpoint inhibitors and basic management strategies for these toxicities Acknowledgements: Dr. Dowell wishes to thank his two outstanding oncology pharmacy specialists at the Dallas VA, Rene Mani and Katherine Kelly, for their invaluable review of the protocol, and his 17- year-old daughter, Eleanor (Power Point consultant!) The past twenty years has seen a dramatic shift in cancer therapy.
    [Show full text]
  • FGF5 Is a Crucial Regulator of Hair Length in Humans
    FGF5 is a crucial regulator of hair length in humans Claire A. Higginsa,1,2, Lynn Petukhovaa,b,1, Sivan Harela, Yuan Y. Hoa, Esther Drilla, Lawrence Shapiroc, Muhammad Wajida,d, and Angela M. Christianoa,e,3 Departments of aDermatology, bEpidemiology, cBiochemistry and Molecular Biophysics, and eGenetics and Development, Columbia University, New York, NY 10032; and dUniversity of Education, Okara Campus, Lahore, Pakistan Edited by Stephen T. Warren, Emory University School of Medicine, Atlanta, GA, and approved April 22, 2014 (received for review February 14, 2014) Mechanisms that regulate the growth of eyelashes have remained homozygosity. Whereas SNP data for FT1 was uninformative for obscure. We ascertained two families from Pakistan who presented linkage, a maximum homozygosity score of 84 was obtained for with familial trichomegaly, or extreme eyelash growth. Using a com- a single region on chromosome 4q21.21 (Fig. 2 A and B), in- bination of whole exome sequencing and homozygosity mapping, dicating a large continuous region of homozygous genotypes we identified distinct pathogenic mutations within fibroblast growth shared among affected individuals and not present in unaffected factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of ones (7). Because exome sequencing has rapidly emerged as this gene in several additional trichomegaly families identified an a powerful means to identify genes that cause rare Mendelian additional mutation in FGF5. We further demonstrated that hair fibers phenotypes, we simultaneously performed whole exome sequenc- from forearms of these patients were significantly longer than hairs ing on two members of FT1, three members of FT2, and five from control individuals, with an increased proportion in the growth unaffected ethnically matched controls.
    [Show full text]
  • Sensitive Cilia – Eyelashes in Health and Disease
    FEATURE Sensitive cilia – eyelashes in health and disease BY RACHNA MURTHY AND JONATHAN ROOS In health our eyelashes protect the eyes, but in disease they can disfigure, impair quality of life and threaten vision. In this review the authors discuss aspects of lashes that are relevant to all professionals working near the eyes and how to keep you and your patients safe. ur eyelashes frame the eyes and are a key facial aesthetic: of the protein keratin also containing melanin and an outermost we have evolved to be preoccupied by the periocular area impermeable cuticle of several layers of scale-like cells. They when we meet someone. Eye tracking studies show that are coated with sebum secreted by a gland named after Dr Zeis Oour gaze is primarily focussed on the eyes and periocular (Figure 1). Like all hair, lashes transition through three phases in area when looking at one another [1]. When we look into someone’s their life but with a short anagen growth phase and long resting eyes we feel we can see their soul – but except for pupil size the eye telogen phase (Figure 2). This means that they reach no more than itself does not change – rather it is the surrounding tissues which around 10mm before growth stops. They then shed naturally after a speak to us. few months. One to four lashes are lost per day. Eyelashes tend to be The eyelashes contribute significantly to this aesthetic and the darkest hairs in the body and the last ones to undergo greying, communication; whole industries have been spawned for their usually late in life [11].
    [Show full text]
  • Eyelash Trichomegaly Following Treatment with Erlotinib in a Non‑Small Cell Lung Cancer Patient: a Case Report and Literature Review
    954 ONCOLOGY LETTERS 10: 954-956, 2015 Eyelash trichomegaly following treatment with erlotinib in a non‑small cell lung cancer patient: A case report and literature review SHAN-BING WANG1, KAI-JIAN LEI1, JIA-PEI LIU2 and YU-MING JIA1 Departments of 1Oncology and 2Laboratory Medicine, The Second People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China Received August 31, 2014; Accepted April 4, 2015 DOI: 10.3892/ol.2015.3265 Abstract. Inhibitors of epidermal growth factor receptor approved erlotinib for the treatment of patients with locally (EGFR), including tyrosine kinase inhibitors (TKIs), present advanced or metastatic NSCLC after progression on at least significant clinical benefits in the treatment of non‑small cell one prior chemotherapy regimen. With the wide use of EGFR lung cancer (NSCLC), particularly in patients with an EGFR tyrosine kinase inhibitors (TKIs) in patients with NSCLC, mutation. However, TKI treatment also results in unwanted an increasing number of side effects have been observed, cutaneous toxic side effects, such as a skin rash. Eyelash including skin rash, diarrhea, stomatitis and eyelash tricho- trichomegaly is rarely reported as a side effect; however, megaly (4,5). The adverse events most frequently reported it causes cosmetic issues or eyeball irritation in patients, by erlotinib-treated patients are rash (56.0%) and diar- which may result in the early termination of TKI treatment. rhea (62.0%) (6). Although erlotinib exhibits a number of side Therefore, although TKI-induced eyelash trichomegaly is rare, effects, it presents significant clinical benefits in the treat- it should be considered carefully by lung cancer physicians.
    [Show full text]