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Keloids and Hypertrophic Scars: Treatment With 1. FRONTISPIECE بسم ہللا الرح ٰمن الرحیم Bismillah hir Rahman nir Raheem In the name of Allah, the Most Beneficent, the Most Merciful KELOIDS AND HYPERTROPHIC SCARS: TREATMENT WITH INTRALESIONAL INTERFERON GAMMA VERSUS TRIAMCINOLONE ACETONIDE Keloids production in a New Zealand White Rabbit using Mannan & Hannan Technique 1 2. TITLE KELOIDS AND HYPERTROPHIC SCARS: TREATMENT WITH INTRALESIONAL INTERFERON GAMMA VERSUS TRIAMCINOLONE ACETONIDE A THESIS SUBMITTED FOR DEGREE OF DOCTOR OF PHILOSOPHY (SURGERY) PROF. DR. ABDUL MANNAN BABAR MBBS, FCPS, FRCS UNIVERSITY OF HEALTH SCIENCES LAHORE, PAKISTAN 22 DEC 2015 (Final) 2 3. DEDICATION This Study is dedicated to AL-AWAAM-UN-NAAS The Common Man 3 4 4. FOREWORD Prof. Dr. Abdul Mannan Babar s/o Ali Akbar, MBBS, FCPS, FRCS, date of birth 07.05.1960, of Pakistani Nationality, with National Identity Card No. 31202-0323879- 3, Passport No. AG3028792, and Pakistan Medical and Dental Council (PMDC) Registration No: 9124-P, belonging to Postgraduate Medical Institute, Ameer-ud-Din Medical College, Lahore General Hospital, Lahore Pakistan, having Telephone No. +92-333-2622227, and Email address [email protected], University of Health Sciences (UHS), Lahore Pakistan Registration No. 2008-PGE-9901-UHS,.performed this Research Work under my direct supervision at Department of Pathology and Experimental Research Laboratory, University of Health Sciences, Lahore Pakistan, for his Doctor of Philosophy (PhD) Degree in Surgery, from 23.12.2008 to 22.12.2015. Dr. Babar did all this work with his both hands, under my direct guidance. Starting from topic selection, literature search, synopsis preparation, synopsis printing and binding, acquiring funds, acquiring materials, pilot studies, animal husbandry, animal anaesthesia, operative work, post-operative care, data collection, data analysis, statistical tests, use of software, photography, information & communication technology work, thesis preparation, and thesis printing and binding. He worked day and night for this project; he was granted special permission by the University authorities to use facilities of Experimental Research Laboratory and Pathology Laboratory 24 hours a day, including holidays. The work done is original, novel, and latest. It includes both basic and applied research. Many permanent facilities were created at the University for this Project only; these facilities are now available 5 for future researchers both in basic and clinical disciplines. My guidance was available to him 24/7. This Thesis has been prepared according to latest standard International Guidelines, keeping in view the recommendations of the Grey Literature Network Service (GreyNet, 1999 [Bib]). The Guidelines of Higher Education Commission (HEC), PMDC, and UHS are also followed. The Thesis is based on the results of Experiments carried out by the candidate at Department of Pathology and Experimental Research Laboratory, University of Health Sciences, Lahore Pakistan, and this Research has not been previously presented for any Degree. I have read the Thesis and found it to be upto the mark for grant of Doctor of Philosophy degree in Surgery. According to my best knowledge and belief no such study has been carried anywhere in the world before. The Thesis has been checked by the University for Plagiarism using Turnitin plagiarism detection software, and is found to be free from plagiarism. Approval from Ethical Review Committee was taken before start of this study. The candidate has fulfilled all statutory requirements, and is qualified to submit this Thesis for Doctor of Philosophy Degree in Surgery. Prof. Dr. Abdul Hannan Nagi MBBS, FCPS, FRCP, FRCPath, PhD Head of the Department of Pathology Incharge Experimental Research Laboratory University of Health Sciences, Lahore, Pakistan Dated 22nd December 2015 6 5. PREFACE Becoming a student again when you are Professor for as long as 20 years is a wonderful experience. I had been trying to start PhD Programme in Clinical Medical Sciences at various institutions of postgraduate medical education in Pakistan for 11 years before was successful to start one such Programme at University of Health Sciences Lahore. That D- Day was 23rd of December 2008 when Advanced Studies & Research Board of UHS approved my Synopsis for PhD in Surgery, and I was registered as PhD Scholar. A lot of teething problems occurred. The main problem to start with was of funding, amounting to Pakistan Rupees (PKR) 5.5 million. Luckily Government of the Punjab Province had allocated PKR 10 million for research to each Government Sector Medical College in Punjab, including my institution ie Postgraduate Medical Institute Lahore. I was a strong contestant for that, but mysteriously that fund disappeared. Then I looked for second option ie Higher Education Commission (HEC), Government of Pakistan. It took my Supervisor and me about two years to get the Project approved and money released. The second problem was procurement of equipment and consumables. As most of these things had to be imported, it took almost six months for one consignment to be delivered. There were many such consignments. Sometimes the problem occurred that the items supplied were not according to our specifications, and so another six months lapsed. For some of these materials no importer was available, and things had to be procured using personal connections. 7 The third problem was establishment of Research facility. There was a rudimentary Animal House available at University of Health Sciences, having only Rats, and one self-trained animal-keeper. After the project started, this animal house was converted into full-fledged Experimental Research Laboratory. Mice, Rats, Guinea Pigs, and Rabbits keeping and breeding facilities were started. A full time Veterinary Officer and a Veterinary Assistant were hired. Necessary equipment was purchased to establish full-fledged Animal Operation Theatre. Now this Laboratory has become a resource centre for replication all over Pakistan. First two years (2009-2010) were spent in Course Work. It was a one-on-one coaching given to me by my Supervisor, 2-4 pm daily, 6 days a week. My supervisor taught me basics of Experimental Research. Professors of Anatomy, Physiology, and Biostatics also taught me in this course work. There was a Comprehensive Examination at the end of this Course Work. I also did a lot of self-study related to Anatomy, Physiology, Pathology, Pharmacology, Surgery, Plastic Surgery, Dermatology, Zoology, Experimental Research, Mathematics, Biostatistics, Computer Software, and Internet Resources. During these 2 years, I was also continuously refining my research project. At the start of third year (2011), was ready to start my research project. First, I had to do a few pilot studies, as exact guidelines about my project were not available in literature. So third year of my course was spent in these Pilot Projects. These included production of Keloid animal model in different animals, dosing of Transforming Growth Factor Beta 1 for production of Keloid animal model, multiple Keloid production in one animal, production of 8 transparent solution of Triamcinolone Acetonide, and dosing of Interferon Gamma for treatment of Keloids in rabbits. Fourth year of my course (2012) was spent on further studies, as new findings had come up based on pilot studies. So further literature search as well as self-reflection was done to make this project fool proof. Moreover, more materials were to be procured, based on findings of these pilot studies. These procurements were done during this period. Fifth & sixth years (2013-2014) were spent in data collection and data analysis. Whole data collection was done by my own hands, and no research assistant was hired. Data analysis was also done by me personally, as I had learned biostatistics myself, including biostatistics software. The study was triple blinded, and de-blinding was done after calculation of p-value. Data collection and data analysis was completed before the final day of sixth year ie 22.12.2014. The last portion of my work was Thesis writing, which took me further one year (2015). This Thesis consists of 100,000 words and 200 Figures and Tables. I wrote my first Thesis in 1983 (Babar, 1983A [Bib]), and second again in 1983 (Babar, 1983B [Bib]), during my final year MBBS. That was the era of manual typewriter, and manual literature search. I wrote my third Thesis in 1987 for Fellowship (Babar, 1987 [Bib]). The computer still had not reached us, but electric typewriter was available. Literature search was again manual, but some institutions had reference retrieval service available, which I used. I also got assistance from National Library of Medicine USA. Now we are in a digital era, with both advantages and disadvantages. 9 In this Thesis, I have used a liberal format keeping in view modern Information & Communication Technology (ICT) developments. For example, I have omitted Roman numerals, and used Arabic numerals starting from Frontispiece. This is in line with the ICT requirements, as two types of numerals cause confusion during downloading/printing. I have also followed recommendations of the Grey Literature Network Service. Grey Literature is that which is created by governments, universities, businesses and industries, whether printed or digital, and is not owned by publishing industry (GreyNet, 1999 [Bib]). It consists of Bibliographies, Conference Proceedings, Non-Commercial Translations, Official Documents, Reports, Technical Specifications & Standards, and Theses
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