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Volume 1, Issue 1, april 2013

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MJHS Editorial BoardEDITOR-IN-CHIEF

PROF. MOHAMMED AL-RUKBANVice Rector, Majmaah University andDean, College of Medicine, Majmaah Uni-versity

EDITORIAL BOARD

DR. IBRAHIM AL-HOQAILAssociate Professor Dermatology,College of Medicine, King SaudUniversity

PROF. ABDULRAHMAN M. AL-MAZROUProfessor of Pediatrics, Consultant, Pediat-ric Infectious Diseases, Department ofPediatrics, College of Medicine, King SaudUniversity, Riyadh, Saudi Arabia

DR. ABDULLAH ALI AL-GHASHAMDean, College of Medicine,Qaseem University, KSA

PROF. FAROOQ KHANProfessor of Medicine, State Universityof New York. Director Research andPublication

PROF. OMAR HASAN K KASULE, SrMB ChB (MUK), MPH (Havard), DrPH(Havard), Professor of Epidemiology andIslamic Medicine at the Institute of Medi-cine University of Brunei and Visiting Pro-fessor of Epidemiology at University Malaya

PROF. MOHAMMAD FAHEEMHead, Department of Physiology,College of Medicine, HamdardUniversity, New Delhi, India

DR. SAMUEL LEE, CANADAProfessor & Head Division ofGastroenterology, Department ofMedicine, University of Calgary,Canada

MJHSMJHSMJHSMAJMAAH JOURNAL OF HEALTH SCIENCES

A JOURNAL PUBLISHED BY MAJMAAH UNIVERSITY

CONTENTS

ForewordDr. Khalid bin Saad Al-Meqrin, Rector, Majmaah University ….……iii

PrefaceDr. Mohammed Othman Al-Rukban, Editor in Chief ……………….iv

MJHS Editorial Guidelines ………………………….…... ………….v

Clinical NoteMedical Hypnosis - A Poorly Understood Therapeutic Modality .…...1Riaz Qureshi

Original ArticlesCDP-choline neuroprotection and vascular remodelling via IRS-1 mech-anisms in Vascular Dementia. Growing neurons atop microelectronicchips as a new model for neurodegeneration…..…………………. 5Raid Al -Baradie, S Lynch, J Borresen, Jerzy Krupinski, Mark Slevin

Gentamycin toxicity to central Nervous System. …….……....…….11Rehan M Asad, Moattar R Rizvi, Sami Waqas, Kamran Afzal

The prevalence of vitamin-D deficiency in type 2 Diabetes mellitus….18Mansoor Al-Zahrani

Knowledge, attitude and practice of parents towards childhood vaccina-tion.……………………………………………………..…..….23Jamaan M. Zahrani

Parental Knowledge, Attitude and Practice on Antibiotic Use for UpperRespiratory Tract Infections in Children…………………………...33Khaled Al-Dossari

Effect of aerobic exercises on Blood Pressure in mild & moderate hyper-tensive middle aged & older patient………………………………..46Abu Shaphe, Irshad Ahmad, Faizan Z Kashoo, Shadabuddin

Review ArticlesRecent insight into Nosocomial Infection a - Review…………..……53Nasser Al-Jarallah

Animal models of Non Cirrhotic portal hypertension (NCPH). ……..58Moattar Raza Rizvi

ISSN: 1658-645XRef No.: 1434/5421

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MJHSMJHSMJHSMAJMAAH JOURNAL OF HEALTH SCIENCES

A JOURNAL PUBLISHED BY MAJMAAH UNIVERSITY

CONTENTS

Case ReportRoach’s Type II Variant of Sturge– Weber Syndrome………………71Saleem Shaikh, Abdur Rahman Al-Atram, Sachdeva Harleen

View pointTuberculosis Time bomb - A Global Emergency: Need for AlternativeVaccines………………………………………………………...77Mir Manzoor Ahmad

Medical QuizMedical Quiz, Wahengbam PS Al Waheed…………………………...83

Upcoming Conferences……………………………………...85

EDITORIAL ASSISTANTS

DR. KHALID TOHAMIMD. Assistant Professor, CommunityMedicine, College of Medicine,Majmaah University

DR. MOHAMMED AL-MANSOURMRCGP (INT), ABFM, SBFM.Assistant Professor, Family MedicineCollege of Medicine, Majmaah University

DR. FUZAIL AHMADPHD PT, Lecturer, Department ofPhysical Therapy & Rehabilitation,College of Applied Medical Sciences,Majmaah University

DR. MOATTAR RAZA RIZVIPHD PHYSIOLOGY, Assistant Professor,Department of Medical Lab Technology,College of Applied Medical Sciences,Majmaah University.

MR. WAQAS SAMIMSC BIOSTATISTICS, Lecturer,Department of Public Health &Community Medicine, College ofMedicine, Majmaah University

ISSN: 1658-645XRef No.: 1434/5421

ABOUT MAJMAAH UNIVERSITY MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

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About Majmaah University

Al Majma'ah is a city and a governorate inAr Riyad Province, Saudi Arabia. It has anarea of 30,000 square kilometers. Thepopulation of the town is around 45,000,while the population of the governorate asa whole is approximately 97,349 . Al-Majma'ah Governorate borders the EasternProvince and Al-Qasim to the north,Thadig and Shaqra to the south, Rumah tothe east, and Zulfi and al-Ghat on the west.Founded in 1417 CE by an immigrantfrom the Shammar tribe, Al-Majma'ah washistorically considered the capital of theregion of Sudair.

Majmaa’h University is considered one ofthe most recent universities in thekingdom, established in Ramadan 1430AH (August , 2009 AD ).

It started with nine colleges and now theyare thirteen and planned to reach thirty sixcolleges in the future. The total number ofthe students are 15000 distributed in fiveProvince, and cities ; Majmaa’h -Zulfa –Al-Ghat - Hawtat Sudair and Rammah,where this university will serve largegeographical area covering severalcounties and cities to achieve the goal ofthe Ministry of higher education which isthe expansion in higher education toinclude all parts of the Kingdom. To servethe community in several areas of socialawareness, education and training. Andthrough research, programs and studiesthat are compatible with what was plannedfor this university to achieve its highmission and to reach its planned goals,Allah willing.

FOREWORD MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

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FOREWORD

I am delighted to present the inaugral issue of Majmaah Journal of

Health Sciences, another initiative of Majmaah University, which

shall be published biannualy. I wish to extend my gratitude to the

Editor-in Chief Prof. Mohammad Othman Al- Rukban and his

editorial team for their passionate and creative contribution in

accomplishing the daunting task of publishing the first issue. I

would also like to thank all the reviweres for their contribution in

examining the scientific content of the manuscripts and providing

their valuble recommendations.

I would like to emphasize the compelling reasons for launching a new open-access peer

reviwed journal in this ever expanding field of health sciences as well as our aspirations and

vision for the future. The focus of this year’s edition is centered upon the development of a

framework for continuity of the Journal’s operations. To achieve this goal, we strive to

improve the formalization of submission review and feedback process, online access, search

engine indexing, and distribution of the journal.

I believe that it is important to have a journal which gives free access to its contents,

promotes high-quality research and intellectual output of reserchers. This journal aims to

bridge the gap between the research and practice in the field of health sciences, thus

providing an opportunity to the authors to disseminate their high-quality scientific

achievements to a wider audience. I believe we will be publishing a significant number of

high-quality original research articles and scientific reviews from authors around the world.

We hope this Journal becomes an increasingly customary piece of the accademic culture at

this university and look forward watching it grow.

Dr. Khalid bin Saad Al-Meqrin,

Rector, Majmaah University

Al-Majmaah, Kingdom of Saudi Arabia

PREFACE MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

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PREFACE

Majmaah University is pleased to announce the launch of Majmaah

Journal of Health Science (MJHS). From time immemorial research

and publication have been the foundation of today's science. Out of

all the thousands of specialty subspecialty journals, the readers focus

on their own specialty and rarely look for other subjects. Due to

inadequate multidisciplinary knowledge, there has been lack of integrated approach to the

patient care and better health.

Majmaah Journal of Health Science (MJHS) is a peer-reviewed, open access biomedical

journal covering all aspects of basic and clinical sciences, medical education, public health,

research and publication ethics from all medical and health sciences background. The Journal

aims at establishing itself as the leading international journal in medical sciences and deals in

publishing original scientific studies, review articles, technical reports, and short

communications commenting on the public health, community health, environmental health,

behavioural health, health policy, health service, health education, health economics, medical

ethics, health protection, and equity in health that are not published or not being considered

for publication elsewhere.

We would like to take this opportunity to thank all those who helped in starting this new

journal. Special thanks to His Excellency Dr. Khalid bin Saad Al-Meqrin, without his

direction & support this endeavour wouldn’t have been possible. I would also like to thank

the then Vice Rector Dr. Mohsen Al-Mohsen and the incumbent Vice Rector Dr. Mohammed

Abdullah Al-Shaya for their proactive role in providing all the support. I commend the efforts

of the members of Editorial Committee and Editorial Board of MJHS who made it possible

for timely publishing of this journal. MJHS heavily rely on their personal epistemology for

reviewing and making their outstanding and invaluable contribution to the journal and we are

really grateful to them for giving their time and expertise.

Prof. Mohammad Othman Al RukbanEditor in Chief, MJHS,Vice Rector, Academic Affairs,Dean, College of Medicine, Majmaah University

EDITORIAL POLICIES MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

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EDITORIAL POLICY

We welcome all contributions that enhanceor illuminate medical sciences. In additionto scientific articles, letters, news, andcomments are welcome if they serve thepurpose of transfer of original and valuableinformation to our readers.

To give an equal publishing chance tomanuscripts from different environments,we will normally publish no more than twopapers by the same author or co-authorwithin one calendar year. This rule alsoapplies to editors. Also, we recommendauthors not to separate fragments of astudy into individual reports, but rather topresent a full report on the topic.

EDITORIAL PROCEDURE

The Editor-in-Chief reads everymanuscript received and assigns it ageneral priority level: (a) manuscripts sentto reviewers immediately; (b) manuscriptsreturned to authors with suggestions forthe improvement of data presentation; and(c) rejected manuscripts. Editors-in-Chiefread the revised manuscript. If themanuscript is improved adequately, it issent to two reviewers for extramuralreview and to the Statistical Editor, if itcontains numerical data. This editorialprocedure reinforces our author helpfulpolicy because all manuscripts undergoeditorial scrutiny and advice.

AUTHORSHIP

According to the International Committeeon Medical Journal Ethics (ICMJE), anauthor is defined as one who has madesubstantial contributions to the conceptionand development of a manuscript.Majmaah Journal of Health Sciencesadheres to the ICMJE guidelines(http://www.icmje.org/#author), whichstate that “authorship credit should bebased on all of the following: 1)substantial contributions to conception and

design, acquisition of data, or analysis andinterpretation of data; 2) drafting thearticle or advising it critically forimportant intellectual content; and 3) finalapproval of the version to be published.All submissions are expected to complywith the above definition. Changes to theauthorship list after submission will resultin a query from the publisher requestingwritten explanation.

SUBMISSION

Majmaah Journal of Health Sciencesaccepts all manuscripts on the strictcondition that they have been submittedonly to us, and had not been published inany other journal, nor are they underconsideration for publication or in presselsewhere. The journal adheres to the Codeof Conduct and Best Practice Guidelinesset forth by the Committee on PublicationEthics (COPE).

PEER REVIEW

All manuscripts will be subjected toconfidential peer review by experts in thefield and, on the basis of reviewers’feedback; papers will be acceptedunconditionally, accepted subject torevision or rejected.

ETHICS AND CONSENT

Do not use patients' names, initials, orhospital numbers, especially in illustrativematerial. Identifying information shouldnot be published in written descriptions,photographs, and pedigrees unless theinformation is essential for scientificpurposes and the patient (or parent orguardian) gives written informed consentfor publication. Informed consent for thispurpose requires that the patient be shownthe manuscript to be published.


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COPYRIGHT AND PERMISSIONS

It is a condition of publication that authorsassign copyright or license the publicationrights in their articles, including abstracts,to Majmaah Journal of Health Sciences.This enables us to ensure full copyrightprotection and to disseminate the article,and the Journal, to the widest possiblereadership in print and electronic formatsas appropriate. Authors may, of course,use the article elsewhere after publicationwithout prior permission from MajmaahJournal of Health Sciences, provided thatacknowledgement is given to the Journalas the original source of publication, and itis notified so that our records show that itsuse is properly authorised.

Authors are required to sign an agreementfor the transfer of copyright to thepublisher. All accepted manuscripts,artwork, and photographs become theproperty of the publisher. A copyrightagreement form can be downloaded bycorresponding authors of acceptedmanuscripts with proofs. This should besigned and returned to Majmaah Journal ofHealth Sciences.

Authors are themselves responsible forobtaining permission to reproducecopyright material from other sources.

DECLARATION OF INTEREST

It is the policy of Majmaah Journal ofHealth Sciences, to adhere in principle tothe Conflict of Interest policyrecommended by the ICMJE. All authorsmust disclose any financial and personalrelationships with other people ororganizations that could inappropriatelyinfluence (bias) their work. It is the soleresponsibility of authors to disclose anyaffiliation with any organization with afinancial interest, direct or indirect, in thesubject matter or materials discussed in themanuscript that may affect the conduct or

reporting of the work submitted. Allsources of funding for research are to beexplicitly stated. If uncertain as to whatmight be considered a potential conflict ofinterest, authors should err on the side offull disclosure. If there are no declarations,authors should explicitly state that thereare none. This must be stated at the pointof submission. Manuscript submissioncannot be completed unless a declarationof interest statement (either stating thedisclosures or reporting that there arenone) is included.

This will be made available to reviewersand will appear in the published article. Ifany potential conflicts of interest are foundto have been withheld followingpublication, the journal will proceedaccording to COPE guidance. The intent ofthis policy is not to prevent authors withany particular relationships or interestfrom publishing their work, but rather toadopt transparency such that reviewers,editors, the publisher, and mostimportantly, readers can make objectivejudgements concerning the work product.

POLICY FOR SUBMISSIONS BYMEMBERS OF THE EDITORIAL

TEAM

As all editors and Editorial Boardmembers are active professionals andresearchers, it may happen that they wouldwant to submit their articles to theMajmaah Journal of Health Sciences. Thisrepresents a potential conflict of interest,especially in cases of submissions fromdecision-making editors. In reviewingsubmissions from its editors and EditorialBoard members, we follows the guidelinesfor good editorial practice set byinternational editorial organizations, suchas World Association of Medical Editors(WAME;http://www.wame.org/resources/publication-ethics-policies-for-medical-journals#conflicts) and Committee on


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Publication Ethics (COPE;http://publicationethics.org/case/editor-author-own-journal).

The review of such manuscripts will not behandled by the submitting editor(s); thereview process will be supervised anddecisions made by a senior editor who willact independently of other editors. In somecases, the review process will be handledby an outside independent expert tominimize possible bias in reviewingsubmissions from editors.

REVIEW PROCESS

1. Authorship statement. Upon the receiptof the submission, authors will receivethe Authorship Statement form, whichshould be filled in, signed and returnedto the Editor. In this way, the authorsconfirm the originality of the report andvalidity of authorship, and assertcompliance with the review process, i.e,that he or she shall not withdraw thepaper until it is published or rejected.We advise the authors to promptly sendback the filled out authorshipstatements, or otherwise the editorialprocessing of the manuscript may bedelayed.

2. Pre-review (if necessary). One to threeweeks after submission of themanuscript, the author may receiveEditor’s letter with a copy of themanuscript with suggestions for theimprovement of data presentation. Thisis the manuscript pre-review. Theauthor should closely follow theinstructions, revise the manuscript, andsubmit the revised version.

3. Peer review. The Majmaah Journal ofHealth Sciences promotes expertrefereeing by peers as a best availablemethod for the maintenance ofstandards of excellence in the scientificcommunity, and is committed to

promoting its peer review quality andfairness, as well as its speed andefficiency. Authors are welcome tosuggest up to three potential reviewersfor their manuscript (excluding co-authors or collaborators for the lastthree years), or to ask for the exclusionof reviewer(s) and the reasons for it.The reviewers are asked to treat themanuscript with confidentiality, andreveal any research conflict of interestwith the reviewed manuscript.Reviewers do not have to sign thereview forms with suggestions to theauthors, but may do so if they wish.Within two months of submission of themanuscript, the authors will receive thereviews. The comments and suggestionsmade by the reviewers should beaddressed and closely followed. In thisrespect, the Editor’s accompanyingletter will give clear general instructionsfor further work on the manuscript.

4. Author’s cover letter accompanying therevised version of the paper. Theauthors should state clearly andprecisely every step taken in accordancewith the reviewers’ requests. Thedescription should be listed on anumbered basis, in the order ofreviewers’ comments. Alteredparagraphs in the new version of themanuscript should be specified usingpage and paragraph numbers. Paragraphon top of a page is considered No. 1,even if it does not begin on that page.

ACCEPTANCE CRITERIA

The reviewers are asked to apply highestinternational standards in their assessmentof the submitted work. The key advice onconcrete criteria that they receive fromeditors is to look for the originality ofwork and its importance/relevance to thesubject as a whole. If the article does notfulfil these primary criteria, it should notbe accepted. The articles which receive


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one or more reviewers’ recommendationsfor “major review,” are sent, after revision,with the respective author’s cover letter, tothe same reviewer, who makes the finalrecommendation on acceptance orrejection. To ensure the transparency ofthe editorial process and responsibilities ofall authors, the formal letter of acceptanceis sent to all authors on the manuscript,and not just to the corresponding author. Inthe case of rejection, the authors have theright to appeal if they think that thereviewers did not understand or appreciatesome points in the manuscript. The editorsof the Majmaah Journal of Health Scienceswill then decide if there are grounds forreconsidering the manuscript.

Scientific integrity The Editorial Board isdevoted to the promotion of scientificintegrity as a vital component of theresearch process. The Research IntegrityEditor will deal with all issues related topossible scientific misconduct inmanuscripts submitted to or published inthe journal. Majmaah Journal of HealthSciences follows the ethics flowchartsdeveloped for dealing with cases ofpossible misconduct. The COPEflowcharts are available at:http://publicationethics.org/flowcharts.The following brief guidelines are aimedto increase awareness of our authors anddecrease misunderstandings about thepublication process in a scientific journal.Although rare events, duplicate publicationand scientific fraud (falsification andfabrication of data, and plagiarism) areimportant issues with serious impact onthe integrity of the scientific community.The Majmaah Journal of Health Scienceswill not consider papers that have alreadybeen published as an article or have beensubmitted or accepted for publicationelsewhere in print or in electronic media.This policy does not precludeconsideration of a paper that has beenrejected by another journal or of a

complete report that follows publication ofa preliminary report, such as an abstract orposter displayed at a professional meeting.Short abstracts (400 words) of preliminaryresearch findings presented at conferencesand included in conference proceedingsare not considered previous publications.Authors should indicate this on the firstpage of the manuscript and in the coverletter. Presentations longer than an abstractmay disqualify the paper. The authorshould alert the Editor if the work includessubjects on which a previous report hasbeen published.

Any such work should be referred to andreferenced in the new paper. If the Editorwas not aware of the violations and thearticle has already been published, a noticeof duplicate publication will be publishedwithout the authors’ explanation orapproval. This policy is based on theinternational copyright laws, ethicalconduct, and cost effective use ofresources). If the Editor discovers or ispresented evidence of such problems, hewill contact the appropriate official(s) atthe institution(s) from which themanuscript originated. It is then left to theinstitution(s) in question to pursue thematter appropriately. Depending on thecircumstances, publish errata, corrigenda,or retractions of manuscripts. In cases ofscientific disagreement about themethodology and/or contents of an articlepublished in the journal, which do notallege fraud, we encourages the concernedindividuals to either directly contact theauthors or write a letter to the Editor.

CLINICAL NOTE MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Medical Hypnosis, Riaz Qureshi 1

Definition of HypnosisIt is a particular state of mind in whichthe suggestions are not only acceptedreadily, but are also acted upon, muchmore powerfully than a wakingstate.(1,3,6)

It is induced in one person by another,but can also be self- induced.

MEDICAL HYPNOSIS – A POORLY UNDERSTOODTHERAPEUTIC MODALITY

1*Riaz Qureshi

It would be difficult to find a subject, whichis more controversial and poorlyunderstood, than hypnosis in the entiremedical field. This controversy related tothe medical use of hypnosis has had aconvoluted rout and history, since the timeof Franz Mesmer in 1765, to the time in1953, when British Medical Associationissued a report, whichsupported its beneficialrole in certainconditions/illnesses(1,6,7).

Franz Mesmer, anAustrian Physician andthe founder ofmesmerism, believedthat the human body isimmersed in amagnetic fluid, which needs to bemanipulated through some means, in orderto get rid of the symptoms a person may besuffering from. The presence of a magneticfluid among the patients, who were treatedby Mesmer, was found to be incorrect by acommission of enquiry, established by theruler of France, the country in whichMesmer had his practice. In response to thisfinding, Mesmer was forced to leaveFrance, in-spite of the fact that, asignificant number of his patients had aremarkable recovery from their illnesses,especially psychoneurotic ones. The levelof interest of physicians in treatment byhypnosis has been variable over the 19th aswell as the early part of 20th century.

In 1953, medical use of hypnosis received amajor boost, when a committee established

by the British Medical Association reportedthat a hypnotic phenomenon does exist,which sheds a great deal of light on the roleplayed by the unconscious mind on humanbehaviour. This report stated thathypnotherapy (treatment by hypnosis)could be a method of choice in thetreatment of certain psychosomatic and

psychoneuroticillnesses. Thereport also foundthat hypnosiscould sometimeplay a part inSurgery, Obstetricsand Dentistry as ananalgesic and ananaesthetic.

The mainobjectives of this brief review of medicalhypnosis are to make the readers aware of:

1. What is hypnosis? Its nature and how itworks in clinical practice?

2. What clinical conditions may bemanaged with hypnosis?

3. Sharing of the author’s own experiencein the practice of hypnotherapy, over thelast 40 years?

In a ‘hypnotic state’, the conscious mindand its power of criticism are suppressedand suggestions consequently enter theindividual’s unconscious mind, which doesnot have the power of criticism andtherefore, unable to reject them.(2,3,6,7)

Susceptibility to Hypnosis

90% of the population can be hypnotized.

Received: 2 December, 2012; Accepted: 5 February, 2013*Correspondence: [email protected], Department of Family & Community Medicine, College of Medicine, King Saud University,Riyadh, Saudi Arabia



Light hypnosis can be achieved by 10%patients medium- depth- hypnosis by 70-80% of patients and deep level of hypnosisby10-20% of the patients. Children,teenagers, members of armed forces, actorsand actresses are usually excellent subjects.

Induction of Hypnosis:

There are many methods of inductinghypnosis in a subject. The following are thesteps of a simple hypnosis inductiontechnique, which the author has himselfpracticed effectively over many years:

Eye-fixtaion, by the patient on an objectof his own choice, with distraction.

Progressive muscle relaxation from oneend of the body to the other end.

Relaxation through deep breathingexercise

Deepening of the relaxation trance byvisual imaging of a nice scene ofpatient’s own choice.

Post-hypnotic suggestions.

o Ego strengtheningo Specific suggestions related to the

problem concerned

Autohypnosis / self-hypnosis training.

Awakening the subject.

Training of patients to practice thehypnotherapy session (self-hypnosis) athome is an essential requirement for thistreatment modality. A patient underhypnotic trance may appear asleep orunconscious, but in reality, he is fullyaware of his surroundings (it is not a truenatural sleep). Under medical hypnosis,patient cannot be made to do anythingagainst his will.

If there is an unexpected emergencysituation during the hypnosis session, thepatient comes out of the trance and copes

with the emergency, even better thannormal. (6,7)

Hypnotic Analgesia:

Complete analgesia (relief from pain) isachieved in less than 20% of subjects withdeep hypnosis. Partial analgesia is achievedthrough medium depth hypnosis. Negligibleanalgesia can be achieved through lighthypnosis.

Pain threshold can be raised throughhypnosis. Distraction theory is applied toachieve hypnotic analgesia

Therapeutics use of Hypnosis (MedicalHypnosis):

Nature of HypnosisTo understand, how hypnosis works, it issuggested, that the concept of the existenceof ‘conscious’ and ‘unconscious’ minds needsto be accepted

Conscious MindIt is the part of the mind, which thinks,feels and acts in the present – it also haspower of criticism

Unconscious MindIt is the seat of all our memories, all ourpast experiences and indeed all that wehave ever learned



A wide variety of medical and dentalconditions/Illnesses respond tohypnotherapy, according to the publishedliterature. The problems/ illnesses quotedbelow belong to a limited number ofconditions/ illnesses, which respond well tohypnotherapy, in the personal experience ofthe author.

Medical Hypnosis in Dentistry helps in

1. Obtaining relaxation – raises patient’spain threshold.

2. Ensuring co-operation.3. Reduction of fear and anxiety.4. Preparation for local and general

anesthesia.

5. The production of amnesia in deeptrance.

6. The control of fainting.

7. Reduced bleeding.

8. Locking of jaw, so that it is widely openfor the procedure.(6,7,9)

Medical Hypnosis in Incurable andPainful Illness:

Hypnosis can reduce: The actual pain itself. The distress that it causes.

Pain is more easily tolerated. It helps the patient to accept his illness

through relaxation and reduction oftension.

It can raise the threshold of pain withreduction in medication.(6,7,8,9).

Medical Hypnosis in Some Other PainfulConditions:

Irritable bowel syndrome and Nervousdyspepsia, Chronic back pain / Neck pain,Tension - headache and Migraine,Dysmenorrhoea, Non-specific pain withSomatization. (6,7,8,9)

Medical Hypnosis in other ClinicalConditions:

1. Respiratory/ENT-Asthma,hyperventilation, frequent Sore Throatand Allergy(5,6)

2. Cardio Vascular-Hypertension andPalpitation (5,6,7)

3. Neurology-Headache / Migraine,Neuropathic pain(6,7,9)

4. Gastroenterology-Irritable bowel,Nervous dyspepsia and Constipation(6,7,8,10)

5. Endocrinology-Obesity (6,7)

6. Psychiatry-Anxiety, Insomnia, Phobia,Substance abuse & Alcohol(6,7)

7. Miscellaneous-Academic field, lack ofconfidence, tics, speech disorder, sports& smoking.(5,6,7)



8. Childhood Behavior Disorders-Nocturnal enuresis, school phobia andnail biting / thumb sucking. (6)

9. Dermatology-Eczema, allergic rashesand warts.(6,7)

Conclusion: Medical Hypnosis is not amiracle-worker, but it can be a valuablenon-pharmacological therapeutic modalityin the treatment of a variety ofconditions/illnesses, in the hands of acaring and competent physician.

ACKNOWLEDGMENTI am grateful to Dr Syed Irfan Karim,Assistant Professor, Family Medicine, King

Saud University, for reviewing themanuscript on a short notice

REFERENCES

1. Tinterow M M. Foundation of Hypnosis:From Mesmer to Freud.Springfield111.Charles. C Thomas ;1970

2. Snaith R P. A method of psychotherapybased on relaxation techniques. BJPsych.1974;124:473-81.

3. Ellenberger H F. The Discovery of theunconcious. New York: Basic Books.1970

4. Stewart H, Fry A. The Scope of hypnosisin general practice. BMJ.1957(1):1325

5. Cracilneck H B, Hall J A. Clinicalhypnosis: Principles and Applications.New York: Grune & Stratton ;1975.

6. Hartland J. Medical and Dental Hypnosisand its Clinical Applications, 2nd ed.London: Baillieére Tindall ;1971.

7. Ambrose A, Newbold G. A Handbook ofMedical Hypnosis, 4th ed. London:Ballieére Tindall ;1980.

8. Wilson S, Madison T, Roberts L,Greenfield S. Systematic review: theeffectiveness of hypnotherapy in themanagement of irritable bowel syndrome.AP&T 2006 Sept;24 (5): 769-80.

9. Grondahi JR, Rosvold E O. Hypnosis as atreatment of chronic widespread pain ingeneral practice: a randomized controlledpilot trial. BMC MusculoskeletalDisorders .2008 Sep 18; 9: 124

10. Lindfors P, Unge P, Arvidsson P, NyhlinH. Effects of gut-directed hypnotherapyon IBS in different clinical settings-resultsfrom two randomized controlled trial. AmJ Gastroenterol.2012 Feb; 107(2): 276-85

11. Madden K, Middleton P, Cyna AM,Mathewson M, Jones L. Hypnosis for painmanagement during labour and childbirth.Chochrane Database of systematicReviews 2012, Available on-http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009356.pub2/abstract :Accessed on 1.2.2013.

Advantages of Medical Hypnosis inObstetrics:

1. Increases the patient’s ability torelax.

2. There is no depression of therespiratory or circulatory functions.

3. There is some shortening of the firststage of labour.

4. Increases the patient’s resistance toobstetric shock and the patient ismuch less exhausted.

5. Does not interfere with themechanics of labour.

6. Reduces pain by relieving the `fearpain tension’ syndrome.

7. Acute pain is most likely to be feltas the head crowns, but its intensitymay be greatly reduced.

8. It affords better control over the rateof expulsion of the head andshoulders.

9. Episiotomy can be performed quitepainlessly.

Most women feel remarkably fit andwell after hypnotic delivery.(4,5,6,7,11)

ORIGINAL ARTICLE MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

New Model of Neurodegeneration, Raid Al-Baradie et al. 5

CDP-CHOLINE NEUROPROTECTION AND VASCULARREMODELLING VIA IRS-1 MECHANISMS IN

VASCULAR DEMENTIAGROWING NEURONS ATOP MICROELECTRONIC CHIPS AS A NEW MODEL FOR

NEURODEGENERATION1*Raid Al -Baradie, 2Stephen Lynch, 3J Borresen, 4Jerzy Krupinski 5Mark Slevin

ABSTRACT

Over the past couple of decades there have been no major improvements in thetreatment of either acute ischaemic stroke or one of its major complications,neurodegenerative dementia. The majority of promising clinical trials associated withattempts to protect against the debilitating effects of Alzheimer's disease have endedprematurely following exasperation of the condition. Citicoline has been usedextensively in patient trials following stroke but strong evidence for its ability toenhance neuroprotection and improve recovery are still lacking. Following ourdemonstration that this molecule can also enhance angiogenesis/vascularization wehypothesized that it could benefit patients suffering from vascular dementia. Here wedescribe our recent findings, discuss citicoline signalling and possible links toneurovascular degradation/protection, and consider novel mathematical-biologicalsystems methodology for the identification of potential protective/therapeutic agentsagainst this disease.

أوالسكتة الدماغیة الحادةفي عالجكبیرتطورك أيلكن ھنایلم العقدین الماضیینعلى مدى:خصملالواعدة التجارب السریریةغالبیة و. االعصابالناتج من تلف الخرفوھوالرئیسیةھامضاعفاتاحد

السیتیكولین خدماست.توقفت قبل اوانھاالزھایمرمرض اآلثار المدمرة لمنلحمایةامحاوالتبالمرتبطةقدرتھ علي قویةال توجد براھین ولكنالسكتة الدماغیةي مرضعلي في التجاربعلى نطاق واسع

ان یعزز تكوین ھذا الجزيءحسب تجربتنا فیمكن ل. شفاءالوتحسینالحمایة العصبیةتعزیزعلىالخرف ین یعانون منالذیستفید منھ المرضىأنھ یمكن أنبضافترلالمما یؤدي األوعیة الدمویة

الروابطو السیتیكولینإشاراتقشوسننا، مؤخراالنتائج التي توصلنا إلیھاھناصفسنو. الوعائيالریاضیةالنظممنھجیةنظر فيكما سن،لحمایة االوعیة الدمویة لألعصاب من التلف الممكنة

.المرضھذا ضدالعالجیة المحتملةالوقائیة وعواملاللتحدیدالبیولوجیة

Received: 20 December, 2012; Accepted: 15 February, 2013*Correspondence: [email protected] Professor, Family Medicine, College of Medicine, Majmaah University, Al-Majmaah, Saudi Arabia,2Senior Lecturer, School of Computing, Mathematics & Digital Technology, Manchester MetropolitanUniversity; E-mail: [email protected]; 3Senior Lecturer, School of Computing, Mathematics & DigitalTechnology, Manchester Metropolitan University; E-mail: [email protected]; 4Professor of ClinicalNeurology, Consultant Neurologist, Head of Cerebrovascular Diseases Unit, Hospital Universitari MútuaTerrassa, Terrassa (Barcelona), Spain E-mail: [email protected]; 5Professor of Cell Pathology,SBCHS, Manchester Metropolitan University; E-mail: [email protected]



INTRODUCTION

Evidence of reduced blood-brain barrier(BBB) integrity preceding otherAlzheimer's disease (AD) pathologyprovides a strong link betweencerebrovascular pathology and AD. Inanimals models, amyloid-β peptide -injected animals exhibited a commonalityin perturbations of microvessels comparedwith those evident in AD brain(22). It wassuggested that amyloidogenesis promotesextensive neoangiogenesis leading toincreased vascular permeability andsubsequent hypervascularization in AD. Inhuman patients hypervascularity wascorroborated in a comparison ofpostmortem brain tissues from AD. Brainmicrovessels derived from patients withAD expressed numerous factors implicatedin vascular activation and angiogenesis.Signaling cascades associated with vascularactivation and angiogenesis wereupregulated in AD-derived brainmicrovessels(21). However, these newlyformed blood vessels may be non-functional. All above provides a newparadigm for integrating vascularremodeling with the pathophysiologyobserved in AD(20). Therefore, vascularactivation hypothesis could be a novel,unexplored therapeutic target in AD.

Background of our own recentinvestigations: In our recent study, wehave, for the first time, demonstrated both avascular protective, and proangiogeniceffect of citicoline using in vivo and in vitromodels(19). Our data suggests a strongprotective effect against the damagingprocess of excitotoxicity and hypoxia,similar to that experienced after acuteischaemic stroke. In regard to the possiblemechanism our protein studiesdemonstrated that citicoline inducedpERK1/2 expression, a key mitogenicsignalling protein known to be involved inangiogenesis and generally stimulated by

growth factors through interaction withtheir receptors(23).

There is the potential of citicoline toactivate intra-cellular signal transductionpathways and induce phosphorylation ofdown-stream angiogenic molecules; hencewe investigated this ability in more detailby analysis of the Kinexus-phospho-proteinWestern screening following treatment ofvascular EC with citicoline.

Interestingly, treatment with citicolinemodified the expression of only several ofthe >500 proteins on the array showing adegree of specificity. Insulin receptorsubstrate-1 (IRS-1) was phosphorylated inthe presence of citicoline. IRS-1 over-expression was attributed to increasedangiogenesis in human EC in associationwith increased Akt and VEGF-Aexpression [Stephens et al, 2012], whilst invivo, antisense IRS-1 sequences deliveredby sub-conjunctival injection inhibited ratcorneal neovascularisation(18), and whendelivered by means of eye-drops (GS-101)were found to be tolerable in a phase-1clinical trial and may be sufficient toprevent neovascularisation in disease suchas retinopathy and neovascular glaucoma(15).

Therefore, IRS-1 represents a potentmodulator of pro-angiogenic signallingcascades in vascular EC and as such, sincewe have shown both in vitro, and in the ratmodel of temporary MCAO that citicolineinduces phosphorylation of IRS-1 andconcomitant EC activation and increasedvascularisation. This could be a key novelmechanism of action of citicolineimplicated in stroke recovery pathways andangiogenesis until now. This may be anextremely valuable novel finding in regardto understanding the potential mechanismsthrough which citicoline treatment resultsin patient recovery, since both protection ofEC and induction and maintenance ofangiogenesis is key to both short-term and



chronic re-vascularization after strokeimpacting indirectly but significantly alsoon neuronal survival and re-integration(17).Figure one for details(19).

IRS-1 in neurodegeneration: Onlyrecently, it has been demonstrated that beta-amyloid (Abeta) oligomers are implicatedin Alzheimer's disease leading tophosphorylation and degradation of theadaptor protein insulin receptor substrate-1(IRS-1). IRS-1 couples insulin and othertrophic factor receptors to downstreamkinases and neuroprotective signaling.Increased phospho-IRS-1 is found in ADbrain. Levels of IRS-1 and their activatedkinases correlated positively with those of

oligomeric Aβ plaques and are negativelyassociated with episodic and workingmemory, even after adjusting for Aβplaques, neurofibrillary tangles, and APOEε4. Brain insulin resistance thus appears tobe an early and common feature of AD, aphenomenon accompanied by IGF-1resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβoligomers and yet promoting cognitivedecline independent of classic ADpathology(17,18)

New assays for neuronal degeneration: Itis now understood that periodic behaviouris not confined to a limited number of

physiological processes but is abundant inmost biological systems. Periodicity inprocesses of the human body encompassphenomena such as genetic interactions,heartbeat rhythms, oscillating secretory,retina and muscle cells, cytoskeletalstructures, bacterial oscillations, rhythmicbehaviour in growth and development, andmost importantly for this study, neuronaloscillations(1-3). In 1952, whilst modellingneurons, Hodgkin and Huxley were able toaccurately model the action potential in thegiant squid axon(4). Their nonlinearordinary differential equations approximateelectrical characteristics of excitableoscillatory cells such as cardiomyocytesand neurons. In 2009, Borresen and Lynch5

published a paper suggesting a novel ideabased on biological neural computingutilising the Hodgkin-Huxley equations,and following this work, three years laterUK and International patents werepublished(6). The patent illustrates how it ispossible to construct binary logic gatesfrom biological neurons grown on a chip. Itis proposed that neurons could be grown ona chip and that they could be trained toperform certain logical operations. Binaryoscillator logic gates could then be used totest drugs that may halt or reversesymptoms of neurological disorders such asAlzheimer’s, Parkinson’s disease andepilepsy. A number of research groups are

Figure 1 shows the operation of a binary half-adder based on Fitzhugh-Nagumo oscillators(which are simplified versions of the Hodgkin-Huxley models).



now able to grow neurons on chips using avariety of techniques including an alignedmicro-contact printing technique, patchclamping (which yields very accurateinformation but is invasive) andextracellular recordings by means ofexternal micro-transducers or opticalmeasurements (which are non-invasive)(8-

13), and it has recently been shown thatParkin diseased neurons can also be grownon a chip(14). In 2012(15), it was shown thatciticoline could be used as a protectivetreatment against Alzheimer’s following astroke.

Based on our previous results and citicolineinvolvement in blood vessel remodellingvia IRS-1 pathway together with a newevidence of vascular hypothesis in AD, weaim to develop an in vitro assay forneuronal degradation of Alzheimer’sdiseased neurons. In this model we willstudy effects of citicoline/IRS-1 pathwayson neurones grown on atop microelectronicchips in conditions of ischemia andneurodegeneration. It is a multidisciplinaryproject drawing on Medicine, Biology,Mathematics, Chemistry, Physics,Engineering and Computing.

Figure 3: Schematic of a binary oscillatorhalf-adder using biological neurons.Neurons N+ depict excitatory neurons andneuron N- depicts an inhibitory interneuron.Using the logic circuitry highlighted byLynch et al(6,7,16), we believe it is possibleto build an assay for neuronal degradation.Implementation of the half-adder usingbiological neurons on a chip will requirethree neurons as neurons are eitherexcitatory or inhibitory, they cannot beboth. Figure 3 shows a schematic of thebiological half-adder

FUTURE DEVELOPMENTSWe have already shown that it is possible toconstruct logic gates and memory usingthreshold oscillator logic(16). Wedemonstrated how coupled thresholdoscillators (neurons) may be used toperform binary logic in a manner entirely

Figure 2: (a) Schematic of a binaryoscillator half-adder. (b) Numericalsimulation: Time series showing correctlogic function of a half-adder. An oscillationcorresponds to a 1 in binary and nooscillation is a zero. The sum oscillatorwill oscillate if either or is active. Thecarry oscillator will oscillate if bothand are active. An inhibitory connection,say , from to suppresses oscillator

if is active.



consistent with modern computerarchitectures.

Figure 2(a) demonstrates a viable circuitschematic for half-adder implementationusing two neuronal oscillators labelledand and two inputs and , whichmay themselves be the output from otherneurons in a more complex circuit. In orderto perform the logical operations it isnecessary that either neurons with differingthresholds be used or the connectionsbetween the neurons should be of differingweights, indicated by and in thefigure. Figure 2(b) displays a time seriesplot of a binary half-adder. Schematics andtime series for a two oscillator full adder, athree oscillator seven input full adder, a 2x2bit binary multiplier and a set reset flip-flop(used for memory) are also displayed(16).

CONCLUSIONS

Future work: Our current work isstructured in five main steps:

1. Growing neurons on chips. 2. Design ofa new model of threshold logic based onbiological neurons. 3. Simulation ofthreshold oscillator logic using a suitablemathematical package. 4. Building neuronallogic circuits using neurons. 5. Growth ofAlzheimer/vascular dementia diseasedneurons on chip and measurement ofneuronal degradation for different citicolinedosages.

This methodology will allow for the sub-cellular resolution (micro-pixel) withinneurobiological preparations for exampleneuron-neuron interfaces and indeed later,entire neuronal networks. This proposedmethodology has potential application in allareas of neuroscience, medical diagnosticsand pharmacology.

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13. Arthur J.V., Merolla P.A., Akopyan F.Building block of a programmableneuromorphic substrate: A digitalneurosynaptic core, International JointConference on Neural Networks 2012.



14. Jiang HB., Ren Y., Yuen EY. Parkincontrols dopamine utilization in humanmidbrain dopaminergic neurons derivedfrom induced pluripotent stem cells, NatureCommunications 2012; 3: Article number668.

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17. Talbot K, Wang HY, Kazi H, Han LY,Bakshi KP, Stucky A, Fuino RL,Kawaguchi KR, Samoyedny AJ, WilsonRS, Arvanitakis Z, Schneider JA, Wolf BA,Bennett DA, Trojanowski JQ, Arnold SE.Demonstrated brain insulin resistance inAlzheimer's disease patients is associatedwith IGF-1 resistance, IRS-1 dysregulation,and cognitive decline.J Clin Invest. 2012Apr 2;122(4):1316-38. doi:10.1172/JCI59903.

18. O'Neill C, Kiely AP, Coakley MF,Manning S, Long-Smith CM Insulin andIGF-1 signalling: longevity, proteinhomoeostasis and Alzheimer'sdisease.Biochem Soc Trans. 2012 Aug;40(4):721-7. doi: 10.1042/BST20120080.

19. Krupinski J, Abudawood M, Matou-NasriS, Al-Baradie R, Petcu E, Justicia C, PlanasA, Liu D, Rovira N, Grau-Slevin M,

Secades J, Slevin M.Citicoline inducesangiogenesis improving survival ofvascular/human brain microvesselendothelial cells through pathwaysinvolving ERK1/2 and insulin receptorsubstrate-1.Vasc Cell. 2012 Dec 10;4(1):20.[Epub ahead of print]

20. Biron KE, Dickstein DL, Gopaul R,Jefferies WAPLoS One. 2011;6(8):e23789.doi: 10.1371/journal.pone.0023789. Epub2011 Aug 31.Amyloid triggers extensivecerebral angiogenesis causing blood brainbarrier permeability and hypervascularity inAlzheimer's disease.

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Gentamicin Induced Neurodegenerative Changes, Rehan M Asad et al. 11

GENTAMICIN INDUCED NEURODEGENRATIVE CHANGES INAUDITORY CORTEX OF ADULT ALBINO RATS

1*Rehan M Asad, 2Moattar R Rizvi, 3Sami Waqas, 4Kamran Afzal

ABSTRACT

Background: Aminoglycoside-induced nephrotoxicity and ototoxicity is a major clinicalproblem. Aminoglycosides have good activity against many multi-drug resistant Gramnegative bacilli and are therefore important for treating serious infections due to theseorganisms in adults and children including neonates. Gentamicin, due to it costeffectiveness has been used in most of the trials as compared to other aminoglycosides.Most studies documented the peripheral toxicities of gentamicin without any concern ofcentral neurotoxicity. Objective: To observe Gentamicin induced neurodegenerativechanges in auditory cortex of adult albino rats. Methods: It was an experimental study.Twenty rats were randomly divided in two groups; Group I (Experimental: n = 10)received intramuscular injection of Gentamicin for twenty one days and Group II(Control: n =10) received normal saline intramuscularly. Histological preparationswere done on sections obtained from the area around lateral sulcus of rat cortex. Thephotomicrographs of the relevant stained sections were taken with the aid of a lightmicroscope. Results: Light microscopic examination of the auditory cortex sectionsobtained from gentamicin injected rats (Group I) revealed severe neurodegenerativechanges as compared to the rats in (Group II). Conclusion: Exposure of rats toGentamicin for three weeks showed severe neurodegenerative changes. Keywords:Aminoglycosides, Auditory Cortex, Nephrotoxicity, Ototoxicity

. الرئیسیةاالكلینیكیةالمشاكلمناألمینوجلیكوزایدمنالناتجاالذنوتسممىالكلتسممیعتبر: ملخصوبالتاليعقار،منألكثرالمقاومةالجرامسلبیةیاتالعصمنكثیرعليالقضاءفيجیدةخاصیةلالمینوجلیكوزاید

. الوالدةحدیثيذلكفيبماواألطفالالبالغینفيالعصیاتھذهمنالناتجةالخطیرةااللتھاباتلعالجمھمةفھياساتالدرمعظم. تكلفتھلقلةنظرااألخرىاألمینوجلیكوزایدمعبالمقارنةالتجاربمعظمفيالجنتامیسینویستخدم

الذيالتلفمالحظة: الھدف. المركزيالعصبيالتسممعليتركیزأيدونللجنتامیسینالطرفيبالتسمماھتمتتقسیمتمحیثتجریبیة،دراسة: الدراسةمنھج. البالغةللجرذانالسمعیةالقشرةفيلألعصابالجنتامیسینیسببھ

العضلفيحقنھاوتم) 10= وعددھالتجریبیةا(األولىالمجموعةمجموعتین،اليعشوائیافأرعشرون. بالعضلملحبمحلولوحقنت) 10= وعددھاللمقارنة(الثانیةوالمجموعة. یوماوعشرونواحدلمدةبالجنتامیسین

منالمجھريالتصویرتم. للفئرانالمخیةللقشرةالخارجيبالتلمالمحیطةالمنطقةمننسیجیةعیناتأخذتوقدالحصولتمالتيالسمعیةالقشرةلنسیجالمجھريالفحصكشف: النتائج. المجھربمساعدةالصلةذاتاألقسام

الفئرانمعبالمقارنةلألعصابشدیدتلفعنكشف) األولىالمجموعة(بالجنتامیسینحقنتالتيالفئرانمنعلیھالألعصابشدیدتلفاليأديأسابیعثةثاللمدةللجنتامیسینالفئرانتعرض: االستنتاج). الثانیةالمجموعة(في

Received: 11 December, 2012; Accepted: 20 February, 2013*Correspondence: [email protected] Professor, Department of Basic Sciences, College of Medicine, Majmaah University. 2AssistantProfessor, Department of Med. Lab Tech, College of Applied Medical Science, Majmaah University; 3Lecturer,Department of Public Health and Community Medicine, College of Medicine, Majmaah University; 4Lecturer,Department of Basic Sciences, College of Medicine, Majmaah University.



INTRODUCTION

Gentamicin is a member ofaminoglycoside family of antibioticsproduced by micrmonospora pupurea. Itcan be used in different type of infections,including gram positive and gram negativebacteria. In addition, it has significanteffect against pseudomonas. Gentamicinworks by inhibiting protein synthesis. Itbinds very strongly to ribosome’s (30 S)sub unit and interferes with Proteinsynthesis. Gentamicin enters the cell bybinding to negatively chargedphospholipids and enters the cytosol viaelectron transport linked system and thusneed oxygen and ATP to enter cytosol andbe effective. Therefore Gentamicinantibiotics are effective only in aerobicbacteria. The structure of Gentamicin isconsistent with the aminoglycosidestructural activity relationship (SAR),except with a few minor changes.Specifically ring one have methylatedamine and one axial hydroxyl group. Themethylation of amine will retain its activityand will lower the susceptibility totransferase, which are the enzyme thatprobably causes inactivation.

Clinically, Gentamicin is used for someurinary tract infection, burns somepneumonia and bone and joint infectioncaused by gram negative bacteria. Themost common clinical application (eitheralone or as part of combination therapy) ofthe Gentamicin is in the treatment ofserious infections caused by aerobic gram-negative bacilli. Gentamicin has also beenused for the treatment of selectedstaphylococcal and enterococcalinfections. Gentamicin is the usual all-purpose agent of choice(11). Gentamicin ismore active against serratia marcescens.Gentamicin has been shown to destabilizethe outer membrane of Pseudomonasaeruginosa and form holes in the cell wall,independent of its action on ribosomes(Kadurangamuwa et al, 1993). This action

of the aminoglycosides may be the mostimportant.

Ototoxicity is the most important adverseeffects clinically, and had dominatedattempts to rationalize aminoglycosidedosing(2). A well-known factor i.e. hearingloss occurred as a result of degeneration ofthe hair cells of the cochlea, beginning atthe basal coil and progressing towards theapex. High frequency hearing loss wasfollowed by loss of lower frequency.According to Takada and Schacht, (1982)disequilibrium and ataxia were mainsymptoms of vestibulotoxicity. Both acute(reversible) and chronic (irreversible)ototoxicity had been observed. Ganesan etal, (1983) described that chronic toxicitywas related to aminoglycoside-phosphoinositol binding, leading to alteredmembrane structure and permeability.According to Kahlmeter and Dahlager(10)

gentamicin toxicity was the most commonsingle known cause of bilateralvestibulopathy. In pathologic studies,severe aminoglycoside toxicity wasassociated with death of inner ear haircells(13). Oei et al described doses that werenot enough to kill hair cells but damagedtheir motion sensitive hairs (sterocilia),making them unable to respond to motion,at least for some months(13). Guan et al(8)

described that the mechanism of toxicitywas through reduction of mitochondrialprotein synthesis and the interference withmitochondrial function would be expectedto cause cellular disruption throughreduction in ATP production. Gentamicinis equally vestibulotoxic and ototoxic(Schacht, 1993).

Neuromuscular blockade is also commonlyreported side effect. Patients withneuromuscular blockade may presentclinically numbness, twitching of musclesand seizures. Said et al(14) had studied thataminoglycoside antibiotic blocked thetransmurally elicited twitches of ileum in aconcentration manner. According to



Santos et al(15) gentamicin enhancesneuromuscular impairment and death ofbotulinum toxin-exposed mice.Aminoglycosides potentiateneuromuscular weakness caused bybotulinum toxin.

Ototoxicity, nephrotoxicity andneuromuscular blockade are well knownside effect but there are few studies thatelaborated neurotoxic effect ofGentamicin. Aminoglycoside antibioticsare known to cross blood brain barrier andwhole nervous system is exposed to thesedrugs. Evidence is available suggestingcentral neurotoxicity of aminoglycosides(6).

Exact mechanism of action on centralnervous system is still unclear. Based onthe literature we planned this study toobserve the neurodegenerative effects ofGentamicin on adult albino rats.

MATERIAL AND METHODS

It was an Experimental study. Twentyadult albino rats weighing 130±20 gramswere obtained from Central Animal House,J. N Medical College, AMU, Aligarh.They were divided into two groups. GroupI: Experimental (n = 10) received aninjection of 135 mg/kg body weight ofGentamicin intramuscularly for twenty onedays (Gentamicin WHO food Additivesseries 34, www.inchem.org\documents).Group II: Controls (n = 10) receivednormal saline in same volume byintramuscular route for twenty onedays.The rats were kept in plastic cages ina room 12:12 light/dark photoperiod,temperature of 20-30C and relativehumidity of 50-60%. Ethical approval wassought and received from the Departmentof Anatomy, JN Medical College, AMU,Aligarh, UP, India.

The rats were decapitated on 22nd day ofthe experiment. The skin as well as softtissues surrounding the cranium wasremoved. Sections were obtained from thearea around lateral sulcus of rat cortex.

The area around the lateral sulcus of ratcerebral cortex is the site of primaryauditory area. Sections of auditory cortexto were obtained from both sides ofcerebrum to observe neurodegenerativechanges. After obtaining samples from theauditory area of cerebral cortex (controland experimental), tissue samples areweighed on digital weighing pan (error ofweighing pan is calculated about 0.022grams). Accurate weight of the sampleshas been calculated by deducting standarderror from estimated weight.

Fig.1 Photomicrograph of the auditorycortex of adult albino rat (Experimentalanimal) showing edema and cytoplasmicvacuolation in II (external granular) andIII (pyramidal) layers (Depicted by Arrow).H&E X100.

The slides with mounted section fromGroup I and Group II were dried in anincubator at 450C for 4 hour for the properattachment of the sections on the slides.The mounted sections were stained byHaematoxylin & Eosin(3) and Thioninstain. The photomicrographs of therelevant stained sections were taken withthe aid of a light microscope.

RESULTS

Auditory cortex of adult albino rat(Experimental) animal showed oedema,cytoplasmic vacoulation in II (Externalgranular) and III (pyramidal) layers[Fig.1].



Photomicrograph of the auditory cortex ofadult albino rat (Experimental) animalshowing neuronal (Pyramidal and Stellate)cells with cytoplasmic swelling and ill-defined cytoplasmic margins due toGentamicin toxicity [Fig.2].

Fig.2 Photomicrograph of auditory cortexof adult albino rat (Experimental) showingneuronal cells with cytoplasmic swellingand ill-defined cytoplasmic margins due togentamicin toxicity

Photomicrograph of the auditory cortex ofadult albino rat (Experimental) animalshows signs of mild degeneration i.e.,cytoplasm swelling and eccentric nucleusin II (External granular) and III (Pyramidalcell l) layers [Fig.3].

Fig. 3 Photomicrograph of the auditorycortex of adult albino rat (Experimental)cytoplasmic swelling and eccentric nucleuswith mild degenerative changes (depictingby arrow). H&E X400

Generalized dispersion of Nissl substancewith swollen cells is present inPhotomicrograph of the auditory cortex of

adult albino rat (Experimental animal)[Fig.6]

Photomicrograph of the auditory cortex ofadult albino rat (Experimental animal)shows cytoplasm vacuolation, mild degreeof degenerative change and lymphocyticinfiltration [Fig.4].

Fig. 4 Photomicograph of the auditorycortex of Albino rat (Experimental)showing cytoplasmic vacuolation, milddegree of degenerative change andlymphocytic infiltration. H&E X 400

Fig. 5 Photomicrograph of the auditorycortex of adult albino rat (Experimentalgroup) showing nuclear (irregularmargins, chromatin clumping andkaryorrhexis) and cytoplasmic(vacoulation) degenerative changes. H&EX400.

Photomicrograph of the auditory cortex ofadult albino rat (Experimental animal)shows signs of nuclear (irregular margins,chromatin clumping and karyorrhexis) andcytoplasmic (vacuolation) degenerativechanges [Fig.5].



.

Fig. 6 Photomicrograph of the auditorycortex of an Albino rat showing cellswhich are swollen and their nisslsubstance showing generalized dispersion.Thionin stain X 400

DISCUSSION

The present study was designed to observethe neurodegenerative effects ofGentamicin on auditory cortex of adultalbino rats. Findings in the literature areavailable showing ototoxicity,neuromuscular blockade and neurotoxicitycaused by aminoglycosides.

Histological findings in present study weresuggestive of degenerative changes inexperimental group. Oedema andcytoplasmic vacuolation [Fig.1] werepresent in layer I (external granular layer)and layer II (pyramidal cell layer).Neuronal cells show cytoplasmic swellingwith ill-defined cytoplasmic margins[Fig.2]. Pyramidal cells of layer II(pyramidal cell layer) show eccentricnuclei with mild degree of degenerativechanges [Fig.3]. Lymphocytic infiltrationwas also found [Fig.5]. Cytoplasmicvacuolation [Fig.5] was also found inpyramidal cells of layer V (ganglioniclayer). Irregular nuclear margins,chromatin clumping, karyorrhexis andcytoplamic vacuolation [Fig.5] werepresent in neuronal cells of layer V(ganglionic layer). Neuronal cell swellingwith generalised dispersion of Nissl

substance was found in Thionin staining[Fig.6]. Neurotoxic injury induces changesin nerve cell body which present asswelling and vacuolization(1). Prominentnuclear changes with increased size,irregular outline and dispersion ofchromatin are characteristic features ofneurotoxic injury(5).

Histological findings of the present studywere in conformity with neurohistologicalstudy on the effect of kanamycin oncentral auditory auditory pathwayconducted by Faruqi et al which showeddegenerative changes in the cochlearnucleus, inferior colliculus and auditorycortex(5). Decreased staining of Nisslsubstance of neurons was found in theauditory cortex of kanamycin intoxicatedrats. It was explained by Hotz et al thataminoglycoside therapy affects both innerear and central auditory pathways(9).

Histochemical study of gentamicinintoxicated rats showed increased activityof acetylcholinesterase in cochlearnucleus(4). Gentamicin might producecentral toxicity by altering concentrationof acetylcholine. Watanabe et al reporteddistinctive lesions occurred in brain stemof patients who were treated withparenteral and intrathecal gentamicinsulfate for Pseudomonas aeruginosameningitis (16).

In an experimental study conducted byWantabe et al, it was reported that a singleintracisternal injection of 0.4 ml of 1.25and 2.5 percent gentamicin sulfate withpreservative to healthy adult rabbitsproduce multiple, minute, disseminated,spongy lesions with cytoplasmicvacuolation of nerve cells (16).

This finding is similar with cytoplasmicvacuolation found in neuronal cells ofauditory cortex in present study.Convulsions, encephalopathy, confusion,hallucinations, mental depression andsometimes pleocytosis observed in



cerebrospinal fluid of humans, are clinicalside effects of gentamicin on centralnervous system(7).

CONCLUSION

Exposure of rats to Gentamicin for threeweeks showed severe Neurodegenerativechanges at microscopic level.

ACKNOWLEDGEMENTS

I am delighted to express my deep sense ofgratitude to my honourable teacherProfessor N A Faruqi, Professor,Department of Anatomy, for his constanthelp and careful guidance and directionduring my work. I would like to thanks myparents, wife for their support. I would liketo thanks my little daughter whose loveand affection was source of inspiration forme.

REFERENCES1. Aschners M and Costa LG. The

reactive astrocytes. The role of Glia inNeurotoxicity, 2nd edition, 2004, 74.

2. Begg EJ and Barclay ML ().Aminoglycosides--50 years on. Br JClin Pharmacol. 1995; 39(6): 597-603.

3. Drury RAB, Wallington EA, CameronR. Carleton's Histological Techniques:4th ed., Oxford University Press NY,U.S.A 1967; 279-280.

4. Faruqi NA, Aslam M, Baitullah andHasan SA. Acetylcholineesteraseactivity in cochlear nucleus afterkanamycin and Gentamicinintoxication. Pakistan Journal ofotorhinolaryngology. 1992; 8: 209-212.

5. Faruqi NA, Hasan M, Hasan SA,Khan MA and Ikramullah.Neurohistological study on the effectof kanamycin on central auditorypathway. Current medical practice1986; 30(11): 289-294.

6. Faruqi NA, Khan HS. Effect ofstreptomycin and kanamycin onCentral nervous system: An

Experimental study. Indian Journal ofExperimental Biology 1986; 24: 97-99.

7. Fernando R and Jayakodi RL.Gentamicin Sulfate. IPCS INCHEMHOME 1994.

8. Guan MX, Fischel-Ghodsian N,Attardi G. A biochemical basis for theinherited susceptibility toaminoglycoside ototoxicity. Hum MolGenet 2000; 9:1787–1793.

9. Hotz MA, Allum JHJ, and KauffmanG. Shift in barin stem latenciesfollowing plasma level controlledanimogylcosides therapy. Europeanarchives of otorhinolaryngology 1990;4:27.

10. Kahlmeter G, Dahlager JI.Aminoglycoside toxicity: a review ofclinical studies published between1975 and 1982. J. Antimicrob.Chemother 1984; 13 (suppl.A): 9-22.

11. Kumana CR and Yuen KY. Parenteralaminoglycoside therapy: Selection,administration and monitoring. Drugs1994; 47(6):902–913.

12. Oei Markus LYM, Segenhout HansM, Dijk Freark, Stokroos Ietse, vander Want, Johannes J. L, Albers FransWJ. Otology & Neurotology 2004; 25(1): 57-64 Vestibular Problems.

13. Polgar and others. Anatomic andmorphometric changes to gerbilposterior cristas followingtranstympanic administration ofgentamicin and streptomycin. JARO2001; 02:147-158.

14. Said AA, Matsuki N, Kasuya Y.Effects of Aminoglycoside Antibioticson Cholinergic Autonomic NervousTransmission. Pharmacology &Toxicology 1995; 76 (2) 128–132.

15. Santos JI, Swenson P, and GlasgowLA. Potentiation of clostridiumbotulinum toxin by aminoglycosideantibiotics. Clinical and laboratoryobservations. Pediatrics 1981; 68:50-54.



16. Wantabe I, Hodges GR, Dworzack,DL. Chemical injury of the spinal cordof the rabbit after intracisternal

injection of gentamicin. J.Neuropath.Exp.Neurol 1979; 38(2):104-13.


Prevalence of Vitamin D Deficiency in type 2 DM patients, Mansour Al-Zaharani 18

THE PREVALENCE OF VITAMIN D DEFICIENCY IN TYPE 2DIABETIC PATIENTS

1*Mansour Al-Zaharani

ABSTRACT

Background: Recently, there is accumulating evidence to suggest that altered vitaminD and calcium homeostasis may play a role in the development and control of type 2DM. Objective: The aim of the current study was to estimate the prevalence of vitaminD deficiency in type 2 DM. Material and Methods: This is a cross-sectional studythrough screening of a random sample of patients with type 2 DM who recruited fromDiabetes Clinics in Family Medicine and Primary Health Care at Health CareSpecialty Clinic (HCSC)-King Abdul-Aziz Medical City in Saudi Arabia, Riyadh. Foreligible patients, who matched the selection criteria, the following laboratory tests wereperformed; vitamin D level in form of (25 OHD), HbA1c, fasting blood glucose andlipid profile. Results: In the current study, 248 type 2 diabetic patients had beenscreened for vitamin D deficiency. The great majority of diabetic patients hadsuboptimal level of vitamin D (98.4%). Almost three-quarters of female diabeticpatients (73.6%) compared to less than half of male diabetic patients (46.9%) hadvitamin D deficiency while approximately half of male patients (50.8% and one quarterof female patients (25.6%) had vitamin D insufficiency. This difference between themwas statistically significant (chi-sq.=18.5, P<0.001). Conclusions: The results of ourstudy show that the great majority of type 2 diabetic patients having suboptimal vitaminD level. The majority of female diabetic patients (73.6%) while 46.9% of male diabeticpatients were vitamin D deficient. Key words: vitamin D, vitamin D deficiency, diabetesmellitus

یلعبقدالجسمفيوموالكالسیدفیتامینمستوىتوازنأنإلىتشیرالتياألدلةتزایدتاألخیرةاآلونةفي: ملخصمعرفةإلىالدراسةھذهھدفت:الدراسةمنالھدف. السكرمستوىفيالتحكمأوالسكريبداءاإلصابةفيدوراً فیھاتممسحیھدراسةھذه:منھج الدراسة.السكريداءمنالثانيالنوعمرضىبیندفیتامیننقصانتشارمعدل

للحرسالطبیةعبدالعزیزالملكلمدینةالتابعةالسكرعیاداتفيكوذليالسكرىمرضمنعشوائیةعینةأخذشروطعلیھمانطبقتالذینللمرضىالتالیةالفحوصاتعملتموقد.بالریاضاالولیةالرعایةمراكزفيالوطني. الدمفيالكولیسترولومستوىالصیامأثناءالسكرمعدل, للسكرالتراكميالمعدل, دفیتامینمستوى: البحثوذلكدفیتامینمستوىفينقصلدیھمالمرضىغالبیةأنوجدحیثمریض248لـالفحوصاتعملتم:النتائجحیثالرجالعندمنھاأكبرالنساءعنددفیتامیننقصنسبةأنالدراسةوجدتكما. المرضىمن% 98.4بنسبةھذهأظھرت: الخاتمة% . 46.9بالرجالمقارنة% 73.6دفیتامینمعدلنقصمنیعانونالذینالنساءنسبةبلغت

فيالنقصنسبةأنأظھرتكما. دفیتامینمعدلفينقصلدیھمالسكرمنالثانيالنوعمرضىغالبیةأنالدراسة.الرجالعندمنھأعلىالنساءعنددفیتامین

Received: 7 December, 2012; Accepted: 1 March, 2013*Correspondence: [email protected] Professor, Family Medicine, College of Medicine, Majmaah University, Al-Majmaah, Saudi Arabia



INTRODUCTION

The prevalence of Diabetes Mellitus inSaudi Arabia is one of the highest reportedin the world, reaching up to 30% in a recentstudy(1).

Recently, researchers have shown anincreased interest in the vitamin Ddeficiency. The major and most well-known function of vitamin D is to maintaincalcium and phosphorus homeostasis andpromote bone mineralization. Morerecently there is accumulating evidence tosuggest that altered vitamin D and calciumhomeostasis may also play a role in thedevelopment of type 2 DM(2, 3). In most,(4-7)

but not all,(8,9) case-control studies, patientswith type 2 DM or glucose intolerance arefound to have lower serum 25-OHDconcentration compared with controlswithout diabetes. Hypovitaminosis D,owing to depletion or relative vitamin Dresistance, has long been suspected to be arisk factor for glucose intolerance. A reportfrom Martins and colleagues on data fromover 15,000 adults in the Third NationalHealth and Nutrition Examination Survey isperhaps the best recent evidence on vitaminD and the general population(21). The25(OH)-vitamin D levels were lower indiabetics, women, the elderly, and racialminorities, groups that are at increased riskof having chronic kidney disease (CKD)(21).

In type 2 diabetes, vitamin D may improvethe cellular transfer of insulin message.Vitamin D may also contribute to survivalof the islets and inhibit inflammatoryprocesses. Some authors(10) report arelationship between low vitamin D levelsin humans and reduced glucose stimulatedinsulin secretion. In some trialsimprovement of (glucose-stimulated)insulin release after vitamin Dsupplementation has been found but otherstudies have not confirmed this(11, 12) Mostprospective studies are short term and givevariable outcomes about the relationship

between vitamin D levels and thedevelopment of diabetes(13, 14).

No local published researches have beenfound that surveyed the prevalence ofvitamin D deficiency in type 2 DM patients.

The aim of the current study was toinvestigate the prevalence of vitamin Ddeficiency in diabetic people.

SUBJECTS AND METHODS

This is a case-control study includedscreening of 248 diabetic patients toestimate the prevalence of suboptimalvitamin D level.

A random sample of patients with type 2DM were recruited in the period from Julyto the end of September 2009, fromDiabetes Clinics in Family Medicine andPrimary Health Care at Health CareSpecialty Clinic (HCSC)-King Abdul-AzizMedical City in Saudi Arabia-Riyadh.HCSC is a primary care and familymedicine center, located at northeasternpart of Riyadh. It services the soldiers andtheir dependents that belong to itscatchments areas. We excluded diabeticpatients with renal insufficiency,gestational diabetes and those takingvitamin D supplements.

For eligible patients, who matched theselection criteria, the following laboratorytests were performed; vitamin D level inform of (25 OHD), HbA1c and fastingblood glucose.

In order to identify diabetic patients withsuboptimal vitamin D levels, the subjectswere given appointment after two to threeweeks to check their vitamin D levelresults. Blood samples were obtained from248 patients who received blood work uprequests. Total serum 25(OH) vit D levelswere measured using the LIAISON ® 25OH Vitamins D TOTAL assay, from



DiaSorin, USA. With following ranges forthe classifications of vitamin D status:

Vitamin D status 25 OH Vitamin D

Deficiency <25 nmol/L

Insufficiency 25-75 nmol/L

Sufficiency 75-250 nmol/L

Toxicity >250 nmol/L

STATISTICAL ANALYSIS

Vitamin D level was treated as anindependent variable and A1C, FBS, lipidprofile, Body Mass Index and bloodpressure were treated as dependentvariables in statistical analysis. Datamanagement and analysis was performedusing Statistical Package for Socialsciences (SPSS) software, version 16.

The study was conducted on humanparticipants. All data was maintained in asecure and confidential manner. Allparticipants' identification and associateddata were separated. All data was analysedas total population in a manner thatindividual privacy was maintained. Allrecords, results and progress, bothelectronic and written will be maintainedwith the researcher for a minimum periodof two years in case of review. Thisstatement was approved by the hospitalresearch committee. A written informedconsent taken from the participants in theintervention group clarifying the mainpurpose of the study, the importance of therespondent's views, the researchers name.Also, open letters explaining the steps ofthe study were distributed to allparticipants.

RESULTS

In the current study, 248 type 2 diabeticpatients had been screened for vitamin Ddeficiency.

Figure 1: prevalence of vitamin Ddeficiency in type 2 diabetic patients of thestudy sample.

Figure (1) illustrates that more than half ofthem (149; 59.8%) were deficient invitamin D (< 25 nmol/L), 96 patients(38.6%) had insufficient vitamin D level(25, 1-74.9 nmol/L) while only 4 patients(1.6%) had optimal vitamin D level (> 75nmol/L). Thus, the great majority ofdiabetic patients had suboptimal level ofvitamin D (98.4%).

Figure 2: Prevalence of vitamin Ddeficiency among type 2 diabetic patientsaccording to gender.

From figure 2, it is obvious that almostthree-quarters of female diabetic patients(73.6%) compared to less than half of malediabetic patients (46.9%) had vitamin Ddeficiency while approximately half ofmale patients (50.8% and one quarter offemale patients (25.6%) had vitamin Dinsufficiency. This difference between them



was statistically significant (chi-sq.=18.5,P<0.001).

DISCUSSION

Vitamin D deficiency or insufficiency isnow recognized as a worldwide problem forboth children and adults. (3) According toseveral studies, 40 to 100% of U.S. andEuropean elderly men and women stillliving in the community (not in nursinghomes) are deficient in vitamin D.(15)

However, even in the sunniest areas,vitamin D deficiency is common whenmost of the skin is shielded from the sun.Studies in Saudi Arabia, the United ArabEmirates, Australia, Turkey, India, andLebanon, 30 to 50% of children and adultshad 25-hydroxyvitamin D levels under 50nmol/L(16-18). Moreover, The prevalence oflow serum 25-hydroxyvitamin D (<50nmol/l) is more common in diabeticscompared with non-diabetics 83% vs. 70%;p = 0.07.(19) The results of our study showthat 98.4% of our participants havingsuboptimal vitamin D level. This studyproduced results which corroborate thefindings of a great deal of the previouswork in this field. The majority of femalepatients 73.6% were vitamin D deficient(<25 nmol/L) while 46.9% of male patients.This result could be attributed to less sunexposure in female patients relative to malepatients in our community.

It is not clear what levels of vitamin D aresufficient. It may be that levels of vitaminD within the normal range for an effect onbone formation and calcium metabolism aretoo low to reduce the emergence of diabetesmellitus and to improve glucosehomeostasis, but a clear minimum level of25(OH)D3 needed for slowing thedevelopment of diabetes mellitus has notbeen established. The prescription of extravitamin D during the early phase ofdiabetes is still experimental(20).

Our study has considerable strength as thefirst local study, up to our knowledge, toestimate the prevalence of vitamin Ddeficiency among type 2 diabetic patients.Also, the measurements of vitamin D wasperformed in one laboratory, hencecomparison of serum 25(OH) D levels wasvalid, we included a considerable largegroup of subjects and the response rate washigh (91.5%).

CONCLUSION

The results of our study show that the greatmajority of our participants havingsuboptimal vitamin D level. The majorityof female patients (73.6%) while 46.9% ofmale patients were vitamin D deficient.

REFERENCES

1. Alqurashi KA, Aljabri KS, Bokhari SA.Prevalence of diabetes mellitus in a Saudicommunity. Ann Saudi Med. 2011 Jan-Feb;31(1):19-23.

2. Bischoff-Ferrari HA, Giovannucci E,Willett WC, Dietrich T, Dawson-HughesB. Estimation of optimal serumconcentrations of 25-hydroxyvitamin D formultiple health outcomes. Am J Clin Nutr2006; 84:18–28.

3. Holick MF. High prevalence of vitamin Dinadequacy and implications for health.Mayo Clin Proc 2006; 81:353–373.

4. Cigolini M, Iagulli MP, Miconi V,Galiotto M, Lombardi S, Targher G.Serum 25-hydroxyvitamin D3concentrations and prevalence ofcardiovascular disease among type 2diabetic patients. Diabetes Care 2006;29:722–724.

5. Hypponen E, Power C. Vitamin D statusand glucose homeostasis in the 1958British birth cohort: the role of obesity.Diabetes Care 2006; 29:2244–2246.

6. Aksoy H, Akcay F, Kurtul N, Baykal O,Avci B. Serum 1,25 dihydroxy vitamin D(1,25(OH)2D3), 25 hydroxy vitamin D(25(OH)D) and parathormone levels indiabetic retinopathy. Clin Biochem 2000;33:47–51.



7. Isaia G, Giorgino R, Adami S. Highprevalence of hypovitaminosis D in femaletype 2 diabetic population. Diabetes Care2001; 24:1496.

8. Ishida H, Seino Y, Matsukura S, Ikeda M,Yawata M, Yamashita G, et al. Diabeticosteopenia and circulating levels ofvitamin D metabolites in type 2(noninsulin-dependent) diabetes.Metabolism 1985; 34:797–801.

9. Lambert PW, Service FJ, Arnaud SB.Calcium homeostasis in diabetes mellitus.J Clin Endocrinol Metab 1979; 49:462–466.

10. Baynes KC, Boucher BJ, Feskens EJ,Kromhout D. Vitamin D, glucose toleranceand insulinaemia in elderly man.Diabetologia1997, 40:344-7.

11. Nyomba BL, Auwers J, Bormans V,Peeters TL, Pelemans W, Reynaert J, et al.Pancreatic secretion in man withsubclinical vitamin D deficiency.Diabetologia 1986, 29:34-8.

12. Orwoll E, Riddle M, Prince M. Effects ofvitamin D on insulin and glucagonsecretion in non-insulin-dependentdiabetes mellitus. Am J Clin Nutr 1994;59:1083-7.

13. Teegarden D, Donkin SS. Vitamin Demerging new roles in insulin sensitivity.Nutr Res Rev 2009; 22:82-92.

14. Sue Penckofer, JoAnne Kouba, Diane E.Wallis, Mary Ann Emanuele. Vitamin Dand Diabetes: Let the Sunshine In. TheDiabetes Educator 2008; 34; 939.

15. Nesby-O’Dell S, Scanlon KS, CogswellME. Hypovitaminosis D prevalence and

determinants among African Americanand white women of reproductive age:Third National Health and NutritionExamination Survey, 1988-1994. Am JClin Nutr 2002; 76: 187-192.

16. Sedrani SH. Low 25-hydroxyvitamin Dand normal serum calcium concentrationsin Saudi Arabia: Riyadh region. Ann NutrMetab 1984; 28:181-5.

17. Marwaha RK, Tandon N, Reddy D, et al.Vitamin D and bone mineral density statusof health schoolchildren in northern India.Am J Ckin Nut 2005; 82:477-82.

18. El-Hajj Fuleihan G, Nabulsi M, ChoucairM, et al. Hypovitaminosis D in healthyschoolchildren. Pediatrics 2001; 107:E53.

19. Tahrani AA, Ball A, Shepherd L. Theprevalence of vitamin D abnormalities inSouth Asians with type 2 diabetes mellitusin the UK. Int J Clin Pract, February 2010;64, 3, 351–355.

20. Trivedi DP, Doll R, Khaw KT. Effect offour monthly oral vitamin D3(cholecalciferol) supplementation onfractures and mortality in men and womenliving in the community: randomiseddouble blind controlled trial. BMJ 2003326 469–475.

21. Martins D, Wolf M, Pan D, et al.Prevalence of cardiovascular risk factorsand the serum levels of 25-hydroxyvitaminD in the United States: data from the ThirdNational Health and NutritionExamination Survey. Arch Intern Med.2007;167:1159-1165.


KAP of parents towards childhood vaccination, Jamman Al-Zahrani 23

KNOWLEDGE, ATTITUDE AND PRACTICE OF PARENTS TOWARDSCHILDHOOD VACCINATION

1*Jamman Al-Zahrani

ABSTRACT

Background: The prevention and treatment of hypertension are a high priority in medicineBackground: It has been recently reported by WHO that a large proportion of children failto complete their immunization schedule. System weaknesses, low public awareness, fearsand misconceptions about vaccines were responsible for that. Despite nearly 100%vaccination rate in Saudi Arabia, often parents delay vaccination and do not fullyunderstand the value of immunization, except that it is mandatory for birth certification andadmission in school. Objectives: To assess parental knowledge and attitude regardingvaccination and their effects on vaccination practice. Methodology: A cross-sectional studywas conducted using a self-administered Arabic questionnaire, including 20 questionsrelated to parental knowledge, attitude, and practice regarding childhood vaccination. Itwas distributed in PHC settings. Results: The study included parents of 390 children.Factors significantly associated with better knowledge score and positive parental attituderegarding child vaccination were source of information about child vaccination from TV,internet and journals/newspapers, parents with first child, younger age, and higher level ofeducation. There was a moderate positive correlation between total knowledge score andtotal attitude score of child vaccination (r=0.382, p<0.001). Conclusion: Positive attitudetowards immunizations was remarkably high in this study group of parents. Knowledge onchildhood immunizations, however, was not significantly higher in those who reportedlyreceive information from health professionals.

إلىالوصولتستطیعالاألطفالمنكبیرةنسبةأنینتبالعالمیةالصحةمنظمةمنالحدیثةاالحصاءات:ملخصضعفسببھالتطعیمخدماتفقدانأنأیضابینتو, المقررالتطعیمجدولتكملأنأوبالتطعیمالخاصةالخدمات

المملكةأنمنالرغمعلى. التطعیمعنالخاطئةاالعتقاداتبعضوالخوف, اآلباءوعيقلةالصحي،النظامالاألحیانمنكثیرفياآلباءأنإال،األطفالتطعیماتمعدلفي٪ 100منیقربماحققتلسعودیةاالعربیةعلىللحصولإلزاميأنھإالالتطعیمأھمیةمنیعرفونالبعضھمو،للتطعیماتالمقررالزمنيالجدولیتبعوننحوتوجھاتھمواآلباءمعرفةمدىستطالعاإلىالبحثیھدف:البحثھدف.المدارسفيوالقبولالمیالدشھادةباللغةاستبیاناستمارةباستخداممقطعیةدراسةإجراءتم:البحثطرق.ممارساتھمعلىذلكأثرواألطفالتطعیم

اعتمادتم. األطفالتطعیممجالفيالممارساتوالتوجھاتواآلباءبمعرفةتتعلقسؤاال20علىتشتملالعربیةالعواملطفالً،390آباءالدراسةضمت:البحثنتائج.المؤلفمناإلذنأخذبعدبندا20علىالمحتوياالستبیان

انترنت،تلیفزیون،(األطفالتطعیمعنالمعلوماتمصادركانتاألمورأولیاءلدىأفضلبمعرفةارتبطتالتيارتفاعالعامالت،األمھاتالسن،فيالصغیراتاألمھاتالعائلة،ترتیبفيأولطفلوجود،)مجالتوصحففكانتاألطفالتطعیمنحواألمورألولیاءإیجابيباتجاهارتبطتالتيالعواملأما. اآلباءواألمھاتتعلیممستوىارتفاعالسن،فيالصغیراتاألمھاتوالصغاراآلباء،)مجالتوصحفانترنت،تلیفزیون،(المعلوماتمصادراألطفالتطعیمنحواالتجاهوالمعرفةبینمعنویةداللةذوایجابيارتباطھناككان. واألمھاتءاآلباتعلیممستوى

كاناألطفالتطعیمنحواالیجابياالتجاهمعدل:الخالصة)0.001>(الداللةمستوىو0.382=االرتباطمعامل(ذاارتفاعامرتفعایكنلماألطفالعیمتطعنالمعرفةمستوىلكن،األمورأولیاءمنالمجموعةھذهفيممتازا.األطباءمنمعلوماتھمتلقوامنبینمعنویةداللة

Received: 5 December, 2012; Accepted: 8 March, 2013*Correspondence: [email protected] of Family Medicine and Primary Healthcare, King Abdulaziz Medical City, National Guard HealthAffairs, Kingdom of Saudi Arabia.



INTRODUCTION

Immunization of children against seriouscommunicable diseases is the most costeffective strategy to decrease overallmorbidity and mortality among children.(1,2)

In order to accomplish this strategy, highcoverage of vaccination is essential to bemaintained.(1,3)

When the Expanded Programme onImmunization (EPI) was launched in 1974,less than 5% of the world's children wereimmunized during their first year of lifeagainst six killer diseases; Polio,Diphtheria, Tuberculosis, Pertussis(Whooping Cough), Measles andTetanus.(4) From 1984 onward, the EPI hasbeen implemented in Saudi Arabia as anintegral and essential element of primaryhealth care.(5)

Over 1.5 million children die from vaccinepreventable diseases as reported by WHO.Previous estimated number of all deaths inchildren under five in 2008 was 8.8 million,and 17% of all deaths in children under fiveare preventable by vaccination.(6) TheWHO estimates that current immunizationprograms save more than 3.2 million liveseach year and the full utilization of existingvaccines could save an additional 1.7million lives per year.(7)

Recent analysis from WHO showed failureof a large proportion of children to accessimmunization services or to complete theirimmunization schedule. Lack of servicesdue to system weaknesses, low publicawareness, or fears and misconceptionsabout vaccines were some of theinfluencing factors.(8)

Vaccination coverage can be affected bymany other factors like low socioeconomicstatus and low education level. Thesefactors can play a role in delay or finishingfull set of vaccination.(9) Despite notableimprovement, still around three millionchildren are permanently disabled each

year.(10, 11) Studies suggest that parents andhealth care providers are uncomfortablewith multiple injections in single visits.(12-

14) Even in areas with high coverage, it isimportant to know attitudes and behaviourstoward immunizations in order to improveservices and maintain high coverage rate.(15)

Since 1979, the government has supportedthe practice of tying the issuing of birthcertificates for successful completion offirst two years of life primaryimmunizations against diseases which aretargeted by available vaccines. TheNational Immunization Program hasachieved eradication of neonatal tetanusand polio. Still efforts are needed toeradicate measles, rubella and mumps, andto reduce the incidence of the remainingcommunicable diseases.(16)

The recent data issued by WHO Office forthe Eastern Mediterranean Region, reportedthat twenty countries in the region are freefrom polio. As for the regularimmunizations against the diseases targetedby childhood vaccination, the rate ofimmunization reached over 97% in SaudiArabia over the past five years.(17, 18)

Despite nearly 100% childhood vaccinationrate in Saudi Arabia, often parents do notfollow the schedule in a timely manner, anddo not fully understand the value ofimmunization except that it is mandatoryfor birth certification and admission inschool. Thus, this study aimed at assessingparental knowledge, attitude and practicetoward vaccination of their children.

METHODS

This cross-sectional study was conducted attwo primary care centers (Health CareSpecialized Centre [HCSC -Khashm Alaan]and King Abdulaziz Housing Clinic[Iskan]), National Guard Health Affairs,Riyadh, Saudi Arabia. These two clinicsserve a total population of over 150,000



patients of which at least one third arechildren.

All parents visiting the primary care withtheir children were enrolled for interview ifthey agreed to participate.

The sample size was estimated based on theassumption that 93% of the parents wouldhave a positive attitude based on the UAEstudy,(19) with a margin of error ± 3%.Using a confidence interval of 98% asample size of 380 was obtained, whichwas adjusted up to 400 for data losses. Byconvenient non-random sampling, parentswho visited the two primary care clinicswith their children were recruited toparticipate in the study after theiragreement. The appointment schedule wasnot influenced by the recruitment processduring the study period.

Eligible participants were asked to fill aself-administered questionnaire including20 statements related to knowledge, attitudeand practice of parents visiting the clinicwith their children. The 20-item ArabicQuestionnaire was adopted after permissionfrom validated questionnaire in Iraq. (20)

The questionnaire included thedemographic data for child (age, birthweight, gender, feeding, number ofpreschool children and child order) anddemographic data for parents (age,employment and education), knowledgerelated questions (14), attitude questions (5)

and one practice Question. For knowledgequestions, scores were summed up forcorrect answers. No negative marking wasdone and higher score indicated higherknowledge level. For attitude, Scores weresummed up for correct answers. Nonegative marking was done and higherscore indicated more positive attitude.

The collection and interview parts weresupervised by assigned staff nurse, toensure good compliance while collecting

the data and help during filling of thequestionnaire.

DATA ENTRY AND ANALYSIS

Data were analysed by using SPSS softwarestatistical program, version 18.Summarization of the data was presentedusing tables and graphs. The followingstatistics were applied: Continuousvariables (total knowledge and attitudescores) were presented as mean andstandard deviation (SD). Categoricalvariables were presented as frequency andpercentage. Significance was determined atp value < 0.05. Chi square test was appliedto test for the association betweencategorical variables while t-test was usedto test for the difference in the means oftwo continuous variables.

Ethical committee approval was obtainedfrom the Family Medicine ResearchCommittee of the Department of FamilyMedicine & Primary Health Care in KingAbdulaziz medical city. Verbal Consentwas taken from respondents, clarifying themain purpose of the study, the importanceof the respondent views, thanking inadvance and assuring strict confidentialityof the information with consent statementon the Questionnaire. All data weremaintained in a secure and confidentialmanner. Data were analysed as cumulativein a manner that individual privacy wasmaintained.

RESULTS

The study included parents of 390 children.Response rate was 96%. Table (1) presentsthe children characteristics. Over 43% ofthe children were below 1 year old. Morethan one-third of them (36.4%) werebetween one and three years old. More thanhalf of them were males (56%). Majority ofchildren (69.7%) had a birth weight ofabove 2.5 kg. Breast feeding was reportedamong only 24% of them while bottle andmixed feeding were reported among 34%



and 42% of them, respectively. Regardingbirth order, most of them were second ormore (72.4%). Mothers represent 60.2% ofthe participants. The majority of them(86.2%) were not employed and 29.7% ofthem were university/college graduates.Fathers represent 39.8% of the participants.Most of the fathers were employed (96.1%)but only 18.8% of them had universitydegree.

Characteristic Frequency(%)

Child age: (385)< one year 166 (43.1)(1 – 3) years 140 (36.4)≥ 4 years 79 (20.5)

Child gender: (389)Male 218 (56)Female 171 (44)

Child birth weight: (386)≤ 2.5 kg 117 (30.3)> 2.5 kg 269 (69.7)

Child feeding: (388)Breast Feeding 93 (24)Bottle Feeding 132 (34)Both 163 (42)

Preschool children: (279)One 165 (43.5)02-Mar 163 (43)≥ 4 51 (13.5)

Child order: (387)First child 107 (27.6)Second or more 280 (72.4)

Parent participating: (384)Father 153 (39.8)Mother 231 (60.2)

Mother employment: (390)Employed 54 (13.8)Not Employed 336 (86.2)

Mother education: (390)Primary 89 (22.8)Intermediate 65 (16.7)Secondary 120 (30.8)College/university 116 (29.7)

Father employment: (389)Employed 374 (96.1)Not Employed 15 (3.9)

Father education: (389)Primary 33 (8.5)Intermediate 86 (22.1)Secondary 197 (50.6)College/university 73 (18.8)

Figure (1) shows that physicians were themain source of information (77.7%) for theparents about immunization, followed byTV (37.6%), Internet (21.7%) andnewspapers (13.3%).

Figure (1): Source of parent information aboutchildhood vaccination

Table (2) shows that fever was the mostcommonly reported adverse effect ofvaccination by parents (74.2%) followed bypain (48.6%). Skin rash and convulsionswere reported by only 4.9% and 4.1% ofthe participants, respectively. Less than halfof the parents (46.5%) reported that themaximum limit for vaccines per visitshould be recommended by physicians.

More than half of the participants (60.2%)believed that vaccine is for all ages. Themajority of them recognized correctly thatvaccination prevents diseases (82.6%), thatthere are different types of vaccines(87.4%), a uniform schedule for childrenunder the age of 2 years (83%), vaccinationenhances immunity (89.2%) and healthychild need vaccination (85.9%). More thanhalf of the parents recognized that there aresituations in which vaccine cannot be given(58.5%). The majority of the parents didnot accept that harm of the vaccine is morethan benefits (92.8%) or multiple vaccinesin one visit decrease immunity (85.6%).

Parents` total knowledge score rangedbetween 1 and 11.4 (out of 11) with a meanof 8.08 and SD of 1.8



Table 2: Parental knowledge about vaccination(right answers).

N Item Frequency(%)

1 Adverse effects of vaccines*:

Fever

Pain

Skin rash

Diarrhoea

Convulsions

Don't know

290 (74.2)

190 (48.6)

19 (4.9)

42 (10.7)

16 (4.1)

49 (12.5)

2 Maximum limit of vaccines per visit:

1-2 vaccines

3-4 vaccines

5 or more

Recommend by physician

149 (38.1)

57 (14.6)

3 (0.8)

182 (46.5)

3 Vaccine for all ages 234 (60.2)

4 Vaccination prevent disease 323 (82.6)

5 Different types of vaccines 339 (87.4)

6 Uniform schedule less than 2 years 322 (83)

7 Vaccination start first week of life 279 (71.7)

8 Situations you can't give the vaccine 227 (58.5)

9 Harm of vaccines more than benefits 28 (7.2)

10 Vaccination enhance immunity 348 (89.2)

11 Healthy child need vaccination 335 (85.9)

12 Multiple vaccines in one visit decreaseimmunity

56 (14.4)

Table (3) presents the significant factorsassociated with better parents` knowledgeof child vaccination. Regarding their sourceof information about child vaccination,those whose source was TV showed highersignificant total knowledge score (8.5±1.69versus 7.83±1.83), p<0.001. Similarly,those whose source was internet showedhigher significant total knowledge score(8.68±1.3 versus 7.91±1.89), p<0.001.Parents whose source of information wasjournals/newspapers showed highersignificant total knowledge score(8.54±1.54 versus 8.01±1.83), p<0.049.

Variables Totalknowledgescore

t-value*(p-value)

Mean SD

TV(source of information)No (242) 7.83 1.83 3.62Yes (146) 8.5 1.69 (<0.001)InternetNo (303) 7.91 1.89 3.53Yes (85) 8.68 1.3 (<0.001)Journals/newspapersNo (336) 8.01 1.83 1.97Yes (52) 8.54 1.54 -0.049Child birth orderFirst (107) 8.42 1.78 2.24Second or more (277) 7.97 1.79 -0.026Mother`s age≥30 (203) 7.79 1.91 3.45<30 (181) 8.42 1.63 -0.001Mother`s employment statusEmployed (54) 8.9 1.55 3.63Not employed (333) 7.95 1.81 (<0.001)Mother`s educationSchool education (271) 7.77 1.79 5.27College degree (116) 8.79 1.64 (<0.001)Father`s educationSchool education (313) 7.91 1.8 3.77College degree (73) 8.78 1.66 (<0.001)

Parents with first order children showedhigher significant total knowledge scoreabout vaccination than those with second ormore child birth order (8.42±1.78 versus7.97±1.79), p<0.026. Younger mothers(<30 years) showed higher significant totalknowledge score about vaccination thanorder (≥30 years) (8.42±1.63 versus7.79±1.91), p=0.001. Employed mothersshowed higher significant total knowledgescore about vaccination than non-employed(8.9±1.55 versus 7.95±1.81), p<0.001.Higher educated mothers had significanthigher total knowledge score about childvaccination than less educated (8.79±1.64versus 7.77±1.79, p<0.001). Highereducated fathers had significant higher totalknowledge score about child vaccinationthan less educated (8.78±1.66 versus7.91±1.80, p<0.001.



Table (4). Parental attitude and practice of childvaccination.

Item Frequency

Practice Regular vaccination 304 (77.7)

Attitude Barriers against vaccination:a) Loss of educationb) Vaccine availabilityc) Limited serviced) Feare) Don't know

172 (44.1)67 (17.2)35 (9)61 (15.6)148 (37.9)

Vaccination not safe 309 (79.4)

Prefer to vaccinate your child 367 (93.9)

Recommend vaccination toothers

378 (96.9)

In favour of vaccinationprogram

337 (96.7)

As illustrated in Table (4), regular childvaccination was reported by 77.7% of theparents. Missing school due to clinic visitfor vaccination (44.1%), vaccine non-availability (17.2%), limited service (9%)and fear (15.6%) were the reported barriersagainst vaccination. Almost one-fifth of theparents (20.6%) believed that vaccination isnot safe. The great majority of thempreferred to vaccinate their child (93.9%),recommend vaccination to others (96.9%)and in favour of vaccination program(96.7%).

Parents` total attitude score ranged betweenzero and 4 (out of 4) with a mean of 3.67and SD of 0.68.

Table (5). Factors significantly affect total parents`attitude score towards child vaccination

VariableTotal Attitude

scoret-value*

(p-value)Mean SD

TV (source ofinformation)No (243)Yes (146)

InternetNo (304)Yes (85)

Journals/newspapersNo (337)Yes (52)

3.573.83

3.603.91

3.643.85

0.780.43

0.740.29

0.710.36

3.68(<0.001)

3.71(<0.001)

2.04(0.042)

Mother`s age≥30 (203)<30 (182)

Father`s age≥35(216)<35 (167)

Mother`s educationSchool education (272)College degree (116)

Father`s educationSchool education (314)College degree (73)

3.583.77

3.603.75

3.623.79

3.623.88

0.760.56

0.750.58

0.690.64

0.720.41

2.73(0.007)

2.19(0.029)

2.25(0.019)

2.93(0.004)

Table (5) presents the significant factorsassociated with positive parents` attitudetowards child vaccination. Regarding theirsource of information about childvaccination, those whose source was TVshowed higher significant total attitudescore (3.83±0.43 versus 3.57±0.78),p<0.001. Similarly, those whose source ofvaccination information was internetshowed higher significant total attitudescore (3.91±0.29 versus 3.6±0.74),p<0.001. Parents whose source ofinformation was journals/newspapersshowed higher significant total attitudescore (3.85±0.36 versus 3.64±0.71),p<0.042. Younger mothers (<30 years)showed higher significant total attitudescore towards vaccination than order (≥30years) (3.77±0.56 versus 3.58±0.76),p=0.007. Younger fathers (<35 years)showed higher significant total attitudescore towards vaccination than order (≥35years) (3.75±0.58 versus 3.60±0.75),p<0.029. Higher educated mothers hadsignificant higher total attitude scoretowards vaccination than less educated(3.79±0.64 versus 3.62±0.69, p=0.019.Higher educated fathers had significanthigher total attitude score towardsvaccination than less educated (3.88±0.41versus 3.62±0.72, p=0.004.

Figure (2) shows that there was asignificant positive correlation betweentotal knowledge score and total attitudescore of child vaccination (r=0.382,p<0.001).



DISCUSSION

It is widely accepted that childhoodimmunization programs have played a greatpart in the prevention of many diseases;hence, vaccination coverage is an indirectway to assess child health care from thepoint of view of public health.(21)

The results of the survey offer insight intothe knowledge, attitude and practices withregards to immunization among the parentsand their source of information and can beutilized to conduct larger community basedsurvey in order to intervene and maintainhigh vaccination status of the population asthe key issue in the maintenance of theexisting high vaccination coverage in theKSA.

As expected, on the basis of highvaccination coverage for infants for thevaccine-preventable diseases in KSA, theattitude towards vaccination was generallypositive in the present study. Over 80% ofrespondents were in favour of vaccinationand believed that it prevents disease. Thisfinding is in line with those reported inother countries.(22, 23) in which majority ofrespondents acknowledged the importanceof Immunization.(24) It is also promisingwhen one notes that the majority of therespondents were confident enough torecommend immunization to others.

It is particularly important to note that 20%of the respondent in our study believesimmunization is not safe. Respondents werenoted to be not well informed aboutpossible side effects of immunization withthe exception of fever and pain. Concernsabout immunization safety are widelyprevalent (25) as well as concerns regardingthe adverse impact of possible side effectson immunization coverage have beenreported earlier.(26) It is to be noted thatphysicians are a main source aboutimmunization for these patients.

Figure (2): Correlation between total knowledgeand total attitude scores

It is heartening to note that doctors areresponsible for informing a majority ofrespondents about immunization but a needexists to work further in this area. There is aneed to educate physician in this area sincethey are found to be deficient in knowledgeabout immunization.(27) The role ofphysician is also very important inpromotion of immunization among thepopulation.(28)

The media is noted to be a strong source forproviding awareness among therespondents about immunization in thecurrent survey where 43.7% of therespondents reported TV/radio as theirsource of information about childvaccination. There again exists a need forfurther improvement in this area. Televisioncan be a good source to promoteimmunization and results of our study pointout a need to further utilize this source forthis purpose as better knowledge andattitude towards child immunization wasreported among those depend on TV as asource of their information. The importantrole that media can play in promotion ofimmunization has been highlighted byearlier reports.(29)

A further important issue arising from theresults is that 77.7% reported that a healthprofessional was the main source ofinformation regarding childhoodimmunizations. This is in contrast to



finding of UAE study where a largeproportion of mothers seem to obtaininformation on side effects from othersources such as the media or the internetwhere opponents of vaccinations mayinvariably publish biased or unreliableinterpretations of proven scientificresults.(30) Unless properly addressed, thiserroneous information on side effects,together with a possible diminishingperception of the lethality of vaccinepreventable diseases, could adversely affectvaccine coverage.

Older mothers were less likely to haveknowledge and positive attitude towardschild vaccination. Perhaps, in older women,this reflects a higher prevalence oftraditional nihilistic views, such as destinybeing the cause of disease. The samefinding has been reported in other gulfcountries (UAE).(19)

It was found that the knowledge score waslower in those women with a compromisededucational standard. It is a truism thatknowledge increases with education. It ishowever, questionable whether those moreinformed women actually received theirinformation from health professionals. Thisobservation could be due to recall bias:someone who remembers being wellinformed also knows more about theprogram. For some women, the informationprovided may not have been targeted totheir level of understanding or to theirspecific questions and concerns. It seemsthat having information from healthprofessionals was not significantly relatedto knowledge level in contrast to havinginformation from TV, internet orjournals/newspapers.

In accordance with what has been reportedIn Iraqi study,(20) the level of knowledgeamong parents was positively correlatedwith their attitude to and practices ofimmunization.

Among limitations of the current research isthat it was conducted in localized centres(King Abdulaziz Medical City in Riyadh,Saudi Arabia). So the generalizability of theresults over Saudi community isquestionable. However, adequate samplesize provided enough statistical power todetect associations and yielded estimates ofpercentages with sufficient precision.

In conclusion, the prevalence of a positiveattitude towards immunizations wasexcellent in this study group of parents, andsatisfaction with the service was high.Knowledge on childhood immunizationshowever was not significantly higher inthose who reportedly receive informationfrom health professionals while it washigher among those received informationfrom TV, internet and newspapers,although a larger percentage of the parentsgot their information from physicians. Theknowledge of child vaccination wasinsufficient in some important points asside effects, situations you can't give thevaccine and that vaccination should begiven for all ages. In order to maintain thecurrent high vaccination coverage in theKSA, it is recommended that healtheducation activities should focusparticularly on parents of a compromisededucation and older in age and should alsotarget their information to appropriatelevels of each parent’s understanding

ACKNOWLEDGEMENTS

I would express my sincere gratitude andgreat appreciation to Dr. Saeed Ur Rahmanfor his sustained help and providing expertadvice during this study. I would like tothank Dr. Omar Al-lela for his kind co-operation in providing the permission forusing his questionnaire in this study.Special thanks also to Dr. Imad Yaseen forhelp during statistical analysis and finalpreparation.



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Parental KAP towards Antibiotics use in URT infection in children. Khaled Al-Dosari 33

PARENTAL KNOWLEDGE, ATTITUDE AND PRACTICE ON ANTIBIOTIC USEFOR UPPER RESPIRATORY TRACT INFECTIONS IN CHILDREN

1*Khaled Al-Dossari

ABSTRACT

Background: Several factors are evidently associated with the overuse of antibiotics both atthe doctor`s level and the parents of children level. Objectives: To assess the level ofknowledge and practice of parents about antibiotics use for upper respiratory tract infection(URTI) in their children as well as to determine the contributing factors for inappropriateuse. Material and Methods: A cross-sectional study was carried out in two PHC centres inNational Guard Health Affairs, Riyadh, between 1 January 2012 and 29 February 2012. Itincluded parents of children (age from birth to 12 years) presenting with URTI symptoms.Results: The study included 352 parents of Saudi children. Most of the parents (71%)reported doctors as their source of antibiotic information. Only 1.4% of the participantsidentified correctly all antibiotics while 35.8% of them did not identify any antibioticcorrectly. Factor analysis showed that the three common underlying factors responsible forantibiotics overuse were: parental self-prescribing tendency, parental tendency of asking forantibiotics from doctor and parental carefree attitude regarding over use and the threecommon underlying factors responsible for cautious approach to antibiotics use were:parental cautious nature, parental preference of advice over antibiotics and parental beliefthat URTI are mostly self-limiting. Conclusions: Parents are self-prescribing because oftheir easy access of antibiotics without prescription and their indifferent attitude towardmicrobial resistance. Keywords: Antibiotics. Saudi Arabia, knowledge, URTI

األطفالعندالعلويالتنفسيالجھازاللتھاباتالحیویةالمضاداتماستخدافيوممارساتھموتوجھاتھمالوالدینمعرفة

أولیاءیخصمامنھاوالطبیبیخصمامنھاالحیویةللمضاداتالمفرطاالستخدامفيعدةعواملتشترك:ملخصیتعلقیمافاألمورأولیاءبینالممارسةوالمعرفةمستوىتقدیرإلىالدراسةھذهتھدف:الدراسةأھداف.األمور

التنفسيالجھازبعدوىالمصابیناألطفالعالجفيلھاالخاطئاالستخدامفيتشتركالتيالعواملوالحیویةبالمضاداتبالریاضالوطنيللحرسالصحیةللشئونتابعینصحیینبمركزینمقطعیةدراسةإجراءتم:البحثطریقة.العلويالثانیةسنحتىوالوالدةمنذاألطفالأمورأولیاءالدراسةشملت. 2012لعاملفبرایر29حتىینایر1منالمدةخاللسعودیینألطفالأمرولي352الدراسةھذهضمت:النتائج. العلويالتنفسيالجھازعدوىبأعراضالمصابینعشركانالحیویةمضاداتالعنمعلوماتھممصدرأن%) 71(المشاركینمعظمأقر%). 59.4(إناثاكانوانصفھممنأكثر

بینماعلیھمعرضتالتيالحیویةالمضاداتكلعلىالتعرففقط% 1.4استطاعالمشاركین،بینمن. األطباءعلىالتعرفاستطاعوا%) 69.9(المشاركینثلثيمنأكثر. حیويمضادأيعلىالتعرفیستطیعوالممنھم% 35.8

رئیسیةعواملثالثةیوجدأنھأوضحالعاملياإلحصائيالتحلیل. الحیویةالمضاداتلفصیلةالمنتمیةغیراألدویةكلمنوصفھالطلبمیلھمبأنفسھم،لوصفھااألمورأولیاءمیل: وھيالحیویةللمضاداتالمفرطاالستخدامفيمؤثرة

الطبیعة: ھيوبحذرالحیویةالمضاداتاستخدامفيمؤثرةعواملثالثةوجدتكما. األفضلبأنھااعتقادھموالطبیبالجھازعدوىأناألمورأولیاءاعتقادأخیراوالحیویةالمضاداتعنالنصائحسمعتفضیلواألمور،ألولیاءالحذرةدونالحیویةللمضاداتالسھلالوصولبسبببأنفسھمالدواءبصرفالوالدانیقوم:الخالصة.تلقائیاتشفىالتنفسيحاجةھناكأنإلىاألمورأولیاءوأشار, الحیویةللمضاداتالمیكروباتمقاومةتجاهالمباليغیروموقفھمطبیة،وصفة

.المناسبةبالطریقةالحیویةالمضاداتالستخدامواألمھاتواآلباءاألطباءمنلكلالتعلیممنمزیدإلى

Received: 18 December, 2012; Accepted: 9 March, 2013*Correspondence: [email protected] of Family Medicine and Primary Healthcare, King Abdulaziz Medical City, National Guard HealthAffairs, Kingdom of Saudi Arabia.



INTRODUCTION

During the winter period, the majority ofcases visiting the primary health carecentres are due to upper respiratory tractsymptoms(1). Literature reports have shownthat upper respiratory tract infectiousdiseases worldwide include: common cold,influenza, rhinorrhea, and bronchitis(2).Despite the predominantly viral cause, withno need for antibiotic therapy(3,4),antibiotics, in practice, are frequentlyprescribed to children with symptoms ofacute respiratory tract infection (URTI)(4-8).Children aged 0 to four years received 53%of all antibiotics prescribed to the pediatricpopulation(9). This misuse of antibiotics iscurrently one of the major public healthissues worldwide(10-13).

Problems associated with the overuse ofantibiotics include development ofantibacterial resistance, increasing theburden of chronic disease, raising costs ofhealth services, and the development ofside effects (e.g. adverse gastrointestinaleffects)(14). In addition, antibiotics mayreduce the duration of fever in childrenwith influenza which could reflect anincreased risk of secondary bacterialinfection for such children(8).

Several contributing factors are evidentlyassociated with the overuse of antibioticsboth at the doctor`s level(15-21) and theparents of sick children level and(22-24),namely: cultural factors, behavioralcharacteristics, socio-economic status, andlevel of education(25-27). Furthermore,doctors usually relate their pattern of overprescribing to parents` pressure(28). Also,lack of health education is one of the majorcontributing factors in the overuse ofantibiotics(29). Thus, Pediatriciansacknowledge prescribing antimicrobialagents when they are not indicated(15).Pediatricians believe educating parents isnecessary to promote the judicious use ofantimicrobial agents(16). Self-medication is

also a behaviour that contributes to themisuse of antibiotics(30,31).

Thus, the current parental knowledge,attitude and practice on antibiotic use incommon childhood URTI is a matter ofgreat interest and importance, and thisstudy is trying to address these issues inparticular

MATERIAL & METHOD

This was a cross-sectional descriptivestudy carried out in two PHC centers[King Abdulaziz Housing Clinic (Iskan)and Health Center for Specialized Care(HCSC Kashm Alaan) , National GuardHealth Affairs, Riyadh, Saudi Arabiabetween 1 January 2012 and 29 February2012.

Parents having children, aged from 0 to 12years, presenting with URTI symptoms(nasal congestion, cough, fever and sorethroat) were included in this study.Children having fever lasting more than 7days, or chronic diseases, or symptomssuch as earache, or those who camewithout one of their parents and childrenwith symptoms of lower respiratory tractsymptoms such as wheezing, stridor andbreathing difficulty were excluded.

The sample size of 352 was estimatedbased on 34% of parents giving theirchildren antibiotics for URTI withoutphysician’s advice, in the Egyptianstudy[36], with a desired precision of +5%, alpha of 0.05 (CI of 95%) and powerof 0.8. Participants of the study wereselected by convenient sampling as theyvisited the clinic during the study period,and presented with inclusion criteria.Participants’ selection comes from therandom order by which they visited theclinic.

A pre-tested questionnaire was used inthis survey adopted from a similar Greek



study(32). Permission was taken by emailfrom the researchers, who used thisquestionnaire in Greece, to translate it inArabic language and use for local study.The questionnaire contains demographiccharacteristics, knowledge of antibiotics,sources of information, practice ofantibiotic use in URTI and awareness offirst-aid resources. The KAP-questionnaire was structured in three mainsections which displayed the Knowledge(Section A), Attitudes (Section B) andPractices (Section C) of parents regardingantibiotics use in URTI of their children.

Section (A) included questions regardingparental knowledge concerningantibiotics. They were asked to markantibiotic names out of seven commonlyused medications and to answer questionsrelevant to antibiotics indications, sideeffects and their use in viral infections.Section (B) studied the parental attitudesregarding URTIs, antimicrobial agents’use and the doctors’ role. Parents whereasked which symptoms and what durationwould lead them to seek medical attentionfor their children, as well as theirexpectations regarding antibioticsprescription. Other questions includedreasons for antibiotic use without medicaladvice (over the counter acquisition ofantibiotic, use of leftover antibiotic fromprevious illness, etc.) or whether theywould seek for a doctor who is morelenient with antibiotic administration.Finally, (Section C) looked into parentalpractices and whether the parent-doctorrelation is influenced by the latter’sattitude on antibiotic prescription. Parentswere asked whether their doctor spendsenough time explaining the illness andsuggested antibiotic treatment for theirchild, whether he is influenced by theirdemand to prescribe antibiotics, as well aswhether their doctors gives theminstructions over the phone (withoutprevious examination) for antibioticadministration to their sick child.

Each question (apart from those includedin the demographic data section) was in aformat of five possible answers (acceptingonly one right answer), according to the 5-point Likert scale: 1 = strongly agree, 2= agree, 3 = uncertain, 4 = disagree and 5= disagree strongly or 1 = always, 2 =most of the times, 3 = often, 4 =sometimes and 5 = never.

To verify parent’s responses consistencyand exclude random completion, threecouples of similar questions (where eachcouple included the same statementexpressed in a different way) and threepairs of contradictory questions (whereeach question included the reversestatement requiring the opposite answer)were entered in the questionnaire’sstructure. All these questions wererandomly placed in the questionnaire tominimize parents’ awareness.Questionnaires with discordant responsesto two or more of these paired questionswere removed.

After we received written permission fromKing Abdullah Research Centre, thequestionnaires were distributed by nursesto all parents attending the PHC with theirchildren with URTI symptoms and beforeentering the doctor’s room. In order toincrease compliance, all nurses werepersonally informed by the researcherabout the study nature and its importance.They were asked to distribute thequestionnaires to parents, collect and mailthem back to the researcher. An informedverbal consent was obtained from everyparent before participation in the study.Participants were assured that collecteddata will be strictly confidential, and willnot be disclosed for any reason, and willbe used only for research purposes.Professional advice was providedregarding appropriate use of antibiotics inURTI in children



RESULTS

The data were verified manually, enteredin computer and IBM-SPSS softwarestatistical program version 19 was utilizedfor data entry and analysis. Categoricalvariables were presented as frequenciesand percentages. Spearman’s Rho wasused to measure correlation between twovariables. P-value of less than 0.05 wasconsidered significant. PrincipleComponent Analysis was carried out onthe items in the questionnaire to find themain underlying factors; beliefs andbehavioural that parents are influenced byin prescribing or avoiding antibiotics.

The study included 352 parents of Saudichildren. Table (1) presented theirbaseline characteristics. (59.4%) of themare female. Almost one-third of themothers were high school educated(35.2%) while 29.3% were universityeducated.

Table 1: Demographic characteristics

Frequency PercentGender

Male 143 40.6Female 209 59.4

Mother’s educational levelPrimary 76 21.6SecondaryHigh schoolCollege

49124103

13.935.229.3

Father’s educational levelPrimary 39 11.1SecondaryHigh schoolCollege

5918866

16.853.418.8

Family incomeLowMiddleHigh

2829628

8.084.08.0

Relation of thepatient to treatingphysicianRelative/familyfriend /formalrelationship

17

335

4.8

95.2

More than half of the fathers were highschool educated, while 18.8% wereuniversity educated. Family income wasmiddle in most of the participants (84%). Inmajority, formal relationship to the treatingphysician was reported (95.2%).As obviousfrom figure (1), the access to health caresystem was described as good by 61.4% ofthe parents, while it was described as badby 3.4% of them.

Fig. 1: Distribution of the parents according to theirperceived access to health care system.

Fig. 2: Distribution of the parents according to theirsource of information about antibiotics.

Most of the parents (71%) reporteddoctors as their source of antibioticinformation, while media andfriends/relatives were reported by 17.9%and 11.1% of them respectively, assources of antibiotic information (Fig. 2).

Parental knowledge about commonly usedantibiotics: As shown in table (2),amoxicillin and Augmentin wererecognized by 44.6% and 38.9% of theparents, respectively as antibioticscompared to clarithromycin that reportedby 16.5% of them as an antibiotic. On theother hand, histop (antihistamine) wasreported as an antibiotic by 21.6% of the



parents while normal saline nasal drops,flagyl and oral rehydration solution werereported as antibiotic by 9.9%, 6.3% and4.5% of the participants, respectively.

Table 2: Knowledge about commonly usedmedications (n=352).Common Medications Yes (%) No (%)

Augmentin 38.9 61.1

Clarithromycin 16.5 83.5

Histop 21.6 78.4

Amoxicillin 44.6 55.4

Flagyl 6.3 93.7

Normal saline nasal drops 9.9 90.1

URTI and practice of parents: As shownin table (4), 79% of the parents expectedprescription of paracetamol and analgesicsby their physicians to treat URTI, while47.4% of them expected prescription ofantibiotics. Antitussives, normal salinenasal drops and antihistamine wereexpected to be prescribed by physiciansfor URTI treatment among 31.8%, 31.3%and 19.3% of parents, respectively.

Table (5): Responses of the participants to thequestions about their likelihood of antibioticprescription to their child by doctors (n=352).

Chi

lds

Sym

ptom

s

Alwa

ys

Mos

t of t

hetim

e

Usu

ally

Som

etim

es

Nev

er

Cold 47(13.4)

53(15.1)

50(14.2)

111(31.5)

91(25.9)

Runnynose

24(6.8)

48(13.6)

46(13.1)

100(28.4)

134(38.1)

Sorethroat

93(26.4)

80(22.7)

63(17.9)

94(26.7)

22(6.3)

Cough 56(15.9)

56(15.9)

62(17.6)

99(28.1)

79(22.4)

Vomiting 57(16.2)

86(24.4)

38(10.8)

78(22.2)

93(26.4)

Fever 97(27.6)

84(23.9)

36(10.2)

67(19.0)

68(19.3)

Ear pain 109(31.0)

92(26.1)

34(9.7)

63(17.9)

54(15.3)

Likelihood of antibiotic prescription totheir child by doctors: On descriptive

analysis, parents were more likely (alwaysor most of the time) to request antibioticfor ear pain (57.1%), fever (51.5%), sorethroat (49%) while less likely to requestantibiotic for vomiting (40.6%), cough(31.8%), cold (28.5%) and runny nose(20.4%).

Antibiotic use without the doctor’sadvice: Non-serious status of the child(23.6%), lack of time or money (20.8%)were the reason for giving antibiotics tothe child without physician’s advice.

Table 4: Parental reasons for giving their childantibiotics without physician’s advice. (n=352).

Reas

on

Alwa

ys

Mos

t of t

hetim

e

Usu

ally

Som

etim

es

Nev

er

Lack of time ormoney to visitphysician

39(11.1)

34(9.7)

38(10.8)

66(18.8)

175(49.7)

Child’s conditiondid not seemserious enough.

28(8.0)

55(15.6)

40(11.4)

73(20.7)

156(44.3)

Knowledge ofantibiotics for thesame symptom soself-prescribed

34(9.7)

33(9.4)

44(12.5)

47(13.4)

194(55.1)

Pharmacistrecommended theantibiotic.

24(6.8)

29(8.2)

39(11.1)

86(24.4)

174(49.4)

Friend or relativerecommended theantibiotic.

12(3.4)

16(4.5)

29(8.2)

41(11.6)

254(72.2)

Lack of time ormoney to visitphysician

39(11.1)

34(9.7)

38(10.8)

66(18.8)

175(49.7)

Child’s conditiondid not seemserious enough.

28(8.0)

55(15.6)

40(11.4)

73(20.7)

156(44.3)

Similarly physician`s prescription(19.1%), pharmacist recommendation(15%) and friend/family relativerecommendation (7.9%) were the reasonsfor giving antibiotics to the child withoutphysician’s advice, respectively.

Parental believes and practice forappropriate use of antibiotics: Themajority of the parents (84%) agreed thatparents and doctors should be informedabout judicious antibiotic use. Almosttwo-thirds of them (66.4%) agreed that



overuse and inappropriate use ofantibiotics reduces efficacy.

More than half of the parents (50.2%)agreed that antibiotics are usedunnecessarily while more than one-thirdof them (39.5%) agreed that most ofURTI are of viral origin. Thirty percent ofthe parents agreed that they may changetheir doctors because of prescribingantibiotics to their children to treat URTI.Slightly less than half of the parents(49.1%) agreed that most of URTI areself-limited.

Fig. 3: Scree Plot for Principal Component Analysis.

Around half of the participants (49.2%)are well informed about judiciousantibiotic use. Almost two-thirds of theparents (63.5%) asked their doctor toprescribe antibiotics to treat URTI of theirchildren. Most of the participants (82.9%)mostly followed doctors` instruction and43.3% of them appreciated the doctorswho did not prescribe antibiotics.

Parental believes and practice for in-appropriate use of antibiotics: Table (8)shows that more than half of the parents(53.4%) agreed that children with flu likesymptoms get better with antibiotics and44.3% agreed that antibiotics can preventURTI complications. Almost one-third ofthem (32.8%) agreed that new antibioticsthat can kill resistant bacteria can beproduced by scientists.

Table (8): Parental beliefs, attitudes & practicesregarding antibiotic use.

Belie

fs a

ndat

titud

es(P

ract

ices

)

Stro

ngly

agr

ee(A

lway

s)

Agre

e(M

ostly

)

Not

sure

(Usu

ally

)

Dis

agre

e(S

omet

imes

)

Stro

ngly

Dis

agre

e(N

ever

)

Lack of time andresources

39(11.1)

34(9.7)

38(10.8)

66(18.8)

175(49.7)

child condition isnot seriousness

28(8.0)

55(15.6)

40(11.4)

73(20.7)

156(44.3)

Similarprescription

34(9.7)

33(9.4)

44(12.5)

47(13.4)

194(55.1)

Pharmacistrecommendation

24(6.8)

29(8.2)

39(11.1)

86(24.4)

174(49.4)

Friend/relativerecommendation

12(3.4)

16(4.5)

29(8.2)

41(11.6)

254(72.2)

Phone antibioticrecommendation

11(3.1)

13(3.7)

22(6.3)

20(5.7)

289(81.3)

Ask antibioticprescriptiondirectly

14(4.0)

32(9.1)

26(7.4)

62(17.6)

218(61.9)

Insist prescribingantibiotics

11(3.1)

33(9.4)

30(8.6)

45(12.9)

231(66.0)

Doctorprescription onlybecause youasked him

14(4.0)

22(6.3)

25(7.1)

58(16.5)

233(66.2)

Almost one-quarter of the parents (26.1%)agreed that they would use any leftoverantibiotics whenever their child presentedwith similar URTI symptoms, 17.1% ofthem agreed that antibiotics have no sideeffects while 20.5% agreed that theywould change their doctors because ofnon-prescription of antibiotics as theythink appropriate.

Only 19.7% of the parents were muchdissatisfied with antibiotic non-prescription. The common reportedreasons for inappropriate antibiotic usealways or most of the time were non-seriousness of the child status (23.6%),lack of time and resources (20.8%),



pediatrician has prescribed the sameantibiotic in the past for the samesymptoms. (19.1%), pharmacist

recommendation (15%) andfriend/relatives recommendation (7.9%).

Table (9): Underlying Factors prompting parents to prescribe or avoid antibiotics for their children.

Rotated Factor Loadings*

Self-

Pres

crib

ing

Ask

ing

for

antib

iotic

s

Cau

tious

abo

utus

e

Ant

ibio

tics a

rego

od

Pref

er a

dvic

eon

ly

Dis

ease

self-

limiti

ng

Faster recovery with antibiotics - - - 0.547 - -

Scientists can produce new antibiotics. - - - 0.504 - -

Inappropriate use reduces efficacy - - - 0.534 - -

Antibiotic use prevents complications of URTI. - - - 0.732 - -

Not enough time or money for doctor visit. 0.751 - - - - -

Thought child’s condition was not serious enough 0.708 - - - - -

Same antibiotic prescribed in past, for same symptoms 0.586 - - - - -

Because a pharmacist recommended the antibiotic. 0.78 - - - - -

Because a friend/ relative recommended the antibiotic 0.694 - - - - -

Would reuse any leftover antibiotics for URTIsymptoms

0.412 - - - - -

Antibiotics are used too much and unnecessarily - - 0.462 - - -

Will change doctor as he prescribes antibiotics a lot - - 0.549 - - -

Parents & doctors should be informed on antibiotic use - - 0.65 - - -

Consider antibiotic adverse reactions when using them - - 0.584 - - -

Antibiotics have no sideeffects. - - -0.552 - - -

Ask doctor if antibiotics is necessary - - - - 0.767 -

Glad if doctor does not prescribe antibiotics - - - - 0.692 -

Doctor recommends antibiotics on the phone - 0.771 - - - -

Ask directly your doctor to prescribe antibiotics - 0.784 - - - -

Insist on prescribing antibiotics as a precaution - 0.711 - - - -

Doctor prescribes antibiotic only because you ask - 0.776 - - - -

Most URTI are viral, not requiring antibiotics - - - - - 0.75

Most URTI are self-limiting, not needing antibiotics - - - - - 0.577

Eigen Value 3.06 2.96 2.08 1.54 1.52 1.48

% of Variance 11.35 10.95 7.72 5.71 5.62 5.46

Cumulative % of Variance 11.35 22.3 30.02 35.73 41.35 46.81

* values > 0.4 only shownKMO and Bartlett's Test*

Kaiser-Meyer-Olkin Measure of Sampling Adequacy. .77Bartlett's Test of Sphericity Approx. Chi-Square 2236.97

Df 351p-value <0.001

* KMO > 0.5 suggest sample sizeadequacy for analysis, and statisticallysignificant Bartlett’s test for Sphericitysuggest correlations between items weresufficiently large for PrincipalComponent Analysis.



Antibiotic recommendation by physicianvia phone was reported always or most ofthe time by 6.7% of parents, 13.1% of theparents asked antibiotic prescriptiondirectly from their physicians, 12.5% ofparents insisted prescribing antibiotics and10.3% of them have mentioned that theirdoctors prescribed antibiotics mostly onlybecause they asked them.

Parental belief that antibiotics were beingused excessively was found to besignificantly correlated to parentalconsideration of antibiotic side effectsbefore use (Spearman’s rho 0.339, p-value0.01).

Parents who believed that antibiotics areused excessively also thought thatphysicians and patients should beinformed well about the judicious use ofantibiotics (Spearman’s rho 0.179, p-value0.01).

Parental belief that most URTI were viralin origin correlated with non-use ofantibiotics for URTI as these would beself-limiting (Spearman’s rho 0.187, p-value 0.01)

Parental belief that antibiotics have noside effects was found to be correlatedwith the behavior of insisting on antibioticprescription on unconfirmed diagnosis(Spearman’s rho 0.266, p-value 0.01).

Parental behavior of reusing leftoverantibiotics was found be correlated to self-prescribing antibiotics without physician’sadvice based on old knowledge for similarsymptoms (Spearman’s rho 0.377, p-value0.01) and to the belief that scientists candiscover antibiotics against resistantmicrobes (Spearman’s rho 0.105, p-value0.049).

Six factor combinations (components)based on screen-plot and having Eigenvalues higher than Kaiser criterion of 1,

were included here for interpretation,although rotated components, 7-9 couldalso be considered for inclusion as Eigenvalues were also higher than 1, but thesewere single items and the Scree plotappears to smooth out after 6.

These six common underlying factorswere responsible for overuse or cautiousapproach to antibiotics: InappropriateUse; Parental self-prescribing tendency,Parental tendency of asking for antibioticsfrom doctor and parental carefree attituderegarding over use while for appropriateUse; Parental cautious nature, Parentalpreference of advice over antibiotics andparental belief that URTI are mostly self-limiting.

DISCUSSION

This is not the first study indicating publicmisconceptions with regards to antibioticuse for common URTIs. In our study,although parents believed that mostURTIs are self-limiting, they expected toreceive antibiotics when this diagnosiswas made. Similarly, in a web-basedquestionnaire among a sample of thegeneral Dutch population, Cals et alshowed that nearly half of the responders(47%) incorrectly identified antibiotics asbeing effective in treating viral infections[38]. In the same study, the term “acutebronchitis” raised an immediateexpectation for an antibiotic prescriptionsimilar to “ear ache-otitis”, as shown inthe current study.

Almost half of parents believed thatURTIs are mostly self-limited althoughapproximately two-thirds of them askedphysicians to prescribe antibiotics fortreating URTI. Slightly less than half ofparents (47%) expected to possiblyreceive antibiotics when such a diagnosiswas given. However, it is incorrect toassume that 47% of the parents desiredonly antibiotic therapy because the



majority of them also preferred otherdrugs given for symptomatic therapy asparacetamol and analgesics.

Ear ache, fever and sore throat were themost common diagnosis for which parentsalways or usually expect to receiveantibiotics. Comparable results have beenreported in a study conducted amongGreek parents(32).

Approximately 15-35% of parents gaveantibiotics to their children withoutconsulting their physician and almost two-thirds of them appreciated thatunnecessary antibiotic use reduces itsefficacy.

Saudi parents also reported thatinformation regarding unnecessaryantibiotic use and resistance came fromtheir physicians, which is similar to whathas been reported by Greek parents(32)

while it is different from findings of apublic survey published by Hawkings et alwhere respondents reported that mostinformation regarding antibiotic resistancewas derived from the media(39). In thesame study, patients had a low sense ofpersonal ability to help contain thisproblem. It is possible that many parentsmight have endorsed their physicians astheir primary health influence and derivedmost of their opinions regardingantibiotics from them.

These different responses between studiesare possibly a reflection of the differencein health care systems. In westerncountries, the great majority of childrenhave regular follow-up by privateconsultant pediatricians who areaccessible either on the phone or with ahome/office visit. This leads to a closeand trusted relationship between theparent-child and the physician.

In KSA, parents have free access to alltypes of antibiotics despite a specific

legislation forbidding antibiotic usewithout a prescription.

It is not uncommon that many parentsbelieve weather change to be the maincause of URTI. Many think their childrenare more vulnerable to URTI, especiallyafter being exposed to colder weather orthe rainy season. This health belief maybe derived from their past experience orcultural belief. In the current study, only40% of parents recognizes that URTImostly of viral origin.

In this study, almost 53% of parents feltthat their child with flu like symptomsneeded antibiotics, which was notprescribed by the doctor. There is awidespread perception that for everysymptom, there is a specific remedy ordrug, and antibiotics are viewed aswonder drugs capable of healing a widevariety of illnesses ranging fromgastrointestinal disorders to headaches(40).Parents may feel that antibiotics couldhelp ease their anxiety and worry if it isgiven to their sick child. In addition, theydo not need to come back again to ask foran antibiotic after one to two days of“poor improvement” of the illness.

Principal component analysis reveals thatparents can be grouped as over-users andproper-users of antibiotics. The over-usershave a tendency to self-prescribe perhapsdue to easy availability of antibioticswithout the need of a doctor’sprescription, coupled with a carefreeindifferent attitude regarding antibioticresistance or irrespective of whosoevermay be giving the condoning advice andeven demanding or having no shyness indemanding the antibiotics from physicianin case his/her advice is sought.

The proper users / under-users ofantibiotics for their children have somecommon characteristics as well: these tendto be cautious in nature regarding



antibiotic use, believe that most URTI areself-limiting or viral in nature, thereforeare better informed and take their doctor’sadvice seriously, giving it value and thatsupersedes their personal preference.

It appears that the parents can be givenmore health education regarding properuse of antibiotics, as many parents alsofeel that it is needed. In addition,physicians need to be educated not bepressured by the parents, however, tighterregulation of pharmacies may be thesolution to curb easy access to antibiotics.This would limit influences of self, media,friends and those other than physiciansencouraging to initiate antibiotics forlesser than necessarily severe symptoms.

In the current research, data werecollected from parents through a self-administered questionnaire with the helpof trained nurses. This kind of datacollection was preferred versus the patternof interviewing the parents, taking intoaccount many drawbacks. First, theinterviewer might influence the parents'response during their conversation, andsecondly interviewees may respond inaccordance with what they believe to bethe "correct" replies. Additionally, theprobability of the responders'embarrassment towards the interviewerwould affect the quality of their answers.Moreover, a large number of interviewerswould have to be trained to be sent tointerview the parents, which wasimpractical. Finally, the variability amongthe interviewers could not be excluded.Using the questionnaires on the otherhand, each responder received the sameset of questions phrased in exactly thesame way, so the answers were derived ina more objective way. Questionnairesmay, therefore, yield data more precisethan information obtained through aninterview(41-42).

Among limitations of the current research,

first: the study was associated with a poorrecall of an URTI experience andantibiotic use. Therefore, parents’knowledge, attitude and practices may notalways be consistent with their actualbehavior. Invalid answers may also haveoccurred because of embarrassment.Second: the language and phrasing used inwriting the questions may not have beenfully understood by parents of lowsocioeconomic status (because of the useof medical terms), leading to inaccurateanswers. Finally, subjective appreciationof URTI symptoms (cough, runny nose,and ear ache) may have influenced theresponses.

In conclusion, this study has documentedmany areas in which parental knowledgeon antibiotic use for acute URTI isconsiderably lacking, resulting ininappropriate attitudes and practices. Halfof the parents attending the physicians fortheir children with URTI expected to getantibiotics. Factors responsible forinappropriate use were parental self-prescribing tendency, parental tendency ofasking for antibiotics from doctor andparental carefree attitude regarding overuse. Parents are self-prescribing becauseof their easy access of antibiotics withoutprescription and their indifferent attitudetoward microbial resistance. Parentspointed out that more education is neededfor both doctors and parents forappropriate antibiotic use.

From the results of the current study, werecommend implementation ofeducational programs on antibiotic use forparents, helping reduce their misuse. It isessential to establish evidence-basedclinical practice guidelines of acute URTIfor doctors with regular medical audit oftreatment for acute URTI to ensure thatpatients receive the best quality of care.The Saudi parents and physicians shouldhave a trusted relationship because mostparents will be happy with the information



provided to them and they would notchange their private physician ifantibiotics were used too much or toolittle. Strict enforcement of over-the-counter sale of antibiotics should beimplemented.

It is hoped that by identifying weak areasin parents’ knowledge and attitude, betterplanned educational and behavioralmodification efforts can be made toreduce unnecessary prescription ofantibiotics and curtail the still burgeoningproblem of bacterial resistance in childrenspecifically and in the community at large.

Acknowledgements

My great appreciation and thanks go to mysupervisor Dr. Saeed Ur Rahman for hissustainment and making himself availablefor expert advice.

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16. Elan P, Katzenstein D, Frankish CJ,Herbert CP, Milner R, Speert D, ChambersK: Prescribing practices and attitudestoward giving children antibiotics.Canadian Family Physician 2001, 47.



17. Pechère JC: Patients’ Interviews andMisuse of Antibiotics. Clinical InfectiousDiseases 2001, 33:S170-S173.

18. Butler CC, Hood K, Verheij T, Little P,Mel bye H, Nuttall J, Kelly MJ, Mölstad S,Godycki-Cwirko M, Almirall J, Torres A,Gillespie D, Rautakorpi U, Coenen S,oossens H: Variation in antibioticprescribing and its impact on recovery inpatients with acute cough in primary care:prospective study in 13 countries. BMJ2009, 338:b2242.

19. Nasrin D, Collignon PJ, Roberts L, WilsonEJ, Pilotto LS, Douglas RM: Effect of betalactam antibiotic use in children onpneumococcal resistance to penicillin:prospective cohort study. BMJ 2002,324:28-30.

20. Yagupsky P: Selection of antibiotic-resistant pathogens in the community.Pediatr Infect Dis J 2006, 25:974-76.

21. Bauchner H, Pelton SI, Klein JO: Parents,physicians, and antibiotic use. Pediatrics1999, 103:395-398.

22. Stivers T. Participating in decisions abouttreatment: overt parent pressure forantibiotic medication in pediatricencounters. SocSci Med 2002, 54(7):1111-30.

23. Mangione-Smith R, McGlynn EA, ElliottMN, McDonald L, Franz CE, Kravitz RL.Parent expectations for antibiotics,physician-parent communication, andsatisfaction. Arch PediatrAdolesc Med2001, 155:800-6.

24. Watson RL, Dowell SF, Jayaraman M, etal. Antimicrobial use for pediatric upperrespiratory infections: reported practice,actual practice, and parent beliefs.Pediatrics 1999, 104:1251-7.

25. Braun B, Fowles J. Characteristics andexperiences of parents and adults who wantantibiotics for cold symptoms. Arch FamMed 2000;9(7):589-595.

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27. Teng C, Leong K, Aljunid S, Cheah M.Antibiotic prescription in upper respiratory

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31. Sarahroodi S, Arzi A, Sawalha A,Ashtarinezhand A. Antibiotics self-medication among southern Iranianuniversity students. International Journal ofPharmacology. 2010; 6: 48-52.

32. Panagakou SG, Spyridis N, PapaevangelouV, Theodoridou KM, Goutziana GP,Theodoridou MN, Syrogiannopoulos GA,Hadjichristodoulou CS. Antibiotic use forupper respiratory tract infections inchildren: a cross-sectional survey ofknowledge, attitudes, and practices (KAP)of parents in Greece. BMC Pediatr. 2011Jul 5;11:60.

33. Chan GC, Tang SF. Parental knowledge,attitudes and antibiotic use for acute upperrespiratory tract infection in childrenattending a primary healthcare clinic inMalaysia. Singapore Med J. 2006Apr;47(4):266-70.

34. Shlomo V, Adi R, Eliezer K. Theknowledge and expectations of parentsabout the role of antibiotic treatment inupper respiratory tract infection--a surveyamong parents attending the primaryphysician with their sick child. BMCFamPract. 2003 Dec 30;4:20.

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36. Alumran A, Hurst C, Hou XY. AntibioticsOveruse in Children with UpperRespiratory Tract Infections in SaudiArabia: Risk Factors and PotentialInterventions. Clinical Medicine andDiagnostics 2011; 1(1): 8-16



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Effect of Aerobic Exercises in Blood Pressure, Abu Shaphe et al. 46

EFFECT OF AEROBIC EXERCISES ON BLOOD PRESSURE IN MILD ANDMODERATE HYPERTENSIVE MIDDLE AGED AND OLDER PATIENTS.

1*Abu Shaphe, 2Irshad Ahmad, 3Faizan Z Kashoo, 4Shadabuddin

ABSTRACT

Background: The prevention and treatment of hypertension are a high priority in medicineand public health. It is well documented that blood pressure reduction with medicationsignificantly reduces cardiovascular risk. Exercise remains a cornerstone therapy for theprimary prevention, treatment, and control of hypertension. This study aims at analysing theeffect of Aerobic exercises on reduction of Blood Pressure in the subject with Pre and Stage1 hypertension. Material and Methods: In this study patient with pre hypertension and stage1 hypertension without any pre medication cardiac therapy were selected. They underwent 6weeks of aerobic exercise training program. The aerobic exercise program consisted ofrepetitive, low resistance movements for at least 30 to 45 min, at 50% to 70% of Max heartrate, 3 to 4 times per week. The systolic & diastolic blood pressure were measured atbaseline and after 6 weeks of aerobic exercises training program usingsphygmomanometer10,13 and pulse rate was measured by manual method. Results: The resultof present study demonstrated a significant difference between group effects in both theSystolic and Diastolic Blood Pressure. It was found that there was significant difference inthe mean systolic blood pressure and diastolic blood pressure values for pre and stagehypertensive subjects. Conclusions: In conclusion, the inclusion of Aerobic exercise indaily activities is an efficient way of blunting the blood pressure changes in hypertensivepatients and it is of high statistical significance (p<0.005). The above mentioned efficiencyis more on Stage 1 hypertensive subjects when compared to pre hypertensive subjects.Keywords: Hypertension, Aerobic Exercise,

باألدویةالدمضغطخفضأنالمؤكدمن. العامةوالصحةالطبأولویاتمنالدمضغطارتفاعمنوالعالجالوقایة: ملخصوالسیطرةاألولیة،الوقایةفيالزاویةحجرتمثلتزالالالریاضةممارسة. الوعائیةالقلبیةالمخاطرمنملحوظبشكلیقلل

قبلمامرحلةفيالدمضغطخفضعلىالھوائیةالتمارینأثرتحلیلإلىالدراسةھذهتھدف. الدمضغطارتفاععلىوالعالجمامرحلةفيالدمضغطمرضياختیارتم: الدراسةمنھج. االوليالمرحلةفيالدمضغطارتفاعوالدمضغطارتفاعظھور

6لمدةریاضيلبرنامجأخضعوا. عالجأليخاضعینوغیرالبسیطالدمضغطارتفاعومرحلةالدمضغطارتفاعظھورقبلبنسبةدقیقة،45حتي30تقلاللمدةالمنخفضةالمقاومةبحركاتالمتكررةالریاضیةالتمارینمنالبرنامجیتألف. أسابیع

قبلواالنبساطياالنقباضيالدمضغطقیاستم. األسبوعفيمرات4إلى3, القلبضرباتمعدلمن٪ 70إلى٪ 50داللةذوكبیرافرقاالدراسةنتیجةأظھرت: النتائج. النبضمعدلقیاستمكماالھوائیةالتمارینمنأسابیع6وبعدجالبرنام

ھوالیومیةاألنشطةفيالریاضیةالتمارینإدراج: االستنتاجاتالتمارینوبعدقبلالدمضغطفي) p<0.005(احصائیةقبلمامرحلةمعبالمقارنةاالوليالمرحلةفيالدمضغطارتفاععلىاكثریةالفعالوتظھر, الدمضغطلخفضفعالةوسیلة.الدمضغطارتفاع

Received: 25 December, 2012; Accepted: 28 February, 2013*Correspondence: [email protected] Professor, Physical Therapy, College of Applied Medical Sciences, Jezan University, Saudi Arabia;2Lecturer, Physical Therapy, College of Applied Medical Sciences, Abha University, Saudi Arabia; 3Lecturer,Physical Therapy, College of Applied Medical Sciences, Majmaah University, Saudi Arabia; 4Lecturer, PhysicalTherapy, College of Applied Medical Sciences, Jezan University, Saudi Arabia



INTRODUCTION

Hypertension generally defined as bloodpressure persistently above 140/90 mm Hgand is extremely common. Even mildblood pressure elevations are associatedwith an increased risk of myocardialinfarction and stroke, and the risk risescontinuously with the severity of thecondition(1). Individuals who have bloodpressure that is more than 160/95 mm Hghave an annual incidence of coronary arterydisease (CAD), congestive heart failure,intermittent claudication, and stroke that isup to three times higher than normotensivepersons(2).They also have an exercisecapacity about 30% less(3).

Consequently, the prevention and treatmentof hypertension are a high priority inmedicine and public health. It is welldocumented that blood pressure reductionwith medication significantly reducescardiovascular risk. But nonpharmacologicstrategies for blood pressure reduction,including weight loss, dietary modification,and exercise, are also effective. Particularlywhen patients have mild to moderatehypertension, these strategies offer thepossibility of reducing blood pressure andcardiovascular risk without any of theadverse side effects associated withmedication.

Exercise remains a cornerstone therapy forthe primary prevention, treatment, andcontrol of hypertension. Exercise programsthat primarily involve endurance activityprevent the development of hypertensionand lower blood pressure (blood pressure)in adults with normal blood pressure andthose with hypertension(4).

With direct effects on circulation,metabolism, and the nervous system,exercise represents a multipronged assaulton cardiovascular risk. Whether used onlywith other lifestyle changes or incombination with medication, exercise is aparticularly attractive tool for hypertension

control. Many studies(5) have validatedexercise for treating high blood pressure.Exercise not only reduces blood pressure, italso lowers levels of low-densitylipoprotein cholesterol, reduces insulinresistance and glucose intolerance, andoften is associated with reduced bodyweight(6).

Influence of gender and weight. There wasno significant correlation between weightchange and blood pressure reduction.Comparable effects have been seen inadolescents, individuals over 60, and thosein between(7).

Generally, it appears that training in therange of 40% to 70% of VO2 max(50% to70% of maximum heart rate) was aseffective as, if not more effective than, amore intense regimen. Blood pressurereductions typically appeared within 3months of the start of training. Generally,no further blood pressure reduction occursafter 3 months of training, except in rareinstances(8). The program should be at least1 to 3 months to reach the stable stage, andtraining should be maintained indefinitely,because the hypotensive effect persists onlyas long as regular endurance exercise ismaintained.

The basic exercise prescription for allgroups is similar to that recommended bythe ACSM(9) to develop and maintaincardiovascular and muscular fitness inhealthy adults: at least a half-hour ofendurance exercise at 50% to 75% ofmaximal oxygen uptake (50% to 70% ofmaximum heart rate) done at least 3 days aweek. Physical activity of moderateintensity involving rhythmic movementswith the lower limbs for 50–60 minutes, 3or 4 times per week reduces blood pressureand appears to be more effective thanvigorous exercise(10).

The type of aerobic exercise is largely amatter of patient preference. Walking at a15-minute/mile pace is ideal for many; it



requires no equipment or special clothingand fits readily into most patients'schedules. Some prefer jogging, biking, orswimming. Exercise machines such astreadmills, stationary cycles, or cross-country ski devices provide an effectiveworkout for individuals who enjoyexercising at home, health club or gym.

The rationale for treating hypertension isthe reduction of cardiovascular morbidityand mortality. It is important to note thataerobic exercise has a positive effect onother cardiovascular risk factors, such asblood lipid levels, body weight, and insulinresistance. Overall, more than 40 clinicalstudies suggest an inverse relationshipbetween physical activity and the incidenceof coronary artery disease. With appropriatescreening and individualized exerciseprescription, regular physical activity canand should be incorporated into the life-style of an individual. Increases in activityamong sedentary persons have the potentialto bring major benefits in functionalcapacity, a sense of well-being and otherhealth outcomes(10).

Drug therapy has for long been themainstay management of hypertension. Thecommonly used drugs causes adverseeffects like bradycardia, bronchospasm,fatigue, deterioration of renal function,adverse metabolic effects like increasedserum cholesterol and reduction in HDLcholesterol. Reduction in blood pressure viaregular aerobic exercise reduces cost andmedication related side effects.

This study aims at analysing the effect ofAerobic exercises on reduction of BloodPressure in the subject with Pre and Stage 1hypertension.

METHODOLOGY

In this study patient with pre hypertensionand stage 1 hypertension without any pre

medication cardiac therapy were selected.They underwent a 6 weeks aerobic exerciseprogram.

After explaining the procedure an informedconsent was obtained from all the patients.Prescribed aerobic exercises were givenafter a brief warm up and the exerciseprogram ends with cool down exercises.The aerobic exercise program consisted ofrepetitive, low resistance movements for atleast 30 to 45 min, at 50% to 70% of Maxheart rate, 3 to 4 times per week. Thesystolic & diastolic blood pressure weremeasured at baseline and after 6 weeks ofaerobic exercises training program usingsphygmomanometer(10-13) and pulse ratewas measured by manual method.

All the patients were requested to attend theexperimental set up daily for the first 2weeks regularly to participate in theexercise program(14). Each patient is giventhe value of their target heart rate andinstructed to rest a while if the pulse ratereaches the target heart rate. Once thepatients were trained they were asked tocontinue the program for the remaining 4weeks at their residence. Patients weretaught to measure pulse rate and asked torecord their pulse rate and discomfort ifany. The blood pressure measurementsbefore and after 6 weeks of exerciseprogram was statistically analysed usingdescriptive and inferential statistics.

RESULTS

In this study 40 subjects with a mean ageof 42.52±5.29 ranging from 35 to 51years, mean systolic pressure of 147.87 ±12.52 and mean diastolic pressure 89.8 ±4.81 were taken. Required statistical testwere performed to find out the effect ofexperiment on the dependent variables,these findings are mentioned below.



The result of present study demonstrated asignificant difference between group effectsin both the Systolic and Diastolic BloodPressure (Table 1). To look for thedifference between the baseline readingstaken on the first day of the study with thepost-test readings of systolic blood pressureon the 45th day an independent t-test was

performed which showed a significantdifference in both group A as well as ingroup B (Table 2). It was found that thesystolic blood pressure decreased 3 mm/hgwhich was found significant (t=11.71,p<=0.001). A similar decrease of 21 mm/hgin group B was seen which was significant(t=22.74, p<=0.001).

From the analysis of systolic blood pressureand diastolic blood pressure changes afterexercise, it was found that there wassignificant difference in the mean systolicblood pressure and diastolic blood pressurevalues for pre and stage hypertensivesubjects. The objective of this study was tocompare the mean difference in systolicblood pressure and diastolic blood pressurefor group A and group B subjects toevaluate the effect of aerobic exercise onhypertension. When we analyse theresponse of group A and group B subjects.It was found that mean systolic blood

pressure of 137mmhg (group a) and158.75mmhg (group b) seen pre-test wasreduced to 134.35 (group a) and 137.75(group b) post-test. Also it was found thatmean diastolic blood pressure of 85.35(group a) and 94.25 (group b) seen pre-testwas decreased to 85 (group a) and88.1(group b) post-test.

DISCUSSION

The physiological basis for this reduction inblood pressure values is that the aerobicendurance training decreases blood pressurethrough a reduction of vascular resistance,

Table 1: Effect of aerobic exercises on systolic blood pressure

Group AM ± SD(n=20)

Group BM ± SD(n=20)

Paired t-test

T P

Pre SBP1 137 ± 1.78 158.75 ± 8.32 -11.43 0.001*

Post SBP45 134.3 ± 2.18 137.75 ± 6.04 -2.41 0.021*

IndependentT-test

t 11.711 22.74p 0.001* 0.001*

Table 2: Effect of aerobic exercises on diastolic blood pressure

Group AM ± SD(n=20)

Group BM ± SD(n=20)

Paired t-test

T P

Pre DBP1 85.3 ± 2.04 94.25 ± 2.65 -11.9 0.001*

Post DBP45 83.2 ± 1.89 88.1 ± 2.17 -2.17 0.001*

IndependentT-test

t 10.3 16.2p 0.001* 0.001*

Keys: Group A: Pre-hypertensive Subjects, Group B: Stage I hypertensive subjects, SBP-Systolic Blood Pressure, DBP- Diastolic Blood Pressure, 1- Baseline reading, 45- After 45day of aerobic exercise training.



in which the sympathetic nervous systemand the renin-angiotensin system appear tobe involved, and favourably affectsconcomitant cardiovascular risk factors(15-

18).

Fig. 1: Comparison of 1st and 45th day’sSystolic BP between pre & stage 1hypertensive patients.

Our results are similar to the studyconducted by A Kiyonaga et al (1985)1 toevaluate the effect of Blood pressure andhormonal responses to aerobic exercise.They selected twelve patients with essentialHypertension (WHO stages I-II) weresubjected to mild aerobic exercises for 10to 20 weeks. A reduction in SBP/DBP(mean) blood pressures by more than 20/10(13) mm Hg was seen in 50% of patientsafter 10 weeks and in 78% after 20 weeksof exercise. The results indicate thatexercise therapy is a potent nonpharmacological tool for the treatment ofessential hypertension, especially of the lowrennin type. When we analyse the meandifference values of systolic blood pressureand diastolic blood pressure in group A andgroup B subjects, the results shows thatthere is a significant difference (p<0.005) inthe values of systolic blood pressure anddiastolic blood pressure. The result showsthat the aerobic exercise plays an importantrole in reducing the blood pressure changesassociated with hypertension (19-20).

The results of this study accord with thefindings of most recent studies that showmoderate intensity aerobic exercise trainingcan lower blood pressure in patients withstage 1 and 2 essential hypertension. Theaverage reduction in blood pressure is 10, 5mm Hg for systolic and 7, 6 mm Hg fordiastolic blood pressure and thesereductions do not appear to be gender orage specific (21-24).

The next objective of this study was tocompare the role of aerobic exercise onsystolic blood pressure and diastolic bloodpressure between pre hypertensive (groupA) and stage 1 hypertensive (group B)subjects. When we analyze the results itwas found that there was significantdifference (p<0.005) in the values ofsystolic blood pressure and diastolic bloodpressure between group A and group Bsubjects. Result shows that patients withstage 1 hypertension showed much changein the systolic blood pressure and diastolicblood pressure values when compared withthe pre hypertensive subjects (25-26).

Fig. 2: Comparison of 1st and 45th day’sDiastolic BP between pre & stage 1hypertensive patients.

The results take a strong support fromKaren T. Lesniak et al (2001)27

Hypertensive subjects appear to experiencegreater reductions than normotensivesubjects. Exercise interventions may be



safely and effectively used with mild tomoderate as well as severe levels ofhypertension. Through this present study itis clear that aerobic exercise plays a majorrole in the control of hypertension and thesebeneficial effects are found more in stage 1hypertensive subjects when compared topre hypertensive patients (28).

CONCLUSION

In conclusion, the inclusion of Aerobicexercise in daily activities is an efficientway of blunting the blood pressure changesin hypertensive patients and it is of highstatistical significance (p<0.005). Theabove mentioned efficiency is more onStage 1 hypertensive subjects whencompared to pre hypertensive subjects.

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REVIEW ARTICLE MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Recent Insight into Nosocomial Infections, Nasser Al-Jarallah 53

RECENT INSIGHTS INTO NOSOCOMIAL INFECTIONS- ANEGLECTED CONDITION

1*Nasser Jarallah

ABSTRACT

Nosocomial infections (NI), also known as hospital acquired infection (HAI), isinfection whose development is favoured by a hospital environment, such as oneacquired by a patient during a hospital visit or one developing among hospital staff.Such infections include fungal and bacterial infections and are aggravated by thereduced resistance of individual patients (4). Nosocomial infections continues to be ofmajor clinical and epidemiologic importance in developing countries (2,3) as itconstitutes a major source of morbidity, mortality and significant incremental healthcare expense for the hospitalized patient, despite major advances in clinical sciences.As per the Study on the Efficacy of Nosocomial Infection Control (SENIC) routinesurveillance of NI has become an integral part of infection control and qualityassurance in US hospitals because its potential of reducing nosocomial infections(1).Studies performed in the United States have demonstrated that an integrated infectioncontrol program that includes targeted device-associated surveillance can reduce theincidence of nosocomial infection by as much as 30% and lead to reduced health carecosts(1).

التيعدوىاليھ،)HAI(المكتسبةالمستشفیاتعدوىباسمأیضاالمعروف،)NI(المستشفیاتعدوىخص:ملفيالعاملینأحدأوالمستشفىزیارةخاللالمریضعلیھاحصلیالتيمثلالمستشفى،بیئةیساعدھا على النمو

منالمقاومةانخفاضجراءمنتفاقمتوالتيوالبكتیریةالفطریةاألمراضتشملاألمراضھذه. المستشفىالبلدانفيوالوبائیةالسریریةكبرىأھمیةذاتتزالالالمستشفیاتعدوى). JS،1996غارنر(الفردیةالمرضى

والمراضةللوفیاترئیسیامصدراشكلتاأنھكما) VD،2004روزنتال؛MA،2005جیفیك(النامیةالعلومفيالكبیرالتقدممنالرغمعلىالمستشفى،فيلمریضاحسابعلى المتزایدةالصحیةالرعایةخاصةو

)NIعلى() SENIC(الروتینیةالمراقبةبالمستشفیاتالمكتسبةالعدوىمكافحةفعالیةحوللدراسةوفقا. السریریةحدللإمكاناتھابسببالمتحدةالوالیاتمستشفیاتفيالجودةوضمانالعدوىمكافحةمنیتجزأالجزءاأصبحت

مكافحةأنالمتحدةالوالیاتفيأجریتالتيالدراساتأظھرتوقد). RW،1985ھالي(المستشفیاتعدوىمنةداخلالمكتسبةالعدوىحدوثمنتقللأنیمكنالمرتبطةالمراقبةجھازاستھدافیتضمنبرنامجةمتكاملالالعدوى

).RW،1985ھالي(ةالصحیالرعایةتكالیفخفضإلىوتؤدي،٪30إلىتصلبنسبة

Received: 13 December, 2012; Accepted: 7 February, 2013*Correspondence: [email protected], College of Applied Medical Sciences, Majmaah University, Al-Majmaah, Saudi Arabia



INTRODUCTION

Nosocomial are caused by a wide variety ofpathogens; including Pseudomonasaeruginosa, Klebsiella spp., Escherichiacoli, Enterococci, Staphylococci etc.Staphylococci and Enterococci are majorcauses of nosocomial infections. Theycause superficial skin lesions such as boils,styes and more serious infections such aspneumonia, mastitis, phlebitis, meningitisand urinary tract infections; and deep-seated infections, such as osteomyelitis andendocarditis. Methicillin-resistant S. aureus(MRSA) is a strain of S. aureus which bydefinition is resistant to the semi- syntheticpenicillins (i.e. methicillin, nafcillin, andoxacillin). As such, it is resistant to all otherbeta-lactam antibiotics (including otherpenicillins, cephalosporins andcephamycins). Additionally, MRSA is oftenresistant to other classes of antibioticsincluding aminoglycosides, macrolides andquinolones. Thus, MRSA is not onlymethicillin resistant but also multiply-resistant as well(19).

Surveillance of NI is a necessary first steptoward reducing the risk of infection amongpatients treated through trained nurseepidemiologists who should assumeincreasing responsibility for education ofpersonnel and for performance of studiesdesigned to elucidate the mechanism andprevention of hospital infections. The nextstep is to apply infection control practicesthat have been shown to preventnosocomial infections.

PREVALENCE OF NOSOCOMIALINFECTION

NI are found to be more prevalent inHospital Departments & IndividualSystems(14,15,16). In general nosocomialinfection rates vary by service and by levelsof invasive management of seriously illpatients. Accordingly the incidence ofNosocomial infections are highest in

Intensive care Unit (ICU) followed byCoronary care unit (CCU), Highdependency Unit, Post-operative ward etcin prevalence to be followed gradually inrank by general surgical and medicaldepartments. Departments with lowinfection rates include Ophthalmology andMaternity.

Studies on Nosocomial infections show thatincidence of HAI is highest in largeteaching or academic hospitals,intermediate in small teaching hospitals andlowest is small non-teaching Hospitals.These studies show that immunity of thepatient is the major factor in HospitalAcquired infection. In large Hospital, moreseriously ill patients are admittedsophisticated therapy is given. Thesepatients are immunocompromised by thedisease as well as the treatment (surgery ±chemotherapy + radiotherapy) that isimmunosuppressive therapy etc.

As for the sites of infection, Urinary tractinfection (UTI) by far, is the commonestinfection Pneumonia, Surgical woundinfections are the next most common, Skininfection, though relatively un-common intemperate zone, are relatively moreprevalent in hot countries. Then comes.Blood stream infection namely septicaemia,bacteraemia , IV infection site infection.Infection of the peritoneal cavity(peritonitis).

CLASSIFICATION OF NOSOCOMIALINFECTION

NI may be endogenous, arising from aninfectious agent present within a patient'sbody, or exogenous, transmitted fromanother source within the hospital. Inaddition to patient-to-patient spread, othersmay be involved, including staff, students,visitors and voluntary workers(18).



Guidelines on hospital hygiene. Disinfection. Sterilization. Cleaning. Laundering. Catering. Waste-disposal.

Guidelines on procedures: Urethral Catheterization. Prevention of surgical wound

infection. Tracheostomy. Intravenous fluid

administration. Prevention of nosocomial

Pneumonia Hand washing etc.

Guidelines on special issues: Prevention of nosocomial

H.I.V Infection. Hepatitis B immunization. Prevention of infection in

hemodialysis unit; transplantunit etc.

COMMON MODES OFTRANSMISSION

1. Direct Contact: E.g. Direct contactbetween patients is the most importantmode of transmission.

2. Self-infection: From patients ownpathognomic floras of skin, nose, mouth,throat periniusn, infected lesions.

3. Indirect Contact: E.g. Indirect contactwith contaminated inanimate objects likeimproperly sterilized instruments,dressing materials; contaminated fomitese.g. bed pans, blankets etc etc.

4. Air Borne Transmission: From outsidehospital-With air flow from infectedareas like-Dustbins, open morgues.

5. Vector Borne Transmission: E.g. Via.Mosquitoes-malaria, Dengue etc.

6. Transmission by Common Vehicles: e.g.via. Food, blood, Water (contaminated)Medications etc.

PREVENTION OF NOSOCOMIALINFECTION

The other frustrating fact regarding thenatural history of Nosocomial or HospitalAcquired Infections is that they cannot beeradicated entirely; but many of them canbe prevented by proper control measures. Inplaces where control programs can beimplemented, there had been a provenreduction of morbidity and mortality.Furthermore, the money that can be savedby reduction of nosocomial infections ismuch more used for infection control(13).

Several approaches have been adopted inorder to limit pathogen colonization. Stricthygienic practices by healthcare personnele such as basic hand washing e along withregular disinfection of the hospitalenvironment are considered by some ofbasic importance. However, it should benoted that routine disinfection of thehospital environment is controversial(21,22,23). Since nosocomial infections remainan important problem even for hospitals

with well-organized and decisivelyimplemented infection control programs,studies of innovative infection controlmeasures are warranted.

Three fundamental principles govern themeasures that should be taken in order toprevent the transmission of HAI in health-care facilities:

Isolation: Identify and separate/segregatefrom other patients:

Known infected patients, Patients with certain symptoms or behaviors (e.g., poor hygiene), Patients with high potential for

contamination of the environment(uncontained, draining surgical wound)

Routes of transmission: Eliminate orminimize potential routes of transmission



from sources of microorganisms (e.g., useaseptic technique when inserting IVcatheters).

Barrier Techniques: Use basic barriertechniques to eliminate or minimize the riskof transmitting infectious agents frompatient to patient, from patient to caregiver,and from caregiver to patient. Presume allpatients are infected until proved otherwise.

Guidelines used in other hospitals orcountries should be adapted so that they areappropriate to be implemented in thehospital. The guidelines should cover mostroutine procedures and treatments asfollow(17).

Nosocomial infection caused byMethicillin resistant Staphylococcusaureus (MRSA)

The worldwide emergence of multidrugresistant bacterial strains is of growingconcern. These infections are difficult toeradicate due to resistance to manyantimicrobials, thus major cause ofmorbidity and mortality, leading directlyand indirectly to an enormous increase incost of hospital stay for the patients andalso emergence of new health hazards forthe community.

MRSA colonization and infection in acuteand non-acute care facilities have increaseddramatically over the past two decades,evidenced by the increasing number ofreported outbreaks in the medical literature.Because of its resistance to antibiotics,management of MRSA infections requiresmore complicated, toxic and expensivetreatment. It is important for the health careprofessional to understand the differencebetween colonization and infection.Colonization indicates the presence of theorganism without symptoms of illness. S.aureus permanently colonizes the anteriornares of about 20% to 30% of the generalpopulation. Hospital workers are more

likely to be colonized than persons in thegeneral population, presumably because ofincreased exposure(20).

IMPROVED HAND HYGIENE-REDUCTION IN NOSOCOMIAL

INFECTION

Hand hygiene is a fundamental aspect ofinfection control, with several studiesshowing a decline in nosocomial infectionrates when compliance with hand hygieneis enhanced5,6,7). Despite universalacknowledgement of the pivotal role thathand hygiene plays in reducing nosocomialinfection, compliance among health careworkers remains poor, with rates rangingfrom 16% to 81% (8,9,10).

Pittet et al studied predictors ofnoncompliance with hand hygiene in anobservational study and found that, inmultivariate analysis, physicians andnursing assistants had lower compliancerates than nurses. Of concern, compliancewas lower in ICUs and during proceduresthat carried a high risk of contamination(11).Dubbert et al found that, althougheducation alone improved compliance ratestransiently, performance feedback resultedin a more sustained improvement incompliance(9). In a pre- and post-intervention study in an inpatientrehabilitation unit, McGuckin et al used apatient education model consisting ofpatients asking HCWs coming into contactwith them whether they had washed theirhands. Compliance (measured throughsoap/sanitizer usage per resident-day)improved to 94% during the 6-weekintervention. However, adherence to handhygiene fell to 40% in the follow-upperiod(12).



REFERENCES

1. Haley RW, Culver DH, White JW, MorganWM, Emori TG, Munn VP, et al. The efficacyof infection surveillance and control programsin preventing nosocomial infections in UShospitals. Am J Epidemiol 1985;121:182-205.

2. Cevik MA, Yilmaz GR, Erdinc FS, Ucler S,Tulek NE. Relationship between nosocomialinfection and mortality in a neurologyintensive care unit in Turkey. J Hosp Infect2005;59:324-30.

3. Rosenthal VD, Guzman S, Crnich C. Device-associated nosocomial infection rates inintensive care units of Argentina. InfectControl Hosp Epidemiol 2004;25:251-5.

4. Garner, J.S., W.R. Jarvis, T.G. Emori, T.C.Horan and J.M. Hughes, 1996. CDCdefinitions for nosocomial infections. In:APIC infection Control and AppliedEpidemiology: Principles and Practice. Ed.,Olmsted, R.N., St. Louis: Mosby, pp: A1-A20.

5. Doebbeling BN, Stanley GL, Sheetz CT, PfallerMA, Houston AK, Annis L, et al. Comparativeefficacy of alternative hand-washing agents inreducing nosocomial infections in intensivecare units. N Engl J Med 1992;327:88-93.

6. Pittet D, Hugonnet S, Harbarth S, Mourouga P,Sauvan V, Touveneau S, Perneger TV.Effectiveness of a hospital-wide programme toimprove compliance with hand hygiene:Infection Control Programme. Lancet2000;356:1307-12.

7. Fendler EJ, Ali Y, Hammond BS, Lyons MK,Kelley MB, Vowell NA. The impact ofalcohol hand sanitizer use on infection rates inan extended care facility. Am J Infect Control2002;30:226-33.

8. Pittet D. Improving adherence to hand hygienepractice: a multidisciplinaryvapproach. EmergInfect Dis 2001;7:234-40.

9. Dubbert PM, Dolce J, Richter W, Miller M,Chapman SW. IncreasingvICU staffhandwashing: effects of education and groupfeedback. InfectvControl Hosp Epidemiol1990;11:191-3.

10. Donowitz LG. Handwashing technique in apediatric intensive carevunit. Am J Dis Child1987;141:683-5.

11. Pittet D, Mourouga P, Perneger TV.Compliance with handwashing in a teachinghospital. Infection Control Program. AnnIntern Med 1999; 130:126-30.

12. McGuckin M, Taylor A, Martin V, Porten L,Salcido R. Evaluation of a patient educationmodel for increasing hand hygiene compliancein an inpatient rehabilitation unit. Am J InfectControl 2004;32:235-8.

13. Sudsukh U, The control of nosocomialinfections in Thailand in the future, J MedAssoc Tahi 1989 72; (supp l 2) 44-5.

14. Danchaivijitr S, Mortensen N. Use ofprevalence data, In: Hospital InfectionPrevalence Survey and Program Guidea WHOManual (Unpublished).

15. Mayon-White RT, Dual G, Kereselidze T,Tikhomirov E. An international survey of theprevalence of hospital acquired infection. JHosp Infect 1988: 11: S43-8.

16. Britt MR, Burk JP, Nordguist AG, et al.Infection control in small hospital: prevalencesurveys in 18 institutions. JAMA 1976; 236:1700-3.

17. S.A. Khan. Nosocomial infection: generalprinciples & the consequences, importance ofit’s control and an outline of the control policy- A Review Article. Bangladesh MedicalJournal 2009; 38(2): 60-64

18. Boyce JM. Infect Control Hosp Epidemiol1992, 13:725.

19. Shrestha B, Pokhrel B, Mohapatra T. NepalMed Coll J. 2009; 11:123

20. Van Hal SJ, Stark D, Lockwood B, MarriottD, Harkness J. J Clin Microbiol 2007; 10:1128

21. Dettenkofer M, Wenzler S, Amthor S, AntesG, Motschall E, Daschner FD. Doesdisinfection of environmental surfacesinfluence nosocomial infection rates? Asystematic review. Am J Infect Control2004;32:84-89.

22. Dettenkofer M, Spencer RC. Importance ofenvironmental decontamination e a criticalview. J Hosp Infect 2007;65: 55-57.

23. Kramer A, Schwebke I, Kampf G. How longdo nosocomial pathogens persist on inanimatesurfaces? A systematic review. BMC InfectDis 2006;6:130.


Non-Cirrhotic Portal Hypertension, Moattar R Rizvi 58

ANIMAL MODELS OF NON CIRRHOTIC PORTALHYPERTENSION (NCPH)

1*Moattar R Rizvi

ABSTRACT

Portal hypertension (PHT) is a common and serious clinical syndrome often associatedwith chronic liver diseases. Portal hypertension may be defined as portal pressuregradients of 12 mmHg or more in the veins of the portal system caused by obstruction inthe liver from intrahepatic or extrahepatic portal venous compression or occlusion(often associated with chronic liver disease), causing enlargement of the spleen andcollateral veins. In the western world, hepatic cirrhosis related to chronic hepatitis Cand B and alcoholic cirrhosis are the conventional rationale for the development portalhypertension. Besides cirrhosis, a number of disorders collectively called as non-cirrhotic portal hypertension (NCPH) can also result in portal hypertension. Evaluationof non-cirrhotic portal hypertension is more difficult than cirrhotic portal hypertension,both from clinical and pathological perspectives.

ویمكن. المزمنةالكبدأمراضمعترتبطماوغالباوخطرةشائعةسریریةمتالزمةھوالبابيالدمضغطارتفاع:ملخصاوانسدادعنوالناتجأكثرأوزئبقملم12اليالبابيالنظاماوردةفيالضغطیصلعندماالبابيالدمضغطارتفاعتعریفواألوردةالطحالتضخمفيیسببمما،) المزمنةالكبدألمراضعادةوالمصاحب(الكبدداخلالبابیةاالوردةعليالضغطاالسبابمنالكحولعنالناتجالكبدوتلیفBوCالمزمنالكبدبالتھابالمتصلالكبدتشمعالغربي،العالمفي. الجانبیةالدمضغطارتفاعباسممجتمعةتسمىاخريباتاضطراھنالكالكبد،تلیفالىباإلضافة. البابيالدمضغطالرتفاعالتقلیدیةبتلیفمرتبطالغیرالبابيالدمضغطارتفاعتقییم. البابيالدمضغطارتفاعإلىأیضایؤديالكبدبتلیفمرتبطالغیرالمدخل

والمرضیةالسریریةالنظرةوجمنالكبدي،التلیفمنالناتجالبابيالدمضغطارتفاعتقییممنصعوبةأكثرھوالكبد

Received: 16 December, 2012; Accepted: 6 March, 2013*Correspondence: [email protected] Professor, Medical Physiology, College of Applied Medical Science Al-Majmaah University,Majma’ah, Kingdom of Saudi Arabia.



INTRODUCTION

Non-cirrhotic portal fibrosis (NCPF) andextra-hepatic portal vein obstruction(EHPVO) are very common in developingcountries and almost always present onlywith characteristic features of portalhypertension. Non-cirrhotic portal fibrosis(NCPF), the equivalent of idiopathic portalhypertension in Japan and hepatoportalsclerosis in the United States of America,is a common cause of portal hypertensionin India and accounts for 15-40% (8,21,37).Its etiopathogenesis is still obscure, aspatients present late when bleeding hasalready occurred from the varices. Thedisease is common in the lower or lower–middle socio-economic strata of society.Improved hygienic standards of living

could explain the relative rarity of thedisease in the West and decliningincidence in Japan.

EXPERIMENTAL MODEL OFPORTAL HYPERTENSION

The inability to solve the enigma of portalhypertension shoots essentially from notbeing able to produce the diseaseexperimentally in animals. Animalmodels, mimicking the human situation,have helped us in exploring thepathophysiology of portal hypertension asethical considerations limit experimentalprocedures in humans. The use of animalmodels as an alternative source hasallowed researchers to investigate the stateof disease in ways which is inaccessible ina human patient. According to the AnimalCare guidelines high-degree resemblanceto human condition, high reproducibilityand homogeneity and a low mortality, arethe basic criteria for animal model ofportal hypertension (Table1).

MODELS OF INTRAHEPATICPORTAL HYPERTENSION

Several models of intrahepatic portalhypertension in animals have beendeveloped.. The most common are modelsof cirrhosis from any causes, secondarybiliary cirrhosis, idiopathic portalhypertension and schistosomiasis.

Table 1: General considerations in choosinganimal models (modified from Mullen &McCullough)4

Reproducibility: Rate of reproducing the modelshould be high with theConsistent time frame to attaindesired state.

Specificity: The model should bear only thecharacteristic anomalieswithout other complicatingproblems.

Costs: Consider not only the directcosts, but also indirect costssuch as animal housing (and,therefore, the time to achievethe desired state). An expensivebut reliable model could becheaper than a cheap butinconsistent model.

Safety: Animal handling shouldinvolve no risk both to theperson engaged in as well asthe animal.

Size: The size should be appropriateenough to have great deal ofvascular study. The size alsodetermines drug spending.

Ethics: Different ethics committees canhave different opinions aboutthe acceptability of one model

Feasibility: Whether the laboratory has theexpertise, manpower facilities,etc, to generated or hand themodel.

Table 2: Effect of arsenic exposure on serum albuminand aspartic lactic transaminase (ALT)Experimental details Albuin (g/dl) ALT (IU/l)

Control 3.40±0.06 51±27

120 ppm for 3months

3.32±0.50 101±56*

240 ppm for 3months

3.02±0.30 136±82*

360 ppm for 3months

3.24±0.90 56±49

360 ppm for 6months

3.3±0.60 183±84*

500 ppm for 1.5months

2.72±0.20* 56±12.2

*P <0.05; Values are expressed as mean ± SE



Whole liver compression – Dog model:Yamana et al(38) produced a unique modelof whole liver compression in dogs wherewhole of the liver was wrapped andcompressed with a tense ligature ofpolypropylene mesh or gauze. Both theintrahepatic resistance and portal venouspressure were raised without developmentof hepatorenal collaterals for nine weeksafter the surgery. Since this whole livercompression method requires nocomplicated surgical maneuver, theexperimental animals survived well.

Cirrhosis induced by carbon-tetrachloride (CCl4): Currently, thecarbon-tetrachloride (CCl4) hepatotoxin-induced model of cirrhosis, mimickinghuman non-biliary cirrhosis, is consideredthe ‘gold standard’ for cirrhosis (22).However, it is associated with majordrawbacks such as low reproducibilityresulting from a mortality rate averaging30% during induction, poor homogeneityand a rather low resemblance to humancirrhosis, as typical features of humancirrhosis, such as nuclear atypia, mitosesand nodular parenchymal regeneration,resulting in a more typical distortedarchitecture, are not so prominent.Additionally, inhalation with CCl4 seems

to be the sole way of achieving a highyield of cirrhosis, which might posepotential health hazards for itsinvestigator(6,7,22).

Secondary billiary cirrhosis induced bybile duct ligation: Chronic cholestasisproduces secondary biliary cirrhosis inanimals as it does in man. The chronic bileduct-ligated rat model (CBDL) iscommonly used model of PHT (6). This

surgically induced model of cirrhosis canbe used after 3–5 weeks and is thereforeless costly than a hepatotoxin-inducedliver damage model(10). There are,however, several disadvantages: highmortality (> 40%), haemodynamicinstability owing to the toxic effect of thecholestasis on renal function, and highersusceptibility for sepsis owing to theabsence of bile in the digestive tract,exaggerated dilatation of the extrahepaticbile duct causing extrinsic compression onportal vascular structures, and the fact thatCBDL rats do not show elevated portalvenous inflow when studied underpentobarbital anaesthesia (6; 22).

Table:3 Collagen and 4-hydroxyproline (4-HP) levels inliver following different dosage of arsenic at 1.5, 3 and 6months of treatment.Duration(months)

Experi-mentalgroup(ppm)

Hepaticcollagen(µg/mgprotein)

Hepatic 4-HP(µg protein)

1.5 Control 11.3±1.47 23.5±4.36120 24.3±0.71a 102.8±6.50c

240 13.6±1.60 152.0±18.80c

360 17.7±1.30a 70.5±1.30b

500 87.8±8.90c 132.5±9.81c

3 Control 12.0±1.11 22.3±4.00120 26.4±2.90a 320.0±15.10c

240 63.1±7.00c 193.0±11.80c

360 71.8±5.80c 200.0±10.10c

6 Control 14.1±2.50 29.9±5.50120 595.4±130.0a 242.0±79.80a

240 397.7±129.4a 164.8±9.80a

360 159.3±3.90a 373.0±14.40a

P values: a <0.05; b<0.01; c<0.001; Values areexpressed as mean ± SE

Table 4: Effect of oral arsenic feeding on liverhistopathology of mice of different groupsGroup(ppm)

Dur

atio

n(m

onth

s)Fi

bros

is (%

)

Infla

mm

atio

n(%

)

Kup

ffer

cell

hype

rpla

sia (%

)

Nor

mal

(%)

Control --- --- --- --- 100120 1.5 --- 25 42 29120 3.0 --- 18 --- 82120 6.0 --- 25 --- 75240 1.5 --- 44 --- 56240 3.0 --- 25 38 37360 1.5 --- 40 13 47360 3.0 --- 44 --- 56360 6.0 --- 40 --- 60500 1.5 30 23 --- 46



Cirrhosis induced by hepatotoxinthioacetamide (TAA): A potentialalternative to these above-mentionedproblems is the induction of cirrhosis inthe rat with the hepatotoxin thioacetamide(TAA), which is suggested to have more incommon with human cirrhosis(1). To datethe problem with TAA has been theheterogeneous production of cirrhosis(varying from 3 to 7 months (28)) whenadministered orally. To overcome theseinconveniences, Li et al.(23) recentlysuggested an intoxication protocol over 12weeks which adapts the dose of TAA indrinking water according to the weeklybody weight, as originally described forintragastric administration of CCl4 by

Proctor(29). W. Laleman in 2006 concludedthat thioacetamide, adapt to weekly weightchanges, leads to a homogenous,reproducible model of cirrhosis in the ratin 18 weeks, which is associated with allthe typical characteristics of portalhypertension, including endothelialdysfunction(36).

Periportal fibrosis: Other cirrhosis orprecirrhosis induced by alcohol have beendescribed in the literature. It has beenshown that portal hypertension develops inalcohol-fed baboons(24). These baboonsdeveloped fatty liver and perivenularfibrosis. Cirrhosis and portal hypertensionalso developed in some monkeys with a

Table 6: Hepatic Glutathione and other Enzymes of the Antioxidant Defense system in Control and Arsenic-Exposed Mice at the End of Different Study Periods

Month

Group G6PDH(nmole NADPreduced/min/mg/protein

GR (umole ofNADPH

oxidation/min/mg protein)

GST (nmoleproduced/min/

mg protein)

Catalase(umoleH202

reduced/min/mg

protein

GSH-Px(umole

NADPHoxidation/min/mg protein)

3 Control (n = 5)Experimental (n = 6)

10.32±0.23011.04±0.56

24.38+0.8927.39±2.66

118.02±1.12130.05±11.04**

6.78±0.227.26±0.59

8.28±0.389.19±0.67^


10.46±0.848.39±0.62#

24.92±0.3725.43±1.31

118.42±2.04121.85±7.30

6.68±0.336.34±1.05

8.27±0.287.49±0.94^


10.05±0.417.02±0.29**

24.99±0.8324.24±2.21

117.41±1.87113.92±4.70

6.78±0.276.06±0.48*

8.29±0.207.01±0.61#


9.80±0.256.39±0.64**

25.04±0.4420.86±1.88**

117.73±2.24102.68±6.90**

6.74±0.295.45±0.50**

8.03±0.245.95±1.01**


9.94±0.265.02±0.87**

24.93±0.7918.43±2.02**

122.28±4.2288.72±18.0**

6.47±0.264.55±0.85**

8.02±0.555.20±1.12**

*p<0.05; ^p<0.02; #p<0.01; **p<0.001

Table 5 Liver function Tests in Control and Arsenic-Exposed Mice at the End of Different Study PeriodsMonth Group T. Protein

(g/dL)Albumin

(g/dL)ALT (IU/L) AST (IU/L) ALP (IU/L)


6.46±0.346.23±0.46

3.24±0.353.08±0.29

22.80±2.7723.83±2.99

23.40±4.4424.10±4.57

107.6±5.02109.8±6.99

6 Control (n = 10)Experimental (n =10)

6.58±0.586.50±0.73

3.42±0.453.17±0.48

24.30±3.8026.30±4.49

23.50±2.2726.00±5.29

108.6±8.03111.7±5.83


6.52±0.546.40±1.32

3.40±0.603.08±0.68

22.80±2.7831.20±9.65

22.60±1.6726.80±4.29

113.4±8.64116.8±11.62

12 Control (n = 9)Experimental (n =14)

6.36±0.916.66±0.86

3.06±0.453.03±0.61

25.00±4.2734.60±6.93**

23.50±2.7832.80±8.21*

121.5±6.8128.4±12.02


6.05±0.265.95±0.32

3.11±0.122.71±0.24*

27.50±4.1040.80±5.60**

25.50+6.6338.16±6.79*

123.7±5.02164.6±10.94**

*p<0.01; **p<0.001



diet for a period of 16 months lackingcholine, low in protein (5%), and rich incholesterol. In dogs it has beendemonstrated that the repeated intraportalinjection of a polyvinyl alcohol suspensionover a 2-6 months period produces portalhypertension (2).

MODELS OF EXTRAHEPATICPORTAL HYPERTENSION:

Portal Vein Stenosis Model: The mostcommon animal model of prehepatic portalhypertension currently used is partialportal vein ligation. This model has beendeveloped in the rats (4,5,35), mice (9, 14) andrabbits(3). Neuhof in 1912 firstconsummate the production of portal

hypertension in animals by partialconstriction of the portal vein. This studywas carried out in dog with the degree ofconstriction of portal vein up to 50%.After a period of recovery, the portal veinwas further stenosed to 25% of its originaldiameter and finally after 6 days the portalvein was completely ligated. Neuhofclearly described anastomoses between thehepatic and diaphragmatic vessels, thegastric and esophageal veins, and theportal system and vena cava in thepostmortem report at 34 days.Splenomegaly was also present but theremaining portal tract appeared to benormal. Later, Reynell stenosed the portal

vein in rats with a 50% mortality rate(30).Most of the surviving rats had portalhypertension. Between 1973-75 it wasshown that the diameter of the stenosis andthe body weight or age of the rat werecritical in determining survival(25).

Portal vein occlusion usingmicrospheres: A new experimental animalmodel for portal hypertension wasdeveloped by an intraportal injection ofDEAE-cross-linked dextran microspheres(100±25 microns in diameter) in thefemale Japanese white rabbit characterizedby elevation in portal pressure and portalsystemic collateral (Komeichi H, 1991).Histology of the liver revealed portal

obstruction by the injected microspheres inalmost all portal triads, resulting in aforeign body granuloma. Since this modelappears to show the two main conditionscharacteristic of portal hypertension,persistent elevation of portal pressure andboth extra- and intrahepatic portalcollaterals, mimicking those in humans,portal obstruction by injecting DEAE-cross-linked dextran microspheres into theportal vein of the rabbit could provide aversatile model for portal hypertension.



MODELS OF PRESINUSOIDALPORTAL HYPERTENSION:

The exact mechanism for the developmentof idiopathic portal hypertension has notbeen clarified but the pathomorphologicalchanges caused by this syndrome havebeen widely studied in animals. Theselesions have been attributed to intra-abdominal infection.

MODELS OF IDIOPATHIC PORTALHYPERTENSION (IPH):

Prolonged sensitization with egg albumin:Okabayashi and Suzuki producedidiopathic portal hypertensive models inrabbits characterized by splenomegaly andportal hypertension. They emphasizedchronic antigenic stimulation as being thecause of splenomegaly with prolongedintravenous administration of egg albumin.Later, the experiment was conducted ondogs as the rabbit could not tolerate morethan three intraportal injections. However,they could not provide the mechanismwhereby the spleen reacts to chronicantigenic stimulation. The histologicalchanges that occurred in these animalswere characterized by early portalinflammation immediately followed byportal fibrosis, aberrant vasculature anddisappearance of portal venules and werevery similar to those in human IPH.

Prolonged sensitization with non-pathogenic E. coli: In rabbits, killednonpathogenic E. coli were administeredintraportally. The animals that received anintraportal mixture of killed E. coli andrabbit antiserum (aggregated E. coli)developed histological changes in the liverand portal hypertension(19). Earlyinflammatory reactions in the portal areaand parenchyma were followed by thedevelopment of portal fibrosis. Threeintraportal challenges with aggregated E.

coli were enough to produce marked portalfibrosis, splenomegaly, and portalhypertension. In dogs, repeated intraportalinjections of a mixture of killednonpathogenic E. coli and dog anti-E. coliserum induced portal fibrosis andintrahepatic presinusoidal portalhypertension(33).However, these investigators have usedrepeated cannulation of the portal veinwhich may itself cause damage to theportal vein intima, portal pyemia andaltered hemodynamic and histologicalpicture in the animal. Another limitation ofthe model is the use of E. coli and anti-E.coli aggregate, which is not onlyunphysiological, but also the largeaggregate can block the hepatic sinusoidcausing a situation akin to portal veinthrombosis. Accordingly, alternativeroutes of introducing E. coli into the portalcirculation have been proposed(17).

Schistosomiasis japonica models: Sinceschistosomiasis japonica and idiopathicportal hypertension share similarhistological changes of the liver,Masayoshi K et al produced rabbit modelby infecting with 200-300 Schistosomacercariae percutaneously andsubcutaneously. The angioarchitecture ofchronic schistosomiasis japonica ischaracterized by narrowing, obstructionand obtuse angles of bifurcation of theperipheral portal veins and this disease isquite similar to IPH in both histologicaland angioarchitecture strongly suggest thatportal change is the primary lesion of thehepatic disorder in IPH. However,splenomegaly invariably noted in IPH isnot necessarily observed in chronicschistosomiasis japonica, suggesting thatthe portal system may be more extensivein IPH than in schistosomiasis japonica.

MODELS OF NON-CIRRHOTICPORTAL HYPERTENSION (NCPH)



Fig 3: Liver histology of mice exposed to arsenic for 15months. The histology shows streaky fibrosis in theliver (hematoxylin-eosin, original magnification x 100).

Fig 4 Normal liver histology of control mice at theend of 15 months of feeding As-free water(hematoxylin-eosin, magnification x 100).

Fig 3: Liver histology of mice exposed to arsenic for 15months. The histology shows streaky fibrosis in theliver (hematoxylin-eosin, original magnification x 100).

Fig 4 Normal liver histology of control mice at theend of 15 months of feeding As-free water(hematoxylin-eosin, magnification x 100).

Chronic arsenic ingestion: Despite theestablishment of an association of non-cirrhotic portal fibrosis with drinking ofarsenic-contaminated water in severaldistricts of West Bengal, India, elucidationof the mechanism of this disorder hasremained conjectural. Chronic arsenictoxicity is a form of hepatic fibrosis thatcauses portal hypertension, but does notprogress to cirrhosis. Hepatotoxic effectsof arsenic in humans have been reported(14,26,32,34). Injury to intrahepatic portal veinand even development of cirrhosis havebeen alleged to occur with prolongedusage of Fowler’s solution containingsodium arsenite.

Sarin SK et al in 1999 produced areproducible and homogenous murinemodel of hepatic fibrogenesis and fibrosiswithout significant hepatocellular necrosisand inflammation through chronic arsenicfeeding (Table 2). In addition theyinvestigated the fibrogenic potential ofchronic ingestion of different dosages ofarsenic in mice. The study pointed thatfibrogenesis could be induced within sixweeks by arsenic. There was relativelymore fibrosis with extended arsenicexposure associated with increased hepaticcollagen deposition much more thanhydroxyproline levels (Table 3-4). Thisfact was also supported by thehistopathological studies which showedthat the fibrosis and collagen depositionwas more at 6 months. This result wasspecially obtained with arsenic dosage of120 ppm. The fibrogenesis and fibrosisproduced with this dosage at 6 months wasnear maximum that could be produced byfeeding arsenic to mice. The mortality ratewith 120 ppm dosage was near to theground. Higher dosages of arsenic givenfor a short period of 6 weeks did enhancecollagen synthesis and deposition; butthere was no dose dependent increase withprolonged exposure.

The main conclusions of the study were:(i) prolonged oral arsenic ingestion in miceleads to significant hepatic fibrogenesis

Fig 5: Liver histology of mice exposed toarsenic for 15 months. The histology showsmature collagen deposition spreading fromthe portal tracts through the liver lobules(Masson Trichrome x 400).



and collagen synthesis with minimalhepato-cellular injury; (ii) arsenicingestion alone is unlikely to cause non-cirrhotic portal fibrosis or cirrhosis ofliver. This murine model of arsenicfeeding could be used for the evaluation ofnew antifibrotic agents for the liver.

Guha Mazumdar et al described in apopulation from West Bengal that chronicarsenic toxicity leads to the development ofhepatic fibrosis with portal hypertension inthe absence of cirrhosis (12,13). The groupalso demonstrated for the first time hepaticfibrosis due to long-term arsenic toxicity ina murine model of NCPF. In this study themice received drinking water contaminatedwith arsenic (3.2 mg/L) or arsenic-free(0.01 mg/L, control) ad libitum till 3, 6, 9,12, and 15 months. The result demonstratedthat after 12 months of arsenic feeding, theliver weights increased significantlyconsistent with raised ALT and AST (Table5). Arsenic feeding after 6 months showedsignificant decrease in hepatic glutathioneand the enzymes glucose-6-phosphatedehydrogenase and glutathione peroxidasethan the control group. Also, the plasmamembrane Na+/K+ ATPase activity wasreduced while lipid peroxidation increasedsignificantly after 6 months of arsenicfeeding. Hepatic catalase activity wassignificantly reduced at 9 months in thearsenic-fed group, while glutathione-S-

transferase and glutathione reductaseactivities were also significantly reduced at12 and 15 months (Table 6).Histopathology of the liver (Fig 1-5)remained normal for the initial 9 months,but showed fatty infiltration after 12months of arsenic feeding. Fibrosis wasonly evident after 15 months. The mainfindings of the study were (i) long termarsenic toxicity produced hepatic fibrosis inmurine model. (ii) Initial biochemicalevidence of hepatic membrane damage,probably due to reduction of glutathioneand antioxidant enzymes, may be seen by 6months. (iii) Continued arsenic feedingresulted in fatty liver with serumaminotransferase and alanineaminotransferase elevated at 12 months andhepatic fibrosis at 15 months.

Fig 6: Photomicrograph showing a sectionfrom spleen with medullary congestion and(→) hemosidrin pigment (H&E x 160).



Repeated immunosensitization by rabbitsplenic extract: A rabbit model of NCPFwas developed by an intramuscularinjection of splenic extract(15). Sixmilligrams of the splenic protein thusprepared was mixed with Freund’scomplete adjuvant in a 1:1 ratio andinjected intramuscularly into theexperimental rabbits every 2weeks for 3

months. The control group of animals wassensitized by normal saline mixed withFreund’s complete adjuvant in an equalratio in the same manner. This animalmodel showed significant splenomegaly atone (0.63±0.19 vs 0.23±0.04 g; p<0.05),three (0.73±0.24 vs 0.38±0.10 g; p<0.05)and six (0.51±0.17 vs 0.23±0.04 g; p<0.05)

Fig 8: Photomicrograph of a section ofliver showing normal hepatic parenchymain NCPF(27)

Fig 9: Photomicrograph showing a section fromspleen with medullary congestion andhemosidrin pigment(27)



with persistent rise in portal pressure at one(19.4±2.9 vs 10.4±2.2 mmHg; p<0.05),three (16.7±1.1 vs 7.2±3.6 mmHg; p<0.05),and six (20.3±5.4 vs 10.3±4.8 mmHg;p<0.05) months without hepaticparenchymal injury, quite akin to NCPFseen in humans. The histologicalexamination of the liver specimen fromNCPF rabbits showed mild portal andlobular inflammation, along with Kupffercell hyperplasia. The major histologicalchanges observed in the spleen from NCPFrabbits were fibrocongestive sp

lenomegaly, that is, medullarycongestion, thick-walled vessels andhemosidrin-laden macrophages (Fig 6).This study also proposes that repeatedimmunostimulation may have an importantrole in the pathogenesis of NCPF.

Repeated low dose endotoxinemia of portalcirculation: Portal pyelephlebitis due torepeated abdominal infections andthrombosis in the portal circulation lead to

obstruction of small and middle branches ofportal vein and development of NCPF.Based on this hypothesis, Omanwar S etal(27) developed an animal model of NCPFby repeated low dose endotoxemia byinjecting E. coli (heat killed) into the portalsystem of the animal through an indwellingcannula (placed in gastrosplenic vein) tounderstand the etiology andpathophysiology of this disease. Heat killedE. coli (LPS, 4 mg/kg b. wt) was injectedthrough an indwelling cannula into thegastrosplenic vein (Fig 7) in pre-sensitized(1.5 mg E. coli protein/kg b. wt + Freund’scomplete adjuvant; 1:1 ratio; IM) rabbits.The control group of rabbits receivednormal saline in the same manner. Themean portal pressure in NCPF rabbits wassignificantly (p<0.05) higher compared tothe control group at one (17.5 ± 3.4 Vs 10.4± 2.2 mmHg), three (17.8 ± 1.3 vs 7.2+3.6mm Hg), and at 6 (19.8 ± 3.1 vs. 10.3 ± 4.8mmHg) months. Similarly, the splenicweight in NCPF rabbits was significantly



(p<0.05) greater than the control rabbits atone, three and six months. Absence ofhepatic parenchymal injury and persistentlyelevated portal pressure makes this modelideal to investigate the vascular reactivity tovarious agents (Fig 8-9).

More recently, Sakhuja P et al(31) studiedthe liver histology in rabbit model of NCPF(induced by injecting LPS) especially withrespect to the changes in portal veins. Fivemicron thick sections were stained withroutine H & E and with Masson’sTrichrome stain. Immunohistochemicalstaining with antibodies to Cytokeratin 7using DAB as chromogen was alsoperformed in all cases to identify bile ductsand portal tracts. Portal tracts (PT) weredivided into small, medium and large basedon size of accompanying bile duct. Portalveins (PV) in each PT were counted asnormal if lumen was seen, or obstructed ifPV was not identified or completelyobscured by inflammatory cells. Number of

obstructed Portal veins was then expressedas a percentage of total PTs. The model wascharacterized with splenomegaly and portalhypertension with normal liver functiontests. Obstructed PVs were seen in 25-80%(mean = 54.12%) of small PTs in theexperimental group in comparison to 15 –26% (mean = 19.75%) in the control group.5 of 8 rabbits in the experimental groupshowed greater than 50% obstructed PVs inthe small PTs. Several PTs showedmononuclear inflammation withaccompanying giant cells andgranulomatous reaction causing obstructionto portal veins. Similar inflammation wasobserved focally in the lobular parenchyma.One animal showed active granulomatousinflammation in the medium sized portalveins. No significant fibrosis or cirrhosiswas seen in any case. No significantinflammation or fibrosis was observed inthe control group. The main conclusion ofthe study was that E.Coli induced portalhypertension is associated with obstructive



venopathy in small portal veins, withoutaccompanying fibrosis(31).

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CASE REPORT MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Sturge-Weber Syndrome, Saleem Shaikh et al. 71

ROACH’S TYPE II VARIANT OF STURGE – WEBERSYNDROME: A CASE REPORT

1*Saleem Shaikh, 2Abdur Rahman Al-Atram, 3Sachdeva Harleen

ABSTRACT

Sturge- weber syndrome is a neurocutaneous disorder caused by persistence oftransitory primordial arteriovenous connection of the foetal intracranial vasculature. Itmanifests with vascular malformations involving the brain, eye and skin with resultingneurological and orbital manifestations. Port wine stain, glaucoma and seizures aresome of the commonly seen symptoms, depending on the presence of these featuressturge weber syndrome has been classified by Roach into three types. We report a caseof a 26 year old female with facial portwine stain and minimal neurologicmanifestations, which according to Roach’s classification falls in type II category. Thisreport also underlines the need for detailed laboratory and neurologic work up of allpatients with facial portwine stain present along the distribution of trigeminal nerve, asthe neurologic manifestations in sturge–weber syndrome may vary in severity fromseizures and mental retardation to minimal radiographic changes. It also emphasizesthe need for identification of such rare variants of this syndrome.

داخلالمؤقتةاألولیةواألوردةالشرایینلاتصااستمرارعنناجمجلديعصبياضطرابھوویبرستیرجمتالزمةملخص:محجرفيوأعراضعصبیةأعراضاليیؤديووالجلدوالعینالمخفيوعائیةتشوھاتشكلفيیظھروالجنین،جمجمة

تصنیفتماالعراضحسب. وتشنجاتالعینضغطارتفاع, القانياالحمرباللونالجلدتلونالشائعةأعراضھمن. العینالوجھبجلدتلونمنتشكوعاما26العمرمنتبلغألنثىحالةسجلنا. أنواعثالثةإلىروتشقبلمنویبرستیرجمتالزمة

التقصيمنمزیدإلىالحاجةأیضایؤكدالتقریرھذا. الثانیةالفئةفيروتشحسبتصنفوالتيبسیطةعصبیةواعراضانوخصوصا،التوائمالثالثيالعصبمسارطولعلىالوجھلونتمنیعانونالذینالمرضىلجمیعالمخبريوالسریري

فيالبسیطةالتغیراتاليالعقليالتخلفوالتشنجاتمنشدتھافيتختلفقدویبرستیرجمتالزمةفيالعصبیةاالعراض.المتالزمةھذهلمثلالنادرةالمتغیراتتحدیدإلىالحاجةعلىأیضایؤكدالتقریر. الشعاعيالفحص

Received: 28 December, 2012; Accepted: 4 March, 2013*Correspondence: [email protected] of dentistry- Zulfi, Majmaah University; 2College of medicine- Majmaah University. E mail:[email protected]; 3Senior Lecturer, Dept. of Oral and Maxillofacial Prosthodontics. Bhabha College ofDental Sciences. India



INTRODUCTION

Sturge-Weber Syndrome also called asencephalotrigeminal angiomatosis is anuncommon condition that is characterizedby hamartomatous vascular proliferationinvolving the tissues of the brain and face.It occurs due to persistence of vascularplexus around the cephalic portion of theneural tube. This plexus develops duringthe sixth week of intrauterine life andusually regresses by the ninth week. Theexact cause is unknown but a “2-hithypothesis” which involves sporadicmutations as well as familial occurrenceshas been suggested as etiological basis(1).Most cases are sporadic but occasionallycases within families have also beenreported. Males and females seem to beequally affected. It has been reported inindividuals of White, Hispanic, Africanand Asian heritage.

Clinically, patients typically presents withconstellation of signs and symptoms suchas congenital facial Angiomas (Port WineStain/PWS)(2,3), glaucoma, and variableneurologic manifestations includingseizures, mental retardation, hemianopia,hemiparesis and learning difficulties(4-6).Patients may also have emotionalproblems, such as depression, low self-esteem, shame, emotional outbursts andisolation. The facial angioma is usuallyunilateral but may be bilateral. It typicallyinvolves at least the upper face, superioreyelid, or periorbital region. The facialangioma conforms to sensory distributionof the trigeminal nerve, Angiomas mayalso involve gingiva, nasopharynx, palate,lips and tongue(7,8). Port wine stain mayalso be found on the trunk or extremities ofsome individuals with Sturge WeberSyndrome.

Seizures and other neurologiccomplications are the result ofleptomeningeal angiomas. The severity ofthe neurological manifestations depends on

the location and amount of area involvedby leptomeningeal angioma.

Glaucoma is also commonly seen inSturge Weber Syndrome and is present in60% of individuals. It can be present atbirth or occur anytime throughout thelifespan. It can be unilateral or bilateral,untreated, glaucoma can cause blindnessand can be extremely painful.

Figure 1: Characteristic unilateralinvolvement of face with ophthalmic andmaxillary nerves affected

Depending on the presence of facialangiomas, leptomeningeal angiomas andglaucoma, Roach has classified SturgeWeber Syndrome as follows(9)

Type I - Both facial and leptomeningealangiomas; may have glaucoma

Type II - Facial angioma alone (no CNSinvolvement); may have glaucoma

Type III - Isolated LA; usually noglaucoma

CASE HISTORY

A 26 year lady reported to the outpatientdepartment with complaint of facial neviinvolving the upper face on right side, shealso complained of bleeding from the



gums. On detailed history patient reportednevi to be congenital, initially with pinkcolour and later progressing to purplishhue. There was no history of seizure ormental retardation but during examinationthe patient was dull and was answeringwith difficulty. On examination, the neviwas extending superiorly from theperiorbital region to the angle of the mouthinferiorly, upto the midline (Fig 1).

Table 1 Clinical Manifestations ofSturge-Weber Syndrome

Risk of SWS with facial PWS 8%SWS without facial nevus 13%Bilateral cerebral involvement 15%Seizures 72-93%Hemiparesis 25-56%Hemianopia 44%Headache 44-62%Developmental delay andmental retardation

50-75%

Glaucoma 30-71%Choroidal Haemangioma 40%

Figure 2: CT scan revealing mild corticalatrophy and focal calvarial thickening.

The CT scan revealed minor changes likegyriform enhancement in parietal lobewith mild cortical atrophy and focalcalvarial thickening (Fig 2). Eye

examination revealed no glaucoma andthere was no history of pain or imperfectvision Intraorally the gingival hyperplasiawas noticed in both upper and lower archon right side characteristically extendingtill midline (Fig 3 and 4).

Figure 3: Hyperplastic maxillary gingivaextending till midline

Intra oral examination revealed gingivalhyperplasia of both the arches extendingup to the midline. Plaque and calculus wasseen in the region of gingival enlargement,but this was because the patient could notbrush that region due to bleeding. Gingivalhyperplasia was more pronounced on themaxillary arch and covered almost thewhole crown, buccal mucosa on the rightside was also erythematous. The MRIfindings revealed enhanced soft tissuemass lesion in the right oropharynx (Fig5).

Figure 4: Gingival enlargement in lowerarch is less compared to upper arch.



DISCUSSION

The Sturge-Weber syndrome (SWS) is aneurocutaneous disorder with angiomasinvolving the leptomeninges and skin ofthe face, typically in the ophthalmic andmaxillary distributions of the trigeminalnerve. SWS is caused by residualembryonal blood vessels and theirsecondary effects on surrounding braintissue. A vascular plexus develops aroundthe cephalic portion of the neural tube, andnormally regresses around the ninth weekof gestation. Failure of this normalregression results in residual vasculartissue, which forms the angiomata of theleptomeninges, face, and ipsilateral eye. Ina study by Tallman et al it was reportedthat 310 patients with PWS; 85% hadunilateral and 15% had bilateralinvolvement, and 68% had involvement ofmore than 1 dermatome. Only patientswith PWS involving the distributions ofthe V1 and V2 branches of the trigeminalnerve had CNS or eye involvement.Overall, in those with trigeminalinvolvement, only 8% had CNS and eyeinvolvement(10). Port wine stain is alsoassociated with soft-tissue hypertrophy:The Sturge-Weber Foundation surveyindicated that body asymmetry was seen in164 of 171 patients, with soft-tissuehypertrophy in 38 of 164 patients andscoliosis in 11 patients. Basal cellcarcinoma has been reported to occurwithin a PWS(11). Intraorally,hypervascular changes may be seen on theipsilateral mucosa and gingiva rangingfrom slight vascular hyperplasia to moremassive hemangiomatous proliferationresembling a pyogenic granuloma.

Neurologic dysfunction results fromsecondary effects on surrounding braintissue, which include hypoxia, ischemia,venous occlusion, thrombosis, infarction,or vasomotor phenomenon. A "vascularsteal phenomenon"(12) may develop aroundthe angioma, resulting in cortical ischemia

and progressing to calcification, gliosis,and atrophy, which in turn increase thechance of seizures and neurologicdeterioration(13). The incidence of epilepsyin patients with SWS is 75-90%; seizuresmay be intractable. Seizures result fromcortical irritability caused by cerebralangioma, through mechanisms of hypoxia,ischemia, and gliosis. Fibronectin is amolecule important in regulatingangiogenesis, maintenance of the blood-brain barrier, blood vessel structure andfunction, as well as brain tissue responsesto seizures. Comi et al reported that, inpatients with SWS, decreased expressionof fibronectin was noted in theleptomeningeal blood vessels(14).

Figure 5: MRI revealing hyperplasia ofright side

The main ocular manifestations (ie,buphthalmos, glaucoma) occur secondaryto increased intra ocular pressure (IOP)with mechanical obstruction of the angleof the eye, elevated episcleral venouspressure, or increased secretion of aqueousfluid. Untreated, glaucoma can causeblindness. It can be extremely painful andmay be a "silent" cause of behavioroutbursts or self-injurious behavior in non-verbal individuals with Sturge WeberSyndrome. The incidences of the major



clinical manifestations of SWS are listed inTable 1(15).

In our case the patient complained only ofthe port wine stain and gingivalhypertrophy with no history of seizure orocular manifestations. The gingivalhyperplasia reported in SWS hassometimes been attributed to themedications used for seizure control, but inour case the patient was not taking anymedications and the hyperplasia was seencharacteristically only upto the midline.The CT scan of brain did not show anyobvious changes or calcifications butminor changes such as gyriformenhancement and some amount of corticalatrophy of the right half can beappreciated. This minimal involvement ofthe brain correlates well with the lack ofneurologic manifestations seen in patient.This type of presentation of SWS is veryrare and only reported by Bioxeda et al in1993(16).

CONCLUSION

This is a rare case of SWS, which hasminimal CNS involvement but noneurologic manifestations and hence thisfalls in Type II SWS according to Roach.Hence we suggest that any case havingfacial nevus along the course of trigeminalnerve should be suspected for SWSbecause the neurologic involvement in agiven case may vary from minimalradiographic changes to overt clinicalmanifestations.

REFRENCES

1. Vishal Madan, Vijay Diwan, SriramRamaswamy, Ashish Sharma. BehavioralManifestations of Struge WeberSyndrome: A case report. Prim CareCompanion J of Clinical Psychiatry2006;8:198-200

2. Bodensteiner JB, Roach ES. Sturge-WeberSyndrome: Introduction and Overview. In:Bodensteiner JB, Roach ES, eds. Sturge-

Weber Syndrome. Sturge WeberFoundation. Mt Freedom, NewJersey. 1999.

3. Aicardi J. Diseases of the Nervous Systemin Childhood. 2nd ed. London: Mac KeithPress. 1998.

4. Thomas-Sohl KA, Vaslow DF, Mari BL.Struge Weber Syndrome: a review. PediatrNeurol 2004; 30:303-310

5. Comi AM. Pathophysiology of StrugeWeber Syndrome. J Child Neurol 2003;18:509-516

6. Lisotto C, Mainardi F,Maggioni F,et al.Headache In Sturge Weber Syndrome: acase report and review of the literature.Cephalgia 2004;24:1001-1004

7. Haslam: RHA. NeurocutaneousSyndromes. In Behrman RE, KliegmanRM, Jenson HB (eds). Nelson Text bookof Pediatrics. 17th edn. WB. SaundersCompany, Philadelphia 2004 : 2015-19.

8. Berg Bo. Neurocutaneous Syndromes. In :Maria BL (ed) Current Management inChild Neurology. Hamilton BC Decker1999.278-80

9. Roach ES. Neurocutaneoussyndromes. Pediatr Clin NorthAm. Aug 1992;39(4):591-620.

10. Tallman B, Tan OT, Morelli JG. Locationof port-wine stains and the likelihood ofophthalmic and/or central nervoussystemcomplications. Pediatrics. Mar 1991;87(3):323-7.

11. Sagi E, Aram H, Peled IJ. Basal cellcarcinoma developing in a nevusflammeus. Cutis. Mar 1984;33(3):311-2,318.

12. Aylett SE, Neville BG, Cross JH. Sturge-Weber syndrome: cerebralhaemodynamics during seizureactivity. Dev Med ChildNeurol. Jul 1999;41(7):480-5

13. Okudaira Y, Arai H, SatoK. Hemodynamic compromise as a factorin clinical progression of Sturge- Webersyndrome. Childs NervSyst. Apr 1997;13(4):214-9

14. Comi AM, Weisz CJ, Highet BH. Sturge-Weber syndrome: altered blood vesselfibronectin expression and morphology. JChild Neurol. Jul 2005;20(7):572-7.

15. Thomas-Sohl KA, Vaslow DF, MariaBL. Sturge-Weber syndrome: a



review. Pediatr Neurol. May 2004; 30(5):303-10

16. Bioxeda P,de Mesa RF, Arrazola JM.[Facial angioma and the sturge – Weber

syndrome Likelihood a study of 121Cases] Med clin (Barc) 1993 May 29, 101(1); 1 – 4.

VIEW POINT MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Tuberculosis Timebomb A Global Emergency, Manzoor Ahmad Mir 77

TUBERCULOSIS TIMEBOMB A GLOBAL EMERGENCY:NEED FOR ALTERNATIVE VACCINES

1,2*Manzoor Ahmad Mir, 2Raid Al-baradie

Tuberculosis (TB) also known as whiteplague is a major infectious disease and aglobal emergency. It is one of the oldestrecorded human afflictions and stillcontinues to cause widespread morbidityand mortality in children and adultsworldwide, despite the extensive use of alive attenuated vaccine and severalantibiotics. One third of the world’spopulation is already infected and about 3million people die and 8 million peopledevelop the active disease each year(1-2).In the last decade there is a sharp rise inthe cases of TB mainly due to emergenceof multi-drug resistant (MTD), extensivelydrug-resistant (XDR) and totally drug-resistant (TDR) strains of Mycobacteriumtuberculosis, which are virtuallyuntreatable(3-7).

In the beginning of the last quarter of the20th century, there was a glimmer of hopethat TB could be brought under control;however, this was dashed with theemergence of HIV/AIDS TB co-infection(8). HIV compromises the immunesystem, which needs to be competent forcontrol of latent M. tuberculosis infection,and hence increases risk of active TBmanifold, from 10% risk over a lifetime to10% risk within of TB is becoming worseday by day. Use of BCG is effective inpreventing TB in efficacies. The onlyapproved and currently available vaccine

against TB i.e. BCG has young childrenthat too with varied the year of co-infection(9). Despite the fact that highestnumber of people on the earth has beenvaccinated with BCG still scenario beengiven 4 billion times over the last 100years since its development; we don’t evenunderstand the precise immunemechanisms that protect BCG vaccinatedinfants and lacks protection in adultsprobably due to absence of generating longlasting memory cells. Thus, an effectivevaccine for the prevention of pulmonaryTB in adolescents and adults, many ofwhom are latently infected with M.tuberculosis in countries in which TB isendemic, is urgently needed to control theTB time bomb.

Immunity to Mtb is a two-edged sword: itprotects the human host againstdisseminating infection, but also facilitatestransmission of TB to contacts. Therefore,TB vaccines not only need to induceoptimal immunity to Mtb, but also abalanced response that favors protectiveand avoids pathogenic mechanisms(10). Butthe most successful vaccines today targetpathogens against which humoralimmunity suffices to achieve protectionand often sterile eradication but TBvaccines need to drive primarily thecellular arm of the immune system.

Received: 17 December, 2012; Accepted: 10 March, 2013*Correspondence: [email protected] Professor, Department of Bioresources University of Kashmir, Srinagar India-190001, 2AssistantProfessor, Department of Medical Lab Technology, College of Applied Medical Sciences MajmaahUniversity, Kingdom of Saudi Arabia.


Tuberculosis Time bomb A Global Emergency, Manzoor Ahmad Mir 78

So the new vaccines candidates are neededwhich are better than BCG and mustprotect not only toddlers but also adults; beeffective when administered pre-exposureand post-exposure with M. tuberculosis;and ultimately the next-generationcandidates should be capable oferadicating or preventing infection with M.tuberculosis, while current vaccine can-didates are aimed at preventing active TBdisease by controlling latent M.

tuberculosis infection(5). Currentlyextensive efforts are being put into thedevelopment of a better vaccine. Some ofthe live vaccine alternatives are quitepromising for prevention of primarydisease. The development of new TBvaccines should follows two basic

+Table 1: Next Generation vaccine candidates against Tuberculosis

Type ofVaccine Product Description Indication Sponsors

RecombinantProtein

r30 30KDa mtb Ag85B protein purifiedfrom rM. Smegmatis B and PI UCLA, NIH, NIAD

R32KDA(Recombinant 85A)

Purified recombinant Ag85Aprotein from BCG B, PI and IT LEPRA Society, Blue Peter

Research Centre, and BMMRC

Latency fusion protein

recombinant fusion proteincomposed of antigens 85A- 85B-Rv3407, Rv3407-Rv1733c-Rv2626c, Rv0867c-Rv-1884-Rv2389c

B Aeras

RecombinantLive

rBCG(mtbB)30rBCG with limited replicationoverexpressing the 30kDa MtbAg85B

P UCLA, NIH, NIAD

HG856-BCGrBCG overexpressing chimericESAT-6/Ag85A DNA fusionprotein

B and PI Shanghai Public Clinical HealthCentre

BCG zmp1 BCG zmp 1 deletion mutant P University of Zurich, TBVI

rBCG38 rBCG Tice strain overexpressingthe38KDa protein P and B Universidad Nacional Autonoma

de Mexico

Disruption of theSapM locus

Recombinant M. bovis BCG inwhich the SapM locus has beendisrupted

P FWO-Ghent University-VIB

rBCG85C rBCG overexpressing antigen 85Cof M tb P University of Delhi; DBT, Govt.

of India

Streptomyces livevector

Recombinant Streptomycesexpressing multiple T and Bepitopes of Mtb.

P, B, PI andIT

Finlay Institute; Institute ofPharmacy and Food Cuba

rBCG T+BrM. Smegmatis T+B

rBCG and rM. Smegmatisexpressing multiple T and Bepitopes of Mtb

P, B and PI Finlay Institute; Universiti SainsMalaysia

Viral VectoredrhPIV2-Ag85B

Replication deficient humanparainfluenza type-2 virusexpressing Ag85B

P and B NIBI Japan; Japan BCGLaboratory

Recombinant LCMV r-LCMV expressing Ag85A,Ag85B or Ag85B-ESAT-6

P, B, PI andIT University of Geneva, TBVI

DNA

HG856A Chimeric DNA vaccines-ESAT-6/Ag85A; Ag85A/Ag85B B and IT Shanghai H&G Biotech

DNAacrDNA vaccine expressing alphacrystalline, a key latency associatedantigen of Mtb

B University of Delhi; DBT, Govt.of India

HVJ-Envelope/HSP65DNA+IL-12 DNA

Combination of DNA vaccinesexpressing Mtb HSP-65 & IL-12 B, PI and IT Osaka University

pUMVC6/7 DNA

DNA vaccine plasmid vectorpUMVC6 or pUMVC7 expressingRv 3872, Rv 3873, Rv3874,Rv3875 or Rv3619c

P Kuwait University

HG85A/B Chimeric DNA vaccines-Ag85A/B B and IT Shanghai H&G BiotechKey: P= Prime, B= Boost, PI= Post Immunization and IT= Immunotherapy



avenues; the first aims at replacing BCGeither by genetically attenuated Mtb or byimproved recombinant (r)BCG. And inboth the cases the vaccine should be: moreimmunogenic, capable of inducing longlasting protection; safer for human use andshould also induce protection againsthighly virulent clinical isolates such

as MDR, XDR, TDR and Mtb Beijingstrains.

The promising alternatives arerecombinant BCG expressing listeriolysinfrom Listeria monocytogenes, over-expression of antigen 85B in BCG orrecombinant BCG expressing cytokineslike IL-18 and IFN-g for more profound

Figure: The three stages of tuberculosiss Disease. Stage 1: Infection of Mycobacteriumtuberculosis (Mtb) frequently occurs at a young age. Metabolically active Mtb are inhaled andsubsequently T-cells are stimulated which carry the major burden of acquired immunity. Theseinclude major histocompatability complex class II (MHC II)-restricted CD4 T-cells and MHC I-restricted CD8 T-cells. B cells are also activated but their protective role in TB remains elusive.Pre-exposure vaccines are given at this early stage. Novel pre-exposure vaccine candidates aregiven very soon after birth and thus generally before infection with Mtb. They either substitute forBacille Calmette Gue´ rin (BCG) or boost immunity induced by BCG. Stage 2: Acquired immunitycomprising CD4 and CD8 T-cells contains Mtb in a dormant stage within solid granulomas. T-cellsproduce type I cytokines and cytolytic effector molecules. They become memory T-cells whichconcomitantly produce multiple cytokines. Individuals remain latently infected without clinical signsof active tuberculosis (TB). Post-exposure vaccines are given to adolescents or adults who arelatently infected but healthy. Stage 3: Mechanisms leading to deficient immunity and diseasereactivation are numerous and include production of suppressive cytokines such as interleukin (IL)-10 and transforming growth factor-beta (TGFb) by T helper 2 (Th2) cells and regulatory T(reg)cells as well as T-cell exhaustion mediated by inhibitory receptor-coreceptor interactions on antigenpresenting cells (APCs) and T-cells. Mtb becomes metabolically active and granulomas becomecaseous. Mtb can be spread to other organs and to other individuals. Therapeutic vaccines aregiven to TB patients in adjunct to chemotherapy. (adopted from Plos pathogen Kaufman S. H. E)



Th1 cell polarization(10,11) and deletion ofantiapoptotic genes to facilitate cross-priming, introduction of genes encodingdormancy antigens such as the DosR-regulated gene products for postexposurevaccination of latently infectedindividuals(12), subunit vaccines of fusedMTB proteins with novel adjuvants,heterologous vectors such as modifiedvaccinia Ankara or adenovirus expressingMTB proteins; attenuating MTB byremoving virulence genes such as secA.One more way to improve BCG is eitherby introducing immunodominant Mtb-specific antigens that are absent fromBCG, such as RD1 locus-encoded antigens(ESAT6, CFP10)(13-17); or by over-expressing antigens that BCG alreadyexpresses by itself (cognates of Ag85complex), but probably not sufficientlyhigh throughout all phases of infection.Another way to improve BCG is byintroducing genetic modifications forsuperior targeting of essential immunepathways, for example, by enhancing orfacilitating cross-priming; and to inhibit itsability to neutralize phagosomalmaturation. The second major avenue todevelop better TB vaccines relies on the

development of subunit vaccines which arenon-live, or in the case of viral vectors,non-replicating vaccines, which can bedelivered safely into the human hostregardless of immune-competence.Researchers are now able to exploit cuttingedge technologies in designing the mostpotent vaccine combination by using theprime BCG vaccine with super BCG (arBCG vaccine that expresses listeriolysin)followed by booster doses with a supersubunit vaccine(18). This logical approachof boost vaccination by introducing asecond vaccine different from BCG at alater time point to use a heterologousprime–boost strategy for prevention of TBis also of high importance.

A booster dose may be used for twopurposes, to strengthen the immunity ofthe BCG to prevent primary disease and tostrengthen the immunity in individualswith latent infection with M.tuberculosis(19). These vaccines wouldcontain antigens secreted by metabolicallyactive Mtb as well as dormancy antigens.However the first attempt might be tocombine current vaccine candidates to

Tuberculosis in different phases of clinical trails

Type of Vaccine Candidate Description Clinical trial status

Fusion protein inadjuvant for pre-exposure booster

vaccination

Hybrid 1+IC31 Fusion of Ag85B and ESAT-6 in adjuvant IC31 Phase I completed

Aeras-404:Hyvac4+IC31 Fusion of Ag85B and TB10.4 in adjuvant IC31 Phase I ongoingM72AS01 or AS02 Fusion of Rv1196 and Rv0125 in Adjuvant

AS01 or AS02Phase II ongoing

Hybrid 1+CAF01 Fusion of Ag85B and ESAT-6 in adjuvantCAF01

Phase I ongoing

Hybrid 56+IC31 Fusion of Ag85B, ESAT-6 and Rv2660c inadjuvant IC31

Phase I ongoing

Recombinant BCG forpre-exposure prime

vaccination

rBCG30 rBCG-expressing Ag85B Phase I completedVPM 1002 rBCG-expressing listeriolysin and urease

deletionPhase II ongoing

Aeras-422 rBCG-expressing listeriolysin Phase I terminated

Viral-vectors for pre-exposure booster

vaccination

AdAg85A Replication deficient adenovirus 5 expressingAg85A

Phase I

Crucell Ad35/Aeras-402 Replication deficient adenovirus 35 expressingAg85A, Ag85B, TB10.4

Phase II ongoing

Oxford MVA85A/Aeras-485

Modified vaccinia Ankara expressing Ag85A Phase II ongoing

Whole bacterial cellvaccine for therapeutic

vaccination

M. vacca Inactivated M. vacca Phase Ii completedRUTI Detoxified M. tuberculosis in liposomes Phase II ongoing



achieve sterile eradication of the pathogen,i.e., prime with the best BCG replacementvaccine followed by a selection of subunitboosters. Further the tremendous progressin standardizing animal models of MTBinfection has allowed completecomparison of genetically manipulatedmycobacteria and new TB vaccines acrossthe research centres around the world(20-23).

In the near future with little bit of focus,we may be ready to reap the fruits of theefforts of decades of research indeveloping one or two vaccines withproven protective efficacy and safety butthis by no means signals the end ofscientific efforts. In fact, an emergingbottleneck may not be the number of pre-clinical TB vaccine candidates that TBresearchers can produce, but rather thenumber of vaccines that can be Table 2:Most Advanced vaccine candidates againsttested clinically in efficacy trials, given thelimited clinical trial capacity worldwide,i.e., a shortage that exists not only inAfrica but also in Asia. Finally, theidentification of TB surrogate end-pointbiomarkers or “correlates of protection"may drastically reduce the need for thecurrent long-term large-scale clinical trials,and thus will speed up TB vaccinediscovery and clinical testing. But this allneeds a special focus on the TB researchfunding and fortunately the EuropeanCommission, the National Institutes ofHealth, and private foundations like theBill and Melinda Gates Foundation, haveinstigated several mechanisms to supportTB-oriented research and clinical trials (24-

25). Hopefully, the sudden political interestin vaccine development will provide aunique opportunity for the TB researchcommunity to come up with a bettervaccine candidate against TB for humanuse in the near future.

ACKNOWLEDGEMENTI am Thankful to Dr. Nasir Jarallah (Dean,CAMS), Dr. Khalid Jarallah (Ex-HOD,MDL), Mr. Esam Elmalky (Vice Dean,CAMS) and Dr. Ahmad Khamees (HODMDL) for their support and co-operation. Iwould also like to thank all the officials ofUniversity of Kashmir for their support.

REFERENCES1. World Health Organization. Multidrug and

extensively drug –resistant TB (M/XDR-TB): Global Report on Surveillance andResponse, Geneva, Switzerland, 2010.

2. Stop TB Partnership. The Global Plan toStop TB 2006–2015. WHO Press, Geneva,Switzerland 2006.

3. Announcement of the national tuberculosisprevention and control plan (2001–2010).State Council of the People’s Republic ofChina, General Office: Beijing, China,.Document No. 75, 2001.

4. Ali Akbar Velayati, Parissa Farnia,Mohammad Reza Masjedi Recurrenceafter treatment success in pulmonarymultidrug-resistant tuberculosis:predication by continual PCR positivity IntJ Clin Exp Med 2012; 5(3):271-272.

5. Gandhi NR, Nunn P, Dheda K, Multidrugresistant and extensively drug-resistanttuberculosis: a threat to global control oftuberculosis. Lancet 2010; 375: 1830–1843.

6. Velayati AA, Masjedi MR, Farnia P,Emergence of new forms of totally drug-resistant tuberculosis bacilli: superextensively drug-resistant tuberculosis ortotally drug-resistant strains in Iran. Chest2009;136:420-425.

7. Velayati AA, Farnia P, Merza MA,Zhavnerko GK, New insight intoextremely drug-resistant tuberculosis:using atomic force microscopy. Eur RespirJ 2010; 36:1490-1493.

8. Ottenhoff TH Overcoming the globalcrisis: ‘‘yes, we can’’, but also for TB?Eur J Immunol 2009; 39: 2014–2020.

9. Kaufmann SH, Hussey G, Lambert PHNew vaccines for tuberculosis. Lancet2010; 375: 2110–2119.



10. Cooper AM Cell-mediated immuneresponses in tuberculosis. Annu RevImmunol 2009; 27: 393–422.

11. Sutherland JS, Adetifa IM, Hill PC,Pattern and diversity of cytokineproduction differentiates betweenMycobacterium tuberculosis infection anddisease. Eur J Immunol 2009; 39: 723–729.

12. Kursar M, Koch M, Mittrucker HW,Cutting Edge: Regulatory T cells preventefficient clearance of Mycobacteriumtuberculosis. J Immunol 2007; 178: 2661–2665.

13. Pym AS, Brodin P, Majlessi L,Recombinant BCG exporting ESAT-6confers enhanced protection againsttuberculosis. Nat Med 2003;9: 533–539.

14. Ottenhoff TH, Doherty TM, van Dissel JT,First in humans: a new molecularlydefined vaccine shows excellent safety andstrong induction of long-livedMycobacterium tuberculosis-specific Th1-cell like responses. Hum Vaccin 2010; 6:1007–1015.

15. Shen HB, Wang C, Yang EZ , Novelrecombinant BCG coexpressing Ag85B,ESAT-6 and mouse TNF-alpha inducessignificantly enhanced cellular immuneand antibody responses in C57BL/6mice. Microbiol Immunol 2010 ; 54: 435–441.

16. Ottenhoff TH, Doherty TM, van Dissel JT,First in humans: a new molecularlydefined vaccine shows excellent safety andstrong induction of long-livedMycobacterium tuberculosis-specific Th1-cell like responses. Hum Vaccin 2010; 6:1007–1015.

17. Shi CH, Wang XW, Zhang H. Immuneresponses and protective efficacy of thegene vaccine expressing Ag85B andESAT6 fusion protein fromMycobacterium tuberculosis. DNA CellBiol 2008; 27: 199–207.

18. Wu J, Ma H, Qu Q Incorporation ofimmunostimulatory motifs in thetranscribed region of a plasmid DNAvaccine enhances Th1 immune responsesand therapeutic effectagainst Mycobacterium tuberculosis inmice. Vaccine 2011; 29: 7624–7630

19. Tchilian EZ, Ronan EO, de Lara C,Simultaneous immunization againsttuberculosis. PLoS ONE 2011; 6: e27477.

20. Skeiky, Y.A. Differential immuneresponses and protective efficacy inducedby components of a tuberculosispolyprotein vaccine, Mtb72F, delivered asnaked DNA or recombinant protein. J.Immunol. 2004; 172:7618–7628.

21. Olsen, A.W Protective effect of atuberculosis subunit vaccine based on afusion of antigen 85B and ESAT-6 in theaerosol guinea pig model. Infect. Immun2004; 72:6148–6150.

22. Kaufmann, S.H., Baumann, S., and NasserEddine. A Exploiting immunology andmolecular genetics for rational vaccinedesign against tuberculosis. Int. J. Tuberc.Lung Dis 2006;10:1068–1079, 2006

23. Ottenhoff T. H. M and Kaufman S. H. EVaccines against tuberculosis; where arewe and where do we need to go? PLoSPathog 8(5): e1002607.doi:10.1371/journal/ppat.1002607, 2012.

24. Coakley C, Bhroin E, Buonadonna P.MEPs urge EU to fight tuberculosisworldwide. European Parliament February3 2011.

25. Kupferschmidt K Infectious disease.Taking a new shot at a TB vaccine.Science 2011; 334: 1488–1490.doi:10.1371/journal.pone.0027477.

MEDICAL QUIZ MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Wahengbam PS Al Waheed 83

Medical Quiz1*Wahengbam PS Al-Waheed

Case Summary: Olfat Mahmoud Magdy is 66 years old female resident from Benghazi,Libya was a known case of Diabetes Mellitus with End Stage Renal Disease(ESRD) onDependant Haemodialysis. The whole Episodes were noticed after her last child birth at theage of 41 years with the detection of Diabetes and later landed into Renal Failure. She wassome of the survival patients in such a prolong period of maintenance Haemodialysis.

The sequence of herdisease is with afluctuating renal profileparameters and repeatedanemia and infection ofhepatitis B and hepatitis Cduring the course ofdisease and later sero-conversion takes placed.She is non-reactive nowwhen last detected sixmonths ago. She is carriedwith MaintenanceHaemodialysis three timesa week and has anuneventful life.

She had repeatedhospitalization due torising renal profile of Serum Creatinine, Serum Potassium and ECG changes with associatedsymptoms of breathlessness and chest pain. Quite often she was required to admit with thisproblem in Emergency and managed with Emergency Haemodialysis.

On the line of further management she was re-investigated including blood, color echocardiography, Immunoserolgyand MRI, the parameters aresuitable for renal transplant,however due to non-availabilityof donor, MaintenanceHaemodialysis is continuing.

The final clinical Impression isLVH (Left VentricularHypertrophy) with DC (DilatedCardiomyopathy) with CRD (Chronic Renal diseases) & ESRD (End Stage Renal Disease)with Diabetes and Hypertension.Received: 9 December, 2012; Accepted: 13 March, 2013*Correspondence: [email protected] of Medicine, Department of Public Health & Community Medicine; College of Medicine, MajmaahUniversity, Majmaah, Kingdom of Saudi Arabia

MEDICAL QUIZ MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

Wahengbam PS Al Waheed 84

Some interacting questions (Select the one of the best answer)

1. What will be the percentage of magnitude of glomerular tubular balance?a) Less than 10%.b) Loss upto 100%.c) More than loss of 50%.d) No loss.

2. What will be the indication and modalities treatment?a) CAVH (continuous arterio-venous

haemofiltration).b) CAVHD (continuous arterio-venous

haemodialysis).c) CRRT (continuous renal replacement

therapies).d) CVVHD (continuous veno-venous

haemodialysis).3. What are the outcomes of long term

prognosis?a) Renal failure associated with multi

organ failure.b) Renal failure occurring less than 50%

of renal impairments.c) Renal failure recovers up to 2%.d) Renal failures approximate 50% over 5 years.

4. What can be the explanation for LVH (Left Ventricular Hypertrophy) and DC (DilatedCardiomyopathy) in CRD (Chronic Renal diseases) & ESRD(End Stage RenalDisease)?a) Due to renal fluid overloadb) Due to low Cardiac Ejection fractionc) Due to Obesity and Diabetesd) Due to prolong hypertension and ECFV (extracellular fluid volume) expansion.

UPCOMING CONFERENCE MAJMAAH J. HEALTH SCIENCES, 2013 – Vol. 1, No. 1

85

UPCOMING CONFERENCES

5th March 2013First Annual Scientific Meeting,

Jezan, Saudi Arabia

17th March 20133rd Annual Bridges Saudi Arabia

Jeddah, Saudi Arabia

9-11 April 2013Patient Safety Forum, 2013,

King Saud bin AbdulazizUniversity for Health Sciences,

Riyadh, Saudi Arabia

10th February 20141st International Conference on

Clinical Teaching/Learning in Nursing& Health Sciences

Jeddah, Saudi Arabia.

23rd April 2013Fourth National Symposium on

InformaticsRiyadh, Saudi Arabia

27th April 2013Jeddah Vascular Conference 2013


14th September 201312th Asian Oceanian Congress

on Child NeurologyRiyadh, Saudi Arabia

16th December 20137th ASCAAD conference


22nd December 2013NOORIC2013

Madinah, Saudi Arabia

16th April 2013The 9th International Conference onPsychiatry “Bridging the gap between

Science, Culture and ClinicalPsychiatry” Jeddah, Saudi Arabia.

15th April 2013"2nd Evidence-Based Surgery

Workshop"Jeddah, Saudi Arabia

3 – 5 June, 2013Hospital Health Middle East

Dubai, UAE

12 – 14 May, 2013Saudi Health 2013

Riyadh, Saudi Arabia

Copyrights© 2013 by Majmaah University. All right reserved. Reproduction without permission is prohibited. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording or any information and retrieval system without permission in writing from the publisher.

All article published, including editorial, letter and book review, represent the opinion of the authors and do not reflect the official policy of the publisher or the institution with which the author is affiliated, unless it is clearly specified.

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