“A STUDY OF C-REACTIVE PROTEIN IN ACUTE ISCHEMIC STROKE”

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    RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,

    KARNATAKA

    ANNEXURE-II

    PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

    1 NAME OF THE CANDIDATEAND ADDRESS

    DR. GAURAV SHIREESH BABAR,

    P.G IN (M.D) GENERAL MEDICINE,

    DEPT.OF MEDICINE

    A.I.M.S., B.G.NAGARA.,

    MANDYA DISTRICT-57!!"

    # NAME OF THE INSTITUTION ADICHUNCHANAGIRI INSTITUTE

    OF MEDICAL SCIENCES,

    B.G.NAGARA.$ COURSE OF STUDY AND

    SUBJECT

    M.D. IN GENERAL MEDICINE

    ! DATE OF ADMISSION TO THE

    COURSE

    $%&MAY #''7

    5 TITLE OF THE TOPIC A STUDY OF C-REACTIVE

    PROTEIN IN ACUTE ISCHEMIC

    STROKE

    * BRIEF RESUME OF INTENDED

    +ORK

    *. NEED FOR THE STUDY

    *.# REVIE+ OF LITERATURE

    *.$ OBJECTIVES OF THE STUDY

    *.! INCLUSION AND

    EXCLUSION CRITERIA

    APPENDIX-

    APPENDIX-A

    APPENDIX-B

    APPENDIX-C

    APPENDIX-D

    7 MATERIALS AND METHODS

    7. SOURCE OF DATA

    7.# METHOD OF COLLECTION

    OF DATA (INCLUDING

    SAMPLING PROCEDURES ANY)

    APPENDIX-II

    APPENDIX-IIA

    APPENDIX-IIB

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    7.$ DOES STUDY REUIRED

    ANY INVESTIGATIONS OR

    INVESTIGATIONS TO BE

    CONDUCTED ON PATIENTS

    OR OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY

    7.! HAS ETHICAL CLEARANCE

    BEEN OBTAINED FROM

    YOUR INSTITUTION IN

    CASE OF 7.$

    YES

    APPENDIX-IIC

    YES

    APPENDIX-IID

    " PROFORMA AND LIST OF

    REFERENCES

    APPENDIX-III

    SIGNATURE OF THECANDIDATE

    ' REMARKS OF THE GUIDE THIS STUDY IS TO KNO+ THE

    ASSOCIATION BET+EEN CRP

    LEVEL IN ISCHEMIC STROKE AND

    THIS IF FOR+ARDED TO RGUHS

    . NAME OF THE GUIDE DR. CHETAN KUMAR J G

    PROFESSORDEPT. OF GENERAL MEDICINE

    A.I.M.S., B.G. NAGARA.

    .# SIGNATURE OF THE GUIDE

    .$ CO-GUIDE --------------

    .! SIGNATURE OF CO-GUIDE

    -------------

    .5 HEAD OF THE

    DEPARTMENT

    DR. PADMANABHA M C

    PROFESSOR HOD

    DEPT.OF GENERAL MEDICINE

    A.I.M.S., B.G.NAGARA.

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    .* SIGNATURE OF

    HEAD OF

    THE DEARTMENT

    # #. REMARKS OF THE

    CHAIRMAN

    AND

    PRINCIPAL

    #.# SIGNATURE

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    APPENDIX

    *. BRIEF RESUME OF THE INTENDED +ORK

    APPENDIX A

    *.. NEED FOR THE STUDY

    Ischemic stroke is a common problem faced day to day . The burden of stroke on

    the community is best reflected by the incidence. There is increasing mortality and

    morbidity with stroke. It has been found convincingly that in ischemic stroke, there

    will be rise in acute phase reactants like C- Reactive protein 1!,"!,#! and $%R.

    &therosclerosis is recogni'ed as an inflammatory process rather than a mere

    obstructive one.

    Increased CR( production is a feature of noninfective as well as infective

    disease and CR( binds to a wide range of autogenous products. )ipids and

    phospholipids, polycations and polyanions all of which are constituents of cells and

    likely to be abnormally e*posed in or released from damaged tissues. In +ivo

    binding of CR( to necrotic cells has been described and contribute to resolution and

    repair. owever, the main role of CR(, for which it evolved and has been conserved

    is to recogni'e in the plasma the potentially to*ic autogenous materials released

    from damaged tissues to bind them and thereby to deto*ify them and or facilitate

    their clearance!,/!,0!.

    APPENDIX-IB

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    *.# REVIE+ OF LITERATURE

    &very and his collaborators characteri'ed the C-reactive material as a protein

    which reuired calcium ions for its reaction with C(% and introduced the term

    2acute phase3 to refer to serum from patients acutely ill with infectious disease and

    containing the C-reactive protein

    )ofstrom independently described a non-specific capsular swelling reaction

    of some strains of pneumococci when mi*ed with acute phase sera and subseuently

    showed that the substance responsible was CR(4! . e detected CR( in non-

    infectious as well as infectious conditions5

    Inflammation is an important feature of atheroma and is associated with

    activation and proliferation of macrophages, endothelial cells and smooth muscle

    cells.

    6ultiple studies additionally confirm that most vascular events occur among

    individuals without evidence of very high cholesterol levels and that the

    intermediate risk group is large, heterogenous and in need of better methods for risk

    stratification.

    7f potential novel risk factors presently available, high sensitivity C-reactive

    protein hs CR(!, a marker of low grade vascular inflammation, is among the most

    promising prospective epidemiologic studies consistently demonstrate that hsCR(

    adds independent prognostic information at all levels of )8) cholesterol and at all

    levels of the 9ramingham Risk %core. In the year since publication of the

    C8C&&:Centre for 8isease Control and (revention&merican eart &ssociation;

    report, abundant data have emerged not only confirming the ability of hs CR(:high

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    sensitivity CR(; to add prognostic information to the 9ramingham Risk %core but

    also linking hs CR( to metabolic syndrome and the development of incident type "

    diabetes.

    In addition, the 9ramingham eart study itself has provided evidence that

    hsCR( independently predicts thrombotic events in the cerebral circulation.

    9inally within the 9ramingham eart study, data have also been presented

    that demonstrate the ability of hsCR( to predict stroke risk independently of the

    9ramingham covariates. &fter ad?.??4! for each

    increasing uartile of hsCR( 1?!.

    Thus, measures of inflammation such as hsCR( seem to provide independent

    and complementary information on risk beyond that achievable by direct measures

    of atherosclerotic burden.

    APPENDIX C

    *.$. OBJECTIVES OF STUDY

    .To study the association of C-Reactive protein CR(! level rise in patients of acute

    ischemic stroke.

    #. To study the short term prognostic value of CR( level in patients of acute ischemic

    stroke.

    $.To compare CR( and $%R levels in patients of acute ischemic stroke.

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    APPENDIX D

    0. INCLUSION CRITERIA

    (atients of first ischemic stroke admitted within A"hrs of symptom

    onset and age and se* matched healthy controls .

    . EXCLUSION CRITERIA

    o &cute infectious disease

    o &ll patients of stable or unstable angina, acute myocardial infarction.

    o Immunological disorders.

    o Bnown or suspected neoplastic disorders

    o Recent:less than # months;ma

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    APPENDIX IIB

    7.# METHOD OF COLLECTION OF DATA

    SAMPLE SI/E0

    /? cases will be studied with eual number of healthy controls.

    PROTOCOL OF THE STUDY0

    9or every case and control selected, clinical data and results of routine

    investigations will be prospectively recorded. In both cases and controls, blood for

    CR( and $%R will be taken by performing venipuncture and estimation will be

    done in Clinical 6icrobiology )aboratory, & I 6 % F.E Dagar.

    P1234614 0 C - reactive protein and $%R estimation.

    P1839:40

    The CR( is a rapid slide agglutination procedure for the direct detection and

    semiuantitation of C-reactive protein. The reagent, a late* particle suspension

    coated with specific antihuman C- reactive protein antibodies, agglutinates in the

    presence of CR( in patients serum.

    P1234614 6;:&;&

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    1. 7ne drop of serum placed in circled area of slide with the help of disposable

    serum dropper.

    ". 7ne drop of CR( late* antigen added to above drop and mi*ed well with

    disposable applicator stick.

    #. 7bserved for agglutination by rocking the slide gently back and forth upto to

    "min using a bright source of light.

    S4=>6;8&;&

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    Third GGGGGGGGGGGGGG. 1H4

    9ourth GGGGGGGGGGGGGG 1H10

    9ifth GGGGGGGGGGGGGGG 1H#"

    %i*th GGGGGGGGGGGGGGG 1H0

    C;:36:;&280

    Concentration of CR( in serum can be calculated.

    CR( ?.0 * highest dilution of serum showing agglutination

    %ensitivity > ?.0 mgd).

    The detection limit of this test is ?-0 mgdl. therefore, values of less than ?.0

    mgd) will be taken as normal concentration of CR(. +alues of more than ?.0

    mgd) will be taken as elevated CR(.

    ESR LEVEL ESTIMATION511

    6$T785

    The International Committee for %tandardi'ation in ematology IC%!

    recommends the use of the Jestergren method.

    $thylenediaminetetraacetic acid $8T&! anticoagulated blood sample is preferably

    diluted in a large bore tube before using the Jestergren tube.Jith this modified

    JestergrenKs method, there is an e*cellent correlation with the IC% reference. Flood

    samples can be stored for up to " hours at LC, but not at room temperature, withoutaffecting the Jestergren level.

    FACTORS AFFECTING THE TEST@#,$

    $rythrocyte aggregation is affected by two ma

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    frictional forces around the red cell. The erythrocytes normally have net negative charges

    and, therefore, repel each other. igh molecular weight proteins, especially when

    positively charged, increase viscosity and favor rouleau* formation and thus would raise

    the $%R. 9ibrinogen, the most abundant acute phase reactant, has the greatest effect on

    the elevation of $%R when compared with other acute phase proteins.

    7n the other hand, a change in the frictional forces around the red blood cell can affect

    the $%R. & drop in the red cell number, as in anemia, slightly elevates the $%R since this

    also physically interferes with rouleau* formation. 6acrocytosis with a small surface-to-

    volume ratio have charge relative to their mass and thus sediment more rapidly.

    Dormal values are 1/ mmhr or less for men and "? mmhr or less for women.

    PROFORMA

    S&6 2 S416= C28348&1;&28 2 C-14;3&

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    P14%48&8 C2=9:;8&%0

    1. Jeakness of H Right upper limb Right lower limb )eft upper limb )eft

    lower limb. %ince MMMMMMMM

    ". 8eviation of mouthH (resent &bsent5 to left right, since MMMMMMMMM

    #. &ltered level of consciousness5 (resent &bsent5 sinceMMMMMMMMMMM

    H%&21 2 914%48&8 32=9:;8&%0

    1. Jeakness of right upper limb right lower limb left upper limb left lower

    limb5 (resent &bsent

    7nset H sudden gradual 7ver minutes ours 8ays

    8uring activity at rest while asleep

    ". Inability to speak altered speech H (resent &bsent

    #. istory of altered level of consciousnessH (resent &bsent

    . istory of eadache H (resent absent

    /. istory of vomiting H (resent absent

    0. istory of convulsionsH (resent absent

    A. istory of sensory disturbancesH (resent absent

    4. istory of bowel bladder disturbance H (resent absent

    @. istory of swaying H (resent absent

    1?. istory of loss of vision diplopia change in voice nasal regurgitation

    P;%& H%&210

    8iabetes mellitus Ischemic heart disease Claudication ypertension

    6igraine R8 Trauma to head and spine stroke Transient Ischemic &ttack R&

    &% 7%

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    F;=: %&210

    %troke hypertension sudden death diabetes I8

    P41%28;: H%&210

    8iet +eg 6i*ed

    &ppetite Eood (oor

    %leep %ound 8isturbed

    6artial status married unmarried

    Fowel regular altered

    Fladder regular altered

    abits %moker alcoholic tobacco chewer

    7bstetric and menstrual history in females!H

    &ge of menarche

    Cycles regular irregular

    &ge of menopause

    P%3;: E;=8;&280

    1. 8ecubitus

    ". Fuilt H Jell built moderately built poorly built

    #. %tate of Dutrition H over weight normal under weight

    . ydration status H Jell hydrated 8ehydrated

    /. $yes H (losis leterus (allor &rcus senilis B9 ring cataract

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    0. $ars

    A. 7ral cavity

    4. )ymphadencopathy (resent &bsent

    (edal $dema

    @. $*amination of peripheral vessels and neck vessels

    V&;: D;&;0

    (ulse rateH Respiratory rateH

    Flood pressureH TemperatureH

    S%&4=;&3 E;=8;&280

    1. Dervous system e*aminationH

    a. anded ness right left

    b. 6ental status e*amination

    i. 6emory H Intact lost

    If alertH

    ii. 6emory H Intact lost

    iii. 7rientation H (resent &bsent5 if present to time

    place person

    iv. %peech and language H Dormal aphasic dysarthric

    c. Cranial nerves e*amination

    i. 1stcranial nerve sense of smell H (reserve altered lost

    ii. "ndcranial nerve acuty of vision normal reduced

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    9ield of vision normal reduced

    Colour vision normal altered

    7ptic fundus e*amination H

    Dormal abnormal

    iii. #rd, thand 0thCranial nervesH

    1. 7cular movements full range restricted

    ". %uint present absent

    #. Dystagmus present absent

    . (tosis (resent &bsent

    /. (upils si'e Right

    )eft

    )ight Refle* Right5 &ccommodation refle* Right

    )eft )eft

    iv. /thcranial nerve nerveH

    1. 6otor

    ". %ensory

    #. %ecretory function

    . Refle*es

    a. corneal (resent absent

    b. Con

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    1. 6otor

    ". %ensory

    #. %ecretory

    vi. 4thcranial nerves

    1. RinneKs test

    ". JeberKs test

    vii. @thand 1?thcranial nerves

    1. (alatal refle* vula central deviates to leftH right

    side

    ". Eag refle* (resent absente*aggerated

    viii. 11thcranial nerve

    1. (ower in sternoceidomastoid and trepi'ius muscle

    i*. 1"thcranial nerve

    d. 6otor system e*aminationH

    Right )eft

    ) )) ) ))

    a. Dutrition

    b. Tone

    c. (ower

    d. Coordination

    e. Involuntary movementsH (resent absent

    f. Refle*esH Right )eft

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    a. %uperficial

    i. &bdominal

    ii. Cremastric

    iii. (lantar

    b. 8eep

    i. Ficeps

    ii. Triceps

    iii. %upinator

    iv. Bnee

    v. &nkle

    c. (rimitive refle* (resent &bsent

    d. %ensory system e*aminationH

    Right )eft

    Touch

    (ain

    Temperature

    +ibration

    Noint sense

    Cortical sensation

    e. Cerebrallar system e*aminationH

    Right )eft

    9inger Dose test

    Bnee eel test

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    8ysdiadokinesia

    g. E&ITH

    h. %igns of &utonomic 8isturbances (resent&bsent

    i. %igns of 6eningeal iriitation

    Deck RigidityBernings signFrud'enski sign

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    I8

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    S8;&614 2 G64

    APPENDIX-IIC

    7.$ DOES THE STUDY REUIRE ANY INVESTIGATIONS ORINTERVENTION TO BE CONDUCTED ON PATIENTS OR

    OTHER ANIMALS, IF SO PLEASE DISCRIBE BRIEFLY

    YES

    CT %can ead plain of the patient

    C-Reactive protein CR(! of patient and age and se* matched healthy controls

    $%R of patient and age and se* matched healthy controls

    APPENDIX-IID

    7.! HAS THE ETHICAL CLEARANCE BEEN OBTAINED FROM

    YOUR INSTITUTION IN CASE OF 7.$

    YES

    APPENDIX-III

    ".' LIST OF REFERANCES

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    1. 8i Dapoli 6, (apa 9, Focola +. 2(rognostic Influence of increased CR( and

    fibrinogen levels in ischemic stroke3. %troke "??15#"H1##-1#4.

    ". Nialal I, 8evara< %. 2Inflammation and atherosclerosis5 the value of the high

    sensitivity c-reactive protein assay as a risk marker3. &m N. Clin (athol.

    "??1H8ecH110H %upplH%1?4-1/

    #. &garwal 6(, %ingh DR, Baur IR. 2C-Reactive (rotein in acute cerebral

    infarction3. N&(I. +ol/158ec "??#

    . Beith J. 6uir, 68, 6RC(5 Christopher N. Jeir, F%C5 Jafa &lwan, 6RC

    (ath5 et al. 2C-Reactive protein and outcome after ischemic stroke3. %troke

    1@@@5#?H@41-@4/.

    /. 8hami

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    1?. Datalia % .Roast, (hilip & Jolf, Carlos %, Base et al,KK(lasma concentration

    of C- reactive protein and risk of ischemic stroke and trancient ischemic

    attackKK. The 9ramingham %tudy. %troke Dov "??15#"5"/A/-"/A@.

    11. International Council for %tandardi'ation in aematology $*pert (anel on Flood

    Rheology!H IC% recommendations for measurement of erythrocyte sedimentation

    rate. N Clin (athol 1@@#5 0H1@4-"?4

    1". Thomas R8, Jestengard NC, ay B), et alH Calibration and validation for

    erythrocyte sedimentation tests. &rch (athol )ab 6ed 1@@#5 11AHA1@-A"#

    1#. %mith $6, %amadian %H se of the erythrocyte sedimentation rate in the elderly. Fr N

    osp 6ed 1@@5 /1H#@-#@A

    APPENDIX-IID

    PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL

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    SECTION A

    A. T&:4 2 &4 %&6 A STUDY OF C-REACTIVE

    PROTEIN IN ACUTE ISCHEMIC

    STROKE

    B. P1839;: 8

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    D24% &4 %&6 8

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    -9;%4 284 ;8 &2 3:83;: &1;:%.

    -4941=48&;: 6%4 8-9;&48&% ;8 4;:&

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    L. +:: &4383;: 861%8 4:9 4 14>614

    21 &4 %&; 2 2%9&;:, 4%,

    :: & 8&41414 & &41 6&4%

    :: 26 14316& 2&41 %&; 21 &4 61;&282 &4 %&6

    I 4%