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Click to edit Master title style<= /div>
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------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/master07.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/pres.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0001.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is an acquired chronic hemolytic anemia which arises from a somatic mutatio= n in a hematopoietic stem cell.  M= ost hematopoitic cell lines may be affected by the intrinsic membrane defect= . This defect renders the red cells highly susceptible to complement mediated <= /b>= lysis resulting in the characteristic hemolysis.
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Paro= xysmal Nocturnal Hemoglobinuria (PNH)
3D=History
3D=Epidemiology
3D=Clinical Features
&= #8211;Relationship to Aplastic Anemia
&= #8211;other diseases
3D=Pathogenesis
3D=Laboratory Diagnosis
3D=Therapy
3D"*"
Topics to be considered
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 H= istory
Investigator   Year        = ;            &n= bsp;       Contribution
<= b>
Gull    1866     Described noctu= rnal and paroxysmal nature of “intermittent haematinuria” in a young = tanner. Strubing         1882 Distinguished PNH from parox= ysmal cold haemoglobinuria and march haemoglobinuria. <= /span>= Attributed the problem to t= he red cells. van den Burgh  1911 Red cells lysed in acidified serum. Suggested a role = for complement. Enneking         1928    Coined the name “paroxysmal nocturnal = haemoglobinuria”. = ;
Marchiafava= 1928- Described perpetual hemosiderinemia in absence of &= #13;
and Micheli= 1931 hemolysis. Their names became eponymous for PNH = in Europe. <= /span>Ham        = ;          1937- Identified the role of compl= ement in lysis of PNH red 1939 cells. Deve= loped the acidified serum test, also called the Ham test, which is stil= l used to diagnose PNH. Demonstrated that only a portion of PNH red cells are = abnormally sensitive to complement. Davitz 1986 Suggests defect in membrane protein anchoring system responsible =
Hall & = Rosse 1996 Flow cytometry for the diagnosis of PNH<= /div>
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Epidemiology
3D=Rare disease -
&= #8211;frequency unknown
= 211;thought to be on the same order as aplastic anemia (2-6 per million)&= #13;
3D=Median age at diagnosis
&= #8211;~ 35 yrs
&= #8211;PNH reported at extremes of age
3D=Female:Male ratio =3D 1.2:1.0
3D=No increased risk of PNH in patient relatives
3D=Median Survival after diagnosis ~ 10-15 yrs
3D"*"
3D"*"
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Clinical Features
3D"=Major symptoms (Hemolysis, Cytopenia, and tendency to thrombosis)
= 211;chronic hemolysis with acute exacerbations (hallmark)
=3D"*"most patient at some stage
=3D"*"only 1/3 exhibit hemolysis at diagnosis
3D"*"Recurrent attacks of intravascular hemolys= is are usually associated with;
&= #8211;hemoglobinuria
&= #8211;abdominal pain
&= #8211;dysphagia
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&= #8211;cytopenia (varying severity)
=3D"*"isolated subclinical thrombocytopenia
=3D"*"classical severe aplastic anemia
&= #8211;tendency to thrombosis
3D"*"venous thrombosis (40%) of patients, main cause o= f morbidity
3D"=Variable expression of above often causes considerable delay in the diagnosis
3D=Major cause of death
&= #8211;venous thrombosis
&= #8211;complications from progressive pancytopenia
3D"*"
3D"*"
Clinical Features
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3D"=25% of PNH patients survive >25 years - one half of these go on to spontaneous remission
3D=Remission patients
&= #8211;hematological values revert to normal
&= #8211;no PHN rbcs or granulocytes detected
= 211;PNH lymphocytes - still detected but no clinical consequence <= /span>
3D=Higher incidence of acute leukemia (6%)
–“preleukemic condition” most likely bone marrow failure not PNH
Clinical Features - Long term
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3D"*"AA described as pancytopenia w= ith nonfunctioning bone marrow. Cytopenia in one or all cell lineages also common to PNH 3D"*"High percentage of patients with AA develo= p clinical PNH or have lab evidence of PNH abnormality at some point (52%) 3D"*"Supports the theory that bone marrow failu= re supports the abnormal PNH cells - more later
Clinical Features - Relationship to aplastic anemia (AA)
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Pat= hogenesis - The Defect
3D"=Defect - Somatic mutation of PIG-A gene (phosphatidylinositol glyc= an complementation group A)  located on the X chromosome in a clone of a hematopoietic stem cell
&#= 8211;>100 mutations in PIG - A gene known in PNH
= 211;The mutations (mostly deletions or insertions) generally result in stop codons - yielding truncated proteins which may be non or partially= functional - explains heterogeneity seen in PNH
–
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3D"*"PIG - A gene codes for 60 kDa protein glycosyltransferase which effects the first step in the synthesis of the glycolipid GPI anchor (glycosylphosphatidylinositol). Results in clones lacking GPI anchor - in <= /span>turn, attached proteins
<= span style=3D'font-size:88%;visibility:hidden'>3D"*"
Pat= hogenesis - The Defect
GPI Anchor
PIG - A protein<= span style=3D'mso-special-format:lastCR;display:none'>
Protein
Phosphoethanolamine
Mannose
Mannose
Glucosamine
Mannose
Phosphatidylinositol
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PNH blood cells deficient in GPI anchor lack <= span style=3D'font-size:88%'>membrane proteins linked via the anchor
–M= embrane proteins w/o anchor degraded in ER
Severity & size of deficiency - variable - <= span style=3D'font-size:88%'>clinical/diagnostic implications
= 3D"*"GPI anchor highly conserved in all eukaryotic cells
–Va= riant surface proteins of Trypanosomes - GPI linked
–S= hed by cleavage of GPI anchor - immune system avoid
–S= wapping GPI linked proteins - CD55 complement resistance - = Schistosoma mansoni
–In Humans
3D"*"signal transduction, co-receptors
3D"*"advantage to this type of anchor?
3D"*"
Pathogenesis - The Defect
GPI Anchor deficiency
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Proteins anchored by GPI Anchor
and=
Surface Proteins Missing on PNH Blood Cells
<= b>
Antigen<= span style=3D'mso-spacerun:yes'>        = ;            &n= bsp;            = ;            &n= bsp;            = ;       Expression Pattern
<= b>
Enzymes<= /u><= b>
Acetylcholi= nesterase (AchE)        = ;       Red blood cell= s
Ecto-5'-nuc= leotidase (CD73)       Some B- and T-lymphocytes
Neutrophil alkaline phosphatase(NAP) Neutrophils
ADP-rybosyl transferase     Some T-lymphs, Neutrophils&= #13;
<= b>
Adhesion molecules
Blast-I/CD4= 8        = ;            &n= bsp;         Lymphocytes= 3;
Lymphocyte function-
associated antigen-3(LFA-3 or CD58) All blood cells
CD66b Neutrophils =
<= b>
<= b>
Compleme= nt regulating surface proteins
Decay accelerating factor (DAF or CD55)        = ;    All blood cells&= #13;
Homologous restriction factor, &#= 13;
Membrance inhibitor of reactive lysis = All blood cells
(MIRL or CD= 59)
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Surface Proteins Missing on PNH Blood Cells
<= b>
Antigen<= span style=3D'mso-spacerun:yes'>        = ;            &n= bsp;            = ;            &n= bsp;            = ;       Expression Pattern
<= b>
Receptor= s<= b>
Fc-g receptor III (Fc g Rlll or CD16)        Neutrophils, NK-cells, macrophages,
some T-lymphocytes =
Monocyte differentiation antigen Monocytes, macrophages
(CD14) =
Urokinase-t= ype Plasminogen Monocytes, granulocytes
Activator Receptor (u-PAR, CD87)
<= b>
Blood gr= oup antigens
Comer antig= ens (DAF)        = ;            &n= bsp;       Red blood cells=
Yt antigens (AchE)        = ;            &n= bsp;      Red blood cells=
Holley Greg= ory antigen        = ;            Red blood cells=
John Milton= Hagen antigen (JMH)    Red blood cells, lymphocytes&= #13;
Dombrock reside        = ;            &n= bsp;   Red blood cell= s
<= b>
Neutroph= il antigens
NB1/NB2        = ;            &n= bsp;            = ;          Neutrophils=
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Surface Proteins Missing on PNH Blood Cells
<= b>
Antigen<= span style=3D'mso-spacerun:yes'>        = ;            &n= bsp;            = ;            &n= bsp;            = ;       Expression Pattern
<= b>
Other su= rface proteins
of unkno= wn functions
CAMPATH-1 a= ntigen (CDw52)        = ;            &n= bsp; Lymphocytes, monocytes
CD24 B-lymphocytes, Neutrophils,=
eosinophils =
p5O-80 Neutrophils =
GP500        = ;            &n= bsp;            = ;       Platelets =
GPI75        = ;            &n= bsp;    Platelets <= /b>
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Pathogenesis - Functional consequences of lack of GPI linked proteins
<= img src=3Dimage003.gif alt=3D"*" style=3D'position:absolute;top:23.8%;left:-4.= 02%; width:2.41%;height:57.14%'>In vivo function of many = of these membrane proteins not fully understood
= 3D"*"However, CD55 and CD59 functions are well known
–CD55 (decay accelerating factor) inhibits the form= ation or destabilizes compl= ement C3 convertase (C4bC2a)
–CD59 (memb= rane inhibitor of reactive lysis, protectin, homologous restriction factor) Protects the membra= ne from attack by the C5-C9 complex
–Inherited absences of both proteins in humans have= been described
<= img src=3Dimage004.gif alt=3D"*" style=3D'position:absolute;top:18.75%;left:-3= .31%; width:2.29%;height:56.25%'>Most inherited deficiencies of CD55 - no distinct clinical hemolytic syndrome
= 3D"*"Inherited absence of CD59 - produces a clinical disease similar to PNH with hemolysis and recurrent thrombotic eve= nts
------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0016.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
C5b-8
RBC Membrane
Protectin (CD59)
<= /span>
= <= /span>
<= /span>
= <= /span>
C9 unable to
insert in catalytically
active form
Mechanism for hemolysis in PNH via lack of CD59
3D"Oval:
C5b-8
RBC Membrane
C9 able to
insert in catalytically
active form and polymerize
<= /span>
= <= /span>
= <= /span>
= <= /span>
<= span style=3D'color:black;mso-special-format:lastCR;display:none'> <= /span>
<= /span>
<= /span>
<= span style=3D'color:black;mso-special-format:lastCR;display:none'> <= /span>
= <= /span>
= <= /span>
= NORMAL
P= NH
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R0lGODlhGgIEAHcAMSH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACH5BAEAAAAALAIAAQAW AgMAgAAAAP///wInjI+py+0Po5y02ouz3rz7D4biSJbmiabqyrbuC8fyTNf2jef6zisFADs= ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0017.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
Pathogenesis - Clonal evolution and cellular selection
<= img src=3Dimage003.gif alt=3D"*" style=3D'position:absolute;top:23.8%;left:-3.= 74%; width:2.24%;height:57.14%'>Expansion of abnormal hematopoietic stem cell required = for PNH disease expression
–T= heories for expansion
<= img src=3Dimage004.gif alt=3D"*" style=3D'position:absolute;top:18.75%;left:-2= .74%; width:1.89%;height:56.25%'>Blood cells lacking GPI-linked proteins have intrinsic ability to gro= w abnormally fast
–In vitro  growth studies demonstrate that t= here are no differences in growth between normal progenitors and PNH phenotype progenitors
–In vivo  - mice deficient for PIG -A gene also demonstrates no growth advantage to repopulation of BM.
<= img src=3Dimage004.gif alt=3D"*" style=3D'position:absolute;top:25.0%;left:-2.= 72%; width:1.88%;height:56.25%'>Additional environmental factors exert selective pressure in favor of= expansion of GPI anchor deficient blood cells =
–PNH hematopoitic cells perferentially engraft SCID= mice compared to phenot= ypically hematopoitic cells
–Close association with AA - PNH hematopoitic cells= cells may be more resist= ant to the IS than normal hematopoitic cells.
<= img src=3Dimage013.gif alt=3D"*" style=3D'position:absolute;top:21.42%;left:-3= .12%; width:1.92%;height:57.14%'>Evidence in AA is that the decrease in hematopoitic cells is due to <= /span>increased apoptosis via cytotoxic T cells by direc= t cell contact or cytokines (escape = via deficiency in GPI linked protein???) 
------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/image013.gif Content-Transfer-Encoding: base64 Content-Type: image/gif R0lGODlhDwAPAHcAACH/C01TT0ZGSUNFOS4wDQAAAAFzUkdCAK7OHOkAIf8LTVNPRkZJQ0U5LjAY AAAADG1zT1BNU09GRklDRTkuMAlmS20eACH/C01TT0ZGSUNFOS4wGAAAAAxjbVBQSkNtcDA3MTIC AAAFC2oeAgAh+QQBAAACACwAAAAADwAPAIOZZplmZmbAwMCZmcxmmZmZmWZmmWaZzJnMmZkBAgMB AgMBAgMBAgMBAgMBAgMBAgMESlDISau9OE8wCigEYABBOR1FFxplOyEDEhYB6UrDQSAgzZoSmOzT uglyu54NKBASVoFfYNMBEJdTCarTixqd1+IEySP4vrFZrRgBADs= ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0018.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
Lab= oratory Evaluation of PNH
= 3D"*"Acidified Serum Test (Ham Test 1939)
–A= cidified serum activates alternative complement pathway resulting in lysis of patient’s rbcs=
–May be positive in congenitial dyserythropoietic <= /span>anemia
–S= till in use today
= 3D"*"Sucrose Hemolysis Test (1970)
–10% sucrose provides low ionic strength which promotes complement binding resulting in lysis of = patient’s rbcs
–M= ay be positive in megaloblastic anemia, autoimmune hemolytic anemia, others
–L= ess specific than Ham test
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= 3D"*"PNH Diagnosis by Flow Cytometry (1986)
–Considered method of choice for diagnosis of PNH (1996) =
= 211;Detects actual PNH clones lacking GPI anchored proteins
–More sensitive and specific than Ham and sucrose hemolysis test = ;
–
Lab= oratory Evaluation of PNH
------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0020.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH Diagnosis by Flow Cytometry
Antigen <= /u>Cell Lineage Function
CD14 monocytes LPS receptor, MDF
CD16 neutrophils FcgIII receptor
CD24 neutrophils B-cell differentiation marker
CD55 all lineages DAF
CD58 all lineages possible adhe= sion
CD59 all lineages MIRL, HRF, protectin <= /div>
CD66b neutrophils CEA-related glycoprotein
Of the long list of GPI anchored protein, monoclonal antibodies to the following antigens have been used in the diagnosis of PNH <= /span>
The most useful Abs are to C= D14, 16, 55, 59, and 66.  Are all = required?  Probably not - more studies neede= d <= /span>
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Antigen expression is generally categorized into three antigen density groups
–t= ype I Normal Ag expression
–t= ype II Intermediate Ag expression
–t= ype III No Ag expression
3D"*"= Patient samples that demonstrate cell populations with diminished or absent GPI-linked <= /span>proteins (Type II or III cells) with multiple antibodies are considered to be consistent with = PNH.
3D"*"= Should examine multiple lineages (ie = granulocytes & monocytes)
3D"*"=
3D"*"=
PNH Diagnosis by Flow Cytometry
------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0022.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH Diagnosis by Flow Cytometry
Examples of variable GPI linked CD59 and CD55 expression= on granulocytes on PNH patient = and normal control
Healthy
Control
PNH
Patient
Type I
Type II
Normal
expression
Normal
expression
Type II
Type I
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charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH Diagnosis by Flow Cytometry
Example of variable expression of several = GPI linked Ags on several lineages
From P= urdue Cytometry CD-ROM vol3 97
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xV2KuxV2KuxV2KuxV2KuxV2KuxV2KuxV2KuxV2KuxV2KuxV2KuxV2Kv/2a== ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0024.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
3D"*"Flow Cytometry is method of choice but only supportive for/against diagnosis
3D"*"More studies are needed to better define whether <= span style=3D'font-size:88%'>the type (I, II, or III), cell lineage, and size of the
circulating clone= can provide additional prognostic
information. =
3D"*"Theoretically - should be very valuable
to correlate incr= easing amount and severity of PNH cells (type I to type III) to bone marrow failure and clinical severity and visa versa
<= span style=3D'visibility:hidden'>3D"*"
PNH Diagnosis by Flow Cytometry
------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/slide0025.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH)
Therapy
= 3D"*"Bone Marrow Transplantation
–O= nly curative treatment
–chronic condition (possiblity of spontaneous remis= sion) - BMT should be avoided
= 3D"*"Immunosuppressive therapy
–A= ntilymphocyte globulin &/or cyclosporine A
3D"*"Does not alter proportion of PNH hemopoiesis
–S= teroids - experimental - controlled studies ??
= 3D"*"Growth Factors
–S= ome improvement
–no evidence that normal clones respond better than PNH clones
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FullScrInit(); =09 MakeSldVis(); ChkAutoAdv() if( runAnimations ) { if( document.all("NSPlay") ) document.all("NSPlay").autoStart =3D false; if( sld.filters && sld.filters.revealtrans ) setTimeout( "document.body.start()", sld.filters.revealtrans.duration * = 1000 ); else document.body.start(); } } function MakeSldVis()=20 { var fTrans=3Dg_showAnimation && SldHasTrans() if( fTrans )=09 { if( g_bgSound ) { idx=3Dg_bgSound.indexOf(","); pptSound.src=3Dg_bgSound.substr( 0, idx ); pptSound.loop=3D -(parseInt(g_bgSound.substr(idx+1))); } SlideObj.filters.revealtrans.Apply()=09 } SlideObj.style.visibility=3D"visible" if( fTrans ) SlideObj.filters.revealtrans.Play() } function MakeNotesVis()=20 { if( !IsNts() ) return false=20 SlideObj.style.display=3D"none" nObj =3D document.all.item("NotesObj") parent.SetHasNts(0) if( nObj ) {=20 nObj.style.display=3D"" parent.SetHasNts(1) } return 1 } function ChkAutoAdv() { if(SldHasTrans()) SlideObj.onfilterchange=3DAutoAdv else AutoAdv() } function AutoAdv() { if(!IsWin("PPTSld") || !gUseSldTimings )return var sld=3DGetCurSld() if( (sld.mAdvDelay>0) && !parent.IsFramesMode() ) setTimeout("parent.GoToNextSld()",sld.mAdvDelay) } function GetObj(id) { if(g_supportsPPTHTML) return document.all(id); else return document.getElementById(id); } function SldHasTrans() { return SlideObj.style.filter !=3D ""; } function GetSldId() { return sId=3Dlocation.href.substring(location.href.la= stIndexOf('/')+1) } function HideMenu() { if( frames["PPTSld"] && PPTSld.document.all.item("ctx= tmenu") && PPTSld.ctxtmenu.style.display!=3D"none" ) { PPTSld.ctxtmenu.styl= e.display=3D'none'; return true } return false } function IsWin( name ) { return window.name =3D=3D name } function IsNts() { return IsWin("PPTNts") } function IsSldOrNts() { return( IsWin("PPTSld")||IsWin("PPTNts") ) } function SupportsPPTAnimation() { return( navigator.platform =3D=3D "Win32"= && navigator.appVersion.indexOf("Windows")>0 ) } function SupportsPPTHTML() { var appVer=3Dnavigator.appVersion, msie=3DappVer.indexOf("MSIE "), ver=3D0 if( msie >=3D 0 ) ver=3DparseFloat( appVer.substring( msie+5, appVer.indexOf(";",msie) ) ) else ver=3DparseInt(appVer) return( ver >=3D 4 && msie >=3D 0 ) } function _RSW() { if( !g_supportsPPTHTML || IsNts() || ( !g_scaleInFrame && (!IsWin("PPTSld") || !parent.IsFullScrMode()) ) ) return var padding=3D0; if( IsWin("PPTSld") && parent.IsFramesMode() ) padding=3D6 cltWidth=3Ddocument.body.clientWidth-padding cltHeight=3Ddocument.body.clientHeight-padding factor=3D(1.0*cltWidth)/g_origW if( cltHeight < g_origH*factor ) factor=3D(1.0*cltHeight)/g_origH newSize =3D g_origSz * factor if( newSize < 1 ) newSize=3D1 s=3DSlideObj.style s.fontSize=3DnewSize+"px" s.posWidth=3Dg_origW*factor s.posHeight=3Dg_origH*factor s.posLeft=3D(cltWidth-s.posWidth+padding)/2 s.posTop=3D(cltHeight-s.posHeight+padding)/2 if( g_scaleHyperlinks ) ScaleHyperlinks( factor ) } function _InitAnimations() { animRuntimeInstalled =3D ''+document.body.localTime !=3D 'undefined'; isFullScreen =3D (window.name =3D=3D "PPTSld") && !parent.IsFramesMode(); g_animUseRuntime =3D g_showAnimation && animRuntimeInstalled && !(isFullSc= reen && parent.IsSldVisited()); if( g_animUseRuntime ) { collSeq =3D document.all.tags("seq"); if( collSeq !=3D null ) { for(ii=3D0;ii numSlds ) gSldJumpIdx =3D numSlds; if ( gSldJumpIdx >=3D 0 ) { if ( gSldJumpIdx =3D=3D 0 ) gSldJumpIdx =3D 1; var jumpTo =3D parseInt(gSldJumpIdx); gSldJump =3D 0; gSldJumpIdx =3D ""; win.GoToSld( parent.GetSldList().mList[jumpTo-1].mSldHref ) } } } function _KDH() { if( event.keyCode =3D=3D 8 ) { event.returnValue =3D 0; parent.GoToPrevSld(); } } function DocumentOnClick() { if( IsNts() || parent.HideMenu() ) return; if( ( g_allowAdvOnClick && !parent.IsFramesMode() ) || (event && (event.keyCode=3D=3D32) ) ) parent.GoToNextSld(); } var g_supportsPPTHTML =3D SupportsPPTHTML(), g_scaleInFrame =3D 1, gId=3D""= , g_bgSound=3D"", g_scaleHyperlinks =3D false, g_allowAdvOnClick =3D 1, g_showInBrowser = =3D 0, gLoopCont =3D 0, gUseSldTimings =3D 1; var g_showAnimation =3D g_supportsPPTHTML && SupportsPPTAnimation() && ( (w= indow.name=3D=3D"PPTSld" && !parent.IsFramesMode()) || g_showInBrowser );va= r g_animManager =3D null; var g_animUseRuntime =3D false; var g_animItemsToHide, g_animInteractiveItems, g_animSlideTime; var g_animMainSequence =3D null; var ENDSHOW_MESG=3D"End of slide show, click to exit.", SCREEN_MODE=3D"Fram= es", gIsEndShow=3D0, NUM_VIS_SLDS=3D25, SCRIPT_HREF=3D"script.js", FULLSCR_= HREF=3D"fullscreen.htm"; var gCurSld =3D gPrevSld =3D 1, g_offset =3D 0, gNtsOpen =3D gHasNts =3D gO= tlTxtExp =3D 0, gHasNarration =3D 0, gOtlOpen =3D true window.gPPTHTML=3DSupportsPPTHTML() var gMainDoc=3Dnew Array(new hrefList("slide0001.htm",1,-1,1),new hrefList(= "slide0002.htm",1,-1,1),new hrefList("slide0004.htm",1,-1,1),new hrefList("= slide0003.htm",1,-1,1),new hrefList("slide0005.htm",1,-1,1),new hrefList("s= lide0006.htm",1,-1,1),new hrefList("slide0007.htm",1,-1,1),new hrefList("sl= ide0008.htm",1,-1,1),new hrefList("slide0009.htm",1,-1,1),new hrefList("sli= de0010.htm",1,-1,1),new hrefList("slide0012.htm",1,-1,1),new hrefList("slid= e0011.htm",1,-1,1),new hrefList("slide0013.htm",1,-1,1),new hrefList("slide= 0014.htm",1,-1,1),new hrefList("slide0015.htm",1,-1,1),new hrefList("slide0= 016.htm",1,-1,1),new hrefList("slide0017.htm",1,-1,1),new hrefList("slide00= 18.htm",1,-1,1),new hrefList("slide0019.htm",1,-1,1),new hrefList("slide002= 0.htm",1,-1,1),new hrefList("slide0021.htm",1,-1,1),new hrefList("slide0022= .htm",1,-1,1),new hrefList("slide0023.htm",1,-1,1),new hrefList("slide0024.= htm",1,-1,1),new hrefList("slide0025.htm",1,-1,1)); /********************************************* Frameset functions These functions control slide navigation and state of the frameset. **********************************************/ function FullScrInit() { g_allowAdvOnClick =3D GetCurSld().mAdvOnClk document.body.style.backgroundColor=3D"black" document.oncontextmenu=3Dparent._CM; document.onkeydown =3D _KDH; document.ondragstart=3DCancel document.onselectstart=3DCancel self.focus() } function Redirect( frmId ) {=09 var str=3Ddocument.location.hash,idx=3Dstr.indexOf('#'), sId=3DGetSldId() if(idx>=3D0) str=3Dstr.substr(1); if( window.name !=3D frmId && ( sId !=3D str) ) { obj =3D GetObj("Main-File") window.location.href=3Dobj.href+"#"+sId return 1 } return 0 } var MHTMLPrefix =3D CalculateMHTMLPrefix();=20 function CalculateMHTMLPrefix() { if ( document.location.protocol =3D=3D 'mhtml:') {=20 href=3Dnew String(document.location.href)=20 Start=3Dhref.indexOf('!')+1=20 End=3Dhref.lastIndexOf('/')+1=20 if (End < Start)=20 return href.substring(0, Start)=20 else=20 return href.substring(0, End)=20 } return ''; } function GetTags(base,tag) { if(g_supportsPPTHTML) return base.all.tags(tag); else return base.getElementsByTagName(tag); } function UpdNtsPane(){ if(frames["PPTNts"]) PPTNts.location.replace( MHTMLP= refix+GetHrefObj( gCurSld ).mNtsHref ) } function UpdNavPane( sldIndex ){ if(gNavLoaded) PPTNav.UpdNav() } function UpdOtNavPane(){ if(gOtlNavLoaded) PPTOtlNav.UpdOtlNav() } function UpdOtlPane(){ if(gOtlLoaded) PPTOtl.UpdOtl() } function SetHasNts( fVal ) { if( gHasNts !=3D fVal ) { gHasNts=3DfVal UpdNavPane() } } function ToggleOtlText() { gOtlTxtExp=3D!gOtlTxtExp UpdOtlPane() } function ClearMedia() { // Clear any sounds playing before launching another browser window. Other= wise, // in fullscreen mode, you'll continue to hear the sound in the frames mod= e. if (PPTSld.pptSound) PPTSld.pptSound.loop =3D 0; } function FullScreen() {=20 if ( PPTSld.g_animUseRuntime ) PPTSld.document.body.pause(); ClearMedia(); var href =3D ( document.location.protocol =3D=3D 'mhtml:') ? FULLSCR_HREF = : FULLSCR_HREF+"#"+GetHrefObj(gCurSld).mSldHref; if(PPTNav.event.ctrlKey) { var w =3D (window.screen.availWidth * 1.0) / 2.0 var h =3D w * (PPTSld.g_origH * 1.0) / PPTSld.g_origW win =3D window.open( MHTMLPrefix+href,null,"toolbar=3D0,resizable=3D1,top= =3D0,left=3D0," + "width=3D"+ w + ",height=3D" + h ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } else { win =3D window.open( MHTMLPrefix+href,null,"fullscreen=3Dyes" ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } } function ToggleVNarration() { rObj=3DPPTSld.document.all("NSPlay") if( rObj && !PPTSld.g_animUseRuntime ) { if( (rObj.playState =3D=3D 1)||(rObj.playState =3D=3D 0) ) rObj.Play() else if( rObj.playState =3D=3D 2 ) rObj.Pause() else return; } else if( PPTSld.g_animUseRuntime ) { narObj =3D PPTSld.document.all("narrationID") if( narObj ) narObj.togglePause() } } function GetCurSldNum() { =20 obj=3DGetHrefObj(gCurSld) if( obj.mOrigVis =3D=3D 1 ) return obj.mSldIdx else =20 return gCurSld } function GetNumSlds() { =20 if( GetHrefObj(gCurSld).mOrigVis =3D=3D 1 ) return GetSldList().mNumVisSlds; else return GetSldList().mList.length } function GetSldNum( href ) { for(ii=3D0; ii 1 ) PopSldList(); else if( !IsFramesMode() ) { if( gLoopCont ) GoToFirst() else EndShow() } } function GoToPrevSld() { ii=3DgCurSld-1 if( ii > 0 ) { obj=3DGetHrefObj(ii) while ( obj && ( obj.mVis =3D=3D 0 ) && ( ii>0 ) ) obj=3DGetHrefObj(--ii) if( ii =3D=3D 0 ) ii=3D1 GoToSldNum(ii) } } function GoToFirst(){ GoToSld( GetHrefObj(1).mSldHref ) } function GoToLast() { ii=3DGetSldList().mList.length if( ii !=3D gCurSld ) GoToSld( GetHrefObj(ii).mSldHref ) } function GoToSldNum( num ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue obj =3D GetHrefObj( num ) obj.mVis=3D1 gPrevSld=3DgCurSld gCurSld =3D num; PPTSld.location.replace(MHTMLPrefix+obj.mSldHref) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function GoToSld( href ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue GetHrefObj( GetSldNum(href) ).mVis=3D1 PPTSld.location.replace(MHTMLPrefix+href) } function SldUpdated( id ) { if( id =3D=3D GetHrefObj(gCurSld).mSldHref ) return gPrevSld=3DgCurSld gCurSld=3DGetSldNum(id) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function PrevSldViewed(){ GoToSld( GetHrefObj(gPrevSld).mSldHref ) } function HasPrevSld() { return ( gIsEndShow || ( gCurSld !=3D 1 && GetHrefO= bj( gCurSld-1 ).mVis =3D=3D 1 )||( GetCurSldNum() > 1 ) ) } function HasNextSld() { return (GetCurSldNum() !=3D GetNumSlds()) } function CloseWindow() { if( HideMenu() ) return; =09 var event =3D PPTSld.event; if( !IsFramesMode() && event && (event.keyCode=3D=3D27 || event.keyCode=3D= =3D32 || event.type=3D=3D"click" ) ) window.close( self ); CatchNumKeys( self, event ); } function Unload() { gIsEndShow=3D0; } function SetupEndShow() { gIsEndShow=3D1; PPTSld.document.body.scroll=3D"no"; PPTSld.document.onkeypress=3DCloseWindow; PPTSld.document.onclick=3DCloseWindow; PPTSld.document.oncontextmenu=3D_CM; } function EndShow() { if( IsFramesMode() ) return if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue doc=3DPPTSld.document var dir =3D doc.body.dir if( dir !=3D "rtl" ) dir =3D "ltr"; doc.open() doc.writeln('


' + ENDSHOW_MESG + '

') doc.close() } function SetSldVisited(){ GetSldList().mList[gCurSld-1].mVisited=3Dtrue } function IsSldVisited(){ return GetSldList().mList[gCurSld-1].mVisited } function hrefList( sldHref, visible, advDelay, advClk ) { this.mSldHref=3D this.mNtsHref =3D sldHref this.mOrigVis=3D this.mVis =3D visible this.mVisited=3D false this.mAdvDelay=3D advDelay this.mAdvOnClk=3D advClk } function SldList(arr,curSld,fEnd) { this.mCurSld =3D curSld; this.mList =3D new Array(); var idx =3D 1; for(ii=3D0;ii 0) { PushSldList(sldList,fEnd); gCurSld =3D 1; } else if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue } function PushSldList(arr,fEnd) { var ii =3D gSldStack.length; gSldStack[ii] =3D new SldList(arr,gCurSld,fEnd); GoToSld( gSldStack[ii].mList[0].mSldHref ); } function PopSldList() { if (gSldStack[gSldStack.length-1].fEndShow) EndShow() else { gCurSld =3D gSldStack[gSldStack.length-1].mCurSld; gSldStack[gSldStack.length-1] =3D null; gSldStack.length--; var sldList =3D gSldStack[gSldStack.length-1]; GoToSld( sldList.mList[gCurSld - 1].mSldHref ); } } var custShowList=3Dnew Array(); /********************************************* Navigation button implementation There are 2 types of buttons: ImgBtn, TxtBtn implemented as function objects. They share a similiar interface so the event handlers can call SetActive, for example, on a button=20 object without needing to know exactly=20 what type of button it is. **********************************************/ //---------------------------------- function ImgBtn( oId,bId,w,action ) //---------------------------------- { var t=3Dthis t.Perform =3D _IBP t.SetActive =3D _IBSetA t.SetInactive=3D _IBSetI t.SetPressed =3D _IBSetP t.SetDisabled=3D _IBSetD t.Enabled =3D _IBSetE t.ChangeIcon =3D null t.UserAction =3D action t.ChgState =3D _IBUI t.mObjId =3D oId t.mBorderId=3D bId t.mWidth =3D w t.mIsOn =3D t.mCurState =3D 0 } function _IBSetA() { if( this.mIsOn ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _IBSetI() { if( this.mIsOn ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0=20 } } function _IBSetP() { if( this.mIsOn ) { obj=3Dthis.ChgState( gShadowClr,gHiliteClr,2 ) obj.style.posLeft+=3D1; obj.style.posTop+=3D1 } } function _IBSetD() { =20 obj=3Dthis.ChgState( gFaceClr,gFaceClr,0 ) obj.style.posTop=3D0=20 } function _IBSetE( state ) { var t=3Dthis GetObj( t.mBorderId ).style.visibility=3D"visible" if( state !=3D t.mIsOn ) { t.mIsOn=3Dstate if( state ) t.SetInactive() else t.SetDisabled() } } function _IBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( t.ChangeIcon ) { obj=3DGetObj(t.mObjId) if( t.ChangeIcon() ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-4)*t.mWidth else obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-0)*t.mWidth } t.SetActive() } =20 } function _IBUI( clr1,clr2,nextState ) { var t=3Dthis SetBorder( GetObj( t.mBorderId ),clr1,clr2 ) obj=3DGetObj( t.mObjId ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-nextState)*t.mWidth-obj= .style.posTop t.mCurState=3DnextState return obj } //----------------------------------------- function TxtBtn( oId,oeId,action,chkState ) //----------------------------------------- { var t=3Dthis t.Perform =3D _TBP t.SetActive =3D _TBSetA t.SetInactive=3D _TBSetI t.SetPressed =3D _TBSetP t.SetDisabled=3D _TBSetD t.SetEnabled =3D _TBSetE t.GetState =3D chkState t.UserAction =3D action t.ChgState =3D _TBUI t.mObjId =3D oId t.m_elementsId=3D oeId t.mIsOn =3D 1 } function _TBSetA() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gHiliteClr,gShadowClr,0,0 ) } function _TBSetI() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) } function _TBSetP() { if( this.mIsOn ) this.ChgState( gShadowClr,gHiliteClr,1,1 ) } function _TBSetD() { =20 this.ChgState( gFaceClr,gFaceClr,0,0 ) this.mIsOn =3D 0 } function _TBSetE() { var t=3Dthis if( !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) else t.ChgState( gShadowClr,gHiliteClr,1,1 ) t.mIsOn =3D 1 } function _TBP() { var t=3Dthis if( t.mIsOn ) {=20 if( t.UserAction !=3D null ) t.UserAction() if( !t.GetState ) return if( t.GetState() ) t.SetPressed() else t.SetActive() } =20 } function _TBUI( clr1,clr2,lOffset,tOffset ) { SetBorder( GetObj( this.mObjId ),clr1,clr2 ) Offset( GetObj( this.m_elementsId ),lOffset,tOffset ) } function Offset( obj, top, left ){ obj.style.top=3Dtop; obj.style.left=3Dle= ft } function SetBorder( obj, upperLeft, lowerRight ) { s=3Dobj.style; s.borderStyle =3D "solid" s.borderWidth =3D 1=20 s.borderLeftColor =3D s.borderTopColor =3D upperLeft s.borderBottomColor=3D s.borderRightColor =3D lowerRight } function GetBtnObj(){ return gBtnArr[window.event.srcElement.id] } function BtnOnOver(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetActive() } function BtnOnDown(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetPressed() } function BtnOnOut(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetInactive() } function BtnOnUp() { b=3DGetBtnObj() if( b !=3D null ) b.Perform() else Upd() } function GetNtsState(){ return parent.gNtsOpen } function GetOtlState(){ return parent.gOtlOpen } function GetOtlTxtState(){ return parent.gOtlTxtExp } function NtsBtnSetFlag( fVal ) { s=3Ddocument.all.item( this.m_flagId ).style s.display=3D"none" if( fVal ) s.display=3D"" else s.display=3D"none" } function _BSetA_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etActive() } function _BSetI_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etInactive() } function _BSetP_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etPressed() } function _BSetA_BorderImg() {=20 b =3D gBtnArr[this.mBorderId]=20 if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _BSetI_BorderImg() {=20 b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } var gHiliteClr=3D"THREEDHIGHLIGHT",gShadowClr=3D"THREEDSHADOW",gFaceClr=3D"= THREEDFACE" var gBtnArr =3D new Array() gBtnArr["nb_otl"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOtlPan= e,GetOtlState ) gBtnArr["nb_otlElem"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOt= lPane,GetOtlState ) gBtnArr["nb_nts"] =3D new ImgBtn( "nb_nts","nb_ntsBorder",10,parent.ToggleN= tsPane ) gBtnArr["nb_nts"].SetActive =3D _BSetA_BorderImg; gBtnArr["nb_nts"].SetInactive =3D _BSetI_BorderImg; gBtnArr["nb_ntsBorder"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.= ToggleNtsPane,GetNtsState ) gBtnArr["nb_ntsElem"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.To= ggleNtsPane,GetNtsState ) gBtnArr["nb_prevBorder"] =3D gBtnArr["nb_prev"]=3D new ImgBtn( "nb_prev","n= b_prevBorder",30,parent.GoToPrevSld ) gBtnArr["nb_nextBorder"] =3D gBtnArr["nb_next"]=3D new ImgBtn( "nb_next","n= b_nextBorder",30,parent.GoToNextSld ) gBtnArr["nb_sldshw"]=3D new ImgBtn( "nb_sldshw","nb_sldshwBorder",18,parent= .FullScreen ) gBtnArr["nb_sldshwBorder"] =3D new TxtBtn( "nb_sldshw","nb_sldshwBorder",pa= rent.FullScreen,null ) gBtnArr["nb_sldshwBorder"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwBorder"].SetInactive =3D _BSetI_Border; gBtnArr["nb_sldshwText"] =3D new TxtBtn( "nb_sldshw","nb_sldshwText",parent= .FullScreen,null ) gBtnArr["nb_sldshwText"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwText"].SetInactive =3D _BSetI_Border; gBtnArr["nb_voice"] =3D gBtnArr["nb_voiceBorder"] =3D new ImgBtn( "nb_voice= ","nb_voiceBorder",18,parent.ToggleVNarration ) gBtnArr["nb_otlTxtBorder"] =3D gBtnArr["nb_otlTxt"]=3D new ImgBtn( "nb_otlT= xt","nb_otlTxtBorder",23,parent.ToggleOtlText ) gBtnArr["nb_ntsBorder"].m_flagId=3D "nb_nts" gBtnArr["nb_ntsBorder"].SetFlag =3D NtsBtnSetFlag gBtnArr["nb_otlTxt"].ChangeIcon=3D GetOtlTxtState /********************************************* Context menu implementation _CM() is the function that's hooked up to the oncontextmenu event. Once we're asked to show the menu, we first build it by creating DIVs on-the-fly. Then we position it=20 within the screen area so it doesn't get clipped. Creating the DIVs using createElement() means we don't have to write out any extra HTML into the slide HTML files. **********************************************/ var sNext=3D"Next",sPrev=3D"Previous",sEnd=3D"End Show",sFont=3D"Arial",sAr= row=3D"Arrow",sFreeform=3D"Freeform",sRect=3D"Rectangle",sOval=3D"Oval" function ShowMenu() { BuildMenu(); var doc=3DPPTSld.document.body,x=3DPPTSld.event.clientX+doc.scrollLeft,y= =3DPPTSld.event.clientY+doc.scrollTop m =3D PPTSld.document.all.item("ctxtmenu") m.style.pixelLeft=3Dx if( (x+m.scrollWidth > doc.clientWidth)&&(x-m.scrollWidth > 0) ) m.style.pixelLeft=3Dx-m.scrollWidth m.style.pixelTop=3Dy if( (y+m.scrollHeight > doc.clientHeight)&&(y-m.scrollHeight > 0) ) m.style.pixelTop=3Dy-m.scrollHeight m.style.display=3D"" } function _CM() { if( !parent.IsFullScrMode() ) return; if(!PPTSld.event.ctrlKey) { ShowMenu() return false } else HideMenu() } function BuildMenu() { if( PPTSld.document.all.item("ctxtmenu") ) return var mObj=3DCreateItem( PPTSld.document.body ) mObj.id=3D"ctxtmenu" mObj.style.visibility=3D"hidden" var s=3DmObj.style s.position=3D"absolute" s.cursor=3D"default" s.width=3D"120px" SetCMBorder(mObj,"menu","black") var iObj=3DCreateItem( mObj ) SetCMBorder( iObj, "threedhighlight","threedshadow" ) iObj.style.padding=3D2 CreateMenuItem( iObj,sNext,M_GoNextSld,M_True ) CreateMenuItem( iObj,sPrev,M_GoPrevSld,M_HasPrevSld ) =09 CreateSeparator( iObj ) CreateMenuItem( iObj,sEnd,M_End,M_True ) mObj.style.visibility=3D"visible" } function Cancel() { window.event.cancelBubble=3Dtrue; window.event.returnVa= lue=3Dfalse } function Highlight() { ChangeClr("activecaption","threedhighlight") } function Deselect() { ChangeClr("threedface","menutext") } function Perform() { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) e.Action() else PPTSld.event.cancelBubble=3Dtrue } function ChangeClr( bg,clr ) { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) { e.style.backgroundColor=3Dbg e.style.color=3Dclr } } function M_HasPrevSld() { return( parent.HasPrevSld() ) } function M_GoNextSld() { if( gIsEndShow ) M_End(); else GoToNextSld() } function M_GoPrevSld() { if( gIsEndShow ) { gIsEndShow=3D0; history.back();= PPTSld.event.cancelBubble=3Dtrue; } else GoToPrevSld() } function M_True() { return true } function M_End() { window.close( self ) } function CreateMenuItem( node,text,action,eval ) { var e=3DCreateItem( node ) e.type=3D"menuitem" e.Action=3Daction e.IsActive=3Deval e.innerHTML=3Dtext if( !e.IsActive() ) e.style.color=3D"threedshadow" e.onclick=3DPerform e.onmouseover=3DHighlight e.onmouseout=3DDeselect s=3De.style; s.fontFamily=3DsFont s.fontSize=3D"9pt" s.paddingLeft=3D2 } function CreateSeparator( node ) { var sObj=3DCreateItem( node ) SetCMBorder(sObj,"menu","menu") var s=3DsObj.style s.borderTopColor=3D"threedshadow" s.borderBottomColor=3D"threedhighlight" s.height=3D1 s.fontSize=3D"0px" } function CreateItem( node ) { var elem=3DPPTSld.document.createElement("DIV") node.insertBefore( elem ) return elem } function SetCMBorder( o,ltClr,rbClr ) { var s=3Do.style s.backgroundColor=3D"menu" s.borderStyle=3D"solid" s.borderWidth=3D1 s.borderColor=3DltClr+" "+rbClr+" "+rbClr+" "+ltClr } ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/fullscreen.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/buttons.gif Content-Transfer-Encoding: base64 Content-Type: image/gif R0lGODlhWAESAPf4AAAAAIAAAACAAICAAAAAgIAAgACAgICAgAQEBISEBASEBISEhAQEhMTExAQE /KTM9Pz8/ERERPz8BAT8/KSkpGRkhMTcxCRkxAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAMDAwP8AAAD/AP//AAAA//8A/wD//////yH5BAEAAPgALAAAAABYARIA QAj/APEJHEiwoMGDCBMqXMiwocOHECNKnEixosWLGCEiQKCRo8YDIEHig2DxAD4LKD1avDDhgUuV GUOGbHBR5QGYFBG4fHAB58EKECJEwCfUYAWPFGAygLCRKQIIUKM6WAohKUGgCikcFWh1INWoYKVS 7SrQ41GbIhGYLAuVQVOoC+IyXUuUAkG1HE3KFDhAwkgJc5/qDZmxsOHDiBMrXsy4sePDGyP7lChT 5MULmDPnlDw5YmW6FTNrfgi0aNGEZPEtbfo2bNTUpYeeRph69dPWrqvCNFuBIGG1A59CYPAVQtwF cw0OxWdTIOiBCQAjaAB17fOFII8voGmRc+eOkilm/z9OvTtnjN4hYk1YoT3H2rnBOphPAB9skgq3 2lcaX/5YnJVt9BloAar12UEIRGCZdQghMABI1Tn32IQUVthYexhmqGGGMBHAgIfEhSiiiATAtOGJ GnYI4ogsEldicAYOGNJGZaml3Y0L3NTZUBz1xlB0PUoUI0jlVWRSVN89xBKSGB1YU1TMoRfVBEle hR9HQs1GEHxQ3RZZbveZthxt/LEmXHyp5XWABSCpaRJwbM13gAACPHVccgJFgF+NEhqUAEkQSCfc ddhVhh5dVTaEAEsTUNlkZUWKN9BNGDE6QU8OrSdbllzpxyVTTrU21Uj3scfhp7nNpyoDaTIEJ3P9 If8J2kbLNYegg9JRBwGhFvbq66+ZUiDssMQWK2yHxiZLrInKNotss8l+B5yBrr5p2UIJvortANoC 6+234IbLla/elRtZjeamh5CC3Sb0YLvixivvYkDFGlZqBNh7r4n6goVvv6/ZlCicN+kL71ALTnpQ dCIZp7CihkLA3UQmoWRBogyxtBPGCTnZncVR1rSTo5nuydC/Eo8kUH+lOoTyyvjoCuZu+PjYIKLD rZybtrM1d10C0QXKEVz48GrQkEeWdFJKlbb0UmEeV0SzyC6RvNB646LWIVjUNeC1zAFb+RDKXksM 9r531bwmpQW9+hQDDsx5pqwDRWBXcFES2hc+gEn/wJGdEEWdE6LoWcoxQweaTNmkhydkKaYMYY2Q p1unbLl/pPKbn3v7EZRvrKvqlja2ONvrtoIw9tn2g32/tQBlhtYkU+MNikZ7QYlPDPuMldpOmuJX nVo5VF3HjI+q89mteX5IDd/fVFClma5kiE4f2XUJhlz09gj2NbTDRifkmu7zXjR++RVJ/lPznuvr QH2iD6S+UewP9Dnon6d2NLwN8n90BB6hC68cFMCHoe+ACASP9c4DowUyEF0OPFcDI0ij/VXPaAKC UfhS95AKGoQ7IBRICI1HwhGaUIQoLGEKT6jCFrLwhSuMoQtlCMMZ2rCGOKShDm+4wxzy8Ic+DGIP B4cIRCKGMCAAOy== ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/frame.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Paroxysmal Nocturnal Hemoglobinuria (PNH) ------=_NextPart_01C70A57.76D1C540 Content-Location: file:///C:/B133CA08/PNH_files/outline.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii"
 No= tes
Slide Show
Outline
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