International Cutaaneous Borreliosis and Molecular ...

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Textbooks , clinical experience

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Three Tick bite sitesEach withoutErythema or painor Itching at the sites

PatientRemovedIxodesScalularisNymphformFromThis tickbite site

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Tick HypostomeIn Human SkinBlue box

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ClassicalSpiralFormsOfBorreliaBurgdorferi [ L ]AndMultipleSmaller“blebs”Or Liposomes {Circles}OfBorreliaBurgdorferiOn anElectronMicroscopeGrid

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Specimen submitted by::Alan B. MacDonald,MD Year 1988Electron Microscopy by:S. F. Hayes, Electron Microscopist,Rocky Mountain Laboratory, Hamilton,MT Note: No DNA

wasDetectedwithinThese Blebsin 1988

In Year 1989::Dr. Claude Garon PhDet al, detected BorreliaDNA molecules inBlebs of B.burgdorferi

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Possible“Transfection”by LiposomesOf BorreliaBurgdorferiScenario--------As aConsequenceOf PenetrationOf the NucleusOf the humanCell byLiposomes“Blebs”OfBorreliaBurgdorferi

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Skin of Trunk

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ClassicalSite andClassicalGrossappearanceSoft parts ofLOBE of EAR

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Comment:(ABM)This case couldBe easilyMisdiagnosed as“relapsingPolychondritis”Because theSoft parts of theLobe of the EarAre Spared.Incredible case!!Unusual for EarInvolvementIn BL!!!

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MultifocalBorreliaLymphocytoma

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Nose

Scalp

Lip

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Classical grossFindings forBorreliaLymphocytoma

“Special site Skin”These sites includeEarlobeAreolaEyelidGenitalPeriumbilical

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Could this beconfusedWith a smallErythemaMigrans???Size 2.5 cmx1.1 cm

What would yourCDC ConsultantDiagnose?

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Monotypic:: Sharp Borders,rubbery, Stable

Oligotropic :: Gradual Increasein Size

Spreads along Lymphatics

Miliary form:: MULTILPLE PinPoint lesions LYMPHATICSpread

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6 MonthsDurationEar lobe

CartilageNotInvolvedSkin ofHelixRegionQuiescent

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Skin of:

ElbowHandArmLegPlantar skin

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Plantar SkinWith ProminentDiseaseNOTE:Very few diseasesInflict INJURYOn thePalmar SkinOf Plantar Skin______________Can you name anotherDisease whichInvolvesPalmar/Plantar??

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Paper thinEpidermis[Epidermalatrophy]Is ahallmarkOf ACA

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Mainly FibroticStageWith scatteredPERSISTENTInflammatoryFocithroughoutThe lesion

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ACA DenseInflammatoryStageLittle to NoFibrosis in thisStage

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Revolutionized the Microscopist’s ability to find borrelia in the Skin

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Focus Floating Microscopy ::Demonstrates Red staining Borrelia – single and in Groups

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ParaproteinemiaN= 5 cases

PlasmacytomaN= 2 cases

World Total NumberOf NXG cases

N=80

FACE >>Trunk>extremitiesAlso in:

Myocardium, Liver, Lungs

Paraproteins :: specificityBIND to LIPOPORTEINs

PCR [ with B31 PCR primers:: Always negative in NXGNO PCR ever done withPrimers for BB sl Group ofBorreliae

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Southern ErythemaMigransCollectionEdwin Masters MDCape GirardeauMissouri

Can You TellMissouri typeErythema Migrans

From

Erythema MigransNew York type?????

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Southern Erythema MigransFrom Dr Edwin Masters’ patients residing inCape Girardeau, Missouri

Can you tellErythema MigransMissouri Type

From

Erythema migransNew York Type??

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CDC Map : National LymeDisease Cases

RED> Yellow>Green

BLUE = VIRTUALLY NOSIGNIFICANT LYME

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A true Case – of LYME Disease in a Resident of aSouthern State in the USAA Reportable Case - -To your State Department of HealthA Statistical point on the USA Map –CDCA disease which Merits – TREATMENT WITHANTIBIOTICS

Not a True Case of Lyme diseaseSouthern State in the USA AND

the Medical Justification to Treat with Antibiotics

Northern State in the USAAmblyomma Americanum [Lone Star] Tick vectorNot a Reportable Case—Not a Statistical point on the USA MAP –CDCA disease which may encounter fiery DEBATE about

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In Vitro biofilm formation by Bb Proven by Dr Eva Sapi et al, inPLOS ONE article epublished October 24, 2012

Tick Midgut :: Ixodes Scapularis, “a Carpet of Spirochetes”

Human Skin :: FFM Positive cases from Dr. Klaus Eisendle and Dr. Bernhard Zelger

Mouse Skin:: Dr.Linda Bockenstedt:: Yale :: Experimental Lyme arthritis model in Mice

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Video Lectures on Biofilm Science by the late Dr. WilliamCosterton, are gratefully received.Conversations with Mr. Richard Longman, are gratefully Received

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A “carpet” of Spiral formAnd interspersedCystic [round body]Forms in acommunity..{sessile}..Attached to tickMidgut epithelial cells

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Amorphous “Globs” of BorreliaIn Deep Mouse DermisIn Chronic ExperimentallyinducedLyme Arthritis

Are these so called “Globs”Actually biofilm Colonies inThe Deep dermis Near theArthritic Mouse Joint??A Community of Specialized[NonSpiral]Borrelia with interspersedRound Body forms in themouse Dermis

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Specilaized Non-SpiralBorrelia , includingRound body forms,Granular forms,In the dermisForming many Colony-Communities in theMouse Dermis—Highly resemblingbiofilm Communities,Because of their highDensity, and lack ofSpiral Borrelia forms

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Spiral Borrelia forms around the Edges of a biofilmCommnity. The specialized borrelia forms [granularforms] dominate the central regions of the Biofilm.Planktonic forms=Spiral :: Specialized formsareINSIDE the Community

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So called “Amorphous Glob”of borrelia burgdorferi

Pure culture of ATCC 35210 [B31 strain] ofBorrelia burgdorferi :: In vitro Biofilm

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In VIVO borrelia biofilmsNot Yet Accepted in a Peer reviewed Journal –YetBut the Image evidence from microscopyIn various articles already publishedDescribing Biofilm-like-communities in Tick, Mouse,HumanIs Very VERY CloseTo the Biofilm Profiles – Now Proven –in PLOS ONE (Sapi,E, etal , Oct24 2102 IN VITRO models

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Number of legitimate kinds of Borrelia Skin DiseasesNumber of Strains of Borrelia burgdorferi SS and SL species infectivefor ManNumber of Tick strains – as COMPETENT to TRANSMITNumber of Continents with Borreliosis as a Public Health problemNumber of Molecular dimensions to borreliosis in mammalian hostsNumber of ”invisible” manifestations [Blebs] [Liposomes of borrelia]Number of Extracutaneous legitimate manifestations of BorreliosisNumber of diverse forms that the borrelia spirochete can take andremain viableNumber of biofilm models {In Vitro, In TickO, In Mouse0, In humanO}Liposomes of borrelia as a model for Transfection of Borrelia DNA toHuman cells

and the LIPOSOME model for activation of the Cellular immuneresponse

with “AUTO IMMUNE” diseasesACA dense Fibrosis/dense inflammation to explain now idiopathic

fatal Fibrosing Diseases ( Retroperitoneal Fibrosis, Mediastinalfibrosis}The “Expanding Clinical Spectrum of Duray” –Lead, Follow, or Get outof the Way!!

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Sir Dr. William Costerton PhD ,Dr. Paul Harrison Duray, MD

The Commentaries and the Opinions [which sometimes go beyond the territoryOf Current Peer Reviewed published Manuscripts]DO NOT NECESSARILY REFLECT THE BELIEFS OF THE ABOVE CAPTIONEDEXPERTs. All Controversial Issues contained within this work are the SOLERESPONSIBILITY of Alan B. MacDonald, MD, FCAP,FASCP Date October 29,2012And are protected by Copyright, All rights Reserved

Dr. Willy Burgdorfer , PhD , MD (hon.), Dr. Alan G. Barbour , MD, Dr. Tom G. SchwanPhD. , Dr. Dan Corwin PhD, Mr. S. F. Hayes , Dr. Scott Samuels PhD, Dr. Justin Radolf,MD., Dr. Linda Bockenstedt MD,., Dr. Bernard W. Berger MD, Dr. Klaus Eisendle MD,PhD , Dr. Med. S. A. Buchner, MD[Basil], Dr. Med. Klaus Weber MD , Dr. Med. EvaAsbrink , Dr. Med. Anders Hovmark, MD, Dr. Med. Elisabeth Aberer, MD, Dr. Med.Dieter Haussler, MD, Dr. Med. M. Leverkus, MD, Dr. Med Th. Hardmeier, MD , Dr.Oystein Brorson, MD, Dr. S.H. Brorson, MD ,Dr. Peter Krause, MD. Dr. Bernhard Zelger ,MD , MSC.. .Dr. Edwin Masters MD, Dr. Steven Norris PhD, Dr. Tao Lin MD PhD, Dr.Maria Esteve-Galant ,PhD , Dr. Guadalupe Gordillo-Perez MD, PhD, Dr. YoshinariNatalino ,MD, Dr. Peter Mayle MD, Dr. Eva Sapi PhD, Dr. Kordula Elbl PhD, Dr. ArminSchwartzbach MD, Dr. Marcia Herman Giddens PhD, Dr. Kerry Clark, PhD ,Dr. Steven Phillips,MD, Mrs. Elizabeth Schmitz,Mr. Richard Longman , Ms. Elena CookSaul Steinberg and New York Magazine,

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