WEBVTT

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*This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.*

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A United States Army Medical Department,

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continuing Education program,

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morphology of recurrent disease and

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transplantation

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with James D Mullin's major US Air Force Medical

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Corps,

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Wilford Hall,

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US Air Force Medical Center,

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Lackland Air Force Base.

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Just real quick.

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I'd like to go back through again.

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What he's talking about when you get some pathological change and more

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likely to change in the of a graph or several things you do have to

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consider.

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Number one is transmission arts,

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the existence of transmission I don't think can really

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be argued if you go back and look at the experience of Peter

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when they transplant the ISS identical twins,

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which there really should be no reason for uh any

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type of his incompatibility.

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17 of the 22 patients in an iso study

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had the I

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when they reviewed the his in the history,

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it felt that 17 to 22 had courses

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consistent with native arthritis.

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All for E M work really wasn't done.

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I got 17 which was felt to have native

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uh or native kidney.

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11 reoccurred with morphological changes of

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arthritis and all that 11,

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either six or seven went on to lose their graft,

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all their life because of the to arthritis.

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So transplant,

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I mean transmission does exist at least in

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the has been well described and the

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autograph becomes much harder problem because here you run into the

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problem,

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the changes you see in the autograph immunity,

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the rejection process itself.

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Plus there's another very important difference between this is

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series and the autograph series.

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I mean nobody in this country,

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I am in Europe.

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Sometimes they will give autographs withhold imm

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suppression and H L A identical grasp in this country.

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Everybody with an autograph gets immuno suppression.

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And that obviously is gonna have some influence on the

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morphological and clinical expression of the transmission of

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arthritis.

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That is group.

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Only three of those people were treated prophylactically with uh

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immunosuppression for at least for the clinicians,

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maybe make you feel happier.

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It seems like at least if you start these people on

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immunosuppression,

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right.

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As soon as they get the kidney,

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you appear to uh at least delay or

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modify the transmission of arthritis from what we can

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tell.

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And most people that lose their kidneys and our experience and I think

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everybody else's experience lose their kidney through the

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process of rejection.

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Whether or not to have some degree of recurrence of

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arthritis or not,

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it seems to be minor except in a few instances in which I'll talk

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about and rejection,

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usually what gets the graft and

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there's other things that can cause morphological changes in the graph

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alluded to the Pacific auto

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autograph immunity.

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There's no reason that you couldn't form uh circulating H L

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A anti H L A antibodies.

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And if we're talking about in a minute,

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it's not uncommon to see deposits and

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graphs who did not have native

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arthritis.

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And maybe this is an example of a uh autograph

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immunity with immune complex disease.

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Like you see with some other instances and

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also the ischemic change you get in to cloud the

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picture somewhat.

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The pacific instance in which transmission arthritis

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is a real problem are focal sclerosing

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opathy.

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Again,

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I use that you really shouldn't even call it a arthritis.

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But we're going to put it in there anyway,

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because it's really not an inflammatory process but whether it's

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inflammatory or not,

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it destroys kidneys.

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This is a lady.

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Doctor mcfall was talking about,

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this is uh a patient of ours had about a

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three year history of Nephritic syndrome went into

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slowly progressive renal failure.

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We went back and looked at her original kidneys and some

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original biopsies.

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And what we saw was classic focus grows and

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the process was focal and segmental.

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Here,

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you can see the loop looks pretty good,

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but you will notice going on here,

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there's completely hypo cellar area,

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s matrix proliferation,

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adhesion to bone capsule.

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Here you can see some high

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drop at seven deposits and

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foam cells.

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A classic his focus and the

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plus on E M,

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she showed the fusion of foot processes which is the other

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component of this disease.

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This is just a higher P an area of focal

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sclerosis.

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You can see this part of the loop looks pretty good.

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This is the P A S stain.

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These sub inter deposits are highland

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deposits stand out very nicely.

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This is not me matrix.

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It does not have a fibular mass matrix and on

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silver stain,

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this material does not stain silver positive like Messan matrix.

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The deposits on E E M correspond to seven or three

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electron dense deposits.

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The exact nature of which nobody should.

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This is an E M on a patient with and,

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and from looking at this one field,

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it's identical to what you see in Neil's disease.

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An opinion of many people who have a lot more experience with E M than I

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do like doctors Fargo uh

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feel that the presence of diffuse fusion of foot

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process is approaching 100% is really found

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only in two disease entity,

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no matter whether there's neurotic syndrome present or not.

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That's Neal's disease and go

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what the relationship of and is to Neil's

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disease is unknown as a subject unto itself.

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This is an example of this lady's graph when it had

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to be removed at approximately two months.

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Although she had normal renal function,

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she had such a horrendous nephritic syndrome.

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But clinically,

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the graph had to be removed for the benefit of the patient.

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Here.

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Again,

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you can see the reoccurrence,

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this peculiar

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sclerosis here with some adhesions to Bowman's capsule.

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Here.

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When you're talking about foot process fusion in the graph,

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it comes a little different.

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You can get significant fusion of foot process and autograph

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rejection.

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But at least in Bush's experience in the porters

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usually doesn't go beyond 70%.

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The Nero syndromes associated with chronic

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rejection again,

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show diffuse fusion of foot processes,

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but they get a massive change in the sub endothelial on

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the basement membrane,

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which I talked about with you before.

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So this lady is showing diffuse fusion of foot

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processes 100% without sub endothelial

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changes in her basement membrane.

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And even though this is in a graph,

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I think it's a still pat of focus

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on E M.

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And then when you combine it with a light,

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my there's really no doubt.

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And this is just her most recent graph again showing a re

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occurrence that peculiar focus crossing.

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Fortunately,

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this time,

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she's not having near as much and she's able to uh

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maintain useful function.

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Despite the syndrome,

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the other entity in which you can see recurrence of

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is fairly commonly.

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I think the only real big series out of Minnesota five of

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nine Children with so called me

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has also been called hyper of

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childhood reoccurred with the disease.

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And they usually show recurrence of the hyper

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aia too if they recur with the disease in the ground.

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The patient of Doctor mcfall talked about priest.

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I really don't have any good slides on,

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I took some slides,

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but unfortunately,

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uh they didn't turn out very well.

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But I will show you some examples of me my

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in a native kidney,

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some people use the term very loosely.

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We use a very strict sense and it is a disease in which

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you get massive with beginning

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libation,

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massive enlargement of the.

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As you see,

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here are 2 to 3 times normal size and some degree

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of thickening the basement membrane,

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which may or may not show splitting.

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This is another example of me,

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you see the mark lobulation,

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increased massage matrix.

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And as you can appreciate here,

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this one here is the type that's showing the

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splitting of the basement membrane due to massage in

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position.

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Here you can see the splitting of the basement

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membrane.

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Now,

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when this disease reoccurs in the graph,

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just the presence of splitting the basement membrane is not significant to

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make it uh sufficient to make a diagnosed meno poly

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circumferential mas inter position is very common in

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graphs.

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I'm sorry,

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I didn't get through to the ems this morning on the graph changes.

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After you get that change,

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the next change you can go into is a

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circumferential masang inter position and chronic graph

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rejection.

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So you've got to see the overall changes it should be marketed,

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enlargement of the the prominent

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lobulation as well as the basement membrane changer before you

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can make a diagnosis of current me

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in contrast to the sang and peripheral basement

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membrane change,

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you can get in just chronic vascular rejection without

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any underlying immunological problem.

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Now,

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this is an example of me Riis

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here is the original basement membrane here here would

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be the urinary space.

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Here is the what happens in these

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people.

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For some reason,

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the cell grow out under the 703

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market thicken it and then lay down a new lamb.

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It's usually a little thinner than the original lama dens.

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A very similar morphology can occur in

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graph rejection.

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So by alone,

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you really can't make the diagnosis of the current meris.

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Some of these people are memoli instead of showing a

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thickening of splitting the base membrane,

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they will show show so called electron dense

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deposits.

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And one time this was separated out of the so called electron

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dense deposit disease.

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But doctor B in France,

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I think most people now feel this is nothing more than just in the

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spectrum of variant of memos and

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this particular variant of memoli nephritis.

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The electron deposit disease seems to be even

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more likely to re occur almost 100%.

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And the French experience than the other form of me,

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the thing is this is so rare.

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You'll probably never see it.

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We've only seen one case I know of in any

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disease.

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Kidney in the four or five years,

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I've been at Hall the Kidney Bobs.

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I told you that the problem that comes up with trying to diagnose with chronic

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arthritis in the graph is a confusion that you run into with the

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same changes that apparently can occur with chronic

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rejection without an underlying immm basis

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immune complex or anti GB M process.

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This is a kidney of a five year old

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boy who had well documented dysplastic kidney

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disease.

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He had his original native kidneys removed at a very young age.

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He had nothing to suggest any type of underlying

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immunological problem over the next couple of

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years,

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he went into chronic vascular rejection at the time of

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autopsy.

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Those previous dark slides showed a tremendous

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some sang thickening and widespread thickening

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memories changed the basement membrane as well as widespread

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split in the basement membrane.

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But in contradistinction to me politic arthritis,

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those were shrunken retracted,

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they looked a trophic as well as showing these other changes I

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talked about and minopoli the is

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marked and large,

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sometimes three and four times the diameter of a

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normal.

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And I think that's part of the best way to differentiate

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between the memo type change you can get is a

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chronic rejection phenomena from those

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of the true recurrent memo plus the

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correlation of clinical and I fluorescent data.

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But this is this child at the time of death.

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You can see he does have typical

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widespread splitting of the basement membrane and he

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also has circumferential mass and positioning

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very similar to what we saw in that well documented

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case of me,

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he does not have deposits,

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the ones with me commonly will have

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deposits but they can be somewhat focal

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and may,

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you may miss them

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another disease entity that Doctor mcfall doesn't

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mention.

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And we have not,

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well,

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we have had some recurring anti GB MS but they really

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haven't expressed themselves moral to the patient.

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Went ahead and lost his graph because of rejection.

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But in early work of Dixon,

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he did have at least one rapidly

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progress.

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Arthritis re occur within the first couple of days of transplantation due

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to anti GB M arthritis.

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And this is just an example of good pastures.

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And the point I wanna make here,

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this is not in a graph.

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If you ever see this degree of crescent

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formation in a graft,

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you can be almost absolutely sure that that

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patients got recurrence of arthritis.

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Crescents are just not prominent and graft rejection

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of any type either hyper acute,

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acute or chronic.

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You may see a few scattered small crescents,

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but crescents of this size are just almost half of the mo

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or occurring to mars in the ground.

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And this is not again,

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it's not a graph,

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it's just a good,

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good pastures.

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But the original case of Dixon did reoccur with a

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morphology identical to this

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and this is a case of just how you

12:41.520 --> 12:43.929
might work up a a problem of the

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current arthritis.

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This patient and his graft

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in about six months or one year.

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I'm not sure.

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Now showed some degree of sang

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proliferation masang thickening as you can see here

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and all of these changes can occur as a part of a graph

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rejection.

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So how are you gonna try to separate them out?

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Well,

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one thing is to look around and see what are the vascular

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changes using?

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The cha changes in the due to rejection

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always less severe than those in the vessels.

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If you look in the vessels look pretty clean and yet

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your is showing this degree of proliferation,

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you really got to start thinking about Ken,

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does this guy have recurrent glome arthritis

13:21.934 --> 13:24.684
or at least part of this problem due to recurrent arthritis.

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We did E M on this particular case

13:30.710 --> 13:30.750
here.

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This is a basement membrane.

13:32.289 --> 13:34.900
Here you see these electron dense deposits.

13:34.909 --> 13:35.440
This is his,

13:35.559 --> 13:37.080
I mean this is his graph,

13:37.429 --> 13:40.179
you can get varying degrees of deposits and the G

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is a part of rejection to that again,

13:42.119 --> 13:44.080
that makes the process difficult.

13:44.090 --> 13:45.250
But our experience,

13:45.770 --> 13:48.609
we just don't see this type of the type of immune

13:48.619 --> 13:51.619
complex electron dense deposits very often and she

13:51.719 --> 13:53.530
have been correlated with arthritis

13:55.260 --> 13:57.700
if you go back and look at his original kidney.

13:58.400 --> 13:59.510
This is one that I didn't,

13:59.520 --> 14:00.469
I don't have pictures of it.

14:00.479 --> 14:02.380
But until you go back and look at the original kidney,

14:02.390 --> 14:05.090
you see he does have this is kind of a non specific sri

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in this case.

14:07.719 --> 14:08.289
But you know,

14:08.299 --> 14:09.729
you look at his native kidney.

14:09.919 --> 14:12.729
Doctor mcfall tells you he had on his native

14:12.739 --> 14:13.299
kidney.

14:13.570 --> 14:16.320
And then sometimes if you have ems on his native kidney,

14:16.330 --> 14:19.239
you had deposit some of those in the graph that pretty much seals the

14:19.250 --> 14:20.119
diagnosis.

14:20.559 --> 14:20.700
Well,

14:20.710 --> 14:21.260
in this case,

14:21.270 --> 14:23.770
we didn't have E M but sometimes you can take the blocks out of

14:24.030 --> 14:25.049
which we did here.

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And we were able to demonstrate that in his native kidney

14:29.070 --> 14:30.549
on paraffin embedded material,

14:30.559 --> 14:31.760
we were able to demonstrate again,

14:31.770 --> 14:34.760
electron dense deposits that have identical location

14:34.770 --> 14:37.099
in the basement membrane to the deposits that he's

14:37.109 --> 14:38.500
manifested in his graph

14:40.169 --> 14:41.419
here is not quite as good.

14:41.429 --> 14:42.929
This was paraffin embedded material.

14:42.940 --> 14:43.940
I know that's not very good,

14:43.950 --> 14:45.349
but considering it's coming from paraffin,

14:45.580 --> 14:48.539
it's it's uh not bad and especially you can make out the

14:48.549 --> 14:50.419
electron dens deposits right in trouble.

14:50.429 --> 14:51.270
So in this case,

14:51.280 --> 14:54.010
by doing a little detective work in correlation clinically and Doctor

14:54.020 --> 14:56.400
mcfall is helping I help him with E M and

14:56.969 --> 14:59.340
you could pretty well establish this guy did have some

14:59.349 --> 15:01.599
degree of recurrent arts.

15:01.840 --> 15:04.299
But I would predict that if this guy loses his graft,

15:04.309 --> 15:06.340
he'll most likely lose it because of rejection,

15:06.349 --> 15:08.369
not really because of the recurrent arthritis.

15:11.599 --> 15:13.969
And we just talked about previously this morning,

15:13.979 --> 15:16.799
the changes you see as part of graph rejection that can be

15:16.809 --> 15:18.409
confused with current fires.

15:18.539 --> 15:21.440
This is a typical change you see in

15:21.450 --> 15:22.090
rejection.

15:24.119 --> 15:26.200
And we've already talked about this memin change.

15:26.210 --> 15:28.729
You can see as part of chronic graph rejection which should not be

15:28.739 --> 15:31.020
mistaken for memin arthritis.

15:36.280 --> 15:38.559
I think what I'm trying to point out is right here.

15:38.809 --> 15:41.400
This is another biopsy an E M done on a

15:41.409 --> 15:44.169
graph and a patient that had documented uh dysplastic

15:44.179 --> 15:46.729
kidneys had no reason to have immune complex uh

15:46.739 --> 15:49.690
anti GB M arthritis in his graph on

15:49.700 --> 15:50.099
E E M.

15:50.109 --> 15:52.000
Although his was negative,

15:52.010 --> 15:54.809
he demonstrated some sub electron dense

15:54.820 --> 15:55.580
deposits.

15:55.830 --> 15:58.552
This is these type of closes that they

15:58.562 --> 15:59.973
look different from a classic.

16:00.143 --> 16:00.833
You seen a cut.

16:01.963 --> 16:04.263
I really don't know what their significance is.

16:04.273 --> 16:05.872
I think are very non specific,

16:05.882 --> 16:08.843
but they are seen fairly commonly in graphs.

16:08.853 --> 16:11.713
They were seen in 10 of 45 of the graphs in series in

16:11.723 --> 16:14.723
which he did E M and they occur where the patient had native

16:15.122 --> 16:15.963
fire or not.

16:16.033 --> 16:18.976
So I would just warn you on articles that are published and

16:18.986 --> 16:21.885
show a few deposits like that and try to push that

16:21.895 --> 16:23.486
off as fires.

16:23.796 --> 16:26.656
I think that may well be debris or it may,

16:26.666 --> 16:29.625
it might actually be a manifestation of a de novo

16:30.216 --> 16:32.716
uh arthritis related to uh

16:32.926 --> 16:35.835
things not transplant fires or

16:35.846 --> 16:37.635
histocompatibility change.

16:37.645 --> 16:39.476
But there's just really no way of knowing at present

16:40.520 --> 16:42.940
morphology of recurrent disease and

16:42.950 --> 16:45.619
transplantation with James D

16:45.630 --> 16:48.169
Mullin's Major US Air Force Medical Corps,

16:48.179 --> 16:50.950
Wilford Hall US Air Force Medical Center,

16:50.979 --> 16:52.469
Lackland Air Force Base

16:54.440 --> 16:57.190
was produced through the mobile facilities of the television

16:57.200 --> 16:57.849
division,

16:57.890 --> 16:59.299
Academy of Health Sciences,

16:59.309 --> 17:01.309
United States Army Fort Sam.

17:01.320 --> 17:01.820
Houston,

17:01.830 --> 17:02.489
Texas.
