A United States Army Medical Department,

continuing Education program,

morphology of recurrent disease and 

transplantation 

with James D Mullin's major US Air Force Medical 

Corps,

Wilford Hall,

US Air Force Medical Center,

Lackland Air Force Base.

Just real quick.

I'd like to go back through again.

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

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

consider.

Number one is transmission arts,

the existence of transmission I don't think can really 

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

when they transplant the ISS identical twins,

which there really should be no reason for uh any 

type of his incompatibility.

17 of the 22 patients in an iso study 

had the I 

when they reviewed the his in the history,

it felt that 17 to 22 had courses 

consistent with native arthritis.

All for E M work really wasn't done.

I got 17 which was felt to have native 

uh or native kidney.

11 reoccurred with morphological changes of 

arthritis and all that 11,

either six or seven went on to lose their graft,

all their life because of the to arthritis.

So transplant,

I mean transmission does exist at least in 

the has been well described and the 

autograph becomes much harder problem because here you run into the 

problem,

the changes you see in the autograph immunity,

the rejection process itself.

Plus there's another very important difference between this is 

series and the autograph series.

I mean nobody in this country,

I am in Europe.

Sometimes they will give autographs withhold imm 

suppression and H L A identical grasp in this country.

Everybody with an autograph gets immuno suppression.

And that obviously is gonna have some influence on the 

morphological and clinical expression of the transmission of 

arthritis.

That is group.

Only three of those people were treated prophylactically with uh 

immunosuppression for at least for the clinicians,

maybe make you feel happier.

It seems like at least if you start these people on 

immunosuppression,

right.

As soon as they get the kidney,

you appear to uh at least delay or 

modify the transmission of arthritis from what we can 

tell.

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

everybody else's experience lose their kidney through the 

process of rejection.

Whether or not to have some degree of recurrence of 

arthritis or not,

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

about and rejection,

usually what gets the graft and 

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

alluded to the Pacific auto 

autograph immunity.

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

A anti H L A antibodies.

And if we're talking about in a minute,

it's not uncommon to see deposits and 

graphs who did not have native 

arthritis.

And maybe this is an example of a uh autograph 

immunity with immune complex disease.

Like you see with some other instances and 

also the ischemic change you get in to cloud the 

picture somewhat.

The pacific instance in which transmission arthritis 

is a real problem are focal sclerosing 

opathy.

Again,

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

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

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

inflammatory or not,

it destroys kidneys.

This is a lady.

Doctor mcfall was talking about,

this is uh a patient of ours had about a 

three year history of Nephritic syndrome went into 

slowly progressive renal failure.

We went back and looked at her original kidneys and some 

original biopsies.

And what we saw was classic focus grows and 

the process was focal and segmental.

Here,

you can see the loop looks pretty good,

but you will notice going on here,

there's completely hypo cellar area,

s matrix proliferation,

adhesion to bone capsule.

Here you can see some high 

drop at seven deposits and 

foam cells.

A classic his focus and the 

plus on E M,

she showed the fusion of foot processes which is the other 

component of this disease.

This is just a higher P an area of focal 

sclerosis.

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

This is the P A S stain.

These sub inter deposits are highland 

deposits stand out very nicely.

This is not me matrix.

It does not have a fibular mass matrix and on 

silver stain,

this material does not stain silver positive like Messan matrix.

The deposits on E E M correspond to seven or three 

electron dense deposits.

The exact nature of which nobody should.

This is an E M on a patient with and,

and from looking at this one field,

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

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

do like doctors Fargo uh 

feel that the presence of diffuse fusion of foot 

process is approaching 100% is really found 

only in two disease entity,

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

That's Neal's disease and go 

what the relationship of and is to Neil's 

disease is unknown as a subject unto itself.

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

to be removed at approximately two months.

Although she had normal renal function,

she had such a horrendous nephritic syndrome.

But clinically,

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

Here.

Again,

you can see the reoccurrence,

this peculiar 

sclerosis here with some adhesions to Bowman's capsule.

Here.

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

it comes a little different.

You can get significant fusion of foot process and autograph 

rejection.

But at least in Bush's experience in the porters 

usually doesn't go beyond 70%.

The Nero syndromes associated with chronic 

rejection again,

show diffuse fusion of foot processes,

but they get a massive change in the sub endothelial on 

the basement membrane,

which I talked about with you before.

So this lady is showing diffuse fusion of foot 

processes 100% without sub endothelial 

changes in her basement membrane.

And even though this is in a graph,

I think it's a still pat of focus 

on E M.

And then when you combine it with a light,

my there's really no doubt.

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

occurrence that peculiar focus crossing.

Fortunately,

this time,

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

maintain useful function.

Despite the syndrome,

the other entity in which you can see recurrence of 

is fairly commonly.

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

nine Children with so called me 

has also been called hyper of 

childhood reoccurred with the disease.

And they usually show recurrence of the hyper 

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

The patient of Doctor mcfall talked about priest.

I really don't have any good slides on,

I took some slides,

but unfortunately,

uh they didn't turn out very well.

But I will show you some examples of me my 

in a native kidney,

some people use the term very loosely.

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

you get massive with beginning 

libation,

massive enlargement of the.

As you see,

here are 2 to 3 times normal size and some degree 

of thickening the basement membrane,

which may or may not show splitting.

This is another example of me,

you see the mark lobulation,

increased massage matrix.

And as you can appreciate here,

this one here is the type that's showing the 

splitting of the basement membrane due to massage in 

position.

Here you can see the splitting of the basement 

membrane.

Now,

when this disease reoccurs in the graph,

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

make it uh sufficient to make a diagnosed meno poly 

circumferential mas inter position is very common in 

graphs.

I'm sorry,

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

After you get that change,

the next change you can go into is a 

circumferential masang inter position and chronic graph 

rejection.

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

enlargement of the the prominent 

lobulation as well as the basement membrane changer before you 

can make a diagnosis of current me 

in contrast to the sang and peripheral basement 

membrane change,

you can get in just chronic vascular rejection without 

any underlying immunological problem.

Now,

this is an example of me Riis 

here is the original basement membrane here here would 

be the urinary space.

Here is the what happens in these 

people.

For some reason,

the cell grow out under the 703 

market thicken it and then lay down a new lamb.

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

A very similar morphology can occur in 

graph rejection.

So by alone,

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

Some of these people are memoli instead of showing a 

thickening of splitting the base membrane,

they will show show so called electron dense 

deposits.

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

dense deposit disease.

But doctor B in France,

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

spectrum of variant of memos and 

this particular variant of memoli nephritis.

The electron deposit disease seems to be even 

more likely to re occur almost 100%.

And the French experience than the other form of me,

the thing is this is so rare.

You'll probably never see it.

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

disease.

Kidney in the four or five years,

I've been at Hall the Kidney Bobs.

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

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

same changes that apparently can occur with chronic 

rejection without an underlying immm basis 

immune complex or anti GB M process.

This is a kidney of a five year old 

boy who had well documented dysplastic kidney 

disease.

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

He had nothing to suggest any type of underlying 

immunological problem over the next couple of 

years,

he went into chronic vascular rejection at the time of 

autopsy.

Those previous dark slides showed a tremendous 

some sang thickening and widespread thickening 

memories changed the basement membrane as well as widespread 

split in the basement membrane.

But in contradistinction to me politic arthritis,

those were shrunken retracted,

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

talked about and minopoli the is 

marked and large,

sometimes three and four times the diameter of a 

normal.

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

between the memo type change you can get is a 

chronic rejection phenomena from those 

of the true recurrent memo plus the 

correlation of clinical and I fluorescent data.

But this is this child at the time of death.

You can see he does have typical 

widespread splitting of the basement membrane and he 

also has circumferential mass and positioning 

very similar to what we saw in that well documented 

case of me,

he does not have deposits,

the ones with me commonly will have 

deposits but they can be somewhat focal 

and may,

you may miss them 

another disease entity that Doctor mcfall doesn't 

mention.

And we have not,

well,

we have had some recurring anti GB MS but they really 

haven't expressed themselves moral to the patient.

Went ahead and lost his graph because of rejection.

But in early work of Dixon,

he did have at least one rapidly 

progress.

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

to anti GB M arthritis.

And this is just an example of good pastures.

And the point I wanna make here,

this is not in a graph.

If you ever see this degree of crescent 

formation in a graft,

you can be almost absolutely sure that that 

patients got recurrence of arthritis.

Crescents are just not prominent and graft rejection 

of any type either hyper acute,

acute or chronic.

You may see a few scattered small crescents,

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

or occurring to mars in the ground.

And this is not again,

it's not a graph,

it's just a good,

good pastures.

But the original case of Dixon did reoccur with a 

morphology identical to this 

and this is a case of just how you 

might work up a a problem of the 

current arthritis.

This patient and his graft 

in about six months or one year.

I'm not sure.

Now showed some degree of sang 

proliferation masang thickening as you can see here 

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

rejection.

So how are you gonna try to separate them out?

Well,

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

changes using?

The cha changes in the due to rejection 

always less severe than those in the vessels.

If you look in the vessels look pretty clean and yet 

your is showing this degree of proliferation,

you really got to start thinking about Ken,

does this guy have recurrent glome arthritis 

or at least part of this problem due to recurrent arthritis.

We did E M on this particular case 

here.

This is a basement membrane.

Here you see these electron dense deposits.

This is his,

I mean this is his graph,

you can get varying degrees of deposits and the G 

is a part of rejection to that again,

that makes the process difficult.

But our experience,

we just don't see this type of the type of immune 

complex electron dense deposits very often and she 

have been correlated with arthritis 

if you go back and look at his original kidney.

This is one that I didn't,

I don't have pictures of it.

But until you go back and look at the original kidney,

you see he does have this is kind of a non specific sri 

in this case.

But you know,

you look at his native kidney.

Doctor mcfall tells you he had on his native 

kidney.

And then sometimes if you have ems on his native kidney,

you had deposit some of those in the graph that pretty much seals the 

diagnosis.

Well,

in this case,

we didn't have E M but sometimes you can take the blocks out of 

which we did here.

And we were able to demonstrate that in his native kidney 

on paraffin embedded material,

we were able to demonstrate again,

electron dense deposits that have identical location 

in the basement membrane to the deposits that he's 

manifested in his graph 

here is not quite as good.

This was paraffin embedded material.

I know that's not very good,

but considering it's coming from paraffin,

it's it's uh not bad and especially you can make out the 

electron dens deposits right in trouble.

So in this case,

by doing a little detective work in correlation clinically and Doctor 

mcfall is helping I help him with E M and 

you could pretty well establish this guy did have some 

degree of recurrent arts.

But I would predict that if this guy loses his graft,

he'll most likely lose it because of rejection,

not really because of the recurrent arthritis.

And we just talked about previously this morning,

the changes you see as part of graph rejection that can be 

confused with current fires.

This is a typical change you see in 

rejection.

And we've already talked about this memin change.

You can see as part of chronic graph rejection which should not be 

mistaken for memin arthritis.

I think what I'm trying to point out is right here.

This is another biopsy an E M done on a 

graph and a patient that had documented uh dysplastic 

kidneys had no reason to have immune complex uh 

anti GB M arthritis in his graph on 

E E M.

Although his was negative,

he demonstrated some sub electron dense 

deposits.

This is these type of closes that they 

look different from a classic.

You seen a cut.

I really don't know what their significance is.

I think are very non specific,

but they are seen fairly commonly in graphs.

They were seen in 10 of 45 of the graphs in series in 

which he did E M and they occur where the patient had native 

fire or not.

So I would just warn you on articles that are published and 

show a few deposits like that and try to push that 

off as fires.

I think that may well be debris or it may,

it might actually be a manifestation of a de novo 

uh arthritis related to uh 

things not transplant fires or 

histocompatibility change.

But there's just really no way of knowing at present 

morphology of recurrent disease and 

transplantation with James D 

Mullin's Major US Air Force Medical Corps,

Wilford Hall US Air Force Medical Center,

Lackland Air Force Base 

was produced through the mobile facilities of the television 

division,

Academy of Health Sciences,

United States Army Fort Sam.

Houston,

Texas.