June 1996 Papers of the Month - Highlights from the
Annual Meeting of the Society for Vascular Surgery and
the North American Chapter of the International Society
for Cardiovascular Surgery, Chicago, June 9-12, 1996.

1. [Poster #3] May J, White GH, Yu W, Waugh RC, Stephen
MS, Harris JP.  Concurrent comparison of endoluminal
repair vs no treatment for small AAA's.  (from the
Harrisburg Polyclinic Medical Center, PA).

Abstract abridged from authors:

Purpose: A concurrent comparison of endoluminal repair
(ER) vs no treatment (NT) for AAA 5 cm or less, over a 3
1/2 year period.

Methods: Decision for ER or NT was made by patient after
CAT scan for appropriateness and consultation.  The
groups turned out to be very similar for co-morbidities,
risk factors, age, sex, and size of AAA.  35 had ER and
48 had NT.

Results: There was one procedure related death in the ER
group, and there was one death from rupture in the NT
group. However, there was a high rate of failure of ER
and conversion to open repair (17%), and an 11% rate of
vascular complication after ER.

Conclusion: A randomized trial of ER vs NT will become
justified in AAA < 5 cm when the incidence of
complications are reduced by further improvements in ER
technology.


Comment by mdt: In other words, ER cannot be recommended
in June 1996 for small AAA's.


2. [Poster #4] Harris EJ, Dalman RL, Moon WK.  Aortic
aneurysmorrhaphy in high risk patients: establishing
concurrent results for comparison with endoluminal
therapies.  (Stanford Univ)

Purpose: As a prelude to direct comparison of endoluminal
repair (ER) vs conventional (OPEN) repair, the authors
reviewed a recent period of results for OPEN repair.

Methods: Results of 73 consecutive OPEN repairs from 8/91
to 1/96 were analyzed.  All patients with AAA's  =/> 5cm
were offerred repair, with no patients refused operation
due to excessive operative risk.  

Results:  There were no peri-operative deaths.  Survival
was 97% at 4 years by life-table, with a mean follow-up
of 13 months.  

Conclusions:  Elective OPEN repair can be safely
performed in high risk patients in their seventh, eight
and ninth decades of life...  Direct comparison of evolving ER
techniques with OPENmethods should utilize concurrent data in
preference to historic control data.


Comment by mdt: *AMEN*


3. [Poster #41]  Paik DC, Ramey WG, Capella JF, Yin X,
Tilson MD.  Neovascularization in the AAA - eNOS, NO, and
elastolysis.  (Columbia Univ, NYC).

Purposes: 1) To quantitatively evaluate the degree of
neovascularization in the non-specific AAA; 2) To study
the distribution of endothelial NO synthetase (e-NOS) in
AAA tissue; 3) To measure tissue content of nitrite in
AAA; and 4) To determine whether nitrite ion is
elastolytic in vitro.

Methods: Bell's method in 12 AAA and 6 normal aortas. 
Immunohistochemistry for e-NOS.  Elastolysis by nitrite
evaluated by incubation of normal human aorta in
solutions with concentrations in the range detected in
AAA tissue.  Standard morphometric methods were used to
quantitate neovascularization.

Results:  Adventitial angiogenesis was increased 15x in AAA.
Nitrite content increased 7x.  Disruption and uncoiling of elastin
fibers, in frozen sections exposed to concentrations similar to
those measured in AAA aorta, were observed.

Conclusion: Nitrite ion can initiate destruction in vitro
of intact lamellar human aortic elastin.  


Comment by mdt:  David Paik has certainly done some very
interesting experiments in my lab (and he is also a great
saxophone player).  His mother and father are biochemists
at Jefferson, who discovered the physiological inhibitor
of NO, methyl-arginine.  So, when David joined me for a
year, we decided to look at a possible role of NO in AAA
pathogenesis.  Even though we found a conspicuous
increase in e-NOS in the neovascularizing endothelial
cells, David has the notion that exogenous NO in tobacco
smoke may be the reason that smoking is such a
significant risk factor in AAA.  Accordingly, he is
trying to switch me to British brands of cigarettes that
have a lower content of NO.  This story will continue, as
he is still doing experiments (even though back on full-
time clinical duty) to study the mechanisms of attack of
NO on matrix proteins.  Stay tuned.

4.  [Poster # 48].  Shireman PK, McCarthy WJ, Pearce WH,
Shively VP, Cipollone M, Yao JST.  Elevations of t-PA and
differential expression of u-PA in diseased aorta.
(Northwestern Univ Medical School, Chicago).

comment by mdt:  Sorry, but I have run out of gas in
producing the whole abridged abstract.  The bottom line
is that u-PA (which is implicated as a key enzyme in
tissue remodeling, as opposed to t-PA which seems to have
the central role in thrombolysis) is elevated
substantially in supernatants of AAA tissue explants vs
supernatants of explants of atherosclerotic aorta.  One
of my former students, Jessie Jean-Claude, reported high
levels of plasmin in AAA specimens.  Thus, this finding,
along with the results of another former student, Jeff
Reilly (now at Wash U, St Louis) may shed light on how
plasminogen gets activated in the cascade of events
leading to AAA.

5. [Forum #9]  Rasmussen TE, Hallet JW Jr, Mathieu-
Metzger RL, Richardson DM, Goronzy JJ, Weynand CM. 
Genetic risk factors in inflammatory AAA's (I-AAA's):
Polymorphic residue 70 in the HLA-DRB1 gene as a key
genetic element.  (Mayo Clinic, Rochester, Minnesota)

Highly abridged abstract:

22 patients with classic I-AAA were genotyped and
compared to ethnically matched healthy controls. 
Distribution of HLA-DRB1 alleles was nonrandom: B1*04 and
B1*15 were frequently found in patients with I-AAA.  The
susceptibility alleles expressed a positively charged Gln
at position 70.  

comment by mdt:  Disclaimer! I haven't had time to be
absolutely sure of this, but I think that the alleles
that we implicated in non-specific AAA in our NY Academy
of Science paper in March (reviewed I think in my March
Papers of the Month) also had a Gln at position 70.  Jeb
Hallett, with his expertise and clinical volume, and Cornelia
Weynand, with her expertise in the autoimmunity of Giant Cell
Arteritis, are happily in the position of making landmark
contributions to the field of autoimmunity in AAA.  

6. [Forum #10].  Hirose H, Ozsvath KJ, Xia S, Tilson MD.  
Molecular cloning and expression of the cDNA for a putative
AAA-antigenic protein (AAAP).  Columbia Univ in the city of 
New York.

PURPOSE:  We have purified and partially sequenced a
protein from the adventitia of the human aorta (Aortic
Aneurysm-Antigenic Protein 40 kDa, AAAP-40) that is
homologous to bovine aortic microfibril-associated
glycoprotein (MAGP-36).  It is immunoreactive with
immunoglobulins (IgG) purified from both serum and aortic
wall of patients with abdominal aortic aneurysms (AAA). 
We have recently reported that it has vitronectin- and
fibrinogen-like domains, along with a putative
calcium-binding domain.  The present experiments were
carried out to clone the cDNA encoding this protein,
express it as a recombinant (rAAAP), and assign the gene
product as a human MAGP.

METHODS:  Human AAA wall and serum IgGs were used to
localize the autoantigen immunohistochemically, and the Gomori
aldehyde fuchsin-peracetic acid reaction was used to
evaluate co-distribution with the elastin-associated
microfibrils.  A glycan differentiation kit was used to
determine that AAAP-40 is a glycoprotein.  mRNA from a
specimen of human aortic adventitia was reverse
transcribed for insertion into the phagemid Uni Zap XR
(Stratagene TM).  A strain of E. Coli, engineered for
expression (XL1-Blue MFR^[(IU, Stratagene TM), was
transfected, and rabbit anti-human vitronectin antibody was used to
identify positive clones.

RESULTS:  Co-distribution of human AAA IgG
immunoreactivity with the elastin-associated microfibrils
was confirmed by the Gomori reaction, and selective
glycan staining confirmed that AAAP-40 was a
glycoprotein.  rAAAP was expressed by selected clones of
transfected E. Coli.  The hypothetical protein of rAAAP
(clone 4) shares sequence motifs with AAAP-40, but it is
not identical.

CONCLUSIONS:  There may be a novel family of human aortic
autoantigenic proteins implicated in AAA disease.