While these three papers (from the Univ of Vermont, Loyola Univ,
and Northwestern Univ) were not all published in the immediately
preceding month, I have selected them for comment because I think
they are three of the more important scientific articles on
aneurysms published in 1994.

1. Abdominal aortic aneurysm expansion rate:  Effect of size and
beta-adrenergic blockade.  Gadowski GR, Pilcher DB, Ricci MA.  J
Vasc Surg  1994; 19: 727-31.

Purpose:  To investigate whether AAA growth rate is influenced by
beta-adrenergic antagonists.

Methods:  121 patients with AAA were monitored by serial ultrasound
exams.  83 received no beta blockers, and 38 did...

Results:  "In patients not undergoing beta-blocker therapy, large
AAA expand at a significantly greater rate than smaller AAA."

Comment (by mdt):  Simpson, Boucek and colleagues (see references
in paper) were the first to report (in the late 70's and early
80's) that propranolol reduced the growth rate of aneurysms in
turkeys.  Subsequently, Brophy ( working in my lab, JSR 1988;
44:687-91 & JSR 1989; 46: 330-2) confirmed this phenomenon in the
aneurysm-prone Blotchy mouse.  Leach SD (Arch Surg 1988; 123:606-9)
made the first observations suggesting that this effect may also
occur in man; although the numbers of patients and controls were
small.  The present study by Ricci and colleagues supports the
underlying hypothesis and provides a rationale for a large-scale
prospective multi-institutional randomized trial to determine
whether patients with small AAA's should be treated with a beta-
blocking agent.


2. Interleukin-1 beta induces differential gene expression in
aortic smooth muscle cells.  Keen RR, Nolan KD, Cipollone M, Scott
E, Shively VP, Yao JST, Pearce WH.  J Vasc Surg 1994; 20: 774-86.

A very detailed and extraordinarily interesting paper.  The
following short abstract will not do it justice.

Purpose:  To examine the gene expression of collagen, elastin,
collagenase, and TIMP by AAA & normal SMC's  after treatment with
IL-1b and TNF-a.

Methods: SMC's from 6 AAA's and 3 normal aortas were cultured and
exposed to the experimental treatment protocols.

Results:  There is so much data here that I cannot encapsulate it
briefly.... Proceed to author's conclusions.

Conclusion:  "These findings suggest that IL-1b, through its effect
on smooth muscle cell collagenase and collagen gene expression,
mediates the increased matrix turnover in aneurysms.  Macrophages
may induce changes in aortic SMC gene expression in a paracrine
manner that could lead to aneurysm formation."


Comment (by mdt):  Our research group also has several papers this
year that are consistent with the above general conclusion.  Newman
et al (Circulation 1994:90 II: 224-227) found that IL-1 beta was
increased in AAA vs control by a factor of approximately 4x; and
that TNF-a was increased by almost two orders of magnitude.  Also,
Hingorani A (from my laboratory, Surg Forum 1994; 375-7) found that
a soluble extract from AAA wall stimulates proteinase secretion in
cultured macrophage-like cells.   The Northwestern University
research group under the leadership of William Pearce continues to
make important contributions to the field.


3. Failure of elastin or collagen as possible critical connective
tissue alterations underlying aneurysmal dilatation. 
Cardiovascular Surgery 1994; 4: 484-8.

Purpose: To identify the element of connective failure that is
critical to aneurysm formation.

Methods: Pressure/diameter studies of human vessels in vitro under
control conditions and after treatment with collagenase or
elastase.  

Results:  The findings "suggest that the critical element in both
the gross enlargement and rupture of aneurysms resides in
collagen."

Comment (by mdt):  Phil Dobrin is a good friend and a sincerely
self-critical scientist.  His first take on the issue of connective
tissue failure in AAA was that loss of elastin causes aneurysmal
dilatation and that loss of collagen is responsible for rupture. 
We have had several long discussions about this issue, which he has
revisited in his laboratory.  His present communication reflects a
second look.  

Incidentally, as of the time I am writing this, Phil could use a
*get well* card.  He is one of the most significant contributors to
the aneurysm research field.