Marshall L. Stoller, MD
Research Interests
Stoller has investigated modalities to improve the management
of urinary stone disease. The etiology of urinary stones remains
unknown and specifically, the origination of calcium-based stones
is ill-defined. Stoller has investigated Randall plaques as the
nidus for the primordial calculus. He has mapped these lesions
endoscopically and correlated them with stone composition and
24-hour urinary constituents. He has been able to visualize them
with high resolution radiography in cadaveric kidneys and has
found them to penetrate deep within the papillae. These lesions
are visible on thin-cut spiral C/T in vivo images. Three-dimensional
reconstructions from papillary specimens may help find where stone
development begins.
The etiology of cystine urinary stone disease is unique and differs
from that seen in patients who form calcium stones. Stoller has
investigated a family pedigree and identified mutations on the
SLC3a1 gene. A DNA library has been developed for cystine stone
formers and their families. A knock-out mouse model for this gene
is being developed in the hopes of developing new prophylactic
agents and to better understand Type 1 cystinuria. Stoller has
found linkage of Type II cystinuria to 19q13.1 gene. He has also
found codominant inheritance of two cystinuric alleles at the
19q13.1 locus that produce an extreme cystine stone-forming phenotype.
Stoller has investigated a variety of agents to optimize the
radiographic visualization of urinary stones. Utilizing a variety
of bisphosphonates, he has successfully demonstrated the potential
topreoperatively determine stone composition with methyldiphosphonates.
The urolithoscintigraph also will have the potential to more optimally
visualize stones for fluoroscopically targeted ESWL-systems. A
variety of bisphosphonates are being developed as delivery agents
to coat stone fragments, with the hopes of inhibiting future stone
growth. In vitro models have demonstrated that numerous bisphosphonates
can inhibit artificial calcium oxalate monohydrate crystals and
real human calculi growth. Inhibition of calculi fragment growth
by metal-bisphosphonate complexes has resulted in a new assay
to assess surface activity of urolithiasis inhibitors.
Patients with urolithiasis are interested in dietary modifications
to help reduce their stone recurrence rates. The role of sodium
has been thought to be uniformly detrimental for calcium-based
calculi. Studies on the role of dietary sodium in hypocitruric
calcium stone formers have shown that sodium may actually be beneficial.
Increased sodium intake in hypocitruric patients significantly
increases voided volumes and reduces recurrent risk factors.
Hypocitruric calcium stone-forming patients have difficulty taking
multiple medications three to four times daily. Research has found
that lemonade can substantially increase voided citrate levels,
a known important inhibitor of urinary stone disease. The reduced
cost and increased long-term compliance with such medications
will hopefully reduce stone recurrence rates.
In vitro studies have found that fluoride has the potential to
dissolve calcium-based stones. A variety of herbal medications
and lentils are being actively investigated as alternative medications
for stone prophylaxis. The role of diet remains critical in our
understanding of stone prevention.
The prevention of urinary stone disease is essential in managing
patients with urolithiasis. A database has been developed with
more than 10,000 patients with complete 24-hour urinary chemistries
and serum parameters. This has resulted in the definition of unique
risk factors in the elderly and will be used for future research
endeavors. Stoller's commitment to urinary stone disease begins
with the most up-to-date and minimally invasive forms of therapy.
He follows this treatment with a comprehensive metabolic evaluation
to help reduce recurrence rates.
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