trauma. Roughly half of the laryngeal fractures in our
and then stapled closed. Third, spectral imaging was used to
series were managed non-operatively although approxi-
determine the distances from the distal end of the flap to the
mately three-quarters required airway intervention rang-
zones of stasis and zones of normal flow. Finally, animals were
ing from intubation to emergent cricothyroidotomy. Cli-
sacrificed and the flaps removed and photographed. Digital
nicians treating maxillofacial trauma need to be familiar
images of the flaps were used to determine the percent of
with the signs and symptoms of this injury. A timely
black, discolored (gray/red), and normal tissue.
evaluation of the larynx and rapid airway intervention
are essential for a successful outcome. The Schaefer
classification of injury severity and corresponding treat-
ment guidelines were consistent with our study.
c. Statistical methods: One-way analysis of variance
Leopold DA: Laryngeal trauma. A historical comparison of treatment
Results: The orthogonal polarization spectral imaging
results showed a significant decrease in the zone of
Schaefer SD, Stringer SP: Laryngeal trauma, in Bailey BJ, Pillsbury
necrosis (no vessels present) in rats treated with silden-
HC, Driscoll BP (eds): Head and Neck Surgery: Otolaryngology. Phila-
afil one and three days after surgery. We also found a
delphia, PA, Lippincott-Raven, 1998, pp 947-956
significant decrease in the total affected area, whichconsists of the zones of necrosis and stasis, in treated rats
Short and Long Term Effects of Sildenafil
three days after surgery. Digital photography analysis
on Skin Flap Survival in Rats
also showed a significant decrease in the area of necrosis(black tissue) at three days. These findings support the
Kristopher L. Hart, DDS, 705 Aumond Rd, Augusta, GA
results obtained using spectral imaging. No significant
30909 (Baur D; Hodam J; Wood LL; Parham M; Keith
differences were found between sildenafil treated and
control animals five and seven days after surgery.
Conclusion: These results demonstrated that 45 mg/
Statement of the Problem: Annually in the United States,
kg/d IP of sildenafil may have a beneficial effect on skin
approximately 175,000 people sustain severe facial trauma
survivability at the early stages of wound healing. Or-
requiring major surgical repair. These injuries often cause
thogonal polarization spectral imaging has been proven
significant loss of facial skin, leading to severe aesthetic and
to predict areas of necrosis more accurately than photo-
functional deficits. Skin flaps are the foundation for recon-
graphic analysis. This method allowed us to observe
structing such defects. The most important factor deter-
differences between sildenafil treated and control rats as
mining the survival of these flaps is the delivery of oxygen
early as 24 hours and as late as three days after surgery.
via the circulation. A number of therapeutic modalities
Although we did not see any benefit when animals were
have been explored to improve blood flow and oxygen-
treated with 45 mg/kg/d IP five and seven days after
ation of flap tissue. One principal approach has been to
surgery, we believe that changes in the treatment regi-
increase blood flow by vasodilation. However, due to their
men may enhance long-term flap survivability.
hypotensive effects, the vasodilators tested thus far havenot been utilized in surgical repair of facial skin. Phospho-
diesterase (PDE)-inhibitors, which includes the drug silden-afil, are a relatively new class of FDA approved drugs whose
Olivier WA, Hazen A, Levine JP, et al: Reliable assessment of skin flap
viability using orthogonal polarization imaging. Plast Reconst Surg
effect on tissue viability has not been widely explored. The
vasodilatory effects of these drugs have the potential to
Sarifakioglu N, Gokrem S, Ates L, et al: The influence of sildenafil on
enhance blood flow to wound sites, improve oxygen sup-
random skin flap survival in rats: An experimental study. Br J Plast Surg
ply, and promote wound repair. In this study, we examined
whether administering sildenafil intraperitoneally at a dose
of 45 mg/kg/d has a beneficial effect on the survival ofsurgical skin flaps in rats.
Materials and Methods: Surgical skin flaps were evaluated
2005 Straumann Resident Scientific
using orthogonal polarization spectral imaging, flap image
Award Winner
analysis, and histology at 1, 3, 5, and 7 days. Orthogonalpolarization spectral imaging provides high quality, high con-
Histomorphometric Assessment of Bony
trast images of the microcirculation of skin flaps. Areas of
Healing of Rabbit Critical-Sized
normal capillary flow are easily differentiated from areas of
Calvarial Defects With Hyperbaric
stasis and areas completely devoid of vessels. First, rats wereassigned to either sildenafil treated (45 mg/kg/day IP), vehicle
Oxygen Therapy
control, or sham (no injection) groups. Second, caudally based
Ahmed M. Jan, DDS, The Hospital for Sick Children,
dorsal rectangular (3 x 10 cm) flaps were completely raised
S-525, 555 University Ave, Toronto, Ontario M5G 1X8,
AAOMS • 2005
Muhonen A, Haaparanta M, Gronroos T, et al: Osteoblastic activity
and neoangiogenesis in distracted bone of irradiated rabbit mandiblewith or without hyperbaric oxygen treatment. Int J Oral MaxillofacSurg 33:173, 2004
Statement of the Problem: A critical-sized defect is the
smallest osseous wound that will not heal spontaneouslywith bony union over the lifetime of an animal. Practi-
Craniofacial Growth Following Cytokine
cally, the defect should not heal spontaneously during
Therapy in Craniosynostotic Rabbits
the experimental period. Hyperbaric oxygen therapy
Harry Papodopoulus, DDS, MD, University of Pittsburgh
(HBO) is used to improve the healing of a variety of
School of Dental Medicine, 3501 Terrace Street,
problem wounds. This study evaluated the effect of HBO
Pittsburgh, PA 15261 (Ho L; Shand J; Moursi AM;
on the healing of critical-sized defects in the rabbit cal-
Burrows AM; Caccamese J; Costello BJ; Morrison M;
varial model and whether HBO administration can result
Cooper GM; Barbano T; Losken HW; Opperman LM;
in the healing of a larger “supracritical-sized” defect.
Materials and Methods: Twenty New Zealand rabbits
were divided into 2 groups of 10 animals. Full thickness
Statement of the Problem: Craniosynostosis affects 300-
calvarial defects were created in their parietal bones bilat-
500/1,000,000 births. It has been suggested that an over-
erally. Defects were critical-sized (15 mm) on one side and
expression of Tgf-beta 2 leads to calvarial hyperostosis and
supracritical (18 mm) on the contralateral side. Group 1
suture fusion in craniosynostotic individuals. This study
received a 90 minute HBO therapy session at 2.4 ATA daily
was to test the hypothesis that neutralizing antibodies to
for 20 consecutive days. Group 2 served as a control group
Tgf-beta 2 may block its activity in craniosynostotic rabbits,
receiving only room air. Five animals in each group were
preventing coronal suture fusion in affected individuals,
sacrificed at 6 and 12 weeks postoperatively.
and allowing unrestricted craniofacial growth.
Method of Data Analysis: Data analysis included qual-
Materials and Methods: Twenty-eight New Zealand
itative assessment of the calvarial specimens as well as
White rabbits with bilateral delayed-onset coronal suture
quantitative histomorphometric analysis to compute the
synostosis had radiopaque dental amalgam markers placed
amount of regenerated bone within the defects. Hema-
on either side of coronal sutures at 10 days of age (synos-
toxylin and eosin stained sections were sliced and cap-
tosis occurs at approximately 42 days of age). At 25 days,
tured by a digital camera (RT Color; Diagnostic Instru-
the rabbits were randomly assigned to three groups: 1)
ments Inc, Sterling Heights, MI). A blinded investigator
Sham control rabbits (n ϭ 10); 2) Rabbits with non-spe-
examined merged images and analyzed them for quantity
cific, control IgG antibody (100ug/suture) delivered in a
of new bone regeneration. Statistical significance was
slow release collagen vehicle (n ϭ 9); and 3) Rabbits with
Tgf-beta 2 neutralizing antibody (100ug/suture) delivered
Results: The HBO group showed bony union and demon-
in slow release collagen (n ϭ 9). The collagen vehicle in
strated more bone formation than the control group at 6
groups Two and Three was injected subperiosteally above
weeks (p Ͻ .001). The control group did not show bony
the coronal suture. Longitudinal lateral and dorsoventral
union in either defect by 12 weeks. There was no significant
head radiographs and somatic growth data were collected
difference in the amount of new bone formed in the HBO
from each animal at 10, 25, 42, and 84 days of age.
group at 6 weeks compared with 12 weeks (p ϭ .309).
Method of Data Analysis: Significant mean differences
However, the bone at 6 weeks was more of a woven charac-
were assessed using a one-way analysis of variance.
ter, while at 12 weeks it was more lamellated and more
Results: Radiographic analysis showed significantly
mature. Again, in the HBO group both the critical-sized and
greater (p Ͻ 0.05) coronal suture marker separation,
the supracritical-sized defects healed equally (p ϭ .520).
overall craniofacial length, cranial vault length and
Conclusion: HBO therapy has facilitated the bony heal-
height, cranial base length, and more lordotic cranial
ing of both critical-sized and supracritical-sized rabbit
base angles in rabbits treated with anti-Tgf-beta-2 anti-
calvarial defects. Since bony healing was achieved early,
body than groups at 42 and 84 days of age.
it is reasonable to assume that an even larger than 18 mm
Conclusion: These data support our initial hypothesis
defect (if it were technically feasible) might have healed
that interference with Tgf-beta-2 production and/or
within the 12 week period of study aided by HBO.
function may rescue prematurely fusing coronal sutures
Adjunctive HBO, based on histomorphometrics, doubles
and facilitate craniofacial growth in this rabbit model.
the amount of new bone formed within both the critical
These findings also suggest that this cytokine therapy
sized and the supracritical-sized defects. It allowed an
may be clinically significant in infants with insidious or
increase in the critical size by more than 20%.
progressive postgestational craniosynostosis.
`ndor GK, Holmes HI, et al: Histomorphometric
Poisson E, Sciote JJ, Koepsel R, et al: Transforming growth factor-
evaluation of bone regeneration using allogeneic and alloplastic bone
beta isoform expression in the perisutural tissue of craniosynostotic
substitutes. J Oral Maxillofac Surg 62:202, 2004
rabbits. Cleft Palate Craniofac J 41:392, 2004
AAOMS • 2005
Management of Type 2 Diabetes Sorting Through the Confusion and Current Clinical Recommendations for Management An Overview for Pharmacists and Pharmacy Technicians Mary Jo Carden, RPh, JD Principal, Carden Associates Marsha K. Millonig, MBA, RPh President/CEO Catalyst Enterprises, LLC E.L.F. Publications, Inc. is accredited by the Accreditation Council for Ph
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