Endovascular treatment of TransAtlantic Inter-Society Consensus D aortoiliac occlusive disease using unibody bifurcated endografts.

OBJECTIVE: Aortobifemoral bypass has been the gold standard treatment for extensive aortoiliac occlusive disease. Endovascular therapy and stenting of aortic and iliac occlusive lesions has proven to be efficacious, especially when dealing with short segment lesions. Endovascular treatment of TransAtlantic Inter-Society Consensus II (TASC) D aortoiliac occlusive lesions remains a challenge, but a valuable treatment option in poor surgical candidates. We present our operative technique and midterm results in treating TASC D aortoiliac occlusive disease using unibody bifurcated endografts. METHODS: We performed a retrospective review of patients with TASC D aortoiliac occlusive disease who underwent transfemoral endovascular revascularization with the Endologix Powerlink unibody bifurcated endograft (Endologix, Irvine, Calif). Demographic data, operative details, and outcomes were collected. Paired t-tests were performed to compare preoperative and postoperative ankle brachial indexes. RESULTS: Between March 2009 and July 2011, 10 high-risk patients (8 male and 2 female) for a traditional aortobifemoral bypass were treated using this endovascular technique. The mean age was 59 ± 6 years (range, 50-69 years). All patients presented with rest pain, and four with tissue loss. Technical success was 100%, with two patients requiring brachial access and eight patients requiring additional stent placement. Postoperatively, all patients reported clinical improvement with resolution of ischemic symptoms. Mean improvement ankle brachial index was 0.50 ± 0.08 (P = .028) and 0.50 ± 0.01 (P = .034) in the left and right legs, respectively. Mean follow-up time was 40 ± 24 months (range, 4-81 months). The primary and secondary patency rates were 80% and 100%, respectively. Complications requiring early reintervention occurred in two patients and included one expanding hematoma from the percutaneous access site and one acute iliac artery thrombosis. Additionally, one patient underwent repeat angioplasty/stenting for threatened endograft limbs at 4 months. One patient expired during follow-up from an unrelated cardiac cause 19 weeks postoperatively. CONCLUSIONS: This series demonstrates that endovascular repair using a unibody bifurcated endograft for TASC D aortoiliac occlusive disease is feasible, effective, and has excellent midterm patency. It should be considered an effective treatment option when the disease process involves the aorta, in particular if the patient is surgically unfit for a traditional aortobifemoral bypass. The unibody configuration preserves the anatomic aortic bifurcation, which is particularly important in patients with peripheral occlusive disease who are deemed to undergo subsequent endovascular interventions.

Repair of an acute blunt popliteal artery trauma via endovascular approach.

Popliteal vascular trauma remains a challenging entity and carries the greatest risk of limb loss among the lower extremity vascular injuries. Operative management of patients presenting with traumatic popliteal vascular injuries continues to evolve. We present a case of successful endovascular repair with stent grafting of an acute blunt popliteal artery injury. Endovascular repair of traumatic popliteal vascular injuries appears as an attractive alternative to surgical repair in a very selective group of patients. Further investigation is still needed to define the safety and feasibility of endovascular approach in the management of traumatic popliteal vascular injuries.

Duplication of surgical site marking.

Wrong-site surgery is a devastating complication, and its avoidance requires uncompromising vigilance. The Joint Commission on Accreditation of Healthcare Organizations has labeled wrong-site surgery as a sentinel event and requires marking the surgical site before initiating an operation. We present a case involving the duplication of a preprocedure mark. A complete review of the patient's medical record averted disaster, but the case emphasizes the need for constant attentiveness by all members of the procedural team.

Aortic aneurysmal repair with surtureless visceral revascularization using novel hybrid vascular graft and a gradual funneling technique.

This article details a novel technique in the treatment of a symptomatic thoracoabdominal aneurysm (TAA) involving the visceral segment and an infrarenal abdominal aortic aneurysm. The patient was treated in a 2-staged hybrid approach combining an endovascular repair of the infrarenal segment, followed by open TAA repair. The large visceral arteries were revascularized using expanded polytetrafluoroethylene GORE Hybrid Vascular Graft (GHVG) and a Gradual Funneling Technique with Dacron graft. This method assured a complete hemostatic seal and minimized visceral ischemic time. To our knowledge, this is the first case of sutureless visceral artery revascularization using GHVG reported in the literature.

Uninsured South Florida vascular surgery patients are less likely to receive optimal medical management than their insured counterparts.

OBJECTIVE: Vascular disease is the most prevalent condition in patients aged >60 years, leading to increasing complications associated with their comorbid conditions. Poor medical compliance could be one reason why the rate of complications may be higher in this patient population, particularly the uninsured. This study was conducted to better assess rates of medication compliance in vascular surgical patients. METHODS: Consecutive patients seen in vascular clinics at a busy tertiary academic center were prospectively studied. Physicians and physician assistants used a standardized questionnaire to collect patient data and evaluated patients for coexisting medical conditions and medication use. Optimal medical therapy was defined according to the 2006 American Heart Association (AHA)/American College of Cardiology (ACC) "Guidelines for Secondary Prevention for Atherosclerotic Vascular Disease." Data were analyzed using multivariate regression. RESULTS: During the 4-month study period, 180 consecutive patients (47% men) were seen in vascular surgery clinics. Most patients (79%) were nonsmokers and only 21% admitted to smoking. Comorbid conditions surveyed included hypertension in 141, diabetes mellitus in 56, coronary artery disease in 24, hypercholesterolemia in 89, and chronic renal failure in 13; of these, 61% were insured and 39% had no insurance. Overall, only 31% of all patients were receiving adequate medical therapy for their comorbid conditions, and about 66% were receiving suboptimal medical treatment for their vascular disease. Uninsured patients were less likely (19%) than insured patients (39%) to receive optimal medical therapy (P = .012). Lack of insurance was a predictor of suboptimal medical therapy for hypertension (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.20-8.16; P = .016), hypercholesterolemia (OR, 5.1; 95% CI, 1.87-13.88; P = .001), peripheral arterial disease (OR, 13.32; 95% CI, 2.84-62.54, P < .001), and any disease overall (OR, 2.43; 95% CI, 1.21-4.88, P = .012). Overall, men and women were equally likely (68%) to receive suboptimal medical therapy; however, women were significantly more likely to be undertreated for coronary artery disease (OR, 0.022; 95% CI, 0.0017-0.293; P < .001). CONCLUSIONS: Compliance with optimal medical therapy for secondary risk factor management amongst our vascular surgery patients is low. Uninsured patients are less likely to receive optimal medical therapy than their insured counterparts. This survey provides sobering statistics regarding medical compliance in our population. This issue deserves further study and may indirectly affect outcomes in minority groups that are disproportionately represented in our uninsured patients.

Thoracic aortic transection treated by thoracic endovascular aortic repair: predictors of survival.

BACKGROUND: We reviewed all patients presenting to our institution with a traumatic thoracic aortic injury (TTAI) between January 2006 and May 2007. Age, gender, injury severity score (ISS), location of injuries, surgical intervention, and length of stay were assessed to determine what characteristics might be predictive of survival. Of the 56 patients who were identified, 23 (41%) were dead on arrival, 15 (20%) died on that admission, and 18 (32%) survived to discharge. Injury severity score was elevated in mortalities (57) compared to survivors (34). Penetrating and blunt aortic injuries had 89% and 58% mortality rates, respectively. Female gender was associated with increased survival (P = .032), as was receiving surgical intervention (P = .03). Patients with a prolonged ICU stay demonstrated increased survival. All eight patients who received thoracic endovascular aortic repair survived to discharge. Injury severity score, mechanism, thoracic endovascular aortic repair (TEVAR), female gender, and surgical treatment were associated with survival after TTAI.

Carotid artery stenting: identification of risk factors for poor outcomes.

OBJECTIVES: Age greater than 80 has been identified as a risk factor for complications, including stroke and death, in patients undergoing carotid artery angioplasty and stenting (CAS). This study evaluates other potential predictors of perioperative complications in patients undergoing CAS. METHODS: All cerebrovascular endovascular procedures performed by the vascular surgery division at our university hospital between July 2003 and December 2005 were retrospectively examined. During the course of 212 admissions, 198 patients underwent 215 procedures. Patient age, comorbidities, and admission status were analyzed as independent (predictor) variables. Complication rate, discharge disposition, and length of hospital stay were considered dependent (outcome) variables. Logistic regression and Fisher exact test or Student t test were performed, as appropriate. RESULTS: Complications included major and minor stroke, myocardial infarction, femoral artery pseudoaneurysm, and death. The rates of perioperative major and minor stroke were 0.5% and 2.8%, respectively. Chronic renal insufficiency was a predictor of perioperative complications, including stroke: patients with serum creatinine greater than 1.3 mg/dL had a 37% complication rate and a 11.1% stroke rate, while those with normal renal function had a 13% complication rate (P = .003) and a 0.6% stroke rate (P =.001). Similar association was seen between creatinine clearance and both stroke and complications. Obesity was a risk factor for complications, but not stroke: obese patients had a complication rate of 28%, while others had a 16% complication rate (P = .024). Emergency admission predicted both extended hospital stay (P < .001) and requirement for further inpatient care in a rehabilitation or nursing facility (P = .007). There was no significant difference in complication rate or stroke rate between octogenarians and others. CONCLUSION: This experience demonstrates that chronic renal insufficiency, obesity, and emergent clinical setting are risk factors for patients undergoing CAS.

Differential effects of carotid artery stenting versus carotid endarterectomy on external carotid artery patency.

PURPOSE: To determine the effect of stent coverage of the external carotid artery (ECA) after carotid artery stenting (CAS) compared to eversion endarterectomy of the ECA after carotid endarterectomy (CEA). METHODS: The records of 101 CAS and 165 CEA procedures performed over 2 years were reviewed. Duplex velocities and history and physical examinations were taken prior to the procedure, at 1 month, and at 6-month intervals subsequently. CAS was performed by extending the stent across the internal carotid artery (ICA) lesion into the common carotid artery (CCA) thereby covering the ECA. CEA was performed with eversion endarterectomy of the ECA. RESULTS: The mean peak systolic velocities (PSV) in the ICA pre-CAS and pre-CEA were 361 and 352 cm/s, respectively. In terms of CAS, there was a significant increase in ECA velocities versus baseline at 12 (p = 0.009), 18 (p = 0.00001), and 24 (p = 0.005) months. In the CEA group, there was a significant decrease in ECA velocities versus baseline at 1 (p = 0.01) and 6 (p = 0.004) months. There were 2 occluded ECAs in follow-up in the CAS group and none in the CEA group. No significant differences were noted when comparing preprocedural ICA or ECA velocities. However, at the 1-, 6-, and 12-month intervals, the ECA velocities in the CAS group were significantly higher than in the CEA group (p = 0.03, p = 0.001, and p = 0.0004, respectively). There were no neurological symptoms in any patients during the study period. CONCLUSION: Although progressive stenosis of the ECA is noted during CAS, the ECA usually does not occlude. Furthermore, there are no associated neurological symptoms. Thus, apprehension for progressive ECA occlusion should not be a contraindication to CAS. In addition, concern for ECA coverage should not deter stent extension from the ICA to the CCA during CAS.

A comparison of renal function between open and endovascular aneurysm repair in patients with baseline chronic renal insufficiency.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is rapidly becoming the predominant technique for repair of abdominal aortic aneurysms. Results from current studies, however, are conflicting on the effect of EVAR on renal function compared with standard open repair. Furthermore, data for open repair in patients with baseline renal insufficiency suggests worse outcomes, including renal function. This analysis compared the effects of open repair vs EVAR on renal function in patients with baseline renal insufficiency. METHODS: We reviewed our records for patients with preoperative chronic renal insufficiency (serum creatinine, 1.5 mg/dL) who underwent open repair or EVAR between 1999 and 2004. The same group of vascular surgeons at a single institution performed aneurysm repair on 98 patients: 46 open (37 men, 9 women) and 52 EVAR (50 men, 2 women). Preoperative, postoperative, and follow-up serum creatinine and creatinine clearance were compared, as was the development of postoperative renal impairment (increase in serum creatinine >30%). RESULTS: Serum creatinine and creatinine clearance were not statistically different between the open and EVAR groups during any time period studied. Likewise when comparing the magnitude of change in serum creatinine in patients between the postoperative and follow-up times with preoperative values, no significant differences existed between the open and EVAR groups. When the change in serum creatinine over time within each group was compared, however, the open group had a significant increase in serum creatinine postoperatively (2.43 +/- 1.20 vs 2.04 +/- 0.64, P = .012), which returned to baseline during follow-up (1.96 +/- 0.94, P = .504). Although serum creatinine in the EVAR group increased compared with preoperative values of 2.04 +/- 0.55 (postoperative, 2.27 +/- 1.04; follow-up, 2.40 +/- 1.37), this failed to reach statistical significance for the postoperative (P = .092) or follow-up (P = .081) periods. A similar pattern was noted in creatinine clearance. Postoperative renal impairment was noted in 13 open (28%) and 15 EVAR patients (29%) and was not statistically different between groups. Overall, two patients (4.3%) from the open group and four (7.7%) from the EVAR group required hemodialysis; one in the EVAR group required permanent hemodialysis. This difference was not statistically significant (P = .681). CONCLUSIONS: Open and endovascular repair of abdominal aortic aneurysms in patients with pre-existent renal insufficiency can be performed safely with preservation of renal function. In contrast to previous reports, no significant differences existed between open repair and EVAR in postoperative alterations in renal function. Although a significant increase in serum creatinine develops in patients with renal insufficiency postoperatively with open repair, this appears to be transient, and preoperative renal dysfunction alone should not exclude either approach. After EVAR, patients with pre-existing renal insufficiency continue to be at risk for progressive renal dysfunction, and protective measures should be taken to preserve renal function in this patient population.

Endovascular therapy of symptomatic innominate-subclavian arterial occlusive lesions.

The purpose of this study was to determine the safety and efficacy of angioplasty and stenting for symptomatic innominate-subclavian lesions by review of records of symptomatic patients undergoing angioplasty and stenting of high-grade lesions (>80%) of the innominate and subclavian arteries. Follow-up consisted of history (symptoms) and physical examination (pulses and blood pressures) at 1, 3, 6, and then every 12 months plus an annual duplex ultrasound examination. Between 1998 to 2003, 25 patients (27 lesions) were treated. Ages ranged from 48 to 89 years. Symptoms included vertebrobasilar/steal (15), claudication (6), ischemia (4), and coronary artery bypass grafting/left internal mammary artery (2). There were 7 occlusions and 20 high-grade stenoses. Access was attempted via brachial cutdown (19) or percutaneous puncture of the brachial (2) or femoral arteries (10). Twenty-two lesions were stented with either self-expanding (13) or balloon-expandable (9) stents. Technical success was 89%; 3 occluded lesions could not be crossed owing to complete occlusion. The remaining 4 occlusions were all crossed via a retrograde approach. The mean difference in systolic blood pressure between upper limbs decreased from 36 mm Hg (preprocedure) to 10 mm Hg (postprocedure). There were no procedure-related complications. Mean follow-up was 18 months (range 1-62 months). One patient died 4 months after the procedure secondary to complications from pulmonary surgery unrelated to the percutaneous transluminal angioplasty/stent. Of the 4 successfully treated occlusions, 2 were followed up to 3 years with continued patency. Three patients developed recurrent stenoses documented by duplex examination. However, these patients remained asymptomatic and were not treated. Endovascular management of high-grade lesions of the subclavian or innominate arteries is safe and efficacious and may be considered as a first line of therapy. Continued follow-up is needed to assess long-term patency.

Outcomes of accessory renal artery occlusion during endovascular aneurysm repair.

OBJECTIVE: Accessory renal arteries are frequently encountered when patients are evaluated for endovascular abdominal aortic aneurysm repair (EVAR). Some have considered their presence a contraindication to EVAR in fear of endoleak and the end result of renal function. We sought to determine whether the coverage of accessory renal arteries during EVAR was associated with any adverse sequelae. METHODS: Retrospective review of the medical records and computed tomographic scans of all patients undergoing EVAR (1998 to 2003) was performed. Note was made of the presence or absence of accessory renal arteries, hypertension, and renal function. Preoperative computed tomographic images were compared with postoperative images to determine the presence of renal infarction. A control group of 26 consecutive patients without accessory renal arteries was used for comparison of the results of EVAR. RESULTS: EVAR was performed in 550 patients over the study interval. The mean follow-up was 16 months (range, 1-48 months). The average age was 74 years (range, 57-90 years). Thirty-five patients (6.6%; 32 male and 3 female) were documented to have accessory renal arteries; the average number of accessory arteries was 2 (range, 1-4). Bilateral accessory arteries were present in 13 patients: all but 1 patient (n = 34) had a left-sided accessory renal artery, and 23 had a right-sided accessory renal artery. EVAR was performed with a variety of endografts: AneuRx (n = 10), Talent (n = 7), PowerLink (n = 7), Zenith (n = 5), LifePath (n = 4), and Ancure (n = 2). There were no mortalities. Twelve endoleaks were documented: three type I, eight type II, and one type III. The accessory renal arteries were not implicated in any of the endoleaks, and none of these accessory vessels was embolized before or after EVAR. Seven patients (20%) had renal infarcts associated with EVAR that were noted on follow-up computed tomographic scans. The mean follow-up for patients with segmental infarction was 23 months (range, 8-48 months). Hypertensive status did not change in any patient in whom an accessory renal artery had been covered. The average serum creatinine was 1.08 mg/dL (range, 0.6-1.8 mg/dL) before EVAR in patients with accessory renal arteries covered by an endovascular graft and did not change significantly in response to EVAR. Serum creatinine increased almost twofold in two patients but spontaneously resolved in follow-up. The average preoperative creatinine clearance was 79 mL/min (range, 35-166 mL/min) in patients without an accessory renal artery and was 80 mL/min (range, 35-167 mL/min) after EVAR. The average preoperative creatinine clearance was 67 mL/min (range, 31-137 mL/min) in patients with an accessory renal artery and 68 mL/min (range, 45-83 mL/min) in patients with renal infarcts. None of the patients required temporary or permanent dialysis. There was no difference between control patients and patients with covered accessory renal arteries with respect to hypertensive status, presence of renal infarcts, serum creatinine, or creatinine clearance after EVAR. CONCLUSIONS: Occlusion of accessory renal arteries is not associated with clinically significant signs or symptoms, even in patients with mild or moderate renal insufficiency. Sacrifice of accessory renal arteries most commonly does not lead to detectable renal infarction, either clinically or radiographically. When segmental infarction of the kidney does result, it seems to be well tolerated in this group of patients. Accessory renal arteries were not found to contribute to endoleaks and should not be prophylactically embolized.

Intrauterine fetal constraint induces chondrocyte apoptosis and premature ossification of the cranial base.

BACKGROUND: The spheno-occipital synchondrosis is an important growth center of the craniofacial skeleton and a primary site of malformation in syndromic forms of craniosynostosis. Clinical and laboratory investigations have demonstrated that premature closure of cranial vault sutures in nonsyndromic craniosynostosis is associated with characteristic alterations in cranial base morphology. However, a causal link between premature fusion of calvarial sutures and changes in the cranial base remains elusive. The purpose of these experiments was to test the hypothesis that intrauterine head constraint produces ultrastructural changes in the spheno-occipital synchondroses of fetal mice. METHODS: Fetal constraint was induced through uterine cerclage of six pregnant C57Bl/6 mice on the eighteenth day of gestation. Fetuses were harvested after growing to 24, 48, and 72 hours beyond the normal 20-day gestational period. Between six and nine fetuses were harvested at all time points in both treatment and control groups. The morphology and cell biology of the spheno-occipital synchondroses, in constrained fetuses and unconstrained controls, were examined using hematoxylin and eosin-stained sections. Chondrocyte apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assays and electron microscopy. RESULTS: In nonconstrained animals, the spheno-occipital synchondrosis demonstrated normal architecture and normal chondrocyte morphology at all time points. In contrast, intrauterine constraint resulted in a progressive disruption of the normal cellular architecture of the spheno-occipital synchondrosis over 72 hours, with premature ossification of the synchondrosis. Widespread chondrocyte apoptosis within the synchondrosial growth center was demonstrated by terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assays and electron microscopy. CONCLUSION: These experiments confirm the ability of intrauterine constraint to induce changes in the morphology and cell biology of the cranial base in synostotic fetuses.

Repair of the immature and mature craniofacial skeleton with a carbonated calcium phosphate cement: assessment of biocompatibility, osteoconductivity, and remodeling capacity.

BACKGROUND: The apatite compounds used most commonly in craniofacial reconstruction are highly crystalline and biologically inert ceramics. Because their capacity to be replaced by native bone is limited, they have found little application in repair of the growing craniofacial skeleton. Carbonated calcium phosphate cements more closely resemble the mineral phase of bone, thereby offering enhanced bioresorption and osteoconductivity, but their fate in the immature and mature craniofacial skeleton has not been investigated. METHODS: The authors hypothesized that the capacity for cell-mediated remodeling of carbonated calcium phosphate cements is based on (1) their crystallographic and compositional similarity to the mineral phase of bone and (2) the osteogenic capacity of the host. Four noncritical-sized calvarial defects were created in six 3-week-old and six 16-week-old Yorkshire pigs. The defects were repaired with autologous bone, sintered carbonated calcium phosphate cement disks with a higher crystal order, or carbonated calcium phosphate cement (Norian CRS; Synthes Maxillofacial, West Chester, Pa.). The fourth defect was left empty as a control. Specimens were harvested at 30 and 90 days postoperatively. RESULTS: Empty defects healed with dense fibroconnective tissue in all groups. Autologous bone grafts underwent complete remodeling and replacement with woven bone at both time points. Sintered carbonated calcium phosphate disks demonstrated no bony ingrowth or remodeling. In immature animals, carbonated calcium phosphate cement implants were progressively replaced with woven bone through osteoclast-mediated resorption and osteoblast-mediated bone formation. Only minimal remodeling of the carbonated calcium phosphate cement implants was observed in skeletally mature animals. CONCLUSIONS: The results of these experiments suggest that the extent of remodeling of carbonated calcium phosphate cement is dependent on both the composition of the implant itself and the osteogenic capacity of the host and that carbonated calcium phosphate cement may be used successfully for inlay applications in the immature craniofacial skeleton.

Immunolocalization of androgen receptor in the developing craniofacial skeleton.

Male predominance in metopic and sagittal craniosynostosis and in nonsynostotic plagiocephaly suggests a role for circulating androgens in early craniofacial development. Androgens have been documented to play an important role in postnatal skeletal growth, and the androgen receptor has been recently demonstrated in human and rat osteoblast-like cell lines and in human long bones. The purpose of this study was to describe the expression of androgen receptor in the fetal craniofacial skeleton. The heads of E18 fetal CD-1 male and female mice were fixed in 10% formalin, decalcified, and embedded in paraffin. Four- to 6-mum coronal and sagittal sections were stained with a monoclonal antibody specific to androgen receptor, which was detected by an avidinbiotin conjugate and peroxidase system. The sections were then examined for androgen receptor expression patterns. Strong androgen receptor immunoreactivity was observed in the dura mater of developing fetuses. Androgen receptor expression was also noted in cells lining the osteogenic fronts and in calvarial osteoblasts. Similar androgen receptor expression patterns were found in male and female mice. Androgen receptor is abundantly expressed in fetal dura mater and calvarial bone. This study confirms the presence of androgen receptor in the murine fetal craniofacial skeleton, suggesting a potential role for the anabolic effects of androgens in the developing craniofacial skeleton.

Stroma formation and angiogenesis by overexpression of growth factors, cytokines, and proteolytic enzymes in human skin grafted to SCID mice.

Reorganization of skin during wound healing, inflammatory disorders, or cancer growth is the result of expression changes of multiple genes associated with tissue morphogenesis. We wanted to identify proteins involved in skin remodeling and select those that may be targeted for agonistic or antagonist therapeutic approaches in various disease processes. Full-thickness human skin was grafted to severe combined immunodeficient mice and injected intradermally with 38 different adenoviral vectors inserted with 37 different genes coding for growth factors, cytokines, proteolytic enzymes and their inhibitors, adhesion receptors, oncogenes, and tumor suppressor genes. Responses were characterized for infiltration of inflammatory cells, vascular density, matrix formation, fibroblast-like cell proliferation, and epidermal hyperplasia. Of the 17 growth factor vectors, 16 induced histological changes in human skin. Members of the VEGF and angiopoietin families induced neovascularization. PDGFs and TGF-betas stimulated connective tissue formation, and the chemokines IL-8 and MCP-1 attracted inflammatory neutrophils and monocytes, respectively. The serine protease uPA induced a vascular response similar to that of VEGF. Vectors with adhesion receptors, oncogenes and tumor suppressor genes had, with few exceptions, little effects on skin architecture. The overall results suggest that adenoviral vectors can effectively remodel the architecture of human skin for studies in morphogenesis, inflammatory skin disorders, wound healing, and cancer development.

Reconstruction of the immature craniofacial skeleton with a carbonated calcium phosphate bone cement: interaction with bioresorbable mesh.

Calcium phosphate cements have been recently introduced for use in craniofacial reconstruction. In the clinical setting, however, pulsations of the underlying brain and dura may interfere with the crystallization of these cements, thereby rendering their use in cranioplasty problematic. To circumvent such problems, many clinicians have interposed synthetic resorbable plates or mesh between the dura and the cement. At the present time, however, little is known about the influence of such materials or their breakdown products on the fate of calcium phosphate cements. The specific aim of this project was to evaluate the biocompatibility, osteoconductivity, and remodeling capacity of a calcium phosphate cement after implantation into experimental calvarial defects when combined with a resorbable mesh underlay. Four 10-mm diameter full-thickness calvarial defects (two frontal, two parietal) were created in each of six 3-week-old Yorkshire pigs. The defects were treated as follows: 1) empty control, 2) macroporous polylactic acid (70/30 L/DL polylactic acid [PLA]) mesh, 3) Norian CRS calcium phosphate cement, and 4) Norian CRS over PLA mesh underlay. Animals were divided into two groups. Half of the animals were killed 30 days after surgery, and half were killed 180 days after surgery, and the graft recipient sites were examined histologically. At 30 days, minimal bone ingrowth was observed in untreated calvarial defects or in those that were treated with PLA plates alone. Defects treated with the cement alone demonstrated a modest amount of new woven bone deposition, primarily at the periphery of the implants. Defects treated with calcium phosphate cement over PLA mesh underlays were characterized by remodeling and woven bone deposition at 30 days, with complete or near-complete osseous bridging of the ectocranial implant surfaces. Progressive bone ingrowth was noted in all defects at 180 days, with near-complete replacement of all Norian CRS implants by host bone. The PLA mesh remained incompletely resorbed at 180 days. No inflammatory response to the implants was observed at either time point. Calcium phosphate cement may be safely used for craniofacial reconstruction in the presence of PLA implants without compromise to its biocompatibility, osteoconductivity, or remodeling capacity.

Repair of the immature craniofacial skeleton with a calcium phosphate cement: quantitative assessment of craniofacial growth.

The potential for growth restriction has limited the use of alloplastic materials for reconstruction of the growing craniofacial skeleton. A calcium phosphate cement that has been introduced recently for craniofacial reconstruction crystallizes in situ into a substance that resembles more closely the mineral phase of bone, thereby offering the potential for enhanced bioresorption and osteoconductivity. The purpose of these experiments was to assess quantitatively craniofacial growth after reconstruction of frontal craniectomy defects in skeletally immature animals with this calcium phosphate bone mineral substitute. To simulate the calvarial defects that result from unilateral fronto-orbital advancement procedures, unilateral frontal bone flaps were removed in 3-week-old female Yorkshire piglets. The bone flaps were trimmed medially and posteriorly, and were then reattached to the supraorbital ridge. The resulting 5-mm gap between the frontal bone flap and the native bone was either filled with Norian CRS bone cement (N = 3) or left empty (N = 3). After 90 days, the animals were killed and the skulls were harvested and cleared. Direct craniometric measurements were performed on the prepared dry skulls to assess craniofacial growth in all dimensions. Extensive remodeling was observed within defects treated with the calcium phosphate cement, with complete or near-complete replacement of the cement by host bone, resulting in a solid bony union. Direct craniometric measurements revealed no differences in craniofacial growth in any dimension between the operated and unoperated sides of the cranium in either group. These studies demonstrate that craniofacial growth is not restricted after reconstruction of frontal craniectomy defects with carbonated calcium phosphate cement in skeletally immature animals. The remodeling capacity of this material offers promise for its safe use in reconstruction of the growing calvarium.

Craniosynostosis and altered patterns of fetal TGF-beta expression induced by intrauterine constraint.

Recent work has demonstrated that fusion of the calvarial sutures is mediated by locally elaborated soluble growth factors, including the transforming growth factor-betas (TGF-betas), leading some to speculate that external biomechanical forces play little role in suture development. Clinical evidence has long suggested, however, that fetal head constraint may play a critical role in the pathogenesis of many cases of nonsyndromic craniosynostosis. The purpose of these experiments was to test the hypothesis that intrauterine constraint leads to an alteration in normal patterns of TGF-beta expression and that these alterations are associated with craniosynostosis. Fetal constraint was induced by allowing C57Bl/6 murine fetuses to grow for 2.5 days beyond the normal 20-day gestation by performing uterine cerclage on the eighteenth day. Cranial suture morphology was examined in hematoxylin and eosin-stained sections and in cleared whole-mount specimens, double stained with alizarin red S and Alcian blue. Expression patterns of TGF-beta1 and TGF-beta3 were examined by immunohistochemical techniques. Gross and microscopic examination of the cranial sutures of 17 constrained fetuses revealed changes that ranged from narrowing to complete osseous obliteration of the coronal and squamosal sutures. All sutures of 14 nonconstrained control pups remained patent. Fetal head constraint was associated with increased TGF-beta1 immunoreactivity within the new bone and the underlying dura when compared with nonconstrained age-matched controls. TGF-beta3 immunoreactivity was associated with the dura underlying patent, nonconstrained sutures, whereas constraint-induced synostosis was characterized by down-regulation of dural TGF-beta3 expression. These experiments confirm the ability of intrauterine constraint to induce premature fusion of the cranial sutures and provide evidence that intrauterine head constraint induces the expression of osteogenic growth factors in fetal calvarial bone and the underlying dura.