Janice F. Lalikos

Development of a strain of rabbits with congenital simple nonsyndromic coronal suture synostosis. Part II: Somatic and craniofacial growth patterns.

In the March 1993 issue of The Cleft Palate-Craniofacial Journal we reported a female rabbit born in our laboratory with complete bilateral coronal suture (CS) synostosis. This follow-up study presents our attempts to breed the animal and establish a strain of craniosynostotic rabbits. The second part of this study presents longitudinal somatic and craniofacial growth data in offspring with coronal suture synostosis. Serial growth data from 72 animals were collected for the present study. The sample consisted of 11 animals (10 offspring and the original female) with complete nonsyndromic unilateral (plagiocephalic) or bilateral (brachycephalic) CS synostosis, 19 animals with partial CS synostosis, and 42 unaffected control litter mates. At 10 days of age, all animals had radiopaque amalgam markers placed on either side of the frontonasal, coronal, anterior lambdoidal, and sagittal sutures. Body weights and serial lateral and dorsoventral head radiographs were taken at 1.5 (10 days), 6, 12, and 18 weeks of age. All animals showed similar body weights at 1.5 weeks of age, while completely synostosed animals exhibited a slight (about 12%), but significantly (p < .001) lowered body weight by 18 weeks of age. Results revealed that by 1.5 weeks of age the completely synostosed animals already exhibited brachycephalic cranial vaults, midfacial hypoplasia, and increased flattening of the cranial base compared to unaffected siblings. This pattern continued through 18 weeks of age, with the partially synostosed animals exhibiting intermediate morphologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin

Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (p<0.001). Further increases over baseline were seen on day 14, but returned to baseline levels by day 21. For perfusion, similar increases were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased below baseline on day 21 (p<0.002). HSI allows for complete visualization and quantification of tissue oxygenation and perfusion changes in irradiated skin, and may also allow prediction of acute skin reactions based on early changes seen after irradiation.

Development of a Strain of Rabbits with Congenital Simple Nonsyndromic Coronal Suture Synostosis Part I: Breeding Demographics, Inheritance Pattern, and Craniofacial Anomalies

The lack of an animal model of congenital coronal suture (CS) synostosis has prompted the widespread use of an experimental rabbit model using adhesive immobilization of the CS. Such postnatal models have helped make significant scientific contributions but may still not fully represent all aspects of the human congenital condition. In the March 1993 issue of The Cleft Palate-Craniofacial Journal we reported a female rabbit born in our laboratory with complete bilateral CS synostosis. This follow-up study presents our attempts to breed this animal and establish a strain of craniosynostotic rabbits. To date, we have accomplished 10 back- and intercrosses with these animals and have produced a total of 71 live offspring; 10 animals exhibited complete nonsyndromic unilateral (plagiocephalic) or bilateral (brachycephalic) CS synostotic deformities at birth, and 19 animals exhibited partial CS synostosis that showed more than 75% growth retardation across the CS (well below the 95% confidence interval for normals). Results revealed that gestational time and litter size averages were consistent with those reported for the strain, although the average litter size decreased with increased inbreeding. By 1.5 weeks of age the completely synostosed animals already exhibited brachycephalic cranial vaults and midfacial hypoplasia compared to unaffected siblings. Initial pedigree analysis suggested an autosomal dominant inheritance pattern with incomplete penetrance and variable expressivity. The development of such a congenital rabbit model may prove useful in helping to understand the etiopathogenesis of this condition in human populations.

Congenital bilateral coronal suture synostosis in a rabbit and craniofacial growth comparisons with experimental models.

Experimental rabbit models of postnatal coronal suture (CS) synostosis have helped make significant contributions towards the understanding and surgical management of human congenital craniosynostosis. The present study compares craniofacial growth patterns in animals with experimental CS immobilization and in a rabbit born in our laboratory with congenital CS synostosis. The study sample consisted of 10 sham controls, 14 experimental animals with bilateral CS immobilization, and one animal with congenital, bilateral CS synostosis. At 1.5 weeks of age, all animals had amalgam markers placed on either side of the frontonasal, coronal, and anterior lambdoid sutures. At this time, the experimental animals had bilateral CS immobilization using methyl-methacrylate. Serial lateral head x-rays were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that by 1.5 weeks of age the congenital animal already exhibited changes in the cranial vault, cranial base, midface, and orthocephalic cranial base angles compared to controls. By 6 weeks of age, animals with experimental immobilization showed compensatory growth patterns similar to the congenital animal, particularly at the calvarial sutures and upper midface. This pattern continued through 18 weeks. Results showed that experimental, postnatal CS immobilization produced similar craniofacial growth patterns to those observed for our single congenital animal, but to a lesser degree, and therefore validates, in part, findings from experimental rabbit models of synostosis.

Accelerated porcine wound healing after treatment with α-gal nanoparticles.

Background: The &agr;-gal epitope is a carbohydrate antigen that interacts specifically with the natural anti-Gal antibody—the most abundant antibody in humans. Anti-Gal/&agr;-gal epitope interaction activates complement to generate chemotactic factors that induce rapid recruitment of macrophages. The authors hypothesized that &agr;-gal epitopes on nanoparticles can accelerate wound healing by inducing rapid recruitment and activation of macrophages in wounds. Methods: &agr;-Gal nanoparticles were generated from phospholipids, cholesterol, and &agr;-gal glycolipids. &agr;-Gal nanoparticle treatment of wounds was studied in 12 &agr;1,3galactosyltrasferase knockout pigs. Like humans, these pigs lack &agr;-gal epitopes and produce the natural anti-Gal antibody. Full-thickness wounds (20 × 20 mm) with tattooed borders were created on the back of pigs. &agr;-Gal nanoparticles (10 or 100 mg) were topically applied onto the wounds. Saline-treated wounds served as control. Wound open surface area was measured every 3 to 4 days during dressing changes. Wounds from euthanized pigs were subjected to histological evaluation. Results: Treated wounds displayed many more macrophages and increased angiogenesis than control wounds in the same pig. On day 10, wounds treated with 10 mg and 100 mg displayed 35 and 60 percent decreased open surface area compared with control wounds, respectively, and 80 and 90 percent less than control wounds on day 13 (p < 0.05). No keloid formation or no increase in scar formation was observed on day 60. Conclusions: &agr;-Gal nanoparticle treatment of wounds accelerates macrophage recruitment, angiogenesis, and wound healing in pigs producing the anti-Gal antibody. As humans produce high titers of anti-Gal antibodies, this treatment may exhibit a similar beneficial effect in the clinical setting.

Induction of Adipogenesis by External Volume Expansion.

Background: External volume expansion by suction is used to prepare the recipient site for fat grafting by increasing its compliance and vascularity. The authors previously developed a mouse model for external volume expansion and demonstrated its pro-proliferative and angiogenic effects. Increased thickness of the subcutaneous tissue was also observed. This study was thus designed to assess the adipogenic potential of external volume expansion stimulation. Methods: A miniaturized external volume expansion device consisting of a rubber dome connected to a −25 mmHg suction source was applied to the dorsum of mice for a single 2-hour stimulation or for 2 hours daily for 5 days. Tissues were harvested up to 48 hours after the last stimulation and analyzed for edema, inflammation, and adipocyte content by staining for hematoxylin and eosin, CD45, and perilipin-A. Expression of peroxisome proliferator-activated receptor-&ggr; (proadipogenic factor) and preadipocyte factor 1 (preadipocyte marker) was evaluated by Western blot analysis. Results: Both a 2-hour stimulation and cyclical 2-hour stimulation for 5 days induced 1.5- and 1.9-fold increases in the number of adipocytes per millimeter. Edema was present in the immediate poststimulation period, and inflammation was seen 2 days later. Peroxisome proliferator-activated receptor-&ggr; was increased at the end of stimulation. Conclusions: Stretch is known to stimulate proliferation, whereas edema and inflammation are both emerging proadipogenic factors. Their combination in external volume expansion seems to produce proadipogenic effects, seen even after a single 2-hour stimulation.

Memory of Dl-polylactic Acid Biodegradable Plates

Biodegradable plates and screws have many advantages over metal plates and screws. Plates were injection-molded and made of DL-polylactic acid. Four-hole plates were bent with the use of a heated tip to angles of 30, 45, and 60 degrees. They were inserted in the subcutaneous space in the back of rabbits. After 2 weeks, the plates straightened, suggesting that the plates had a memory. The results were confirmed by similar in vitro investigations. The in vitro experiment was repeated with tempering of the plates. The plates were heated to a temperature of 200°C for 45 seconds, cooled, and then again heated to 200°C for 40 seconds. This process resulted in loss of memory of the plates. After 4 weeks, there was a change of the bending angle of less than 2.5 degrees.

Isolated mandibular metastasis of hepatocellular carcinoma

Received from the University of Pittsburgh, Pittsburgh, PA. * Craniomaxillofacial Research Fellow, Division of Plastic, Reconstructive and Oral-Maxillofacial Surgery, Department of Surgery, Presbyterian University Hospital. t Associate Professor of Surgery, Division of Plastic, Reconstructive and Oral-Maxillofacial Surgery, Department of Surgery, Presbyterian University Hospital. # Chief Resident of Oral Surgery, Division of Plastic, Reconstructive, and Oral-Maxillofacial Surgery, Department of Surgery, Presbyterian University Hospital. Q Associate Professor of Surgery, Division of Transplant Surgery, Department of Surgery, Children’s Hospital of Pittsburgh. Address correspondence and reprint requests to Dr Lalikos: Division of Plastic, Reconstructive and Oral-Maxillofacial Surgery, Department of Surgery, University of Pittsburgh, 686 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 1526 I.

Brachioradialis musculocutaneous flap closure of the elbow utilizing a distal skin island: a case report.

A brachioradialis musculocutaneous flap with a distal skin island is described to close a chronic elbow wound. This newly described distal skin island directly over the brachioradialis tendon provides viable and durable coverage for the olecranon/posterior elbow region. The advantages and disadvantages of this treatment as compared with other historical reconstructive options for this region are analyzed. The patient has a stable healed wound at 2 years of follow-up.

Inpatient versus outpatient cleft lip repair and alveolar bone grafting: a cost analysis

BackgroundThe lifetime cost of a child with an orofacial cleft is estimated at