Effect of use of slow release of bone morphogenetic protein-2 and transforming growth factor-Beta-2 in a chitosan gel matrix on cranial bone graft survival in experimental cranial critical size defect model.

Bone grafts, used for providing structural integrity of cranial vault remodeling, could not always integrate with the remaining bone structures. All efforts are focused on increasing incorporation of the applied bone grafts. Allografts were covered by chitosan so that slow release of bone morphogenetic protein-2 (BMP-2) and Transforming growth factor-beta-2 (TGF-beta-2) was achieved. Two hundred forty Wistar-Albino rats were distributed equally in 8 study groups. Study groups were designed as; defect group, autograft group, allograft group, chitosan group, allograft + chitosan, TGF-beta-2 group, BMP-2 group, and TGF-Beta-2 +BMP-2 group. Bone biopsies were obtained at second, eight, and 14th weeks. Bone regeneration was evaluated by morphologic studies detecting histologic bone healing and radiologic studies detecting bone density. Histologic findings were evaluated in 2 categories; tissue response to the implant and defect healing. Additionally, scanning electron microscopy for detailed morphologic evaluation was done. Bone density of the applied scaffold and the parietal bone at the same computed tomography section were measured in Hounsfield scale and this ratio was used for densitometry evaluations. Kruskal-Wallis test was used to analyze difference among groups according to the histologic and radiologic data. Pairwise comparisons were done using Mann-Whitney U test with Bonferroni correction. P < 0.05 was considered significant. In the morphologic studies, bone regeneration in BMP-2 group was found to be compatible with bone regeneration in gold standard autograft group and even better than it within 15 days. Chitosan is a biocompatible material. TGF-Beta-2 alone is not effective enough in bone regeneration; BMP-2 alone has a positive effect in every step of bone regeneration. Combining TGF-Beta-2 with BMP-2 does not lead to a better bone regeneration than using BMP-2 alone. A synergistic effect is not obtained by using these 2 factors together.

Volumetric assessment of results of treatment of vascular malformations of the head and neck regions treated with a minimally invasive surgical technique after embolization procedure.

Treatment of large soft tissue vascular lesions, one of the greatest challenges facing plastic surgeons, is patient specific in almost all cases, and preoperative angiographic evaluation and embolization of these lesions are standards of care. The aim of this study was to evaluate the usefulness of 3-dimensional demonstration and volumetric assessment of soft tissue vascular lesions both in the treatment of these lesions with curettage and in the participation of the patients to the decision-making process of the disease. Five patients with vascular malformation of the head and neck regions were included to this prospective trial. All patients were evaluated with preoperative angiography, and selective embolizations of the soft tissue vascular lesions were done in the same session by the same interventional radiologists. The amount of embolic agent injected was determined according to the size and vascularization of the lesions. Surgery was done by curettage of the embolized lesions 7 to 10 days after the embolization procedure. The raw data obtained from preoperative and postoperative high-resolution computed tomographic scans of the patients were processed with a Mimics 9.22 Software (Materialise's Interactive Medical Image Control System, Leuven, Belgium). Volume and surface area of the injected embolic agent were assessed. Statistical analysis was performed using the software package SPSS 10.0 for Windows (SPSS Inc, Chicago, IL). Wilcoxon signed rank test was used to compare the measurements of the volume and the surface area of injected sclerosing agent preoperatively and postoperatively. There were no complications related to either the preoperative angiography or embolization procedure. All the patients emphasized (assessed) that the 3-dimensional demonstration of the lesions and their relation with other anatomic structures helped them to understand the extent of their pathology and aim of the proposed treatment. The difference between the volumetric measurements before and after the treatment was found statistically significant. Treatment of large soft tissue vascular lesions with curettage after embolization has acceptable cosmetic results. Although it is not possible to remove all of the sclerosing agent from its injection site with this technique, a significant amount of it can be removed, and the 3-dimensional vascular architecture of the lesion is disturbed. Reactive chronic inflammation against the remaining sclerosing agent and the intralesional scarring caused by curettage lead to further improvement. Using 3-dimensional imaging modalities helps patients and/or their relatives to understand their disease and participate in the decision-making process.

Vacuum-assisted wound closure for the management of a foot ulcer due to Buerger's disease.

SUMMARY: Thromboangiitis obliterans is a segmental inflammatory disease of the small- and medium-sized vessels mainly affecting the extremities. Although there are numerous reports concerning the treatment of these debilitating, chronic ulcers, such as skin grafting, local flaps, and free flaps, this report is the first published case of a patient with Buerger's disease, successfully managed with vacuum-assisted closure (VAC) application. This therapy decreases the period of hospital stay and increases patient comfort between dressings. Further clinical studies are needed to demonstrate the effectiveness and safety of VAC therapy in treatment of ulcers due to different kinds of vasculitis.

Mandibular reconstruction in Goldenhar syndrome using temporalis muscle osteofascial flap.

Goldenhar syndrome is a well-known developmental anomaly of the maxillofacial skeleton and hemifacial soft tissue. Maxillofacial anomalies of that syndrome can be managed by a variety of means such as inlay- or onlay-applied nonvascularized bone grafts, vascularized osteocutaneous/osseous flaps, or distraction osteogenesis. Vascularized full-thickness calvarial bone grafting is an important option for mandibular reconstruction for cases in which, for one reason or another, other techniques are not available, not applicable, or have failed. A mandibular defect of a 6-year-old boy presenting with bilateral preauricular skin tags, right microtia, right mandibular hypoplasia (with missing right condylar head and ascending ramus of the mandible) was reconstructed with right vascularized full-thickness calvarial bone grafting. Preoperative three-dimensional computed tomographic scans were used to acquire the stereolithographic biomodeling of the patient for assessing the amount of bone defect and precise planning of the surgery. Panoramic, anteroposterior, and lateral cephalograms and three-dimensional computed tomographic scans were obtained before and after the surgery and in the follow-up period for the evaluation of amount of relapse in the follow-up period. Clinical follow up and bone scintigraphy were used to assess the viability of transferred vascularized calvarial bone graft in the postoperative period. Plain radiographic evaluation with anteroposterior radiographs showed that mandibular symmetry increased and normooclusive closure of incisive teeth was achieved after surgery and retained in the postoperative period. Radiographs taken 1 year after surgery demonstrated that there was a slight relapse (1 mm) to the right side in the mandible when the results were compared with early postoperative ones. Postoperative three-dimensional computed tomographic evaluation of bony structures 3 months after operation showed that the transferred bone retained its volume. Sequential bone scintigraphies, performed to assess the vascularity of the grafts 1 week, 1 month, and 1 year after the operation, demonstrated the viability of transferred vascularized bone graft. The temporalis muscle osteofascial flap is a reliable method for mandibular reconstruction. It lessens the operative time, lessens surgical team labor, minimizes postoperative morbidity and discomfort, minimizes the hospital stay period, and minimizes financial expenses without renouncing the bone-healing capacity and increases aesthetic outcome by camouflaging the donor site scar in scalp and minimizing the facial scarring.

Effect of slow-release 5-Fluorouracil on capsule formation around silicone breast implants: an experimental study with mice.

BACKGROUND: Capsule formation around breast implants, development of tendon adhesions after tendon repair, intestinal brits after laparatomies, hypertrophic scars in skin incisions all are the results of excessive collagen synthesis to the extracellular matrix by fibroblasts. Any intervention that leads to cessation of collagen synthesis in these clinical situations may help to prevent these untoward results of wound healing. Although 5-fluorouracil (5-FU) is used mainly as a cytotoxic drug in chemotherapy protocols, it decreases cellular metabolism and blocks protein synthesis only at lower concentrations. Findings have shown that 5-FU downregulates fibroblast proliferation and differentiation in vitro. It has been used to treat fibroproliferative disorders of the eye and skin and is thought to inhibit thymidylate synthetase, blocking DNA replication. METHODS: This study used five treatment groups: (1) gelatin only, (2) silicone only, (3) silicone + gelatin, (4) silicone + gelatin containing 1 mg of 5-FU, and (5) silicone + gelatin containing 5 mg of 5-FU. The release kinetics of 5-FU from gelatin have been investigated by means of ultraviolet spectrophotometric analysis. Specimens were obtained on postoperative day 30. Gross evaluation and histopathologic examination were conducted for capsule formation and the development of inflammation. RESULTS: The silicone group had the most prominent capsule formation among all the groups. The gelatin group was second, and the silicone + gelatin group was third. As compared with the other groups, the 5-FU-containing groups had the least capsule formation. The 5-mg 5-FU-containing group had the most inflammation. The silicone + gelatin group was second in inflammation. Although the silicone, gelatin, and 1-mg 5-FU-containing groups had the same means, the results of the silicone group showed the most divergent data within the group. CONCLUSIONS: Because 5-FU loaded to a gelatin carrier for its slow release seems to prevent capsule formation around silicone blocks, it may be used to prevent capsule formation around silicone breast implants.

Results of botulinum toxin: an application to blepharospasm Schwartz-Jampel syndrome.

Schwartz-Jampel syndrome (SJS) is a rare congenital disorder of continuous myotonia, causing visual and eyelid problems such as blepharospasm, acquired ptosis, and blepharophimosis. We report the management of blepharospasm in two sisters with Schwartz-Jampel syndrome with application of botulinum toxin type A (BTX-A), as an alternative to the surgical treatments, such as orbicularis oculi myectomy, levator aponeurosis resection, and lateral canthopexy as described in the literature. Three consequent doses of commercially available BTX-A (Botox-Allergan, Inc. 100 u/via) were injected to orbicularis oculi muscle in two sisters with Schwartz-Jampel syndrome. At the least, the authors waited for a six-month interval to prevent development of sensitivity to BTX-A in patients. No significant improvement was observed after the injection of first dose of BTX-A, with the total dose of 25 units of BTX-A to each orbicularis oculi muscle of the eyes. The muscle tone weakened after the second dose, which was the twice as such of the first applied total dose (50 units of BTX-A to each orbicularis oculi muscle of the eyes) and significant functional and cosmetic improvements were achieved after injection of the third dose, in which the total applied dose was the same as the one applied in second dose. The blepharospasm and eyelid alterations caused by Schwartz-Jampel syndrome should be treated to provide functional and cosmetic improvements. Application of BTX-A to orbicularis oculi muscle for the treatment of blepharospasm could be considered as an alternative to levator resection, and lateral canthopexy in Schwartz-Jampel syndrome.

Blood loss and transfusion rates during repair of craniofacial deformities.

Surgical procedures for correction of craniofacial deformities resulted in unavoidable and extensive blood loss in small children and infants. Almost all of the patients undergoing these procedures will undergo a blood transfusion either during or immediately after the operation. A retrospective review of 30 patients who underwent craniofacial surgery was performed in this study to determine the magnitude of transfusion required for craniofacial surgery, document transfusion morbidity, and identify variables associated with the transfusion. The mean estimated blood loss was 566.8 mL, the mean intraoperative transfusion was 394.8 mL, the mean postoperative transfusion was 103.2 mL, and the mean total transfusion was 505 mL. The mean operative time was 450 minutes, the mean preoperative hemoglobin and the mean postoperative hemoglobin before hospital discharge were 11.6 g/dL and 10.3 g/dL, respectively. Craniofacial surgical procedures involve extensive scalp dissection and calvarial and facial bone osteotomies in patients with a low total blood volume. Every medical and surgical strategy for minimizing the need for blood transfusion should be considered.

Solvent-dehydrated calvarial allografts in craniofacial surgery.

Craniofacial surgery almost always requires the use of bone grafting. Although autografts are the standard procedure for bone grafting, it is sometimes not possible to harvest bone, and autografts have particular risks. The use of allograft bone provides a reasonable alternative to meet the need for graft material. Solvent dehydration is a multistage procedure in which human cadaveric bone is processed by osmotic exchange baths and gamma sterilization. This processing avoids the risk of infection transmission, decreases antigenicity, and does not weaken the mechanical properties of the bone. Solvent-dehydrated, gamma-irradiated human calvarial bone allografts were used for reconstruction of craniofacial deformities in 24 patients between 1988 and 2002. Resorption of the allografts and results of the surgical intervention were evaluated with plain radiographs and three-dimensional computed tomography 12 months after surgery, in 21 patients. Serologic tests for human immunodeficiency virus-1 antibody, hepatitis B surface antigen, and hepatitis C antigen were also performed. Biopsy specimens were taken from the allografts. Average follow-up in this group was 30 months (range, 8 to 60 months), and results of serologic tests were negative in all patients. Seventy-one percent of the patients (15 of 21) showed no resorption, with partial and complete allograft fusion. One patient had nearly total graft loss and the remaining five patients had 10 to 25 percent graft resorption. Rigid fixation of the allograft, contact with the dura and periosteum, and prevention of dead spaces around the allograft are the most important factors in achieving a satisfactory result. In solvent-dehydrated bone allografts, sterilization and antigenic tissue cleaning are achieved after several steps with a minimal dose of radiation. The result is a nonantigenic, sterile mechanical scaffold that can tolerate external forces. Although autografts are the standard in craniofacial surgery, solvent-dehydrated calvarial bone allografts produced successful results in selected cases.

Isolated supraorbital rim fracture displaced out of scalp: a case report.

Isolated fractures of the supraorbital rim are rarely seen. In this report, an isolated supraorbital rim fracture is presented in which the segment of the rim was completely removed from its location onto the frontal bone in a traffic accident. It was thought to be a foreign body and was delivered outside the scalp in the emergency service. It was replaced 24 hours after the trauma, and the patient healed without any problem.

Effects of growth factors on doxorubicin-induced skin necrosis: documentation of histomorphological alterations and early treatment by GM-CSF and G-CSF.

Extravasation of vesicant antineoplastic agents such as doxorubicin into the skin or subcutaneous tissues may result in loss of the full thickness of the skin or underlying structures. Several treatment methods have been advocated but none has demonstrated any superiority to the others. The authors designed a controlled animal study in 88 rats to test three methods of early treatment of extravasation of the vesicant antineoplastic agent doxorubicin. The first step of the study included 48 Sprague-Dawley rats. All animals received intradermal injections of 1 mg doxorubicin superficially to the panniculus carnosus in the dorsum. The rats were then divided into four groups of 12 rats each, as follows: group 1, no treatment; group 2, immediate intradermal injection of 0.1 ml saline to the same site; group 3, immediate intradermal injection of 10 microg granulocyte macrophage-colony stimulating factor (GM-CSF) in 0.1 ml saline to the same site; group 4, immediate intradermal injection of 10 microg granulocyte-colony stimulating factor (G-CSF) in 0.1 ml saline to the same site. During the next 6 weeks the rats were observed for the development of necrosis. Ulcers developed and reached maximum size two weeks after the injections. The largest ulcers according to area were observed in group 1 and the mean value was 21.25 mm (p < 0.05). Although wound areas were significantly smaller in the saline group than in the control group and the mean value was 7.58 mm (p < 0.05), the smallest lesions were observed in groups 3 and 4, and the mean values were 1.08 mm and 0.83 mm respectively (p < 0.05). There was statistically no difference with regard to mean ulcer area between groups 3 and 4. During the second step of the experiment, the remaining 40 Sprague-Dawley rats were used. Groups containing 10 rats each were designed similarly after all animals received intradermal injections of 1 mg doxorubicin into the back. On the 10th day after the injection, the entire area of the ulcer together with the underlying panniculus carnosus was excised for pathological examination and for determination of glucose 6-phosphate dehydrogenase (G6PD) activity. On microscopic examination, the extravasated ulcer consisted of a large area of ischemic necrosis. There was marked damage to small blood vessels in the form of fibrinoid necrosis and vasculitis. Injured vessel counts were higher in the control group (group 1; p < 0.05). No difference was observed in G6PD activity between the groups. The authors conclude that both saline and tissue growth factors (GM-CSF and G-CSF) are useful for the early treatment of doxorubicin extravasation; however, GM-CSF and G-CSF are more beneficial.

Tissue response to N-butyl-2-cyanoacrylate after percutaneous injection into cutaneous vascular lesions.

Despite the fact that cyanoacrylates, a group of rapidly polymerizing adhesives, are used widely in general surgery, neuroradiology, otolaryngology, and plastic surgery, scientific data on histopathological changes resulting from the deposition of -butyl-2-cyanoacrylate (NBCA), a new-generation cyanoacrylate derivative, in human tissues is based largely on experimental observations in animals and sporadic postmortem studies in humans. The authors report the consecutive pathological findings of a patient who underwent surgery for facial hemangioma after percutaneous injection of NBCA for devascularization of a lesion, and underwent additional surgery 1 and 6 months after the initial operation for the removal of the residual NBCA cast from the injection site. Acute inflammatory findings after injection of NBCA and the development of a chronic granulomatous foreign body reaction support the histological findings of experimental animal studies and postmortem examinations on humans. Additionally, their findings support the proposed hypothetical sequence of events for the recanalization of cyanoacrylate-embolized vascular structures.

Reinnervation of denervated muscle in a split-nerve transfer model.

This study was performed to quantify the reinnervation of denervated muscle in a split-nerve transfer model and to determine any possible downgrading effects on the donor nerve and its end organ. Fifty-four adult Wistar rats weighing 200 to 250 g were used. The experimental design consisted of two groups. The motor nerve branch to the anterior tibial muscle and gastrocnemius muscle of the right hind limb were dissected in all rats. In the experimental group (N = 36), the motor nerve branch of the tibial nerve to the gastrocnemius muscle was exposed, cut, and ligated. The motor nerve branch to the anterior tibial muscle was split and transected longitudinally, and the medial half was routed posteriorly. End-to-end neural anastomosis was performed between this medial half of the split nerve and the distal stump of the gastrocnemius nerve. In the control group (N = 18), while the same surgical preparation was performed, the motor nerve branch to the anterior tibial muscle and gastrocnemius nerve were exposed and transected, and the nerve endings were ligated, but neural anastomosis was not performed between these nerves. The left hind limb of all rats served as a normal comparison side without any surgical intervention. Both of the groups were divided into three subgroups (12 rats each for the experimental groups and 6 rats each for the control group) to evaluate the results after periods of 1, 3, and 6 months. Electromyography, light microscopic and morphometric examination, and muscle weight measurements were used to document the results. Although stimulation of the peroneal and tibial nerves did not produce any compound muscle action potential (CMAP) recordings from either the anterior tibial or the gastrocnemius muscle in the control group, the normalized CMAP areas of the tibial nerve were (mean +/- standard deviation) 16.2 +/- 30.8% in the 1-month group, 63.4 +/- 34.7% in the 3-month group, and 72.4 +/- 16.3% in the 6-month group. For the peroneal nerve, the normalized CMAP areas were 17.0 +/- 32.2%, 53.4 +/- 29.4%, and 54.4 +/- 14.5% for the 1-, 3-, and 6-month groups in the experimental groups respectively. A high number of regenerating myelinated nerve fibers was identified in the distal part of the coapted motor nerve branch to the gastrocnemius muscle. The average number of myelinated fibers in the lateral half of the split nerve in the experimental group was 15,108 fibers per square millimeter, 14,167 fibers per square millimeter, and 19,830 fibers per square millimeter at months 1, 3, and 6 respectively. The average number of fibers proximal to the nerve anastomotic site was 15,423 fibers per square millimeter, 19,200 fibers per square millimeter, and 20,774 fibers per square millimeter. Distal to the nerve anastomotic site, the number of myelinated fibers was 17,941 fibers per square millimeter, 18,885 fibers per square millimeter, and 18,895 fibers per square millimeter at 1, 3, and 6 months respectively. There were no myelinated fibers in the control group sections. There were significant differences in muscle weight between the experimental and control groups at the end of month 6. The difference between the experimental side and the untouched normal healthy side was not significant in the weight measurements of both muscles. The results show acceptable reinnervation by split-nerve transfer with minimal functional impairment of the donor muscle. This study confirms that split-nerve transfer is a reliable method of reconstruction for paralyzed muscle with minimal donor area morbidity.

A new experimental hypertrophic scar model in guinea pigs.

Many aspects of the biology and effective therapy of proliferative scars remain undefined, in part due to a lack of an accurate, practical, reproducible, and economical animal model for systematically studying hypertrophic scars. This study was designed to investigate whether hypertrophic scar formation could be induced in guinea pigs by removal of the panniculus carnosus alone, and by a combination of the removal of the panniculus carnosus with application of coal tar afterwards. Whole thickness skin excision or deep partial thickness injury was used to create the lesions on intact skin. Different anatomic locations were tested in different groups. Scars thus developed were examined morphologically by light microscopy and electron microscopy (TEM and SEM) and biochemically by measuring the activity of glucose-6-phosphate dehydrogenase (G6PD) to check whether these scars had morphological and biochemical properties specific to hypertrophic scars. The albino guinea pigs used in this study were divided into three groups. Removal of the panniculus carnosus was performed from the ventral aspect of the torso in animals in groups I and II. On the skin overlying the area of panniculectomy, circular skin excision was performed in group I, and deep partial thickness burn injury was inflicted in group II, to see whether wounds would heal with hypertrophic scars. In group III, dorsal aspect of the torso were used and wounds were produced by circular skin excisions followed by panniculectomy on both sides but coal tar was applied to only one side. Tissue samples were taken from the scars that were hypertrophic in appearance, and from normal scars and normal skin for comparison. Light and electron microscopic examinations and G6PD activity measurements were performed on these samples. While hypertrophic scar development was not seen in group I and group II, scars with morphological and biochemical properties specific to hypertrophic scars developed in one third of animals in group III after healing of the wounds treated with coal tar. In conclusion, it is shown that it is possible to develop experimental hypertrophic scars in guinea pigs with morphological and biochemical properties similar to those of human proliferative scars. Therefore this model is a new, practical, and economical experimental animal model to study proliferative scars, although improvements are needed to increase yield.

Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder.

Primary intraosseous vascular anomaly, previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is exclusively described in sporadic cases and no hereditary component has yet been reported. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequently observed. Here, we report two consanguineous families containing a total of four affected patients manifesting primary intraosseous vascular malformation (VMOS (vascular malformation osseous)) of the craniofacial region. The phenotypic expression is remarkably similar in both families. The characteristic findings include severe blood vessel expansions within the craniofacial bones and midline abnormalities such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation is restricted to the mandibular and maxillary area in the prepubertal age, and rapid expansion starts after age 12 or 13. A 15-year follow-up of one of the patients demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull. Detailed clinical and radiological evaluation provided neither evidence of soft-tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region. An antibody against a universal proliferation marker, Ki-67, detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. alpha-actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly. Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2-q21, 7p15-p13, and 3q35.2-q27, respectively. To the best of our knowledge, this is a new disorder, which we call hereditary intraosseous vascular malformation of the craniofacial region.