Christian Linz

Face perception in patients with unilateral cleft lip and palate and patients with severe Class III malocclusion compared to controls

Although there is principal agreement that increased facial asymmetry is associated with decreased facial attractiveness, there are no studies analysing face perception in patients with a unilateral cleft lip and palate (CLP) (uCLP) compared to orthognathic Class III patients. To this end, three-dimensional (3D) data on the faces of 30 adults with a complete uCLP, 20 orthognathic patients with a severe skeletal Class III, and 20 adults with a skeletal Class I as a control group were generated. The 3D asymmetry of the facial soft-tissue was analysed. These data were compared with subjective ratings for attractiveness carried out by 100 laypersons. Compared to the controls, uCLP patients and orthognathic patients had a significantly higher facial asymmetry. No difference was found between uCLP patients and orthognathic patients. The attractiveness ratings showed that uCLP patients and orthognathic patients were rated less attractive compared to the controls. However, although there were no differences in the facial asymmetry between uCLP patients and orthognathic patients, the uCLP patients were rated significantly less attractive. This leads to the conclusion that not only the extent of asymmetry has an influence on attractiveness but also the location of asymmetry. For clinical use, these findings underline the importance of accurate as possible surgical reconstruction of the nasal morphology in uCLP patients.

Three-dimensional analysis of cranial growth from 6 to 12 months of age

The aim of this study was to generate three-dimensional data of the physiological growth of the infants cranium in the significant growth phase from 6 to 12 months of age. In a longitudinal observational study non-invasive 3D data using an optical surface scanner were generated of the entire head of 52 Caucasian infants (27 females and 25 males) between the ages of 6 (T1) and 12 (T2) months. The circumference of the head increased by 6.51 per cent (from 43.50 to 46.33cm). Analysis of width and length showed that the head grows 2.84 per cent more in length, resulting in a decrease in the cranial index of 2.52 per cent (from 83.87 to 81.76 per cent). The highest increment observed was in the total volume of the cranium, with an increase of 18.76 per cent (from 1229.01 to 1459.57cm(3)). Comparison of the left and right sides of the head by measuring the diagonal symmetry difference showed a difference of only 0.37cm. Overall, the symmetry-related parameters showed an almost symmetric development of the cranium in infants. The findings should provide valuable information on physiological growth and development of the infants cranium. Therefore the high growth rate of the cranium in the first year of life suggests that this period is a critical period in which the disruption of developmental processes may have long-lasting effects on the morphology of the cranium with a prognostically unfavourable effect of the further growth of the viscerocranium.

Three-dimensional analysis of positional plagiocephaly before and after molding helmet therapy in comparison to normal head growth

ObjectiveStereophotogrammetry enables a simple and radiation free longitudinal analysis of skull asymmetries: in a three-dimensional coordinate system various distances (length, breadth, cephalic index, oblique diameters, ear shift, head circumference) can be analyzed. We also defined separate volume sections in order to further quantify the degree of asymmetry in the posterior and anterior components of both sides of the head.Patients and methodsIn 51 infants (mean age, 6 months; SD 0.97) with positional plagiocephaly, we determined these parameters at the beginning as well as at the end of molding helmet therapy (mean therapy time 4.9 months). Thirty-seven infants without positional deformity (mean age, 6.4 months; SD 0.3) served as control group and provided data about what appears to be normal and how these parameters change during growth over a comparable period of time.ResultsCompared with the control group, the plagiocephalic heads were more brachycephalic, but closely approximated the normal shape under molding therapy. The striking volume difference between the left and right posterior sections in the plagiocephalic children (the mean volume of the flattened side being 21 % smaller than the one on the contralateral side) improved as well (to a residual difference of mean 8 %) and ended up with a value close to the control group (mean 6 %).ConclusionThere is a broad clinical application area for stereophotogrammetry analyzing skull morphology: In plagiocephalic infants we demonstrate impressive changes of head shape under molding therapy; in normal-looking infants we describe the extent of unperceived asymmetry.

Influence of epidermal growth factor receptor expression on the cetuximab and panitumumab response rates of head and neck carcinoma cells

OBJECTIVES To examine the impact of epidermal growth factor receptor (EGFR) expression level on the efficacy of monoclonal antibodies against the EGFR. METHODS In four human head and neck carcinoma cell lines, epidermal growth factor expression was knocked down by lentiviral RNA interference. Next, the efficacies of cetuximab and panitumumab at concentrations of 4, 40, and 400 μg/ml were measured by real time cell analysis for a 48-h duration. Finally, the different response rates to the drugs were statistically analyzed. RESULTS The lentiviral EGFR knockdown efficiency ranged from 18 to 54 % across all of the cell lines. All original cell lines exhibited rather poor or inverse responses with regard to EGFR-AB treatment. In contrast, inhibiting EGFR expression in the same cell lines yielded statistically significant better responses to cetuximab or panitumumab treatment. CONCLUSIONS The cell lines used in this study responded poorly to cetuximab and panitumumab. Better anti-EGFR treatment efficacy was related to lower EGFR expression in head and neck cancer cell lines. These findings might influence the selection of patients to receive cetuximab and panitumumab treatment for head and neck cancer.

Occipital plagiocephaly: unilateral lambdoid synostosis versus positional plagiocephaly

Objective We defined parameters that could differentiate between positional and synostotic plagiocephaly and defined a diagnostic chart for decision making. Design Prospective study. Setting We examined 411 children with non-syndromic skull abnormalities between January 2011 and December 2012. Participants A total of 8 infants under 1 year of age with proven unilateral non-syndromic lambdoid synostosis (LS) and 261 children with positional deformity were examined to outline the specific clinical features of both diagnoses. After clinical examination, an ultrasound revealed either a closed suture suggestive of LS or a patent lambdoid suture suggestive of positional deformity. For patients with synostosis, plain radiographs, MR imaging and follow-up examinations were performed. In cases of open sutures, only follow-ups were completed. Main outcome measure Clinical, imaging, genesis and treatment differences between positional plagiocephaly and LS. Results In all 8 cases of unilateral LS and 258 cases of positional plagiocephaly, the diagnosis was established by clinical examination alone. In three cases of positional plagiocephaly, diagnosis was determined after an additional ultrasonography. MR imaging revealed a unilateral tonsillar herniation in five of the eight children with LS and hydrocephalus in one child. Conclusions We have suggested a list of clinical features that specify the underlying cause of posterior plagiocephaly. An additional ultrasound scanning confirmed the diagnosis without any risks of ionising radiation or sedation as in a CT scan.

3D stereophotogrammetric analysis of operative effects after broad median craniectomy in premature sagittal craniosynostosis

IntroductionThere is ongoing discussion on the diagnostic methods, the need of surgical treatment, and the surgical strategies for premature craniosynostosis.Materials and methodsThis study examined the operative procedure of a standardized broad median craniectomy, active tilting of the forehead, and bitemporal greenstick fracturing in children with premature sagittal craniosynostosis. To objectively analyze the direct surgical results, we used a 3D stereophotogrammetry scanner, as previously described.ResultsA 3D analysis showed a significant increase in the width, cranial index (CI), head and coronal circumferences, intracranial volume, and cranial base width after surgery. Head length was the only parameter that demonstrated a significant decrease postoperatively. Asymmetry and the 30° diagonal difference showed no significant changes.Conclusion3D stereophotogrammetry is a reliable and valuable tool with no side effects. It demonstrated that the extended surgical procedure achieves good postoperative results with a reduced length and increased width and, therefore, an improved CI. Additionally, the total intracranial volume was significantly increased after surgery.

Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw.

Abstract This study evaluates the diagnostic utility of 3-phase bone scintigraphy for diagnosing osteoradionecrosis of the jaw (ORNJ). Methods Thirty-two consecutive patients with a history of radiation to the head and neck region (range, 62–70 Gy; mean, 68 Gy; median, 69 Gy) due to squamous cell cancer and suspected ORNJ underwent 3-phase bone scans after injection of 520 to 750 MBq of 99mTc-MPD. In addition to planar scans, tomographic images (SPECT) were acquired in the second phase and SPECT/CT images during the third phase. Histopathologic findings (n = 18) and clinical follow-up (n = 14) served as reference standard for osteoradionecrosis. Results The first, second, and third phases of planar images were rated positive in 18/32 patients (56.3%), 25/32 (78.1%), and 27/32 patients (84.4%), respectively. The late SPECT was positive in all patients (32/32, 100%), respectively. Histopathologic findings available in 18/32 patients (56.3%) confirmed ORNJ in all subjects. Acute inflammation was histologically proven in 18/18 specimens (100%) and additional chronic inflammation in 12/18 (66.7%). In 13/18 (72.2%) specimens, superinfection was evident histopathologically. A photopenic defect with surrounding hypermetabolism, a reported hallmark of ORJN, was found in less than 5%. Conclusions The predominant scintigraphic pattern of osteoradionecrosis includes increased bone mineralization phase in all patients. Central photopenia, reportedly a typical bone scan finding in bisphosphonate-induced osteonecrosis, was not characteristic for ORNJ. A differentiation of acute from chronic inflammatory processes was not possible.

Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines

ObjectivesHead and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines.MethodsFive different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot.ResultsIncubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination.ConclusionThis is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro-apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161.Clinical relevanceSMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy.

Cryopreservation of autologous bone grafts: an experimental study on a sheep animal model.

A sheep animal model was used to investigate the clinical behavior of autologous bone transplants after cryopreservation. The aim of the present study was to compare fresh, cryopreserved and deep-frozen bone transplants in terms of their osseointegration. We used a serum-free cryopreservation protocol with DMSO as cryoprotectant for the bone transplants, which were harvested from the iliac crest of the sheep. The bicortical iliac bone grafts were either cryopreserved or immediately frozen to –80°C for 4 weeks. Four, 8, 12 and 16 weeks after the autologous transplantation of the cryopreserved, fresh or deep-frozen bone transplants to the contralateral iliac crest, the animals were sacrificed and the bone specimens were evaluated clinically, by staining for hematoxylin/eosin and for tartrate-resistant acid phosphatase, by quantified computed tomography, immunohistochemistry (Ki67) and polychrome sequential labeling. The best results were obtained for the fresh specimens with 83% bone healing compared with 75% (cryopreserved bone) and 50% (deep frozen bone). All parameters indicate that bone formation and remodeling processes take place in fresh and cryopreserved transplants. The deep-frozen specimens displayed no fluorochrome uptake in the sequential labeling. These findings indicate that osseointegration of the fresh transplants was the most successful and that osteogenic effects in fresh and cryopreserved transplants are located in the surface area, whereas only the osteoconductive effects are important in the center of the transplants. Thus, cryopreservation is a useful method for the clinical routine because it keeps the osteogenic cells viable, making it superior to deep freezing of abundant bone.

Perception of children’s faces with unilateral coronal synostosis—an eye-tracking investigation

PurposePremature unilateral coronal craniosynostosis results in distinctive cranial and facial abnormalities of varying severity, including orbital dystopia and an abnormal head shape. As the face is affected, these children may encounter stigmatization. To avoid this scenario, many parents elect for their child to undergo surgical correction. Laypeople’s perception of children with either untreated or treated unilateral coronal craniosynostosis (UCS) has not yet been objectively evaluated.MethodsThis study introduces eye tracking as an objective instrument in order to evaluate the perception of 14 children with coronal synostosis, both pre- and postoperatively. Age-matched healthy children served as a control group. Using standardized photos, the involuntary eye movements and the fixations of 30 unaffected laypeople were evaluated.ResultsIn the untreated children, whose faces were characterized by striking orbital dystopia, the eyes drew more attention than those of the healthy children. The results of our study demonstrate that the operative correction of unilateral coronal synostosis results in the normalization of the asymmetry of the fronto-orbital region, whereas the C-shaped deformity of the midface, which is not addressed via surgery, subsequently attracts more attention.ConclusionEye tracking objectively evaluates both the perception of craniofacial abnormalities and the extent of the approximation of normality after surgical correction. We introduce eye tracking as an objective measurement tool for craniofacial abnormalities for the first time.