Current concepts in cleft care: A multicenter analysis.

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.

Dental status, dental treatment procedures and radiotherapy as risk factors for infected osteoradionecrosis (IORN) in patients with oral cancer - a comparison of two 10 years' observation periods.

OBJECTIVES: Dental status, dental treatment procedures and radiotherapy dosage as potential risk factors for an infected osteoradionecrosis (IORN) in patients with oral cancers: Retrospective evaluation of 204 patients treated in two observation periods of approximately ten years each. PATIENTS AND METHODS: In group A, 90 patients were treated in the years 1993-2003, in group B 114 patients in the years 1983-1992 (data in brackets). All patients had histopathologically proven squamous cell cancers, mainly UICC stages III and IV. 70% (85%, n.s.) had undergone surgery before radiotherapy. All patients were referred to the oral and maxillofacial surgeon for dental rehabilitation before further treatment. Radiotherapy was performed using a 3D-conformal technique with 4-6MV photons of a linear accelerator (Co-60 device up to 1987). The majority of patients were treated using conventional fractionation with total doses of 60-70 Gy in daily fractions of 2 Gy. Additionally, in group A, hyperfractionation was used applying a total dose of 72 Gy in fractions of 1.2 Gy twice daily (time interval > 6 hours). In group B, a similar schedule was used up to a total dose of 82.8 Gy (time interval 4-6 hours). 14 (0) patients had radiochemotherapy simultaneously. After therapy, the patients were seen regularly by the radiooncologist and - if necessary - by the oral and maxillofacial surgeon. The duration of follow-up was 3.64 years (5 years, p = 0.004). RESULTS: Before radiotherapy, the dental health status was very poor. On average, 21.5 (21.2, n.s.) teeth were missing. Further 2.04 teeth (2.33, n.s.) were carious, 1.4 (0.3, p = 0.002) destroyed. Extractions were necessary in 3.6 teeth (5.8, p = 0.008), conserving treatment in 0.4 (0.1, p = 0.008) teeth. After dental treatment, 6.30 (4.8, n.s.) teeth remained. IORN was diagnosed after conventionally fractionated radiotherapy in 15% (11%, n.s.), after hyperfractionation in 0% (34%, p = 0.01). CONCLUSION: Within more than 20 years there was no improvement in dental status of oral cancer patients. Extensive dental treatment procedures remained necessary. There was an impressive reduction of the IORN frequency in patients treated in a hyperfractionated manner probably resulting from a dose reduction and an extension of the interfraction time.

Scaling of Rényi entanglement entropies of the free fermi-gas ground state: a rigorous proof.

In a remarkable paper [Phys. Rev. Lett. 96, 100503 (2006)], Gioev and Klich conjectured an explicit formula for the leading asymptotic growth of the spatially bipartite von Neumann entanglement entropy of noninteracting fermions in multidimensional Euclidean space at zero temperature. Based on recent progress by one of us (A. V. S.) in semiclassical functional calculus for pseudodifferential operators with discontinuous symbols, we provide here a complete proof of that formula and of its generalization to Rényi entropies of all orders α>0. The special case α=1/2 is also known under the name logarithmic negativity and often considered to be a particularly useful quantification of entanglement. These formulas exhibiting a "logarithmically enhanced area law" have been used already in many publications.

H2rs: deducing evolutionary and functionally important residue positions by means of an entropy and similarity based analysis of multiple sequence alignments.

BACKGROUND: The identification of functionally important residue positions is an important task of computational biology. Methods of correlation analysis allow for the identification of pairs of residue positions, whose occupancy is mutually dependent due to constraints imposed by protein structure or function. A common measure assessing these dependencies is the mutual information, which is based on Shannon's information theory that utilizes probabilities only. Consequently, such approaches do not consider the similarity of residue pairs, which may degrade the algorithm's performance. One typical algorithm is H2r, which characterizes each individual residue position k by the conn(k)-value, which is the number of significantly correlated pairs it belongs to. RESULTS: To improve specificity of H2r, we developed a revised algorithm, named H2rs, which is based on the von Neumann entropy (vNE). To compute the corresponding mutual information, a matrix A is required, which assesses the similarity of residue pairs. We determined A by deducing substitution frequencies from contacting residue pairs observed in the homologs of 35 809 proteins, whose structure is known. In analogy to H2r, the enhanced algorithm computes a normalized conn(k)-value. Within the framework of H2rs, only statistically significant vNE values were considered. To decide on significance, the algorithm calculates a p-value by performing a randomization test for each individual pair of residue positions. The analysis of a large in silico testbed demonstrated that specificity and precision were higher for H2rs than for H2r and two other methods of correlation analysis. The gain in prediction quality is further confirmed by a detailed assessment of five well-studied enzymes. The outcome of H2rs and of a method that predicts contacting residue positions (PSICOV) overlapped only marginally. H2rs can be downloaded from http://www-bioinf.uni-regensburg.de. CONCLUSIONS: Considering substitution frequencies for residue pairs by means of the von Neumann entropy and a p-value improved the success rate in identifying important residue positions. The integration of proven statistical concepts and normalization allows for an easier comparison of results obtained with different proteins. Comparing the outcome of the local method H2rs and of the global method PSICOV indicates that such methods supplement each other and have different scopes of application.

Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation.

PURPOSE: Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. METHODS: A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients' general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. RESULTS: The patients' dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. CONCLUSION: The occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature.

Treatment results at 10, 15, and 18 years of age in patients with complete bilateral cleft lip and palate: an intercenter comparison.

Objective : The aim of this study was to investigate and compare the skeletal treatment outcome in patients aged 18 years with complete bilateral cleft lip and palate who received their complete treatment until early adulthood in two centers with different treatment protocols. Design : Twenty-two patients (13 from center 1, nine from center 2) with complete primary bilateral cleft lip alveolus and palate were included. Lateral cephalograms were studied at the ages of 10 (T(1)), 15 (T(2)), and 18 (T(3)) years. Sagittal, vertical, and dental parameters were measured and compared. Statistics included tests for normal distribution, a three-way analysis of variance, and bilateral t tests for associated and nonassociated random samples with the significance level p < .05. Results : Data from center 1 showed a significant decrease in ANB, WITs appraisal, and NL-NSL and an increase in Ui/NL. Data from center 2 showed a significant increase in SNB; a decrease in ANB, WITs appraisal, and ML-NSL; and an increase in Ui/NL. The intercenter comparison of means at the end of treatment (T(3)) revealed no significant differences for any parameter, despite few significant differences at T(1) and T(2). Conclusion : The different treatment concepts did not yield significant differences in treatment outcome at early adulthood. All final skeletal parameters were comparable to those of patients without a cleft. These results indicate treatment execution may be more important than the treatment protocol.

Removing biofilms from microstructured titanium ex vivo: a novel approach using atmospheric plasma technology.

The removal of biofilms from microstructured titanium used for dental implants is a still unresolved challenge. This experimental study investigated disinfection and removal of in situ formed biofilms from microstructured titanium using cold atmospheric plasma in combination with air/water spray. Titanium discs (roughness (Ra): 1.96 µm) were exposed to human oral cavities for 24 and 72 hours (n = 149 each) to produce biofilms. Biofilm thickness was determined using confocal laser scanning microscopy (n = 5 each). Plasma treatment of biofilms was carried out ex vivo using a microwave-driven pulsed plasma source working at temperatures from 39 to 43°C. Following plasma treatment, one group was air/water spray treated before re-treatment by second plasma pulses. Vital microorganisms on the titanium surfaces were identified by contact culture (Rodac agar plates). Biofilm presence and bacterial viability were quantified by fluorescence microscopy. Morphology of titanium surfaces and attached biofilms was visualized by scanning electron microscopy (SEM). Total protein amounts of biofilms were colorimetrically quantified. Untreated and air/water treated biofilms served as controls. Cold plasma treatment of native biofilms with a mean thickness of 19 µm (24 h) to 91 µm (72 h) covering the microstructure of the titanium surface caused inactivation of biofilm bacteria and significant reduction of protein amounts. Total removal of biofilms, however, required additional application of air/water spray, and a second series of plasma treatment. Importantly, the microstructure of the titanium discs was not altered by plasma treatment. The combination of atmospheric plasma and non-abrasive air/water spray is applicable for complete elimination of oral biofilms from microstructured titanium used for dental implants and may enable new routes for the therapy of periimplant disease.

[Implant-borne prosthesis for an edentulous maxilla with a large maxillectomy defect--a step-wise therapy concept]. / Implantatgetragene Versorgung eines ausgedehnten Resektionsdefektes der Maxilla. Ein mehrstufiges Therapiekonzept.

Due to the great variety of maxillectomy defects standardized restorative treatment protocols are rarely documented. For the practitioner it is from highest importance to consider the specific defect morphology and, even more important, the individual needs of affected patients. The presented case shows the planning and realization of the restoration of a maxilla with an extended resection defect following tumor surgery. Because the demanding patient remained edentulous after extraction of the residual teeth for periodontal reasons, an implant retained obturator prosthesis was inserted. Following interdisciplinary planning a treatment protocol with stepwise extraction, augmentation and implant insertion in the os zygomaticum as well as in the residual alveolar ridge was carried out, which make successive adjustment of the temporary obturator prosthesis possible. This procedure resulted in a long lasting treatment duration, but made also a sufficient temporary restoration during healing periods feasible. The definitive restoration was retained by a bar splinting four implants in the residual alveolar ridge and a special retentive anchoring abutment on two implants in the os zygomaticum.

Molar inclination in panoramic x-rays as an indicator for extraction decisions.

OBJECTIVE: Recommendations concerning the necessity of extraction therapy are often based upon clinical findings and panoramic x-rays. Since the success of this approach greatly depends on the individual examiner's clinical expertise, we believed it to be of interest to evaluate whether panoramic x-ray findings alone suffice for making the decision to extract. The aim of this study was to evaluate whether the need for extraction therapy can be verified by measuring the angulations between the first and second lower molars. MATERIAL AND METHODS: Orthopantomograms of 30 patients who underwent extraction of four premolars were examined prior to and after treatment. Initial study casts were also evaluated for any correlations between molar inclination and other examination parameters. Orthopantomograms of 30 patients who had experienced comprehensive orthodontic treatment without extraction served as age- and gender-matched controls. RESULTS: Contrary to expectation, the lower second molars showed a stronger mesial inclination before rather than after treatment, and the changes were highly significant. The controls also showed highly significant changes on the left side. The extraction and non-extraction groups did not differ significantly in terms of molar inclination at the beginning of treatment. Gender differences occurred in both groups, but only on one side. No other findings indicated gender differences in terms of molar inclination. CONCLUSION: Our data failed to prove a correlation between distally- inclined lower second molars in the panoramic x-ray and the indication of extraction therapy.

Pharmacokinetics of the photosensitizers aminolevulinic acid and aminolevulinic acid hexylester in oro-facial tumors embedded in the chorioallantois membrane of a hen's egg.

BACKGROUND: Oral squamous-cell carcinoma is a frequent form of cancer in the head and neck region. The survival rate is poor. Therapy success is highly dependent on the stage of cancer development at which diagnosis is made. The disease is mostly diagnosed at a late stage. Photodynamic diagnosis is a new tool for screening examinations. This technique calls for reliable photosensitizers, such as aminolevulinic acid (ALA) and aminolevulinic acid hexylester (h-ALA). ALA and h-ALA are the source material for the synthesis of protoporphyrin IX in tumor cells. Protoporphyrin IX has a high detection rate for tumor tissue within a reasonable period of time. METHODS: Tumor specimens were harvested from oral carcinomas and basaliomas of the face. The vital cells of the specimens and the human tumor cell line (CLS- 354) were cultured in a 90% RPMI and 10% fetal bovine serum medium. A constant number of 50,000 cells from each specimen and the cell line were transferred to an in vivo model on the hen's egg model. The grown specimens were tested for tumor fluorescence with ALA and h-ALA. The intensity of tumor fluorescence during the following 24 hours was measured spectroscopically as the degree of concentration of protoporphyrin IX within the cells. RESULTS: All tumors showed higher protoporphyrin IX enrichment and fluorescence, compared to healthy tissue. Using h-ALA, the peak concentration of protoporphyrin IX was achieved 20%-25% more quickly with 3- or 6-mM solutions than with ALA. The highest contrast between tumorous and healthy tissue achieved owing to fluorescence was 1:11 using h-ALA, compared to 1:5 using ALA with the peak concentrations of protoporphyrin IX. CONCLUSIONS: Using h-ALA, the peak concentration of protoporphyrin IX, compared to ALA, is achieved 20% percent more quickly and with twice as much contrast between tumorous and healthy tissue (1:11 compared and 1:5, respectively). This facilitates a faster, better discrimination between tumorous and healthy tissue.

Improvement of nutritive perfusion after free tissue transfer by local heat shock-priming-induced preservation of capillary flowmotion.

BACKGROUND: Capillary flowmotion protects pedicled flaps during critical perfusion conditions. However, free tissue transfer, causing ischemia-reperfusion and surgical trauma, have been shown to blunt these protective blood flow fluctuations. Because heat shock priming protects tissue after transfer, we herein studied whether heat shock protein expression is capable to preserve critical perfusion-induced capillary flowmotion in transferred composite flaps. METHODS: In Sprague Dawley rats (n = 16), osteomyocutaneous flaps were subjected to critical perfusion after harvest and 1 h and 4 h after free transfer. In eight animals additional heat shock priming was induced 24 h before flap harvest. Microcirculation including capillary flowmotion was analyzed using intravital fluorescence microscopy. RESULTS: After harvest, critical perfusion induced capillary flowmotion in skeletal muscle tissue of all flaps. By this, functional capillary density (FCD), an indicator of nutritive perfusion, was maintained not only in muscle but also in periosteum, subcutis, and skin. In contrast, 1 h after flap transfer muscle capillary flowmotion was completely abrogated, resulting in a significant decrease of FCD in all tissues. Heat shock-priming completely restored capillary flowmotion, and, by this, maintained tissue FCD. CONCLUSIONS: The loss of muscle capillary flowmotion after free tissue transfer-associated ischemia-reperfusion can be prevented by heat shock-priming. This may represent the mechanism of protection by local heat application.

Segment distraction to reduce a wide alveolar cleft before alveolar bone grafting.

OBJECTIVE: To demonstrate a method for reduction of wide alveolar clefts prior to bone grafting. This method aims to facilitate bone grafting and achieve adequate soft tissue coverage of the graft with attached gingiva. CASE REPORT: Treatment of a patient with bilateral cleft lip and palate with a severe alveolar defect on the left side is illustrated. Distraction osteogenesis was used to mesialize the left segment so that the alveolar cleft was reduced to a minimum. After a 10-week retention period, bone grafting of the reduced alveolar defect was successfully performed. After consolidation of the bone graft, the alveolar cleft was found to have an osseous closure with adequate soft tissue coverage. CONCLUSION: In patients with a wide alveolar cleft, soft tissue coverage with keratinized mucosa can be more readily assured by reducing the alveolar cleft by callus distraction to mesialize the lateral segment prior to bone grafting.

Protective skeletal muscle arteriolar vasomotion during critical perfusion conditions of osteomyocutaneous flaps is not mediated by nitric oxide and endothelins.

BACKGROUND: After flap surgery, vasomotion, defined as oscillation of the arteriolar diameter, may protect tissue during critical perfusion conditions. The mechanisms that regulate vasomotion are still unclear; therefore, we studied the incidence of vasomotion in peripheral tissue and whether nitric oxide or endothelins are involved in regulation of vasomotion. MATERIALS AND METHODS: In Sprague-Dawley rats, an osteomyocutaneous flap was prepared. To induce critical perfusion conditions, we reduced arterial blood flow supplying the flap to 0.15 ml/min. Seven animals received NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor, and six animals bosentan, an endothelin A/B receptor antagonist. Microcirculation of muscle, skin, subcutis and periosteum was assessed by intravital microscopy before and after drug application. RESULTS: In all animals, reduction of arterial blood supply induced arteriolar vasomotion in muscle (100%), but not in periosteum, subcutis and skin. Vasomotion was found to be affected by neither L-NAME (frequency 2.6+/-0.2 versus 2.4+/-0.2 cycles/min; amplitude 67+/-19 versus 55+/-20%; share of dilation period in vasomotion cycle 59+/-2 versus 58+/-3%) nor bosentan (1.8+/-0.1 versus 1.7+/-0.1 cycles/min; 60+/-10 versus 64+/-6%; 50+/-2 versus 53+/-1%). CONCLUSIONS: Our study indicates that during critical perfusion conditions, arteriolar vasomotion develops only in muscle, not in skin, subcutis and periosteum, and that nitric oxide and endothelins are not involved in the regulation of this protective vascular response.