A modular software concept for individual numerical simulation (FEM) of the human mandible]

A new modular software concept for individual numerical simulation of the human mandible using the finite element method (FEM) is presented. The main task is an individual analysis of regional stress and stress-compatibility on the basis of computed tomographic data in individual patients. Simulation should, however, also be possible in parallel with biomechanical experiments, or for further research projects. For this purpose, rapid and uncomplicated generation of the FEM model, easy modification of input data, and short computation times are required. Practical use in the clinical setting makes appreciable additional demands on the individual software components.     

Successful human long‐term application of in situ bone tissue engineering

Tissue Engineering (TE) and Regenerative Medicine (RM) have gained much popularity because of the tremendous prospects for the care of patients with tissue and organ defects. To overcome the common problem of donor‐site morbidity of standard autologous bone grafts, we successfully combined tissue engineering techniques for the first time with the arteriovenous loop model to generate vascularized large bone grafts. We present two cases of large bone defects after debridement of an osteomyelitis. One of the defects was localized in the radius and one in the tibia. For osseus reconstruction, arteriovenous loops were created as vascular axis, which were placed in the bony defects. In case 1, the bone generation was achieved using cancellous bone from the iliac crest and fibrin glue and in case 2 using a clinically approved β‐tricalciumphosphate/hydroxyapatite (HA), fibrin glue and directly auto‐transplanted bone marrow aspirate from the iliac crest. The following post‐operative courses were uneventful. The final examinations took place after 36 and 72 months after the initial operations. Computer tomogrphy (CT), membrane resonance imaging (MRI) and doppler ultrasound revealed patent arterio‐venous (AV) loops in the bone grafts as well as completely healed bone defects. The patients were pain‐free with normal ranges of motion. This is the first study demonstrating successfully axially vascularized in situ tissue engineered bone generation in large bone defects in a clinical scenario using the arteriovenous loop model without creation of a significant donor‐site defect utilizing TE and RM techniques in human patients with long‐term stability.     

Dynamics of Correlated Genetic Systems. V. Rates of Decay of Linkage Disequilibria in Experimental Populations of DROSOPHILA MELANOGASTER

The dynamic behavior of four-locus gametic frequency distributions was studied in five replicate cage populations of Drosophila melanogaster for up to 50 generations. The joint frequency distributions were resolved into gene frequencies and various disequilibrium measures. In addition, F statistics for marginal single-locus genotypic frequency distributions were followed through time. The gene frequency, disequilibrium and F statistics were obtained for four chromosome 3 enzyme marker loci [isocitrate dehydrogenase (3–27.1), esterase-6 (3–36.8), phosphoglucomutase (3–43.4) and esterase-C (3–49.0)]. The initial structure of the experimental populations featured random mating proportions, and two complementary gametic types with respect to the marker loci, thus assuring complete pairwise linkage disequilibrium among the markers.——The experimental results indicate: (1) the between-replicate variance in gene frequency varied substantially among loci, with isocitrate dehydrogenase showing the greatest between-replicate variance, and esterase-C the least. (2) The F statistics initially were strongly negative but decayed to the neighborhood of zero for all marker loci except esterase-C. The rate at which the F statistics approached zero varied among the marker loci, indicating substantial differences in the distribution of selective effects along the chromosome. The centromeric region, marked by esterase-C, shows the strongest selective effects. (3) The rate of decay of linkage disequilibrium was much faster than expected for pairs of neutral loci, averaging 1.82 times the neutral rate over all replicates and pairs of loci. This acceleration, which was observed for all six pairwise combinations of loci, was interpreted as resulting from the interaction between selection and recombination. Our experimental results are consistent with many investigations of linkage disequilibrium in natural populations of Drosophila melanogaster that show little or no disequilibrium among enzyme loci. (4) A fortuitous contamination of two cages revealed an apparent regulatory interaction between the migrant and nonmigrant chromosomes at the esterase-C locus. The migrant chromosomes were very rapidly absorbed into the recipient populations, despite this interaction. This result suggests that the dynamics of migration in populations may be phenomenologically richer than anticipated by simple theory.     

T17b murine embryonal endothelial progenitor cells can be induced towards both proliferation and differentiation in a fibrin matrix

Endothelial progenitor cells (EPC) may enhance blood vessel formation in a variety of clinical settings such as ischaemia and tumour angiogenesis as well as in tissue-engineered matrices. In the present study, we cultured a murine endothelial progenitor cell line, T17b, in vitro in cell culture as well as in an FDA-approved fibrin matrix and investigated cell proliferation, differentiation and secretion patterns of the angiogenic growth factor VEGF under hypoxia and differentiation. We show that T17b EPC remain viable for at least 8 days in the fibrin matrix where they proliferate and form clusters including lumen-like structures. Proliferation in fibrin clots overlayed with basal medium (BM) was confirmed morphologically and immunohistochemically by positive Ki67 staining, indicating mitotic activity. Significant cell proliferation and Ki-67 expression were absent when cells were incubated with dibutyryl-cAMP and retinoic acid (RA). Incubation with dibutyryl-cAMP and RA stimulated the expression of the EPC differentiation markers von Willebrand Factor (vWF) and VEGF receptor 2 (VEGFR-2), indicating successful differentiation in the fibrin clot. EPC differentiation induced by dibutyryl-cAMP and RA was confirmed in 2-D chamber slide cultures by positive vWF immunostaining, which was absent in BM controls. EPC chamber slides also displayed positive vWF staining when exposed to hypoxia under BM conditions, indicating EPC activation and differentiation could also be induced by hypoxia. Taken together, T17b EPC secrete increased levels of VEGF when submitted to either hypoxia or differentiation and can be differentiated into mature endothelial cells not only in cell and matrigel cultures but also in a fibrin matrix that is FDA approved for clinical application.     

The rectus abdominis free flap as an emergency procedure in extensive upper extremity soft-tissue defects

Stable wound coverage after extensive soft-tissue loss of the upper extremity remains a difficult problem in the management of large defects of the upper limb. To prevent further tissue loss owing to infection or inadequate cover when important structures such as vessels, tendons, nerves, joints, and bones are exposed, various free flaps have been introduced into the therapeutic armamentarium of acute plastic surgical management options. Emergency or delayed early reconstruction has been proposed to prevent chronic infection and further tissue loss. We report a series of 12 emergency and delayed early reconstructions of the forearm, wrist, carpus, metacarpus, and hand using the free rectus abdominis muscle flap with split-skin coverage, demonstrating the versatility of this flap within this special context. Emergency free rectus muscle flap transfer is safe, technically easy, and expandable.     

Numerical simulation (FEM) of the human mandible: validation of the function of the masticatory muscles]

The article describes part of a research project aiming to develop a new modular software tool for the individual dynamic numerical simulation of the human mandible using the finite element method (FEM). Its planned use in the clinical setting makes it very important to validate the results of the simulations. Here, the function of the masticatory muscles is to be tested. On the basis of biomechanical data from the literature, standard movements, such as closing the mouth, forward movement, lateral movement or backward movement, were dynamically simulated. Apart from muscle activity, the movements of the mandible are defined by the temporomandibular joint. At present, translating the condylar dynamics to the simulation still poses problems. For this reason, therefore, simulations of the two extreme cases "fixed" and "force-free" condyles are compared. While in the case of fixed condyles, some of the movements could be reproduced either not at all or only weakly, in the case of force-free condyles, all standard movements were reproduced qualitatively, albeit without the guiding effect of the joint capsule or the articular disc.     

Insulin resistance in adolescents with Down syndrome: a cross-sectional study

Background

The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS) than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model Assessment) method, in DS adolescents, describing it according to the sex, body mass index (BMI) and pubertal development.

Methods

15 adolescents with DS (8 males and 7 females) were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN), weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score.

Results

Five patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II – IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively.

Conclusion

The obese and overweight, female and adult patients showed the highest values of HOMA and insulin.