Abstract Force-elongation responses of the human abdominal wall in the linea alba region were determined by tensile tests in which the linea alba was seen to exhibit a nonlinear elastic, anisotropic ...behavior as is frequently observed in soft biological tissues. In addition, the geometry of the abdominal wall was determined, based on MRI data. The geometry can be specified by principal radii of curvature in longitudinal of approximately 470 mm and in the transverse direction of about 200 mm. The determined radii agree with values found in other studies. Mechanical stresses, deformations and abdominal pressures for load cases above 6% elongation can be related using Laplace's formula and our constitutive and geometrical findings. Results from uni- and biaxial tensile tests can thus be compared using this model. Calculations confirm that abdominal pressures of approximately 20 kPa correspond to related biaxial forces of about 3.4 N/mm in the transverse and 1.5 N/mm in the longitudinal direction. Young's moduli can be calculated with respect to the uniaxial as well as the biaxial loading. At these physiological loadings, a compliance ratio of about 2:1 between the longitudinal and transversal directions is found. Young's moduli of about 50 kPa occur in transversal direction and of about 20 kPa in longitudinal direction at transverse and longitudinal strains both in the order of 6%. These findings coincide with results from other investigations in which the properties of the abdominal wall have been examined.
Despite the significance of tumour neoangiogenesis and the extensive knowledge on the molecular basis of blood vessel formation currently no quantitative data exist on the 3D microvascular ...architecture in human primary tumours and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events.
Abstract Background An ideal prosthetic mesh for incisional hernia repair should mimic the anisotropic compliance of the abdominal wall, and at lower loads should exhibit higher distensibility ...without impairment of safety at higher loads. This study evaluated the biomechanical properties of six meshes in a rabbit model. Methods New Zealand white rabbits were used for this study. Two meshes of the same brand (Ethicon Physiomesh™, Bard Composix® L/P, Gore Dualmesh® , Bard Sepramesh® , Ethicon Proceed® or Parietex™ Composite) were implanted into each animal for assessment of intra-abdominal hernia repair, with a total of ten meshes per group. Twelve weeks after implantation, the abdominal walls with ingrown meshes were harvested and examined biomechanically with a plunger test. The mesh–tissue compliance was evaluated by the forces exerted at given displacements and also described through a simple mathematical approximation. Abdominal wall samples were collected for histopathology, cell turnover and morphometry. Results No mesh-related complications were seen. The adhesion score was significantly higher in Bard Composix® L/P and Ethicon Proceed® meshes. Significant shrinkage was seen in Gore Dualmesh® and Parietex™ Composite meshes. Physiomesh™ exhibited the highest compliance during plunger testing, characterized by lower, more physiological reaction forces against tissue displacement than the competitor meshes. In contrast, the safety modulus was comparable in all groups. Histology showed less collagen and less foreign body reaction in the Physiomesh™ samples contributing to patient's comfort. Conclusion In terms of safety, this study showed no superiority of any single mesh. The comfort modulus however differed, being lowest in the newly developed Physiomesh™.
Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that ...intimal vessels occur in advanced lesions of apolipoprotein E-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice.
ApoE -/- mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg. kg-1. d-1; group 2, fumagillin analogue TNP-470, 30 mg/kg every other day; and group 3, control animals that received a similar volume of buffer. Average cholesterol levels were similar in all groups. Plaque areas were quantified at the aortic origin. Median plaque area before treatment was 0.250 mm2 (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321 (0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during the treatment period by 85% and 70%. Intimal smooth muscle cell contents of plaques from control and treated mice were similar.
Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.
Background and Objective
Recently, porcine acellular dermal matrix (PADM) has been proposed as a possible alternative to autogenous grafts in periodontal plastic surgery. The aim of the present study ...was to investigate the in vitro responses of four different oral cell lines cultured on a novel PADM. Furthermore, tissue reaction to PADM was evaluated histologically after subcutaneous implantation in mice.
Material and Methods
Human gingival fibroblasts (HGF), human osteoblast‐like cells, human umbilical vein endothelial cells and human oral keratinocytes (HOK) were cultured and transferred on to the PADM. A tissue culture polystyrene surface served as the control. The viability of all tested cell lines on PADM was measured by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide colorimetric assay and PrestoBlue® reagent. The ToxiLight® assay was performed to analyze the effect of PADM on adenylate kinase release. PADM was implanted into nude mice subcutaneously and subjected to histological analysis after 21 d.
Results
Using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide colorimetric assays, all tested cell lines cultured on PADM demonstrated a significant increase of viability compared to the control group (each p < 0.001) with the exception of HGF and HOK after 3 d (each p > 0.05). According to the PrestoBlue® analysis, all cell lines demonstrated a significant increase of viability compared to the control group at the particular points of measurement after 18 h (HGF p < 0.01; human osteoblast‐like cells, human umbilical vein endothelial cells, HOK each p < 0.001). No significant cytotoxic effects of PADM on the tested cell lines could be observed, as assessed by changes in adenylate kinase release. Subcutaneous implantation of PADM into nude mice demonstrated good integration with surrounding tissues and significant revascularization of its collagen structure.
Conclusion
Overall, the results suggest that PADM is a promising substitute for autogenous soft tissue grafts in periodontal surgery.
Summary
A variety of diseases can lead to loss of lung tissue. Currently, this can be treated only symptomatically. In mice, a complete compensatory lung growth within 21 days after resection of the ...left lung can be observed. Understanding and transferring this concept of compensatory lung growth to humans would greatly improve therapeutic options. Lung growth is always accompanied by a process called angiogenesis forming new capillary blood vessels from preexisting ones. Among the processes during lung growth, the formation of transluminal tissue pillars within the capillary vessels (intussusceptive pillars) is observed. Therefore, pillars can be understood as an indicator for active angiogenesis and microvascular remodelling. Thus, their detection is very valuable when aiming at characterization of compensatory lung growth. In a vascular corrosion cast, these pillars appear as small holes that pierce the vessels. So far, pillars were detected visually only based on 2D images. Our approach relies on high‐resolution synchrotron microcomputed tomographic images. With a voxel size of 370 nm we exploit the spatial information provided by this imaging technique and present the first algorithm to semiautomatically detect intussusceptive pillars. An at least semiautomatic detection is essential in lung research, as manual pillar detection is not feasible due to the complexity and size of the 3D structure. Using our algorithm, several thousands of pillars can be detected and subsequently analysed, e.g. regarding their spatial arrangement, size and shape with an acceptable amount of human interaction. In this paper, we apply our novel pillar detection algorithm to compute pillar densities of different specimens. These are prepared such that they show different growing states. Comparing the corresponding pillar densities allows to investigate lung growth over time.
Lay description
A variety of diseases can lead to loss of lung tissue. For example, bronchial carcinoma require operative removal of the diseased side of the lung. Currently, the resulting loss in lung capacity can be treated only symptomatically. This is different for some other species. In mice, for instance, the lung completely regains its original capacity within 21 days after resection of the left lung. Understanding and transferring this concept of compensatory lung growth to humans would greatly improve therapeutic options.
Lung growth is always accompanied by a process called angiogenesis, i.e., the forming of new capillary blood vessels from preexisting ones. During this processes, the formation of torus‐shaped holes within the capillary vessels (“intussusceptive pillars”) is observed. Therefore, pillars can be understood as an indicator for active angiogenesis and their detection is very valuable when aiming at characterization of compensatory lung growth.
So far, intussusceptive pillars had been detected visually based on 2D images, only. That approach yields only limited information about the spatial distribution of these growth indicators within the lung, and is therefore insufficient for a full understanding of the underlying growth processes. Therefore, our approach relies on high resolution micro computed synchrotron tomographic images. This yields three dimensional information with significantly higher contrast. In this paper, we present the first algorithm to detect intussusceptive pillars in 3D images. Taking the third dimension into account enables us to quantify pillars more precisely. Furthermore, our detection algorithm works automatically. This is essential in lung research, as manual pillar detection is not feasible due to the complexity and size of the 3D structure.
Using our algorithm, several thousands of pillars can be detected and analyzed regarding their spatial arrangement, size and shape. From this, the degree of active angiogenesis along with compensatory lung growth can be measured.
Objectives
Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is an adverse side effect of long-term bisphosphonate treatment. One theory of BP-ONJ etiology suggests a negative influence of ...these agents on angiogenesis and vascularization. This in vivo study analyzed the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay.
Materials and methods
Matrigel plugs were implanted into fifty 6–8-week-old female nude mice. Ten animals each were treated either with clodronate, ibandronate, pamidronate, zoledronate, or carrier solution as controls. The microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in Matrigel plugs were analyzed after 21 days of treatment by immunohistochemistry and exemplary 3D microvascular corrosion castings.
Results
All bisphosphonates induced a statistically significant decrease of MVD (
p
each <0.001), whereby the nitrogen-containing bisphosphonates (N-BPs) demonstrated a clearly stronger effect than non-nitrogen-containing bisphosphonates (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm
2
). Referring to MVA, similar results could be detected. MVS was significantly increased especially by ibandronate (103 %) compared to control group (
p
< 0.001). Scanning electron microscope scans of the corrosion castings confirmed these results.
Conclusions
The stronger influence on MVD by N-BPs compared to the NN-BP clodronate may explain for the lack of BP-ONJ after treatment with NN-BPs.
Clinical relevance
Ibandronate induced a strong increase of MVS. In combination with the reduced MVD, this could result only in a fractional reduced perfusion which might be an explanation for the lower occurrence of BP-ONJ in patients receiving ibandronate compared to patients receiving pamidronate or zoledronate.
Abstract In modern motor vehicles with automatic power windows, a potential hazard exists for jam events of fingers between the window glass and seal entry. This study determined entrapment forces ...acting on adult fingers at the subjective maximum pain threshold during entrapment in such windows. The length and the girth of the proximal and distal interphalangeal joints of the triphalangeal fingers of the right hands of 109 participants (60 men, 49 women) were measured; the diameter was calculated from girth, which was assumed to be circular. The automatic power window system of a motor vehicle side door was changed to a mechanical system. During entrapment the force distributed across the four proximal interphalangeal joints (PIPs), and separately on the proximal interphalangeal (iPIP) and then the distal interphalangeal (iDIP) joints of the index finger was measured using a customized force sensor. The maximum bearable entrapment force was 97.2±51.8 N for the PIPs, 43.4±19.9 N for the iPIP, and 36.9±17.8 N for the iDIP. The positive correlation between finger diameter and maximum entrapment force was significant. Particularly with regard to the risk to children's fingers, the 100 N statutory boundary value for closing force of electronic power windows should be reduced.
In order to perform effective translational research for cancer therapy, we need to employ pre-clinical models which reflect the clinical situation. The purpose of this study was to quantitatively ...compare the vascular architecture of human colorectal cancer and experimental tumour models to determine the suitability of animal models for vascular studies and antivascular therapy.
In this study we investigated the three-dimensional properties of colonic tumour vasculature in both human clinical tissues (normal mucosa control n=20, carcinoma n=20 and adenoma n=6) and murine colorectal xenografts (LS147T n=6 and SW1222 n=6). Scanning Electron Microscope Stereoimaging (SEM) and X-ray Micro-Computed Tomography (Micro-CT) methods were employed for 3D analyses of the vascular corrosion casts from these tissues.
Morphological measurements showed that there were significant differences in the underlying morphology in the different tissues. Of the studied xenografts, LS147T is more consistently similar to the vascular architecture of the human carcinoma than SW1222. The only reversal of this is for the inter-vessel distance.
While SEM stereoimaging provided better surface detailed resolution of the corrosion casts, it was complimented by the fully 3D micro-CT method. Comparison made between the xenografts and clinical tumours showed that the LS147T xenografts shared many similarities with the clinical tumour vasculature. This study provides insight into how to select the most suitable pre-clinical models for translational studies of clinical cancer therapy.
OBJECTIVE: Our purpose was to improve the therapeutic index of radical hysterectomy by extending the resection of parametrial tissue without further impairing pelvic autonomic nerve functions.
STUDY ...DESIGN: We studied the topographic anatomy of the parametrial tissue with high-resolution magnetic resonance imaging and by dissection of fresh human cadavers. We then performed a clinical feasibility study of the liposuction-assisted nerve-sparing extended radical hysterectomy.
RESULTS: Magnetic resonance imaging demonstrated that the perispinous adipose tissue is retained after type III radical hysterectomy and is a frequent site of tumor recurrence. The perispinous adipose tissue contains the pelvic plexus, the pelvic splanchnic nerves, small blood vessels, and lymphatic tissue. We developed the liposuction-assisted nerve-sparing extended radical hysterectomy and applied it to seven consecutive patients with cervical or vaginal cancer. No intraoperative or postoperative complications occurred. Postoperative magnetic resonance imaging assured us that perispinous adipose tissue was cleared in all cases. A metastatic lymph node was found in the perispinous adipose tissue removed by liposuction from one patient. Suprapubic cystostomies could be removed after a median period of 12 days.
CONCLUSION: The nerve-sparing removal of perispinous adipose tissue by liposuction is a feasible addition to wide en bloc parametrectomy in anatomically defined planes. (Am J Obstet Gynecol 1998;178:971-6.)