Induction of periimplantitis in dental implants.

Development, progression, and therapy of periimplantitis are nonresolved emerging problems. The aim of this pilot study was to establish a model for periimplantitis in mice to have a base for tests with immune-deficient knockout organisms to improve the knowledge about development and progression of periimplantitis and to develop further therapeutic options.In 8 mice, titanium implants were inserted in the median of the palate. Four of these implants had ligatures (periimplantitis group). After 2 weeks, the animals received a special diet enriched with sugar and flavor. After 9 weeks, micro-computed tomography (micro-CT) examinations to evaluate the periimplant tissue and histologies were performed.Dental implant insertions within the oral cavity are possible in living mice. Implants with ligatures showed significantly larger periimplant bone defects than controls. The radiologic findings were confirmed by histology. At the end of the observation period, the portion of implants lost was higher in the ligature group.This is the first publication to describe the insertion of dental implants in living mice. In addition, it is the first time that periimplant infection could be induced in that species. This model will pave the way to study knockout mice with reduced or even enhanced resistance to periimplantitis.

Evaluation of ultra-low dose CT in the diagnosis of pediatric-like fractures using an experimental animal study.

OBJECTIVE: The aim of this prospective study was to evaluate the performance of ultra-low dose CT for the diagnosis of pediatric-like fractures and ascertain the lowest dose level sufficient for diagnostics. MATERIALS AND METHODS: Fifty-one bones of young pig cadavers were artificially fractured and subsequently examined by using a 64 multi-detector CT with 36 various dose levels down to a dose comparable with that of X-rays. Two pediatric radiologists analysed the CT scans according to the presence or absence of a fracture, determination of the fracture type and the displacement as well as the diagnostic certainty. For each dose protocol, a success rate for the correct determination of the above-mentioned CT analyses was calculated. A success rate of at least 95% was considered sufficient for diagnostics. RESULTS: All but the lowest dose levels were sufficient to identify the fracture. Only the two lowest dose levels were insufficient to detect the fracture type. All dose levels were adequate for the identification of the displacement. The lowest dose level sufficient for diagnostics was 120 kVp, 11 mAs, and pitch 1.5, with a CTDIvol of 10% of a standard dose and an effective dose three times as large as that of X-rays. CONCLUSION: Ultra-low dose CT provides the feasibility of a significant dose reduction, still allowing sufficient diagnostics of pediatric-like fractures.

Prospective, randomized single-center trial to compare cryoplasty versus conventional angioplasty in the popliteal artery: midterm results of the COLD study.

PURPOSE: To evaluate safety and efficacy of cryoplasty versus conventional angioplasty for focal popliteal arterial occlusive disease. MATERIALS AND METHODS: Patients with focal atherosclerotic stenoses and occlusions of the popliteal artery were randomized to cryoplasty or conventional angioplasty as the initial treatment strategy. The primary objective was target lesion patency. The secondary endpoint was treatment success without the need for stents. Duplex ultrasonography was performed at 3, 6, 9, and 15 months. RESULTS: Eighty-six patients (mean age, 72 years; age range, 50-94 years) were enrolled in this study. Forty patients were randomized to cryoplasty and 46 to conventional angioplasty. Demographics, risk factors, clinical stage of disease, and lesion details were comparable. On intention-to-treat basis, initial success was 35% for cryoplasty versus 54% for conventional angioplasty (P = .02). The rate of grade C dissection was 35% after cryoplasty and 26% after conventional angioplasty (P = .4). Optional long-term percutaneous transluminal angioplasty (PTA) was performed in 58% of cryoplasty patients. The rate of stent placement for dissection and/or residual stenosis was 30% after cryoplasty (including long-term dilation) and 39% after conventional angioplasty (P = .34). The mean (+/-standard deviation) target lesion patency at 9 months was 79.3% +/- 7.5 for cryoplasty and 66.7% +/-8.1 for conventional angioplasty; however, the results are not significant (P = .14). CONCLUSIONS: Cryoplasty of the popliteal artery alone showed a lower anatomic success when compared with conventional angioplasty. Combined with optional long-term PTA, however, stent placement was not needed more often. There was a trend toward higher patency after cryoplasty, but differences were not statistically significant and results of long-term follow-up have to be awaited.

CT fluoroscopy-guided lung biopsy with novel steerable biopsy canula: ex-vivo evaluation in ventilated porcine lung explants.

The purpose was to evaluate ex-vivo a prototype of a novel biopsy canula under CT fluoroscopy-guidance in ventilated porcine lung explants in respiratory motion simulations. Using an established chest phantom for porcine lung explants, n = 24 artificial lesions consisting of a fat-wax-Lipiodol mixture (approx. 70HU) were placed adjacent to sensible structures such as aorta, pericardium, diaphragm, bronchus and pulmonary artery. A piston pump connected to a reservoir beneath a flexible silicone reconstruction of a diaphragm simulated respiratory motion by rhythmic inflation and deflation of 1.5 L water. As biopsy device an 18-gauge prototype biopsy canula with a lancet-like, helically bended cutting edge was used. The artificial lesions were punctured under CT fluoroscopy-guidance (SOMATOM Sensation 64, Siemens, Erlangen, Germany; 30mAs/120 kV/5 mm slice thickness) implementing a dedicated protocol for CT fluoroscopy-guided lung biopsy. The mean-diameter of the artificial lesions was 8.3 +/- 2.6 mm, and the mean-distance of the phantom wall to the lesions was 54.1 +/- 13.5 mm. The mean-displacement of the lesions by respiratory motion was 14.1 +/- 4.0 mm. The mean-duration of CT fluoroscopy was 9.6 +/- 5.1 s. On a 4-point scale (1 = central; 2 = peripheral; 3 = marginal; 4 = off target), the mean-targeted precision was 1.9 +/- 0.9. No misplacement of the biopsy canula affecting adjacent structures could be detected. The novel steerable biopsy canula proved to be efficient in the ex-vivo set-up. The chest phantom enabling respiratory motion and the steerable biopsy canula offer a feasible ex-vivo system for evaluating and training CT fluoroscopy-guided lung biopsy adapted to respiratory motion.

Endocultivation: does delayed application of BMP improve intramuscular heterotopic bone formation?

INTRODUCTION: The time point of Bone morphogenetic protein (BMP) delivery on matrices in vivo may play an important role. Delayed application could be advantageous as this would allow soft tissue (ST) ingrowth and vascularisation of scaffolds prior to BMP-loading. The aim of this study was to compare the application of BMP injected simultaneously during matrix implantation with delayed application four weeks after matrix implantation for endocultivation in a rat model. MATERIAL AND METHODS: Bovine hydroxyapatite blocks were placed in pouches in the Musculus latissimus dorsi in 6 Lewis rats unilaterally to allow for soft tissue ingrowth. Four weeks later, a second block was inserted on the contralateral side of each rat. At that time point, 100microg rhBMP-2 in 2ml sodium chloride was injected on both sides to induce bone formation. For eight weeks, bone regeneration was monitored by computed tomography (CT) and fluorescent labelling. RESULTS: The simultaneous and delayed BMP application groups were significantly different (p=0.01). Slightly lower bone densities were seen for the delayed BMP application with a mean of 588 Hounsfield Units (HU) (standard deviation (SD) 30HU). Simultaneous BMP application revealed slightly higher densities with a mean of 633HU (SD 30HU). The largest differences were observed when comparing bone density directly after implantation or at the end of the observation period (p<0.0001). CONCLUSION: Bone density was slightly lower in the case of delayed application of BMP-2. The increase of bone density after application of BMP-2 was similar for both groups. Thus, delayed application of BMP had no advantageous effect in this particular study design. Further studies are needed to explore if varying delays, different material designs or special BMP application devices may alter these results.

Endocultivation: 3D printed customized porous scaffolds for heterotopic bone induction.

The aim of this study was to evaluate the ability of computer assisted designed (CAD) synthetic hydroxyapatite and tricalciumphosphate blocks to serve as precise scaffolds for intramuscular bone induction in a rat model. A central channel to allow for vessel pedicle or nerve integration was added. Natural bovine hydroxyapatite blocks served as controls to evaluate and compare biocompatibility of the new matrices. Individually designed 3D-printed rounded and porous hydroxyapatite (HA) and tricalcium phosphate (TCP) blocks were placed in pouches in the Musculus latissimus dorsi in 12 Lewis rats bilaterally. Bovine hydroxyapatite blocks with and without a central channel served as controls. Simultaneously, 200 microg rhBMP-2 in 1 ml sodium chloride was injected on both sides. For 8 weeks, bone generation was monitored by computer tomography and fluorescence labeling. The increase rates of bone density in CT examinations were higher in the HA groups (184-220 HU 8 weeks after implantation) compared to the TCP group (18 HU; p<0.0001). Microradiography and fluorescence microscopy 8 weeks after implantation showed new bone formation for all materials tested. For all scaffolds, toluidine staining revealed vital bone directly on the scaffold materials but also in the gaps between. It can be concluded from our data that the specially shaped hydroxyapatite and tricalcium phosphate blocks tested against the bovine hydroxyapatite blocks showed good biocompatibility and osteoinductivity in vivo. Further studies should explore if the stability of the individually designed blocks is sufficient to cultivate larger replacements without an external matrix for support.

Total percutaneous endovascular aneurysm repair with the dual 6-F Perclose-AT preclosing technique: a case-control study.

PURPOSE: To determine the safety and efficacy of total percutaneous access closure for endovascular aortic aneurysm repair with a suture-mediated preclosing technique. MATERIALS AND METHODS: One hundred thirty-two femoral access sites in 70 patients who underwent endovascular aortic aneurysm repair were closed percutaneously with off-label use of two F-6 Perclose AT devices preapplied at a 90 degrees angle. Femoral access sizes ranged from 12 to 24 F. Technical success, complications, and procedure and access closure times were evaluated. Follow-up with computed tomography and/or magnetic resonance imaging was scheduled at 1-4 days and 3, 6, and 12 months and used to obtain groin hematoma and scar severity scores (grades 1-3). Data were compared with those from a cohort of 67 patients who underwent endovascular aortic aneurysm repair with surgical femoral cutdown. RESULTS: Technical success was achieved with the preclosing technique in 127 of the 132 arteries (96.2%). Two to four closure devices were used per groin. Five technical failures were managed intraoperatively with surgical suture. There was no access-related mortality and no late groin complications. The mean procedure duration was 91 minutes +/- 32, and the mean access closure time was 12 minutes +/- 9. For surgical management, the mean procedure time was 153 minutes +/- 112 (P < .05), and the mean closure time was 12 minutes +/- 13 (not statistically significant). Hematoma severity score at 1-4 days was 1.8 for total percutaneous endovascular aneurysm repair and 2.1 for surgical closure. Scar severity scores at 3, 6, and 12 months were 1.1, 1.0, and 1.0 for total percutaneous endovascular aneurysm repair and 2.4, 2.4, and 2.3 for surgical management, respectively. CONCLUSIONS: Total percutaneous endovascular aneurysm repair with a dual 6-F-Perclose preclosing technique is safe and effective. Compared with femoral cutdown, there are fewer late groin complications and scar tissue formation is less severe.

Reduction of cerebral embolization in carotid angioplasty: an in-vitro experiment comparing 2 cerebral protection devices.

PURPOSE: To evaluate the efficiency of 2 distal filtration devices designed for cerebral protection during carotid angioplasty in an in-vitro bench-top model. METHODS: After positioning the respective protection devices (RX Accunet and DynaCap) 5 cm distal to the bifurcation, embolization from carotid angioplasty was simulated by injecting polyvinyl alcohol particles in groups of small (150 to 250-microm diameter, approximately 500 particles), medium (250 to 355-microm diameter, approximately 200 particles), and large (700 to 1000-microm diameter, approximately 80 particles). Five milligrams of each group were injected separately into the internal carotid artery (ICA) model proximal to the protection filters. Particles passing the protection devices were caught in 100-microm filters and weighed. RESULTS: For small particles, the amount in the effluent of the ICA was 0.34+/-0.12 mg (6.8%) for the RX Accunet and 0.51+/-0.16 mg (11.2%) for the Occam DynaCap (p<0.05). For the other particle sizes, there was no statistical difference between the filters (p>0.05). CONCLUSION: In all test runs, neither of the tested devices prevented embolization completely, with approximately 3% to 6% of particles penetrating. For small particles, the lowest amount of particles passing the protection device was achieved using the RX Accunet system.

4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system.

PURPOSE: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT). METHODS AND MATERIALS: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility. RESULTS: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16). CONCLUSIONS: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

Standardized quantification of pulmonary fibrosis in histological samples.

The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment. Based on the knowledge that this procedure is not standardized in animals and results are highly variable, we hypothesized that modification of this method may improve quantification of lung fibrosis in small animals. To prove our hypothesis, we evaluated pulmonary fibrosis in Lewis rats induced by a single intratracheal injection of 0.3 mg/kg body weight bleomycin (n = 13) compared with the same amount of saline in a control group (n = 4). We modified the Ashcroft scale by precisely defining the assignment of grades from 0 to 8 for the increasing extent of fibrosis in lung histological samples. Thirty-two observers were randomly assigned to evaluate 108 photographs of slides using either the Ashcroft scale or the modified scale. Consistent with our hypothesis, there was a significant reduction in the variability of standard deviations with the modified scale compared with the Ashcroft scale (mean of variability 0.25 versus 0.62, P < 0.0001). Applying the kappa index, the Ashcroft scale showed only a fair to moderate agreement (0.23-0.59) between the observers and a low intra-observer agreement (0.51-0.74) in contrast to the modified scale, which demonstrated a moderate to good agreement between the observers (0.65-0.93, P < 0.0001) and a high intra-observer agreement (0.87-0.91, P < 0.05). To test the modified scale in vivo, we compared both scales with the results of computed tomography (CT) of the lungs obtained from the same mice. In agreement, the modified scale demonstrated a better correlation to CT scans (R = 0.58) compared with the Ashcroft scale (R = 0.33). In summary, quantification of lung fibrosis in histological lung sections using the modified scale is reliable and reproducible.

Retrospective study of rapid-exchange monorail versus over-the-wire technique for femoropopliteal angioplasty.

PURPOSE: The purpose of this study was to compare procedural outcome of rapid-exchange (RX) monorail versus conventional over-the-wire (OTW) technique for femoropopliteal angioplasty. MATERIALS AND METHODS: Demographic data, procedure details, angioplasty success, and complications of 328 consecutive percutaneous transluminal angioplasties (PTAs) were collected from a prospective database and retrospectively analyzed. Procedure details included duration of fluoroscopy, area-dose product, amount of contrast agent, sheath sizes, access route, length of stenosis, presence of total occlusion, technical and anatomical success (residual stenosis < 30% in the absence of complications), need for bail-out stenting, and periprocedural complications. The RX technique alone was used in 102 of 328 cases (31%); the OTW technique, in 226 of 328 of cases (68%). RESULTS: Technical success was 98% for the RX versus 95.4% for the OTW technique (p = 0.2). A significantly greater number of stents had to be implanted due to angioplasty failure when the OTW technique was used (RX, 5.9%; OTW, 13.7%; p = 0.04). There were no significant differences in fluoroscopy time, dose-area product, or amount of contrast medium used. The RX system facilitated the use of smaller sheath sizes (5 Fr = 38% and 6 Fr = 59% for RX versus 5 Fr = 16.8% and > or = 6 Fr = 82.5% for OTW) but showed only a tendency toward lower overall complication rates (16.6% [17/102] in the RX group versus 19.9% [45/226] in the OTW group; p = 0.09). There was no effect on length of hospitalization. RX monorail systems were not associated with higher procedural costs when compared to conventional OTW technique. CONCLUSION: We conclude that RX monorail systems seem to enhance the technical success of femoropopliteal angioplasty. Although smaller sheath sizes can be used due to the lower profile of the RX systems, there is only a tendency toward lower complication rates.

Respiratory-gated helical computed tomography of lung: reproducibility of small volumes in an ex vivo model.

PURPOSE: Motion-adapted radiotherapy with gated irradiation or tracking of tumor positions requires dedicated imaging techniques such as four-dimensional (4D) helical computed tomography (CT) for patient selection and treatment planning. The objective was to evaluate the reproducibility of spatial information for small objects on respiratory-gated 4D helical CT using computer-assisted volumetry of lung nodules in a ventilated ex vivo system. METHODS AND MATERIALS: Five porcine lungs were inflated inside a chest phantom and prepared with 55 artificial nodules (mean diameter, 8.4 mm +/- 1.8). The lungs were respirated by a flexible diaphragm and scanned with 40-row detector CT (collimation, 24 x 1.2 mm; pitch, 0.1; rotation time, 1 s; slice thickness, 1.5 mm; increment, 0.8 mm). The 4D-CT scans acquired during respiration (eight per minute) and reconstructed at 0-100% inspiration and equivalent static scans were scored for motion-related artifacts (0 or absent to 3 or relevant). The reproducibility of nodule volumetry (three readers) was assessed using the variation coefficient (VC). RESULTS: The mean volumes from the static and dynamic inspiratory scans were equal (364.9 and 360.8 mm3, respectively, p = 0.24). The static and dynamic end-expiratory volumes were slightly greater (371.9 and 369.7 mm3, respectively, p = 0.019). The VC for volumetry (static) was 3.1%, with no significant difference between 20 apical and 20 caudal nodules (2.6% and 3.5%, p = 0.25). In dynamic scans, the VC was greater (3.9%, p = 0.004; apical and caudal, 2.6% and 4.9%; p = 0.004), with a significant difference between static and dynamic in the 20 caudal nodules (3.5% and 4.9%, p = 0.015). This was consistent with greater motion-related artifacts and image noise at the diaphragm (p <0.05). The VC for interobserver variability was 0.6%. CONCLUSION: Residual motion-related artifacts had only minimal influence on volumetry of small solid lesions. This indicates a high reproducibility of spatial information for small objects in low pitch helical 4D-CT reconstructions.

Four-dimensional multislice helical CT of the lung: qualitative comparison of retrospectively gated and static images in an ex-vivo system.

PURPOSE: To analyse the image quality of retrospectively gated helical CT using controlled respiratory motion of porcine lung explants. MATERIALS AND METHODS: Five porcine lungs were examined inside a chest phantom. A silicone membrane was rhythmically inflated and deflated to simulate diaphragmatic respiration. Dynamic images (regular respiration at 8/min) and static scans (w/o respiration) at 0/25/50/75 and 100% of maximum inspiration were acquired with a 40-row detector CT scanner (rotation time 1s, pitch 0.1). Image quality on multi-planar reformations was evaluated by two observers. Partial projection artifacts, stepladder-artifacts and noise were compared for upper, middle and lower parts of the lung and different respiratory phases (scores 0-3 for absent, minimal, moderate and diagnostically relevant artifacts). RESULTS: Partial projection effects were limited to dynamic scans (mean score 1.33). Stepladder artifacts predominated in dynamic series compared to static series (mean score 0.55 versus 0.1; p<0.001). Image noise was not related to lung motion (mean scores 0.68-0.81). All artifacts predominated close to the diaphragm compared to the upper and middle parts of the lung (p<0.001 to p=0.02, respectively). Partial projection and stepladder artifacts were less in end-inspiration and end-expiration than within the respiration (p<0.001 and p=0.17, respectively). Diagnostically relevant artifacts were noted 9 times (9/9 close to diaphragm, 7/9 partial-projection). CONCLUSIONS: Even in ideal realistic conditions, helical 4D-CT produced tolerable artifacts which could be overcome by radiologists.

Craniectomy and noggin application in an infant model.

INTRODUCTION: Noggin is an antagonist of bone morphogenetic proteins (BMP)-2, -4 and -7. Little data are available regarding its clinical utility. Two hypotheses were put forward: firstly, that spontaneous regeneration of calvarial defects with noggin protein would result in diminished bone volume when compared with calvarial defects not so treated. Secondly, that centrifugal cranial expansion would remain undisturbed whether noggin was applied or not. MATERIAL AND METHODS: A unilateral defect of the frontal and parietal bones (2x4cm) was generated by excising the right coronal suture in 2-month-old minipigs (n=10) and in group 1 (n=5) no further intervention was undertaken. In the second group (n=5), a collagen type I tissue fleece and noggin protein (1.05mg/ml) were applied. After 4 months the coronal suture regions of frontal sides were examined in each animal by computed tomography and non-decalcified histology. RESULTS: Bony gaps of equivalent size remained in animals of both groups. The differences in bone volumes of the experimental sides of group 1 were not statistically significantly different (p=0.117) when compared with those of group 2. A significant difference in the bone volumes of the experimental versus control (unoperated) sides was found in both group 1 (p=0.043) and group 2 (p=0.043). Internal skull diameters increased by 16.4% in both groups but the physiological centrifugal cranial expansion remained undisturbed. Bone densities of the experimental and control sides of groups 1 and 2 were not statistically significantly different (both p>0.05). CONCLUSIONS: The first hypothesis was contradicted: the quantity and quality of spontaneous bone regenerates was not altered by application of noggin protein. The second hypothesis was confirmed: no disruption of subsequent cranial development was seen. It may be that a single application of noggin protein in this study was insufficient. However, it may well be suggested that the continuous supplementation of noggin, for example by adenoviral noggin gene transfer may significantly reduce the quantity of spontaneous bone regeneration in a similar experiment.

Pulmonary nodule detection with digital projection radiography: an ex-vivo study on increased latitude post-processing.

To evaluate increased image latitude post-processing of digital projection radiograms for the detection of pulmonary nodules. 20 porcine lungs were inflated inside a chest phantom, prepared with 280 solid nodules of 4-8 mm in diameter and examined with direct radiography (3.0x2.5 k detector, 125 kVp, 4 mAs). Nodule position and size were documented by CT controls and dissection. Four intact lungs served as negative controls. Image post-processing included standard tone scales and increased latitude with detail contrast enhancement (log-factors 1.0, 1.5 and 2.0). 1280 sub-images (512x512 pixel) were centred on nodules or controls, behind the diaphragm and over free parenchyma, randomized and presented to six readers. Confidence in the decision was recorded with a scale of 0-100%. Sensitivity and specificity for nodules behind the diaphragm were 0.87/0.97 at standard tone scale and 0.92/0.92 with increased latitude (log factor 2.0). The fraction of "not diagnostic" readings was reduced (from 208/1920 to 52/1920). As an indicator of increased detection confidence, the median of the ratings behind the diaphragm approached 100 and 0, respectively, and the inter-quartile width decreased (controls: p<0.001, nodules: p=0.239) at higher image latitude. Above the diaphragm, accuracy and detection confidence remained unchanged. Here, the sensitivity for nodules was 0.94 with a specificity from 0.96 to 0.97 (all p>0.05). Increased latitude post-processing has minimal effects on the overall accuracy, but improves the detection confidence for sub-centimeter nodules in the posterior recesses of the lung.

Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible.

In 2004, we reported a novel method of repairing a human mandible by in vivo tissue engineering. The patient served as his own bioreactor as the exogenously prepared customized mandible replacement was grown inside his latissimus dorsi muscle prior to transplantation to repair the existing defect. Our technique was developed through extensive experience with an animal model. We describe our and the patient's experiences with this procedure. We give details to the benefits and limitations of this technique as it stands and outline issues that should be addressed in future human clinical trials.

Reproducibility of computer-aided volumetry of artificial small pulmonary nodules in ex vivo porcine lungs.

OBJECTIVE: The main purpose of this study was to investigate the reproducibility of computed tomography (CT)-based volumetric measurements of small pulmonary nodules. METHODS: We implanted 70 artificial pulmonary nodules in 5 ex vivo porcine lungs in a dedicated chest phantom. The lungs were scanned 5 times consecutively with multislice-CT (collimation 16 x 0.75 mm, slice thickness 1 mm, reconstruction increment 0.7 mm). A commercial software package was used for lesion volumetry. The authors differentiated between intrascan reproducibility, interscan reproducibility, and results from semiautomatic and postprocessed volumetry. RESULTS: Analysis of intrascan reproducibility revealed a mean variation coefficient of 6.2% for semiautomatic volumetry and of 0.7% for human adapted volumetry. For interscan reproducibility a mean variation coefficient of 9.2% and for human adapted volumetry a mean of 3.7% was detected. CONCLUSION: The presented volumetry software showed a high reproducibility that can be expected to detect nodule growth with a high degree of certainty.

2005 Dr. Gary J. Becker Young Investigator Award: periprocedural oral administration of the leflunomide analogue FK778 inhibits neointima formation in a double-injury rat model of restenosis.

PURPOSE: To test the efficacy of limited oral administration of the new leflunomide analogue FK778 for suppression of neointima proliferation in a double-injury restenosis model in the rat. MATERIALS AND METHODS: For induction of aortic lesions, silicon cuffs were placed operatively around the infrarenal aortas of Lewis rats. After 21 days, the aortic cuffs were removed and the lesions were dilated with 2-F Fogarty catheters inserted via the left common carotid artery. The novel immunosuppressant FK778 was administered at a dose of 5 mg/kg body weight (group 1) or 15 mg/kg body weight (group 2) in a total of 38 animals. For both doses, three different periinterventional time periods, each with a 5-day course of oral FK778, were defined as follows: (i) days -2 to 2, (ii) days 1-5, and (iii) days 7-11, with six or seven rats in each group. After 3 weeks, intima/media ratios were assessed morphometrically and immunohistochemistry for quantification of intimal alpha-actin expression was performed. RESULTS: In both dose groups, there was a trend toward inhibition of neointima formation when the 5-day course of FK778 was started before or 1 day after the intervention. However, in the lower-dose group, inhibition of neointima was not statistically significant regardless of the time frame of treatment (groups 1a-c). With the higher dose, suppression of intimal hyperplasia was significant when FK778 was administered between days 1 and 5 after angioplasty (group 2b; P<.01). Expression of alpha-actin in the intima of FK778-treated rats was significantly reduced when the drug was started 2 days before angioplasty in group 1a (P<.05) or 1 day after angioplasty in both dosage groups (group 1b, P<.01; group 2b, P<.05). CONCLUSION: In the double-injury rat model presented, balloon-mediated proliferation of smooth muscle cells in the intima with consecutive intimal thickening was influenced by FK778 in a dose-dependent manner. However, long-term studies are needed to exclude a delay of vascular healing in this particular model.

Low-profile stent placement with the monorail technique for treatment of renal artery stenosis: midterm results of a prospective trial.

PURPOSE: To determine feasibility, safety, and midterm patency of a monorail balloon stent device for the treatment of renal artery stenosis (RAS). MATERIALS AND METHODS: During a period of 30 months, 47 patients (with severe hypertension, n=45; renal insufficiency, n=20) with 50 cases of RAS and indications for stent implantation (calcified ostial lesion, n=41; insufficient percutaneous transluminal angioplasty, n=6; dissection, n=3) were enrolled into the prospective evaluation. After predilation, 59 stents (Rx-Herculink 4 mm, n=2; 5 mm, n=19; 6 mm, n=35; 7 mm, n=3) were implanted under manometer control with use of the long-sheath technique (5 F; 6 F for 7-mm stents) via a femoral (n=44) or transbrachial approach (n=6). Parameters of hypertension and renal insufficiency were determined before and after the procedure and for a maximum of 18 months. Restenosis rate was determined with color duplex ultrasonography. RESULTS: Renal artery stent placement (mean diameter, 5.7 mm; mean length, 16 mm) was technically successful in all cases (100%). Mean blood pressure and serum creatinine level decreased from 177/93 mm Hg to 145/78 mm Hg and from 1.8 mg/dL to 1.5 mg/dL, respectively. Within 48 hours after the implantation, acute occlusions occurred in two patients, supposedly triggered by cholesterol embolization. Primary and primary assisted patency rates were 87% and 92% at 6 months and 75% and 84% at 18 months. CONCLUSIONS: Renal artery stent placement with the rapid-exchange monorail system is a safe procedure with promising patency rates. In combination with the long-sheath technique, adequate control of stent deployment is guaranteed during the entire intervention. The low profile of the device facilitates the use of small sheaths (5 F) to minimize access-site complications.

RhBMP-7 improves survival and eruption in a growing tooth avulsion trauma model.

Long-term loss of avulsed and replanted teeth is a frequent clinical problem. Bone morphogenetic protein-7 (BMP 7) induces cementogenesis in periodontitis-associated periodontal ligament (PDL) defects. This study's aim was to assess the utility of rhBMP 7 in a tooth avulsion trauma model in growing individuals. Immature primary incisors of 12 minipigs were extracted. PDL and cementum were removed either partially (group 1: 4 mm2 [n=28 teeth]; group 2: 16 mm2 [n=26 teeth]) or totally (group 3 [n=26 teeth]). 500 microg rhBMP 7/g collagen matrix was applied to the teeth from one side while the corresponding teeth on the contralateral side served as controls (split mouth model). After an experimental period of 4 months, microradiography, fluorescence and light microscopy of nondecalcified sections were performed. All teeth of group 1 survived and all teeth of group 3 were lost, whether rhBMP-7 was applied or not. In group 2, nine out of ten teeth survived when rhBMP-7 was applied and four out of ten teeth were lost when rhBMP-7 was not applied. In the presence of rhBMP-7, eruption of teeth in group 2 was significantly improved (difference [median]: 5 mm, P<0.05, n=6). Even though there was a tendency towards increased deposition rates of cementum under rhBMP-7, this difference was not significant (Wilcoxon: P>0.05, ANOVA: P=0.002; n=6/group). In conclusion, rhBMP-7 improved survival rates and eruption of replanted teeth in growing individuals. No adverse effects were seen. Based on the present results, future clinical trials appear to be warranted.