Histological demonstration of healing in experimental aneurysms.

INTRODUCTION: Recanalisation of aneurysms after interventional therapy is still an unsolved problem. The aim of this study is to demonstrate the angiographic and histological evidence of healing after endovascular embolisation of experimental aneurysms. METHODS: We evaluated the healing reaction in experimental aneurysms treated with HydroCoils and platinum coils. After microsurgical construction of aneurysms in 24 rabbits, embolisation was performed. Four animals were sacrificed immediately after embolisation and 5 after 1 month, 3 months and 6 months, respectively, the remaining served as control group. Serial plastic-embedded ground sections of the parent arteries-aneurysm complexes were evaluated by light microscopy. RESULTS: Thrombus organisation in the aneurysms resulted in fibrovascular tissue formation between bare platinum and HydroCoils from the walls of the aneurysms towards the centre of the sac over time. In the clefts between HydroCoils only thin strands of granulation tissue were observed. From one month on, there was a neointimal layer covering the coil mass at the aneurysm orifice. CONCLUSION: Progressive occlusion by the expanding hydrogel polymers on the coils seemed to result in a durable healing reaction in the aneurismal sac in a short-term follow-up period.

Computerized assessment of angiographic occlusion rate and coil density in embolized human cerebral aneurysms.

BACKGROUND AND PURPOSE: Computerized methods have been introduced for more objective quantification of angiographic occlusion rate and coil density as parameters of successful embolization. This study aimed 1) to evaluate this new computerized method for angiographic occlusion rating and coil density calculations by comparison with corresponding histometric parameters from retrieved human aneurysms, and 2) to compare the new computerized method with the present standard of subjective angiographic occlusion rating. MATERIALS AND METHODS: From 14 postmortem-retrieved human aneurysms, angiographic occlusion rate was determined by contrast medium attenuation-gradient distinction on digital subtraction angiographs after Guglielmi detachable coil (GDC) embolization. Angiographic coil density was calculated, approximating aneurysms as ellipsoid and coils as cylindric volumes. On surface-stained histologic ground sections of the respective aneurysms, the occluded aneurysm area and coil area were measured. Then, we calculated and compared the histometric occlusion rates and coil densities with the corresponding angiographic parameters by using the Wilcoxon paired signed-rank test and the Spearman rank correlation. RESULTS: Computerized angiographic occlusion rates (75%-100%) showed good correlation (r = 0.799; P < .01) with histometric occlusion-rates (61%-100%), resulting in no statistically significant differences (P = .2163). With 5.1% (+/-3.8), the mean difference between computerized angiographic occlusion rates and histometry was substantially lower compared with 10.7% (+/-8.7) mean difference between subjective angiographic estimations and histometry. Calculated angiographic coil density (13%-32%) significantly differed from histometric coil density (8%-35%; P < .05). CONCLUSIONS: For recanalized aneurysms, computerized angiographic occlusion rating showed better correspondence with histometry compared with subjective angiographic occlusion rating. Clinical application of this new tool may lead to more objective cutoff values for re-embolization indications. The value of coil density calculations seems limited by the approximation of the aneurysms as ellipsoid volumes.

Cartilage and bone neoformation in rabbit carotid bifurcation aneurysms after endovascular coil embolization.

Occurrence and histomorphology of cartilage and bone neoformations was retrospectively evaluated in rabbit experimental aneurysms after endovascular coil embolization. During product development, 115 carotid bifurcation aneurysms were treated with hydrogel-containing devices (HydroCoil or target, n=77; HydroSoft or target, n=28; prototype Hydrogel-only, n=10; MicroVentionTerumo, Aliso Viejo, CA). Additional 29 aneurysms were treated with standard (n=22) or with degradable polymer-covered (n=7) platinum coils. After 4 to 52 weeks, the retrieved aneurysms were methylmethacrylate embedded, and ground sections were surface-stained with Rapid Bone Stain and Giemsa solution. Cartilage and/or bone tissue was assessed by light microscopy; respective tissue areas in the aneurysms were determined by computerized histomorphometry. Cartilage neoformation was observed from 26 to 52 weeks. Single chondrocytes to hyaline or fibrous cartilage areas, occupying up to 29% of the aneurysm cavity, were found in 6 aneurysms, treated with HydroCoil (n=4), Hydrogel-only (n=1), and resorbable polymer (n=1) devices. Chondral ossification associated cartilage neoformation in 2 of these 4 HydroCoil-treated aneurysms. Membranous woven and lamellar bone ossicles were observed from 13 to 52 weeks in 7 aneurysms, treated with HydroCoil (n=3) and platinum coil (n=4) devices. Altogether, cartilage and/or bone neoformation was observed in 13 (9%) of 144 rabbit bifurcation aneurysms treated with various embolic devices. Incidence was low until 26 weeks, but increased at 52 weeks in both, HydroCoil and standard platinum coil treated aneurysms. As the neoformations were predominantly located in proximity to the aneurysm neck, they could be related to the long-term mechanobiology of cell differentiation during fibrovascular healing of blood flow-exposed embolized aneurysms.

Retrieval analyses of highly cross-linked polyethylene acetabular liners four and five years after implantation.

Two Durasul highly crosslinked polyethylene liners were exchanged during revision surgery four and five years after implantation, respectively. The retrieved liners were evaluated macroscopically and surface analysis was performed using optical and electron microscopy. A sample of each liner was used to determine the oxidation of the material by Fourier transform infrared spectroscopy. Samples of the capsule were examined histologically. The annual wear rate was found to be 0.010 and 0.015 mm/year, respectively. Surface analysis showed very little loss of material caused by wear. Histological evaluation revealed a continuous neosynovial lining with single multinucleated foreign-body giant cells. Our findings showed no unexpected patterns of wear on the articulating surfaces up to five years after implantation and no obvious failure of material.

[Osteonecrosis of the hip in adults]. / Die Osteonekrose des Hüftgelenkes im Erwachsenenalter.

Osteonecrosis of the hip (ON) in the adult is still an unsolved therapeutic problem. New pathophysiological findings have increased our knowledge of the disease course. Technical progress in imaging modalities and a better understanding of pathomorphology have improved the diagnostic procedure. The most significant progress for pathophysiology, early diagnosis and therapeutic decision making has been evolved by the routine use of MR-imaging. Using the international ARCO staging system, the pathomorphological and imaging changes during the different ON stages are described in this review. A diagnostic algorithm for ON is proposed. There are numerous conservative and surgical therapeutic approaches to ON, and the number of these is still increasing. A short overview of the most common therapeutic concepts is given. Finally, recommendations for therapeutic decision making for daily practice are proposed.

[Osteonecrosis of the hip joint in adulthood]. / Die Osteonekrose des Hüftgelenks im Erwachsenenalter.

Osteonecrosis (ON) of the hip joint remains an unsolved therapeutical problem. Diagnosis of ON of the hip has been improved by the technical progress of imaging modalities and better understanding pathomorphology. Over a long period only plain radiographs have been available. Scintigraphy and computed tomography contributed to differential diagnosis and early detection of bone necrosis. Diagnosis in an early reversible stage is of importance. Understanding of pathophysiology, early diagnosis and therapeutical approach has been significantly improved by MR imaging. Using the ARCO system all imaging modalities and their diagnostic viability are described in the five ARCO stages. At the end a diagnostic algorithm will be proposed.

Adverse tissue reactions to wear particles from Co-alloy articulations, increased by alumina-blasting particle contamination from cementless Ti-based total hip implants. A report of seven revisions with early failure.

We revised seven alumina-blasted cementless hip prostheses (Ti-alloy stems, cp Ti threaded sockets) with low- or high-carbon Co-alloy bearings at a mean of 20.1 months after implantation because of pain and loosening. Histological examination of the retrieved periprosthetic tissues from two cases in which the implant was stable and three in which the socket was loose showed macrophages with basophilic granules containing metal and alumina wear particles and lymph-cell infiltrates. In one of the two cases of stem loosening the thickened neocapsule also contained definite lymphatic follicles and gross lymphocyte/plasma-cell infiltrates. Spectrometric determination of the concentration of elements in periprosthetic tissues from six cases was compared with that of joint capsules from five control patients undergoing primary hip surgery. In the revisions the mean concentration of implant-relevant elements was 693.85 microg/g dry tissue. In addition to Cr (15.2%), Co (4.3%), and Ti (10.3%), Al was predominant (68.1%) and all concentrations were significantly higher (p < 0.001) than those in the control tissues. The annual rates of linear wear were calculated for six implants. The mean value was 11.1 microm (heads 6.25 microm, inserts 4.82 microm). SEM/EDXA showed numerous fine scratches and deep furrows containing alumina particles in loosened sockets, and stems showed contamination with adhering or impacted alumina particles of between 2 and 50 microm in size.

The dermis-prelaminated scapula flap for reconstructions of the hard palate and the alveolar ridge: a clinical and histologic evaluation.

Ideal reconstructions of complex defects in the midface require the restitution not only of bone and soft tissue, but also of a thin and durable lining of the oral cavity. So far, split-thickness skin grafts, intestinal grafts, and in vitro cultured mucosal grafts have been used for the reconstruction of the oral lining. The use of skin as a substitute for oral mucosa is controversial because contraction, hair growth, maceration, and dysplastic changes can occur. This clinical and histologic study was performed to evaluate the suitability of dermis as a substitute for oral lining. Twelve complex defects of the midface were reconstructed with dermis-prelaminated scapula flaps. A bony flap from the lateral border of the scapula was prepared, and osseointegrated implants were placed. The bone flap was then prelaminated with dermis and covered with a Gore-Tex membrane to prevent adhesions. The composite flap was transferred to the midface 2 to 3 months later. The oral lining of the flap was evaluated clinically and histologically at 2, 4, and 6 weeks and at 3 to 41 months after the reconstruction. In all patients, the reconstructed bone was covered with a thin and lubricated surface without hair growth. None of the patients showed any signs of maceration. Histologically, these findings corresponded to a keratinized stratified squamous epithelium with highly developed connective-tissue papillae. These features closely resemble those of the normal mucosa of the hard palate and the gingiva. Thus, dermis prelamination is an effective method for reconstructing the mucosa of the alveolar ridge and the hard palate.

Radical cavities and cochlear implantation.

Profoundly deaf patients with chronic suppurative otitis media have been contraindicated for cochlear implantation in the past. Complications such as infection of the radical cavity, fat necrosis, skin flap problems, change in electrode position and cholesteatoma have occurred in subjects with radical cavities. The aim is to create a dry, self-cleansing, infection-free cavity. This is essential in patients about to receive a cochlear implant, as infection may be introduced into the cochlea at the implantation site and destroy any remaining neural elements. The aim of this paper was to show that it is possible to obliterate the radical cavity and perform cochlear implantation using a one-step surgical technique. Eight patients suffering from long-term bilateral chronic middle ear diseases with chronic sepsis leading to severe hearing impairment underwent cochlear implant surgery. No major complications were observed in these subjects.

Functional and biological test of a 20 channel implantable stimulator in sheep in view of functional electrical stimulation walking for spinal cord injured persons.

A newly developed implantable stimulator with 20 output channels, mainly intended for the stimulation of lower extremities in paraplegics, was implanted in 6 sheep over a time period of 26 weeks. Five epineural electrodes each were used to contact various nerves at different locations to elicit hip and knee extension and flexion and to make carrousel and selective stimulation possible. Different electrode application strategies in view of paraplegic standing and walking were investigated. Additional implanted electrodes allowed M-wave monitoring for selectivity investigations in 3 sheep. Stimulator, electrode leads, and electrodes proved to be reliable. Selective stimulation with electrodes placed on the trunk of the sciatic nerve could be demonstrated but with bad reproducibility. Histological investigation of the tissues surrounding electrodes and leads showed the expected stable foreign body response. Strong hip and knee extension could be gained in all cases while only weak flexion forces could be elicited in most cases. Muscle biopsies showed that daily stimulation for 8 h at threshold level caused an increase in muscle Type I fibers and a decrease in Type IIc fibers. Implants and electrodes fulfill the most important functional and biological criteria for their clinical application for paraplegic walking. The intention to provide selective flexion functions via epineural stimulation could not be demonstrated sufficiently in this animal model.

Perimodiolar electrodes in cochlear implant surgery.

Perimodiolar-positioned cochlear implant electrodes have been developed in order to bring the electrode contacts as close as possible to the spiral ganglion cells, which are the target of electrostimulation. This results in lower electrical thresholds, higher dynamic ranges and less channel interaction when compared with normal implant electrodes which are usually located peripherally within the scala tympani. In this study we evaluated 4 different types of perimodiolar electrode: the Clarion Preformed electrode, the Clarion Preformed electrode with positioner, the Nucleus Contour electrode and the Med-El Perimodiolar Combi 40 electrode. These devices require different approaches to achieve a perimodiolar electrode position. The electrodes were inserted in fresh human temporal bones. After processing these bones with the electrodes in situ by employing a sawing, grinding and polishing technique, the inner ear structures as well as the electrode positions could be evaluated in detail. All electrode types studied had a more or less perimodiolar position; however, each type produced a certain amount of trauma to cochlear structures which is discussed in relation to mechanical properties. Further human temporal bone studies with improved perimodiolar cochlear implant electrodes are necessary in order to find an optimized type of electrode.

Magnetic resonance imaging and histology of repair in femoral head osteonecrosis.

Different repair processes affect the clinical course of nontraumatic avascular femoral head osteonecrosis, not just necrotic lesion size and location. Fourteen femoral heads were retrieved at total hip arthroplasty after core decompression treatment, or after conservative treatment was done on 13 male patients diagnosed with different stages of femoral head osteonecrosis. To determine repair types, features of coronal magnetic resonance images were correlated with light microscopy findings on corresponding coronal undecalcified sections and microradiographs of the retrieved femoral heads. In five femoral heads, repair of necrotic bone and marrow remained restricted to the reactive interface for as many as 63 months, producing the diagnostic osteosclerotic rim with adjacent hypervascularity (limited repair). Nine femoral heads showed extension of the repair process into the necrosis. In five femoral heads, predominant resorption of necrotic bone led to femoral head breakdown within 2 to 50 months (destructive repair). In four femoral heads, reparative bone formation had started from subchondral fractures and/or the reactive interface, definitely reducing the size of the necrotic area (reconstructive repair). In the latter, the disease progressed slowly or stopped for as many as 45 months, irrespective of treatments, but elimination of risk factors seemed beneficial. Although core decompression did not always reach the necrotic area and improve repair, it reduced accompanying bone marrow edema and could delay the disease progress. Osteonecrosis with limited repair can be identified on magnetic resonance images obtained at followup, but the similar signal changes of destructive and reconstructive repair cannot be distinguished on magnetic resonance images alone. The evidence of reconstructive repair in nontraumatic osteonecrosis, however, gives hope for treatments that can improve repair to a sufficient creeping substitution of the affected femoral head.

Evidence for reperfusion injury in cortical bone as a function of crush injury ischemia duration: a rabbit bone chamber study.

A model for critical limb ischemia was produced by occluding femoral vessels in 24 rabbits with a pneumatic cuff for 0, 2, 4, or 6 hours. Immediate sequelae and subsequent creeping substitution of cortical bone were observed in vivo using an implanted tibial window, the optical bone chamber implant (with intravital microscopy), and then by light and fluorescence microscopy of fluorochrome-labeled and surface-stained ground sections of retrieved implants. Six rabbits were used as controls (0 h) for each ischemia treatment, and the animals were monitored for 5 weeks postocclusion. A subpopulation of 13 implants was retrieved after euthanization and then histologically assessed for bone necrosis and remodeling. The hypothesis tested was that reperfusion injury during the 24 h after occluder release (reperfusion phase), and vessel perfusion/caliber, angiogenesis, and net bone resorption during the 5 subsequent weeks (creeping substitution phase), would exhibit ischemia duration-dependent effects. All animals could bear weight on the affected limb to ambulate by 1 week posttreatment. Two-way analysis of variance (ANOVA) comparison of the resulting data confirmed a significant difference between control and ischemia-treated rabbits for: (1) vessel perfusion/reperfusion; (2) vessel caliber; and (3) net bone resorption. Vascular responses to 4 vs. 6 h of ischemia were not significantly different, but net bone resorption was strictly ischemia duration-dependent. The conclusion that reperfusion injury was the mechanism spreading ischemia to more vessels was supported by a decrease in reperfusion and caliber of vessels, and an increase in vascular permeability and leukocyte adherence during the reperfusion phase. It is postulated that reperfusion injury produces a secondary ischemia that amplifies the occlusion-created primary ischemia and, in the present work, may have been succeeded by progressive episodes of ischemia, similar to the infarction pattern of ischemic hearts.

Light and electron microscopic study of stress-shielding effects on rat patellar tendon.

In this second part of our study, the histomorphologic changes occurring in the patellar tendon (PT) of rats after sole stress-shielding were evaluated. In seven adult albino rats, both PTs were exposed by straight skin incision and then stress-shielded on one side by a cerclage, while the contralateral PT served as the sham-operated control. One animal died after the operation and was used as a negative control. After 10 weeks of otherwise unrestricted motion, the rats were killed, and the histomorphology of all PT specimen pairs compared by light and transmission electron microscopy. Light microscopy showed mid-portion thickening and irregularity of collagen bundles in the stress-shielded tendons. Intense remodelling was demonstrated by increased cellularity and vascularity, as well as by enrichment in acidic proteoglycans. Ultrastructural evaluation and morphometry revealed a predominance of large diameter (peak between 180 and 260 nm) collagen fibrils in the sham-operated controls, while in the stress-shielded tendons the number of apparently new, small-diameter (peak between 40 and 60 nm) collagen fibrils increased (up to 77% per cross-sectional field of view). The difference in peak diameters was statistically significant (p < 0.0005). This rat model demonstrated that sole stress-shielding not only causes biomechanical alterations, but also intense tissue remodelling and significant morphological changes in the collagen fibrils in the patellar tendon, comparable to so-called 'ligamentization' in experimental and clinical patellar tendon grafts for anterior cruciate ligament reconstruction.

Alumina ceramic bearings for hip endoprostheses: the Austrian experiences.

The current authors review clinical and retrieval experiences with hemispheric monolithic alumina ceramic sockets (Group 1), implanted between 1976 and 1979, and similar modular titanium sockets with alumina ceramic inlays (Group 2), implanted between 1990 and 1995. Both cementless sockets articulated with alumina ceramic femoral ball heads for total hip joint replacements. Clinical followup of patients with hemispheric monolithic alumina ceramic sockets (Group 1, 138 sockets) resulted in a total failure rate of 19.6% after 5 to 20 years. Radiologic analysis of eight stable sockets showed migration of 0.2 mm to 2.89 mm, but in four sockets at risk for late aseptic failure after an average followup of 12.5 years as much as 13.4 mm of migration was seen. Histologic evaluation revealed pseudosynovial membranes as thick as 1 mm with fine birefringent wear particles within mononuclear macrophages around two stable retrieved sockets. The membranes around four loose sockets were 6 to 10 mm thick and also heavily loaded with larger alumina wear particles. After 7 years followup clinical analysis of patients with modular titanium sockets with alumina ceramic inlays (Group 2, 30 sockets) resulted in four revisions, compared with one revision of 50 identical sockets (control group) with polyethylene instead of alumina ceramic inlays. Wear particle analyses in scanning electron microscopy showed significantly more particles (x 10(9) +/- standard deviation/g dry tissue) from the control group (4.26+/-6.38), compared with alumina ceramic bearings of Group 1 (0.70+/-0.79), and of Group 2 (1.62+/-2.13). The alumina particle sizes ranged between 0.13 and 78.38 microm. The mean annual linear wear of 38.8 microm was calculated for the bearings in Group 1, and of 26.94 microm for bearings in Group 2. These results support the good tribologic and biologic performance of alumina ceramic bearings for total hip arthroplasty.

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1.

Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.

Wear debris from two different alumina-on-alumina total hip arthroplasties.

We compared wear particles from two different designs of total hip arthroplasty with polycrystalline alumina-ceramic bearings of different production periods (group 1, before ISO 6474: group 2, according to ISO 6474). The neocapsules and interfacial connective tissue membranes were retrieved after mean implantation times of 131 months and 38 months, respectively. Specimen blocks were freed from embedding media, either methylmethacrylate or paraffin and digested in concentrated nitric acid. Particles were then counted and their sizes and composition determined by SEM and energy-dispersive x-ray analysis (EDXA). The mean numbers and sizes of most alumina wear particles did not differ for both production periods, but the larger sizes of particle in group 1 point to more severe surface destruction. The increased metal wear in group 2 was apparently due to alumina-induced abrasion of the stems. In this study the concentrations of particles in the periprosthetic tissues were 2 to 22 times lower than those observed previously with polyethylene and alumina/polyethylene wear couples.

[Intracochlear position of cochlear implant electrodes]. / Intracochleäre Position von Cochlear-Implantat-Elektroden.

The insertion of cochlear implant electrodes in human temporal bones may be associated with the destruction of structures within the cochlea. The aim of this study was to measure such insertional trauma by means of histologic processing of implanted human temporal bones following implantation of a Combi 40/40+ electrode array (Med-El, Innsbruck). We implanted 6 human temporal bones with original electrodes (3 with Combi 40 and 3 with Combi 40+). In 4 bones Healon was used for electrode insertion. The histological investigation was performed after radiographic evaluation of the position of the electrode. For the histological procedure we used a technique which keeps the electrodes in position within the cochlea. In these slides we could clearly identify the electrodes in the tympanic scale. When inserted properly (point of first resistance) no trauma occurred in the basal portion of the cochlea and minimal trauma in the middle portion of the cochlea.

[Diagnostic imaging in femur head necrosis]. / Bildgebung bei der Hüftkopfnekrose.

Diagnosis of avascular necrosis (AVN) of the hip has been improved by the technical progress of imaging modalities during the last decade. For a long period, only plain radiographs had been available. Scintigraphy and computed tomography contributed to differential diagnosis and early detection of bone necrosis. In the meantime, MR imaging has gained special value in the evaluation of AVN. It is now the method of choice for early detection as well as for assessment in later stage disorders. Using the ARCO system, all imaging modalities and their diagnostic viability are described. Findings regarding the different stages of AVN are correlated to tissue-specific changes.