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The main obstacle in realization of a totally implantable hearing aid is a lack of reliable implantable microphone. In this paper we have described a potentially miniature fiber-optic vibrometer based on a modified Michelson interferometer, designed to serve as a middle-ear microphone for totally implantable cochlear- or middle-ear hearing aids. A model of the sensing system was used for in-vitro and in-vivo investigation of acoustical response of sheep's middle-ear ossicles. Surgical and implantation procedure of introducing the sensing optical fiber into the middle-ear and its aiming at the incus was investigated and described here in detail. The frequency responses of the incus was measured while a cadaver and living sheep was exposed to the sinusoidal acoustical excitation of 40-90dB SPL, in the frequency range from 100Hz to 10kHz. The amplitude of the incus vibration was found to be in the range between 10pm to 100nm, strongly depending on the frequency, with a lot of resonant peaks, corresponding mainly to the natural outer ear canal gain. The noise floor in the experiments was about 2pm/Hz1/2, but recently we have decreased it to < 0.5pm/Hz1/2, which corresponds to a minimal detectable sound level of 31-35dB(A) SPL for humans. The histological examination of temporal bones of cadaver animals and the intensity of in-vivo optical signal demonstrated that the aiming of the sensing fiber to the target has been preserved for five months after the implantation.

Detailed knowledge of histomorphology is a prerequisite for the understanding of function, variation, and development. In bats, as in other mammals, penis and baculum morphology are important in species discrimination and phylogenetic studies. In this study, nondestructive 3D-microtomographic (microCT, µCT) images of bacula and iodine-stained penes of Pipistrellus pipistrellus were correlated with light microscopic images from undecalcified surface-stained ground sections of three of these penes of P. pipistrellus (1 juvenile). The results were then compared with µCT-images of bacula of P. pygmaeus, P. hanaki, and P. nathusii. The Y-shaped baculum in all studied Pipistrellus species has a proximal base with two club-shaped branches, a long slender shaft, and a forked distal tip. The branches contain a medullary cavity of variable size, which tapers into a central canal of variable length in the proximal baculum shaft. Both are surrounded by a lamellar and a woven bone layer and contain fatty marrow and blood vessels. The distal shaft consists of woven bone only, without a vascular canal. The proximal ends of the branches are connected with the tunica albuginea of the corpora cavernosa via entheses. In the penis shaft, the corpus spongiosum-surrounded urethra lies in a ventral grove of the corpora cavernosa, and continues in the glans under the baculum. The glans penis predominantly comprises an enlarged corpus spongiosum, which surrounds urethra and baculum. In the 12 studied juvenile and subadult P. pipistrellus specimens the proximal branches of the baculum were shorter and without marrow cavity, while shaft and distal tip appeared already fully developed. The present combination with light microscopic images from one species enabled a more reliable interpretation of histomorphological structures in the µCT-images from all four Pipistrellus species.

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.

The acetabular socket "Model Gersthof" is a spheric polyethylene component which can be anchored cement-free by means of three symmetrically arranged pegs at the outside. Between July 1979 and October 1986, 1316 implants of cement-free sockets were performed at our own department. The evaluation of the socket was based on the criterium of radiological instability (= aseptic loosening). After five years of observation, this design-oriented evaluation of success shows a survival of 92% +/- 2.9%.

OBJECTIVE: Occlusion rates (OR) and coil densities were quantified by computer-assisted morphometry on angiograms and histological ground sections of coil-embolized experimental aneurysms. The aims of this study were 1) to develop computer-assisted evaluations of angiographic OR and histometrical OR, 2) to compare these results to subjectively estimated angiographic OR from clinical practice, and 3) to test the correlation between histometrical data of coil density and occlusion. METHODS: Eight rabbit carotid-bifurcation aneurysms had been followed by digital subtraction angiography (DSA) before and after Guglielmi detachable coil embolization and at sacrifice (1 h to 24 wk postembolization). Angiographic OR was subjectively estimated, then determined by computer-assisted density-gradient distinction on digitized DSAs. Histometrically, maximum length, neck width, total area, recanalized area, and coil-occupied area were measured on digitized and calibrated color micrographs from surface-stained histological ground sections of the aneurysms. Histometrical OR and coil density were calculated as indirect parameters. RESULTS: Subjective versus computer-assisted angiographic OR yielded for one aneurysm, 100% versus 100%, and for three aneurysms less than 90% versus 65 to 60% occlusion. For four aneurysms, OR was estimated greater than 90%, whereas computer-assisted OR ranged between 45 to 80%, the latter being more precise because of better definition of the aneurysm's total area on digitized DSA. Histometrical OR ranged between 32.8 and 87.6%, but did not correlate significantly with computer-assisted angiographic OR (r = 0.467, P> 0.1) because of differences in two aneurysms. Coil densities between 5.5 and 22.1% were slightly lower than reported in literature but significantly correlated to histometrical OR (r = 0.646, P < 0.05). CONCLUSION: Computer-assisted DSA evaluation, delivering more precise values than subjectively estimated occlusion, may be a useful tool for follow-up studies. Comparing computer-assisted angiographic with histometrical occlusion demonstrates limits of DSA in displaying the real morphology of coil-embolized aneurysms. The clinically postulated correlation of OR and coil densities was statistically corroborated.

The purpose of this study was to compare the periapical tissue responses and cementum regeneration in response to three widely used root-end filling materials, amalgam, SuperEBA, and Mineral Trioxide Aggregate (MTA). These materials were placed using modern microsurgical techniques on endodontically treated dog premolars and molars. After 5 months, the cell and tissue reactions of surface-stained un-decalcified ground sections were evaluated by light microscopy and statistically analyzed. The major difference in the tissue responses to the three retrofilling materials were the degree of inflammation and types of inflammatory cells, number of fibrous capsule formations, cementum neoformation over these materials, osseous healing and resulting periodontal ligament thickness. MTA showed the most favorable periapical tissue response, with neoformation of cemental coverage over MTA. SuperEBA was superior to amalgam as a root-end filling material.

Objectives: Soft and hard tissue healing around submerged and nonsubmerged versions of one dental implant design was evaluated in an experimental canine peri-implantitis model. Material and methods: Forty-eight c.p. Ti-implants with integrated (one-piece=OPI) or screw-on (two-piece=TPI) abutments were inserted in edentulous mandibles of eight beagle dogs, one OPI and one TPI with connected abutments for nonsubmerged and one TPI without abutment (SMI) for submerged healing. After 3 months, all implants were functionally loaded, and at 4 months peri-implantitis was ligature-induced in one jaw side. Intravital polyfluorochrome labeling, monthly conventional radiography and gingival probing of all 48 implants were performed until sacrifice 8 months postimplantation. Undecalcified ground sections in the bucco-lingual and mesio-distal planes of four dogs (23 implants, one implant lost) were evaluated by light and fluorescence microscopy. The immunohistochemical and SEM-vascular corrosion cast results of the four other dogs (24 implants) will be reported elsewhere. Levels of alveolar bone-to-implant contact (ABICL), alveolar crest (ACL) and junctional epithelium-to-implant contact were determined by computer-assisted histometry. Peri-implant alveolar bone loss (=saucerization) was assessed on the radiographs and calculated as ACL minus ABICL from histometric data. Results: Around SMIs and OPIs without ligature less plaque adhesion and lower gingival indices were found when compared to TPIs. Radiologically, all ligatured, but also some nonligatured implants showed alveolar bone loss. Histometry demonstrated reduced ABICL around all these implants. Saucerization was more pronounced on the lingual and mesio-distal sides. Particularly around TPIs, bone resorption was still active or bone formation was impaired on fluorochrome labeling. Only around SMIs and one OPI without ligature continuing alveolar bone formation reflected by gains in ABICL were found. Conclusion: The clinical and histometric results of this study demonstrate that healing of submerged SMIs was not impaired by the two-stage procedure, resulting in equally good healing as around nonsubmerged OPIs. However, peri-implantitis plaque-induced by ligature and/or dilated abutment connection microgaps in TPIs affected alveolar bone-to-implant contacts more than transmucosal or submerged healing mechanisms.

CONCLUSION: The intraoperative application of glucocorticoid-loaded hydrogels seems to cause a reduction in neutrophil infiltration. No beneficial effect on hearing thresholds was detected. OBJECTIVES: To evaluate the application of dexamethasone- and triamcinolone acetonide-loaded hydrogels for effects on hearing preservation and foreign body reaction in a guinea pig model for cochlear implantation (CI). METHODS: A total of 48 guinea pigs (n = 12 per group) were implanted with a single channel electrode and intraoperatively treated with 50 μl of a 20% w/v poloxamer 407 hydrogel loaded with 6% dexamethasone or 30% triamcinolone acetonide, a control hydrogel, or physiological saline. Click- and tone burst-evoked compound action potential thresholds were determined preoperatively and directly postoperatively as well as on days 3, 7, 14, 21, and 28. At the end of the experiment, temporal bones were prepared for histological evaluation by a grinding/polishing technique with the electrode in situ. Three ears per treatment group were serially sectioned and evaluated for histological alterations. RESULTS: The intratympanic application of glucocorticoid-loaded hydrogels did not improve the preservation of residual hearing in this cochlear implant model. The foreign body reaction to the electrode appeared reduced in the glucocorticoid-treated animals. No correlation was found between the histologically described trauma to the inner ear and the resulting hearing threshold shifts.

The aim of this study was to lengthen the sheep mandible with a fully buried device and to quantitatively analyze the tissue regenerate in the distraction gap by means of two-dimensional and three-dimensional histomorphometry. A custom-made device for continuous distraction was used in five adult sheep and fixed with three bicortical screws on either side of an osteotomy, anterior to the premolar region of the mandible. A cable-connected power and control unit was implanted in the neck region. After a 5-day latency period, distraction was activated every 2 hours and advanced at a rate of 1.01 mm per day. The distraction period was planned for 14 days, but because of stability problems and cable breakage, the actual distraction period ranged from 2 to 17 days, resulting in gap distances from 1.7 to 17.1 mm (mean, 0.95 mm/day). Osteogenesis was followed by radiographic imaging, and after a 6-week consolidation period, the harvested mandibles were serially sectioned for histologic and two-dimensional histomorphometric analysis, with three-dimensional reconstruction. Histologic examination of the specimens demonstrated predominantly membranous bone formation with remodeling bridging the distraction gap mainly in the periosteal region of the lingual side. In addition, cartilaginous areas and chondral bone formation were observed where the bridging appeared incomplete. Because of device fixation on the buccal side of the mandible, the preservation of the lingual periosteum seemed to play the major role for sufficient bone repair in the distraction gap. Cartilage within the distraction gap suggests fixation instability in this animal model.

Detailed knowledge of histomorphology is a prerequisite for the understanding of function, variation, and development. In bats, as in other mammals, penis and baculum morphology are important in species discrimination and phylogenetic studies. In this study, nondestructive 3D-microtomographic (microCT, µCT) images of bacula and iodine-stained penes of Pipistrellus pipistrellus were correlated with light microscopic images from undecalcified surface-stained ground sections of three of these penes of P. pipistrellus (1 juvenile). The results were then compared with µCT-images of bacula of P. pygmaeus, P. hanaki, and P. nathusii. The Y-shaped baculum in all studied Pipistrellus species has a proximal base with two club-shaped branches, a long slender shaft, and a forked distal tip. The branches contain a medullary cavity of variable size, which tapers into a central canal of variable length in the proximal baculum shaft. Both are surrounded by a lamellar and a woven bone layer and contain fatty marrow and blood vessels. The distal shaft consists of woven bone only, without a vascular canal. The proximal ends of the branches are connected with the tunica albuginea of the corpora cavernosa via entheses. In the penis shaft, the corpus spongiosum-surrounded urethra lies in a ventral grove of the corpora cavernosa, and continues in the glans under the baculum. The glans penis predominantly comprises an enlarged corpus spongiosum, which surrounds urethra and baculum. In the 12 studied juvenile and subadult P. pipistrellus specimens the proximal branches of the baculum were shorter and without marrow cavity, while shaft and distal tip appeared already fully developed. The present combination with light microscopic images from one species enabled a more reliable interpretation of histomorphological structures in the µCT-images from all four Pipistrellus species.

CT assessment of the entire course of the inferior alveolar artery (IAA) within the mandibular canal.After contrast medium injection (180 or 400 mg/ml iodine concentration) into the external carotid arteries of 15 fresh human cadaver heads, the main IAA's position in the canal (cranial, buccal, lingual or caudal) was assessed in dental CT images of partially edentulous mandibles.The course of the main IAA could be followed at both iodine concentrations. The higher concentration gave the expected better contrast, without creating artefacts, and improved visibility of smaller arteries, such as anastomotic sections, dental branches and the incisive branch. The main IAA changed its position in the canal more often than so far known (mean 4.3 times, SD 1.24, range 2-7), but with a similar bilateral course. A cranial position was most often detected (42 %), followed by lingual (36 %), caudal (16 %) and buccal ( 6 %).With this non-invasive radiologic method, the entire course of the main IAA in the mandibular canal could be followed simultaneously with other bone structures on both sides of human cadaver mandibles. This methodology allows one to amend existing anatomical and histological data, which are important for surgical interventions near the mandibular canal.• Contrast medium injection displayed the inferior alveolar artery's course on mandibular CTs • An iodine concentration of 400 mg/ml enabled visibility until the chin • Frequent position changes of the artery in the mandibular canal were detected • Cranial and lingual positions were most often determined • Course similarities on the respective left and right sides were found.

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.

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.

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.

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.

Nichttraumatische Osteonekrosen (ON) des Femurkopfes zeigen trotz unterschiedlichen pathogenetischen Faktoren meist sehr ahnliche pathomorphologische Veranderungen. Ausdehnung und Lage des nach ischamischen Ereignissen nekrotisch gewordenen subchondralen Knochen- und Knochenmarksegments einerseits, und Art der ausgelosten Reparaturvorgange anderseits bestimmen den zeitlichen Ablauf und damit das Schicksal dieser Erkrankung des Huftgelenks. Anhand von 4 ausgewahlten Fallen konservativ oder durch Entlastungsbohrung behandelter Femurkopf-ON werden beispielhaft unterschiedlich suffiziente Reparaturmechanismen aufgezeigt und im Hinblick auf derzeitige Therapiekonzepte diskutiert. Diagnostische Kriterien der Magnetresonanztomographiebilder werden mit lichtmikroskopischen Befunden von unentkalkten Dunnschliffen und Mikrotomschnitten der bei Totalgelenkersatz gewonnenen Huftkopfe verglichen. Im Initialstadium (ARCO 0) und reversiblen Fruhstadium der ON (ARCO I) kann es nach inkompletter Ischamie noch zur suffizienten Reparatur kommen. Nach einem ausgepragten ischamischen Schaden entwickelt sich jedoch das irreversible Fruhstadium der ON (ARCO-Stadium 2). In seltenen Ausnahmefallen (kleine Nekroseareale mit medialer Lokalisation) kann es auch jetzt noch zu einer spontanen suffizienten Reparatur kommen. Ublicherweise findet sich aber in diesem ARCO-Stadium 2 mit noch intakter Gelenkflache kein Umbau des subchondralen nekrotischen Knochen- und Fettmarkgewebes, sondern nur insuffiziente Reparatur durch fibrovaskulare Invasion und Knochenresorption an der Grenze zum vitalen Knochengewebe. Wiederholter Knochenanbau auf teilresorbierten nekrotischen Trabekeln fuhrt zur sklerotischen Verdichtung dieser pathognomonischen reaktiven Randzone. Unterhalb des Nekroseareals und der reaktiven Randzone kann jedoch der Knochenanbau ebenfalls verstarkt sein, wenn die ON von einem begleitenden Knochenmarksodem umgeben ist. Entlastungsbohrungen im ARCO-Stadium 2, auch wenn sie das Nekroseareal erreicht hatten, konnen bestenfalls ein Fortschreiten der Erkrankung verzogern, aber nicht zu einer suffizienten Reparatur im Nekroseareal fuhren. Vielmehr kommt es bei konservativ oder operativ behandelter ON durch uberwiegend destruktiven Knochenumbau fruher oder spater zum Zusammenbruch der Gelenkflache und damit zum mechanisch instabilen Ubergangsstadium der ON (ARCO-Stadium 3). Die subchondrale Fraktur kann jedoch auch von rekonstruktiven Reparaturvorgangen begleitet sein, die mit chondraler und desmaler Knochenneubildung unter dem Frakturspalt durch „schleichenden Gewebeersatz“ das Nekroseareal zwar teilweise verkleinern, aber den Ubergang in das Spatstadium der ON mit sekundaren Gelenkdestruktionen (ARCO-Stadium 4) nicht verhindern konnen. Prinzipiell konnen daher neben suffizienter Reparatur in seltenen Initial-und Fruhstadien drei Formen der insuffizienten Reparatur im Nekroseareal unterschieden werden: fehlender Umbau, destruktiver Umbau, oder rekonstruktiver Umbau. Bis heute konnte mit keiner therapeutischen Masnahme eine vollige Ausheilung der irreversiblen Fruh- bis Spatstadien der ON durch rekonstruktiven Umbau erzielt werden. Verbessertes Verstandnis von Pathomorphologie und Reparaturmechanismen konnte jedoch zukunftig Therapiekonzepte fur eine vollstandige Regeneration des Osteonekroseareals ermoglichen.

We studied the short- and long-term histological responses induced by conventional and modified electronically detachable coils (GDCs) in experimental aneurysms. Eighteen carotid bifurcation aneurysms were produced microsurgically in rabbits. Six animals each were treated either with conventional or with GDCs coated with a mixture of tissue-thromboplastin to enhance intra-aneurysmal thrombus formation and of plasminogen activator inhibitor type-1 (PAI-1) in inhibit intra-aneurysmal clot fibrinolysis. Six served as untreated controls. Follow-up angiograms were obtained immediately and at 3, 6, 9, 12, 17, and 24 weeks after embolization prior to sacrifice of the animals. All aneurysms were studied macroscopically and histopathologically with the coils in situ. Five of six control aneurysms remained patent. Endovascular occlusion rates between > 90% and 100% were achieved in nine of twelve coiled aneurysms. Follow-up angiography demonstrated recanalization and coil compaction in 5 of them. Gross and microscopic histopathological examination revealed a membrane covering the orifice, intra-aneurysmal scar formation, and development of a neo-intima in both treatment groups at 17 and 24 weeks postembolization. The granulation tissue response appeared to be equally distributed in aneurysms treated with either uncoated or coated coils. Further quantitative morphometric studies are needed to prove if a thrombogenic/antithrombolytic coil-coating might be of value in providing a more enduring anatomic result after GDC-treatment of human brain aneurysms.

In this overview, which is based on selected books and reviews, the microscopic appearances of prosthesis-bone interfaces resulting from clinically relevant implantation techniques are highlighted. The following techniques are distinguished to insert and attach prostheses in the recipient bone: impaction into bone, primary mechanical interlocking, cement fixation, bone ongrowth and secondary mechanical interlocking with bioinert materials, and enhanced bone ongrowth and bone bonding to bioactive materials. The resulting typical histomorphologies of orthopedic and dental prostheses-bone interfaces are described and illustrated from the author's studies employing light, fluorescence, and backscattered electron microscopy, and corresponding microradiographs of undecalcified ground sections of bone and implants. Special emphasis is given to the mineralization-demineralization kinetics of the interfacial bone matrix interacting with specific surface reactions of some implant materials. Consequently, the distinction between bioinert and bioactive prosthetic materials is critically analyzed.

The etiology of avascular necrosis (AVN) is multifactorial. Independent of its etiology and localization it shows typical pathologies and radiological images. In the early stages localized subchondral edema is characteristic. In 50 % of all cases accompanying joint effusion may be found. Due to necrosis of the cells of bone marrow and bone fibrovascular, reactions with hyperemia can be delineated. These reactions allow us to visualize necrosis indirectly. The best imaging methods are MRI and, to a lesser extent, bone scintigraphy. In later stages calcification as well as new bone formation and microfractures are typically demonstrated and visualized best with plain X-rays and CT. Why reparations in many cases, particularly in the hip, are incomplete and may stop in any stage is unknown. Over years clinically complete silent AVNs are not an uncommon finding. Prognosis depends on the localization and size of the AVN. The number of repair mechanisms is best outlined with contrast-enhanced MRI and return of fatty marrow.

We have recently undertaken deep insertions of the Combi-40 cochlear implant electrode (Med-E1 Corp., Innsbruck, Austria) into apical regions of the scala tympani using a cochleostomy approach. In order to examine the extent of the insertional trauma, 12 fresh human temporal bones were implanted with original Combi-40 electrodes. The specimens were histologically processed with the implants in place by employing a sawing and grinding technique. In most cases, only very discrete distortions of the epithelium of the spiral ligament occurred within the middle cochlear turns. Furthermore, a slight displacement of the basilar membrane caused by the electrode was occasionally seen. However, in 2 cases more severe damage such as basilar membrane rupture and electrode displacement was found. Attempts to insert the electrode beyond the point of first resistance resulted in electrode kinking within the basal cochlear turn with subsequent fracture of the osseous spiral lamina. According to our results, deep electrode insertions do not aggravate the insertional trauma provided no force is applied when resistance is felt.

The biocompatibility of all metallic, polymeric, or ceramic materials used for functional electrical stimulation is governed by the inevitable inflammatory tissue response, but possibly also by immunological reactions to the bulk material or released constituents. Besides chemical, physical, and corrosion properties of the conductive electrode materials, increased surface area and roughness of the electrode can influence tissue contact and signal delivery, and can also affect electrode-tissue impedance due to increased connective tissue encapsulation. The polymeric materials used for electrode insulation and those for leads and stimulator packaging seem more or less compatible in an aggressive biological environment. For the long-term performance of electrodes and leads, the relative motion in the various implant bed situations also has to be considered.

Animal models are necessary to develop and test innovations in aneurysm therapy before clinical introduction. This review aims at identifying the most likely candidates for standardizing preclinical testing of aneurysm devices. We systematically searched electronic databases for publications on animal aneurysm models from 1961-2008 to assess the methodologic quality of the studies and collect data on the patency and angiographic and pathologic outcomes of treatments. There has been a steady increase in the annual number of publications with time. Species that were most frequently used were dogs, rabbits, and rodents, followed by swine. Most publications are single-laboratory studies with variables and poorly validated outcome measures, a small number of subjects, and limited standardization of techniques. The most appropriate models to test for recurrences after endovascular occlusion were the surgical bifurcation model in dogs, and the elastase-induced aneurysm model in rabbits. A standardized multicenter study is needed to improve the preclinical evaluation of endovascular devices in aneurysm therapy.

Bone marrow oedema syndrome (BMOS) of the hip includes severe hip joint pain, focal loss of radiodensity in radiographs, increased uptake in bone scintigrams and the pattern of bone marrow oedema in the femoral heads in MRI scans. In 15 patients (16 hip joints) we found the clinical and radiological signs of BMOS. On T1-weighted MRI images areas of low signal intensity could be observed in the head, neck and the intertrochanteric region of the femur in various extensions. These areas showed a significant increase in signal intensity on the T2-weighted images. Because pain was resistant to conservative therapy all these patients were treated by core decompression of the femoral head in a prospective study. Bone cores were evaluated histologically using undecalcified sections and quantitative microradiography. The existence of intramedullary oedema in exactly the regions exhibiting the MRI pattern of bone marrow oedema was verified histologically; however, bone and marrow changes similar to those of early avascular necrosis (AVN) were also visible. These findings support our assumption that BMOS might be a transitory initial phase of AVN. Therefore core decompression treatment for patients suffering pain from BMOS is recommended after excluding other diseases.

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.

For the first time, the histomorphology of the penis bone of a bat (Plecotus austriacus) was examined in detail. From Plecotus austriacus, 14 whole penes and 11 isolated bacula were studied and compared to bacula of Plecotus auritus and Plecotus macrobullaris. The baculum was located on specimen microradiographs and in micro-CT images in the tip of the penis. Using serial semithin sections and surface-stained, undecalcified ground sections, the types of bone and other tissues constituting the baculum were examined by light microscopy. 3D reconstructions were generated from the serial semithin sections and from micro-CT images. The shaft and the proximal branches of the Y-shaped baculum form a tubular bone around a medullary cavity. Since the small diameter of this channel and the main lamellar bone around it resemble a Haversian canal, the baculum is equivalent to a single-osteon bone. Several oblique nutrient canals enter this medullary cavity in the shaft and branches. All ends of the baculum consist predominantly of woven bone. The collagen fiber bundles of the tunica albuginea of both corpora cavernosa insert via fibrocartilage into the woven bone of the branches. Thus, the microscopic structures support the hypothesis that the baculum functions as a stiffening element in the erect penis. In this study, several microscopic imaging techniques were evaluated for displaying the microscopic structures of the baculum. Specimen microradiography, but especially micro-CT proved to be suitable nondestructive methods for accurate and reproducible demonstration and comparison of the three-dimensional structures of the baculum in different bat species.

Magnetic resonance imaging is an extremely sensitive technique for evaluation of bone marrow changes at an early stage of avascular necrosis (AVN) of the hip. We therefore examined 11 painful hips whose clinical symptoms led us to suspect idiopathic AVN. The radiographs of all of these either were normal or demonstrated a minimal decrease in radiodensity. Magnetic resonance demonstrated diffuse signal loss of the bone marrow at short TR/TE images of the femoral head in all hips, with various extensions in the head, neck, and intertrochanteric area. These regions turned iso- to hyperintense on long TR/TE images compatible with bone marrow edema (BME). Focal abnormalities characteristic for AVN were not seen in any of the cases. Radionuclide studies performed in six cases were positive. All patients underwent core decompression treatment. Hydrostatic bone marrow pressure measurement and intraosseous venography were positive in five cases when measured. Histology available in eight cases confirmed the presence of BME. Furthermore, the bone changes corresponded to those of early AVN. Follow-up examinations after core decompression with MR showed normal signal intensity in all cases. Magnetic resonance represents a viable diagnostic tool for BME and can monitor the therapeutic success of core decompression. Whether BME of the femoral head constitutes a distinct transient syndrome or represents an early form of AVN is controversial at present. Our findings support those who believe that BME may represent an initial stage of idiopathic AVN.

& Introduction: Recanalisation of aneurysms after interventional therapy is still an unsolved problem. The aim of this study is to demon-strate the angiographic and histological evidence of healing after endovascular embolisation of experimental aneurysms. Methods: We evaluated the healing reaction in experimental aneurysms treated with Hydro-Coils and platinum coils. After microsurgical construction of aneurysms in 24 rabbits, emboli-sation was performed. Four animals were sacri-fi ced 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 aneu-rysms resulted in fi brovascular 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 Hydro-Coils only thin strands of granulation tissue were observed. From one month on, there was a neointimal layer covering the coil mass at the aneurysm orifi ce. 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.

Objectives: A new method is introduced for the esthetic evaluation of the periimplant mucogingival complex through collection of standardized oral photographs and computer-assisted measurement of reproducible data. Using this method, different soft tissue and crown parameters in the dentogingival complex can be measured and the esthetic outcome monitored. Material and methods: A photographic device for standardized oral photography and a standard protocol for the esthetic evaluation of the crown–mucogingival complex is presented, comprising six soft tissue parameters: (1) mesial and (2) distal papilla areas, (3) mesial and (4) distal papilla heights, (5) soft tissue–crown perimeter, and (6) gingival recession. In order to demonstrate the reproducibility of standardized oral photographs and the accuracy of the measurement of the six parameters, the data obtained in each of two such standardized clinical photographs, taken at 10–14 days intervals, of the anterior maxillary region from 10 patients with no apparent dental disease were compared. For the statistical analysis of the reproducibility of these dependent data the 95% confidence interval and the coefficients of variation were calculated from measurement means and ranges of each of the above parameters, pooled from all 10 patients. Results: Statistical analysis revealed high reproducibility with no significant differences between the range of mean values of all six parameter measurements on the first and second standardized oral photograph of the same patient, respectively. Conclusion: Gingivomorphometry on standardized oral photographs can be considered to be an accurate and reproducible method for the evaluation and measurement of different dentogingival and periimplant parameters.

Scanning Electron Microscopy (SEM) revealed that the palate of Cuora amboinensis has a flat surface with keratinized and non-keratinized regions. Keratinization is reflected in disc-shaped keratinized dead cells with rough microplicae on the surface, and is concentrated close to the rhamphotheca. The surface of the non-keratinized hexagonal epithelial cells is dotted with microvilli and sometimes with cilia. Taste buds are present both in lightly keratinized and non-keratinized regions and exhibit a crater-like shape. Light microscopy shows the different tissue layers of the oral mucosa and the different epithelial structures. In keratinized regions, keratinocytes mature from basal to superficial, where they build up keratin layers of varying thickness. In non-keratinized regions, the epithelial cells are arranged in a stratified fashion, and cuboidal to cylindric cells form a superficial layer. Goblet cells appear to be diffusely distributed, but are often organized in goblet cell fields which can be folded into crypts. Taste buds consist of slender epithelial cells, exhibit the typical barrel-like shape and are specially concentrated in the anterior, praechoanal palate. This anterior concentration of taste buds is shown by kinematographic analysis to correlate with the food prehension mode in Cuora amboinensis. The lamina propria of the palatal mucosa consists of loose connective tissue with inflammatory cells between capillaries. All these structures of the oral mucosa act as a functional entity and help determine how successfully an organism adapts ecologically to the environment.

Radiation therapy influence on bone healing around 3 types of endosseous dental implants in dogs was evaluated.Implants with 3 different surfaces (A = machined commercially pure titanium screws, B = commercially pure titanium plasma spray-coated cylinders, C = hydroxyapatite [HA] -ceramic coated cylinders) were first implanted unilaterally into the right posterior edentulous mandibles of 7 dogs as nonirradiated controls. After 12 weeks without functional loading and after sequential fluorochrome labeling these implants were retrieved by block dissection. In this same surgery, implants were placed on the contralateral side. Three weeks postimplantation the implant-containing hemimandibles were Cobalt 60 irradiated with the biologic equivalent of 5,000 cGy. Twelve weeks postimplantation and after labeling these irradiated implants were retrieved at sacrifice. On scanning electron, light, and fluorescence microscopic images of undecalcified longitudinal ground sections of the implants with surrounding tissues, percent bone-to-implant contact (% BIC), bone formation, and remodeling were histometrically and subjectively evaluated.Woven bone formation started 1 week after implantation at the implant interfaces on both the nonirradiated and the irradiated sides. Average BICs (total/cortical/spongious bone bed) of 26%/49%/36% for surface A, 46%/48%/64% for surface B, and 81%/83%/78% for surface C were observed. In the irradiated hemimandibles average BICs (total/cortical/spongious bone bed) were reduced to 11%/9%/4% for surface A, 43%/46%/43% for surface B, and 63%/85%/76% for surface C, with increased resorption of peri-implant bone and retarded bone formation after irradiation.Reductions of total % BIC in all irradiated implants, though not statistically significant, were significant (Por = .05) on implant surfaces A and B in the spongious bone bed.Retarded bone formation on surfaces A and B in the spongious bone bed represented a more radiation-sensitive situation at the time of radiation onset compared to advanced bone formation and maturation at surface C.

To evaluate the feasibility and efficacy of the local application of a replication-defective adenovirus construct for the expression of the antiinflammatory protein I kappa B alpha, inhibitor of nuclear factor kappa B (NF-kappa B), to reduce neointimal formation after stent placement.Nitinol stents were implanted in the iliac arteries of hypercholesterolemic rabbits, followed by balloon dilation (30 seconds at 6 atm). Local adenovirus-mediated transfer of I kappa B alpha (3 mL of 10(9) plaque-forming units per milliliter at 6 atm) was performed and compared with three control groups: stent alone, stent plus local delivery of phosphate-buffered saline (PBS) (3 mL at 6 atm), and stent plus local delivery of control adenovirus coding for green fluorescent protein (GFP) (3 mL of 10(9) plaque-forming units per milliliter at 6 atm). A multichannel balloon was used for local drug delivery and balloon dilation. Animals were sacrificed 1 or 4 weeks after treatment. Effective transfection was demonstrated with immunofluorescence staining. Angiographic patency and luminal diameter were evaluated at quantitative angiography. Luminal and neointimal areas were measured on surface-stained ground sections with methylmethacrylate embedding and the cutting-grinding technique.All vessels with stents were patent at angiography. Neointimal area was negligible in all groups 1 week after stent placement (range, 0.42-0.52 mm(2); P =.44; analysis of variance). Neointimal formation was demonstrated in all groups 4 weeks after implantation but was significantly reduced with I kappa B alpha treatment compared with treatment with stent alone (by 22%, from 2.80 mm(2) +/- 0.20 to 2.28 mm(2) +/- 0.14, P =.05), stent plus PBS (by 43%, from 3.26 mm(2) +/- 0.25 to 2.28 mm(2) +/- 0.14, P =.005), and stent plus GFP (by 53%, from 2.32 mm(2) +/- 0.19 to 1.51 mm(2) +/- 0.08, P.005).Local adenovirus-mediated I kappa B alpha gene transfer has the potential to reduce intimal hyperplasia after stent placement.

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.

It is my privilege, being one of the pioneers using plasticembedded ground sections for the light microscopic evalua-tion of coil-embolized aneurysms, to oppose with a commenttothepaperpublished2009inActa Neurochirurgica [5]. LeoDe Ridder, Ghent University, Belgium, had criticized thattwo-dimensional (ground) sections, only stained on theirsurfaces, are not representative for microscopic evaluation ofa three-dimensional, coil-filled aneurysm.Plastic-embedded ground sections are now regarded thegold standard for hard tissue implant evaluation. Metallic,ceramic, and also polymeric implant materials can be cuttogether with undecalcified bone or teeth [6]. It was only alogical consequence to section also soft tissue implants,with the advantage of preserving, for example, the metalliccoils in situ when evaluating aneurysms. To my knowledge,first reports of using ground sections for the evaluation ofpostmortem retrieved human aneurysms [1, 7]andofexperimental aneurysms in rabbits [2]appearedin1999.Incontrast to conventional paraffin-embedded microtome sec-tions,wherethemetalliccoilsdamagetheknifeandfallout,orhave to be removed before sectioning as again advertised [4],in ground sections, the coil–tissue interfaces are preservedfor evaluating also the biocompatibility aspects of thevarious coil devices. At least for me, surface-stained groundsections can now also be regarded the gold standard forpathohistological aneurysm evaluation.Furthermore, it has to be pointed out that all conven-tional 5- to 10-µm-thick microtome sections of aneurysmsare also two-dimensional slices of a three-dimensionalstructure. Only consecutive serial microtome sections,which are technically not feasible because of artifacts andtoo elaborate, could represent the three-dimensional bodyof a coiled aneurysm. Depending on size, at least two ormore consecutive 100-µm-thick ground sections are madefrom aneurysms in my and other laboratories, eachrepresenting an initial specimen thickness of about0.5 mm. Thus, a considerable volume of the aneurysm,still containing all the loops of the coils in cross ortangential sections, is available for microscopic evaluation.Since surface stains penetrate only a few microns into thefinally 60- to 100-µm-thick ground sections of the resin-embedded tissues, solely this surface-stained layer isfocused under the light microscope, providing resolutionof cellular detail equally good to much thinner microtomesections. Our group has shown by computer-assistedmorphometry that the coil density measured in groundsections of experimental [8] and retrieved human aneur-ysms [9] corresponded well with the calculated coildensities in respective angiograms. Combined applicationof computer-assisted morphometry on angiograms andground sections allowed even for a comparison of differentcoil types in different aneurysm models from independentexperimental studies [3].Therefore, the weakness of the above cited study [5]israther the subjective estimation of angiographic aneurysmocclusion, serving as sole basis for performance ranking ofthese second-generation and bare platinum embolic devices.Apparently, only not-blinded scoring according to theRaymond scale was performed by one observer, and alsomore objective histomorphometry was not used. It is only aminor further complaint that neither the origin of thehistological specimens nor of the pathohistological evalu-ation was even acknowledged by the authors.

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.

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.

SUMMARY. Distraction osteogenesis with external or intraoral devices is an established method for lengthening human mandibles. In this preliminary study in three sheep a newly designed, fully implantable electromechanical device for mandibular lengthening was used. After osteotomy, the device was screw fixed to the mandible, and the power and control unit was inserted subcutaneously in the neck region. After a healing period of five days, the device was activated magnetically, allowing calibrated distraction steps of 0.04 mm/h, resulting in a total of 1.0 mm/day. Over a period of 14 days, a maximum mandibular lengthening of 13.6 mm could be achieved without transmucosal activation. Depending on stability of the screw fixation, membranous and/or cartilaginous bone formation was observed in the callus by radiological and histological evaluation. Further experimental research is ongoing to prove the clinical usefulness of this device.

There are many different types of cochlear implants available on the market today and they are constantly being re-evaluated and changed. Knowledge of the exact position of the electrode within the cochlea is important in order to improve the electrical stimulation of the hearing nerve by the implants. The stimulating electrodes are usually located peripherally within the scala tympani, although several attempts have been made to develop peri-modiolar located electrode arrays. In this study, our goal was to evaluate the intracochlear positions of Nucleus, Combi 40/Combi 40 +, and newly developed peri-modiolar positioned electrodes by inserting them into fresh human temporal bones. After insertion, the bones were then histologically processed with the electrodes in situ, following perilymphatic formalin perfusion and methylmethacrylate embedding. Sections of the bones 80-100 microm thick were prepared using a sawing, grinding and polishing technique. This technique resulted in excellent preservation of the inner ear structures and clear identification of each electrode. The different types of electrodes were then evaluated as to their insertion depth, trauma to cochlear structures and location in relation to the scala tympani walls.

Osteopetrosis describes a group of skeletal metabolic diseases of heterogeneous etiology and varied severity that produces a generalized accumulation of skeletal mass, the result of reduced bone resorption. Inherited in a variety of species including humans, the most severe forms are lethal. Among common features are progressive blindness and deafness of controversial etiologies for which there are no universally effective treatments. We have studied the auditory responsiveness and auditory ossicle quantitative histomorphology and temporal bone vasculature in the toothless (tl) rat, a lethal osteopetrotic mutation with few osteoclasts, very low bone turnover, and limited angiogenesis in the axial skeleton. Compared with normal littermates, 3-week-old mutants showed significantly reduced auditory responsiveness, a hearing loss due to abnormalities in both form and tissue composition of the stapes, and little capillary sprouting in the vascular bed of the temporal bone. Treatment of mutants with colony-stimulating factor 1 (CSF-1), known to greatly reduce sclerosis in the axial skeleton, significantly improved hearing, stapedial form and tissue composition, and angiogenesis in the temporal bone. In normal rats, the stapes consisted of 89.3% bone, 9.1% mineralized cartilage, and 0.8% porosity. In osteopetrotic rats, the stapes consisted of 48.3% bone, 35.9% mineralized cartilage, and 15.9% porosity, while after CSF-1 treatment, the bone content increased to 55.2%, cartilage was decreased to 21.7%, and porosity increased to 23.0%, respectively. This is the first demonstration of an auditory abnormality in an osteopetrotic animal mutation and shows that the hearing loss in tl rats can be significantly improved following treatment with CSF-1.

Bioprosthetic heart valves removed 76 to 150 months after implantation were morphologically investigated to correlate structural alterations with clinical failure modes. Traditional morphologic methods of evaluating valvular heterografts, such as microradiography and electron microscopy, were complemented by undecalcified ground sections, a new technique for analyzing the distribution of mineral deposits. Apart from well-investigated mechanisms that accelerate tissue degeneration, our observations point to additional facts: (1) phagocytosis of collagen fibrils and elastic material by macrophages and foreign body giant cells in areas near tears and perforations and (2) initial calcification indicated by delicate crystals in the intercellular space arranged in close relation to the periodicity of the cross-striation pattern of collagen fibrils. The present report not only calls attention to degenerative changes that are enhanced by mechanical stress but also underlines phagocytosis as an important mechanism in the destruction of bioprosthetic heart valves. (J T horac C ardiovasc S urg 1992;104:14–21)

During autopsy, a reconstructed partial mandibular resection was recovered and subjected to histological examination. The mandible had been reconstructed 12 weeks earlier with a caudal plate and autologous cancellous bone from the iliac crest. Undecalcified microsections showed that the plate was firmly anchored by screws on both sides and on one side there was bony union. However, most of the free transplant bone had undergone ‘unreplaced resorption’. Nevertheless, this method offers advantages over the conventional method of seating the plate on the buccal aspect and has interesting potential for further development.

The shape, the typical orientation, and the average size of mineral crystals in different types of mineralized tissues were investigated by means of small-angle x-ray scattering (SAXS). To rule out eventual artifacts due to sample preparation, four different standard preparation techniques were used and a comparison showed that the SAXS results were identical for all four methods. In mineralized turkey leg tendon, a frequently used model system for bone, the crystals were found to be typically plate-like with a thickness of the order of 2 nm. This stands in contrast to the case of bone (calvaria, femur, and iliac crest) from mouse, rat, and dog, where mainly needle-like crystals were found. The thickness of these crystals ranged from 3 to 4 nm but was remarkably constant for different bones of a given animal. The preferred orientation of the needle-like crystals was along the main axis of the femur and within the surface of the calvaria (for mouse, rat, and dog). The mineral plates in turkey leg tendon were located inside the hole zone and oriented along the fibril axis. Finally, no periodic arrangement of the crystals inside the hole zone of the collagen could be found.

Intraarterial structures, known as ‘polypoid cushions’ and ‘valve-like’ projections at arterial branching sites, were observed in serial sections of human cleft lip and nasal mucous membrane biopsies. A particular type of ‘polypoid cushions’, which additionally contains a small artery in its center, is distinguished. It is suggested that both the particular type of ‘polypoid cushions’ and these ‘valve-like’ projections originate from the invagination of the entire vessel wall at arterial branching sites according to the location of the dissection or damage. The differences between these ‘valve-like’ formations and genuine arterial valves are mentioned.

A perfusion method of incubation to show horseradish peroxidase in the bone of young mice is presented. After perfusion fixation, the incubation medium is perfused from the descending aorta into the entire lower half of the animal. From the vessels there is good penetration of the medium into all tissues. This allows the preparation of any one perfused bone to ground-, semithin-, and ultrathin sections. Differences in peroxidase distribution in the entire bone suggest regional differences in vascular supply. The tracer enzyme diffuses freely from the vessels into the extracellular fluid of bone. 3 min. after injection, peroxidase is found between all bone lining cells and in osteocyte lacunae.