Karl Grossschmidt

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.

COMPUTER-ASSISTED QUANTIFICATION OF OCCLUSION AND COIL DENSITIES ON ANGIOGRAPHIC AND HISTOLOGICAL IMAGES OF EXPERIMENTAL ANEURYSMS

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 aneurysms 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 impact of colony-stimulating factor-1 on fracture healing: an experimental study.

The role of colony stimulating factor‐1 (CSF‐1) in the regulation of osteoclasts and bone remodeling suggests that CSF‐1 may also be involved in regulation of bone healing. The ability of CSF‐1 to promote healing of bone defects was tested in a rabbit model. Twenty‐four New Zeeland rabbits were included in the study. Animals were assigned to two groups: the control group (n = 12) was treated by plate fixation. The animals in the second group (n = 12) were also stabilized by conventional plating and received additionally CSF‐1 for 2 weeks systemically. Histologic, histomorphometric, and radiologic examinations were performed to evaluate the healing process at 4, 8, and 12 weeks following surgery. Animals that were treated by CSF‐1 produced a significantly higher amount of mineralized bone over the first 8 weeks after fracture compared to the control animals. Furthermore, a higher number of osteoclasts was found in CSF‐1‐treated animals within the first 8 weeks, compared to the controls. The present data emphasize for the first time the importance of CSF‐1 in the bone healing. The use of CSF‐1 in addition to conventional fixation might be a novel approach for the treatment of bone defects.

Combination of anorganic bovine‐derived hydroxyapatite with binding peptide does not enhance bone healing in a critical‐size defect in a rabbit model

Anorganic bovine‐derived hydroxyapatite (ABM) in combination with binding peptid (P‐15) has demonstrated the capacity to improve the healing of periodontal defects. This study evaluated the benefit of ABM/P‐15 to promote healing of cortical long bone defects in a rabbit model. A 5‐mm segmental bone defect was created in the femur and fixed with a plate. There were two treatment groups: no implant (n = 12) and ABM/P‐15 (n = 12). At 4, 8, and 12 weeks, healing of the defect was evaluated with radiographs and histomorphometric examination of the treated femora. After 4 weeks, radiographs showed bone formation without signs of complete consolidation in three of four animals in the control group and two of four ABM/P‐15 treated animals. At the later course of the treatment, no radiologic difference was evident between the treatment groups. Histomorphometric evaluation revealed an area of 1.29 ± 0.11 mm2 and 0.97 ± 0.21 mm2 of newly produced bone in animals of the control group and ABM/P‐15 group after 4 weeks. After 8 and 12 weeks, animals in the control group had an area of 2.44 ± 0.62 mm2 and 2.5 ± 0.2 mm2 of newly produced bone within the osteotomy gap compared to 1.6 ± 0.65 mm2 and 1.56 ± 0.27 mm2 in the ABM/P‐15 group (p = 0.0004). An enhanced or accelerated ingrowth of bone, as reported in previous studies, was not observed. Our results imply that the ABM/P‐15 is not a suitable graft for the treatment of critical‐sized segmental defects in long bones.

Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating factor-1.

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.

Stable Isotope and Trace Element Studies on Gladiators and Contemporary Romans from Ephesus (Turkey, 2nd and 3rd Ct. AD) - Implications for Differences in Diet

The gladiator cemetery discovered in Ephesus (Turkey) in 1993 dates to the 2nd and 3rd century AD. The aim of this study is to reconstruct diverse diet, social stratification, and migration of the inhabitants of Roman Ephesus and the distinct group of gladiators. Stable carbon, nitrogen, and sulphur isotope analysis were applied, and inorganic bone elements (strontium, calcium) were determined. In total, 53 individuals, including 22 gladiators, were analysed. All individuals consumed C3 plants like wheat and barley as staple food. A few individuals show indication of consumption of C4 plants. The δ13C values of one female from the gladiator cemetery and one gladiator differ from all other individuals. Their δ34S values indicate that they probably migrated from another geographical region or consumed different foods. The δ15N values are relatively low in comparison to other sites from Roman times. A probable cause for the depletion of 15N in Ephesus could be the frequent consumption of legumes. The Sr/Ca-ratios of the gladiators were significantly higher than the values of the contemporary Roman inhabitants. Since the Sr/Ca-ratio reflects the main Ca-supplier in the diet, the elevated values of the gladiators might suggest a frequent use of a plant ash beverage, as mentioned in ancient texts.

A probable case of congenital syphilis from 18th century Vienna

Archaeological excavation of a historic cemetery in Vienna, Austria, dating to the Josephinian period (CE 1765-1790) yielded a likely case of congenital syphilis. The individual displays intensive alteration of the permanent and deciduous dentition such as the mulberry molar and a tapered, fang-like canine. Traits rarely documented in paleopathological literature such as unnotched Hutchinsons incisors or pitting on the base of the cusps of deciduous second molars complement the finding. The present contribution describes this first probable case of congenital syphilis from Central Europe based on dental morphology. Beyond this documentation the specimen is compared to previous cases reported elsewhere.

Ancient pathogens in museal dry bone specimens: analysis of paleocytology and aDNA

SummaryBone samples investigated in this study derive from the pathologic–anatomical collection of the Natural History Museum of Vienna. In order to explore the survival of treponemes and treponemal ancient DNA in museal dry bone specimens, we analyzed three individuals known to have been infected with Treponema pallidum pallidum. No reproducible evidence of surviving pathogen’s ancient DNA (aDNA) was obtained, despite the highly sensitive extraction and amplification techniques (TPP15 and arp). Additionally, decalcification fluid of bone sections was smear stained with May-Gruenwald-Giemsa. The slides were examined using direct light microscope and dark field illumination. Remnants of spirochetal structures were detectable in every smear. Our results demonstrate that aDNA is unlikely to survive, but spirochetal remains are stainable and thus detectable.ZusammenfassungDie Knochenproben dieser Studie stammen aus der Pathologisch-anatomischen Sammlung des Naturhistorischen Museums in Wien. Um eine Aussage über den Erhalt von Treponemen und ihrer DNA in musealen Knochen treffen zu können, wurden drei Knochenpräparate von klinischen Syphilis Fällen untersucht. Trotz hochsensitiver Extraktions- und Amplifikationstechniken, konnte keine DNA des Syphiliserregers nachgewiesen werden. Zum zytologischen Nachweis von Treponemen, wurde Entkalkungsflüssigkeit der Knochenpräparate ausgestrichen und mit May-Grünwald-Giemsa gefärbt. Die Ausstriche wurden im Lichtmikroskop und im Dunkelfeld untersucht. Überreste von Strukturen mit großer Spirochäten Ähnlichkeit konnten in jedem Ausstrich in unterschiedlicher Ausprägung nachgewiesen werden. Obwohl der Nachweis der Erreger DNA nicht gelang, konnten Spirochäten Reste gefärbt und damit detektiert werden.