Background and Purpose-Cerebral ischemia has been proposed as a contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). The search for surrogate parameters that allow treatment stratification for spontaneous ICH continues. We sought to assess the presence and prognostic effect of perihemorrhagic ischemic changes and hypoperfusion in a prospective stroke MRI study. Methods-We performed stroke MRI in 32 patients with hyperacute ICH (mean, 16.9Ϯ17.2 mL) within 6 hours after symptom onset (mean, 3.1Ϯ1.3 hours). Clinical data at baseline (National Institutes of Health Stroke Scale) and on day 90 (Barthel Index, modified Rankin Scale) were assessed. Perihemorrhagic perfusion-and diffusion-weighted imaging changes were assessed in a 1-cm-wide area around the clot. Results-Despite a mild perihemorrhagic mean transit time prolongation of 0.7Ϯ1.1 second, there were no significant perihemorrhagic apparent diffusion coefficient or mean transit time changes indicating irreversible ischemia or hypoperfusion. ICH size, time to imaging, or clinical severity at baseline or outcome were not reflected by changes of relative apparent diffusion coefficient or perfusion-weighted imaging. ICH size correlated with baseline clinical severity (rϭ0.51, Pϭ0.005). There was a significant association (Pϭ0.0494) and a significant negative correlation (rϭϪ0.468, Pϭ0.0103) of perihemorrhagic perfusion change with time from symptom onset not associated with ICH size. Conclusions-Perihemorrhagic hypoperfusion probably is a consequence of reduced metabolic demand (diaschisis) rather than a sign of ischemia. We found no evidence for a perihemorrhagic and potentially salvageable ischemic penumbra in hyperacute ICH. Further studies should address metabolic, toxic, apoptotic, and microvascular aspects.

The aim of this study was to compare the osseointegration of four different implant surfaces in the Göttingen minipig femur model. They were prepared by glasspearlblasting (A), sandblasting (B) and titaniumplasma spraying (C and D). Surface D received additionally an electrochemically deposited layer of a resorbable calcium phosphate (CaP) layer, made mainly of brushite. Sample size was n = 20 per group. Implants were placed in the intertrochanteric and intercondylar sites of both femora. After 12 weeks, implant anchorage was measured by the pull-out test and histomorphometry measurements were carried out at the bone-implant interface. Implant anchorage was 0.7 +/- 0.3 MPa for surface A, 3.2 +/- 0.6 MPa for surface B, 6.5 +/- 1.5 MPa for surface C and 7.3 +/- 1.9 MPa for surface D. The differences between surfaces were statistically significant, with exception of C and D. The stiffness of the bone-implant interface showed no statistically significant difference between surfaces. After pull-out, surface A and B showed nearly no bone spots, while on surfaces C and D bone remains were found. Bone-implant contact was 1.9 +/- 1.1% for surface A, 10.5 +/- 3.6% for surface B, 22.4 +/- 4.5% for surface C and 48.8 +/- 4.5% for surface D. The differences were statistically significant. Implant location, intertrochanteric and intercondylar, did not affect the data. In this minipig model, rougher surfaces showed better osseointegration. After 12 weeks of healing, the resorbable CaP layer enhanced significantly the bone-implant contact but not the level of anchorage. The findings also suggest that the pull-out test should be critically evaluated to determine the shear strength between bone and porous surfaces.

Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out--it does not require radiation and it permits functional-morphological correlation.

The characterization of regenerated articular cartilage (AC) can be based on various methods, as there is an unambiguous accepted criterion neither for the natural cartilage tissue nor for regenerates. Biomechanical aspects should be considered as well, leading to the need for more equivalent samples. The aim of the study was to describe a large animal model where 8 specimens of regenerated AC can be created in one animal plus the impact of two surgeries on the welfare of the animals. The usefulness of the inclusion of a group of untreated animals (NAT) was to analyzed. Based on the histological results the conditions of the regenerates were to be described and the impact on knee joints were to be explored in terms of degenerative changes of the cartilage. The usefulness of the statistical term “effect size” (ES) will be explained with histological results. We analyzed an animal model where 8 AC regenerates were obtained from one Göttingen Minipig, on both sides of the trochleae. 60 animals were divided into 6 groups of 10 each, where the partial thickness defects in the trochlea were filled with matrices made of Collagen I with or without autologous chondrocytes or left empty over the healing periods of 24 and 48 weeks. One additional control group consisting of 10 untreated animals was used to provide untouched “external” cartilage. We harvested 560 samples of regenerated tissue and “external” controls, besides that, twice the number of further samples from other parts of the joints referred to as “internal” controls were also harvested. The animals recovered faster after the 1st operation when the defects were set compared to the 2nd operation when the defects were treated. 9% of all animals were lost. Other complications were for example superficial infections, seroma, diarrhea, febrile state and an injury of a claw. The histological results of the treatments proved the robustness of the study design where we included an “external” control group (NAT) in which the animals were not operated. Comparable significant differences between treated groups and the NAT group were detected both after ½ year and after 1 year. Spontaneous regenerated AC as control revealed differences after an observation time of nearly 1 year. The impact of the treatment on cartilage adjacent to the defect as well as the remaining knee joint was low. The ES was helpful for planning the study as it is shown that the power of a statistical comparison seems to be more influenced by the ES than by the sample size. The ranking of the ES was done exemplarily, listing the results according to their magnitude, thus making the results comparable. We were able to follow the 3 R requirements also in terms of a numerical reduction of animals due to the introduction of a group of untreated animals. This makes the model cost effective. The presented study may contribute as an improvement of the standardization of large animal models for research and regulatory requirements for regenerative therapies of AC.

Postoperative complications after HB resection are frequent and associated with worsened OS of patients with HR-HB. One possible reason is delay in postoperative chemotherapy. The approach to precarious liver resection should be carefully planned and executed by specialists.

SummaryT here is no reliable anim al model of the early stages of osteonecrosis of the femoral head (ONFH) for the evaluation of new therapeutic approaches. In this study, we propose a new anim al model of femoral head osteonecrosis. Pure ethanol was injected into the centre of the fem oral head in adult Merino sheep under¯uoroscopic control. After 3, 6 and 12 weeks the anim als were killed and the femoral heads were harvested. Microradiograph ic and histological changes were analysed and recorded. Partial necrosis was documented over a period of 12 weeks in all animals. T he appearance of necrosis in combinat ion with intact macrotexture, macrocirculation and joint cartilage is similar to the features described in early ONFH in humans. Due to its ef®cacy and its similarit y to the early stages of ONFH in humans, this model may be suitable to evaluate new therapeutic techniques in the treatm ent of ONFH. Keywords Osteonecrosis of the femoral head; ONFH; animal model; ethanolOsteonecrosis of the femoral head (ONFH) is diagnosed with increasing frequency in young adults and is a disease with a signi®cant socioeconomic impact (Fi cat 1985, Mankin 1992. Most authors agree that surgical intervention is preferable to a conservative treat ment (Mont e t a l. 1996 ), but some argue that this procedure is not suf®-cient for all patients. New therapeutic approaches have been proposed, such as growth factor therapy (Hungerford & Mont 2000). T he aim of this study was to develop an anim al model, which allows the evaluation of different therapeutic approaches under controlled conditions, especially for the early and pre-collapse stages of ONFH.Since the pathogenesis of ONFH is unknown, the criteria for a valid anim al model are dif®cult to de®ne. T he characteristic features of the early stages of ONFH include an intraosseous necrosis with intact trabecular structure, maintenance of joint cartil age and an intact macrocirculation. Although many surgical and non-surgical animal models have been published (Kistler 1934, Gold e t a l. 1978, Jones & Hungerford 1984, Liu & Ho 1991, Malizos e t a l. 1993, Matsui e t a l. 1995, Seiler e t a l. 1996, Nishino e t a l. 1997), we could not ®nd a simple, standardized and reliable model of the early, pre-collapse stages in the literature. T he aim of this study was to create a de®ned, partial necrosis of the femoral head in sheep, which ful®ls the mentioned criteria. Material and methods

The significance of delayed tissue tracer transit (TTT) of 99m Tcmercaptoacetyltriglycine ( 99m Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Methods: Twenty 2-to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with 99m Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Results: Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both followups. In these 12 kidneys, the SKF declined from 51% 6 4% to 18% 6 14%, and the THS was 9.0 6 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 6 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 6 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. Conclusion: In hydronephrosis, a delayed TTT of 99m Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.

Abstract. The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characteri zing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1 is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage.