First Evidence for cos2ß>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.

We present first evidence that the cosine of the CP-violating weak phase 2ß is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2ß=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2ß=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle ß of the CKM Unitarity Triangle is ß=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2ß>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-ß=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.

[Nephrotic syndrome and microhematuria in a patient with nutcracker syndrome: Report of a case and review of the literature]. / Nephrotisches Syndrom und Mikrohämaturie bei einer Patientin mit Nussknacker-Syndrom: Ein Fallbericht mit Literaturübersicht.

We report about a 43-year-old woman with polyvalent drug addiction (i.e. alcohol, nicotine, methadone maintenance program with parallel consumption of heroin) who presented to the emergency department with peripheral edema, generalized weakness, and arthralgia. Laboratory findings revealed, among others, proteinuria, hyperlipoproteinemia and hypoproteinemia defining nephrotic syndrome. Computed tomography of the abdomen and iliocavography further revealed compression of left renal vein between aorta and superior mesenteric artery with distention of left ovarian vein as a possible cause of nephrotic syndrome (i. e. nutcracker syndrome). After excluding other possible causes of nephrotic syndrome, we decided against an interventional procedure due to poor compliance of the patient and potential risk of secondary stent dislocation. Instead, we opted for a surgical approach (i. e. veno-venous bypass, meaning transposition of left vena ovarica on vena cava inferior). The operative and postoperative course was uneventful. Postoperatively, proteinuria, microhematuria, arthralgia and edema receded.

Transforaminal lumbar interbody fusion vs. posterolateral instrumented fusion: cost-utility evaluation along side an RCT with a 2-year follow-up.

PURPOSE: Long-lasting low back pain is an increasing problem, and for some patients surgery is the final option for improvement. Several techniques for spinal fusion are available and the optimal technique remains uncertain. The objective of this study was to assess the cost-effectiveness and cost-utility of transforaminal lumbar interbody fusion (TLIF) compared to posterolateral instrumented fusion (PLF) from the societal perspective. METHODS: 100 Patients were randomized to TLIF or PLF (51/49) and followed for 2 years. Cost data were acquired from national registers, and outcomes were measured using the Oswestry Disability Index and SF-6D questionnaires. Conventional cost-effectiveness methodology was employed to estimate net benefit and to illustrate cost-effectiveness acceptability curves. The statistical analysis was based on means and bootstrapped confidence intervals. RESULTS: Results showed no statistically significant difference in either cost or effects although a tendency for the TLIF regimen being more costly on bed days (2,554) and production loss (1,915) was observed. The probability that TLIF would be cost-effective did not exceed 30 % for any threshold of willingness to pay per quality-adjusted life year. Sensitivity analysis was conducted and supported the statistical model for handling of missing data. CONCLUSION: TLIF does not seem to be a relevant alternative to PLF from a socioeconomic, societal point of view.

Review of metastatic spine tumour classification and indications for surgery: the consensus statement of the Global Spine Tumour Study Group.

Choosing the right operation for metastatic spinal tumours is often difficult, and depends on many factors, including life expectancy and the balance of the risk of surgery against the likelihood of improving quality of life. Several prognostic scores have been devised to help the clinician decide the most appropriate course of action, but there still remains controversy over how to choose the best option; more often the decision is influenced by habit, belief and subjective experience. The purpose of this article is to review the present systems available for classifying spinal metastases, how these classifications can be used to help surgical planning, discuss surgical outcomes, and make suggestions for future research. It is important for spinal surgeons to reach a consensus regarding the classification of spinal metastases and surgical strategies. The authors of this article constitute the Global Spine Tumour Study Group: an international group of spinal surgeons who are dedicated to studying the techniques and outcomes of surgery for spinal tumours, to build on the existing evidence base for the surgical treatment of spinal tumours.

Investigation of particle-functionalized tissue engineering scaffolds using X-ray tomographic microscopy.

A low-density, porous chitosan/poly-(dl-lactide-co-glycolide) (PLGA) microparticle composite scaffold was produced by thermally induced phase separation followed by lyophilization, to provide a bicontinuous microstructure potentially suitable for tissue engineering and locally controlled drug release. PLGA particles were mixed into the chitosan solution and subsequent phase separation during chitosan solidification forced PLGA particles into chitosan phase (Plateau borders). The distributions of volume, surface area, and elongation of 15,422 inclusions of agglomerated PLGA particles were calculated and approximated with log-normal distribution functions from nanotomography reconstructions. Cluster analysis revealed a homogenous inclusion distribution throughout the scaffold. The spatial location and orientation of individual inclusions within the Plateau borders of the scaffold were determined and from these the nearest-neighbor inter-inclusion distance distribution calculated, showing a mean of 2.5 microm. The depth of the inclusions in Plateau borders peaks at 700 or 125 nm, respectively, indicating a step-wise drug release from inclusions successively exposed during scaffold decomposition. Particle diameter ranged from 400 nm to 3 microm and inclusion Feret lengths ranged from 800 nm to 12 microm. These findings on composite morphology and distribution of inclusions are fundamental for predicting scaffold deterioration and particle-mediated drug release during ex vivo and in vivo cell cultivation.

Surgical repair of annulus defect with biomimetic multilamellar nano/microfibrous scaffold in a porcine model.

Annulus defect is associated with reherniation and disc degeneration after discectomy; currently there is no effective treatment that addresses this problem. The annulus is a hierarchical lamellar structure, where each lamella consists of aligned collagen fibres, which are parallel and tilted at 30° to the spinal axis. In this study, a biomimetic biodegradable scaffold consisting of multilamellar nano/microfibres, sharing nanotopography and microporosity similar to the native lamellar structure, was assessed in a porcine model, aided by sealing with fascia and medical glue and subsequent suture fixation. After 6- and 12-week observation, we found that this treatment restored nucleus volume and slowed down disc degeneration, as indicated by magnetic resonance imaging of T1/T2-weighted, T2-mapping, T1-ρ imaging. Histological analysis showed aligned collagen fibres organized in the scaffold and integrated with surrounding native annulus tissue. The autologous bone marrow concentrate-seeded scaffolds showed slightly earlier collagen fibre formation at 6 weeks. This novel treatment could efficiently close the annulus defect with newly formed, organized and integrated collagen fibres in a porcine model. Copyright © 2016 John Wiley & Sons, Ltd.

Anastomotic stenting in a porcine aortoiliac graft model.

The purpose of the study was to evaluate the feasibility of anastomotic stent application in a porcine aortoiliac graft model. In a total of 10 pigs, a polytetrafluoroethylene aortobi-iliac graft was implanted through a midline abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1 mm to produce irregularities at the downstream anastomosis. After transverse graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites were left untreated. After two weeks, the patency of graft limbs was evaluated by contrast-enhanced computed tomography (CT). Both metal and polymeric stent designs provided adequate flexibility to manoeuvre across the anastomotic site for expansion in the chosen position. After deployment, the stent-arterial wall contact was complete on a macroscopic view. On CT scan, all metal and PLLA-stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary, this model is feasible to assess preclinically the deployment and patency rate of an anastomotic stent and to test future stent developments.

Surgery for metastatic spine tumors in the elderly. Advanced age is not a contraindication to surgery!

BACKGROUND: With recent advances in oncologic treatments, there has been an increase in patient survival rates and concurrently an increase in the number of incidence of symptomatic spinal metastases. Because elderly patients are a substantial part of the oncology population, their types of treatment as well as the possible impact their treatment will have on healthcare resources need to be further examined. PURPOSE: We studied whether age has a significant influence on quality of life and survival in surgical interventions for spinal metastases. STUDY DESIGN: We used data from a multicenter prospective study by the Global Spine Tumor Study Group (GSTSG). This GSTSG study involved 1,266 patients who were admitted for surgical treatments of symptomatic spinal metastases at 22 spinal centers from different countries and followed up for 2 years after surgery. PATIENT SAMPLE: There were 1,266 patients recruited between March 2001 and October 2014. OUTCOME MEASURES: Patient demographics were collected along with outcome measures, including European Quality of Life-5 Dimensions (EQ-5D), neurologic functions, complications, and survival rates. METHODS: We realized a multicenter prospective study of 1,266 patients admitted for surgical treatment of symptomatic spinal metastases. They were divided and studied into three different age groups: <70, 70-80, and >80 years. RESULTS: Despite a lack of statistical difference in American Society of Anesthesiologists (ASA) score, Frankel neurologic score, or Karnofsky functional score at presentation, patients >80 years were more likely to undergo emergency surgery and palliative procedures compared with younger patients. Postoperative complications were more common in the oldest age group (33.3% in the >80, 23.9% in the 70-80, and 17.9% for patients <70 years, p=.004). EQ-5D improved in all groups, but survival expectancy was significantly longer in patients <70 years old (p=.02). Furthermore, neurologic recovery after surgery was lower in patients >80 years old. CONCLUSIONS: Surgeons should not be biased against operating elderly patients. Although survival rates and neurologic improvements in the elderly patients are lower than for younger patients, operating the elderly is compounded by the fact that they undergo more emergency and palliative procedures, despite good ASA scores and functional status. Age in itself should not be a determinant of whether to operate or not, and operations should not be avoided in the elderly when indicated.

Bone nanostructure near titanium and porous tantalum implants studied by scanning small angle x-ray scattering.

Bone sections including either titanium or porous tantalum implant devices used for interbody spinal fusion were investigated with position-resolved small angle X-ray scattering (sSAXS). The samples were obtained from six-month-old pigs that had undergone surgery three months prior to sacrifice. The aim of the study was to explore the possibility of using sSAXS to obtain information about thickness, orientation and shape/arrangement of the mineral crystals in bone near the implant surfaces. Detailed sSAXS scans were carried out in two different regions of bone adjacent to the implant in each of the implant samples. In the implant vicinity the mineral crystals tended to be aligned with the surface of the implants. The mean crystal thickness was between 2.1 and 3.0 nm. The mineral crystal thickness increased linearly with distance from the implant in both regions of the porous tantalum implant and in one of the regions in the titanium sample. In the second region of the titanium sample the thickest mineral crystals were found close to the implant surface. The observed differences in mineral thickness with distance from the implant surfaces might be explained by differences in mechanical load induced by the implant material and the geometrical design of the implant. The study shows that sSAXS is a powerful tool to characterize the nanostructure of bone near implant surfaces.

Biodegradable polymeric stents for vascular application in a porcine carotid artery model: English version.

Over the past years the development of biodegradable polymeric stents has made great progress; nevertheless, essential problems must still be solved. Modifications in design and chemical composition should optimize the quality of biodegradable stents and remove the weaknesses. New biodegradable poly-L-lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were implantedendovascularly into both common carotid arteries of 10 domestic pigs. At 4 weeks following implantation, computed tomography (CT) angiography was carried out to identify the distal degree of stenosis. The PLLA/P4HB group showed a considerably lower distal degree of stenosis by additional oral application of atorvastatin (mean 39.81 ± 8.57 %) compared to the untreated PLLA/P4HB group without atorvastatin (mean 52.05 ± 5.80 %). The 316L stents showed no differences in the degree of distal stenosis between the group treated with atorvastatin (mean 44.21 ± 2.34 %) and the untreated group (mean 35.65 ± 3.72 %). Biodegradable PLLA/P4HB stents generally represent a promising approach to resolving the existing problems in the use of permanent stents. Restitutio ad integrum is only achievable if a stent is completely degraded.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly.

Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells.

Bone morphogenetic proteins (BMPs) have important functions for the differentiation of bone cells, but the exact role for bone remodeling and bone healing still needs to be defined. Migration of bone forming cells is an important physiological event both during bone healing and bone remodeling. The chemotatic properties of the bone morphogenetic protein family of growth factors have not been investigated. In this study the chemotactic effects of the bone morphogenetic proteins BMP-2, -4, and -6 have been quantitated toward human osteoblasts, human marrow stromal osteoblasts, and U2-OS human osteosarcoma cells. BMP-2 stimulated the migration of human stromal osteoblasts, human osteoblasts, and U2-OS cells with bell-shaped response curves in a dose-dependent manner with a 300% increase in cell migration at 1.0 ng/mL for human stromal osteoblasts and a 170-180% increase for human osteoblasts and U2-OS cells. At higher concentrations, migration decreased to background levels. BMP-4 and -6 did not show any effect on cellular migration. This study shows that BMP-2 can stimulate in vitro migration of human osteoblasts and human osteosarcoma cells. BMP-2 might play a role in the chemotactic recruitment of especially undifferentiated osteoblasts during bone remodeling and bone healing.

Chemotaxis of human osteoblasts. Effects of osteotropic growth factors.

The in vitro chemotactic response of human osteoblasts was investigated towards the following growth factors: TGF-beta, PDGFs, FGFs and IGFs. Human osteoblasts grown from trabecular bone after enzymatic digestion were studied. TGF-beta stimulated the migration of human osteoblasts in a dose-dependent manner with a four-fold increase in migrated cells at 100 pg/ml, which was the optimum concentration. PDGF-BB also stimulated migration four-fold in a dose-dependent manner with a maximum response at 10 ng/ml. PDGF-AA, IGF-I and IGF-II stimulated migration two-fold at 100 ng/ml. The results show that TGF-beta and PDGF-BB are important regulators of human osteoblast migration, but other growth factors IGF-I, IGF-II and PDGF-AA may also stimulate osteoblast migration. Our results additionally suggest that TGF-beta and PDGF-BB may participate in the recruitment of osteoblasts during bone remodeling since both TGF-beta and PDGF-BB are found in bone matrix and could be released during osteoclastic bone resorption. They furthermore support a possible use of TGF-beta and PDGF-BB in growth factor-induced osteogenesis.

Changes in lipoxygenase products from synovial fluid in carrageenan induced arthritis in dogs.

A non-suppurative chronic arthritis was induced in the juvenile dog knee by intra-articular instillations with Carrageenan. Lipoxygenase products of arachidonic acid were separated from synovial fluid by reversed-phase high-performance liquid chromatography (RP-HPLC). After ten weeks we observed an accumulation of leukotriene B4 (LTB4) in synovial fluid in five out of six experimental knees (0.94 to 5.5 ng/ml), as judged by integrated optical density. Biological activity of LTB4 was confirmed by chemokinesis. LTB4 was not detected in control knees. The 15-lipoxygenase products, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODD), being inhibitors of 5-lipoxygenase, were found in relatively high levels in the control knees compared to the arthritic knees. The results denote LTB4 as a pro-inflammatory local mediator during carrageenan-induced arthritis; possibly, the decreased levels of 15-HETE and 13-HODD in the arthritic knees may have a regulatory function, thus facilitating LTB4 generation.

Improved bone anchorage of hydroxypatite coated implants compared with tricalcium-phosphate coated implants in trabecular bone in dogs.

Tricalcium phosphate (TCP) and hydroxyapatite (HA) ceramic coatings are bioactive coatings that have been shown to stimulate bone apposition onto ceramic-coated implants. TCP and HA ceramics have well-documented differences in physical properties, but both types of ceramics are used for stimulation of bone ongrowth to cementless endo-prosthetic components clinically. However, little is known about the difference in osteoconductive properties between these coatings when inserted into trabecular bone in a controlled experimental situation. Unloaded cylindrical gritblasted titanium (Ti-6A1-4V) implants (6 x 10 mm) coated with either hydroxyapatite (HA) or tricalcium phosphate (TCP) ceramic were inserted into the proximal humerus of 20 skeletally mature dogs. The implants were initially surrounded by a 2 mm gap. Each animal received one HA-coated implant and one TCP-coated implant. All dogs were sacrificed 6 weeks after surgery. Results were evaluated by histomorphometry and mechanical push-out test. Push-out tests demonstrated that HA-coated implants were 10-fold stronger fixated in comparison to TCP-coated implant. Bone ongrowth was significantly higher for HA-coated implants compared to TCP-coated implants. Bone volume in the gap showed a tendency to less bone volume around HA-coated implants compared to TCP-coated implants but this difference was insignificant. As expected almost all of the TCP coating were resorbed after 6 weeks and almost none of the HA coating. HA-coated implants with a grit-blasted surface provide a favorable early mechanical implant anchorage most likely due to superior ceramic stability compared to TCP-coated implants.

Transforming growth factor-beta1 adsorbed to tricalciumphosphate coated implants increases peri-implant bone remodeling.

Increasing experimental interest has emerged for the use of growth factors to stimulate bone healing and bone formation in various clinical situations. We and others have demonstrated that recombinant human transforming growth factor-beta1 (rhTGF-beta1) adsorbed onto tricalcium phosphate (TCP)-coated implants can improve mechanical fixation and bone ongrowth. The present study evaluated bone remodeling in newly formed bone and adjacent trabecular bone around TCP-coated implants with and without rhTGF-beta1 adsorption. Unloaded cylindrical grit-blasted titanium alloy implants coated with TCP were inserted bilaterally into the femoral condyles of 10 skeletally mature mongrel dogs. The implants were initially surrounded by a 2 mm gap. Implants with 0.3 microg rhTGF-beta1 were compared with implants without growth factor. The dogs were sacrificed after six weeks. Bone remodeling was evaluated by histomorphometry on Goldner-stained undecalcified sections. The bone volume in the gap was increased significantly from 17.6% in the control group to 25.6% in the rhTGF-beta1 group (p = 0.03). Also bone surface was increased in the rhTGF-beta1 group. The osteoclast covered surfaces were increased from 3.6% in the control group to 5.9% in the rhTGF-beta1 group (p = 0.02). In the surrounding trabecular bone no significant changes in bone remodeling parameters was demonstrated. This study suggests that rhTGF-beta1 adsorbed onto TCP-ceramic coated implants accelerates repair activity in the newly formed bone close to the implant, but it does not seem to influence bone remodeling in preexisting bone at a greater distance from the implant.

Role of different loading conditions on resorption of hydroxyapatite coating evaluated by histomorphometric and stereological methods.

The role of different loading conditions on resorption of plasma-sprayed hydroxyapatite coating was investigated in an experimental study. Resorption of hydroxyapatite was quantified by histomorphometric and stereological methods on backscattered scanning electron images. Hydroxyapatite-coated titanium implants were inserted unilaterally into the medial femoral condyle of the knee in 14 mature dogs. Initially, all implants were subjected to controlled micromotion of 150 microns. After 4 weeks, the dogs were randomly assigned either to have the implant surgically immobilized to prevent further micromovement or to have a sham operation. Sixteen weeks after the first operation, the implants were analyzed. Six noninserted implants served as controls. The surface area and volume of the hydroxyapatite coating were reduced on the immobilized implants by 53 and 67% (p < 0.05), respectively, and were further significantly reduced on the continuously loaded implants by 83 and 87%, respectively, compared with the control implants. The hydroxyapatite coating was significantly thinner on immobilized (15 microns) and continuously loaded (15 microns) implants as compared with control implants (23 microns), but no difference between the inserted implants was found. Areas not covered with hydroxyapatite had 29 and 24% bone coverage on the immobilized and continuously loaded implants (not significant). Resorption of hydroxyapatite coating did occur in vivo. Continuous loading of the implants accelerated resorption significantly compared with immobilization of the implants. It is suggested that completely resorbed hydroxyapatite was partly replaced by bone in direct contact with the metal implant surface.

Vasoactive substances in subchondral bone of the dog knee.

The purpose of the present study was to investigate regulatory mechanisms for subchondral bone blood flow. A model including elevation of joint cavity pressure in the immature dog knee was applied. The role of prostaglandins in bone blood flow regulation was indirectly examined by indomethacin blockade. In six puppies, both venous tamponade of the joint cavity [50% of the mean arterial blood pressure (MAP)] and arterial tamponade (150% of MAP) resulted in a significant increase in the intraosseous pressure of the distal femoral epiphyses (p less than 0.05). During venous tamponade no changes were registered in pO2, pCO2, pH, potassium, and lactate in blood withdrawn from the distal femoral epiphyses. Arterial tamponade resulted in hypoxia, a decrease in pH, and increased lactate. Inhibition of the prostaglandin synthesis did not alter this response pattern. Thus, the present study suggests the presence of a regulatory mechanism for subchondral bone blood flow since venous tamponade did not significantly alter intraosseous gas tensions, pH, lactate, or potassium in spite of elevated venous outlet resistance. The study does not allow any conclusion as to the exact nature of the regulatory mechanism, but local metabolic regulation is likely to be involved as indicated by accumulation of vasoactive substances at higher tamponade levels. Prostaglandins are probably of minor importance in this regulation.

Adrenergic responses in human small arteries isolated from the femoral neck.

Many pathological bone conditions are accompanied by changes in bone perfusion. However, no method has yet allowed investigation of vascular reactivity in human bone tissue. In the present study, arterial segments (diameter approximately 0.25 mm) were isolated from human bone biopsies and mounted as ring preparations in vitro. The viability of the arteries and the effects of adrenoceptor stimulations were investigated. Combined alpha- and beta-adrenoceptor stimulation (noradrenaline 10(-8)-10(-5) M) and specific alpha1-adrenoceptor stimulation (phenylephrine, 10(-8)-10(-4.5) M) induced concentration-dependent contractions in all arteries. Selective stimulation of alpha2-receptors (B-HT 933, 10(-8)-10(-3.5) M) only induced contraction in three of eight arteries. Stimulation of beta-receptors with isoprenaline (10(-6) M) resulted in vasorelaxation in 3 of 10 arteries. In all arteries, acetylcholine (10(-10)-10(-5) M) induced vasorelaxation, demonstrating preserved function of the endothelium. The results suggest that primarily alpha1-receptors are responsible for adrenoceptor induced vasoconstriction in human bone while functional alpha2- and beta-receptors may not be consistently expressed. The model is the first to allow investigations on vascular reactivity in human bone tissue and may become valuable for assessment of both normal and pathological bone physiology.