An interleukin-1 polymorphism additionally intensified by atopy as prognostic factor for aseptic non-mechanical complications in metal knee and hip arthroplasty.

Background: In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood. Objective: To assess the association of IL-1ß polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty. Methods: In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis. Results: We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy. Conclusion: The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele.

Generation of a series of Bn fused oligo-naphthalenes (n = 1 to 3) from a B1-polycyclic aromatic hydrocarbon.

A series of Bn-PAHs have been prepared by functionalisation of a B1-PAH, leading to the first only boron doped B3-PAH to the best of our knowledge. These Bn-PAHs represent the first three members of a series of {B-Mes} fused oligo-naphthalenes and trends in key properties of this series have been elucidated.

Interaction of 5-hydroxy-l-tryptophan and negative dietary cation-anion difference on calcium homeostasis in multiparous peripartum dairy cows.

Hypocalcemia affects almost 50% of all dairy cows. Our laboratory has previously demonstrated that infusions of the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP) increase circulating calcium concentrations in the Holstein transition cow. It is unknown whether feeding a negative dietary cation-anion difference (DCAD) diet alters the relationship between 5-HTP and hypocalcemia. The main objective of this study was to determine whether feeding a negative DCAD (-DCAD) diet before calving in conjunction with 5-HTP treatment could further diminish the magnitude of hypocalcemia at the time of calving. We used a randomized complete block design with a 2 × 2 factorial arrangement. Thirty-one multiparous Holstein cows were fed either a positive (+13 mEq/100 g) or negative (-13 mEq/100 g) DCAD diet 21 d before parturition and were intravenously infused daily with saline or 5-HTP (1 mg/kg) starting 7 d before the estimated date of parturition. Cows were blocked by parity and were randomly assigned to 1 of 4 treatment groups: positive DCAD plus saline, positive DCAD plus 5-HTP, negative DCAD plus saline, and negative DCAD plus 5-HTP, resulting in n = 8 per group. Total calcium (tCa), ionized calcium (iCa), and feed intake were recorded. The iCa was elevated prepartum in the -DCAD/5-HTP group compared with the other treatment groups as well as on d 0 and 1 postpartum. Although differences in tCa were not significant across the pre- or postpartum periods, tCa was numerically higher on d 0 and significantly higher on d 1 in -DCAD/5-HTP cows compared with all other groups. Prepartum the -DCAD/5-HTP treatment group ate less than the other treatment groups; however, postpartum dry matter intake differences were not significant. These findings demonstrate that feeding a -DCAD diet in conjunction with 5-HTP prepartum can increase postpartum circulating iCa concentrations and therefore diminish the magnitude of hypocalcemia at the time of parturition.

A modular route to boron doped PAHs by combining borylative cyclisation and electrophilic C-H borylation.

Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach for modifying key physical properties, however, there are extremely few modular routes that enable facile formation of B-, B2- and B,N-(specifically not containing direct B-N bonds) doped PAHs despite the growing importance of these materials. Sequential, one pot borylative cyclisation/intramolecular electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to access novel B-, B,N- and B2-doped (PAHs). The initial products, dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with [Ph3C][BF4]/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However, for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior to Trip installation due to preferential oxidation of an isopropylaryl moiety to the styrene. This alternative sequence enables access to Trip-B-PAHs and to structurally constrained B and B2-PAHs. Analysis of the solid state structures and optoelectronic properties of these PAHs confirm that frontier orbital energies, extended packing structures, Stokes shift and quantum yields all can be rationally modified using this methodology. The simplicity of this synthetic approach makes it a powerful tool for rapidly generating novel bench stable boron doped PAHs, which is important for facilitating further structure-property relationship studies and the wider utilisation of these materials in optoelectronic applications.

RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells.

Pancreatic cancer is characterized by a microenvironment suppressing immune responses. RIG-I-like helicases (RLH) are immunoreceptors for viral RNA that induce an antiviral response program via the production of type I interferons (IFN) and apoptosis in susceptible cells. We recently identified RLH as therapeutic targets of pancreatic cancer for counteracting immunosuppressive mechanisms and apoptosis induction. Here, we investigated immunogenic consequences of RLH-induced tumor cell death. Treatment of murine pancreatic cancer cell lines with RLH ligands induced production of type I IFN and proinflammatory cytokines. In addition, tumor cells died via intrinsic apoptosis and displayed features of immunogenic cell death, such as release of HMGB1 and translocation of calreticulin to the outer cell membrane. RLH-activated tumor cells led to activation of dendritic cells (DCs), which was mediated by tumor-derived type I IFN, whereas TLR, RAGE or inflammasome signaling was dispensable. Importantly, CD8α(+) DCs effectively engulfed apoptotic tumor material and cross-presented tumor-associated antigen to naive CD8(+) T cells. In comparison, tumor cell death mediated by oxaliplatin, staurosporine or mechanical disruption failed to induce DC activation and antigen presentation. Tumor cells treated with sublethal doses of RLH ligands upregulated Fas and MHC-I expression and were effectively sensitized towards Fas-mediated apoptosis and cytotoxic T lymphocyte (CTL)-mediated lysis. Vaccination of mice with RLH-activated tumor cells induced protective antitumor immunity in vivo. In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors. In summary, RLH ligands induce a highly immunogenic form of tumor cell death linking innate and adaptive immunity.

The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses.

Inhibitors of dipeptidylpeptidase IV (DPP-IV) represent a novel class of frequently used anti-diabetic drugs. In addition to its function in metabolic regulation, DPP-IV also plays a role in the immune system. Whether the DPP-IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. Here, we investigated the effect of these agents on both innate and adaptive immunity. We found that the DPP-IV inhibitors did not affect the innate immune response induced by Toll-like receptor (TLR) ligands, as cytokine secretion and induction of co-stimulatory molecules by human blood mononuclear cells was not impaired. Furthermore, proliferation of T cells and suppressive function of regulatory T cells was preserved. Mice treated with vildagliptin showed normal cytokine production, immune cell activation and lymphocyte trafficking upon TLR activation. Thus, crucial immunological parameters remain unaffected upon treatment with DPP-IV inhibitors, a fact that is reassuring with respect to safety of these drugs.

[Ultrasound-based treatment of proximal humerus fractures in children]. / Ultraschallbasierte Therapiesteuerung bei subkapitalen Humerusfrakturen im Wachstumsalter.

INTRODUCTION: The treatment of juvenile proximal humerus fractures is based on the extent of the deformity. The standard diagnosis with X-ray images in 2 directions is error-prone and can lead to a suboptimal treatment. The aim of this study was to evaluate if ultrasound imaging can improve the measurement of the deformity of proximal humerus fractures. MATERIAL AND METHODS: In a prospective, multicentre trial children aged 0-12 years with a suspected proximal humerus fracture were initially examined with a 10-MHz linear transducer in 4 directions and the maximum deformity was determined. Afterwards the standard X-rays were taken and the results of both methods compared. The certainty of both methods was compared with a standardised nominal scale. RESULTS: From 8/2010 to 5/2011 6 consultants in 4 hospitals examined 30 patients (16 m, 14 f, mean age 7.9 years). In 15 cases the ultrasound showed a larger deformation than the X-rays and in 2 cases vice versa. In 11 cases the measurement was identical 6 of which were undisplaced. The mean difference of the measurement of the deformity was + 8.6°, with 14.2° in the displaced fractures. The certainty of the ultrasound was rated significantly higher (p < 0.05) than that of radiography. DISCUSSION: With a correct technique the deformity cannot be overestimated by ultrasound means and the safeness is rated significantly higher in comparison to the X-ray imaging. It seems that ultrasound is a meaningful method to improve the measurement of the deformity of proximal humerus fractures in children. Deficiencies are found only in cases with massive deformities which demand a reduction and stabilisation.

[Total hip arthroplasty by neuromuscular impairment: functional outcome]. / Hüftendoprothetik bei neuromuskulärem Impairment: Funktionelles Outcome.

INTRODUCTION: Studies which deal with the problems of total hip arthoplasty (THA) in patients with neuromuscular impairments are rare. The aim of this study was to examine whether THA for painful coxarthrosis in such patients relieved pain and improved functional outcome and how high the complication rate was. MATERIAL AND METHODS: For this study 10 patients (13 hips) with neuromuscular impairment who had received a total hip arthroplasty for painful coxarthrosis were retrospectively identified. A chart review determined the preoperative functional level. For postoperative evaluation all patients completed a questionnaire, including a self-created modified hip score. RESULTS: The average age of the patients at the time of follow-up was 42.1 years (range 26.5-62.2 years, standard deviation SD 9.9 years) and the minimum follow-up was 24 months (average 80.3 months, range 24-143 months, SD 47 months). Pain relief was obtained for all patients but two patients had a postoperative dislocation and four patients had a major complication (infection) requiring removal of the implant. Therefore, the follow-up rate at the final examination with completed questionnaires was 69% (9 out of 13 excluding patients with removal of THA). These patients showed an improved function from 42.2-83.66 points in the hip score (p=0.0006) and there was general satisfaction with the procedure. DISCUSSION: Total hip arthroplasty can provide improved function in patients with neuromuscular impairment and severe coxarthrosis. The rate of complications was moderate in this series; however, the high infection rate in these patients should be kept in mind.

Shield kyphoplasty through a unipedicular approach compared to vertebroplasty and balloon kyphoplasty in osteoporotic thoracolumbar fracture: a prospective randomized study.

OBJECTIVE: Currently, there are no clinical studies comparing different cement augmentation methods, and no clinical observational studies of a unipedicular approach. DESIGN, PATIENTS, INTERVENTIONS, MAIN OUTCOME MEASUREMENTS: The present study compared three commercially available vertebral augmentation systems: balloon kyphoplasty, vertebroplasty and shield kyphoplasty. The primary objective was to assess change in subjective severity of backache on a visual analog scale (VAS) and subjective improvement in quality of life on the Oswestry Disability Index (ODI), at a mean 6 months post-surgery. The secondary objective was to analyze current radiological imaging (X-ray, and in some cases CT) with regard to height restoration, cement distribution and leakage and recurrent fracture. RESULTS: Mean follow-up was 5.8 months. Mean preoperative Beck vertebral height index did not significantly differ between the three augmentation system groups (P>0.05). Comparing surgery time, fluoroscopy time and dose-area-product (cGy × cm(2)) showed a statistically significant difference (P<0.01) in favor of the vertebroplasty technique. Augmentation provided significant improvement in VAS pain assessment, but with no significant difference between augmentation systems. Results on the ODI were less pronounced, with significant improvement of 22% to 45%, but again without significant difference between augmentation systems. CONCLUSIONS: Overall, apart from mostly asymptomatic cement leakage, vertebroplasty could be considered as the surgical procedure of choice.

Angiogenesis and healing with non-shrinking, fast degradeable PLGA/CaP scaffolds in critical-sized defects in the rabbit femur with or without osteogenically induced mesenchymal stem cells.

Cost effective and safely to apply tissue engineered constructs of big volume bone transplants for the reconstruction of critical sized defects (CSD) are still not available. Key problems with synthetic scaffold materials are shrinkage and fast degradation of the scaffolds, a lack of blood supply and nutrition in the central scaffold volume and the absent or the scarce development of bone tissue along the scaffold to bridge the bone defect. The use of composite scaffolds made of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium phosphates (CaP) revealed promising therapeutical options for the regeneration of critical sized bone defects. In this study interconnectively macroporous PLGA scaffolds loaded with microporous and coated with nanoporous calcium phosphates were either seeded in fixed bed bioreactors with allogenic osteogenically induced mesenchymal stem cells and implanted or implanted unseeded into critical sized femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was excised where the proximal and distal parts of the femur were fixed and stabilized by the use of an eight-hole linear reconstruction plate and secured with three bicortical screws (2.7 mm diameter) on every side of the osteotomy. Aim of the study was if we could find a way to load and coat PLGA scaffolds with CaP so that shrinkage of scaffolds could be avoided, which would favour angiogenesis, blood supply and nutrition in the construct and thus avoid central necroses regularly observed so far in transplants not vascularized and which would be inhabited by cells of he bone lineage forming new bone and healing the defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided and scaffolds were practically not degraded. Both scaffolds, loaded and loaded and coated, revealed blood vessels in all parts of the implants after 4 weeks. Only in scaffolds seeded with allogenic mesenchymal stem cells the development of bridging bone constructs between proximal and distal edges of the femur was observed after four weeks without further supplementation of growth factors. In case of the implantation of non-seeded scaffolds no obvious scaffold bound bone development could be shown.

High flexion total knee arthroplasty - mid-term follow up of 5 years.

Because of demographic changes, ever greater demands are made of knee replacement systems by patients and surgeons. To meet these demands, knee joint systems with increased flexion are currently being marketed. The main hypothesis of the present study was to evaluate the functional outcome of a high flexion TKA in amid-term follow up. 75 consecutive patients (29 men and 46 women) who had primary arthritis of the knee with similar deformity and range of motion undergo TKA using a NexGen Cr Flex mobile.Knee Society knee and functional scores and range of motion were assessed.The follow-up duration was 5 years. There was a highly significant improvement in comparison to the preoperative status (p<0.005). The maximum flexion was 122° in mean and the mean KSS was 167 (SD: 21) at final follow up. Despite positive results in the first 5 postoperative years, the NexGen Cr Flex mobile TKA shows no advantages with regard to ROM and KSS compared to the recent literature. Long-term studies are needed to determine a superiority of high flexion knee implants versus traditional TKA´s.

Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn's Registry.

Aldosterone excess in the context of primary aldosteronism (PA) has been associated with impaired glucose tolerance and diabetes mellitus. We retrospectively assessed the prevalence of diabetes mellitus in patients from the German Conn's Register and compared the data with those from hypertensive subjects of a population-based survey. In a case-control study, we have compared 638 patients with PA from the German Conn's registry who were treated in 6 German centers with 897 hypertensive control subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg (KORA). The samples were matched for age, sex, and blood pressure in a 1:1 ratio. Risk factors associated with the presence of diabetes mellitus were calculated in 638 patients with PA and 897 hypertensive controls. In the case control study, the diabetes prevalence was calculated in 338 cases and controls. In patients with primary aldosteronism, age, BMI, and a higher number of antihypertensive drugs (lowest tertile vs. highest tertile) were variables associated with diabetes mellitus. In contrast, serum potassium and plasma aldosterone concentrations were not associated with higher diabetes prevalence, whereas diastolic blood pressure was inversely associated with diabetes mellitus. Diabetes mellitus was more prevalent in patients with PA than in 338 matched controls (23 vs. 10% in controls). Our data for the German population show that diabetes mellitus is more prevalent in patients with primary aldosteronism than in hypertensive controls.

Zetos: a culture loading system for trabecular bone. Investigation of different loading signal intensities on bovine bone cylinders.

The objective of this investigation was to test the effects of different intensities (1000, 1500, 2000, 3000, and 4000 microstrain) of a physiological loading signal (jumping) on trabecular bone stiffness and osteoid thickness using the ZETOS culture and loading system. Fourty eight bovine bone samples were randomised equally across 6 groups: 5 loading groups and 1 control group. The bone samples were cultured for 26 days (DMEM high glucose medium) and subjected to mechanical stress on 23 days. The stiffness of the samples was determined each day before loading in the loading groups and every 3rd day in the control group. The stiffness measurements in the loaded groups were significantly higher than in the control group. The degree of stiffness increased continuously throughout the observation period in the 1500, 2000, and 3000 microstrain groups. Maximum stiffness was achieved in the 4000 microstrain after a very short time (8th loading day) and then remained constant to the end of the investigation. The osteoid thickness in this group was, however, not higher than in the 2000 and 3000 microstrain groups. The 2000 microstrain group showed the highest proportion of newly formed osteoid. The amounts of osteoid deposited in the 2000, 3000 and 4000 microstrain groups were significantly greater than in the control group. Moreover, a correlation between increasing intensity of the signal and increase in osteoid deposition was observed. Histological investigations were conducted on non-decalcified bone and showed a well-preserved trabecular architecture and cell morphology.

Gamma irradiation. An effective procedure for bone banks, but does it make sense from an osteobiological perspective?

BACKGROUND: Bone grafts promote bone healing by supplying a three-dimensional structure that supports bone ingrowth. Autologous bone therefore still remains the "gold standard" for grafts. Unfortunately, autologous bone grafts are associated with an increased morbidity. In order to avoid such problems, intensive research has been carried out on alternative materials such as allogeneic bone. However, its use is dependent on bone banks and its availability is limited. Gamma irradiation is now becoming established as a procedure for inactivating bacteria, fungal spores and viruses. Its effects on the biomechanical properties of bone have been analyzed in numerous studies. However, the current literature provides little information as to the effects of gamma sterilization on the osteobiology of allogeneic bone grafts. PURPOSE: The purpose of this study was to evaluate the effect of gamma-sterilized bone grafts on immunocompetent cells by an in vitro model (a culture of human bone marrow cells). METHODS: We decided to use the model of human bone marrow cells in culture for the in vitro analysis because the physiological conditions in the human body can best be simulated in this model and the observed reactions are applicable to humans. RESULTS AND INTERPRETATION: In sum, we found a maximum immune response in gamma-irradiated bone grafts, which, interpreted as a sole result, must be seen as a negative biological effect. However, in view of the good clinical results for gamma-sterilized bone grafts other influences would seem to be the determining factors in clinical outcome. Further research is needed to gain a more exact understanding of these factors.

Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry.

CONTEXT: Primary aldosteronism (PA) is associated with vascular end-organ damage. OBJECTIVE: Our objective was to evaluate differences regarding comorbidities between the hypokalemic and normokalemic form of PA. DESIGN AND SETTING: This was a retrospective cross-sectional study collected from six German centers (German Conn's registry) between 1990 and 2007. PATIENTS: Of 640 registered patients with PA, 553 patients were analyzed. MAIN OUTCOME MEASURES: Comorbidities depending on hypokalemia or normokalemia were examined. RESULTS: Of the 553 patients (61 +/- 13 yr, range 13-96), 56.1% had hypokalemic PA. The systolic (164 +/- 29 vs. 155 +/- 27 mm Hg; P < 0.01) and diastolic (96 +/- 18 vs. 93 +/- 15 mm Hg; P < 0.05) blood pressures were significantly higher in hypokalemic patients than in those with the normokalemic variant. The prevalence of cardiovascular events (angina pectoris, myocardial infarction, chronic cardiac insufficiency, coronary angioplasty) was 16.3%. Atrial fibrillation occurred in 7.1% and other atrial or ventricular arrhythmia in 5.2% of the patients. Angina pectoris and chronic cardiac insufficiency were significantly more prevalent in hypokalemic PA (9.0 vs. 2.1%, P < 0.001; 5.5 vs. 2.1%, P < 0.01). Overall, cerebrovascular comorbidities were not different between hypokalemic and normokalemic patients, however, stroke tended to be more prevalent in normokalemic patients. CONCLUSIONS: Our data indicate a high prevalence of comorbidities in patients with PA. The hypokalemic variant is defined by a higher morbidity than the normokalemic variant regarding some cardiovascular but not cerebrovascular events. Thus, PA should be sought not only in hypokalemic but also in normokalemic hypertensives because high-excess morbidity occurs in both subgroups.

Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model.

BACKGROUND: Tumour-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by vaccination with dendritic cells (DCs). However, clinical responses to DC-based vaccination have only been observed in a minority of patients with solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells. It has been shown previously that gemcitabine sensitises human pancreatic carcinoma cells against CTL-mediated lysis. Here, a murine pancreatic carcinoma model was used to investigate whether combination with gemcitabine increases therapeutic efficacy of DC-based vaccination. METHODS: Bone marrow-derived DCs from C57BL/6 mice were loaded with UV-irradiated, syngeneic Panc02 carcinoma cells and were administered subcutaneously. For prophylactic vaccination, mice were vaccinated three times at weekly intervals prior to tumour challenge with Panc02 cells. Therapeutic vaccination was started when tumours formed a palpable nodule. Gemcitabine was administered intraperitoneally twice weekly. RESULTS: Prophylactic DC-based vaccination completely prevented subcutaneous and orthotopic tumour development and induced immunological memory as well as tumour antigen-specific CTLs. In the subcutaneous tumour model, therapeutic DC-based vaccination was equally effective as gemcitabine (14% vs 17% survival at day 58 after tumour challenge; controls, 0%). Combination of the two strategies significantly increased survival of tumour-bearing mice (50% at day 58 after tumour challenge). DC-based vaccination also prevented death from pulmonary metastatisation after intravenous injection of Panc02 cells. CONCLUSION: DC-based immunotherapy may not only be successfully combined with gemcitabine for the treatment of advanced pancreatic carcinoma, but may also be effective in preventing local recurrence or metastatisation in tumour-free patients.

[Comparative in vitro analysis of vacuum plasma-sprayed titanium implants--evaluation of OPG, Osteokalzin and AP expression]. / Vergleichende In-vitro-Analyse vakuum-plasmagespritzter Titanprobenkörper--Evaluation der OPG-, Osteokalzin- und AP-Expression.

INTRODUCTION: The purpose of this study was to evaluate the influence of different surface topographies on the expression of bone cell-associated proteins, such as osteoprotegerin (OPG), osteocalcin and alkaline phosphatase (AP), and the production of the extracellular matrix (ECM) in vitro. Another aspect was the question as to whether a hydroxyapatite (HA) coating offers additional advantages. Vacuum plasma-sprayed (VPS) pure titanium was used to generate different surface topographies. MATERIALS AND METHODS: The in vitro response of human bone marrow cells to VPS implants (porosity ranging from 25 to 50%, pore size ranging from 50 to 200 microm and roughness ranging from 0.191 to 0.547 mm) and cancellous structured titanium (cs-Ti) as a reference material (55% porosity, pore size of 500 microm, roughness 0.836 mm) were compared. The expression of bone cell-associated proteins, such as OPG, osteocalcin and alkaline phosphatase (AP), was evaluated. Scanning electron microscopy (SEM) was used to judge the production of ECM. RESULTS: All implant materials induced the release of OPG, osteocalcin and AP. Significant differences were evident between the cs-Ti and the different VPS-Ti surface structures. There was no difference in the response between the VPS-Ti surfaces. SEM showed a dense and increased production of ECM on the VPS-Ti surfaces. An additional HA coating caused a faster production of ECM and higher levels of OPG. CONCLUSIONS: The in vitro data presented here demonstrate the superiority of VPS-Ti surfaces over cs-Ti, which is already in clinical use. Differences between the VPS-Ti surfaces were not evident. Presumably, VPS-Ti surfaces offer good prerequisites for a successful integration of the implant in the surrounding tissue. An additional HA coating could influence these events positively.

Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells.

Dendritic cells (DC) are inducers of primary immune responses and represent an attractive vector for cancer immunotherapy. Sphingosine kinase (SphK) and its product sphingosine-1-phosphate (S1P) play an important role in the regulation of immune cells and cancer, affecting processes such as differentiation, growth or migration. We studied the role of SphK and S1P on migration of DC. RT-PCR showed mRNA expression of SphK in DC, declining from immature (iDC) to mature DC (mDC) to antigen-loaded mDC. Expression of S1P receptors was S1P(1) > S1P(2) = S1P(3), unrelated to maturation or antigen uptake. In transwell assays, iDC migrated towards SDF-1, MIP-1alpha, MCP and S1P, whereby S1P combined with a chemokine had a synergistic effect. mDC migrated towards 6Ckine and MIP-3beta, but not towards S1P. The SphK-inhibitor dihydro-sphingosine (DHS) reduced migration of iDC but not of mDC. In addition S1P(3)-inhibitor suramin inhibited DC migration in response to S1P. DHS had a reverse effect on endocytosis, enhancing the uptake of FITC dextran. We also observed an anti-apoptotic effect of S1P on mDC for the first time. This indicates that SphK/S1P may play a role in accumulation of peripheral iDC at the location of antigen and subsequent antigen-uptake. These findings may help to optimise DC-based cancer immunotherapy by modulation of SphK/S1P.

[Patellar instability]. / Femoropatellare Instabilität.

We report a retrospective study of patients with patellar instability, all treated by operation and followed up for 3 years. Patients with recurrent dislocation of the patella, lateral displacement and primary patella dislocation were treated by a Elmslie-Trillat reconstruction combined with a soft tissue intervention. Preoperative and follow-up radiographic evaluation included weight bearing anteroposterior view and merchant view. Evaluation was done using the Insall-Salvati index, sulcus and congruence angle. The operation was performed on 23 patients. The clinical evaluation at follow-up was performed using the Knee-Society- and Tegner-Score. Subjective results of the operation were excellent or good in 22 of the 23 at three years with a redislocation rate of only 1 out of 26. Most patients were able to return to the same level of sporting activity as before the injury. The technique described in this paper tries to correct as much as possible of the abnormal parameters in patellar instability to achieve a dynamic stability of the patella through the full range of motion. The excellent results are presumable explained by the use of the combined technique.