Crosstalk of cardiomyocytes and fibroblasts in co-cultures.

Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter space relevant for fibrotic cardiac tissue development comprising the following essential processes: (i) adhesion to substrates with varying elasticity, (ii) dynamics of contractile function, and (iii) electromechanical connectivity. By combining electric cell-substrate impedance sensing (ECIS) with conventional optical microscopy, we could measure the impact of fibroblast-cardiomyocyte ratio on the aforementioned parameters in a non-invasive fashion. Adhesion to electrodes was quantified via spreading rates derived from impedance changes, period analysis allowed us to measure contraction dynamics and modulations of the barrier resistance served as a measure of connectivity. In summary, we claim that: (i) a preferred window for substrate elasticity around 7 kPa for low fibroblast content exists, which is shifted to stiffer substrates with increasing fibroblast fractions. (ii) Beat frequency decreases nonlinearly with increasing fraction of fibroblasts, while (iii) the intercellular resistance increases with a maximal functional connectivity at 75% fibroblasts. For the first time, cardiac cell-cell junction density-dependent connectivity in co-cultures of cardiomyocytes and fibroblasts was quantified using ECIS.

[Modern unicondylar knee arthroplasty. Tips and tricks]. / Moderne unikondyläre Kniearthroplastik. Tipps und Tricks.

BACKGROUND: Unicondylar knee arthroplasty (UKA) is an established therapeutic option for advanced medial or lateral gonarthrosis. OBJECTIVES: The cornerstones of a successful UKA, careful patient selection, preoperative planning and precise operation technique, are discussed in this overview article. IMPORTANCE: In contrast to total knee arthroplasty, UKA allows preservation of the contralateral and patellofemoral compartments as well as the cruciate ligaments and is often associated with rapid postoperative recovery, improved knee kinematics and knee function. However, UKA is technically very demanding. High revision rates have been reported in particular with widespread application, according to national joint replacement registries. CONCLUSION: Successful UKA relies on meticulous patient selection, preoperative planning and surgical technique. It is justified to broaden classic UKA indications. In medial and lateral UKA three types of mechanical varus-valgus deformity can be encountered: type 1 (isolated intraarticular deformity), type 2 (pronounced deformity due to extraarticular varus deformity in medial UKA or valgus deformity in lateral UKA), type 3 (reduced deformity due to extraarticular valgus deformity in medial UKA or varus deformity in lateral UKA). We believe these deformities should be addressed accordingly with surgical technique.

Survivorship of second-generation metal-on-metal primary total hip replacement.

BACKGROUND: Second generation metal-on-metal total hip replacements (THR) were introduced in the late 1980s and various studies reported conflicting data on their outcome. METHODS: Implant survival of 1,270 second-generation 28 mm metal-on-metal primary THR in 1,121 patients followed prospectively at a mean of 6.8 years postoperatively was evaluated retrospectively. The probability of survival at 10 years was estimated using the method of Kaplan and Meier, and relative risk factors including age, gender, BMI, type of implant fixation and component size were calculated using the Cox proportional-hazards model. RESULTS: Sixty-three (5%) THRs were revised, these being 28 hips for aseptic loosening and 35 for reasons other than aseptic loosening. The probability of survival at 10 years, with revision for any reason as the endpoint, was 0.90 (95% confidence interval (CI) 0.86-0.94) for the THR as a whole, 0.91 (95% CI 0.87-0.95) for the cup, and 0.96 (95% CI 0.94-0.98) for the stem. No demographic factors or covariates were found to significantly affect the implant survivorship. DISCUSSION: As there was no superior probability of survival, and there have been concerns on putative local and systemic toxicity of metal debris, the use of second-generation metal-on-metal articulations for primary THR remains moot.

The 12-item Oxford Knee Score: cross-cultural adaptation into German and assessment of its psychometric properties in patients with osteoarthritis of the knee.

OBJECTIVE: To cross-culturally adapt and validate the Oxford Knee Score (OKS) for use in German-speaking patients with osteoarthritis of the knee. METHODS: After the cross-cultural adaptation (OKS-D), the following metric properties of the questionnaire were assessed in 100 consecutive patients (mean age 66.5 years, 61 women) undergoing total knee replacement: feasibility (percentage of fully completed questionnaires), reliability (Intraclass Correlation Coefficients [ICC] and Bland and Altman's limits of agreement), and construct validity (correlation with the Western Ontario and McMaster Universities Index [WOMAC], Knee Society Score [KSS], Activities of Daily Living Scale [ADLS], and Short Form 12 [SF-12]), floor and ceiling effects, and internal consistency (Cronbach's Alpha, CA). RESULTS: We received 91.9% fully completed questionnaires. Reliability of the OKS-D was excellent (ICC 0.91). Bland and Altman's limits of agreement revealed no significant bias (-0.2) and a random error of 6.2. Correlation coefficients with the other questionnaires ranged from -0.22 (SF-12 Mental Component Scale [MCS]) to -0.77 (ADLS). We observed no floor or ceiling effects. The CA was 0.83. CONCLUSIONS: The German version of the OKS is a reliable and valid measure for the self-assessment of pain and function in German-speaking patients with osteoarthritis of the knee.

Fracture of the lateral process of the talus in snowboarders.

We investigated the clinical and radiological outcome after unilateral fracture of the lateral process of the talus in 23 snowboarders with a mean follow-up of 3.5 years (12 to 76 months). In this consecutive cohort study both operative and non-operative cases were considered. The mean American Orthopaedic Foot and Ankle Society hindfoot score was 94 (82 to 100). The non-operative group of seven with a minimally-displaced fracture scored higher (98 points) than the operative group of 16 with displaced or unstable fractures (93 points). In 88% of operative cases, significant concomitant hindfoot injuries were found at operation. All but eight (35%) patients (six operative and two non-operative) regained their pre-injury level of sporting activity. Subtalar osteoarthritis was present in nine (45%) of the 20 patients available for radiological review, including one late-diagnosed non-operative case and eight operative cases with associated injuries or fracture comminution. The outcome after fracture of the lateral process of the talus in snowboarders is favourable provided an early diagnosis is made and adequate treatment, which is related to the degree of displacement and associated injuries, is undertaken.

Polyethylene particle-induced bone resorption in substance P-deficient mice.

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening.

Effects of cefuroxime on human osteoblasts in vitro.

The local application of antibiotics in bone cement achieves high local effective antibiotic concentrations. Cefuroxime is widely used for antibiotic prophylaxis in orthopedic surgery, and several reports highlighted a beneficial outcome if cefuroxime-impregnated bone cement was used, but there is a lack of information of direct cefuroxime effects on human bone cells. We, therefore, cultured osteoblasts, previously derived from human trabecular bone specimens and used as a cell-pool further on, with different concentrations of cefuroxime (0-1000 microg/mL) for 24, 48, or 72 h. For reversibility testing, osteoblasts were cultivated for 24 h with cefuroxime followed by 48 h without antibiotics. Cell proliferation (MTT), cytotoxicity (lactate dehydrogenase (LDH)-activity), cell metabolism (alkaline phosphatase (ALP)-activity), and extracellular matrix calcification (Alizarin staining) were assessed after antibiotic treatment. Cefuroxime concentrations of 25-100 microg/mL had little or no effect on cellular proliferation. Proliferation was significantly stimulated at 250 and 1000 microg/mL at each time. LDH-activity significantly increased at the highest concentration of 1000 microg/mL at 72 h. ALP-activity first increased at lower concentrations and then significantly decreased at 1000 microg/mL at 48 and 72 h. Similar to ALP-activity, calcification increased at lower concentrations and was not detectable at 1000 microg/mL. All revealed effects at 24 h were at least partially reversible. In the present study, we demonstrated that cefuroxime at lower concentrations had no inhibiting effects on human osteoblasts. In contrast, higher concentrations significantly altered osteoblastic function. When administered locally in total joint arthroplasty, for example, in antibiotic-impregnated bone cement, cefuroxime might critically impair osteoblastic function and periprosthetic bone metabolism.

[Structural femoral head allografts in revision surgery of loosened acetabular cups]. / Strukturelle Femurkopfallografts in der Revisionschirugie von gelockerten Hüftendoprothesenpfannen.

BACKGROUND: Treatment of acetabular bone defects presents a great challenge in revision total hip arthroplasty (THA). Many methods of acetabular reconstruction have been described. The purpose of this study was to evaluate the midterm results of structural femoral head allografts for acetabular reconstruction. METHODS: Thirty-six patients (33 females and 3 males) with acetabular defects ranging from type 2C to type 3B according to Paprosky's classification were included in the study. In all cases acetabular defects were closed using allografts from femoral heads. In 13 cases an uncemented press-fit cup, in 17 cases a cemented polyethylene socket, and in 6 cases a Burch-Schneider antiprotrusion cage was implanted. The mean follow-up period was 84.2 months (range: 5-147). RESULTS: Four acetabular components failed. All 36 grafts were osseointegrated radiographically and formed a mechanically stable construction. The mean Harris Hip Score at the most recent follow-up was 79.8 points. The distance from the obturator line to the prosthesis head center was 3.73 cm (1.17-5.80 cm) preoperatively and 2.79 cm (0.85-4.8 cm) postoperatively (p<0.05). The distance from the teardrop figure to the prosthesis head center was 3.02 cm (1.0-5.8 cm) preoperatively and 3.25 cm (1.6-4.8 cm) postoperatively (p<0.001). CONCLUSIONS: Closure of acetabular defects of types 2C to 3B according to Paprosky's classification can be satisfactorily accomplished using femoral head allografts. These allografts may facilitate future revision surgery. Femoral heads are readily available due to widespread primary total hip replacement surgery. However, the use of structural femoral head allografts for acetabular reconstruction is cost intensive. Individual patient-related aspects, such as the function of revision arthroplasty, have to be considered when planning revision arthroplasty using femoral head allografts.

Trochleaplasty for recurrent patellar dislocation in association with trochlear dysplasia. A 4- to 14-year follow-up study.

We investigated the clinical and radiological outcome of trochleaplasty for recurrent patellar dislocation in association with trochlear dysplasia in 38 consecutive patients (45 knees) with a mean follow-up of 8.3 years (4 to 14). None had recurrence of dislocation after trochleaplasty. Post-operatively, patellofemoral pain, present pre-operatively in only 35 knees, became worse in 15 (33.4%), remained unchanged in four (8.8%) and improved in 22 (49%). Four knees which had no pain pre-operatively (8.8%) continued to have no pain. A total of 33 knees were available for radiological assessment. Post-operatively, all but two knees (93.9%) had correction of trochlear dysplasia radiologically but degenerative changes of the patellofemoral joint developed in 30% (10) of the knees. We conclude that recurrent patellar dislocation associated with trochlear dysplasia can be treated successfully by trochleaplasty, but the impact on patellofemoral pain and the development of patellofemoral osteoarthritis is less predictable. Overall, subjective patient satisfaction with restored patellofemoral stability after trochleaplasty appeared to outweigh its possible sequelae.

[Localization of the neurokinin 1 receptor in hip joints of patients with painful osteoarthritis]. / Die Lokalisation des Neurokinin 1-Rezeptors im Hüftgelenk von Patienten mit schmerzhafter Osteoarthrose.

INTRODUCTION: Recent studies on osteoarthritis have focused on nociceptive substance P (SP) containing afferent nerve fibres. The effects of SP are known to be mainly mediated by the tachykinin receptor neurokinin 1 (NK1-R). AIM: The aim of the present study was to demonstrate the NK1-R in human joint tissues. METHODS: The hip joint capsule of three patients with painful hip osteoarthritis (Group 1), three patients with femoral neck fracture showing no cartilage destruction (Group 2, controls) and the soft tissue of the fossa acetabuli of Group 1 were resected during hip arthroplasty implantation. The tissue samples were cut into small blocks and immersion-fixed in Zamboni's fixative. The specimens were frozen, cut into 50 microm sections and immunostained using a standard immunohistochemical staining protocol. RESULTS: In Groups 1 and 2 the NK1-receptor was localised in the wall of venous vessels, on Schwann cells of nerve bundles and on nerve fibres. In the osteoarthritis group the staining pattern was similar but the number of NK1-bearing cell structures seemed to be enhanced. CONCLUSIONS: The present study provides the first evidence of NK1-R in the human hip joint. In patients with painful osteoarthritis the density of NK1-R-positive cell structures seemed to be increased. The localisation of the NK1 receptor on different cell types suggests multiple effects of SP in normal and osteoarthritic joints.

[A comparison of the antiresorptive effects of bisphosphonates and statins on polyethylene particle-induced osteolysis]. / Ein Vergleich der antiresorptiven Effekte von Bisphosphonaten und Statinen auf Polyethylenpartikel-induzierte Osteolysen.

An ongoing unraveling of the molecular mechanisms in aseptic loosening of hip arthroplasty has opened up novel potential pharmacological interventions. In this study the antiresorptive effects of the bisphosphonate zoledronate and the statin simvastatin on ultra high molecular weighted polyethylene (UHMWPE) particle-induced osteolysis were compared. Two previous studies of our group based on the murine calvarial model of UHWMPE particle-induced osteolysis were pooled to form four study groups. Animals in group I (n=14) underwent sham surgery only. In groups II (n=14), III (n=7) and IV (n=7) UHMWPE particles were implanted on the calvariae. Animals in groups III and IV were additionally treated with zoledronate (single 25 microg/kg s.c. injection) and simvastatin (120 mg/day p.o. for 14 days), respectively. After two weeks, calvaria were processed for undecalcified histomorphometry. Bone resorption was measured using Giemsa staining. Osteoclast numbers were determined using TRAP-staining. UHMWPE particle implantation resulted in a grossly pronounced osteolytic activity with significantly increased values of bone resorption (p < 0.001) and osteoclast numbers (p < 0.001). Additional treatment with zoledronate or simvastatin counteracted the particle-induced effects. A comparison of the two medical treatments revealed no statistically significant differences in bone resorption (p = 0.63) and osteoclast numbers (p = 0.41). A single dose of the bisphosphonate zoledronate decreased UHMWPE particle-induced osteolysis in a murine calvarial model as effectively as a daily treatment with simvastin. Both drug groups may have a preventive and therapeutic role as antiresorptive agents in wear particle-induced bone resorption following total joint replacement.

[Surface cleaning of cemented orthopedic implants with conservation of surface properties]. / Oberflächenreinigung zementierter orthopädischer Implantate unter Schonung der Oberflächeneigenschaften.

Prior to the analysis of explanted cemented orthopedic implants, complete removal of foreign material, blood and residual tissue and thorough cleaning of the surface without compromising its characteristics is essential. We describe a reprocessing procedure comprising the following 4 steps: 1) retrieval and storage, 2) removal of residual bone cement, 3) chemical cleaning in an enzymatic solution, and 4) mechanical cleaning in an ultrasound bath.

Skeletal cystic angiomatosis with severe hip joint deformation resembling massive osteolysis.

An aggressive destruction pattern resulting in joint deformation has not been described in skeletal cystic angiomatosis (SCA) so far. We present the case of a 6-year-old boy with such findings strongly resembling Gorham's disease (massive osteolysis). Since the prognosis of the latter entity tends to be less favorable than in SCA, particularly SCA without extraskeletal involvement, careful differentiation of both disorders appears to be important.

Intracellular measurement of polyethylene particles. A histomorphometric study.

A histological and histomorphometric study was carried out on pseudo-capsules retrieved from patients during revision surgery of cementless total hip replacement. Polyethylene loading and areal polyethylene particle size in different cells of the reticuloendothelial cell line were determined within the tissue by histomorphometry. In the reticuloendothelial cell line, foreign-body giant cells are considered to be the result of confluence of mononuclear macrophages caused by large particles or other unknown stimuli. The aim of this study was to investigate whether polyethylene particle size and polyethylene loading are different in mononuclear macrophages and foreign-body giant cells. The specimens were examined under the light-optical microscope with plain and polarized light. The polyethylene loading of 329 macrophages (mononuclear), 81 small foreign-body giant cells (2-5 visible nuclei), and 103 large foreign-body giant cells (6 or more visible nuclei) was determined and the intracellular polyethylene particle size analyzed by histomorphometry. The mean polyethylene loading was 13 +/- 8 microm2, 25 +/- 16 microm2, and 49 +/- 42 microm2, respectively. This difference was statistically significant (Student's t-test, P < 0.05). The mean polyethylene particle size was 2.34 +/- 3.2 microm2, 3.02 +/- 3.46 microm2, and 4.70 +/- 11.25 microm2, respectively. This difference was statistically significant between macrophages and large foreign-body giant cells (t-test, P < 0.05). The findings of this light-optical study show that the mean intracellular polyethylene particle size is greater in foreign-body giant cells. In addition, absolute polyethylene loading tends to be higher in foreign-body giant cells than in mononuclear macrophages.

Chiral metal-dithiolene/viologen ion pairs: synthesis and electrical conductivity.

Enantiomerically pure dithiolene complexes NBu4[Ni[(R,R)-diotte)2] and NBu4[Ni((S,S)-diotte]2] (diotte2- = a 1,3-dioxolane-tetrathiaethylene), were prepared from the corresponding enantiomers of a diotte2- precursor. The structure of the precursor was solved by single-crystal X-ray analysis; desulfurization afforded a novel tetrathiafulvalene derivative. Combination of the complex monoanion with the enantiomers of the viologen derivative bis(2-methyl-3-hydroxypropyl)-4,4'-dipyridinium (HiBV2+) afforded enantiomeric and diastereomeric ion-pair complexes of the type HiBV[Ni(diotte)2]2. For comparison, the analogous compounds A[Ni(diotte)2]2, (A2+ = methyl (MV2+), octyl (OV2-), stearyl (StV2+) viologen or two 2,2'-bipyridinium acceptors), HiBV-[Ni(diotte)L] [L = mnt2- (maleonitrile-1,2-dithiolate), dmit2- (2-thioxo-1,3-dithiol-4,5-dithiolate)], MV[Ni(dmit)2)]2, [Ni(diotte)2], and [Ni(diotte)(dmit)] were synthesized. An X-ray powder diffraction structural analysis of MV-[Ni(dmit)2)]2 revealed the presence of mixed stacks that contain the sequence anion-anion-cation. While no short contacts are observable within a stack, these are observed between the stacks for the dication-anion interaction by short S...H distances in the range of 2.77 to 2.86 A, and for the anion-anion interaction short S...S distances of 3.55 to 3.65 A. In agreement with the absence of intrastack interactions, no ion-pair charge-transfer band can be detected in this and the other complexes. ESR and UV/Vis data suggest that in [Ni(diotte)2]- electron delocalization is less pronounced than in the corresponding mnt2- and dmit2- complexes. The specific electrical conductivity (sigma) of pressed powder pellets ranges from 10(-2) to 10(-12) ohm(-1) cm(-1) and in all cases increases with increasing temperature (293 - 393 K) according to an Arrhenius law. Corresponding activation energies vary from 0.14 to 0.93 eV and increase linearly with log a for structurally similar ion pairs. Charge generation is postulated to occur by disproportionation of the monoanion as suggested by the almost linear increase of log(sigma) with decreasing disproportionation energy. The conductivity of diastereomers of ions with two unlike configurations like [(S,S)-HiBV]-[Ni[(R,R)-diotte]2]2 (1.1 x 10(-1) ohm(-1) cm(-1)) is one to two orders of magnitude higher as compared to the diastereomers with two like-configured ions.

Total knee arthroplasty in a patient with chronic occlusion of the superficial femoral artery.

In a 67-year-old patient with severe valgus gonarthrosis and chronic occlusion of the superficial femoral artery on the same side, total knee replacement was performed without preceding angioplasty because the collateral circulation was intact. No tourniquet was used. To leave the peripatellar arterial ring intact on one side in this case of lateral patellar maltracking, a lateral approach was used. In this approach, a lateral release forms part of the approach itself. To achieve gentle eversion of the patella, the tibial tubercle was osteotomized. One year postoperatively, the patient was satisfied with the outcome and showed no clinical signs of any vascular deterioration. It is concluded that total knee replacement may be possible in the presence of chronic occlusion of the superficial femoral artery provided that the collateral circulation is intact.

A new articulated elbow external fixation technique for difficult elbow trauma.

Articulated external fixation of the elbow allows aggressive elbow range of motion while protecting the joint and periarticular structures from excessive forces. A technique for aligning a monolateral-hinged fixator to the rotational axis of the elbow without the use of an invasive axis pin has been developed. Thirteen patients with acute and chronic post-traumatic elbow problems were treated over a four year period with this technique. An average arc of motion of 84 degrees was achieved in the frame. Frames were removed at an average of 7.6 weeks. Complications were confined to pin tract infections. In 11 patients followed for an average of 35 weeks the average arc of motion was 81 degrees. Further experience is required to determine the role of this device and to identify which elbows achieve the most benefit compared to conventional techniques.

[Polyethylene content and cell size of foreign body giant cells in aseptic hip prosthesis loosening--a histomorphometric study]. / Polyethylenbeladung und Zellgrösse von Fremdkörperriesenzellen bei der aseptischen Hüftendoprothesenlockerung--Eine histomorphometrische Untersuchung.

INTRODUCTION: In aseptic loosening of cementless hip arthroplasty polyethylene particles are phagocytized by macrophages and foreign-body giant cells. This initiates an osteolytic cascade. In this study, the authors investigated if there are correlations between the size of foreign-body giant cells and the polyethylene loading and number of intracellular particles as determined by light microscopy. MATERIAL AND METHOD: Histological specimens were processed from tissues retrieved during revision surgery of 7 cases of cementless hip arthroplasty which had become aseptically loose. The specimens were analyzed by histolomorphology and histomorphometry. The cell size, polyethylene loading and intracellular particle number of 111 foreign-body giant cells were determined. A regression analysis was performed to investigate if there was a correlation between these variables. RESULTS: The mean cell size was 1417 +/- 487 micron 2, the mean polyethylene loading was 49 +/- 42 micron 2 and the mean intracellular particle number was 10.4 +/- 5.4. The cell size correlated with both the intracellular particle number (r = 0.25) and the polyethylene loading (r = 0.39). CONCLUSIONS: In the cellular reaction to polyethylene particles in aseptic loosening of cementless total hip arthroplasty, the size of foreign-body giant cells correlates with intracellular polyethylene loading and intracellular polyethylene particle number as determined by light microscopy. The presence of large foreign body giant cells might be associated with a high particle load of the tissue and a high osteolytic activity.