Proximal tibial osteophyte volumes are correlated spatially and with knee alignment: a quantitative analysis suggesting the influence of biochemical and mechanical factors in the development of osteophytes.

OBJECTIVE: To characterize the differences and correlations in osteophyte volumes between and within proximal tibial compartments, and to assess the correlations between osteophyte volumes and the femorotibial angle. DESIGN: CT scans of 73 knees with predominantly medial femorotibial osteoarthritis (21 K/L2, 28 K/L3, 24 K/L4) were retrospectively analyzed using a new, reproducible method measuring total and subregional osteophyte volumes in the medial and lateral compartments. Non-parametric statistics was used for comparison and correlation analyses. RESULTS: Total osteophyte volumes were larger in the medial than in the lateral compartment for all severity groups (p < 0.05). Additionally, statistically significant differences were observed among subregions of the lateral compartment in K/L3 and K/L4 knees. Statistically significant positive correlations were found between the medial and lateral total osteophyte volumes in K/L3 and K/L4 knees (ρ ≥ 0.44, p = 0.03), and among most subregional osteophyte volumes within each compartment in K/L3 knees. Markedly fewer statistically significant correlations were present in K/L2 and K/L4 knees. In K/L3 knees, the femorotibial angle was statistically significantly positively correlated with the total osteophyte volume in the medial compartment (ρ = 0.50, p = 0.01), with osteophyte volumes in most medial subregions, and with the osteophyte volume in the lateral posterior subregion (ρ = 0.40, p = 0.05). CONCLUSIONS: Quantitative assessment of osteophytes may bring insight on factors influencing their development. Positive correlations of osteophyte volumes found between and within compartments suggest the influence of biochemical mediators acting on the entire joint, while positive correlations between the femorotibial angle and osteophyte volumes suggest a role of mechanical factors. These hypotheses are to be further confirmed.

Relationships between cartilage thickness and subchondral bone mineral density in non-osteoarthritic and severely osteoarthritic knees: In vivo concomitant 3D analysis using CT arthrography.

OBJECTIVE: To test whether subchondral bone mineral density (sBMD) and cartilage thickness (CTh) of femoral condyles are correlated in knees without and with severe medial femorotibial osteoarthritis (OA), using a subregional analysis with computerized tomography (CT) arthrography. METHODS: CT arthrograms of 50 non-OA (18 males, 58.7 (interquartile range (IQR) = 6.6 years)) and 50 severe medial OA (24 males, 60.5 (IQR = 10.7) years) knees, were retrospectively analyzed. Bone and cartilage were segmented using custom-designed software, leading to 3D models on which each point of the subchondral surface is given a CTh and sBMD value. The average sBMD and CTh were then calculated for the entire weight-bearing regions as well as specific subregions of interest. Linear bivariate and multivariable analyses were performed to test for relationships between sBMD and CTh (regional and subregional measures, or medial-to-lateral ratios), with confounders of age, gender, femoral bone size and femorotibial angle. RESULTS: In non-OA knees, the sBMD and CTh medial-to-lateral ratios were positively correlated for the total region and the external and internal subregions (r ≥ 0.341, P ≤ 0.015). In OA knees, sBMD and CTh medial-to-lateral ratios were negatively correlated for the total region and the external and central subregions (r ≤ -0.538, P < 0.001). Additional positive/negative relationships in the non-OA/OA knees were observed between sBMD and CTh measures in the medial compartment. CONCLUSIONS: The positive correlation between sBMD and CTh in non-OA knees, and the negative one in OA knees, bring support to the theory of a subchondral bone/cartilage functional unit, which could help to better understand the pathophysiology of OA.

Modeling knee osteoarthritis pathophysiology using an integrated joint system (IJS): a systematic review of relationships among cartilage thickness, gait mechanics, and subchondral bone mineral density.

OBJECTIVE: To introduce an integrated joint system (IJS) model of joint health and osteoarthritis (OA) pathophysiology through a systematic review of the cross-sectional relationships among three knee properties (cartilage thickness, gait mechanics, and subchondral bone mineral density). METHODS: Searches using keywords associated with the three knee properties of interest were performed in PubMed, Scopus, and Ovid databases. English-language articles reporting cross-sectional correlations between at least two knee properties in healthy or tibiofemoral OA human knees were included. A narrative synthesis of the data was conducted. RESULTS: Of the 5600 retrieved articles, 13 were included, eight of which reported relationships between cartilage thickness and gait mechanics. The 744 tested knees were separated into three categories based on knee health: 199 healthy, 340 at-risk/early OA, and 205 late OA knees. Correlations between knee adduction moment and medial-to-lateral cartilage thickness ratios were generally positive in healthy, inconclusive in at-risk/early OA, and negative in late OA knees. Knee adduction moment was positively correlated with medial-to-lateral tibial subchondral bone mineral density ratios in knees of all health categories. One study reported a positive correlation between lateral tibial subchondral bone mineral density and femoral cartilage thickness in at-risk/early OA knees. CONCLUSIONS: The correlations identified between knee properties in this review agreed with the proposed relationship-based IJS model of OA pathophysiology. Accordingly, the IJS model could provide insights into overcoming current barriers to developing disease-modifying treatments by considering multiple aspects of OA disease, aspects that could be assessed simultaneously at an in vivo system level.

Quantitative regional and sub-regional analysis of femoral and tibial subchondral bone mineral density (sBMD) using computed tomography (CT): comparison of non-osteoarthritic (OA) and severe OA knees.

OBJECTIVE: This study aimed to compare subchondral bone mineral density (sBMD) between non-radiographic osteoarthritic (OA) and medial femorotibial OA knees, using computed tomography (CT). DESIGN: CT exams from 16 non-radiographic OA (KL grade < 2) and 16 severe medial OA (KL grade ≥ 3) knees (average age of 61.7 ± 3 and 62.2 ± 5 years old respectively, 50% male in each group), were retrospectively analyzed. CT exams were segmented and 3D maps of sBMD based on the CT number in the most superficial 3 mm of femoral and tibial subchondral bone were computed. Average sBMD and medial-to-lateral sBMD ratios were calculated for total load-bearing regions and for sub-regions of interest in the femur and tibia. RESULTS: The analysis of total load-bearing regions did not reveal any significant difference between groups, except for the lateral tibia, where OA knees had lower sBMD. Sub-regional analysis unveiled differences with some sub-regions of the femur and tibia presenting significantly lower (in the lateral compartment) or higher (in the medial compartment) sBMD in OA knees compared to non-OA knees. The M/L sBMD ratios were significantly higher for OA knees compared to non-OA knees for all regions and sub-regions, except for the internal sub-regions. CONCLUSIONS: sBMD locally differs between non-OA and OA knees, in agreement with prior knowledge on biomechanics. CT proved to be a valuable tool for 3D analysis of femoral and tibial sBMD, which can be used in future studies to describe the chronology of sBMD alterations and improve our understanding of the role of subchondral bone in knee OA.

Tibial tunnel placement in posterior cruciate ligament reconstruction: a systematic review.

PURPOSE: Reconstruction of the posterior cruciate ligament (PCL) yields less satisfying results than anterior cruciate ligament reconstruction with respect to laxity control. Accurate tibial tunnel placement is crucial for successful PCL reconstruction using arthroscopic tibial tunnel techniques. A discrepancy between anatomical studies of the tibial PCL insertion site and surgical recommendations for tibial tunnel placement remains. The objective of this study was to identify the optimal placement of the tibial tunnel in PCL reconstruction based on clinical studies. METHODS: In a systematic review of the literature, MEDLINE, EMBASE, Cochrane Review, and Cochrane Central Register of Controlled Trials were screened for articles about PCL reconstruction from January 1990 to September 2011. Clinical trials comparing at least two PCL reconstruction techniques were extracted and independently analysed by each author. Only studies comparing different tibial tunnel placements in the retrospinal area were included. RESULTS: This systematic review found no comparative clinical trial for tibial tunnel placement in PCL reconstruction. Several anatomical, radiological, and biomechanical studies have described the tibial insertion sites of the native PCL and have led to recommendations for placement of the tibial tunnel outlet in the retrospinal area. However, surgical recommendations and the results of morphological studies are often contradictory. CONCLUSIONS: Reliable anatomical landmarks for tunnel placement are lacking. Future randomized controlled trials could compare precisely defined tibial tunnel placements in PCL reconstruction, which would require an established mapping of the retrospinal area of the tibial plateau with defined anatomical and radiological landmarks.

Changes in lower limb biomechanics when following floor-projected foot placement visual cues for gait rehabilitation.

BACKGROUND: Lately, the projection of foot placement visual cues onto the floor has been considered for use in gait rehabilitation. While promising, this approach needs further basic assessment to ensure proper uses. RESEARCH QUESTION: Does following floor-projected foot placement visual cues of one's natural walking pattern induce gait mechanics changes immediately or after a practice period? METHODS: Gait mechanics data from fifteen healthy individuals (7 female, 25.4 ±â€¯5.0 years, 21.5 ±â€¯1.68 kg/m2) was collected during normal walking without visual cues, and during two testing phases (immediate and after 45-60 min of practice) of walking with floor-projected visual cues depicting their normal spatial parameters. Magnitudes and variabilities of spatial gait parameters and sagittal plane lower limb kinematics and kinetics were compared between the three testing phases using repeated measures ANOVA and post-hoc paired t-tests. RESULTS: Compared to normal walking without foot placement visual cues, there was a statistically significant (p < 0.05) increase in stride length (maximum change of 0.01 ±â€¯0.01 m), stance phase knee flexion (2.0 ±â€¯2.5°), and swing phase hip flexion (1.2 ±â€¯1.3°) in both immediate and post-practice testing phases, along with an increase in terminal stance hip (0.28 ±â€¯0.38 %BW*Ht) and knee (0.25 ±â€¯0.25 %BW*Ht) flexion moments in the immediate testing phase. All of these changes between testing phases were smaller than their corresponding normal gait smallest real differences (SRD). With the addition of visual cues, variability was statistically significantly decreased in spatial parameters and increased in knee flexion angle at heel strike and knee flexion moment in terminal stance. SIGNIFICANCE: While biomechanical changes were observed, their magnitudes were small enough to suggest that floor-projected visual cues can be used in gait retraining without introducing unintended gait changes. Furthermore, the results suggested that lengthy practice periods are not necessary. The validity of these observations will, however, need to be confirmed in cases of severe impairments.

Computer-assisted placement technique in hip resurfacing arthroplasty: improvement in accuracy?

Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.

Ambulatory measurement of 3D knee joint angle.

Three-dimensional measurement of joint motion is a promising tool for clinical evaluation and therapeutic treatment comparisons. Although many devices exist for joints kinematics assessment, there is a need for a system that could be used in routine practice. Such a system should be accurate, ambulatory, and easy to use. The combination of gyroscopes and accelerometers (i.e., inertial measurement unit) has proven to be suitable for unrestrained measurement of orientation during a short period of time (i.e., few minutes). However, due to their inability to detect horizontal reference, inertial-based systems generally fail to measure differential orientation, a prerequisite for computing the three-dimentional knee joint angle recommended by the Internal Society of Biomechanics (ISB). A simple method based on a leg movement is proposed here to align two inertial measurement units fixed on the thigh and shank segments. Based on the combination of the former alignment and a fusion algorithm, the three-dimensional knee joint angle is measured and compared with a magnetic motion capture system during walking. The proposed system is suitable to measure the absolute knee flexion/extension and abduction/adduction angles with mean (SD) offset errors of -1 degree (1 degree ) and 0 degrees (0.6 degrees ) and mean (SD) root mean square (RMS) errors of 1.5 degrees (0.4 degrees ) and 1.7 degrees (0.5 degrees ). The system is also suitable for the relative measurement of knee internal/external rotation (mean (SD) offset error of 3.4 degrees (2.7 degrees )) with a mean (SD) RMS error of 1.6 degrees (0.5 degrees ). The method described in this paper can be easily adapted in order to measure other joint angular displacements such as elbow or ankle.

Modulation of the efficiency of a siRNA directed against MDR1 expression in MCF7-R cells when combined with a second siRNA.

Effective silencing of MDR1, one of the genes involved in the multidrug resistance phenotype, can be achieved by the use of an efficient siRNA transfected into the doxorubicin-selected MCF7-R human cell line, alone or combined with a moderately efficient siRNA. On the contrary, there is no MDR1 silencing when it is co-transfected with a control siRNA that does not target the human genome. This results from the limited amount of RISC (RNA-Induced Silencing Complex) in human cells, leading to competition between siRNAs. In the case where the energy difference between the extremities of one of the siRNAs is largely superior to that of the other one, competition between the siRNAs appear to be favorable for the former. It is suggested that designing efficient siRNAs from thermodynamic characteristics is favored when siRNAs are incorporated into the RISC Loading Complex (RLC) rather than directly loaded into RISC.

Total hip arthroplasty using a cementless dual-mobility cup provides increased stability and favorable gait parameters at five years follow-up.

BACKGROUND: Rates of dislocation following primary total hip arthroplasty (THA) vary from 0.5 to 10%. Dual-mobility cups in THA demonstrate increased stability. Clinical outcomes following THA with dual-mobility cups have been reported, but gait has not been assessed. Therefore we performed a retrospective case control study to answer: (1) is gait better in patients following THA with a dual-mobility cup than in frail, elderly patients of the same age? (2) Are clinical outcomes better in patients following THA with a dual-mobility cup than in frail, elderly patients? (3) What is the dislocation rate following THA with a dual-mobility cup? HYPOTHESIS: We hypothesized that patients who underwent THA with a dual-mobility cup have a better gait compared to frail, elderly patients of the same age. PATIENTS AND METHODS: Twenty patients (22 hips), mean age 79.9±7.7 (range, 62.3-88.3) years were assessed in this retrospective case-control series 5.6±1.4 (range: 4.1-8.8) years following dual-mobility cup THA. A reference group consisted of 72 "frail elderly" patients in a rehabilitation hospital for health problems unrelated to the lower limb, with no lower limb surgery or neurological conditions. Temporal and spatial gait performance were measured with four miniature gyroscopes, mounted on each thigh and calf, while patients walked freely along a 30m corridor. Harris Hip Score, WOMAC, radiological outcomes, and dislocation rate were determined. RESULTS: All gait parameters were better in the dual-mobility group compared to the frail elderly group. The dual-mobility group had a higher cadence (100.3 steps/minute versus 75.6 steps/minute), shorter (relative to gait cycle time) stance (61.6% versus 67.8%), shorter (relative to gait cycle time) double stance (23.3% versus 36.0%), longer stride (1.13m versus 0.80m), and faster walking speed (0.96m/s versus 0.52m/s). Range of motion of the shank, thigh and knee were better in the dual-mobility group. Harris Hip Score was 87.6±13.9 (range 51-100) and WOMAC score was 11.3±12.1 (range 0-34) in the THA group. We observed no dislocations. DISCUSSION: Gait patterns five years following THA with the dual-mobility cup were better or comparable to published study populations. LEVEL OF EVIDENCE: III, retrospective case-control series.

Intra-articular steroid injection for osteoarthritis of the hip prior to total hip arthroplasty : is it safe? a systematic review.

AIMS: Using a systematic review, we investigated whether there is an increased risk of post-operative infection in patients who have received an intra-articular corticosteroid injection to the hip for osteoarthritis prior to total hip arthroplasty (THA). METHODS: Studies dealing with an intra-articular corticosteroid injection to the hip and infection following subsequent THA were identified from databases for the period between 1990 to 2013. Retrieved articles were independently assessed for their methodological quality. RESULTS: A total of nine studies met the inclusion criteria. Two recommended against a steroid injection prior to THA and seven found no risk with an injection. No prospective controlled trials were identified. Most studies were retrospective. Lack of information about the methodology was a consistent flaw. CONCLUSIONS: The literature in this area is scarce and the evidence is weak. Most studies were retrospective, and confounding factors were poorly defined or not addressed. There is thus currently insufficient evidence to conclude that an intra-articular corticosteroid injection administered prior to THA increases the rate of infection. High quality, multicentre randomised trials are needed to address this issue. Cite this article: Bone Joint J 2016;98-B:1027-35.

Interactions of iron-anthracycline complexes with living cells: a microspectrofluorometric study.

The interaction of iron-anthracycline complexes with tumor cells has been studied using microspectrofluorometry. The anthracyclines used were adriamycin, 4'-O-tetrahydropyranyladriamycin and daunorubicin. In every case, a 1:3 Fe(III)-anthracycline complex is formed. The three daunorubicin molecules that bind to one Fe(III) are not chemically modified through complexation with iron. In the case of the Fe(III)-adriamycin and Fe(III)-4'-O-tetrahydropyranyladriamycin complexes, about one of the three anthracycline molecules is chemically modified, yielding a highly lipophilic derivative, the 7,8-dehydro-9,10-desacetyladriamycin. The others molecules remain unchanged, i.e., highly hydrophilic in the case of adriamycin. These two species have a different fluorescent spectrum and can be identified inside the cell, using microspectrofluorometry. In the case of the Fe(III)-adriamycin complex, the lipophilic derivative is more rapidly internalized in the cell than the hydrophilic one. Diffusion into the plasmic membrane is the limiting step for the uptake of anthracycline by cells; this means that the plasmic membrane speeds up the dissociation of the Fe(III)-anthracycline complex.

Computer-assisted two-dimensional preoperative planning for total hip arthroplasty: clinical evaluation.

The purpose of this study is to clinically validate a new two-dimensional preoperative planning software for cementless total hip arthroplasty (THA). Manual and two-dimensional computer-assisted planning were compared by an independent observer for each of the 30 patients with osteoarthritis who underwent THA. This study showed that there were no statistical differences between the results of both preoperative plans in terms of stem size and neck length (<1 size) and hip rotation center position (<5 mm). Two-dimensional computer-assisted preoperative planning provided successful results comparable to those using the manual procedure, thereby allowing the surgeon to simulate various stem designs easily.

In vivo electrochemical corrosion study of a CoCrMo biomedical alloy in human synovial fluids.

The present study was initiated with the aim to assess the in vivo electrochemical corrosion behaviour of CoCrMo biomedical alloys in human synovial fluids in an attempt to identify possible patient or pathology specific effects. For this, electrochemical measurements (open circuit potential OCP, polarization resistance Rp, potentiodynamic polarization curves, electrochemical impedance spectroscopy EIS) were carried out on fluids extracted from patients with different articular pathologies and prosthesis revisions. Those electrochemical measurements could be carried out with outstanding precision and signal stability. The results show that the corrosion behaviour of CoCrMo alloy in synovial fluids not only depends on material reactivity but also on the specific reactions of synovial fluid components, most likely involving reactive oxygen species. In some patients the latter were found to determine the whole cathodic and anodic electrochemical response. Depending on patients, corrosion rates varied significantly between 50 and 750 mg dm(-2)year(-1).

Enhancing clinically-relevant shoulder function assessment using only essential movements.

Kinematic functional evaluation with body-worn sensors provides discriminative and responsive scores after shoulder surgery, but the optimal movements' combination has not yet been scientifically investigated. The aim of this study was the development of a simplified shoulder function kinematic score including only essential movements. The P Score, a seven-movement kinematic score developed on 31 healthy participants and 35 patients before surgery and at 3, 6 and 12 months after shoulder surgery, served as a reference. Principal component analysis and multiple regression were used to create simplified scoring models. The candidate models were compared to the reference score. ROC curve for shoulder pathology detection and correlations with clinical questionnaires were calculated. The B-B Score (hand to the Back and hand upwards as to change a Bulb) showed no difference to the P Score in time*score interaction (P > .05) and its relation with the reference score was highly linear (R(2) > .97). Absolute value of correlations with clinical questionnaires ranged from 0.51 to 0.77. Sensitivity was 97% and specificity 94%. The B-B and reference scores are equivalent for the measurement of group responses. The validated simplified scoring model presents practical advantages that facilitate the objective evaluation of shoulder function in clinical practice.

[Resonance Raman spectroscopy of polynucleotides]. / Spectroscopie Raman de résonance des polynucléotides.

Resonance Raman Spectroscopy allows a selective study of the bases of DNA and therefore of the interactions of these bases with ligands. This technique is also sensitive to structural modifications. We show here that, first, the structures of native poly(dA-dT).poly(dA-dT) and poly(dA).poly(dT) are not the same and that, secondly, it is possible to characterize the B----Z transition of poly(dG-dC).poly(dG-dC). The study of the Raman hypochromism during the thermal denaturation of the polynucleotides reveals that the stacking of the adenines in poly(dA).poly(dT) is near that observed in poly(rA) but differs of this stacking in poly(dA-dT).poly(dA-dT). The enhancement of the intensity of the guanine line at 1193 cm-1 and of the cytosine lines at 780 cm-1, 1 242 cm-1 and 1268 cm-1 as well as the shift of the guanine line at low frequency should allow to characterize a small proportion of base pairs in Z form in any DNA.

Evaluation of the structural modifications induced by mitomycin C on nucleic acids.

The interaction of poly(dG-dC).poly(dG-dC) with mitomycin C, an antitumor antibiotic, has been studied by various spectroscopic methods: circular dichroism, Fourier transform infrared resonance Raman scattering and using fluorescence emission of terbium bound to unpaired guanines as local conformation probe. The results allowed us to confirm the lack of long range modification of the DNA secondary structure upon binding. They also brought first information concerning the modification of the local structure of the nucleic acid at the level of mono- or bifunctional adducts.

Contribution of the resonance Raman spectroscopy to the identification of Z DNA.

Poly(dG-dC).poly(dG-dC) at low salt concentration (0.1 M NaCl) and at high salt concentration (4.5 M NaCl) has been studied by Raman resonance spectroscopy using two excitation wavelengths: 257 nm and 295 nm. As resonance enhances the intensity of the lines in a proportion corresponding to the square of the molar absorption coefficient, the intensities of the lines with 295 nm wavelength excitation are enhanced about sevenfold during the B to Z transition. With 257 nm excitation wavelength the 1580 cm-1 line of guanosine is greatly enhanced in the Z form whereas with 295 nm excitation several lines are sensitive to the modifications of the conformation: the guanine band around 650 cm-1 and at 1193 cm-1 and the bands of the cytosines at 780 cm-1, 1242 cm-1 and 1268 cm-1. By comparison with the U.V. resonance Raman spectra of DNA, we conclude that resonance Raman spectroscopy allows one to characterize the B to Z transition from one line with 257 nm excitation wavelength and from three lines with 295 nm excitation. The conjoined study of these four lines should permit to observe a few base pairs being in Z form in a DNA.

A resonance Raman spectroscopic study of the quadruplex form of polyriboinosinic acid.

The four stranded form of polyriboinosinic acid, or poly(rl), formed under conditions of high ionic strength, has been studied principally by resonance Raman spectroscopy excited in the ultraviolet absorbent band of the hypoxanthine residues. UV Absorption and circular dichroism studies were made, principally in order to verify the presence of the quadruplex form at the low concentrations of poly(rl) used, and a trial experiment with the structural probe Tb3+ was also performed. Experimental evidence is found for highly stacked metastable forms present at low concentrations of polynucleotide, which are destroyed by heating in favor of the two well known forms.

Fluorescence resonance energy transfer analysis of the degradation of an oligonucleotide protected by a very stable hairpin.

In vitro degradation of antisense oligonucleotides protected or not on their 3' side against enzymatic attack by a naturally forming hairpin has been studied by fluorescence resonance energy transfer (FRET). The two oligonucleotides d(5"TTCTCGCGAAGC3') forming the hairpin and d(5"TTCTCCGGAAGC3') as a control were labeled on their 5' side by tetramethylrhodamine and on their 3' side by fluorescein. Fluorescein has been shown not to hinder the hairpin formation and to give an additional protection against nucleases. The FRET technique proved adequate for an in situ study of these protected antisense oligonucleotides in living cells.