Advertisement for orthosearch.org.uk
Results 1 - 50 of 95
Results per page:
The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 5 | Pages 742 - 750
1 Jul 2001
Kim Y Kim J Cho S

We have reviewed 70 patients with bilateral simultaneous total hip arthroplasties to determine the rate of failure and to compare polyethylene wear and osteolysis between an implant with a cobalt-chrome head and Hylamer liner with that of a zirconia head and Hylamer liner. The mean thickness of the polyethylene liner was 11.0 mm (8.8 to 12.2) in the hip with a zirconia head and 10.7 mm (8.8 to 12.2) in that with a cobalt-chrome head. At follow-up at 6.4 years no acetabular or femoral component had been revised for aseptic loosening and no acetabular or femoral component was loose according to radiological criteria in both the cemented and cementless groups. The mean rate of linear wear and annual wear rate were highest in the 22 mm zirconia femoral head (1.25 mm (SD 1.05) and 0.21 mm (SD 0.18), respectively) and lowest in the 22 mm cobalt-chrome femoral head (0.70 mm (SD 0.39) and 0.12 mm (SD 0.07), respectively). The mean volumetric wear was highest in the 28 mm zirconia femoral head (730.79 mm. 3. ) and lowest in the 22 mm cobalt-chrome femoral head (264.67 mm. 3. ), but if the results were compared by size of the femoral head and type of material there was no statistical difference (p > 0.05). Sequential measurements of annual wear showed that the zirconia femoral head had a relatively higher rate of penetration than the cobalt-chrome head over the first three years; thereafter the rate of wear was reduced and compared favourably with that of cobalt-chrome heads. There was a statistically significant relationship between the wear of the polyethylene liner and the age of the patient, male gender and the degree of abduction angle of the cup, but not diagnosis, weight, hip score, range of movement, or amount of anteversion. Osteolysis was identified on both sides of the acetabulum in six patients (9%). Of 12 hips with acetabular osteolysis, six had a 28 mm cobalt-chrome femoral head and the remaining six a 28 mm zirconia head. Osteolysis was observed in zones 1A and 7A of the femur in two hips (3%) with a 28 mm zirconia head (cemented hip) and in four (6%) with a 28 mm cobalt-chrome femoral head (cementless hip). Our findings suggest that although the performance of a zirconia femoral head with a Hylamer liner was not statistically different from that of a cobalt-chrome femoral head and Hylamer liner, there was a trend for the zirconia head to be worse than the cobalt-chrome femoral head


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 413 - 416
1 Mar 2007
van Riet RP van Glabbeek F de Weerdt W Oemar J Bortier H

We undertook a study on eight arms from fresh cadavers to define the clinical usefulness of the lesser sigmoid notch as a landmark when reconstructing the length of the neck of the radius in replacement of the head with a prosthesis. The head was resected and its height measured, along with several control measurements. This was compared with in situ measurements from the stump of the neck to the proximal edge of the lesser sigmoid notch of the ulna. All the measurements were performed three times by three observers acting independently. The results were highly reproducible with intra- and interclass correlations of > 0.99. The mean difference between the measurement on the excised head and the distance from the stump of the neck and the lesser sigmoid notch was −0.02 mm (−1.24 to +0.97). This difference was not statistically significant (p = 0.78). The proximal edge of the lesser sigmoid notch provides a reliable landmark for positioning a replacement of the radial head and may have clinical application


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1256 - 1259
1 Sep 2008
Kedgley AE DeLude JA Drosdowech DS Johnson JA Bicknell RT

This study compared the effect of a computer-assisted and a traditional surgical technique on the kinematics of the glenohumeral joint during passive abduction after hemiarthroplasty of the shoulder for the treatment of fractures. We used seven pairs of fresh-frozen cadaver shoulders to create simulated four-part fractures of the proximal humerus, which were then reconstructed with hemiarthroplasty and reattachment of the tuberosities. The specimens were randomised, so that one from each pair was repaired using the computer-assisted technique, whereas a traditional hemiarthroplasty without navigation was performed in the contralateral shoulder. Kinematic data were obtained using an electromagnetic tracking device. The traditional technique resulted in posterior and inferior translation of the humeral head. No statistical differences were observed before or after computer-assisted surgery. Although it requires further improvement, the computer-assisted approach appears to allow glenohumeral kinematics to more closely replicate those of the native joint, potentially improving the function of the shoulder and extending the longevity of the prosthesis


Bone & Joint Research
Vol. 7, Issue 2 | Pages 196 - 204
1 Feb 2018
Krull A Morlock MM Bishop NE

Objectives. Taper junctions between modular hip arthroplasty femoral heads and stems fail by wear or corrosion which can be caused by relative motion at their interface. Increasing the assembly force can reduce relative motion and corrosion but may also damage surrounding tissues. The purpose of this study was to determine the effects of increasing the impaction energy and the stiffness of the impactor tool on the stability of the taper junction and on the forces transmitted through the patient’s surrounding tissues. Methods. A commercially available impaction tool was modified to assemble components in the laboratory using impactor tips with varying stiffness at different applied energy levels. Springs were mounted below the modular components to represent the patient. The pull-off force of the head from the stem was measured to assess stability, and the displacement of the springs was measured to assess the force transmitted to the patient’s tissues. Results. The pull-off force of the head increased as the stiffness of the impactor tip increased but without increasing the force transmitted through the springs (patient). Increasing the impaction energy increased the pull-off force but also increased the force transmitted through the springs. Conclusions. To limit wear and corrosion, manufacturers should maximize the stiffness of the impactor tool but without damaging the surface of the head. This strategy will maximize the stability of the head on the stem for a given applied energy, without influencing the force transmitted through the patient’s tissues. Current impactor designs already appear to approach this limit. Increasing the applied energy (which is dependent on the mass of the hammer and square of the contact speed) increases the stability of the modular connection but proportionally increases the force transmitted through the patient’s tissues, as well as to the surface of the head, and should be restricted to safe levels. Cite this article: A. Krull, M. M. Morlock, N. E. Bishop. Maximizing the fixation strength of modular components by impaction without tissue damage. Bone Joint Res 2018;7:196–204. DOI: 10.1302/2046-3758.72.BJR-2017-0078.R2


Bone & Joint 360
Vol. 12, Issue 4 | Pages 44 - 46
1 Aug 2023
Burden EG Whitehouse MR Evans JT


Bone & Joint 360
Vol. 12, Issue 6 | Pages 49 - 51
1 Dec 2023
Burden EG Whitehouse MR Evans JT


Bone & Joint Research
Vol. 9, Issue 3 | Pages 146 - 151
1 Mar 2020
Waldstein W Koller U Springer B Kolbitsch P Brodner W Windhager R Lass R

Aims. Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing. Methods. The present study provides an update of a previously published prospective randomized controlled study, evaluating the serum cobalt levels of a consecutive cohort of 100 patients following THA with a MoM or a CoP articulation. A total of 31 patients were available for clinical and radiological follow-up examination. After exclusion of 11 patients because of other cobalt-containing implants, 20 patients (MoM (n = 11); CoP (n = 9)) with a mean age of 69 years (42 to 97) were analyzed. Serum cobalt levels were compared to serum cobalt levels five years out of surgery. Results. The median cobalt concentration in the MoM group was 1.04 μg/l (interquartile range (IQR) 0.64 to 1.70) at a mean of 21 years (20 to 24) postoperatively and these values were similar (p = 0.799) to cobalt levels at five years. In the CoP control group, the median cobalt levels were below the detection limit (< 0.3 μg/l; median 0.15 μg/l, IQR 0.15 to 0.75) at 20 years. The mean Harris Hip Score was 91.4 points (61 to 100) in the MoM group and 92.8 points (63 to 100) in the CoP group. Conclusion. This study represents the longest follow-up series evaluating the serum cobalt levels after 28 mm head MoM bearing THA and shows that serum cobalt concentrations remain at low levels at a mean of 21 years (20 to 24) after implantation. Cite this article:Bone Joint Res. 2020;9(3):145–150


Bone & Joint 360
Vol. 11, Issue 4 | Pages 44 - 46
1 Aug 2022
Evans JT Walton TJ Whitehouse MR


Bone & Joint 360
Vol. 10, Issue 6 | Pages 48 - 50
1 Dec 2021
Evans JT French JMR Whitehouse MR


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 973 - 976
1 Jul 2009
Kralinger F Unger S Wambacher M Smekal V Schmoelz W

The medial periosteal hinge plays a key role in fractures of the head of the humerus, offering mechanical support during and after reduction and maintaining perfusion of the head by the vessels in the posteromedial periosteum. We have investigated the biomechanical properties of the medial periosteum in fractures of the proximal humerus using a standard model in 20 fresh-frozen cadaver specimens comparable in age, gender and bone mineral density. After creating the fracture, we displaced the humeral head medial or lateral to the shaft with controlled force until complete disruption of the posteromedial periosteum was recorded. As the quality of periosteum might be affected by age and bone quality, the results were correlated with the age and the local bone mineral density of the specimens measured with quantitative CT. Periosteal rupture started at a mean displacement of 2.96 mm (. sd. 2.92) with a mean load of 100.9 N (. sd. 47.1). The mean maximum load of 111.4 N (. sd. 42.5) was reached at a mean displacement of 4.9 mm (. sd. 4.2). The periosteum was completely ruptured at a mean displacement of 34.4 mm (. sd. 11.1). There was no significant difference in the mean distance to complete rupture for medial (mean 35.8 mm (. sd. 13.8)) or lateral (mean 33.0 mm (. sd. 8.2)) displacement (p = 0.589). The mean bone mineral density was 0.111 g/cm. 3. (. sd. 0.035). A statistically significant but low correlation between bone mineral density and the maximum load uptake (r = 0.475, p = 0.034) was observed. This study showed that the posteromedial hinge is a mechanical structure capable of providing support for percutaneous reduction and stabilisation of a fracture by ligamentotaxis. Periosteal rupture started at a mean of about 3 mm and was completed by a mean displacement of just under 35 mm. The microvascular situation of the rupturing periosteum cannot be investigated with the current model


Bone & Joint Research
Vol. 6, Issue 1 | Pages 52 - 56
1 Jan 2017
Hothi HS Kendoff D Lausmann C Henckel J Gehrke T Skinner J Hart A

Objectives. Mechanical wear and corrosion at the head-stem junction of total hip arthroplasties (THAs) (trunnionosis) have been implicated in their early revision, most commonly in metal-on-metal (MOM) hips. We can isolate the role of the head-stem junction as the predominant source of metal release by investigating non-MOM hips; this can help to identify clinically significant volumes of material loss and corrosion from these surfaces. Methods. In this study we examined a series of 94 retrieved metal-on-polyethylene (MOP) hips for evidence of corrosion and material loss at the taper junction using a well published visual grading method and an established roundness-measuring machine protocol. Hips were retrieved from 74 male and 20 female patients with a median age of 57 years (30 to 76) and a median time to revision of 215 months (2 to 324). The reasons for revision were loosening of both the acetabular component and the stem (n = 29), loosening of the acetabular component (n = 58) and infection (n = 7). No adverse tissue reactions were reported by the revision surgeons. Results. Evidence of corrosion was observed in 55% of hips. The median Goldberg taper corrosion score was 2 (1 to 4) and the annual rate of material loss at the taper was 0.084 mm. 3. /year (0 to 0.239). The median trunnion corrosion score was 1 (1 to 3). Conclusions. We have reported a level of trunnionosis for MOP hips with large-diameter heads that were revised for reasons other than trunnionosis, and therefore may be clinically insignificant. Cite this article: H. S. Hothi, D. Kendoff, C. Lausmann, J. Henckel, T. Gehrke, J. Skinner, A. Hart. Clinically insignificant trunnionosis in large-diameter metal-on-polyethylene total hip arthroplasty. Bone Joint Res 2017;6:52–56. DOI: 10.1302/2046-3758.61.BJR-2016-0150.R2


Bone & Joint 360
Vol. 10, Issue 4 | Pages 49 - 51
1 Aug 2021
Evans JT Welch M Whitehouse MR


Bone & Joint Research
Vol. 6, Issue 2 | Pages 82 - 89
1 Feb 2017
Nagra NS Zargar N Smith RDJ Carr AJ

Objectives. All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods. A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Results. Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (. se). 17.6) compared with the all-suture anchors (mean 133.1 N . se. 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm . se. 2.5 versus 12.5 mm . se. 0.3; and 29.6 mm . se. 4.8 versus 17.0 mm . se. 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion. We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 2 | Pages 331 - 336
1 Mar 1997
Kusaba A Kuroki Y

We retrieved 159 femoral heads at revision surgery to determine changes in surface configuration. Macroscopic wear of the head was observed in three bipolar hip prostheses as a result of three-body wear. There was a considerable change in surface roughness in the internal articulation of bipolar hip prostheses. Roughness in alumina heads was almost the same as that in new cobalt-chromium heads. The annual linear wear rate of polyethylene cups with alumina heads was less than that of cups with cobalt-chromium alloy heads. Polyethylene wear was increased in the prostheses which had increased roughness of the head


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 5 | Pages 894 - 899
1 Sep 1998
Minakawa H Stone MH Wroblewski BM Lancaster JG Ingham E Fisher J

We examined stainless-steel, cobalt-chrome, titanium and alumina and zirconia ceramic femoral heads retrieved at revision surgery. All the heads had articulated against ultra-high-molecular-weight-polyethylene (UHMWPE) acetabular cups. We studied the simulation of third-body damage and the wear of UHMWPE against the various materials used for the heads. The surfaces of the retrieved heads were analysed using a two-dimensional contacting profilometer. Third-body damage was characterised by the mean height of the scratches above the mean line (R. pm. ). The alumina ceramic and zirconia ceramic retrieved heads were found to have significantly less damage. In laboratory studies the ceramics were also more resistant to simulated third-body damage than the metal alloys. We studied the wear of UHMWPE against the damaged counterfaces in simple configuration tests. The damaged ceramics produced less polyethylene wear than the damaged metal counterfaces. The wear factor of UHMWPE against the damaged materials was dependent on the amount of damage to the counterface (R. p. ). Our study has shown the benefit of using the harder and more damage-resistant ceramic materials for femoral heads


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 3 | Pages 447 - 451
1 Apr 2002
Eggli S z’Brun S Gerber C Ganz R

In this prospective, randomised study, we have compared the wear rate of cemented, acetabular polyethylene cups articulating with either a 22 mm or a 32 mm cobalt-chromium head. We evaluated 89 patients who had a total of 484 radiographs. The mean follow-up period was 71.4 months (SD 29.1). All the radiographs were digitised and electronically measured. The linear wear rate was significantly higher during the first two years and decreased after this period to a constant value. We suggest that this is partly due to a ‘run-in’ process caused by irregularities between surfaces of the cup and head and an initial plastic deformation of the polyethylene. The mean volumetric wear was 120.3 mm. 3. /year for the 32 mm head, which was significantly higher than the 41.5 mm. 3. /year for the 22 mm heads. The mean linear wear rate was not significantly different. We were, however, unable to find radiological signs of osteolysis in the patients who had higher wear rates


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 1 | Pages 140 - 146
1 Jan 1997
Robinson RP Simonian PT Gradisar IM Ching RP

A three-dimensional computer model of a total hip replacement was used to examine the relationship between the position of the components, the range of motion and the prosthetic joint contact area. Horizontal acetabular positions with small amounts of acetabular and femoral anteversion provide the largest contact areas, but result in limited joint movement. These data will allow surgeons to select implant positions that will provide the largest possible joint contact area for a given joint range of motion although these are conflicting goals. In some component positions a truncated spherical prosthetic head resulted in smaller contact areas than a completely spherical head


Bone & Joint 360
Vol. 9, Issue 1 | Pages 10 - 14
1 Feb 2020
Ibrahim M Reito A Pidgaiska O


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 1012 - 1018
1 Jul 2005
Beck M Kalhor M Leunig M Ganz R

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification. Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone


Bone & Joint 360
Vol. 9, Issue 2 | Pages 46 - 48
1 Apr 2020
Evans JT Whitehouse MR


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1471 - 1474
1 Oct 2010
Chang Y Shih H Chen DW Lee MS Ueng SWN Hsieh P

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 131 - 137
1 Jan 2009
Boraiah S Dyke JP Hettrich C Parker RJ Miller A Helfet D Lorich D

In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 741 - 744
1 May 2005
Beaulé PE Krismer M Mayrhofer P Wanner S Le Duff M Mattesich M Stoeckl B Amstutz HC Biedermann R

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse - femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be ± 1.6 mm for the x-direction and ± 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty


Bone & Joint Research
Vol. 8, Issue 2 | Pages 41 - 48
1 Feb 2019
Busse P Vater C Stiehler M Nowotny J Kasten P Bretschneider H Goodman SB Gelinsky M Zwingenberger S

Objectives

Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro.

Methods

Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 2 | Pages 345 - 350
1 Mar 1998
Önsten I Carlsson ÅS Besjakov J

We used radiostereometric analysis to compare wear rates between uncemented porous sockets and cemented all-polyethylene sockets in a series of 102 hips randomised for either a Harris-Galante or a Charnley cup. Wear was evaluated in 95 hips at a mean of five years (2 to 7). All hips had a cemented, 22 mm head mono-bloc Charnley stem. The mean annual wear rate was 0.09 mm in the Charnley sockets and 0.10 mm in the Harris-Galante sockets, with no statistically significant differences in wear, migration or rotation. We conclude that, up to five years, the wear characteristics of the modular and porous Harris-Galante socket resemble that of the Charnley socket


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 598 - 603
1 May 2001
Nevelos JE Prudhommeaux F Hamadouche M Doyle C Ingham E Meunier A Nevelos AB Sedel L Fisher J

We compared and quantified the modes of failure and patterns of wear of 11 Mittelmeier and 11 Ceraver-Ostal retrieved alumina-alumina hip prostheses with reference to the corresponding clinical and radiological histories. Macroscopic wear was assessed using a three-dimensional co-ordinate measuring machine. Talysurf contacting profilometry was used to measure surface roughness on a microscopic scale and SEM to determine mechanisms of wear at the submicron level. The components were classified into one of three categories of wear: low (no visible/measurable wear), stripe (elliptical wear stripe on the heads and larger worn areas on the cups) and severe (macroscopic wear, large volumes of material lost). Overall, the volumetric wear of the alumina-alumina prostheses was substantially less than the widely used metal and ceramic-on-polyethylene combinations. By identifying and eliminating the factors which accelerate wear, it is expected that the lifetime of these devices can be further increased


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 4 | Pages 611 - 617
1 May 2003
Tingart MJ Apreleva M von Stechow D Zurakowski D Warner JJP

The operative treatment of fractures of the proximal humerus can be complicated by poor bone quality. Our aim was to evaluate a new method which allows prediction of the bone quality of the proximal humerus from radiographs. Anteroposterior radiographs were taken of 19 human cadaver humeri. The cortical thickness was measured at two levels of the proximal humeral diaphysis. The bone mineral density (BMD) was determined for the humeral head (HH), the surgical neck (SN), the greater tuberosity (GT) and lesser tuberosity (LT) using dual-energy x-ray absorptiometry. The mean cortical thickness was 4.4 ± 1.0 mm. Specimens aged 70 years or less had a significantly higher cortical thickness than those aged over 70 years. A significant positive correlation was found between cortical thickness and the BMD for each region of interest. The cortical thickness of the proximal diaphysis is a reliable predictor of the bone quality of the proximal humerus


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 720 - 725
1 Jul 1998
Sano H Uhthoff HK Backman DS Brunet JA Trudel G Pham B Ishii H

We examined macroscopically and microscopically 55 cadaver rotator-cuff tendons attached to their humeral heads to determine the distance between the edge of the articular cartilage and the tendon insertion of the supraspinatus (the width of the sulcus) and the score of regressive changes at the sulcus. In 33 specimens we measured the tensile strength. The width of the sulcus was correlated with the score of regressive changes and with the ultimate tensile strength of the supraspinatus tendon. The width of the sulcus correlated positively with the score of regressive changes (r = 0.66, p < 0.0001), but there was a negative correlation between the latter and the ultimate tensile strength (r = −0.81, p = 0.001) and between the width of the sulcus and the ultimate tensile strength (r = −0.74, p = 0.004). We believe that the width of the sulcus is a simple and useful clinical indicator of the integrity and the tensile strength of the supraspinatus tendon


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 701 - 705
1 May 2007
Thiele OC Eckhardt C Linke B Schneider E Lill CA

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft. A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r. 2. = 0.867, p < 0.01) and also between its thickness (r. 2. = 0.826, p < 0.01) and bone mineral density (r. 2. = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378). We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 4 | Pages 595 - 600
1 May 2000
Brooks RA Sharpe JR Wimhurst JA Myer BJ Dawes EN Rushton N

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10. 4. , 10. 6. or 10. 8. high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10. 8. particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 5 | Pages 857 - 865
1 Sep 1997
Boileau P Walch G

We have studied the three-dimensional geometry of the proximal humerus on human cadaver specimens using a digitised measuring device linked to a computer. Our findings demonstrated the variable shape of the proximal humerus as well as its variable dimensions. The articular surface, which is part of a sphere varies individually in its orientation as regards inclination and retroversion, and it has variable medial and posterior offsets. These variations cannot be accommodated by the designs of most contemporary humeral components. Although good clinical results can be achieved with current modular and non-modular components their relatively fixed geometry prevents truly anatomical restoration in many cases. To try to restore the original three-dimensional geometry of the proximal humerus, we have developed a new type of humeral component which is modular and adaptable to the individual anatomy. Such adaptability allows correct positioning of the prosthetic head in relation to an individual anatomical neck, after removal of the marginal osteophytes. The design of this third-generation prosthesis respects the four geometrical variations which have been demonstrated in the present study. These are inclination, retroversion, medial offset and posterior offset


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 8 | Pages 1182 - 1190
1 Nov 2001
Minovic A Milosev I Pisot V Cör A Antolic V

We analysed revised Mathys isoelastic polyacetal femoral stems with stainless-steel heads and polyethylene acetabular cups from eight patients in order to differentiate various types of particle of wear debris. Loosening of isoelastic femoral stems is associated with the formation of polyacetal wear particles as well as those of polyethylene and metal. All three types of particle were isolated simultaneously by tissue digestion followed by sucrose gradient centrifugation. Polyacetal particles were either elongated, ranging from 10 to 150 μm in size, or shred-like and up to 100 μm in size. Polyethylene particles were elongated or granules, and were typically submicron or micronsized. Polyacetal and polyethylene polymer particles were differentiated by the presence of BaSO. 4. , which is added as a radiopaque agent to polyacetal but not to polyethylene. This was easily detectable by back-scattered SEM analysis and verified by energy dispersive x-ray analysis. Two types of foreign-body giant cell (FBGC) were recognised in the histological specimens. Extremely large FBGCs with irregular polygonal particles showing an uneven, spotty birefringence in polarised light were ascribed to polyacetal debris. Smaller FBGCs with slender elongated particles shining uniformly brightly in polarisation were related to polyethylene. Mononucleated histiocytes containing both types of particle were also present. Our findings offer a better understanding of the processes involved in the loosening of polyacetal stems and indicate why the idea of ‘isoelasticity’ proved to be unsuccessful in clinical practice


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 2 | Pages 280 - 285
1 Mar 1996
Wroblewski BM Siney PD Dowson D Collins SN

We report the findings from independent prospective clinical and laboratory-based joint-simulator studies of the performance of ceramic femoral heads of 22.225 mm diameter in cross-linked polyethylene (XLP) acetabular cups. We found remarkable qualitative and quantitative agreement between the clinical and simulator results for the wear characteristics with time, and confirmed that ceramic femoral heads penetrate the XLP cups at only about half the rate of otherwise comparable metal heads. In the clinical study, 19 hips in 17 patients were followed for an average of 77 months. In the hip-joint simulator a similar prosthesis was tested for 7.3 million cycles. Both clinical and simulator results showed relatively high rates of penetration over the first 18 months or 1.5 million cycles, followed by a very much lower wear thereafter. Once an initial bedding-in of 0.2 mm to 0.4 mm had taken place the subsequent rates of penetration were very small. The initial clinical wear during bedding-in averaged 0.29 mm/year; subsequent progression was an order of magnitude lower at about 0.022 mm/year, lower than the 0.07 mm/year in metal-to-UHMWP Charnley LFAs. Our results show the excellent tribological features of alumina-ceramic-to-XLP implants, and also confirm the value of well-designed joint simulators for the evaluation of total joint replacements


Bone & Joint 360
Vol. 7, Issue 1 | Pages 41 - 42
1 Feb 2018
Foy MA


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives

Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts.

Methods

Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 57 - 65
1 Jan 2017
Gumucio JP Flood MD Bedi A Kramer HF Russell AJ Mendias CL

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Methods

Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 403 - 411
1 Sep 2016
Mrosek EH Chung H Fitzsimmons JS O’Driscoll SW Reinholz GG Schagemann JC

Objectives

We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling.

Materials and Methods

Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.


Bone & Joint Research
Vol. 4, Issue 3 | Pages 29 - 37
1 Mar 2015
Halim T Clarke IC Burgett-Moreno MD Donaldson TK Savisaar C Bowsher JG

Objectives

Third-body wear is believed to be one trigger for adverse results with metal-on-metal (MOM) bearings. Impingement and subluxation may release metal particles from MOM replacements. We therefore challenged MOM bearings with relevant debris types of cobalt–chrome alloy (CoCr), titanium alloy (Ti6Al4V) and polymethylmethacrylate bone cement (PMMA).

Methods

Cement flakes (PMMA), CoCr and Ti6Al4V particles (size range 5 µm to 400 µm) were run in a MOM wear simulation. Debris allotments (5 mg) were inserted at ten intervals during the five million cycle (5 Mc) test.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 130 - 138
1 Apr 2014
Shapiro F Connolly S Zurakowski D Flynn E Jaramillo D

Objectives

An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.

Methods

Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 141 - 144
1 Jan 2015
Hughes AW Clark D Carlino W Gosling O Spencer RF

Reported rates of dislocation in hip hemiarthroplasty (HA) for the treatment of intra-capsular fractures of the hip, range between 1% and 10%. HA is frequently performed through a direct lateral surgical approach. The aim of this study is to determine the contribution of the anterior capsule to the stability of a cemented HA through a direct lateral approach.

A total of five whole-body cadavers were thawed at room temperature, providing ten hip joints for investigation. A Thompson HA was cemented in place via a direct lateral approach. The cadavers were then positioned supine, both knee joints were disarticulated and a digital torque wrench was attached to the femur using a circular frame with three half pins. The wrench applied an external rotation force with the hip in extension to allow the hip to dislocate anteriorly. Each hip was dislocated twice; once with a capsular repair and once without repairing the capsule. Stratified sampling ensured the order in which this was performed was alternated for the paired hips on each cadaver.

Comparing peak torque force in hips with the capsule repaired and peak torque force in hips without repair of the capsule, revealed a significant difference between the ‘capsule repaired’ (mean 22.96 Nm, standard deviation (sd) 4.61) and the ‘capsule not repaired’ group (mean 5.6 Nm, sd 2.81) (p < 0.001). Capsular repair may help reduce the risk of hip dislocation following HA.

Cite this article: Bone Joint J 2015;97-B:141–4.


Bone & Joint 360
Vol. 3, Issue 3 | Pages 39 - 40
1 Jun 2014
Arastu M


Bone & Joint Research
Vol. 2, Issue 9 | Pages 193 - 199
1 Sep 2013
Myers KR Sgaglione NA Grande DA

The treatment of osteochondral lesions and osteoarthritis remains an ongoing clinical challenge in orthopaedics. This review examines the current research in the fields of cartilage regeneration, osteochondral defect treatment, and biological joint resurfacing, and reports on the results of clinical and pre-clinical studies. We also report on novel treatment strategies and discuss their potential promise or pitfalls. Current focus involves the use of a scaffold providing mechanical support with the addition of chondrocytes or mesenchymal stem cells (MSCs), or the use of cell homing to differentiate the organism’s own endogenous cell sources into cartilage. This method is usually performed with scaffolds that have been coated with a chemotactic agent or with structures that support the sustained release of growth factors or other chondroinductive agents. We also discuss unique methods and designs for cell homing and scaffold production, and improvements in biological joint resurfacing. There have been a number of exciting new studies and techniques developed that aim to repair or restore osteochondral lesions and to treat larger defects or the entire articular surface. The concept of a biological total joint replacement appears to have much potential.

Cite this article: Bone Joint Res 2013;2:193–9.


Bone & Joint Research
Vol. 3, Issue 1 | Pages 14 - 19
1 Jan 2014
James SJ Mirza SB Culliford DJ Taylor PA Carr AJ Arden NK

Aims

Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee.

Methods

We prospectively measured bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline (DPD), a type I collagen crosslink, normalised to creatinine.


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1150 - 1150
1 Aug 2013
Ross A Birch R

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 718 - 718
1 May 2013
Pijls BG van der Heide HJL Nelissen RGHH

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1703 - 1709
1 Dec 2010
Aoki H Nagao Y Ishii S Masuda T Beppu M

In order to evaluate the relationship between acetabular and proximal femoral alignment in the initiation and evolution of osteoarthritis of the dysplastic hip, the acetabular and femoral angles were calculated geometrically from radiographs of 62 patients with pre-arthrosis and early osteoarthritis. The sum of the lateral opening angle of the acetabulum and the neck-shaft angle was defined as the lateral instability index (LII), and the sum of the anterior opening angle of the acetabulum and the anteversion angle of the femoral neck as the anterior instability index (AII). These two indices were compared in dysplastic and unaffected hips. A total of 22 unilateral hips with pre-arthrosis were followed for at least 15 years to determine whether the two indices were associated with the progression of osteoarthritis.

The LII of the affected hips (197.4 (sd 6.0)) was significantly greater than that of the unaffected hips (1830 (sd 6.9)). A follow-up study of 22 hips with pre-arthrosis showed that only the LII was associated with progression of the disease, and an LII of 196 was the threshold value for this progression.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1632 - 1637
1 Dec 2009
Sonnabend DH Young AA

While the evolution of the bony skeleton of the shoulder girdle is well described, there is little information regarding the soft tissues, in particular of the rotator cuff. We dissected the shoulders of 23 different species and compared the anatomical features of the tendons of the rotator cuff. The alignment and orientation of the collagen fibres of some of the tendons were also examined histologically. The behaviour of the relevant species was studied, with particular reference to the extent and frequency of forward-reaching and overhead activity of the forelimb.

In quadrupedal species, the tendons of supraspinatus, infraspinatus and teres minor were seen to insert into the greater tuberosity of the humerus separately. They therefore did not form a true rotator cuff with blending of the tendons. This was only found in advanced primates and in one unusual species, the tree kangaroo. These findings support the suggestion that the appearance of the rotator cuff in the evolutionary process parallels anatomical adaptation to regular overhead activity and the increased use of the arm away from the sagittal plane.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1460 - 1465
1 Oct 2010
Rauh PB Clancy WG Jasper LE Curl LA Belkoff S Moorman CT

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method.

Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 552 - 556
1 Apr 2009
Hannouche D Ballis R Raould A Nizard RS Masquelet AC

We describe a lateral approach to the distal humerus based on initial location of the superficial branches of the radial nerve, the inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm. In 18 upper limbs the superficial branches of the radial nerve were located in the subcutaneous tissue between the triceps and brachioradialis muscles and dissected proximally to their origin from the radial nerve, exposing the shaft of the humerus. The inferior lateral cutaneous nerve of the arm arose from the radial nerve at the lower part of the spiral groove, at a mean of 14.2 cm proximal to the lateral epicondyle. The posterior cutaneous nerve of the forearm arose from the inferior lateral cutaneous nerve at a mean of 6.9 cm (6.0 to 8.1) proximal to the lateral epicondyle and descended vertically along the dorsal aspect of the forearm. The size and constant site of emergence between the triceps and brachioradialis muscles constitute a readily identifiable landmark to explore the radial nerve and expose the humeral shaft.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 977 - 982
1 Jul 2009
Terrier A Merlini F Pioletti DP Farron A

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data.

After one year of use, the volumetric wear was 8.4 mm3 for the anatomical prosthesis, but 44.6 mm3 for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required.