Unique combination of patellofemoral joint arthroplasty with Osteochondral Autograft Transfer System (OATS) - a case series of six knees in five patients.

Patellofemoral arthroplasty (PFA) is an accepted procedure for the treatment of isolated patellofemoral osteoarthritis. However its failure rate has been attributed to progressive femorotibial arthritis. Autologous osteochondral transplantation is an established procedure for the repair of focal cartilaginous defects on the medial and lateral femoral condyles. We present our case series of six knees in five patients where we combined the two procedures and extended the indication for PFA and delayed the need for total knee arthroplasty (TKA) in all but one patient over a mean follow up period of 3.8 years.

Functional outcome following modified Elmslie-Trillat procedure.

The aim of this study was to evaluate the mid- and long-term outcome of the modified Elmslie-Trillat procedure, as well as to detect factors affecting it. Thirty-eight patients (44 procedures) with a mean age of 31 years were included in this study. The reason for operation was patellar instability in 10 cases, anterior knee pain with malalignment of the extensor mechanism in 15 cases and a combination of both in 19 cases. Patients were followed for an average of 40 months (range=18-130 months). The functional outcome was very satisfactory or satisfactory for 73% of patients. According to Cox's criteria it was excellent in 13 cases (30%), good in 18 (41%), fair in 7 (16%) and poor in the remaining 6 (13%). Patients scored an average of 3.5 (range=2-8) in their Tegner Activity Scale, while their score in Activities of Daily Living Scale of the Knee Outcome Survey ranged from 43 to 98 (average=76). Result analysis revealed a better functional outcome when the operation was performed for patellar instability, as well as in the absence of grade 3 or 4 chondral changes in the patellofemoral joint at the time of operation. Elmslie-Trillat procedure satisfactorily restores patellofemoral stability and offers a very good functional outcome, especially in the absence of significant chondral changes in the patellofemoral joint at the time of operation.

Double-layered lateral meniscus. A rare anatomical aberration.

We report a case of double-layered lateral meniscus, where an accessory proximal hemimeniscus was overlying the body and posterior horn of the lateral meniscus. It lay 1-2 mm proximal and parallel to the normal lateral meniscus with its periphery attached to the capsule and was significantly thinner and more mobile than its underlying counterpart. The accessory hemimeniscus was resected arthroscopically. This case demonstrates an interesting and extremely rare anatomical abnormality of the lateral meniscus and is the first one described outside a Japanese population.

Comparative study of ortho- and meta-nitrated inhibitors of catechol-O-methyltransferase: interactions with the active site and regioselectivity of O-methylation.

In this work, we present a comparative case study of "ortho-" and "meta-nitrated" catecholic inhibitors of catechol-O-methyltransferase (COMT), with regard to their interaction with the catalytic site of the enzyme and the in vitro regioselective formation of their mono-O-methyl ether metabolites. In particular, the effects of altering the attachment position of the inhibitors' side-chain substituent, within the classic nitrocatechol pharmacophore, were investigated. For this purpose, we compared two simple regioisomeric nitrocatechol-type inhibitors of COMT, BIA 3-228 and BIA 8-176, which contain the benzoyl substituent attached at the meta and ortho positions, respectively, relative to the nitro group. The two compounds were slowly O-methylated by COMT in vitro, but the particular substitution pattern of each compound was shown to have a profound impact on the regioselectivity of their O-methylation. To provide a plausible interpretation of these results, a comprehensive analysis of the protein-inhibitor interactions and of the relative chemical susceptibility to O-methylation of the catechol hydroxyl groups was performed by means of docking simulations and ab initio molecular orbital calculations. The major structural and chemical factors that determine the enzyme regioselectivity of O-methylation were identified, and the X-ray structure of the complex of COMT with S-adenosyl-l-methionine and BIA 8-176 is herein disclosed. This is the first reported structure of the soluble form of COMT complexed with a nitrocatecholic inhibitor having a bulky substituent group in adjacent position (ortho) to the nitro group. Structural and dynamic aspects of this complex are analyzed and discussed, in the context of the present study.

Functional outcome following reconstruction in chronic multiple ligament deficient knees.

Multiligament knee injuries are rare but potentially limb-threatening conditions. In this study we aim to evaluate the mid- and long-term functional outcome of patients who underwent arthroscopically assisted multiple ligament reconstruction for chronic multiple knee ligament deficiency. Thirty-five patients (27 males and 8 females) with an average age of 35.1 years (range: 17-60) were included in this study. Follow-up ranged from 12 to 124 months (average: 40.3). On final follow-up patients had a mean loss of extension of 3.1 degrees , while flexion ranged from 95 degrees to 135 degrees (average: 118.4 degrees ). The functional outcome according to Clancy's criteria was excellent in 7 patients (20%), good in 14 (40%), fair in 11 (31.4%), while 3 reconstructions resulted in failure (8.6%). Patients scored an average of 4.03 (range: 1-9) in their Tegner Activity Scale, while their score in Activities of Daily Living Scale of the Knee Outcome Survey ranged from 25 to 98 with an average of 72.7. Sixteen patients returned to sporting activities and all but three returned to work. Early operative treatment of multiple ligament injuries is preferable, as it may allow for anatomic repair instead of reconstruction of ligamentous structures. This study demonstrates though, that even if acute reconstruction has not or could not be performed, reconstruction in chronic multiple ligament deficient knees should be attempted. Although this complex and technically demanding procedure rarely results in a "normal" knee, it offers in most cases very satisfactory stability and a significant improvement in knee function.

The practical limitations of resurfacing hip arthroplasty.

Resurfacing hip arthroplasty has recently experienced a resurgence in popularity, associated with an unprecedented amount of coverage in the media. This article assesses what proportion of a consecutive series of young adults presenting for total hip arthroplasty would have been suitable for resurfacing arthroplasty. Retrospective review of the preoperative radiographs was performed, with templating for the resurfacing prostheses. The hips were divided into those appropriate and those inappropriate for the procedure, and those in whom the procedure would be technically challenging. Sixty-one hips in 57 patients were reviewed, with ages ranging from 17 to 49 years. Twenty-eight hips were assessed as suitable, 26 as unsuitable, and 7 as technically challenging. Reasons for unsuitability included collapse and/or cystic degeneration of the femoral head.

Accuracy of needle placement in ACJ injections.

Localization of the Acromioclavicular joint (ACJ) even at arthroscopic surgery may be difficult because of its small size, osteophytes, variable anatomy of the joint and capsule. Therefore injection of the ACJ in the clinic may well be inaccurate. The aim of this study was to review the clinical accuracy of needle placement in ACJ injections, if performed without the aid of image intensification. Sixty patients with 66 shoulders were injected in the Day Unit in our department. The joint was palpated clinically, and the needle was placed in the site thought to be in the AC Joint. An image intensifier was then used to check the position of the needle in the AP and axillary views. The needle was considered correctly placed if between the bony boundaries of the acromion and clavicle. This was found in only 26 injections (39.4%). The remaining 40 injections (60.6%) were misplaced, either laterally in 21 injections (31.8%), medially in 13 (19.8%), anteriorly in 3 (4.5%) and inferiorly in 3 injections (4.5%). Theses were then reinserted under image intensifier guidance. The misplaced injections would have lead to inaccurate clinical outcomes, and decision making. This study is similar to other studies in that X-ray guidance improves the accuracy of injections and surgery. However the potential error rate for the small, anatomically variable AC joint is high. There is a 60% potential for ACJ injections to be out of the joint if performed by palpation alone, and we recommend the routine use of image intensification guidance.

Autologous osteochondral transplantation for the treatment of chondral defects of the knee.

Full-thickness chondral defects of weight-bearing articular surfaces of the knee are a difficult condition to treat. Our aim is to evaluate the mid- and long-term functional outcome of the treatment of osteochondral defects of the knee with autologous osteochondral transplantation with the OATS technique. Thirty-six patients (37 procedures) were included in this study. Twenty-three patients were male and thirteen were female with a mean age of 31.9 years (range: 18-48 years). The cause of the defect was OCD in 10 cases, AVN in 2, lateral patellar maltracking in 7, while in the remaining 17 patients the defect was post-traumatic. The lesion was located on the femoral condyles in 26 cases and the patellofemoral joint in the remaining 11. The average area covered was 2.73 cm(2) (range: 0.8-12 cm(2)) and patients were followed for an average of 36.9 months (range: 18-73 months). The average score in their Tegner Activity Scale was 3.76 (range: 1-8), while their score in Activities of Daily Living Scale of the Knee Outcome Survey ranged from 18 to 98 with an average of 72.3. Thirty-two out of 37 patients (86.5%) reported improvement of their pre-operative symptoms. All but 5 patients returned to their previous occupation while 18 went back to sports. No correlation was found between patient age at operation, the size or site of the chondral lesion and the functional outcome. We believe that autologous osteochondral grafting with the OATS technique is a safe and successful treatment option for focal osteochondral defects of the knee. It offers a very satisfactory functional outcome and does not compromise the patient's future options.

Management of big osteochondral defects of the knee using osteochondral allografts with the MEGA-OATS technique.

Treatment of osteochondral defects in weight-bearing areas of the knee, especially when they are sizeable and involve considerable subchondral bone loss, is a challenging problem. We report our experience on the use of osteochondral allografts with the MEGA-OATS technique in the management of large osteochondral defects of the knee in young patients. Five patients (3 male and 2 female) were included in this study; their age ranged from 22 to 41 years and the mean size of the defect covered was 30 x 30 mm. They were followed for a minimum of 2.5 years (mean: 32.8 months, range 30-36). An age- and size-matched fresh frozen, non-irradiated distal femoral allograft was used to obtain the donor plug, which was then inserted in the recipient area in a press-fit fashion. Patients' Lysholm knee score increased from 37.8 pre-operatively to 73.8 post-operatively. Tegner activity score increased in all five patients; it improved from a mean of 2 pre-operatively (range 1-3) to 4 post-operatively (range 2-7). Four out of five patients returned to work and three went back to sporting activities. With this technique one can cover sizeable osteochondral defects, and compensate for significant subchondral bone loss, while accurate reconstruction of the curvature of the femoral condyle is allowed. We believe that it is a viable salvage option in young patients with big osteochondral defects of the knee. It offers very satisfactory functional results and does not compromise patients' future options.

Molecular modeling and metabolic studies of the interaction of catechol-O-methyltransferase and a new nitrocatechol inhibitor.

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) plays a central role in the metabolic inactivation of neurotransmitters and neuroactive xenobiotics possessing a catechol motif. 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone (BIA 3-202) is a novel nitrocatechol-type inhibitor of COMT, the potential clinical benefit of which is currently being evaluated in the treatment of Parkinson's disease. In the present work we characterize the molecular interactions of BIA 3-202 within the active site of COMT and discuss their implication on the regioselectivity of metabolic O-methylation. Unrestrained flexible-docking simulations suggest that the solution structure of this complex is better described as an ensemble of alternative binding modes, in contrast to the well defined bound configuration revealed by the X-ray structures of related nitrocatechol inhibitors, co-crystallized with COMT. The docking results wherein presented are well supported by experimental evidence, where the pattern of in vitro enzymatic O-methylation and O-demethylation reactions are analyzed. We propose a plausible explanation for the paradoxical in vivo regioselectivity of O-methylation of BIA 3-202, as well as of its related COMT inhibitor tolcapone. Both compounds undergo in vivo O-methylation by COMT at either meta or para catechol hydroxyl groups. However, results herein presented suggest that, in a subsequent step, the p-O-methyl derivatives are selectively demethylated by a microsomal enzyme system. The overall balance is the accumulation of the m-O-methylated metabolites over the para-regioisomers. The implications for the general recognition of nitrocatechol-type inhibitors by COMT and the regioselectivity of their metabolic O-methylation are discussed.

A new technique for posterior cruciate ligament reconstruction.

We describe a new technique for arthroscopically assisted posterior cruciate ligament reconstruction. We use the TransFix (Arthrex, Naples, FL) pin to provide a single and strong tibial attachment point for the 4-stranded semitendinosus and gracilis tendons. The TransFix technique for anterior cruciate ligament reconstruction has been found to give better initial fixation strength than other techniques using semitendinosus and gracilis grafts, and it provides adequate graft length for secure fixation. Strong and secure graft fixation in knee ligament reconstruction is very important for early and fast rehabilitation.

Synthesis, anticonvulsant properties and pharmacokinetic profile of novel 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide derivatives.

A series of novel derivatives of oxcarbazepine (5), 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide was synthesised and evaluated for their anticonvulsant activity and sodium channel blocking properties. The oxime 8 was found to be the most active compound from this series, displaying greater potency than its geometric isomer 9 and exhibiting also the highest protective index value. Importantly, the metabolic profile of 8 differs from the already established dibenz/b,f/azepine-5-carboxamide drugs such as 1 and 5 which undergo rapid and complete conversion in vivo to several biologically active metabolites. In contrast 8 is metabolised to only a very minor extent leading to the conclusion that the observed anti-convulsant effect is solely attributable to 8. It is concluded that 8 may be as effective as 1 and 5 at controlling seizures and that the low toxicity and consequently high protective index should provide the compound with an improved side-effect profile.

Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives.

A series of esters of the major metabolite of oxcarbazepine (2), 10, 11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, were synthesized and evaluated for their anticonvulsant and brain sodium channel-blocking properties. The compounds were assayed intraperitoneally and per os in rats against seizures induced by maximal electroshock (MES). Neurologic deficit was evaluated by the rotarod test. The enantiomeric acetates (R)-11 and (S)-12 were the most active of the series against MES-induced seizures with oral ED(50) values at t(max) of 10.9 +/- 2.3 and 4.7 +/- 0.9 mg/kg, respectively. After intraperitoneal administration, carbamazepine (1) behaved more potently than 2 and all other new dibenz[b, f]azepine-5-carboxamide derivatives in the MES test; compounds 2 and 12 were equally potent. In the rotarod test, low doses of 1 produced considerable motor impairment, which did not occur with 2, enantiomeric alcohols (S)-6, (R)-7, and racemic alcohol 8, or racemic acetate 10 or (R)-11. The potencies of the racemic and enantiomerically pure alcohols 8, (S)-6, and (R)-7 derived from 2 in the MES and rotarod test were found to be similar between them, and consequently they exhibit similar protective index values. All three forms of the alcohol and their corresponding acetates (pairs 8 & 10, 6 & 12, and 7 & 11) were found to differ in the MES or rotarod tests; the ED(50) value for (S)-6 against MES-induced seizures was nearly 3-fold that for (S)-12. The protective index also differed markedly between all stereoisomers of the alcohol and their corresponding acetates, most pronouncedly for compound (S)-12 which attained the highest value (12.5) among all compounds tested. Blockade of voltage-sensitive sodium channels was studied by investigating [(3)H]batrachotoxinin A 20-alpha-benzoate ([(3)H]BTX) binding. Acetates (R)-11 and (S)-12 were more potent than the standards 1 and 2 at inhibiting the binding of [(3)H]BTX to sodium channels and the influx of (22)Na(+) into rat brain synaptosomes. It is concluded that acetates (R)-11 and (S)-12 are not simple metabolic precursors of alcohols (R)-7 and (S)-6 in rodents but that they possess anticonvulsant and sodium channel-blocking properties in their own right.

Binding characteristics of anti-atrazine monoclonal antibodies and their fragments synthesised in bacteria and plants.

Single-chain antibody fragments (scAb), specific for the herbicide atrazine, have been expressed in the bacterium Escherichia coli and in transgenic tobacco plants. The scAb could be purified as a monomer (monovalent) via a hexa-histidine tail or as a dimer (divalent) by antibody affinity chromatography. In competition ELISA, the bacterial scAb showed the same specificity for atrazine and related triazine herbicides as the parental mAb cell line, but both plant and bacterial monomeric scAbs showed increased sensitivity to free atrazine. Surface plasmon resonance (BIAcore 2000) analysis confirmed that purified scAb, derived from plant or bacteria, retained similar association rates as the mAb. However, the monomeric plant and bacterial scAbs showed a lower affinity for immobilised antigen, than the equivalent dimeric scAbs or mAb. This decrease in affinity was due to a 10 fold slower dissociation rate and is likely due to loss of the avidity contribution of dimeric molecules.

Expression and characterisation of single-chain antibody fragments produced in transgenic plants against the organic herbicides atrazine and paraquat.

Single-chain antibody fragments (scAbs), which have a human C-kappa constant domain and a hexa-histidine tail attached to the carboxy terminus of the single-chain Fv (ScFv) fragments to facilitate purification, have been raised against the herbicides paraquat and atrazine and expressed in transgenic Nicotiana tabacum cv. Samsun NN. Prior to purification, the anti-atrazine scAb is expressed as up to 0.014% of soluble leaf protein and has a binding profile in ELISA, against an atrazine-bovine serum albumin (BSA) conjugate, similar to that of the scAb produced in Escherichia coli. Competition ELISA has shown that the plant-derived scAb also recognises free atrazine. Following antibody affinity purification to isolate dimers, the affinity for immobilised antigen approaches that of the parental monoclonal antibody. This was confirmed by surface plasmon resonance analysis. The purified scAb also recognises related triazine herbicides. When isolated from cell-suspension cultures, the anti-paraquat scAb binds to a paraquat conjugate in a concentration-dependent manner, with a profile similar to the parental monoclonal antibody. This is the first demonstration that functional scAbs against organic pollutants can be produced in transgenic plants and that the scAbs may be appropriate for the development of immunoassay-based detection systems.

Production of a functional single chain antibody attached to the surface of a plant virus.

A potato virus X (PVX) vector was used to express a single chain antibody fragment (scFv) against the herbicide diuron, as a fusion to the viral coat protein. The modified virus accumulated in inoculated Nicotiana clevelandii plants and assembled to give virus particles carrying the antibody fragment. Electron microscopy was used to show that virus particles from infected leaf sap were specifically trapped on grids coated with a diuron-BSA conjugate. The results demonstrate that the PVX vector can be used as a presentation system for functional scFv.

Direct measurement of hoop strains in the intact and torn human medial meniscus.

OBJECTIVE: To measure the circumferential or hoop strains generated in the medial meniscus during loading of the knee joint and to examine the effect of longitudinal and radial tears in the meniscus on these strain values. DESIGN: An in vitro investigation measuring the circumferential strains in the medial menisci of cadaveric human knees as they were loaded in a materials testing machine. BACKGROUND: The menisci transmit approximately 50% of the load through the knee, the rest being transmitted by direct contact of the articular cartilage. Damage to the menisci will alter the pattern of load transmission as will meniscectomy. This study examined the changes in the mechanics of the meniscus in situ as a result of simulated tears to assess the effect of its load carrying capacity and the implications of surgery to remove part or all of a damaged meniscus. METHODS: Nineteen human cadaveric knees were tested. Windows were made in the joint capsule and strain gauges inserted into the anterior, middle and posterior sections of the medial meniscus. The knees were then loaded to three times body weight at speeds of 50 and 500 mm/min, with the knee joint at 0 degrees and 30 degrees of flexion. The tests were repeated following the creation of a longitudinal or a radial tear in the meniscus. RESULTS: The intact menisci showed significantly less strain in the posterior section compared to the anterior and middle sections (P < 0.003, with strains of 1.54%, 2.86% and 2.65% respectively). With a longitudinal tear this pattern changed with strains decreasing anteriorly and increasing posteriorly. There were also significant differences at different angles of knee joint flexion not seen in the intact meniscus. 50% radial tears reduced the strains anteriorly whilst a complete radial tear completely defunctioned the meniscus. CONCLUSIONS: This study has shown that there are significantly different hoop strains produced in different sections of the medial meniscus under load and the patterns of strain distribution are disturbed by meniscal tears. RELEVANCE: These results provide important data for mathematical models which must include non-uniform behaviour. They also have implications for the surgical management of torn menisci. Undamaged portions should be preserved and the integrity of the circumferential fibres maintained to ensure the menisci retain a load bearing capability.

Expression of monovalent and bivalent antibody fragments in Escherichia coli.

The technology of humanization of rodent antibodies has opened the way for a broad range of therapeutic antibodies with very low immunogenicity, which are, therefore, suitable for repeated dosing. Such intact antibodies have extended serum half-lives and biodistribution profiles very similar to human antibodies. For some applications, however, the ideal therapeutic should have reduced serum half-life and altered biodistribution patterns typical of antibody fragments, such as Fab or single chain Fv. Bispecific antibody fragments offer exciting additional therapeutic possibilities, but their successful manufacture and purification on a large scale require the development of new methods. Antibody fragments often assemble in Escherichia coli as monovalent fragments with reduced affinities. We describe the spontaneous assembly of bivalent antibody fragments in E. coli and methods of purification that yield either bivalent or monovalent molecules as required.

Mechanical properties of the human anterior cruciate ligament.

The aim was to measure the stiffness and strength of the femur-anterior cruciate ligament-tibia complex tested in a physiological manner with a force exerted anteriorly on the tibia, at knee joint flexion angles of 0 degrees, 10 degrees and 30 degrees and at speeds of 50 and 500 mm/min. Ligaments were preconditioned by cycling five times, with data from the fifth cycle used to determine the stiffness of the ligament in a low-load range. The ligaments were then tested to failure with the knee at 30 degrees flexion. The specimens were divided into two groups, middle-aged (40-60) and old (>60). For each group no statistical difference was observed between stiffness of the ligament at different joint flexion angles or speeds. Seven of the 21 specimens in the older age group failed by avulsion at the bone-ligament interface. All the other specimens failed by tears in the substance of the ligament. Ultimate failure load was found to have a significant correlation with bodyweight. It was 1.6 and 1.3 times bodyweight for the middle-aged and older age groups respectively. This study has highlighted the importance of identifying different modes of failure, of making corrections for bodyweight and testing in a physiological manner. The results allow a better understanding of the mechanical behaviour of the anterior cruciate ligament and provide design data for anterior cruciate ligament grafts and prostheses. RELEVANCE:--Our clinical experience indicates that the anterior cruciate ligament is frequently ruptured during uncoordinated contraction of the quadriceps mechanism. The results of this study, in which the mechanical properties of the anterior cruciate ligament have been measured with force exerted anteriorly on the tibia, allow a more complete understanding of the mechanical behaviour of the anterior cruciate ligament and provide design data for anterior cruciate ligament grafts and prostheses.

Knee effusions, radiology and acute knee trauma.

Sixty patients with acute knee trauma were examined radiographically at presentation and subsequently examined under anaesthetic, when arthroscopy was performed. The aim was to assess whether a normal radiograph at presentation excluded significant knee pathology. Nine patients with significant pathology (25%) had normal radiographs at presentation.