Should return to pivoting sport be avoided for the secondary prevention of osteoarthritis after anterior cruciate ligament reconstruction? A prospective cohort study with MRI, radiographic and symptomatic outcomes.

OBJECTIVE: To evaluate if returning to pivoting sport following anterior cruciate ligament reconstruction (ACLR) is associated with longitudinal structural and symptomatic osteoarthritis outcomes. DESIGN: Eighty-one adults aged 18-50 years were followed prospectively 1- to 5-years post-ACLR. Return to pivoting sport was assessed at 1-, 3- and 5-years. Longitudinal changes in osteoarthritis features were evaluated from 1- and 5-year magnetic resonance imaging (MRI)s using MRI Osteoarthritis Knee Score (MOAKS). Radiographic osteoarthritis and self-reported knee symptoms, function and quality of life were assessed using the Osteoarthritis Research Society International (OARSI) atlas and Knee injury Osteoarthritis Outcome Score (KOOS), respectively, at 5 years post-ACLR. Generalised linear models (adjusted for baseline characteristics) assessed whether returning to pivoting sport was associated with risk of worsening osteoarthritis features on MRI, radiographic osteoarthritis and KOOS. RESULTS: Thirty participants returned to pivoting sport 1-year post-ACLR and 50 returned at any time (i.e., 1-, 3- or 5-years). Returning to pivoting sport was not associated with worsening of any MRI osteoarthritis feature (risk ratio (RR) range: 0.59-2.91) or 5-year KOOS (ß range: -2.73-3.69). Returning to pivoting sport at 1-year and up to 5-years post-ACLR was associated with a 50% (RR 0.49, 95%CI 0.10-2.37) and 40% (RR 0.60, 95%CI 0.16-2.17) reduced risk of radiographic osteoarthritis, respectively, but these risk reductions were inconclusive due to wide confidence intervals. CONCLUSION: After ACLR, returning to pivoting sport was not associated with increased risk of worsening knee osteoarthritis features on MRI, radiographic osteoarthritis or knee symptoms. Participation in pivoting sport need not be avoided as part of osteoarthritis secondary prevention strategies.

Knee kinematics and kinetics are associated with early patellofemoral osteoarthritis following anterior cruciate ligament reconstruction.

OBJECTIVE: Patellofemoral osteoarthritis (PFOA) commonly occurs following anterior cruciate ligament reconstruction (ACLR). Our study aimed to compare knee kinematics and kinetics during a hop-landing task between individuals with and without early PFOA post-ACLR. DESIGN: Forty-five individuals (mean ± SD 26 ± 5 years) 1-2 years post-ACLR underwent 3T isotropic MRI scans and 3D biomechanical assessment of a standardised forward hop task. Knee kinematics (initial contact, peak, excursion) in all three planes and sagittal plane kinetics (peak) were compared between 15 participants with early PFOA (MRI-defined patellofemoral cartilage lesion) and 30 participants with no PFOA (absence of patellofemoral cartilage lesion on MRI) using analysis of covariance (ANCOVA), adjusted for age, BMI, sex and the presence of early tibiofemoral OA. RESULTS: Compared to participants without PFOA, those with early PFOA exhibited smaller peak knee flexion angles (mean difference, 95% confidence interval [CI]: -5.2°, -9.9 to -0.4; P = 0.035) and moments (-4.2 Nm/kg.m, -7.8 to -0.6; P = 0.024), and greater knee internal rotation excursion (5.3°, 2.0 to 8.6; P = 0.002). CONCLUSIONS: Individuals with early PFOA within the first 2-years following ACLR exhibit distinct kinematic and kinetic features during a high-load landing task. These findings provide new information regarding common post-ACLR biomechanical patterns and PFOA. Since management strategies, such as altering knee load, are more effective during the early stages of disease, this knowledge will help to inform clinical management of early PFOA post-ACLR.

Cutaneous basal cell carcinoma of the back metastasizing to the ipsilateral latissimus dorsi muscle.

Metastases from cutaneous basal cell carcinomata are extremely rare phenomena. The majority of haematogenous metastases occur (in descending order) in the lung, skin and liver. The ratio of lymphogenic to haematogenic metastases is approximately 1 to 1. An exceedingly rare case of a metastasis to skeletal muscle is presented.

An improved method for the structural profiling of keratan sulfates: analysis of keratan sulfates from brain and ovarian tumors.

A previously developed method for the structural fingerprinting of keratan sulfates (Brown et al., Glycobiology, 5, 311-317, 1995) has been adapted for use with oligosaccharides fluorescently labeled with 2-aminobenzoic acid following keratanase II digestion. The oligosaccharides are separated by high-pH anion-exchange chromatography on a Dionex AS4A-SC column. This methodology permits quantitative analysis of labeled oligosaccharides which can be detected at the sub-nanogram ( approximately 100 fmol) level. Satisfactory calibration of this method can be achieved using commercial keratan sulfate standards. Keratan sulfates from porcine brain phosphocan and human ovarian tumors have been examined using this methodology, and their structural features are discussed.

Thickness of tibial inserts in total knee arthroplasty.

The thickness of the ultrahigh-molecular-weight polyethylene used in the tibial inserts of total knee arthroplasties has become topical in recent years. A discrepancy has been found between the nomenclature of tibial inserts and the actual minimum thickness of polyethylene. Although the recommended minimum thickness is being discussed, it is important to clarify what is actually being used, with an indication to change and unify how these inserts are named.

Prosthetic reconstruction of the proximal femur after resection for bone tumors.

Thirty-one cases of endoprosthetic proximal femoral reconstruction after resection for bone tumors are reported. The minimum follow-up period was 2 years (average, 63 months). There were two local recurrences, two deaths from pulmonary metastases, two postoperative infections (1 superficial and 1 deep), both responding to therapy, one postoperative dislocation of a bipolar endoprosthesis, and two cases of loosening of acetabular cups on the same patient. Clinical results (Enneking grade) showed 27% E, 56% G, 14% F, and 3% P. Diaphyseal remodeling results (Rizzoli grade) were 29% A, 6% B, 49% C, 10% D, and 6% E. Anchorage (International Society of Limb Salvage grade) was assessed as 97% E and 3% F, whereas interface (International Society of Limb Salvage grade) was 100% E. Hip (bipolar) articulation was graded as 30% E, 56% G, 11% F, and 3% P. Initial rigid stabilization of the stem with cross-fixation screws allows for excellent bone ingrowth, but presents the problem of proximal cortical atrophy. Bipolar hip components are easy to insert and offer greater inherent stability and so are to be recommended for use in tumor surgery. The results suggest good medium- to long-term results with respect to wear. A new radiographic grading system is presented for bipolar arthroplasty. Survivorship of the femoral component in this series is 100% at a maximum follow-up period of 8 years.

Skeletal keratan sulphate structural analysis using keratanase II digestion followed by high-performance anion-exchange chromatography.

A semi-quantitative fingerprinting method has been developed for the structural analysis of skeletal keratan sulphates. This involves the digestion of the parent keratan sulphate chains with the enzyme keratanase II (Bacillus sp.), followed by reduction of the resulting oligosaccharides with sodium borohydride and chromatography on a Dionex AS4A-SC column. This column has been calibrated for the elution positions of 26 previously characterized oligosaccharides (Brown et al., Biochemistry, 33, 4836-4846, 1994; Brown et al., Eur. J. Biochem., 224, 281-308, 1994). The technique permits sample analysis with pulsed electrochemical detection (sensitive to approximately 5 ng of oligosaccharide) or by monitoring [3H] or [35S] radiolabel (potentially sensitive to approximately 1 pg or less of an oligosaccharide); thus permitting the study of sub-microgram amounts of keratan sulphates. Skeletal keratan sulphates from a number of sources have been examined in this chromatographic system and their structural features are discussed.

Modular endoprosthetic replacement after total resection of the femur for malignant tumour.

Seven patients underwent total resection of the femur with replacement by the Kotz modular femur and tibia reconstruction system (KMFTR); three of these operations were for primary malignant tumours and four were salvage procedures after failed limb-sparing surgery. Clinical and radiological results were excellent or good at final follow up at an average of 23 months. A new method of radiological assessment has been used for the acetabular component of bipolar hip endoprosthesis. The polyethylene bush of the hinged knee component may wear. Reattachment of the abductors to the endoprostheses often fails and we now suture the abductors to the fascia lata. The rectus femoris muscle should be saved, if possible, after resection. When total excision of the quadriceps is indicated, the knee should be arthrodesed. The KMFTR is easy to use and has provided good medium to long term results in our cases.

Oligosaccharides derived from bovine articular cartilage keratan sulfates after keratanase II digestion: implications for keratan sulfate structural fingerprinting.

Keratan sulfate chains were isolated from bovine articular cartilage (6-8-year-old animals) and digested with keratanase II, an endo-beta-N-acetylglucosaminidase [Nakazawa, K., Ito, M., Yamagata, T., & Suzuki, S. (1989) in Keratan Sulphate: Chemistry, Biology and Chemical Pathology (Greiling, H., & Scott, J. E., Eds.) pp 99-110, The Biochemical Society, London]. Twenty-five borohydride-reduced oligosaccharides were purified chromatographically and characterized by one- and two-dimensional NMR spectroscopy. From the structures of these oligosaccharides the following conclusions can be drawn about the mode of action of keratanase II: (1) The enzyme cleaves the beta (1-->3)-glycosidic bond between 6-O-sulfated N-acetyl-glucosamine and galactose, the major products being mono- and disulfated disaccharides. (2) Larger oligosaccharides containing keratanase II susceptible bonds are produced which are resistant to further degradation, e.g., tetrasaccharides from the sulfated poly(N-acetyllactosamine) repeat sequence, fucose-containing penta- and hexasaccharides, and hexa- and heptasaccharides from the linkage region. (3) The enzyme cleaves the beta (1-->3)-glycosidic bond of a fucosylated 6-O-sulfated N-acetylglucosamine. (4) Sialic acid-containing capping fragments are always recovered as pentasaccharides, despite the presence of an apparently susceptible bond. Two new elements of skeletal keratan sulfate structure, namely, the highly sulfated cap NeuAc alpha 2-3Gal(6S) beta 1-4GlcNAc (6S) beta 1-3Gal(6S) beta 1-4GlcNAc (6S)-ol and the difucosylated sequence Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, have been identified. A structural model for articular cartilage keratan sulfate is proposed. The potential of the enzyme keratanase II for the structural fingerprinting of subnanogram quantities both of keratan sulfates and of sulfated oligosaccharide selectin ligands is discussed.

Modular uncemented prosthetic reconstruction after resection of tumours of the distal femur.

We report the use of the uncemented Kotz modular femur and tibia reconstruction system after 95 distal femoral resections performed from 1983 to 1989. The average follow-up was 51 months; 62 patients had at least 36 months' follow-up and 36 at least 60 months. Complications required reoperation in 55%. The postoperative infection rate was 5% for primary cases, 6% for revision cases, and 43% for revision of previously infected cases. The polyethylene bushes failed in 42% of cases at an average of 64 months postoperatively. Stem breakage occurred in 6% and was associated with the use of narrow stems and extensive quadriceps excision. The radiological results were excellent or good in most cases and were related to the initial screw fixation, but not to age, chemotherapy, length of resection or size of stem. The clinical results were excellent or good in 75%, failure usually being associated with a complication, especially infection.

A sub-population of keratan sulphates derived from bovine articular cartilage is capped with alpha(2-6)-linked N-acetylneuraminic acid residues. Affinity chromatography using immobilized Sambucus nigra lectin and characterization using 1H n.m.r. spectroscopy.

Alkaline borohydride-reduced keratan sulphate (KS) chains derived from bovine femoral head cartilage were fractionated by lectin affinity chromatography with Sambucus nigra agglutinin (SNA) into binding and non-binding populations. Analysis of the SNA-binding and non-binding KS chains using 600 MHz 1H n.m.r. spectroscopy showed that the former population contained alpha(2-6)-N-acetylneuraminic acid residues and the latter contained primarily alpha(2-3)-N-acetylneuraminic acid residues as chain terminators. Both populations contained a similar proportion of alpha(2-3)-N-acetylneuraminic acid residues within their protein-linkage regions, and similar sulphation and fucosylation levels. Analysis of these two fractions by gel-permeation chromatography (g.p.c.) on a TSK-30 XL column showed them to have the same size distributions. It was concluded from the n.m.r. spectra and g.p.c. data that the populations differed primarily in the mode of linkage of the chain-terminating sialic acids.

Degradation of articular cartilage keratan sulphates using hydrazinolysis and nitrous acid. Environment of fucose residues.

Alkaline borohydride-reduced keratan sulphate (KS) chains from bovine articular cartilage (6-8-year-old animals) were fragmented by an anhydrous hydrazine/nitrous acid procedure, previously used on KS by Hopwood & Elliott to isolate the major disaccharides from the poly-N-acetyl-lactosamine repeat sequence [Hopwood & Elliott (1983) Carbohydr. Res. 117, 263-274]. The resulting oligosaccharides were reduced with NaB3H4 or NaBH4 and subjected to ion-exchange chromatography on a Nucleosil 5SB column. In addition to the major disaccharides, two fucose-containing oligosaccharides were examined by high-field 1H n.m.r. spectroscopy, and shown to have the following structures (where AnManOH is 2,5-anhydro-D-mannitol): [formula: see text] It is evident that the presence of fucose protects the N-acetylglucosamine residue from de-N-acetylation, and therefore fragments are produced which preserve the immediate environment of the fucose residue. It may be of biosynthetic significance that these two oligosaccharides contain an unsulphated galactose on the non-reducing side of the fucose residue. The hydrazine/nitrous acid/NaB3H4 method followed by h.p.l.c. provides a sensitive fingerprinting technique for the assay of KS composition and sub-populations.

Fucose content of keratan sulphates from bovine articular cartilage.

Alkaline-borohydride-reduced keratan sulphate chains were isolated from bovine articular cartilage (6-8-year-old animals). Nine keratan sulphate fractions of increasing molecular weight were prepared by gel-permeation chromatography on a calibrated column of TSK 30 XL. The samples were analysed for fucose and galactose contents (% by wt. of keratan sulphate) and fucose/galactose ratio. The fucose content increased with molecular size, but the galactose content remained constant. It was concluded that the alpha(1----3)-linked fucose [Thornton, Morris, Cockin, Huckerby, Nieduszynski, Carlstedt, Hardingham & Ratcliffe (1989) Biochem. J. 260, 277-282] was located within the poly-N-acetyl-lactosamine repeat sequence of articular-cartilage keratan sulphate.

Skeletal keratan sulfate chain molecular weight calibration by high-performance gel-permeation chromatography.

A method has been developed for the molecular sizing of skeletal keratan sulfate chains using an HPLC gel-permeation chromatography system. Keratan sulfate chains and keratanase-derived oligosaccharides were prepared from the nucleus pulposus of bovine intervertebral disc (6-year-old animals). A Bio-Gel TSK 30 XL column eluted in 0.2 M NaCl and at 30 degrees C was calibrated with keratan sulfate oligosaccharides of known size as well as 3H-end-labeled keratan sulfate chains to yield the relationship.

There are two major types of skeletal keratan sulphates.

High-field 1H-n.m.r.-spectroscopic studies supported by chemical carbohydrate analyses show that skeletal keratan sulphates (KS-II) of bovine origin may be sub-classified into two groups. Keratan sulphate chains from articular and intervertebral-disc cartilage (KS-II-A) contain two structural features, namely alpha(1----3)-fucose and alpha(2----6)-linked N-acetyl-neuraminic acid residues, that are absent from keratan sulphates from tracheal or nasal-septum cartilage (KS-II-B).

Structural and immunological studies of keratan sulphates from mature bovine articular cartilage.

Two populations of alkaline-borohydride-reduced keratan sulphate (KS) chains were prepared from the two peptido-keratan sulphate trypsin fragments of proteoglycan aggregates isolated from bovine femoral head cartilage (6-year-old animals). Each population was separated by high-performance ion-exchange chromatography on a Pharmacia Mono-Q column into eight pools, Q1-Q8. These were analysed by gel permeation chromatography, radioimmunoassay with the monoclonal antibody MZ15, and 500 MHz 1H n.m.r. spectroscopy. Upon chromatography on Sephadex G-75 the Mono-Q fractions were shown to increase in hydrodynamic size progressively from Q1 to Q8 for both KS populations. For each population the strongest antigenic response with the anti-KS monoclonal antibody MZ15 was expressed by the two fractions of greatest size and charge density, Q7 and Q8. Proton n.m.r. spectroscopic studies on the two series of fractions demonstrated: (i) a progressive increase in the level of galactose sulphation from Q1 to Q8, (ii) the presence of approximately one alpha(1-3)-linked fucose residue per chain in every sample, and (iii) the presence of N-acetylneuraminic acids in three discrete environments, two alpha(2-3)- and one alpha(2-6)-linked in every sample. The results are discussed in terms of a possible heterogeneity in the carbohydrate-protein linkage region of keratan sulphates from bovine articular cartilage.

Structural studies of two populations of keratan sulphate chains from mature bovine articular cartilage.

Two discrete peptido-keratan sulphate fragments were isolated via chondroitinase ABC and trypsin digestion of a proteoglycan aggregate fraction prepared from bovine femoral head cartilage (six year old animals). The larger fragments (K(av) = 0.07, CL-6B) contained peptides substituted with several keratan sulphate (KS) chains from the KS-rich region of the proteoglycan and the smaller fragments (K(av) = 0.5, CL-6B) contained peptides with, perhaps, only one KS chain and the stubs of post-chondroitinase-treated chondroitin sulphate chains. The two peptido-KS samples and the KS chains derived from these by alkaline borohydride reduction were characterised by 13C-NMR spectroscopy. The two populations of KS chains were also examined by chromatography (Sephadex G-75), and keratanase digestion followed by chromatography on Bio-Gel P-10. From the results it was concluded that the KS chains from the two major trypsin-derived peptido-KS fragments had similar sulphation levels, distributions of hydrodynamic sizes and susceptibilities to keratanase.

An update on treatment of asthma with inhaled steroids.

This paper reviews current information on the pharmacology of inhaled steroid preparations, advances in the methods for delivering such agents to the lung, and the clinical experience with these agents during more than a decade of use for treatment of patients with asthma.