The colonisation of the glenohumeral joint by Propionibacterium acnes is not associated with frozen shoulder but is more likely to occur after an injection into the joint.

AIMS: Our aim was to investigate the prevalence of Propionibacterium (P.) acnes in the subcutaneous fat and capsule of patients undergoing shoulder surgery for frozen shoulder or instability. PATIENTS AND METHODS: A total of 46 patients undergoing either an arthroscopic capsular release or stabilisation had biopsies taken from the subcutaneous fat and capsule of the shoulder at the time of surgery. These samples were sent for culture in enrichment, and also for Nucleic Acid Amplification testing. The prevalence of P. acnes and other microbes was recorded. Fisher's exact test of binary variables was used to calculate the association with significance set at p < 0.05. Assessment of influence of independent variables including a pre-operative glenohumeral injection, fat colonisation and gender, was undertaken using binary linear regression. RESULTS: A total of 25 patients (53%) had P. acnes in one or more tissue samples and 35 (74%) had other bacterial species. The same microbe was found in the subcutaneous fat and the capsule in 13 patients (28%). There was no statistically significant association between the surgical pathology and capsular colonisation with P. acnes (p = 0.18) or mixed identified bacterial species (p = 0.77). Male gender was significantly associated with an increased capsular colonisation of P. acnes (odds ratio (OR) 12.38, 95% confidence interval (CI) 1.43 to 106.77, p = 0.02). A pre-operative glenohumeral injection was significantly associated with capsular P. acnes colonisation (OR 5.63, 95% CI 1.07 to 29.61, p = 0.04. Positive fat colonisation with P. acnes was significantly associated with capsular P. acnes (OR 363, 95% CI 20.90 to 6304.19, p < 0.01). Regression models pseudo R2 found fat colonisation with P. acnes to explain 70% of the variance of the model. Patients who had a pre-operative glenohumeral injection who were found intra-operatively to have fat colonisation with P. acnes had a statistically significant association with colonisation of their capsule with P. acnes (OR 165, 95% CI 13.51 to 2015.24, p < 0.01). CONCLUSION: These results show a statistically significant association between subcutaneous skin P. acnes culture and P. acnes capsular culture, especially when the patient has undergone a previous injection. The results refute the hypothesis that P. acnes causes frozen shoulder. Cite this article: Bone Joint J 2017;99-B:1067-72.

Anatomy of the terminal branch of the posterior circumflex humeral artery: relevance to the deltopectoral approach to the shoulder.

AIMS: Despite the expansion of arthroscopic surgery of the shoulder, the open deltopectoral approach is increasingly used for the fixation of fractures and arthroplasty of the shoulder. The anatomy of the terminal branches of the posterior circumflex humeral artery (PCHA) has not been described before. We undertook an investigation to correct this omission. PATIENTS AND METHODS: The vascular anatomy encountered during 100 consecutive elective deltopectoral approaches was recorded, and the common variants of the terminal branches of the PCHA are described. RESULTS: In total, 92 patients (92%) had a terminal branch that crossed the space between the deltoid and the proximal humerus and which was therefore vulnerable to tearing or avulsion during the insertion of the blade of a retractor during the deltopectoral approach to the shoulder. In 75 patients (75%) there was a single vessel, in 16 (16%) a double vessel and in one a triple vessel. CONCLUSION: The relationship of these vessels to the landmark of the tendon of the insertion of pectoralis major into the proximal humerus is described. Damage to these previously undocumented branches can cause persistent bleeding leading to prolonged surgery and post-operative haematoma and infection, as well as poor visualisation during the procedure. Cite this article: Bone Joint J 2016;98-B:1395-8.

Early weight-bearing in operatively fixed ankle fractures: a systematic review.

BACKGROUND: Ankle fractures are among the most common lower limb fractures and they can cause significant detrimental effects on quality of life and work. OBJECTIVE: The objective of the review was to evaluate if there is any advantage of early weight-bearing after open reduction and internal fixation of the ankle. METHODS: Electronic databases, reference lists of included studies and relevant systematic reviews were searched for randomized and non-randomized controlled trials in adults comparing early and late weight-bearing after open reduction and internal fixation of the ankle. The search was inclusive up to February 2012. RESULTS: Nine studies comprising 555 subjects were included for review. There were significantly better outcomes for improved early dorsiflexion, time to full weight-bearing, early return to previous work and shorter hospital stay (patient<60 years of age) in the early weight-bearing group. CONCLUSION: The evidence base contained many methodological limitations and was generally poor, and so any conclusion drawn from the research must be done so with caution. The literature suggests that early weight-bearing may allow for quicker rehabilitation and earlier return to work. Future studies should focus on randomized controlled trials with narrow range of clinically useful outcome measures and consistent immobilization strategy between experimental groups.

Anatomical variations of the deltoid artery: relevance to the deltopectoral approach to the shoulder.

Despite the expansion of arthroscopic surgery of the shoulder, the open deltopectoral approach to the shoulder is still frequently used, for example in fracture fixation and shoulder replacement. However, it is sometimes accompanied by unexpected bleeding. The cephalic vein is the landmark for the deltopectoral interval, yet its intimate relationship with the deltoid artery, and the anatomical variations in that structure, have not previously been documented. In this study the vascular anatomy encountered during 100 consecutive elective deltopectoral approaches was recorded and the common variants described. Two common variants of the deltoid artery were encountered. In type I (71%) it crosses the interval and tunnels into the deltoid muscle without encountering the cephalic vein. However, in type II (21%) it crosses the interval, reaches the cephalic vein and then runs down, medial to and behind it, giving off several small arterial branches that return back across the interval to the pectoralis major. Several minor variations were also seen (8%). These variations in the deltoid artery have not previously been described and may lead to confusion and unexpected bleeding during this standard anterior surgical approach to the shoulder.

Cervical spinal abscess: an insidious presentation and unusual pathology.

Spinal abscess is a rare condition. Its presentation can often be subtle and insidious. This report describes the diagnosis and management of an 87-year-old man who presented to our orthopaedic clinic. We would like to emphasise the importance of rapid diagnosis and prompt treatment in such cases.

The Delta III reverse shoulder replacement for cuff tear arthropathy: a single-centre study of 50 consecutive procedures.

The combination of an irreparable tear of the rotator cuff and destructive arthritis of the shoulder joint may cause severe pain, disability and loss of independence in the aged. Standard anatomical shoulder replacements depend on a functioning rotator cuff, and hence may fail in the presence of tears in the cuff. Many designs of non-anatomical constrained or semi-constrained prostheses have been developed for cuff tear arthropathy, but have proved unsatisfactory and were abandoned. The DePuy Delta III reverse prosthesis, designed by Grammont, medialises and stabilises the centre of rotation of the shoulder joint and has shown early promise. This study evaluated the mid-term clinical and radiological results of this arthroplasty in a consecutive series of 50 shoulders in 43 patients with a painful pseudoparalysis due to an irreparable cuff tear and destructive arthritis, performed over a period of seven years by a single surgeon. A follow-up of 98% was achieved, with a mean duration of 39 months (8 to 81). The mean age of the patients at the time of surgery was 81 years (59 to 95). The female to male ratio was 5:1. During the seven years, six patients died of natural causes. The clinical outcome was assessed using the American Shoulder and Elbow score, the Oxford Shoulder Score and the Short-form 36 score. A radiological review was performed using the Sirveaux score for scapular notching. The mean American Shoulder and Elbow score was 19 (95% confidence interval (CI) 14 to 23) pre-operatively, and 65 (95% CI 48 to 82) (paired t-test, p < 0.001) at final follow-up. The mean Oxford score was 44 (95% CI 40 to 51) pre-operatively and 23 (95% CI 18 to 28) (paired t-test, p < 0.001) at final follow-up. The mean maximum elevation improved from 55° pre-operatively to 105° at final follow-up. There were seven complications during the whole series, although only four patients required further surgery.

Clinical and radiological follow-up of the Aequalis third-generation cemented total shoulder replacement: a minimum ten-year study.

There are no long-term published results on the survival of a third-generation cemented total shoulder replacement. We describe a clinical and radiological study of the Aequalis total shoulder replacement for a minimum of ten years. Between September 1996 and May 1998, 39 consecutive patients underwent a primary cemented total shoulder replacement using this prosthesis. Data were collected prospectively on all patients each year, for a minimum of ten years, or until death or failure of the prosthesis. At a follow-up of at least ten years, 12 patients had died with the prosthesis intact and two had emigrated, leaving 25 available for clinical review. Of these, 13 had rheumatoid arthritis and 12 osteoarthritis. One refused radiological review leaving 24 with fresh radiographs. Survivorship at ten years was 100% for the humeral component and 92% for the glenoid component. The incidence of lucent lines was low. No humeral component was thought to be at risk and only two glenoid components. The osteoarthritic group gained a mean 65 degrees in forward flexion and their Constant score improved by a mean 41.4 points (13 to 55). The rheumatoid group gained a mean of 24 degrees in flexion and their Constant score improved by 29.4 points. This difference may have been due to failure of the rotator cuff in 75% of the patients with rheumatoid arthritis. Thus a third-generation total shoulder replacement gives an excellent result in patients with osteoarthritis and an intact rotator cuff. Patients with rheumatoid arthritis have a 75% risk of failure of the rotator cuff at ten years.

Constrained total hip arthroplasty in a paediatric patient with cerebral palsy and painful dislocation of the hip. A case report.

We describe a patient with cerebral palsy, of normal intelligence, who could not walk but who by the age of 16 had been successfully managed with a staged bilateral total hip arthroplasty using a constrained liner.

Meralgia paraesthetica. A complication of a patient-positioning device in total hip replacement.

We describe three patients who developed meralgia paraesthetica after the use of a well-padded and carefully-placed patient-positioning device in total hip replacement.

DR3 regulates negative selection during thymocyte development.

DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death domain-containing tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a variety of developmental events including the regulation of cell proliferation, differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3 by generating mice congenitally deficient in the expression of the DR3 gene. We show that negative selection and anti-CD3-induced apoptosis are significantly impaired in DR3-null mice. In contrast, both superantigen-induced negative selection and positive selection are normal. The pre-T-cell receptor-mediated checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3-deficient mice. These data reveal a nonredundant in vivo role for this TNF receptor family member in the removal of self-reactive T cells in the thymus.

Patellar tendon length following opening wedge high tibial osteotomy using an external fixator with particular reference to later total knee replacement.

The aim of this retrospective study was to examine a cohort of patients who had undergone high tibial osteotomy (HTO) using the method of opening wedge hemicallotasis, and who later required conversion to total knee replacement (TKR). The incidence of patella infra and any technical difficulties encountered during TKR operation were examined. A consecutive series of 76 valgus osteotomies in 65 patients were carried out by one surgeon using a dynamic axial fixator (DAF). Later conversion to TKR, required for the progression of symptoms, was carried out in nine knees (seven patients) at a mean time from the initial osteotomy of 7 years (1.5-11). All of those patients who underwent HTO and subsequently required conversion to TKR were followed up. The patellar height was assessed by one observer in all knees pre- and post-HTO using the Insall and Salvati and Blackburne and Peel ratios. Using these criteria, only one case of patella infra occurred. There were no added technical difficulties in performing TKR as a result of the previous osteotomy and clinical outcomes using the Oxford knee score were satisfactory (34 where 48 is maximum).

Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3).

WSL-1/TRAMP (DR3) is a member of the tumour necrosis factor (TNF) receptor superfamily which exhibits effects on NF-kappaB activation and apoptosis. TWEAK, a novel TNF-related molecule, has been proposed as the ligand for this receptor. Utilising both human and murine TWEAK ligand, it is shown that TWEAK and WSL-1/TRAMP do not interact in an in vitro binding assay and that TWEAK binds strongly to cells that do not express WSL-1/TRAMP on the cell surface. Biological activity of TWEAK is also observed in these cells. Finally, cells isolated from WSL-1/TRAMP knockout mice are shown to retain their ability to interact with TWEAK. These results suggest that WSL-1/TRAMP is not the major receptor for TWEAK

Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human neuroblastoma.

The human DR3 gene, whose product is also known as Wsl-1/APO-3/TRAMP/LARD, encodes a tumor necrosis factor-related receptor that is expressed primarily on the surface of thymocytes and lymphocytes. DR3 is capable of inducing both NF-kappa B activation and apoptosis when overexpressed in mammalian cells, although its ligand has not yet been identified. We report here that the DR3 gene locus is tandemly duplicated on human chromosome band 1p36.2-p36.3 and that these genes are hemizygously deleted and/or translocated to another chromosome in neuroblastoma (NB) cell lines with amplified MYCN. Duplication of at least a portion of the DR3 gene, including the extracellular and transmembrane regions but not the cytoplasmic domain, was demonstrated by both fluorescence in situ hybridization and genomic Southern blotting. In most NB cell lines, both the DR3 and the DR3L sequences are simultaneously deleted and/or translocated to another chromosome. Finally, DR3/ Wsl-1 protein expression is quite variable among these NB cell lines, with very low or undetectable levels in 7 of 17 NB cell lines.

A death-domain-containing receptor that mediates apoptosis.

The cell-killing effects of the cytokines TNF-alpha and FasL are mediated by the distinct cell-surface receptors TNFR1, TNFR2 and Fas (also known as CD95/APO-1), which are all members of a receptor superfamily that is important for regulating cell survival. The cytoplasmic regions of TNFR1 and Fas contain a conserved 'death' domain which is an essential component of the signal pathway that triggers apoptosis and activation of the transcription factor NF-kappaB (refs 5,6). Here we report the isolation of a 54K receptor that is a new member of the TNFR superfamily, using the death domain of TNFR1 in a yeast two-hybrid system. This protein, WSL-1, is most similar to TNFR1 itself, particularly in the death-domain region. The gene wsl-1 is capable of inducing apoptosis when transfected into 3T3 and 293 cells, and can also activate NF-kappaB in 293 cells. Like TNFR1, WSL-1 will homodimerize in yeast. WSL-1 also interacts specifically with the TNFR1-associated molecule TRADD. The tissue distribution is very restricted and significantly different from that of Fas and TNFR1.

Expression of plasminogen activators and plasminogen activator inhibitors in cutaneous melanomas of transgenic melanoma-susceptible mice.

The Tyr-SV40E transgenic mouse model of malignant skin melanoma has been used here to generate melanomas in genetically identical (C57BL/6) mice for analysis of the plasminogen activator (PA) system during tumor development and progression. Twenty-two melanocytic lesions were examined by in situ zymography for PA activity and by immunohistochemistry for concomitant visualization of PA proteins; these lesions encompassed 3 nevi and 19 primary melanomas ranging from melanotic through mixed tumors to amelanotic tumors. Although urokinase-type plasminogen activator (u-Pa) activity was not detected at premalignant stages, it began to appear early in tumorigenesis and became more prominent in later stages of a majority of the tumors. The activity was largely attributable to the endothelium of sprouting capillaries and to a lesser degree to granulocytes, fibroblastic cells, and occasional melanoma cells within tumors. Tissue-type plasminogen activator (t-PA) was undetectable or low in all cases. Of the inhibitors (PAI), PAI-1 was seen in endothelial and fibroblastic cells and in the extracellular matrix, whereas PAI-2 occurred in only one case and was melanoma cell associated. Eleven additional melanomas were analyzed by reverse transcription-PCR for PA expression in RNA extracts from relatively large tumor samples. These were obtained from eight primary melanomas and three metastases, again spanning melanotic, mixed, and amelanotic cases. From four of the mixed primary tumors with distinct melanotic and amelanotic zones, the respective components were propagated separately in transgenic hosts as s.c. transplants to obtain data for clearly identifiable melanotic versus amelanotic parts. u-PA and PAI-1 mRNAs were expressed in all. t-PA expression varied greatly and was notably high in several amelanotic tumors or tumor components, possibly as a result of large blood vessels, as such vessels were seen to be t-PA positive in normal tissue. The u-PA activity in sprouting capillaries may indicate a role in neoangiogenesis. Therefore, according to these mouse models, u-PA may indirectly be a potential therapeutic target against melanoma progression.

Role of RNA in enzymatic activity of the reverse transcriptase of hepatitis B viruses.

The hepadnavirus reverse transcriptase is a multifunction enzyme. In addition to its role in DNA synthesis, the polymerase is required for RNA packaging and also functions as the primer for minus-strand DNA synthesis. Previously, we demonstrated that the protein-priming activity of the polymerase requires a viral RNA segment, termed epsilon, which serves as a template for the synthesis of a short DNA oligomer that is covalently attached to the reverse transcriptase (G.-H. Wang and C. Seeger, J. Virol. 67:6507-6512, 1993). We now report that epsilon is sufficient for activation of the reverse transcriptase to prime DNA synthesis through the formation of a stable RNA-protein (RNP) complex. We also demonstrate that the binding reaction depends on sequence-specific determinants on epsilon. Moreover, our results indicate that two genetically separated domains of the reverse transcriptase are required for formation of the RNP complex. Finally, we show that the polymerase has a DNA polymerase activity in the absence of epsilon which does not depend on the protein-priming mechanism.