Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes.

OBJECTIVE: These studies investigated cytokine and chemokine receptor profiles in nucleus pulposus (NP) cells, and the effects of receptor stimulation on mRNA levels of extracellular matrix (ECM) components, degrading enzymes and cytokine and chemokine expression. METHOD: Immunohistochemistry (IHC) was performed to localise expression of CD4, CCR1, CXCR1 and CXCR2 in human NP tissue samples. Effects of cytokine and chemokine stimulation was performed to investigate effects related to ECM remodelling and modulation of cytokine and chemokine mRNA expression. RESULTS: IHC identified CD4, CCR1, CXCR1 and CXCR2 expression by NP cells. Differential expression profiles were observed for CD4 and CXCR2 in tissue samples from degenerate and infiltrated IVDs. In vitro stimulations of primary human NP cultures with IL-16, CCL2, CCL3, CCL7 or CXCL8 did not identify any modulatory effects on parameters associated with ECM remodelling or expression of other cytokines and chemokines. Conversely, IL-1 was seen to modulate ECM remodelling and expression of all other cytokines and chemokines investigated. CONCLUSION: This study demonstrates for the first time that NP cells express a number of cytokine and chemokine receptors and thus could respond in an autocrine or paracrine manner to cytokines and chemokines produced by NP cells, particularly during tissue degeneration. However, this study failed to demonstrate regulatory effects on ECM genes and degradative enzymes or other cytokines and chemokines for any target investigated, with the exception of IL-1. This suggests that IL-1 is a master regulator within the IVD and may exert regulatory potential over a plethora of other cytokines and chemokines.

The incidence of deep vein thrombosis and pulmonary embolism following cast immobilisation and early functional bracing of Tendo Achilles rupture without thromboprophylaxis.

PURPOSE: The routine use of thromboprophylaxis during cast immobilisation for lower leg trauma is controversial. The concern involves the perceived increased risk of deep vein thrombosis (DVT) and its sequelae following leg immobilisation. However, immobilisation is used for a spectrum of trauma and for varying duration. This heterogenicity in management is reflected in the current evidence and coupled with the risks of thromboprophylaxis; no clear consensus has been made. METHODS: In this retrospective study, we report the incidence of DVT and pulmonary embolism (PE) observed following cast immobilisation and early functional management of patients with Tendo Achilles rupture. Over 12 years, 945 consecutive patients (949 tendons) were treated without additional thromboprophylaxis. RESULTS: The incidence of DVT was 1.05 % and PE was 0.32 %. Females were significantly more likely to develop a DVT but not a PE. When compared to the incidence of DVT and PE observed in the general population, DVT rate was statistically significantly higher than that observed in the general population. There was no significant difference in PE rates. The number needed to treat to reduce the DVT incidence is 106. The number needed to treat to reduce the PE incidence is 475. CONCLUSIONS: Although we can conclude that conservative treatment for Tendo Achilles does increase the incidence of symptomatic DVT from the general population, we feel that large randomised control trials are required to evaluate the efficacy, compliance and cost effectiveness of routine DVT thromboprophylaxis in the outpatient setting.

The non-operative functional management of patients with a rupture of the tendo Achillis leads to low rates of re-rupture.

Controversy surrounds the most appropriate treatment method for patients with a rupture of the tendo Achillis. The aim of this study was to assess the long term rate of re-rupture following management with a non-operative functional protocol. We report the outcome of 945 consecutive patients (949 tendons) diagnosed with a rupture of the tendo Achillis managed between 1996 and 2008. There were 255 female and 690 male patients with a mean age of 48.97 years (12 to 86). Delayed presentation was defined as establishing the diagnosis and commencing treatment more than two weeks after injury. The overall rate of re-rupture was 2.8% (27 re-ruptures), with a rate of 2.9% (25 re-ruptures) for those with an acute presentation and 2.7% (two re-ruptures) for those with delayed presentation. This study of non-operative functional management of rupture of the tendo Achillis is the largest of its kind in the literature. Our rates of re-rupture are similar to, or better than, those published for operative treatment. We recommend our regime for patients of all ages and sporting demands, but it is essential that they adhere to the protocol.