Joint stiffness is heritable and associated with fibrotic conditions and joint replacement

ObjectiveJoint stiffness is a common, debilitating, age-related symptom, which may be seen after total joint replacement (TJR). Stiffness also occurs in fibrotic conditions such as shoulder capsulitis and Dupuytren's contracture. We speculated that the two traits (TJR and fibrotic disease) are linked pathogenically.MethodsUsing the TwinsUK NIHR BRC BioResource we tested the hypotheses that 1) joint (hip and knee) stiffness, TJR (hip and knee), and fibrotic conditions are associated and 2) genetic factors contribute to them.ResultsParticipating twins (n = 9718) had completed self-reported questionnaires on the traits of interest. All three traits were significantly associated with increasing age and body mass index (BMI), as well as female sex, on univariate analysis. Multivariable logistic regression analyses showed a significant association between TJR and joint stiffness (OR = 3.96, 95% confidence interval, CI 2.77-5.68) and between fibrotic conditions and joint stiffness (OR = 2.39, 1.74-3.29), adjusting for age, sex, BMI and twin relatedness. Monozygotic versus dizygotic intraclass correlations gave heritability estimates for TJR = 46% and joint stiffness = 32%.ConclusionThat fibrotic conditions, joint stiffness and TJR are significantly associated suggests a common disease process, possibly fibrosis, which is genetically mediated

Post-radiation sciatic neuropathy: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Post-radiation peripheral neuropathy has been reported in brachial and cervical plexuses and the femoral nerve.</p> <p>Case presentation</p> <p>We describe a patient who developed post-radiation sciatic neuropathy after approximately 3 years and discuss the pathophysiology, clinical course and treatment options available for the deleterious effects of radiation to peripheral nerves.</p> <p>Conclusion</p> <p>This is the first case of post-radiation involvement of the sciatic nerve reported in the literature.</p

Slow stretching that mimics embryonic growth rate stimulates structural and mechanical development of tendon-like tissue in vitro.

A distinctive feature of embryonic tendon development is the steady increase in collagen fibril diameter and associated improvement of tissue mechanical properties. A potential mechanical stimulus for these changes is slow stretching of the tendon during limb growth. Testing this hypothesis in vivo is complicated by the presence of other developmental processes including muscle development and innervation. Here we used a cell culture tendon-like construct to determine if slow stretch can explain the increases in fibril diameter and mechanical properties that are observed in vivo. Non-stretched constructs had an ultrastructural appearance and mechanical properties similar to those of early embryonic tendon. However, slowly stretching during 4 days in culture increased collagen fibril diameter, fibril packing volume, and mechanical stiffness, and thereby mimicked embryonic development. 3D EM showed cells with improved longitudinal alignment and elongated nuclei, which raises the hypothesis that nuclear deformation could be a novel mechanism during tendon development. Developmental Dynamics 240:2520–2528, 2011. © 2011 Wiley Periodicals, Inc

Tenocyte contraction induces crimp formation in tendon-like tissue

Tendons are composed of longitudinally aligned collagen fibrils arranged in bundles with an undulating pattern, called crimp. The crimp structure is established during embryonic development and plays a vital role in the mechanical behaviour of tendon, acting as a shock absorber during loading. However, the mechanism of crimp formation is unknown, partly because of the difficulties of studying tendon development in vivo. Here we used a 3D cell culture system in which embryonic tendon fibroblasts synthesize a tendon-like construct comprised of collagen fibrils arranged in parallel bundles. Investigations using polarized light microscopy, scanning electron microscopy and fluorescence microscopy showed that tendon-constructs contained a regular pattern of wavy collagen fibrils. Tensile testing indicated that this superstructure was a form of embryonic crimp producing a characteristic toe region in the stress-strain curves. Furthermore, contraction of tendon fibroblasts was the critical factor in the buckling of collagen fibrils during the formation of the crimp structure. Using these biological data, a finite element model was built that mimics the contraction of the tendon fibroblasts and monitors the response of the ECM. The results show that the contraction of the fibroblasts is a sufficient mechanical impulse to build a planar wavy pattern. Furthermore, the value of crimp wavelength was determined by the mechanical properties of the collagen fibrils and inter-fibrillar matrix. Increasing fibril stiffness combined with constant matrix stiffness led to an increase in crimp wavelength. The data suggest a novel mechanism of crimp formation, and the finite element model indicates the minimum requirements to generate a crimp structure in embryonic tendon

Multiple schwannomas of the upper limb related exclusively to the ulnar nerve in a patient with segmental schwannomatosis

Summary Schwannomas are benign encapsulated tumours arising from the sheaths of peripheral nerves. They present as slowly enlarging solitary lumps, which may cause neurological defects. Multiple lesions are rare, but occur in patients with neurofibromatosis type 2 or schwannomatosis. Positive outcomes have been reported for surgical excision in solitary schwannomas. However, the role of surgery in patients with multiple lesions is less clear. The risk of complications such as iatrogenic nerve injury and the high likelihood of disease recurrence mean that surgical intervention should be limited to the prevention of progressive neurological deficit. We report a case of a 45 year old male who presented with multiple enlarging masses in the upper limb and sensory deficit in the distribution of the ulnar nerve. The tumours were found to be related exclusively to the ulnar nerve during surgical exploration and excision, a rare phenomenon. The masses were diagnosed as schwannomas following histopathological analysis, allowing our patient to be diagnosed with the rare entity segmental schwannomatosis. One year post-operatively motor function was normal, but intermittent numbness still occurred. Two further asymptomatic schwannomas developed subsequently and were managed conservatively

Tenocyte contraction induces crimp formation in tendon-like tissue

Abstract Tendons are composed of longitudinally aligned collagen fibrils arranged in bundles with an undulating pattern, called crimp. The crimp structure is established during embryonic development and plays a vital role in the mechanical behaviour of tendon, acting as a shock-absorber during loading. However, the mechanism of crimp formation is unknown, partly because of the difficulties of studying tendon development in vivo. Here, we used a 3D cell culture system in which embryonic tendon fibroblasts synthesise a tendonlike construct comprised of collagen fibrils arranged in parallel bundles. Investigations using polarised light microscopy, scanning electron microscopy and fluorescence microscopy showed that tendon constructs contained a regular pattern of wavy collagen fibrils. Tensile testing indicated that this superstructure was a form of embryonic crimp producing a characteristic toe region in the stress-strain curves. Furthermore, contraction of tendon fibroblasts was the critical factor in the buckling of collagen fibrils during the formation of the crimp structure. Using these biological data, a finite element model was built that mimics the contraction of the tendon The results show that the contraction of the fibroblasts is a sufficient mechanical impulse to build a planar wavy pattern. Furthermore, the value of crimp wavelength was determined by the mechanical properties of the collagen fibrils and inter-fibrillar matrix. Increasing fibril stiffness combined with constant matrix stiffness led to an increase in crimp wavelength. The data suggest a novel mechanism of crimp formation, and the finite element model indicates the minimum requirements to generate a crimp structure in embryonic tendon

Do changes in gastro-intestinal blood flow explain high-altitude anorexia?

Background  Gastrointestinal symptoms are common on acute exposure to high-altitude (HA). Underlying mechanisms are not understood, but vascular shunting away from the gut could be responsible. Therefore, blood flow in the superior mesenteric artery (SMA) and hepatic portal vein (HPV) was examined at sea level (SL) and after ascent to 4392 m (HA). Materials and methods  Twelve subjects [eight male, mean age 40 (22–72) years] were studied following an overnight fast and a standard meal. Cross-sectional vessel area and blood velocity were measured by ultrasound, systolic and diastolic flow calculated for the SMA (HR × vessel area × velocity, cm3 min−1) and mean flow for the HPV. Results  All subjects experienced reduced appetite at HA. Blood flow in the SMA and HPV increased following food at SL (mean SMA systolic flow 1024 vs. 3316 cm3 min−1, P < 0·001; HPV 505 vs. 1789, P < 0·001) and at HA (2020 vs. 3767, P < 0·001; HPV 708 vs. 1727, P < 0·001). Pre-prandial flow in the SMA and HPV was significantly increased at HA compared with SL. The changes were due to increased vessel diameter and increased flow velocity. There was no difference in post-prandial flow between SL and HA in the HPV, although the increase in post-prandial flow was greater at SL than HA (254% increase vs. 144%). Conclusions  These results show that resting blood flow in the gastrointestinal tract is increased during exposure to high-altitude hypoxia, and that the vascular response of increased blood flow following food ingestion is maintained. Therefore, reduced flow is unlikely to cause gastrointestinal symptoms and reduced appetite at HA