Osteochondral impaction of the posterior acetabular surface without cortical fracture of any wall or column: an undescribed pattern of acetabular injury

Surgical treatment of a unusual acetabular fracture is described. This fracture was characterized by impaction and breaking down of the posterior articular surface and comminution of lamina quadrilatera lower portion, without cortical fracture of both columns. The fracture was treated surgically through the Kocher–Langenbeck approach. A small hole was created in the acetabulum posterior wall, the impacted fragment was reduced, and the bone defect was filled with autologous bone from the greater trochanter. A plate was shaped in order to fix both bone graft and fractured fragment

Neurofilaments form flexible bundles during neuritogenesis in culture and in mature axons in situ

Neurofilaments (NFs) undergo cation-dependent phospho-mediated associations with each other and other cytoskeletal elements that support axonal outgrowth. Progressive NF-NF associations generate a resident, bundled population that undergoes exchange with transporting NFs. We examined the properties of bundled NFs. Bundles did not always display a fully linear profile but curved and twisted at various points along the neurite length. Bundles retracted faster than neurites and retracted bundles did not expand following extraction with Triton, indicating that they coiled passively rather than due to pressure from the cell. Bundles consisted of helically wound NFs, which may provide flexibility necessary for turning of growing axons during pathfinding. Interactions between NFs and other cytoskeletal elements may be disrupted en masse during neurite retraction or regionally during remodeling. It is suggested that bundles within long axons that cannot be fully retracted into the soma could provide maintain proximal support yet still allow more distal flexibility for remodeling and changing direction during pathfinding

Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology

The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson\u27s disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects

High throughput screening for identification of mycolactone targets : Relations between M. ulcerans and nervous system

Buruli ulcer is an infectious disease transmitted by arthropod vectors harboring Mycobacterium ulcerans, a mycobacterium which belong to the same family of bacteria causing tuberculosis and leprosy. The infection causes painless swelling and severe skin lesions. One key feature of M. ulcerans bacterium is its ability to secrete a necrotic toxin, the mycolactone within small lipophilic vesicles, which are critical for the bacterial induced cytotoxicity. The biological knowledge as well as the preventive and therapeutic means for this invalidating disease is still very limited.   Our first approach was to investigate whether the mycolactone toxin could be involved in the neutralization of pain by acting directly on the peripheral nervous system without causing destruction of nervous fibers. By use of live time fluorescence microscopy and appropriate markers, we showed that the addition of toxin at sub-toxic dose provokes modification of ionic currents of neuron cells. Based on this ability of the toxin, a molecular high throughput methodology was developed for the screening of a genome wide siRNA library and small molecules inhibitors to enable the search of the cellular targets for the toxin. The cell-based assay relies on automated confocal microscopy on macrophages coupled with dedicated image analysis. These two screening allowed us to identify a putative toxin target, and a toxin inhibitor. A binding assay confirmed that the putative target is a receptor of the toxin. Together these results allowed us to build a potential signaling pathway activated by the mycolactone and implicated in ionic channel activities.   The second approach was to confirm this model in the mouse model of M. ulcerans infection and its role in the hypoesthesia of the lesions. Toxin inhibitor, daily administered to mice, which were experimentally infected by M. ulcerans, conducted to the absence of the hypoesthesia of the lesions. Furthermore, a histological study of neuronal fibers did not show a destruction of neuronal cells. Moreover, in vitro studies have showed that M. ulcerans are able to colonize neuronal cells. Then, these results suggested that the hypoesthesia of the M. ulcerans lesions could be caused by a non-destructive process of nervous cells.

Evaluation of alpha-synuclein immunohistochemical methods for the detection of Lewy-type synucleinopathy in gastrointestinal biopsies

The observation showing that Lewy type synucleinopathy (LTS), the pathological hallmark of Parkinson’s disease (PD), is found in the gut of almost all PD subjects led to a substantial amount of research to develop a diagnostic procedure in living patients based on endoscopically obtained gastrointestinal biopsies. However, the existing studies have provided conflicting results regarding the sensitivity and specificity of gastrointestinal biopsies for the detection of LTS. We therefore undertook a multi-center staining and blinded judging of a common set of slides from colonic biopsies to determine the optimal protocol for the detection of LTS. Four different immunohistochemical methods, developed in four separate expert laboratories, were evaluated for their sensitivity and specificity to detect enteric LTS. Test sets of formalin-fixed, paraffin-embedded sections from biopsies of 9 PD subjects and 3 controls were stained with the 4 methods and graded by 4 different observers. Four types of staining morphology (granular staining in the lamina propria, perivascular/vascular wall staining in the submucosa, lacy-granular pattern in the submucosa and epithelial cell nuclear staining) were variably observed in the slides stained by the 4 methods. Positive alpha-synuclein staining was observed by all 5 judges in most of the slides from control cases, regardless of the staining methods that were used. Moreover, none of the tested method or staining pattern had a specificity and sensitivity more than 80 % regarding to PD. Overall, our study suggest that the tested methods are not adequate for the prediction of PD using gastrointestinal biopsies. Future studies are warranted to test new immunostaining methods

Is M. ulcerans able to colonize neuronal cells?

Buruli ulcer, or Mycobacterium ulcerans infection, is an emerging disease, principally diagnosed in humid tropical countries and inducing large skin ulcers. These lesions are painless, a distinct feature that suggests that the mycolactone toxin and/or M. ulcerans impedes the signal transmission by the nervous system. In this context, the aim of this work was to study the interaction between M. ulcerans and neuronal cells by using in vitro and in vivo models. We showed that a virulent strain of M. ulcerans is able to enter into neurons cultivated from neonatal rat hippocampus. On the contrary, this phenomenon was less observed with a mycolactone-deficient strain. To support these data, we analysed nerve fibres from mouse-infected tissues and few bacilli were found in close contact with nerve fibres. The invasion process established by M. ulcerans to colonize the nervous system remains uncharacterised, but we hypothesise that this ability could be involved in the painless of the M. ulcerans infection

Acute isolated acetabular fracture following a game of squash: a case report

Although hip injuries do not account a large amount of the Sports Physician's workload they can result in significant morbidity. We present a case where an acetabular fracture was sustained in a relatively young female while playing squash without any history of fall or injury but was treated successfully non-operatively. Such patients who present with acute hip pain must not be dismissed as simply having a soft tissue injury

Traumatic fracture-dislocation of the hip following rugby tackle: a case report

Posterior fracture-dislocation of hip is uncommonly encountered in rugby injuries. We report such a case in an adult while playing rugby. The treating orthopaedician can be caught unaware and injuries in such sports can be potentially misdiagnosed as hip sprains. Immediate reduction of the dislocation was performed in theatres. The fracture was fixed with two lag screws and a neutralization plate. This led to early rehabilitation and speedy recovery with return to sporting activities by 12 months

Melanoma tumour vasculature heterogeneity: from mice models to human

Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment