Skull base angiomatous leiomyoma: a case report and review of literature.

Leiomyomas, benign neoplasms of mesenchymal origin, are common in gastrointestinal and genitourinary tracts. They are comprised of well-differentiated smooth muscle cells with few mitotic figures. Leiomyomas should not exhibit metastatic potential, though metastasis has been reported. Primary intracranial lesions remain rare. Only 4 cases have been reported in immunocompetent patients. Here we report an intracranial leiomyoma in an immunocompetent patient. A 60 year-old woman with unremarkable past medical history presented with a right sixth nerve palsy. On examination, there was a right sixth nerve palsy with numbness over the right V2 and V3 areas. CT scan showed a well-defined lesion within the right middle cranial fossa adjacent to the cavernous sinus with bony remodelling of the lateral wall of the sphenoid sinus and greater wing of the right sphenoid. MRI showed extra axial mass lesion arising from the right Meckel´s cave/cavernous sinus. The lesion was T2 hyperintense and T1 isointense. Homogenously enhancing centrally with little enhancement peripherally. CT CAP showed no primary lesions. Differential diagnosis at that stage was between meningioma, schwannoma or metastasis. The patient underwent craniotomy and debulking of tumour. Histological analysis confirmed leiomyoma. Post-operative MRI showed residual enhancement in the region of Meckel's cave. As residual tumour was significant, the patient underwent STRS. Further MRI at 1 year showed regression of the tumour. Majority of intracranial leiomyomas are discovered in immunocompromised patients incidentally. Histology reveals spindle shaped cells with blunt ends and few mitotic figures. The best treatment option to date for primary intracranial leiomyomas remains surgical gross total resection without adjuvant radiation therapy. Intracranial leiomyoma transitioning to leiomyosarcoma post radiotherapy has been reported before and therefore follow up with serial imaging is warranted.

Ossified lumbar ligamentum flavum in a caucasian - A case report and literature review.

To our best knowledge, this is the first reported case of ossified ligamentum flavum in the lumbar spine in a Caucasian patient from the United Kingdom. It is an important risk factor to recognise during spinal operation as it can significantly increase its difficulty and the rate of complications.

Usefulness of antero-posterior radiograph and variability of management in non-major thoracolumbar injuries: a single centre pilot study and review of literature.

BACKGROUND: Most adult trauma protocols suggest that where there has been a dangerous mechanism of injury or the patient exhibits abnormal physiology, CT scan is the primary radiological investigation. Other patients who may have suffered thoraco-lumbar (T-L) trauma initially have antero-posterior (AP) and lateral plain X-rays performed. Our clinical experience suggests AP views are not particularly useful in the management of these relatively low-velocity injuries. This is the first study intended to determine the contribution made by AP X-rays in these cases. METHODS: Adults with a history of T-L trauma referred to our tertiary spinal service over 20 weeks were reviewed. Those with a CT scan performed prior to X-rays were excluded. Four spine surgeons and four neuroradiologists were independently shown lateral X-rays along with the clinical details and asked to provide a management plan. Then they were shown the AP X-rays and asked if they would like to change their advice. RESULTS: Fifty-two patients were identified. Thirty-four sets of supine and 40 sets of erect X-rays were included (four people only had lateral X-rays performed), yielding 1152 film views. Average patient age was 58.3 years with 30 (58%) males. Forty-five (87%) were AO type A (compression-type) fractures. Seven (13%) had been erroneously referred with a diagnosis of acute fracture, which on review was not considered to be the case. Fifty-four percent of fractures were between T11 and L2. Forty-six percent appeared osteoporotic.In no instance did evaluation of the AP X-ray change the management plan which had been suggested following the evaluation of the lateral X-ray alone. However, there was significant variation in advice on further management between consultants. CONCLUSIONS: Our results suggest AP X-rays do not contribute to the management of low-velocity thoraco-lumbar traumas. Larger studies are required to support these findings, but there appears to be a potential to reduce both cost and radiation exposure. More importantly, it demonstrates there is large variability in the management of such patients due to the lack of evidence-based protocols.

Overexpression of hyaluronan synthase 2 alters hyaluronan distribution and function in proximal tubular epithelial cells.

The functional consequences of increased renal cortical hyaluronan that is associated with both acute injury and progressive scarring are unclear. The aim of this study was to characterize hyaluronan synthase-2 (HAS2)-driven HA synthesis and determine its effect on renal proximal tubular epithelial cell (PTC) function, because this is known to be the inducible form of HA synthase in this cell type. Overexpression of HAS2 mRNA increased HA generation, which in the supernatant predominantly was HA of large molecular weight, whereas there was an increase in low molecular weight HA in cell-associated fractions. This was associated with increased expression of hyaluronidases, inhibition of HA cable formation concurrent with reduction in HA-dependent monocyte binding, and increased pericellular HA matrix. Overexpression of HAS2 led to enhanced cell migration. HA can be modified by the covalent attachment of heavy chains that are derived from the serum protein inter-alpha-inhibitor (IalphaI), a process that is known to be catalyzed by TNF-alpha-stimulated gene 6 (TSG-6; an inflammation-associated protein). Enhanced migration was abrogated by blocking antibodies to either IalphaI or TSG-6. Addition of recombinant full-length TSG-6 (TSG-6Q) or TSG-6Q_Y94F, a mutant variant with impaired HA binding, increased cell migration. Both of these proteins were able to mediate the covalent transfer of heavy chains, from IalphaI and pre-alpha-inhibitor, onto HA. Addition of the isolated TSG-6-Link module (Link_TSG-6), which binds HA but is unable to form covalent complexes with IalphaI/pre-alpha-inhibitor, had no effect on migration, suggesting that TSG-6-mediated formation of heavy chain-HA complexes is critical in the formation of a pericellular HA matrix.

Bone morphogenic protein-7 inhibits monocyte-stimulated TGF-beta1 generation in renal proximal tubular epithelial cells.

It has been demonstrated that bone morphogenic protein-7 (BMP-7) stimulates formation of hyaluronan (HA)-based cables on the cell surface of renal proximal tubular cells and that these cables mediate monocyte binding. Furthermore, interaction of monocytes with proximal tubule cell (PTC) surface intracellular adhesion molecule (ICAM) stimulates the synthesis of TGF-beta1. This study examined the effect of BMP-7 on monocyte-stimulated TGF-beta1 synthesis under conditions of basal and stimulated ICAM expression. Monocyte (U937 cells)-dependent stimulation of TGF-beta1 promoter activity and protein synthesis was reduced by addition of BMP-7 for 24 h before addition of U937 cells. Removal of cell surface HA or inhibition of monocyte interaction with HA using antibody to CD44 prevented this effect of BMP-7. These data suggest that BMP-7 enhances HA-dependent binding and reduces ICAM-dependent binding, which is known to stimulate TGF-beta1 synthesis. This hypothesis was examined further by stimulation of PTC ICAM expression by TNF-alpha. After TNF-alpha stimulation, monocyte-dependent TGF-beta1 synthesis increased. This was abrogated by inhibition of ICAM-CD18 interactions. TNF-alpha stimulation alone did not increase TGF-beta1 synthesis. TNF-alpha stimulation of PTC in the presence of BMP-7 failed to increase monocyte-dependent TGF-beta1 stimulation. Although stimulation of PTC by BMP-7 alone decreased cell surface ICAM expression, it did not affect TNF-alpha-induced ICAM expression. The effect of BMP-7 on TGF-beta1 synthesis in TNF-alpha-stimulated cells was abrogated by disruption of CD44-HA interactions, suggesting that it was due to increased monocyte binding to HA on the cell surface.

Renal proximal tubular epithelial cell transforming growth factor-beta1 generation and monocyte binding.

With increasing awareness of the importance of renal cortical interstitial fibrosis, interest has focused on the mechanisms that stimulate generation of profibrotic factors including transforming growth factor (TGF)-beta1, by resident cells, such as proximal tubular epithelial cells (PTCs). Infiltration of monocytes, has been implicated in the pathogenesis of a wide variety of renal diseases, however, how interaction between monocytes and PTCs may affect the generation of TGF-beta1 by the resident cell is unknown. We demonstrate that monocytes stimulate TGF-beta1 transcription and protein synthesis by PTCs. This was dependent on direct cell contact and TGF-beta1 transcriptional activation that was dependent on ICAM-1 binding of unstimulated monocytes. This was mimicked by antibody cross-linking of PTC surface ICAM-1. We have previously identified hyaluronan (HA)-based structures on the surface of PTCs, both primary cultures and the HK-2 cell line. Removal of cell-surface HA increased ICAM-1-dependent monocyte binding and stimulation of TGF-beta1 synthesis. Furthermore, we demonstrate that binding of monocytes to HA-based structures on the cell surface of HK-2 cells interferes with this response. In summary, we have demonstrated that HA-based pericellular structures down-regulate proinflammatory and profibrotic responses by modulation of monocyte-driven ICAM-1-dependent cell activation and TGF-beta1 generation.

BMP-7 modulates hyaluronan-mediated proximal tubular cell-monocyte interaction.

Increased synthesis of hyaluronan (HA) in the renal corticointerstitium has been documented in renal injury, although the functional significance of this is unclear. The aim of the work presented in the current study was to examine the role of HA in monocyte binding by proximal tubular cells (PTC). Using the PTC line HK-2, the authors show that unstimulated cells formed pericellular HA cable-like structures that bound mononuclear leukocytes via their cell surface CD44. Stimulation with bone morphogenic protein-7 (BMP-7) led to increased formation of HA cable-like structures and also a dose-dependent increase in CD44-dependent binding of radiolabeled U937 cells. The authors have previously demonstrated that stimulation with IL-1beta is a potent stimulus for induction of HAS gene expression and HA synthesis. In this study, addition of IL-1beta influenced neither HA cable formation nor CD44-mediated monocyte binding. Rather IL-1beta led to an increase in intercellular adhesion molecule (ICAM)-dependent monocyte binding. Characterization of HA synthesis by addition of [(3)H]-glucosamine to cells at the time of stimulation demonstrated that increased HA in response to IL-1 was most apparent in the culture medium, while BMP-7 led to an increase in cell associated HA. Stimulation of cells with BMP-7 induced HAS2 mRNA expression and decreased the expression of Hyal1 and Hyal2. In contrast to BMP-7, IL-1beta did not influence Hyal expression. The data presented in this manuscript provide insight into how alterations in HA synthesis in the renal cortex may be involved in modulation of the interaction between infiltrating inflammatory cells and resident cells.