Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of breast cancer.

Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 modulates expression of metastasis-influencing microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis using PELP1-overexpressing and PELP1-underexpressing model cells revealed that miR-200 and miR-141 levels inversely correlated with PELP1 expression. Consistent with this, PELP1 knockdown resulted in lower expression of miR-200a target genes ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis compared with parental cells in an orthotopic xenograft tumor model. Furthermore, re-introduction of miR-200a and miR-141 mimetics into PELP1-overexpressing cells reversed PELP1 target gene expression, decreased PELP1-driven migration/invasion in vitro and significantly reduced in vivo metastatic potential in a preclinical model of experimental metastasis. Our results demonstrated that PELP1 binds to miR-200a and miR-141 promoters and regulates their expression by recruiting chromatin modifier histone deacetylase 2 (HDAC2) as revealed by chromatin immunoprecipitation, small interfering RNA and HDAC inhibitor assays. Taken together, our results suggest that PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141.

Delayed migration of a self-expanding intracranial microstent.

A 43-year-old patient with a basilar apex aneurysm had a 4.5-mm x 14-mm Enterprise stent placed from the midbasilar artery to the left P1 segment of the posterior cerebral artery. The patient experienced vertigo 4 months after stent placement and 1 week after stopping clopidogrel. At 5 months postembolization, angiography showed stent migration into the proximal basilar artery. This is the first described case of the spontaneous delayed migration of a self-expanding intracranial microstent.

Marginal sinus arteriovenous fistulas mimicking carotid cavernous fistulas: diagnostic and therapeutic considerations.

Marginal sinus fistulas (MSFs) are uncommon vascular anomalies. Occasionally, the dominant venous drainage is forced retrograde up the inferior petrosal sinus and into the cavernous sinus, causing chemosis, proptosis, and ocular hypertension, mimicking a carotid cavernous fistula. This atypical clinical presentation may lead to misdiagnosis and inappropriate hazardous treatment of an MSF. Identifying the site of the fistula and understanding the anatomy of the venous drainage are critical in providing appropriate, safe, and efficacious endovascular treatment.

Electrical stimulation and gene-based neuromodulation for control of medically-refractory epilepsy.

The failure of available antiepileptic medications to adequately control seizures in a substantial number of patients underscores the need to develop novel epilepsy therapies. Recent advancements in technology and the success of neuromodulation in treating a variety of neurological disorders have spurred interest in exploring promising therapeutic alternatives, such as electrical stimulation and gene-based synaptic control. A variety of different stimulation approaches to seizure control targeting structures in the central or peripheral nervous system have been investigated. Most studies have been based on uncontrolled observations and empirical stimulation protocols. Today the vagus nerve stimulator is the only FDA approved adjunctive treatment for epilepsy that utilizes electrical stimulation. Other potential strategies including direct stimulation of the epileptogenic cortex and deep brain stimulation of various targets are currently under investigation. Chronically implanted devices for electrical stimulation have a variety of limitations. First, they are susceptible to malfunction and infection. Second, most systems require battery replacement. Finally, electrical stimulation is incapable of manipulating neuronal function in a transmitter specific fashion. Gene delivery to epileptogenic targets or targets implicated in regulating seizure threshold has been investigated as an alternative means of neuromodulation in animal models. In summary, positive preliminary results and the lack of alternative treatment options provide the impetus for further exploration of electrical stimulation and gene-based therapies in pharmacoresistant epilepsy. Various specific targets and approaches to modulating their activity have been investigated in human studies.

Anterior cervical plating.

Although anterior cervical instrumentation was initially used in cervical trauma, because of obvious benefits, indications for its use have been expanded over time to degenerative cases as well as tumor and infection of the cervical spine. Along with a threefold increase in incidence of cervical fusion surgery, implant designs have evolved over the last three decades. Observation of graft subsidence and phenomenon of stress shielding led to the development of the new generation dynamic anterior cervical plating systems. Anterior cervical plating does not conclusively improve clinical outcome of the patients, but certainly enhances the efficacy of autograft and allograft fusion and lessens the rate of pseudoarthrosis and kyphosis after multilevel discectomy and fusions. A review of biomechanics, surgical technique, indications, complications and results of various anterior cervical plating systems is presented here to enable clinicians to select the appropriate construct design.

Pituitary apoplexy with optic tract oedema and haemorrhage in a patient with idiopathic thrombocytopenic purpura.

Bilateral optic tract oedema, left optic tract haemorrhage and subarachnoid haemorrhage occurred in a 70-year-old man with pituitary apoplexy associated with idiopathic thrombocytopenic purpura. Left optic tract haemorrhage was confirmed on MRI.

Warfarin and chronic subdural haematomas.

There is a perception that patients who develop a chronic subdural haematoma (CSDH), whilst taking warfarin, do less well than those not taking warfarin. This study looks at such patients to determine the truth of this perception. A retrospective analysis of two time periods (1990-1992 and 1995-1997) looking at all patients with CSDH admitted to this neurosurgical unit for treatment, to determine the incidence and to look more closely at those on warfarin. The influence of warfarin on the incidence, severity and outcome has been studied. Between 1990 and 1992, 11.8% of those patients with CSDH were taking warfarin, whilst in 1995-1997 20% were on warfarin. The overall number of referrals of CSDH increased from 34 to 150 patients during these time periods. There were no differences in age, sex or other medical disorders between the two groups. No adverse events occurred when the warfarin was stopped temporarily for treatment of the CSDH. There was no increase in recurrence rate in those on warfarin, compared with those not on warfarin. This study, whilst demonstrating an increase in the number of referrals of CSDH and patients with CSDH taking warfarin, has not demonstrated an adverse effect of the warfarin on the outcome of treatment for CSDH. The authors suggest recommencing warfarin 3 weeks after surgical evacuation of CSDH in anticoagulated patients.