Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas.     

Protracted neurocardiogenic reaction

Vasovagal reactions following catheterization procedures are relatively common complications, mostly in their milder forms. We present a case report of a young male undergoing selective coronarography with a dramatic postprocedural course including haemodynamic instability, and especially very late normalization of the neurological status.     

T2 mapping with magnetization‐prepared 3D TSE based on a modified BIR‐4 T2 preparation

The purpose of this work was to investigate the performance of the modified BIR‐4 T₂ preparation for T₂ mapping and propose a method to remove T₂ quantification errors in the presence of large B₁ and B₀ offsets. The theoretical investigation of the magnetization evolution during the T₂ preparation in the presence of B₁ and B₀ offsets showed deviations from a mono‐exponential T₂ decay (two parameter fit). A three parameter fit was used to improve T₂ accuracy. Furthermore, a two parameter fit with an additional saturation preparation scan was proposed to improve T₂ accuracy and precision. These three fitting methods were compared based on simulations, phantom measurements and an in vivo healthy volunteer study of the neck musculature using a 3D TSE readout. The results based upon the pure two parameter fit overestimated T₂ in regions with high B₀ offsets (up to 40% in phantoms). The three parameter fit T₂ values were robust to B₀ offsets but with higher standard deviation (up to 40% in simulations). The two parameter fit with the saturation preparation yielded high robustness towards B₀ offsets with a noise performance comparable to that of the two parameter fit. In the volunteer study the T₂ values obtained by the pure two parameter fit showed a dependence on the field inhomogeneities, whereas the T₂ values from the proposed fitting approach were shown to be insensitive to B₀ offsets. The proposed method enabled accurate and precise T₂ mapping in the presence of large B₁ and B₀ offsets.     

Triple Leads Programmed to Perform as Longitudinal Guarded Cathodes in Spinal Cord Stimulation: A Modeling Study

Objective: In spinal cord stimulation, neurosurgeons increasingly tend to implant dual leads. Dual leads (longitudinal bipole/tripole) provide medio‐lateral control over the recruited dorsal column (DC) area by steering the injected cathodal currents. However, the DC recruited area is suboptimal when dual aligned leads straddling the midline programmed as longitudinal guarded cathodes (+−+) are used instead of a single lead placed over the spinal cord midline with the same configuration. As a potential improvement, an additional third lead between the two aligned leads is modeled to maximize the medio‐lateral extent of the DCs at the low‐thoracic vertebral region (T10‐T12). Methods and Materials: The University of Twente Spinal Cord Stimulation software (UT‐SCS) is used in this modeling study. Longitudinal guarded cathodes were modeled on the low‐thoracic vertebral region (T10‐T12) using percutaneous triple lead configurations. The central lead was modeled over the spinal cord midline and the two lateral leads were modeled at several transverse distances to the midline lead. Medio‐lateral field steering was performed with the midline lead and the second lead on each side to achieve constant anodal current ratios and variable anodal current ratios. Results: Reducing the transverse lead separation resulted in increasing the depths and widths of the recruited DC area. The triple lead configuration with the least transverse separation had the largest DC recruited area and usage range. The maximum DC recruited area (in terms of both depth and width) was always found to be larger under variable anodal current ratio than constant anodal current ratio conditions. Conclusions: Triple leads programmed to perform as longitudinal guarded cathodes provide more postoperative flexibility than single and dual leads in covering a larger width of the low‐thoracic DCs. The transverse separation between the leads is a major determinant of the area and distribution of paresthesia.     

New Therapeutic Options in Patients Prone to Hypertension: A Focus on Direct Renin Inhibition and Aldosterone Blockade

Certain patient populations have a high prevalence of hypertension, including black, elderly, or obese patients; patients with metabolic syndrome, or frank diabetes; and patients with chronic kidney disease. Many of these patients experience renin-angiotensin-aldosterone system (RAAS) dysregulation, which is important because the RAAS plays a pivotal role in the pathogenesis of hypertension, cardiovascular disease, and renal dysfunction. Data available regarding newer approaches that target the RAAS, including direct renin inhibition and aldosterone receptor antagonism, in patients who often have hypertension are reviewed. Aliskiren, the first direct renin inhibitor, is effective in a number of these patient groups, including those who are black or obese or who have metabolic syndrome, renal impairment, or diabetes. In addition, in the setting of long-term angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, aldosterone receptor antagonists (spironolactone and eplerenone) provide another rational therapeutic approach for patients whose blood pressure is not controlled by standard therapies.