SURGERY OF INTRINSIC CEREBRAL TUMORS

Neurosurgery ◽  
2007 ◽  
Vol 61 (suppl_1) ◽  
pp. SHC-279-SHC-305 ◽  
Author(s):  
Mitchel S. Berger ◽  
Costas G. Hadjipanayis
Keyword(s):  
Paradigm Shift ◽  
Extent Of Resection ◽  
Activation Function ◽  
Comprehensive Analysis ◽  
Surgical Strategies ◽  
Functional Localization ◽  
Cerebral Localization ◽  
Eloquent Cortex ◽  
And Function ◽  
Oscillatory Rhythms

Abstract TUMORS AND OTHER structural lesions located with and adjacent to the cerebral cortex present certain challenges in terms of the overall management and design of surgical strategies. This comprehensive analysis attempts to define the current understanding of cerebral localization and function and includes the latest advances in functional imaging, as well as surgical technique, including localization of tumors and neurophysiological mapping to maximize extent of resection while minimizing morbidity. Finally, it remains to be seen whether or not stimulation mapping will be the most useful way to identify function within the cortex in the future. Another potential paradigm would be to actually record baseline oscillatory rhythms within the cortex and, following presentation of a given task, determine if those rhythms are disturbed enough to identify eloquent cortex as a means of functional localization. This would be a paradigm shift away from stimulation mapping, which currently deactivates the cortex, as opposed to identifying an activation function which identifies functional cortex.

scholarly journals Functional preoperative and intraoperative mapping and monitoring: increasing safety and efficacy in glioma surgery

2015 ◽  
Vol 38 (1) ◽  
pp. E3 ◽  
Author(s):  
Malte Ottenhausen ◽  
Sandro M. Krieg ◽  
Bernhard Meyer ◽  
Florian Ringel
Keyword(s):  
Diffusion Tensor ◽  
Imaging Techniques ◽  
Extent Of Resection ◽  
Low Grade ◽  
Glioma Surgery ◽  
Intraoperative Mapping ◽  
Fiber Tracts ◽  
Functional Localization ◽  
Eloquent Cortex ◽  
Cortical Regions

Greater extent of resection (EOR) of low-grade gliomas is associated with improved survival. Proximity to eloquent cortical regions often limits resectability and elevates the risk of surgery-related deficits. Therefore, functional localization of eloquent cortex or subcortical fiber tracts can enhance the EOR and functional outcome. Imaging techniques such as functional MRI and diffusion tensor imaging fiber tracking, and neurophysiological methods like navigated transcranial magnetic stimulation and magnetoencephalography, make it possible to identify eloquent areas prior to resective surgery and to tailor indication and surgical approach but also to assess the surgical risk. Intraoperative monitoring with direct cortical stimulation and subcortical stimulation enables surgeons to preserve essential functional tissue during surgery. Through tailored pre- and intraoperative mapping and monitoring the EOR can be maximized, with reduced rates of surgery-related deficits.

scholarly journals The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance

2021 ◽  
Vol 22 (19) ◽  
pp. 10677
Author(s):  
Huqiang Wang ◽  
Haolin Zhong ◽  
Chao Gao ◽  
Jiayin Zang ◽  
Dong Yang
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Domains ◽  
Comprehensive Analysis ◽  
Disordered Proteins ◽  
Functional Constraints ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
And Function ◽  
Disordered Regions

The consecutive disordered regions (CDRs) are the basis for the formation of intrinsically disordered proteins, which contribute to various biological functions and increasing organism complexity. Previous studies have revealed that CDRs may be present inside or outside protein domains, but a comprehensive analysis of the property differences between these two types of CDRs and the proteins containing them is lacking. In this study, we investigated this issue from three viewpoints. Firstly, we found that in-domain CDRs are more hydrophilic and stable but have less stickiness and fewer post-translational modification sites compared with out-domain CDRs. Secondly, at the protein level, we found that proteins with only in-domain CDRs originated late, evolved rapidly, and had weak functional constraints, compared with the other two types of CDR-containing proteins. Proteins with only in-domain CDRs tend to be expressed spatiotemporal specifically, but they tend to have higher abundance and are more stable. Thirdly, we screened the CDR-containing protein domains that have a strong correlation with organism complexity. The CDR-containing domains tend to be evolutionarily young, or they changed from a domain without CDR to a CDR-containing domain during evolution. These results provide valuable new insights about the evolution and function of CDRs and protein domains.

Individualized surgical strategies for Rathke cleft cyst based on cyst location

2013 ◽  
Vol 119 (6) ◽  
pp. 1437-1446 ◽  
Author(s):  
Jun Fan ◽  
Yuping Peng ◽  
Songtao Qi ◽  
Xi-an Zhang ◽  
Binghui Qiu ◽  
...  
Keyword(s):  
Extent Of Resection ◽  
Gross Total Resection ◽  
Surgical Approaches ◽  
Subtotal Resection ◽  
Total Resection ◽  
Surgical Strategies ◽  
Minimal Invasiveness ◽  
Rathke Cleft Cyst ◽  
Csf Leakage ◽  
Keyhole Craniotomy

Object An assessment regarding both surgical approaches and the extent of resection for Rathke cleft cysts (RCCs) based on their locations has not been reported. The aim of this study was to report the results of a large series of surgically treated patients with RCCs and to evaluate the feasibility of individualized surgical strategies for different RCCs. Methods We retrospectively reviewed 87 cases involving patients with RCCs (16 intrasellar, 50 intra- and suprasellar, and 21 purely suprasellar lesions). Forty-nine patients were treated via a transsphenoidal (TS) approach, and 38 were treated via a transcranial (TC) approach (traditional craniotomy in 21 cases and supraorbital keyhole craniotomy in 17). The extent of resection was classified as gross-total resection (GTR) or subtotal resection (STR) of the cyst wall. Patients were thus divided into 3 groups according to the approach selected and the extent of resection: TS/STR (n = 49), TC/STR (n = 23), and TC/GTR (n = 15). Results Preoperative headaches, visual dysfunction, hypopituitarism, and diabetes insipidus (DI) resolved in 85%, 95%, 55%, and 65% of patients, respectively. These rates did not differ significantly among the 3 groups. Overall, complications occurred in 8% of patients in TS/STR group, 9% in TC/STR group, and 47% in TC/GTR group, respectively (p = 0.002). Cerebrospinal fluid (CSF) leakage (3%), new hypopituitarism (9%), and DI (6%) were observed after surgery. All CSF leaks occurred in the endonasal group, while the TC/GTR group showed a higher rate of postoperative hypopituitarism (p = 0.7 and p < 0.001, respectively). It should be particularly noted that preoperative hypopituitarism and DI returned to normal, respectively, in 100% and 83% of patients who underwent supraorbital surgery, and with the exception of 1 patient who had transient postoperative DI, there were no complications in patients treated with supraorbital surgery. Kaplan-Meier 3-year recurrence-free rates were 84%, 87%, and 86% in the TS/STR, TC/STR, and TC/GTR groups, respectively (p = 0.9). Conclusions It is reasonable to adopt individualized surgical strategies for RCCs based on cyst location. Gross-total resection does not appear to reduce the recurrence rate but increase the risk of postoperative complications. The endonasal approach seems more appropriate for primarily intrasellar RCCs, while the craniotomy is recommended for purely or mainly suprasellar cysts. The supraorbital route appears to be preferred over traditional craniotomy for its minimal invasiveness and favorable outcomes. The endoscopic technique is helpful for either endonasal or supraorbital surgery.

LVMI: A detrimental paradigm shift of left ventricular geometry and function in accidently detected hypertensives

2018 ◽  
Vol 5 (4) ◽  
pp. 491-496
Author(s):  
Deepak Kumar Das ◽  
Jugal Kishore Bajpai ◽  
Sunil Kumar ◽  
Praveen Kumar K ◽  
Sudhir Modala
Keyword(s):  
Paradigm Shift ◽  
Left Ventricular ◽  
Left Ventricular Geometry ◽  
Ventricular Geometry ◽  
And Function

Integrated image- and function-guided surgery in eloquent cortex: a technique report

2006 ◽  
Vol 2 (1) ◽  
pp. 75-83 ◽  
Author(s):  
James P. O'Shea ◽  
Stephen Whalen ◽  
Daniel M. Branco ◽  
Nicole M. Petrovich ◽  
Kyle E. Knierim ◽  
...  
Keyword(s):  
Guided Surgery ◽  
Eloquent Cortex ◽  
And Function

scholarly journals Comprehensive Analysis of Combinatorial Pharmacological Treatments to Correct Nonsense Mutations in the CFTR Gene

2021 ◽  
Vol 22 (21) ◽  
pp. 11972
Author(s):  
Arianna Venturini ◽  
Anna Borrelli ◽  
Ilaria Musante ◽  
Paolo Scudieri ◽  
Valeria Capurro ◽  
...  
Keyword(s):  
Comprehensive Analysis ◽  
Cftr Gene ◽  
Loss Of Function ◽  
Pharmacological Treatments ◽  
Protein Maturation ◽  
Nonsense Mutations ◽  
Nonsense Mediated Decay ◽  
Cftr Mutations ◽  
Cftr Protein ◽  
And Function

Cystic fibrosis (CF) is caused by loss of function of the CFTR chloride channel. A substantial number of CF patients carry nonsense mutations in the CFTR gene. These patients cannot directly benefit from pharmacological correctors and potentiators that have been developed for other types of CFTR mutations. We evaluated the efficacy of combinations of drugs targeting at various levels the effects of nonsense mutations: SMG1i to protect CFTR mRNA from nonsense-mediated decay (NMD), G418 and ELX-02 for readthrough, VX-809 and VX-445 to promote protein maturation and function, PTI-428 to enhance CFTR protein synthesis. We found that the extent of rescue and sensitivity to the various agents is largely dependent on the type of mutation, with W1282X and R553X being the mutations most and least sensitive to pharmacological treatments, respectively. In particular, W1282X-CFTR was highly responsive to NMD suppression by SMG1i but also required treatment with VX-445 corrector to show function. In contrast, G542X-CFTR required treatment with readthrough agents and VX-809. Importantly, we never found cooperativity between the NMD inhibitor and readthrough compounds. Our results indicate that treatment of CF patients with nonsense mutations requires a precision medicine approach with the design of specific drug combinations for each mutation.

scholarly journals Structural basis of altered potency and efficacy displayed by a major in vivo metabolite of the anti-diabetic PPARγ drug pioglitazone

2018 ◽  
Author(s):  
Sarah A. Mosure ◽  
Jinsai Shang ◽  
Richard Brust ◽  
Jie Zheng ◽  
Patrick R. Griffin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Activation Function ◽  
Structural Basis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exchange Mass Spectrometry ◽  
Pparγ Agonist ◽  
A Cell ◽  
And Function

ABSTRACTThe thiazolidinedione (TZD) pioglitazone (Pio) is an FDA-approved drug for type 2 diabetes mellitus that binds and activates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). Although TZDs have potent antidiabetic effects, they also display harmful side effects that have necessitated a better understanding of their mechanisms of action. In particular, little is known about the effect of in vivo TZD metabolites on the structure and function of PPARγ. Here, we present a structure-function comparison of Pio and a major in vivo metabolite, 1-hydroxypioglitazone (PioOH). PioOH displayed a lower binding affinity and reduced potency in coregulator recruitment assays compared to Pio. To determine the structural basis of these findings, we solved an X-ray crystal structure of PioOH bound to PPARγ ligand-binding domain (LBD) and compared it to a published Pio-bound crystal structure. PioOH exhibited an altered hydrogen bonding network that could underlie its reduced affinity and potency compared to Pio. Solution-state structural analysis using NMR spectroscopy and hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PioOH stabilizes the PPARγ activation function-2 (AF-2) coactivator binding surface better than Pio. In support of AF-2 stabilization, PioOH displayed stabilized coactivator binding in biochemical assays and better transcriptional efficacy (maximal transactivation response) in a cell-based assay that reports on the activity of the PPARγ LBD. These results, which indicate that Pio hydroxylation affects both its potency and efficacy as a PPARγ agonist, contribute to our understanding of PPARγ-binding drug metabolite interactions and may assist in future PPARγ drug design efforts.

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