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1.
J Surg Res ; 302: 836-844, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39241292

RESUMEN

INTRODUCTION: Surgeon assessment tools are subjective and nonscalable. Objective performance indicators (OPIs), machine learning-enabled metrics recorded during robotic surgery, offer objective insights into surgeon movements and robotic arm kinematics. In this study, we identified OPIs that significantly differed across expert (EX), intermediate (IM), and novice (NV) surgeons during robotic right colectomy. METHODS: Endoscopic videos were annotated to delineate 461 surgical steps across 25 robotic right colectomies. OPIs were compared among two EX, two IM, and eight NV surgeons during mesenteric dissection, vascular pedicle ligation, right colon and hepatic flexure mobilization, and preparation of the proximal and distal bowel for transection. RESULTS: Compared to NV's, EX's exhibited greater velocity, acceleration and jerk for camera, dominant, nondominant, and third arms across all steps. Compared to NV's, IM's exhibited more arm swaps and master clutch use, higher camera-related metrics (movement, path length, moving time, velocity, acceleration, and jerk), greater dominant wrist pitch and nondominant wrist articulations (roll, pitch, and yaw), longer dominant and nondominant arm path length, and higher velocity, acceleration and jerk for dominant, nondominant, and third arms across all steps. Compared to NV's, EX/IM surgeons utilized more arm swaps, higher camera-related metrics (movement, path length, velocity, acceleration, and jerk), longer nondominant arm path length, and greater velocity, acceleration and jerk for dominant, nondominant, and third arms across all steps. CONCLUSIONS: We report OPIs that discriminate EX, IM, and NV surgeons during RRC. This study is the first to demonstrate feasibility of using OPIs as an objective, scalable way to classify surgeon skill during RRC steps.

2.
Surgery ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39304451

RESUMEN

BACKGROUND: Robotic surgery is perceived to be more complex in obese patients. Objective performance indicators, machine learning-enabled metrics, can provide objective data regarding surgeon movements and robotic arm kinematics. In this feasibility study, we identified differences in objective performance indicators during robotic proctectomy in obese and nonobese patients. METHODS: Endoscopic videos were annotated to delineate individual surgical steps across 39 robotic proctectomies (1880 total steps). Thirteen patients were obese and 26 were nonobese. Objective performance indicators during the following steps were analyzed: splenic flexure mobilization, left colon mobilization, pelvic dissection, and rectal transection. RESULTS: The following differences were noted during robotic proctectomy in obese patients: during splenic flexure mobilization, more arm swaps, longer camera path length and velocity; during left colon mobilization, longer step time, more arm swaps, higher camera-related metrics (movement, path length, velocity, acceleration, and jerk), greater dominant arm path length, moving time, and wrist articulation; during anterior pelvic dissection, longer energy activation time, camera path length, and moving time; during posterior pelvic dissection, lower nondominant arm velocity, jerk, and acceleration; during left pelvic dissection, longer energy activation time; during right pelvic dissection, greater camera-related metrics (movement, path length, moving time, and velocity); and during rectal transection, longer step time, more arm swaps, master clutch use and camera movements, greater dominant wrist articulation, and longer dominant arm path length. CONCLUSION: We report step-specific objective performance indicators that differ during robotic proctectomy for obese and nonobese patients. This is the first study to use objective performance indicators to correlate a patient attribute with surgeon movements and robotic arm kinematics during robotic colorectal surgery.

3.
J Am Coll Surg ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268949

RESUMEN

SUMMARY: Objective intra-operative performance metrics are an new resource for the field of surgical data science. In this study, we conducted a comprehensive review to analyze the existing literature on robotic surgical objective performance indicators (OPIs). OPIs have been used to assess surgical skill and provide automated, objective feedback in multiple settings. Clinically, OPIs have been utilized to predict post-operative patient outcomes and measure intra-operative efficiency. OPIs have shown promise in preliminary surgical education and patient outcomes related studies, and further multi-center collaborative research will be imperative to validate the use of OPIs in the field of surgery.

4.
Front Med (Lausanne) ; 11: 1382609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219795

RESUMEN

Introduction: The curriculum for a da Vinci surgeon in gynecology requires special training before a surgeon performs their first independent case, but standardized, objective assessments of a trainee's workflow or skills learned during clinical cases are lacking. This pilot study presents a methodology to evaluate intraoperative surgeon behavior in hysterectomy cases through standardized surgical step segmentation paired with objective performance indicators (OPIs) calculated directly from robotic data streams. This method can provide individual case analysis in a truly objective capacity. Materials and methods: Surgical data from six robot-assisted total laparoscopic hysterectomies (rTLH) performed by two experienced surgeons was collected prospectively using an Intuitive Data Recorder. Each rTLH video was annotated and segmented into specific, functional surgical steps based on the recorded video. Once annotated, OPIs were compared through workflow analysis and across surgeons during two critical surgical steps: colpotomy and vaginal cuff closure. Results: Through visualization of the individual steps over time, we observe workflow consistencies and variabilities across individual surgeons of a similar experience level at the same hospital, creating unique surgeon behavior signatures across each surgical case. OPI differences across surgeons were observed for both the colpotomy and vaginal cuff closure steps, specifically reflecting camera movement, energy usage and clutching behaviors. Comparing colpotomy and vaginal cuff closure time needed for the step and the events of energy use were significantly different (p < 0.001). For the comparison between the two surgeons only the event count for camera movement during colpotomy showed significant differences (p = 0.03). Conclusion: This pilot study presents a novel methodology to analyze and compare individual rTLH procedures with truly objective measurements. Through collection of robotic data streams and standardized segmentation, OPI measurements for specific rTLH surgery steps can be reliably calculated and compared to those of other surgeons. This provides opportunity for critical standardization to the gynecology field, which can be integrated into individualized training plans in the future. However, more studies are needed to establish context surrounding these metrics in gynecology.

5.
Surgery ; 176(4): 1036-1043, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39025692

RESUMEN

BACKGROUND: Current surgical assessment tools are subjective and nonscalable. Objective performance indicators, calculated from robotic systems data, provide automated data regarding surgeon movements and robotic arm kinematics. We identified objective performance indicators that significantly differed among expert and trainee surgeons during specific steps of robotic right colectomy. METHODS: Endoscopic videos were annotated to delineate surgical steps during robotic right colectomies. Objective performance indicators were compared during mesenteric dissection, ascending colon mobilization, hepatic flexure mobilization, and bowel preparation for transection. RESULTS: Twenty-five robotic right colectomy procedures (461 total surgical steps) performed by 2 experts and 8 trainees were analyzed. Experts exhibited faster camera acceleration and jerk during all steps, as well as faster dominant and nondominant arm acceleration and dominant arm jerk during all steps except distal bowel preparation. During mesenteric dissection, experts used faster camera and dominant arm velocity. During medial-to-lateral ascending colon mobilization, experts used less-dominant wrist yaw and pitch, faster nondominant arm velocity, shorter dominant arm path length, and shorter moving times for camera, dominant arm, and nondominant arm. During lateral-to-medial ascending colon mobilization, experts had faster dominant and nondominant arm velocity and third-arm acceleration. During hepatic flexure mobilization, experts exhibited more camera movements, greater velocity for camera, dominant and nondominant arms, and faster third-arm acceleration. During distal bowel preparation, experts used greater dominant wrist articulation, faster camera velocity, and longer nondominant arm path length. During proximal bowel preparation, experts demonstrated faster nondominant arm velocity. CONCLUSION: Objective performance indicators can differentiate experts from trainees during distinct steps of robotic right colectomy. These automated, objective and scalable metrics can provide personalized feedback for trainees.


Asunto(s)
Competencia Clínica , Colectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Colectomía/métodos , Colectomía/normas , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/educación , Cirujanos/educación , Grabación en Video , Masculino
6.
Int J Med Robot ; 20(2): e2625, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38439215

RESUMEN

BACKGROUND: Surgical workflow assessments offer insight regarding procedure variability. We utilised an objective method to evaluate workflow during robotic proctectomy (RP). METHODS: We annotated 31 RPs and used Spearman's correlation to measure the correlation of step time and step visit frequency with console time (CT) and total operative time (TOT). RESULTS: Strong correlations were seen with CT and step times for inferior mesenteric vein dissection and ligation (ρ = 0.60, ρ = 0.60), lateral-to-medial splenic flexure mobilisation (SFM) (ρ = 0.63), left rectal dissection (ρ = 0.64) and mesorectal division (ρ = 0.71). CT correlated strongly with medial-to-lateral (ρ = 0.75) and supracolic SFM visit frequency (ρ = 0.65). TOT correlated strongly with initial exposure time (ρ = 0.60), and medial-to-lateral (ρ = 0.67) and supracolic SFM visit frequency (ρ = 0.65). CONCLUSION: This study correlates surgical steps with CT and TOT through standardised annotation, providing an objective approach to quantify workflow.


Asunto(s)
Proctectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Flujo de Trabajo , Disección , Tempo Operativo
7.
Surg Endosc ; 37(11): 8540-8551, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37789179

RESUMEN

BACKGROUND: The increased digitization in robotic surgical procedures today enables surgeons to quantify their movements through data captured directly from the robotic system. These calculations, called objective performance indicators (OPIs), offer unprecedented detail into surgical performance. In this study, we link case- and surgical step-specific OPIs to case complexity, surgical experience and console utilization, and post-operative clinical complications across 87 robotic cholecystectomy (RC) cases. METHODS: Videos of RCs performed by a principal surgeon with and without fellows were segmented into eight surgical steps and linked to patients' clinical data. Data for OPI calculations were extracted from an Intuitive Data Recorder and the da Vinci ® robotic system. RC cases were each assigned a Nassar and Parkland Grading score and categorized as standard or complex. OPIs were compared across complexity groups, console attributions, and post-surgical complication severities to determine objective relationships across variables. RESULTS: Across cases, differences in camera control and head positioning metrics of the principal surgeon were observed when comparing standard and complex cases. Further, OPI differences across the principal surgeon and the fellow(s) were observed in standard cases and include differences in arm swapping, camera control, and clutching behaviors. Monopolar coagulation energy usage differences were also observed. Select surgical step duration differences were observed across complexities and console attributions, and additional surgical task analyses determine the adhesion removal and liver bed hemostasis steps to be the most impactful steps for case complexity and post-surgical complications, respectively. CONCLUSION: This is the first study to establish the association between OPIs, case complexities, and clinical complications in RC. We identified OPI differences in intra-operative behaviors and post-surgical complications dependent on surgeon expertise and case complexity, opening the door for more standardized assessments of teaching cases, surgical behaviors and case complexities.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Cirujanos , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Colecistectomía/efectos adversos , Cirujanos/educación
8.
Res Sq ; 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37886442

RESUMEN

Aim: Assessments of surgical workflow offer insight regarding procedure variability, case complexity and surgeon proficiency. We utilize an objective method to evaluate step-by-step workflow and step transitions during robotic proctectomy (RP). Methods: We annotated 31 RPs using a procedure-specific annotation card. Using Spearman's correlation, we measured strength of association of step time and step visit frequency with console time (CT) and total operative time (TOT). Results: Across 31 RPs, a mean (± standard deviation) of 49.0 (± 20.3) steps occurred per procedure. Mean CT and TOT were 213 (± 90) and 283 (± 108) minutes. Posterior mesorectal dissection required most visits (8.7 ± 5.0), while anastomosis required most time (18.0 [± 8.5] minutes). Inferior mesenteric vein (IMV) ligation required least visits (1.0 ± 0.0) and lowest duration (0.9 [± 0.5] minutes). Strong correlations were seen with CT and step times for IMV dissection and ligation (ρ = 0.60 for both), lateral-to-medial splenic flexure mobilization (SFM) (ρ = 0.63), left rectal dissection (ρ = 0.64) and mesorectal division (ρ = 0.71). CT correlated strongly with medial-to-lateral and supracolic SFM visit frequency (ρ = 0.75 and ρ = 0.65). There were strong correlations with TOT and initial exposure time (ρ = 0.60), as well as visit frequency for medial-to-lateral (ρ = 0.67) and supracolic SFM (ρ = 0.65). Descending colon mobilization was nodal, rectal mobilization convergent and rectal transection divergent. Conclusion: This study correlates individual surgical steps with CT and TOT through standardized annotation. It provides an objective approach to quantify workflow.

9.
Surgery ; 174(6): 1349-1355, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37718171

RESUMEN

BACKGROUND: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy. METHODS: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores. RESULTS: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55). CONCLUSION: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Cirugía Torácica , Animales , Porcinos , Benchmarking , Disección
10.
Surg Endosc ; 37(10): 7908-7913, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430122

RESUMEN

INTRODUCTION: Teaching residents robotic-assisted inguinal hernia repair (RIHR) is an increasingly common extension of contemporary surgical training. This study sought to investigate what variables would influence operative time (OT) and resident prospective entrustment in RIHR cases. METHODS: We prospectively collected 68 resident RIHR operative performance evaluations with a validated instrument. Outpatient RIHR cases performed by 11 general surgery residents during 2020-2022 were included. The overall OT of matched cases was extracted from hospital billing; matched procedural step-specific OT was obtained from Intuitive Data Recorder (IDR). Statistical analysis was performed using Pearson correlation and one-way ANOVA. RESULTS: The evaluation instrument reliably assessed residents' RIHR performance (Cronbach's α = 0.93); residents' prospective entrustment strongly correlated with overall guidance provided by attending surgeon (r = 0.86, p < 0.0001) and operative plan and judgment (r = 0.85, p < 0.0001). The overall OT was significantly associated with resident's team management (r = - 0.35, p = 0.011). Procedural step-specific OT was significantly associated with residents' step-specific skill (r = - 0.32, p = 0.014). On average, RIHR cases with the highest level of prospective entrustment (Resident can teach junior) showed the shortest step-specific OT. Entrustment level 3 (Reactive guidance needed) was the turning point of all four RIHR procedural step-specific OT. CONCLUSIONS: Our findings suggest that in RIHR, attending guidance, resident operative plan and judgment, and resident technical skill contribute to resident prospective entrustment; resident team management, technical skill, and attending guidance influence operative time, which in turn impacts attendings' determination of resident prospective entrustment. Future studies with a larger sample size are needed to further validate the findings.


Asunto(s)
Cirugía General , Hernia Inguinal , Internado y Residencia , Procedimientos Quirúrgicos Robotizados , Humanos , Hernia Inguinal/cirugía , Tempo Operativo , Estudios Prospectivos , Competencia Clínica , Cirugía General/educación
11.
Am Surg ; 89(8): 3416-3422, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36898676

RESUMEN

BACKGROUND: Our group investigates objective performance indicators (OPIs) to analyze robotic colorectal surgery. Analyses of OPI data are difficult in dual-console procedures (DCPs) as there is currently no reliable, efficient, or scalable technique to assign console-specific OPIs during a DCP. We developed and validated a novel metric to assign tasks to appropriate surgeons during DCPs. METHODS: A colorectal surgeon and fellow reviewed 21 unedited, dual-console proctectomy videos with no information to identify the operating surgeons. The reviewers watched a small number of random tasks and assigned "attending" or "trainee" to each task. Based on this sampling, the remainder of task assignments for each procedure was extrapolated. In parallel, we applied our newly developed OPI, ratio of economy of motion (rEOM), to assign consoles. Results from the 2 methods were compared. RESULTS: A total of 1811 individual surgical tasks were recorded during 21 proctectomy videos. A median of 6.5 random tasks (137 total) were reviewed during each video, and the remainder of task assignments were extrapolated based on the 7.6% of tasks audited. The task assignment agreement was 91.2% for video review vs rEOM, with rEOM providing ground truth. It took 2.5 hours to manually review video and assign tasks. Ratio of economy of motion task assignment was immediately available based on OPI recordings and automated calculation. DISCUSSION: We developed and validated rEOM as an accurate, efficient, and scalable OPI to assign individual surgical tasks to appropriate surgeons during DCPs. This new resource will be useful to everyone involved in OPI research across all surgical specialties.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Proctectomía , Procedimientos Quirúrgicos Robotizados , Robótica , Cirujanos , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Competencia Clínica
12.
PLoS One ; 15(5): e0232991, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32407359

RESUMEN

Following nerve stimulation, there are two distinct phases of Ca2+-dependent neurotransmitter release: a fast, synchronous release phase, and a prolonged, asynchronous release phase. Each of these phases is tightly regulated and mediated by distinct mechanisms. Synaptotagmin 1 is the major Ca2+ sensor that triggers fast, synchronous neurotransmitter release upon Ca2+ binding by its C2A and C2B domains. It has also been implicated in the inhibition of asynchronous neurotransmitter release, as blocking Ca2+ binding by the C2A domain of synaptotagmin 1 results in increased asynchronous release. However, the mutation used to block Ca2+ binding in the previous experiments (aspartate to asparagine mutations, sytD-N) had the unintended side effect of mimicking Ca2+ binding, raising the possibility that the increase in asynchronous release was directly caused by ostensibly constitutive Ca2+ binding. Thus, rather than modulating an asynchronous sensor, sytD-N may be mimicking one. To directly test the C2A inhibition hypothesis, we utilized an alternate C2A mutation that we designed to block Ca2+ binding without mimicking it (an aspartate to glutamate mutation, sytD-E). Analysis of both the original sytD-N mutation and our alternate sytD-E mutation at the Drosophila neuromuscular junction showed differential effects on asynchronous release, as well as on synchronous release and the frequency of spontaneous release. Importantly, we found that asynchronous release is not increased in the sytD-E mutant. Thus, our work provides new mechanistic insight into synaptotagmin 1 function during Ca2+-evoked synaptic transmission and demonstrates that Ca2+ binding by the C2A domain of synaptotagmin 1 does not inhibit asynchronous neurotransmitter release in vivo.


Asunto(s)
Proteínas de Drosophila/metabolismo , Neurotransmisores/metabolismo , Sinaptotagmina I/metabolismo , Sustitución de Aminoácidos , Animales , Animales Modificados Genéticamente , Sitios de Unión/genética , Calcio/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Genes de Insecto , Mutagénesis Sitio-Dirigida , Dominios Proteicos , Transmisión Sináptica , Vesículas Sinápticas/metabolismo , Sinaptotagmina I/química , Sinaptotagmina I/genética
13.
PLoS One ; 12(9): e0184817, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28953919

RESUMEN

During chemical transmission, the function of synaptic proteins must be coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the Ca2+ sensor for fast, synchronized neurotransmitter release at the human neuromuscular junction, has recently been implicated in a dominantly inherited congenital myasthenic syndrome associated with a non-progressive motor neuropathy. In one family, a proline residue within the C2B Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The functional significance of this residue has not been investigated previously. Here we show that in silico modeling predicts disruption of the C2B Ca2+-binding pocket, and we examine the in vivo effects of the homologous mutation in Drosophila. When expressed in the absence of native synaptotagmin, this mutation is lethal, demonstrating for the first time that this residue plays a critical role in synaptotagmin function. To achieve expression similar to human patients, the mutation is expressed in flies carrying one copy of the wild type synaptotagmin gene. We now show that Drosophila carrying this mutation developed neurological and behavioral manifestations similar to those of human patients and provide insight into the mechanisms underlying these deficits. Our Drosophila studies support a role for this synaptotagmin point mutation in disease etiology.


Asunto(s)
Drosophila melanogaster , Mutación , Síndromes Miasténicos Congénitos/genética , Sinapsis , Sinaptotagminas/genética , Secuencia de Aminoácidos , Animales , Calcio/metabolismo , Simulación por Computador , Femenino , Heterocigoto , Humanos , Locomoción/genética , Longevidad/genética , Masculino , Modelos Biológicos , Modelos Moleculares , Fatiga Muscular/genética , Síndromes Miasténicos Congénitos/metabolismo , Síndromes Miasténicos Congénitos/fisiopatología , Conformación Proteica , Ratas , Sinapsis/metabolismo , Sinaptotagminas/química , Sinaptotagminas/metabolismo
14.
Neurotoxicology ; 33(3): 500-11, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22387230

RESUMEN

The occurrence of status epilepticus (SE) is considered the main cause of brain lesions and morphological alterations, such as hippocampal neuron loss, that result in chronic epilepsy. Previous work demonstrated the convulsive and widespread neuropathological effects of soman, an organophosphorus compound that causes SE and severe recurrent seizures as a result of exposure. Seizures begin rapidly after exposure, can continue for hours, and contribute to prolonged physical incapacitation of the victim. This study attempts to identify anticonvulsive and neuroprotective drugs against soman exposure. Male Sprague-Dawley rats were exposed to 1.0 LD(50) soman. EEGraphical and neuropathological (Fluoro-Jade B staining) effects were analyzed at 72 h post-exposure to soman and subsequent treatments with diazepam (DZP) alone or in combination with histone deacetylase inhibitors, suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). The extent of brain damage was dependent on the length of SE and not on the number of recurrent seizures. DZP treatment alone decreased SE time and damage in hippocampus, amygdala, thalamus and cortex, but not in piriform nuclei. The combination of DZP and VPA 100 mg/kg showed more anticonvulsive effects, decreased SE time, and afforded more neuroprotection in the hippocampus, mainly the ventral portion. The combination DZP and SAHA 25 mg/kg was more neuroprotective, but not more anticonvulsant than DZP alone. The DZP combination with VPA HDAC inhibitor proved to be a good treatment for SE and neuronal damage caused by soman exposure.


Asunto(s)
Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Sustancias para la Guerra Química/toxicidad , Diazepam/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Convulsiones/prevención & control , Soman/toxicidad , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Ondas Encefálicas/efectos de los fármacos , Citoprotección , Quimioterapia Combinada , Electroencefalografía , Ácidos Hidroxámicos/farmacología , Masculino , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Convulsiones/inducido químicamente , Convulsiones/patología , Convulsiones/fisiopatología , Factores de Tiempo , Ácido Valproico/farmacología , Vorinostat
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