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1.
Cells ; 13(9)2024 May 04.
Article in English | MEDLINE | ID: mdl-38727321

ABSTRACT

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells' reactive phenotype.


Subject(s)
Disease Models, Animal , Lipopolysaccharides , Muscular Atrophy, Spinal , Animals , Lipopolysaccharides/pharmacology , Muscular Atrophy, Spinal/pathology , Muscular Atrophy, Spinal/metabolism , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscle, Skeletal/metabolism , Microglia/metabolism , Microglia/drug effects , Microglia/pathology , Survival of Motor Neuron 1 Protein/metabolism , Survival of Motor Neuron 1 Protein/genetics , Mice, Inbred C57BL , Astrocytes/metabolism , Astrocytes/drug effects , Astrocytes/pathology , Inflammation/pathology
2.
J Exp Orthop ; 11(1): e12010, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38455456

ABSTRACT

Purpose: To investigate whether and how extra-synovial autografts can enhance the reconstruction of chronic and large rotator cuff tears in a rabbit subscapularis model. Methods: Twenty rabbits were used to create a large subscapularis tear bilaterally. Six weeks later, the right shoulder of each rabbit was operated to repair the tear with an extra-synovial autograft, whereas the left shoulder did not undergo any surgery. At 6 and 12 weeks after the second procedure, the specimens underwent biomechanical and histological evaluation. Six more rabbits were used only as a normal reference. Results: Biomechanical evaluation demonstrated that the ultimate load to failure of the Graft group (184.1 ± 35.7 N) was significantly higher (p = 0.04) than that of the Defect group (144.5 ± 32.2 N) at 12 weeks after repair, rising to 76% of the normal subscapularis tendon tensile strength. Histological analysis revealed an enhanced healing environment with neoangiogenesis and decreased inflammatory response at the repair site. Moreover, the tendon maturing score of the Graft group increased substantially from 6 (15.8 ± 0.9) to 12 (23.1 ± 0.6) weeks after repair (p = 0.01). Conclusion: In vivo data support the efficacy of extra-synovial autograft interposition in repairing chronic and large rotator cuff tears in a rabbit subscapularis model. The autografts were capable of enhancing the biomechanical properties of the repaired tendons, as evidenced by increased tensile strength, and forming new connective tissue simulating a fibrocartilage zone, as revealed by histological evaluation. Level of Evidence: N/A.

3.
Brain Sci ; 13(11)2023 Nov 09.
Article in English | MEDLINE | ID: mdl-38002534

ABSTRACT

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

4.
Front Psychiatry ; 14: 1214067, 2023.
Article in English | MEDLINE | ID: mdl-37663605

ABSTRACT

Background: Functional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM). Methods: Sixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique. Results: In the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup. Conclusion: ICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research.

5.
Int J Mol Sci ; 23(24)2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36555816

ABSTRACT

Hypoxic ischemic (HI) brain injury that occurs during neonatal period has been correlated with severe neuronal damage, behavioral deficits and infant mortality. Previous evidence indicates that N-acetylcysteine (NAC), a compound with antioxidant action, exerts a potential neuroprotective effect in various neurological disorders including injury induced by brain ischemia. The aim of the present study was to investigate the role of NAC as a potential therapeutic agent in a rat model of neonatal HI brain injury and explore its long-term behavioral effects. To this end, NAC (50 mg/kg/dose, i.p.) was administered prior to and instantly after HI, in order to evaluate hippocampal and cerebral cortex damage as well as long-term functional outcome. Immunohistochemistry was used to detect inducible nitric oxide synthase (iNOS) expression. The results revealed that NAC significantly alleviated sensorimotor deficits and this effect was maintained up to adulthood. These improvements in functional outcome were associated with a significant decrease in the severity of brain damage. Moreover, NAC decreased the short-term expression of iNOS, a finding implying that iNOS activity may be suppressed and that through this action NAC may exert its therapeutic action against neonatal HI brain injury.


Subject(s)
Brain Injuries , Hypoxia-Ischemia, Brain , Neuroprotective Agents , Animals , Rats , Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Acetylcysteine/metabolism , Animals, Newborn , Rats, Sprague-Dawley , Hypoxia-Ischemia, Brain/metabolism , Brain Injuries/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/metabolism , Brain/metabolism
6.
Brain Inj ; 36(6): 703-713, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35476710

ABSTRACT

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.


Subject(s)
Brain Concussion , Intracranial Hemorrhage, Traumatic , Brain Concussion/complications , Fibrinolytic Agents/adverse effects , Humans , Intracranial Hemorrhage, Traumatic/diagnostic imaging , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/etiology , Retrospective Studies , Tomography, X-Ray Computed
7.
Stroke ; 50(4): 931-938, 2019 04.
Article in English | MEDLINE | ID: mdl-30852968

ABSTRACT

Background and Purpose- Acute stroke treatment is challenging, and stroke remains a major cause of death and disability. The purpose of this meta-analysis is to investigate the effects of postacute stroke intravenous administration of the neuroprotectant magnesium sulfate (MgSO4) on global outcome, functional outcome, and mortality 90 days poststroke (ischemic and nonischemic). Methods- We searched in Pubmed, Science Direct, CENTRAL, and ClinicalTrials.gov, up to November 11, 2017, and we conducted a systematic review and meta-analysis of randomized controlled trials. We synthesized results by using random-effects model, weighted mean differences, standardized mean differences, and odds ratios. Results- Seven randomized controlled trials (4347 patients) met our criteria. Compared with placebo, treatment did not improve functional outcome defined as Barthel Index >60 (odds ratio =1.05; 95% CI, 0.92-1.19) and >95 (odds ratio =0.95; 95% CI, 0.76-1.20), 90 days poststroke. It also did not improve global outcome measured with modified Rankin Scale (standardized mean difference =-0.01; 95% CI, -0.12 to 0.10), 90 days poststroke. In an additional subgroup meta-analysis that exclusively included ischemic stroke patients, intravenous MgSO4 resulted in lower modified Rankin Scale score (improved global outcome; weighted mean difference =-0.96; 95% CI, -1.34 to -0.58; I2=0%], 90 days poststroke. Finally, mortality stayed unaltered (odds ratio =1.10; 95% CI, 0.94-1.29). Conclusions- The findings of our meta-analysis showed that intravenous MgSO4 generally did not improve global/functional outcomes and mortality at 90 days after stroke (combined ischemic stroke and nonischemic stroke). The finding of favorable neurological outcome, selectively in ischemic stroke patients, should be viewed with extreme caution given the limited number of patients included in this subgroup meta-analysis.


Subject(s)
Brain Ischemia/drug therapy , Intracranial Hemorrhages/drug therapy , Magnesium Sulfate/therapeutic use , Neuroprotective Agents/therapeutic use , Stroke/drug therapy , Administration, Intravenous , Humans , Survival Rate , Treatment Outcome
8.
Acta Medica (Hradec Kralove) ; 61(2): 47-52, 2018.
Article in English | MEDLINE | ID: mdl-30216182

ABSTRACT

Introduction-Aim: Newer methods, such as infrared digital pupillometry and electrodermal activity (EDA) measurement have been suggested as good alternatives for analgesia monitoring in critically ill patients. This study analyzed EDA changes due to pain stimulus in sedated adult critical care patients Methods: Skin conductance variability, selected hemodynamic and respiratory parameters, Bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime in an adult ICU. 4h-Measurements were divided into 2 groups, based upon the sedation level of the patients: Group A - Ramsay Sedation Score 2-4 and Group B - Ramsay Sedation Score of 5-6. Selected recordings before and after pain stimulus were performed. The stimulus chosen was the pressure applied to nail bed for 10 sec, which was performed routinely during neurological examination. Patients' demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed by 2 independent observers via Critical Care Pain Observation Tool (CPOT) and Adult Non Verbal Pain Score (ANVPS) Results: In both groups the rate of EDA changes was greater than other monitoring parameters: more in Group A than in Group B. Yet, the difference between groups was not statistically significant. CONCLUSION: EDA measurements are greater to pain stimuli, than cardiovascular, respiratory or even BIS monitoring. These encouraging results suggest that, further studies are needed to better define EDA role in ICU.


Subject(s)
Conscious Sedation , Galvanic Skin Response , Monitoring, Physiologic , Pain Measurement , Physical Stimulation , Aged , Female , Humans , Intensive Care Units , Male , Middle Aged , Pilot Projects , Prospective Studies
9.
Folia Med (Plovdiv) ; 60(1): 92-101, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29668462

ABSTRACT

BACKGROUND: Endotracheal suctioning of respiratory secretions is one of the most common causes of pain and discomfort in Intensive Care Unit environment. The electrical properties of the skin, also known as electrodermal activity (EDA), are considered as an indirect measure of autonomous nervous system. AIM: This study explores EDA changes during endotracheal suction in sedated adult critical care patients; and compares these changes to other monitoring parameters. MATERIALS AND METHODS: Skin conductance variability, selected hemodynamic and respiratory parameters, bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime intensive care nursing and treatment in an adult Intensive Care Unit. 4h-measurements were divided into 2 groups, based upon the sedation level (group A: Ramsay sedation scale 2-4 and group B: 5-6 respectively) of the patients. Selected recordings before and after endotracheal suction (stress events) were performed. Seven stress events from Group A and 17 from Group B were included for further analysis. Patients' demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed via 2 independent observers. RESULTS: In both groups the rate of EDA changes was greater than in other monitoring parameters. Yet, in group A only selected parameters were significantly changed after the start of the procedure, while in group B, every parameter showed significant change (p<0.05). Groups were similar for other co-founding factors. CONCLUSION: EDA measurements are more sensitive to stress stimuli, than cardiovascular, respiratory or even BIS monitoring. Deeper sedation seems to affect more the intensity of EDA changes during suction.


Subject(s)
Conscious Sedation/statistics & numerical data , Deep Sedation/statistics & numerical data , Galvanic Skin Response/physiology , Intubation, Intratracheal/adverse effects , Suction , Aged , Female , Humans , Intensive Care Units , Male , Middle Aged , Pain Measurement , Prospective Studies , Suction/adverse effects , Suction/methods , Suction/statistics & numerical data
10.
Med Sci (Basel) ; 6(1)2018 Mar 06.
Article in English | MEDLINE | ID: mdl-29509711

ABSTRACT

Electrodermal activity (EDA) is considered a measure of autonomous nervous system activity. This study performed an exploratory analysis of the EDA changes during blood pooling for arterial blood gas analysis in sedated adult critical care patients and correlated the variations to other monitored parameters. EDA, along with other parameters, were monitored during 4 h routine daytime intensive care nursing and treatment in an adult ICU. 4 h measurements were divided into two groups based upon the sedation level. Selected recordings before and after blood pooling for arterial blood gases analysis (stress event) was performed. Nine stress events from Group A and 17 from Group B were included for further analysis. Patients' demographics, laboratory exams, and severity scores were recorded. For both sedation levels, EDA changes are much greater than any other monitoring parameters used. The changes are noticed in both measurement (15 s and 60 s), even though in the 60 s measurement only selected EDA parameters are significantly changed after the start of the procedure. EDA measurements are more sensitive to a given stress event than cardiovascular or respiratory parameters. However, the present results could only be considered as a pilot study. More studies are needed in order to identify the real stress-load and clinical significance of such stimuli, which are considered otherwise painless in those patients.

12.
J Shoulder Elbow Surg ; 23(12): 1822-1830, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24981552

ABSTRACT

BACKGROUND: Massive rotator cuff tear repair is frequently complicated by unsatisfactory clinical results due to possible tendon retraction, muscle atrophy, and fatty degeneration. The objective of this study was the development of a chronic massive tear in a rat model and the evaluation of the muscle force in vivo and of the histologic changes in a 3- dimensional manner. METHODS: To simulate massive rotator cuff tears, both the supraspinatus (SS) and the infraspinatus (IS) tendons were surgically detached from the right humerus of 15 male adult Sprague-Dawley rats. Twelve weeks postoperatively, all animals underwent isometric tension recordings of both the SS and IS muscles. Histologic analysis and image deconvolution processing were performed to estimate the presence and the distribution of atrophy in 3 dimensions. RESULTS: An overall 30% and 35% reduction in muscle force of the SS and IS muscles, respectively, was observed compared with the left uninjured shoulder (P < .005). Histologic analysis revealed that the degeneration and the fatty infiltration were more evident near the tendon and at the dorsal side in both muscle groups. CONCLUSIONS: These results show that functional impairment of SS and IS muscles after chronic massive tendon tears could be attributed to the decrease in muscle force production during their repair on the greater tuberosity and, second, to the comparatively greater degeneration of their dorsal part.


Subject(s)
Muscle, Skeletal/pathology , Rotator Cuff Injuries , Tendon Injuries/pathology , Animals , Chronic Disease , Male , Muscle Strength , Muscle, Skeletal/physiopathology , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Rats , Rats, Sprague-Dawley , Rotator Cuff/pathology , Rotator Cuff/physiopathology , Rupture , Tendon Injuries/physiopathology , Tendons/pathology , Tendons/physiopathology
13.
Muscle Nerve ; 48(6): 951-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23512745

ABSTRACT

INTRODUCTION: Quantitative descriptions of fiber type organization in hind limb muscles are incomplete or rare. METHODS: Fiber morphometrics for both rat tibialis anterior (TA) muscles were measured in 3 dimensions. RESULTS: Slow oxidative fiber area and perimeter varied in all zones. Fast oxidative glycolytic fibers (FOG) were predominant in the mediolateral and posterior zones, and fast glycolytic fibers (FG) predominated in the anterior zone. The mean area of FOG and succinate dehydrogenase intermediate fibers was lowest in the anterior zone. Mean area of FG was highest in the proximal and distal parts of the muscle. The area and perimeter of fast fibers differed significantly between the right and left limbs in the medial zone. In the middle and lateral zones, they differed at the proximal and distal parts. CONCLUSIONS: This detailed analysis in a high resolution, 3-dimensional map provides an essential tool for understanding the structure and function of TA muscles.


Subject(s)
Muscle Fibers, Skeletal , Muscle, Skeletal/anatomy & histology , Animals , Diagnosis, Computer-Assisted , Glycolysis/physiology , Male , Models, Biological , Muscle Fibers, Skeletal/classification , Muscle Fibers, Skeletal/metabolism , Rats , Rats, Wistar , Succinate Dehydrogenase/metabolism
14.
BMC Physiol ; 12: 5, 2012 May 02.
Article in English | MEDLINE | ID: mdl-22551202

ABSTRACT

BACKGROUND: It is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury. METHODS: Wistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (injection of 0.9% NaCl solution) b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months). RESULTS: 1. Administration of DAP5 alone provoked no apparent adverse effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p < 0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their locomotor behaviour were significantly improved compared to axotomized ones (p < 0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p < 0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p < 0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles. CONCLUSIONS: Our results confirm that contractile properties and locomotor behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.


Subject(s)
2-Amino-5-phosphonovalerate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Motor Neurons/drug effects , Movement/drug effects , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , N-Methylaspartate/antagonists & inhibitors , Animals , Animals, Newborn , Axotomy/methods , Behavior, Animal , Female , Male , Motor Neurons/physiology , Movement/physiology , Muscle Contraction/physiology , Muscle Denervation/methods , Nerve Crush/methods , Rats, Wistar
15.
BMC Cancer ; 12: 3, 2012 Jan 03.
Article in English | MEDLINE | ID: mdl-22214427

ABSTRACT

BACKGROUND: In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. METHODS: We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. RESULTS: In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). CONCLUSIONS: Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore, volumetry could help not only to improve the prediction of outcome but also the outcome itself by identifying patients at high risk of treatment failure and, thus, seek alternative treatment for these patients. In this small series, MGMT protein was associated with less aggressive tumor characteristics.


Subject(s)
Brain Neoplasms/enzymology , Brain Neoplasms/pathology , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Glioblastoma/enzymology , Glioblastoma/pathology , Tumor Burden , Tumor Suppressor Proteins/metabolism , Adult , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/mortality , Brain Neoplasms/therapy , Chemoradiotherapy/methods , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Disease-Free Survival , Female , Gene Expression Profiling , Glioblastoma/mortality , Glioblastoma/therapy , Humans , Magnetic Resonance Imaging/methods , Male , Methylation , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Prospective Studies , Survival Analysis , Temozolomide , Tumor Suppressor Proteins/genetics
16.
Muscles Ligaments Tendons J ; 2(2): 64-9, 2012 Apr.
Article in English | MEDLINE | ID: mdl-23738276

ABSTRACT

It has been shown in the rat, that during the first five postnatal days, motoneurons are particularly vulnerable to excitotoxic cell death and glutamate receptors play a significant role in this time-dependent process. Various categories of glutamate blockers (MK-801, Mg, PNQX, DAP-5) have various actions on the respective receptors. Furthermore, the different response between mature and immature motoneurons following injury is attributed to the quantity of glutamate receptors on the cell membrane. The effect of these substances on the recovery of fast and slow muscles after sciatic nerve crush, at critical developmental stages, shows a variable but impressive reversal of the devastating effects on rat muscle properties, which is different between fast and slow muscles. In addition, blocking of NMDA receptors by various substances rescues motoneurons and increases the number of motor units surviving into adulthood. In this way, glutamate receptor blockers may represent a promising therapeutic approach to retain nerve and muscle function during neurodegenerative events.

17.
Strahlenther Onkol ; 185(11): 743-50, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19899008

ABSTRACT

BACKGROUND AND PURPOSE: The importance of tumor volume as a prognostic factor in high-grade gliomas is highly controversial and there are numerous methods estimating this parameter. In this study, a computer-based application was used in order to assess tumor volume from hard copies and a survival analysis was conducted in order to evaluate the prognostic significance of preoperative volumetric data in patients harboring glioblastomas. PATIENTS AND METHODS: 50 patients suffering from glioblastoma were analyzed retrospectively. Tumor volume was determined by the various geometric models as well as by an own specialized software (Volumio). Age, performance status, type of excision, and tumor location were also included in the multivariate analysis. RESULTS: The spheroid and rectangular models overestimated tumor volume, while the ellipsoid model offered the best approximation. Volume failed to attain any statistical significance in prognosis, while age and performance status confirmed their importance in progression-free and overall survival of patients. CONCLUSION: Geometric models provide a rough approximation of tumor volume and should not be used, as accurate determination of size is of paramount importance in order to draw safe conclusions in oncology. Although the significance of volumetry was not disclosed, further studies are definitely required.


Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional , Magnetic Resonance Imaging/methods , Models, Theoretical , Radiosurgery , Tumor Burden , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Brain Neoplasms/surgery , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Chemotherapy, Adjuvant , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Disease-Free Survival , Female , Glioblastoma/drug therapy , Glioblastoma/mortality , Glioblastoma/surgery , Humans , Irinotecan , Kaplan-Meier Estimate , Male , Middle Aged , Regression Analysis , Statistics as Topic , Temozolomide
18.
Clin Neurol Neurosurg ; 109(10): 905-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17870234

ABSTRACT

An isolated spinal demyelinating lesion is very rare and almost always associated with multiple sclerosis. There are only a few reports of biopsy or resection of MS-associated lesions. Sometimes the radiological and the histopathological findings can lead to a false diagnosis of a tumour. A 15-year-old girl presented with a progressive spastic tetraparesis and various associated clinical symptoms. Magnetic resonance imaging (MRI) suggested a possible intramedullary tumour extending from C4 to C7 and the need for surgical intervention. There was no previous neurological or other history and the brain MRI was normal. The performing surgeons based their procedures on oncological criteria. The extracted lesion was finally diagnosed as a demyelinating plaque. The postoperative course was uneventful without deterioration of the neurological status and the young patient improved completely after 4-months of rehabilitation. After an 8-year follow-up, the patient remains in remission and free of neurological defects. Apart from the radiological findings, the CSF exam as well as the evoked potentials does not suggest a diagnosis of MS. A demyelinating plaque in the cervical spinal cord can occasionally imitate a cervical intramedullary tumour leading to an operation. Such lesions underscore the sensitivity of present-day lesion detection procedures. An addition of a MS work up could be beneficial in some cases of intramedullary tumours without a typical history, although in the case presented this type of workup was negative.


Subject(s)
Demyelinating Diseases/diagnosis , Hypesthesia/etiology , Neck Pain/etiology , Quadriplegia/etiology , Spinal Cord Diseases/diagnosis , Spinal Cord Neoplasms/diagnosis , Adolescent , Cervical Vertebrae/pathology , Cervical Vertebrae/surgery , Demyelinating Diseases/pathology , Demyelinating Diseases/surgery , Diagnostic Errors , Female , Follow-Up Studies , Humans , Hypesthesia/pathology , Hypesthesia/surgery , Laminectomy , Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Neck Pain/pathology , Neck Pain/surgery , Quadriplegia/pathology , Quadriplegia/surgery , Spinal Cord Diseases/pathology , Spinal Cord Diseases/surgery , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery
19.
Pediatr Neurosurg ; 40(4): 196-202, 2004.
Article in English | MEDLINE | ID: mdl-15608494

ABSTRACT

OBJECTIVE AND IMPORTANCE: Disorders of thermoregulation are occasionally noticed after operations in the region of the third ventricle. Various factors are usually implicated, but the actual contribution of each of them is rather vague. Apart from the presumed derangement in the functional connections of the hypothalamic region, mechanical reasons of compression should be thoroughly considered. CLINICAL PRESENTATION: An 8.5-year-old patient was subjected to a radical excision of a craniopharyngioma compressing the third ventricle. Three months after the operation, he presented with a febrile syndrome of unknown origin. All usual investigations proved negative. INTERVENTION: A chronic subdural hygroma was evacuated, an encapsulated CSF cyst of the suprachiasmatic cistern was drained and the lamina terminalis incised resulting in a moderate control of pyrexia. The administration of chlorpromazine contributed to the final resolution of hyperthermia. CONCLUSION: Postoperative hyperthermia may result following resection of tumors of the hypothalamic floor. It should not be blindly attributed to hypothalamic dysfunction as surgical causes could be implicated as well. Chlorpromazine could be a useful adjunct to the correction of the disorder.


Subject(s)
Craniopharyngioma/surgery , Fever/etiology , Pituitary Neoplasms/surgery , Postoperative Complications , Subdural Effusion/etiology , Analgesics, Non-Narcotic/therapeutic use , Child , Fever/drug therapy , Fever/surgery , Humans , Male , Subdural Effusion/surgery , Time Factors
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