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121.
Yang WW Sidman RL Taksir TV Treleaven CM Fidler JA Cheng SH Dodge JC Shihabuddin LS 《Experimental neurology》2011,227(2):287-295
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. However, recent reports suggest an active role of non-neuronal cells in the pathogenesis of the disease. Here, we examined quantitatively the temporal development of neuropathologic features in the brain and spinal cord of a mouse model of ALS (SOD1G93A). Four phases of the disease were studied in both male and female SOD1G93A mice: presymptomatic (PRE-SYM), symptomatic (SYM), endstage (ES) and moribund (MB). Compared to their control littermates, SOD1G93A mice showed an increase in astrogliosis in the motor cortex, spinal cord and motor trigeminal nucleus in the SYM phase that worsened progressively in ES and MB animals. Associated with this increase in astrogliosis was a concomitant increase in motor neuron cell death in the spinal cord and motor trigeminal nucleus in both ES and MB mice, as well as in the ventrolateral thalamus in MB animals. In contrast, microglial activation was significantly increased in all the same regions but only when the mice were in the MB phase. These results suggest that astrogliosis preceded or occurred concurrently with neuronal degeneration whereas prominent microgliosis was evident later (MB stage), after significant motor neuron degeneration had occurred. Hence, our findings support a role for astrocytes in modulating the progression of non-cell autonomous degeneration of motor neurons, with microglia playing a role in clearing degenerating neurons. 相似文献
122.
123.
P. M. Gaye L. Mesbah L. Kanouni N. Benjaafar B. K. El Gueddari 《Journal africain du cancer / African Journal of Cancer》2010,2(1):36-40
Esthesioneuroblastoma (ENB) or olfactive neuroblastoma is a rare tumor of the olfactive neuroepithelium of the third superior of the nasal septum, the cribriforme blade and superior cornets. The treatment widely accepted in the literature stays the previous craniofacial resection followed by a postoperative radiotherapy (RT) for locally extended stage, with a good local control of the disease. We report series of 12 patients treated to the National institute of oncology of Rabat to Morocco with review of literature. The treatment consisted of a surgery by maxillectomy followed by postoperative RT for an average period (delay) of one month for 58% of the patients. Neoadjuvant chemotherapy (platinium-based) was administered to 50% of the patients. The compliance was not good during the systemic treatment. The median time to progression was of six months (1–12 months). Three patients were lost of sight without controlled disease in 5 and 14 months respectively. The local relapse was observed for two patients (16%). No node or distant failure was noted in 44 months. The weak number of patients included in our series and the relatively insufficient follow-up does not authorize specific recommendations. There is a need for standard treatment for ENB. 相似文献
124.
The purpose of this review is to provide a critical examination of the reported solubilization of drugs by bile salt micelles. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. The common means of comparing the reported values was chosen to be the solubilization ratio. This is equal to the moles of drug solubilized per mole of bile salt. The values were segregated according to bile salt type, temperature, ionic strength, and the presence and absence of added lipids. Only segregation by bile salt type was pairwise statistically significant. From the solubilization ratios and the reported values of the aqueous solubility, the logarithms of the mole fraction micelle partition coefficients, log K(m/a), were calculated. The log K(m/w) was found to be correlated with the reported logarithm of the octanol/water partition coefficient. The rank order of slopes of the log K(m/a) as a function of log K(o/w) was cholate approximately taurodeoxycholate > glycocholate approximately taurocholate approximately glycodeoxycholate, with deoxycholate not being statistically different from the other data sets. The slope and intercept for the bile salt mixed micelle systems were 0.600 and 2.44, respectively, which were statistically indistinguishable from glycocholate, taurocholate, and glycodeoxycholate bile salt data. The existence of statistically significant correlations suggests that predicting the solubilization in the intestine may be possible with in vitro measurements if additional information is gathered in the appropriate micellar solutions. 相似文献
125.
Rajesh Krishnamurthy Amol Pednekar Lamya A Atweh Esben Vogelius Zili David Chu Wei Zhang Shiraz Maskatia Prakash Masand Shaine A Morris Ramkumar Krishnamurthy Raja Muthupillai 《Journal of cardiovascular magnetic resonance》2015,17(1)
Background
Cine balanced steady-state free precession (SSFP), the preferred sequence for ventricular function, demands uninterrupted radio frequency (RF) excitation to maintain the steady-state during suspended respiration. This is difficult to accomplish in sedated children. In this work, we validate a respiratory triggered (RT) SSFP sequence that drives the magnetization to steady-state before commencing retrospectively cardiac gated cine acquisition in a sedated pediatric population.Methods
This prospective study was performed on 20 sedated children with congenital heart disease (8.6 ± 4 yrs). Identical imaging parameters were used for multiple number of signal averages (MN) and RT cine SSFP sequences covering both the ventricles in short-axis (SA) orientation. Image quality assessment and quantitative volumetric analysis was performed on the datasets by two blinded observers. One-sided Wilcoxon signed rank test and Box plot analysis were performed to compare the clinical scores. Bland-Altman (BA) analysis was performed on LV and RV volumes.Results
Scan duration for SA stack using RT-SSFP (3.9 ± 0.8 min) was slightly shorter than MN-SSFP (4.6 ± 0.9 min) acquisitions. The endocardial edge definition was significantly better for RT than MN, blood to myocardial contrast was better for RT than MN without reaching statistical significance, and inter slice alignment was comparable. BA analysis indicates that the variability of volumetric indices between RT and MN is comparable to inter and intra-observer variability reported in the literature.Conclusions
The free breathing RT-SSFP sequence allows diagnostic images in sedated children with significantly better edge definition when compared to MN-SSFP, without any penalty for total scan time. 相似文献126.
Ghalib M. Alanazi Turki F. ALOsaimi Ali H. Alwadei Ali D. Al-Otaibi Lamya A. Jad Alawi A. Al-Attas 《Neurosciences (Riyadh, Saudi Arabia)》2022,27(2):59
Objectives:To compare the efficacy and safety of corpus callosotomy versus vagus nerve stimulation (VNS) as long-term adjunctive therapies in children with Lennox–Gastaut syndrome.Methods:This retrospective study was conducted in King Fahad Medical City between 2010 and 2019. The authors identified and followed 9 patients with Lennox–Gastaut syndrome (LGS) who underwent corpus callosotomy or VNS implantation for at least 12 months; seizure frequency and major complications were monitored. Five patients with a mean age of 10.8±1.3 years had corpus callosotomy, and 4 patients with a mean age of 13.8±3.9 years were implanted with VNS stimulators.Results:Reduction in seizure frequency was achieved in all 5 patients who underwent corpus callosotomy, with greater than 75% seizure reduction in more than 50% in one, and greater than 25% in 2 respectively. However, in those implanted with VNS, 2 (50%) patients achieved a reduction in seizure frequency of greater than 75% and 2 (50%) greater than 25%, respectively. No significant difference was observed between the 2 treatment groups. One patient who underwent corpus callosotomy suffered cerebrospinal fluid leakage, and swallowing difficulties in one patient who underwent VNS.Conclusion:Both corpus callosotomy and VNS are safe and effective as adjunctive treatments for LGS patients. Lennox–Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy that was first described by Dr. Henri Gastaut in 1966. 1 In 1950, Dr. William G. Lennox described the electroencephalogram features of this condition. 2 It is characterized by a triad of several types of seizures, cognitive impairment, and a distinctive awake interictal EEG pattern of diffuse slow basic rhythm interrupted by spike–wave complexes (1.5–2.5 Hz) while non-REM sleep characterized by discharges that are more generalized and more frequent, comprising polyspikes and slow waves; this condition is considered to be an epileptic encephalopathy. 3-6 Lennox–Gastaut syndrome accounts for approximately 2-5% of all childhood epilepsies. 7-8 Particularly in children, the incidence is estimated at 2 per 100,000, 9 and it is more common in males. 10 The LGS is one of the most commonly encountered drug-resistant epileptic encephalopathies, with mortality rates ranging between 3% and 7%. Moreover, the history of infantile spasms, or West syndrome, has been associated with an unfavorable prognosis. 11-12 There are many treatment options for LGS patients, such as antiepileptic medications, ketogenic diets, VNS therapy, corpus callosotomy, and resective epilepsy surgery. 11 Systematic review and meta-analysis showed that Cannabidiol (CBD) has an antiseizure mechanism in adults and children with drug-resistant epilepsy. Furthermore, it shows a significant reduction. in drop, non‑drop, and All Seizures frequency. However, it has not yet been approved by the Saudi Food and Drug Authority. 12 Due to the difficulty of identifying and localizing single epileptogenic lesions and the presence of multifocal characteristics, most LGS patients are ineligible for resective surgery. 11 Palliative surgical procedure for refractory epilepsy, such as corpus callosotomy, was introduced in the 1940s by Van Wagenen and Herren. 13 Since then, it has been widely used and indicated for different types of intractable generalized seizures. 14 On the other hand, VNS therapy was first performed in 1988. 15 It was approved by the US Food and Drug Administration as an adjunctive therapy for drug-resistant epilepsy in those who are not surgical candidates. 16 Both procedures can be used to reduce seizure frequency and severity in LGS patients. 17,18 The corpus callosum is a bundled white matter fiber that connects both hemispheres to allow slow brain waves to travel back and forth between both cerebral hemispheres during slow-wave sleep (SWS). Avvenuti et al suggest that having a well-connected corpus callosum is essential for the cross-hemispheric dispersion of slow waves during sleep slow waves, non-rapid eye movement (NREM) sleep. According to the authors, this is the first time that sleep researchers have identified that non-REM sleep “slow waves” travel between brain hemispheres via so-called “anatomical highways” in the corpus callosum. 19 Open in a separate windowFigure 1- Improvement (%) during follow-up (months) for the 2 groups. Improvement (%) during follow-up (months) for the 2 groups. VNS - Vagus nerve stimulation, CC - Corpus callosotomyTable 1- Demographic analysis and clinical characteristics of the study subjects.
Open in a separate windowVNS - Vagus nerve stimulationTable 2- Comparison of seizure reduction rates (all seizure types) and documented complications of patients treated with corpus callosotomy and vagal nerve stimulation.
Open in a separate windowVNS - Vagus nerve stimulationOur study evaluates the efficacy and safety of corpus callosotomy versus VNS as long-term adjunctive therapies in children with LGS in King Fahad Medical City. To our knowledge and as revealed by a search of the relevant literature, this study is a unique of its novelty in Saudi Arabia and the Middle East. 相似文献
Patient characteristics | Corpus callosotomy | VNS | P-value |
---|---|---|---|
Number of patients | 5 | 4 | |
Age (years) | 10.8±1.3 | 13.8±3.9 | 0.15 |
Male/female | 4/1 | 0/4 | 0.02 |
Age of seizure onset (months) | 20.6±30.6 | 18.8±20.5 | 0.68 |
Seizure duration before surgery (years) | 8.2±3.1 | 12.0±3.6 | 0.13 |
Follow-up duration (months) | 15.2±3.6 | 24.5±16.5 | 0.25 |
Mean age at surgery (years) | 9.6±1.1 | 11.7±3.3 | 0.21 |
Length of surgery (minutes) | 291.4±61.6 | 113.75±12.5 | 0.002 |
Length of hospitalization (days) | 9.6±4.4 | 7.25±3.5 | 0.41 |
Main seizure types | |||
Atonic/tonic with head drops | 5 | 2 | |
Generalized tonic seizure | 0 | 1 | |
Generalized tonic–clonic seizure | 0 | 1 | |
MRI findings | |||
Atrophic change | 0 | 2 | |
Pachygyria–lissencephaly with band heterotopias | 1 | 0 | |
Normal | 4 | 2 | |
Number of antiepileptic medications | |||
Before surgery | 3.4±1.1 | 3.5±1.3 | 0.91 |
After surgery | 3.4±1.1 | 3.0±1.1 | |
Change in antiepileptic medications | |||
Not changed | 3 | 3 | 0.5 |
Increased | 0 | 0 | |
Decreased | 2 | 1 |
Seizure reduction rate | Corpus callosotomy | VNS | Comparison p-value |
---|---|---|---|
>75% | 2 | 2 | 0.64 |
>51–74% | 1 | 0 | 0.34 |
≤50% | 2 | 2 | 0.83 |
Complications | 1/5 | 1/4 | |
Cerebrospinal fluid | 1 | 0 | 0.72 |
Swallowing difficulty | 0 | 1 | |
No | 4 | 3 |
127.
Refractory immune thrombocytopenia (ITP) is a challenging disease that can be defined by refractoriness to second-line treatments. In this review, we list and comment available evidence about clinical and biological factors associated with refractoriness to splenectomy, thrombopoietin receptor agonists (TPO-RAs), rituximab and fostamatinib, as well as those associated with multirefractory ITP (active disease with failure of rituximab, TPO-RAs and splenectomy). 相似文献