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1.
Sensors (Basel) ; 22(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36433330

RESUMO

In clinical practice, acute post-stroke paresis of the extremities fundamentally complicates timely rehabilitation of motor functions; however, recently, residual and distorted musculoskeletal signals have been used to initiate feedback-driven solutions for establishing motor rehabilitation. Here, we investigate the possibilities of basic hand gesture recognition in acute stroke patients with hand paresis using a novel, acute stroke, four-component multidomain feature set (ASF-4) with feature vector weight additions (ASF-14NP, ASF-24P) and supervised learning algorithms trained only by surface electromyography (sEMG). A total of 19 (65.9 ± 12.4 years old; 12 men, seven women) acute stroke survivors (12.4 ± 6.3 days since onset) with hand paresis (Brunnstrom stage 4 ± 1/4 ± 1, SIAS 3 ± 1/3 ± 2, FMA-UE 40 ± 20) performed 10 repetitive hand movements reflecting basic activities of daily living (ADLs): rest, fist, pinch, wrist flexion, wrist extension, finger spread, and thumb up. Signals were recorded using an eight-channel, portable sEMG device with electrode placement on the forearms and thenar areas of both limbs (four sensors on each extremity). Using data preprocessing, semi-automatic segmentation, and a set of extracted feature vectors, support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbors (k-NN) classifiers for statistical comparison and validity (paired t-tests, p-value < 0.05), we were able to discriminate myoelectrical patterns for each gesture on both paretic and non-paretic sides. Despite any post-stroke conditions, the evaluated total accuracy rate by the 10-fold cross-validation using SVM among four-, five-, six-, and seven-gesture models were 96.62%, 94.20%, 94.45%, and 95.57% for non-paretic and 90.37%, 88.48%, 88.60%, and 89.75% for paretic limbs, respectively. LDA had competitive results using PCA whereas k-NN was a less efficient classifier in gesture prediction. Thus, we demonstrate partial efficacy of the combination of sEMG and supervised learning for upper-limb rehabilitation procedures for early acute stroke motor recovery and various treatment applications.


Assuntos
Gestos , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Atividades Cotidianas , Paresia , Extremidade Superior , Acidente Vascular Cerebral/complicações
2.
J Fluoresc ; 31(1): 73-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33078252

RESUMO

Boron neutron capture therapy (BNCT), a binary cancer therapeutic modality, has moved to a new phase since development of accelerator-based neutron sources and establishment of BNCT centers in Finland and Japan. That stimulated efforts for better boron delivery agent development. As liposomes have shown effective boron delivery properties and sufficient tumor retention, fluorescent liposome labelling may serve as a rapid method to study initial ability of newly synthesized liposomes to be captured by tumor cells prior to experiments on boron accumulation and neutron irradiation. In this work, we studied the accumulation and biodistribution of pegylated liposomes with encapsulated borocaptate (BSH) and a fluorescent label (Nile Red) in U87 (human glioblastoma), SW-620 (human colon carcinoma), SK-MEL-28 (human melanoma), FetMSC (mesenchymal human embryo stem cells), and EMBR (primary embryocytes) cell lines as well as an orthotopic xenograft model of U87 glioma in SCID mice. Results indicate that fluorescent microscopy is effective at determining the intracellular localization of the liposomes using a fluorescent label. The synthesized, pegylated liposomes showed higher accumulation in tumors compared to normal cells, with characteristic concentration peaks in SW-620 and U87 cell lines, and provided in vivo tumor selectivity with several-fold higher tumor tissue fluorescence at the 6-h timepoint. Graphical abstract Fluorescent images of U-87 glioma cells after 24 hours of incubation with BSH-containing liposomes labeled with lipophilic Nile Red (red color)and water-soluble FITC-Dextran (green color); cell nuclei in blue color (DAPI-staining) (×400). Scale bar is 50 µm. Fluorescent labelling serves as anexpress method to study liposome delivery efficiency prior to boron accumulation evaluation and BNCT irradiation experiments.


Assuntos
Boroidretos/química , Corantes Fluorescentes/química , Lipossomos/química , Boroidretos/uso terapêutico , Linhagem Celular Tumoral , Glioma/patologia , Humanos
3.
Br J Neurosurg ; 35(6): 749-752, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32530358

RESUMO

INTRODUCTION: Remote traumatic intracranial haemorrhage (RTIH) may develop after neurosurgery. Recognition of the risk factors for RTIH before surgery might be of great value. The purpose of this study was to verify if the fibrin/fibrinogen degradation product (FDP) value may be a risk factor for RTIH. METHODS: This was a retrospective study of the data of 56 patients with traumatic intracranial hematomas shown on initial computed tomography (CT) who were treated with craniotomy or decompressive craniectomy and underwent a follow-up CT at a single centre over a period of approximately 10.5 years. We divided the patients into 2 groups: those who developed RTIH (Positive: P-group) and those who did not (Negative: N-group). We compared the 2 groups in terms of not only the laboratory data before surgery, but also patient age, sex, antiplatelet/antithrombotic medications received, cause of injury, and GCS score on arrival. RESULTS: RTIH was observed in 22 patients (P-group, 39.3%). The FDP value was the only significant risk factor identified in this study (p = 0.00076). The cut-off value was estimated on the basis of the area under the receiver operating characteristic (ROC) curve. The cut-off FDP value was 120 µg/mL (63.6% sensitivity and 85.3% specificity). CONCLUSIONS: FDP levels over 120 µg/mL were determined to be a risk factor for progressive RTIH after neurosurgery. We suggest the FDP level be checked before surgery for traumatic intracranial haemorrhage and follow-up CT be done as soon as possible after the surgery if the serum FDP level is over 120 µg/mL.


Assuntos
Hemorragia Intracraniana Traumática , Procedimentos Neurocirúrgicos/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Hemorragia Intracraniana Traumática/diagnóstico por imagem , Hemorragia Intracraniana Traumática/etiologia , Hemorragia Intracraniana Traumática/cirurgia , Estudos Retrospectivos , Fatores de Risco
4.
BMC Neurol ; 20(1): 21, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941461

RESUMO

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA. CASE PRESENTATION: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA. CONCLUSIONS: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Feminino , Humanos , Adulto Jovem
5.
J Stroke Cerebrovasc Dis ; 28(4): 1078-1084, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30638941

RESUMO

BACKGROUND: Stroke mimics (SMs)are medical conditions that are at first considered to be of cerebrovascular etiology but turn out to be a condition other than stroke. While many reports on SMs have been published, there have been none from Japan. Thus, we sought to assess the current state of SMs in a Japanese population. METHODS: We collected data of patients referred with suspicion of stroke to neurosurgeons by emergency department (ED) doctors, and we retrospectively evaluated the diagnosis concordance rate between the ED doctors and the neurosurgeons. We also assessed the plausible causes leading to misdiagnosis of stroke. RESULTS: Of the 226 consecutive referrals with suspicion of stroke, only 71.7% were accurate. Furthermore, 75% of the SMs were disorders unrelated to neurosurgery, such as psychiatric disorders, peripheral dizziness/vertigo, and cardiovascular events. In other words, referring those patients to neurosurgeons was inappropriate. We found that perceived notion or premature assumption of stroke accounted for 43.8% of the stroke mimic patients and was the most important reason for the misdiagnosis. CONCLUSIONS: This is the first report on SMs in a Japanese population. About one-third of all referrals with suspicion of stroke made by ED doctors were inappropriate. Including more information on stroke diagnosis in the educational program for young doctors in Japan would be beneficial for improving the quality of the initial medical examination of patients with suspected stroke.


Assuntos
Serviço Hospitalar de Emergência , Médicos , Encaminhamento e Consulta , Acidente Vascular Cerebral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neurocirurgiões , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Especialização , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Adulto Jovem
6.
Acta Neurochir (Wien) ; 160(8): 1557-1561, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29915889

RESUMO

Although liposarcomas are the most common soft tissue sarcomas, their intracranial variants are extremely rare. Here, we present a case of a primary intracranial myxoid liposarcoma in a 23-year-old Japanese man who presented with generalized seizures and a mass in the left frontal lobe. The tumor was totally removed, and histological analyses pointed to liposarcoma. Thirteen years after his initial treatment, the patient presented with right-side weakness and local recurrence of tumor was discovered. Histology from the second resection confirmed the diagnosis of myxoid liposarcoma. Shortly after the second resection, progressive, new intracranial lesions were observed and despite a third resection, extensive intracerebral invasion by the tumor proved fatal. The histological features of myxoid liposarcoma were essentially similar with each recurrence, but the aggressive tumor behavior after the second operation did not align with expectations based on histological classification.


Assuntos
Lipossarcoma Mixoide/patologia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/patologia , Humanos , Lipossarcoma Mixoide/cirurgia , Masculino , Neoplasias Meníngeas/cirurgia , Adulto Jovem
7.
Radiat Environ Biophys ; 54(4): 423-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26242374

RESUMO

Core-inner-valence ionization of high-Z nanoparticle atomic clusters can de-excite electrons through various interatomic de-excitation processes, thereby leading to the ionization of both directly exposed atoms and adjacent neutral atoms within the nanoparticles, and to an enhancement in photon-electron emission, which is termed the nanoradiator effect. To investigate the nanoradiator-mediated dose enhancement in the radio-sensitizing of high-Z nanoparticles, the production of reactive oxygen species (ROS) was measured in a gadolinium oxide nanoparticle (Gd-oxide NP) solution under core-inner-valence excitation of Gd with either 50 keV monochromatic synchrotron X-rays or 45 MeV protons. This measurement was compared with either a radiation-only control or a gadolinium-chelate magnetic resonance imaging contrast agent solution containing equal amounts of gadolinium as the separate atomic species in which Gd-Gd interatomic de-excitations are absent. Ionization excitations followed by ROS measurements were performed on nanoparticle-loaded cells or aqueous solutions. Both photoexcitation and proton impact produced a dose-dependent enhancement in the production of ROS by a range of factors from 1.6 to 1.94 compared with the radiation-only control. Enhanced production of ROS, by a factor of 1.83, was observed from Gd-oxide NP atomic clusters compared with the Gd-chelate molecule, with a Gd concentration of 48 µg/mL in the core-level photon excitation, or by a factor of 1.82 under a Gd concentration of 12 µg/mL for the proton impact at 10 Gy (p < 0.02). The enhanced production of ROS in the irradiated nanoparticles suggests the potential for additional therapeutic dose enhancements in radiation treatment via the potent Gd-Gd interatomic de-excitation-driven nanoradiator effect.


Assuntos
Gadolínio/química , Gadolínio/efeitos da radiação , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Espécies Reativas de Oxigênio/síntese química , Espécies Reativas de Oxigênio/efeitos da radiação , Meios de Contraste/química , Meios de Contraste/efeitos da radiação , Relação Dose-Resposta à Radiação , Transferência Linear de Energia/efeitos da radiação , Teste de Materiais , Nanopartículas Metálicas/ultraestrutura , Prótons , Doses de Radiação , Espalhamento de Radiação , Raios X
8.
Acta Neurochir (Wien) ; 157(10): 1801-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26266880

RESUMO

Too few cases of isolated abducent nerve palsy caused by neurovascular compression syndrome have been reported. We here report on a case of abducent nerve palsy caused by neurovascular compression syndrome that was successfully treated by microvascular decompression (MVD). A 46-year-old male presented with a 6-month history of right-sided persistent abducent nerve palsy. High-resolution magnetic resonance imaging revealed a neurovascular contact of the vertebral artery with the right abducent nerve. MVD was performed via a retrosigmoid craniotomy, with remarkable improvement of the palsy. Our report suggests that MVD might be considered as an optional treatment if the symptoms progress or persist.


Assuntos
Doenças do Nervo Abducente/cirurgia , Cirurgia de Descompressão Microvascular , Doenças do Nervo Abducente/patologia , Humanos , Masculino , Pessoa de Meia-Idade
9.
Surg Neurol Int ; 15: 289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246768

RESUMO

Background: Neurofibromatosis type 1 (NF-1) is often characterized by vascular disorders related to vessel vulnerability that can lead to unfavorable outcomes. Here, we describe a case of NF-1 complicated with a massive subcutaneous hematoma posing a risk of visual impairment for which rapid decompression and a subsequent less invasive approach result in a favorable outcome. Case Description: A 40-year-old woman with NF-1 presented with a massive left subcutaneous temporal hematoma following a mild head contusion. Four days after hospitalization, the hematoma increased in size and severely compressed the left eye, prompting immediate hematoma removal to preserve visual function. Immediately after the hematoma removal, a superficial temporal arteriovenous fistula was found on the digital subtraction angiography and embolized by the endovascular procedure. Her visual acuity was preserved, and no bleeding recurrence was observed throughout the follow-up. Conclusion: Surgical hematoma removal followed by endovascular treatment was effective in preserving visual function. Since vessel fragility is characteristic of patients with NF-1, it should be kept in mind that vascular complications may lead to serious clinical outcomes. In certain NF-1 cases, less invasive treatments for vascular abnormalities may be preferable.

10.
World Neurosurg ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39116940

RESUMO

BACKGROUND: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG. METHODS: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up. CONCLUSIONS: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy.

11.
Pharmaceutics ; 16(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931918

RESUMO

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.

12.
Surg Neurol Int ; 14: 366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941640

RESUMO

Background: Intracranial germinomas are rare tumors, accounting for 0.5-2% of primary intracranial neoplasms. While they typically occur in the pineal gland, suprasellar region, basal ganglia, and thalamus, germinomas arising in the medulla oblongata are exceptionally rare. Diagnosis of medulla oblongata germinoma is challenging, potentially leading to misdiagnosis and poor prognosis. Case Description: We present a case of a 29-year-old man complaining of left leg numbness. Radiological findings revealed a contrast-enhanced lesion in the medulla oblongata. The patient underwent tumor biopsy, and intraoperative pathological diagnosis (IOD) suspected the diagnosis of medulla oblongata germinoma. He underwent chemoradiotherapy after confirming the diagnosis of germinoma. Intracranial germinoma arising in the medulla oblongata differs from germinomas in other locations due to its higher incidence in individuals in their 20s and a slight female predominance. Conclusion: When encountering lesions in the medulla oblongata, germinoma should be considered as one of the differential diagnoses, and surgical strategies including IOD should be planned accordingly.

13.
Vet Sci ; 10(4)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37104429

RESUMO

We conducted a clinical veterinary study on neutron capture therapy (NCT) at a neutron-producing accelerator with seven incurable pets with spontaneous tumors and gadolinium as a neutron capture agent (gadolinium neutron capture therapy, or GdNCT). Gadolinium-containing dimeglumine gadopentetate, or Gd-DTPA (Magnevist®, 0.6 mL/kg b.w.), was used. We observed mild and reversible toxicity related to the treatment. However, no significant tumor regression in response to the treatment was observed. In most cases, there was continued tumor growth. Overall clinical improvement after treatment was only temporary. The use of Gd-DTPA for NCT had no significant effects on the life expectancy and quality of life of animals with spontaneous tumors. Further experiments using more advanced gadolinium compounds are needed to improve the effect of GdNCT so that it can become an alternative to boron neutron capture therapy. Such studies are also necessary for further NCT implementation in clinical practice as well as in veterinary medicine.

14.
Bioengineering (Basel) ; 10(7)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37508895

RESUMO

In myoelectrical pattern recognition (PR), the feature extraction methods for stroke-oriented applications are challenging and remain discordant due to a lack of hemiplegic data and limited knowledge of skeletomuscular function. Additionally, technical and clinical barriers create the need for robust, subject-independent feature generation while using supervised learning (SL). To the best of our knowledge, we are the first study to investigate the brute-force analysis of individual and combinational feature vectors for acute stroke gesture recognition using surface electromyography (EMG) of 19 patients. Moreover, post-brute-force singular vectors were concatenated via a Fibonacci-like spiral net ranking as a novel, broadly applicable concept for feature selection. This semi-brute-force navigated amalgamation in linkage (SNAiL) of EMG features revealed an explicit classification rate performance advantage of 10-17% compared to canonical feature sets, which can drastically extend PR capabilities in biosignal processing.

15.
NMC Case Rep J ; 10: 337-342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125931

RESUMO

Cavernous sinus hemangioma (CSH) is a rare vascular malformation, arising from the cavernous sinus. Because of its anatomically complex location, a large lesion can cause a variety of symptoms due to cranial nerve compression. A 69-year-old woman with an unsteady gait was admitted to our hospital, and magnetic resonance imaging revealed an extra-axial giant tumor in the cavernous sinus and enlarged ventricles. A radiographic diagnosis of CSH was made. As the risk of surgical removal was considered high, the patient underwent intensity-modulated radiation therapy of 50.4 Gy in 28 fractions. The size of the tumor decreased markedly over time, and the symptoms improved soon after treatment. A 61.8% reduction in tumor size was confirmed immediately after irradiation, and a 75.9% reduction was revealed at a follow-up visit one year later. We reported a case of a giant CSH with hydrocephalus, where tumor shrinkage was confirmed immediately after radiation therapy, and the symptoms of hydrocephalus improved without surgical intervention.

16.
Biology (Basel) ; 11(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35053138

RESUMO

(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

17.
Cureus ; 14(5): e24894, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35698711

RESUMO

Background Brain tumor patients tend to develop postoperative epileptic seizures, which can lead to an unfavorable outcome. Although the incidence of postoperative epileptic seizures and adverse events are improved with the advent of levetiracetam (LEV), postoperative epilepsy occurs at a frequency of 4.6% or higher. In brain tumor patients, the addition of sodium channel blockers (SCBs) to LEV significantly reduces seizures, though confirmed in a non-postoperative study. Thus, the combination of SCBs with LEV might be promising. Objective In this prospective randomized controlled trial we investigated the safety, evaluated by adverse events during one and two weeks after surgery, and the efficacy, evaluated by the incidence of early epilepsy, including non-convulsive status epilepticus (NCSE), of using LEV alone or SCBs added to LEV in patients who underwent craniotomy or biopsy for brain tumors or brain mass lesions. Methods Patients with brain tumors or brain mass lesions undergoing surgical interventions, excluding endoscopic endonasal surgery (EES), with a diagnosis of epilepsy were eligible for this study. Patients are randomized into either Group A or B (B1 or B2) after the informed consents are taken; LEV alone in Group A patients, while LEV and SCBs in Group B patients (GroupB1, intravenous fosphenytoin plus oral lacosamide (LCM) and GroupB2, intravenous LCM plus oral LCM) were administered postoperatively. Fifty-three patients were enrolled during the first two and a half years of the study and four of them were excluded, resulting in the accumulation of 49 patients' data. Results Postoperative epileptic seizures occurred only in three out of 49 patients during the first week (6.1%) and in seven patients within two weeks after surgery (14.3%, including the three patients during the first week). In Group A, epileptic seizures occurred in two out of 26 patients during the first week (7.7%) and in five patients within two weeks (19.2%) after surgery. In Group B, epileptic seizures occurred in one out of 23 patients during the first week (4.3%) and in two patients during the first two weeks (8.7%). Low complication grade of epileptic seizures was observed in Group B rather than in Group A, however, without significant difference (p=0.256). There was no difference in the frequency of adverse effects in each group. Conclusion Although not statistically significant, the incidence of epileptic seizures within one week after surgery was lesser in LEV+SCBs groups than in LEV alone. No hepatic damage or renal function worsening occurred with the addition of LCM, suggesting the safety of LEV+SCBs therapy.

18.
Pharmaceutics ; 14(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35456595

RESUMO

Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments.

19.
Pharmaceutics ; 14(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35056988

RESUMO

Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently being developed to control airway inflammation and prevent exacerbations and fibrosis. These medications are delivered through mechanical methods, with various inhalers (with benefits and drawbacks) existing, and new types offering some variety in delivery. Of particular interest is the progress being made in nanosized materials for efficient penetration into the epithelial mucus layer and delivery into the deepest parts of the lungs. Liposomes, nanoparticles, and extracellular vesicles, both natural and synthetic, have been explored in animal models of asthma and have produced promising results. This review will summarize and synthesize the latest developments in both macro-(inhaler) and micro-sized delivery systems for the purpose of treating asthma patients.

20.
Biology (Basel) ; 10(11)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34827117

RESUMO

(1) Background: Developments in accelerator-based neutron sources moved boron neutron capture therapy (BNCT) to the next phase, where new neutron radiation parameters had to be studied for the treatment of cancers, including brain tumors. We aimed to further improve accelerator-BNCT efficacy by optimizing dosimetry control, beam parameters, and combinations of boronophenylalanine (BPA) and sodium borocaptate (BSH) administration in U87MG xenograft-bearing immunodeficient mice with two different tumor locations. (2) Methods: The study included two sets of experiments. In Experiment #1, BPA only and single or double irradiation in higher doses were used, while, in Experiment #2, BPA and BSH combinations and single or double irradiation with dosage adjustment were analyzed. Mice without treatment or irradiation after BPA or BPA+BSH injection were used as controls. (3) Results: Irradiation parameter adjustment and BPA and BSH combination led to 80-83% tumor-growth inhibition index scores, irradiation:BNCT ratios of 1:2, and increases in animal life expectancy from 9 to 107 days. (4) Conclusions: Adjustments in dosimetry control, calculation of irradiation doses, and combined use of two 10B compounds allowed for BNCT optimization that will be useful in the development of clinical-trial protocols for accelerator-based BNCT.

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