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1.
Proc Natl Acad Sci U S A ; 119(26): e2202912119, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35727967

RESUMO

VEGF was initially discovered due to its angiogenic activity and therefore named "vascular endothelial growth factor." However, its more recently discovered neurotrophic activity may be evolutionarily more ancient. Our previous work showed that all the changes produced by axotomy on the firing activity and synaptic inputs of abducens motoneurons were completely restored after VEGF administration. Therefore, we hypothesized that the lack of VEGF delivered by retrograde transport from the periphery should also affect the physiology of otherwise intact abducens motoneurons. For VEGF retrograde blockade, we chronically applied a neutralizing VEGF antibody to the lateral rectus muscle. Recordings of extracellular single-unit activity and eye movements were made in alert cats before and after the application of the neutralizing antibody. Our data revealed that intact, noninjured abducens motoneurons retrogradely deprived of VEGF exhibited noticeable changes in their firing pattern. There is a general decrease in firing rate and a significant reduction in eye position and eye velocity sensitivity (i.e., a decrease in the tonic and phasic components of their discharge, respectively). Moreover, by means of confocal immunocytochemistry, motoneurons under VEGF blockade showed a marked reduction in the density of afferent synaptic terminals contacting with their cell bodies. Altogether, the present findings demonstrate that the lack of retrogradely delivered VEGF renders abducens motoneurons into an axotomy-like state. This indicates that VEGF is an essential retrograde factor for motoneuronal synaptic drive and discharge activity.


Assuntos
Movimentos Oculares , Neurônios Motores , Terminações Pré-Sinápticas , Fator A de Crescimento do Endotélio Vascular , Animais , Anticorpos Neutralizantes , Axotomia , Gatos , Movimentos Oculares/efeitos dos fármacos , Movimentos Oculares/fisiologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/fisiologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/fisiologia
2.
Ophthalmology ; 128(12): 1766-1776, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34176652

RESUMO

PURPOSE: To review the available evidence comparing the effectiveness of extraocular muscle botulinum toxin type A (BTXA) injection with eye muscle surgery for restoring ocular alignment in children and adults with nonparalytic, nonrestrictive horizontal strabismus. METHODS: Literature searches in the PubMed Cochrane Library, and clinical trial databases with no date restrictions, but limited to articles published in English, were conducted last on January 10, 2021. The searches yielded 515 citations, 40 of which were reviewed in full text by the first author. Fourteen articles met the criteria for inclusion (randomized or nonrandomized comparative studies, or case series with a minimum 50 patients; evaluating extraocular muscle BTXA injection for initial or repeat treatment of horizontal, nonparalytic, nonrestrictive strabismus; with at least 6 months of follow-up) and were graded by a methodologist. RESULTS: The 14 included studies consisted of 2 randomized clinical trials, 3 nonrandomized comparative studies, and 9 case series. All 5 comparative studies were graded level II evidence, and the 9 case series were graded level III evidence. Successful motor outcomes after BTXA injection were relatively consistent across 4 of the 5 comparative studies at 60%, when adjustment was made for differential selection bias in 1 of the studies. In the 4 studies, successful motor outcomes after surgery ranged from 66% to 77% with a mean follow-up of 23 to 75 months, and the outcomes were not significantly different from those after BTXA injection. In the fifth level II study, success was significantly higher with BTXA injection than with surgery (94% vs. 72%). The level III BTXA case series demonstrated higher motor success rates of 87% to 89% when children were treated in 2 muscles at a time; rates were lower in adults treated with single-muscle BTXA injection. CONCLUSIONS: Extraocular muscle injection of BTXA achieves a high rate of successful motor alignment, comparable with that achieved after eye muscle surgery for nonparalytic, nonrestrictive horizontal strabismus. Good alignment may require multiple BTXA injections, and it is not yet clear whether sensory outcomes are equivalent for BTXA injections versus eye muscle surgery in young children.


Assuntos
Academias e Institutos , Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/administração & dosagem , Músculos Oculomotores/efeitos dos fármacos , Oftalmologia/organização & administração , Estrabismo/tratamento farmacológico , Pré-Escolar , Feminino , Humanos , Injeções Intramusculares , Masculino , Músculos Oculomotores/fisiopatologia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estrabismo/fisiopatologia , Estrabismo/cirurgia , Avaliação da Tecnologia Biomédica , Estados Unidos
3.
Clin Radiol ; 76(2): 159.e1-159.e8, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33010933

RESUMO

AIM: To evaluate the performance of T2 mapping histograms at the extraocular muscles (EOMs) in predicting the response to glucocorticoid therapy in the patients with active and moderate-severe thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Thirty active and moderate-severe TAO patients (responsive group, n=20; unresponsive group, n=10) were enrolled, and evaluated using T2 mapping before treatment. Histogram parameters (mean, median, max, min, 10th, 90th percentiles, skewness, and kurtosis) of T2 relaxation time (T2RT) at the EOMs for each orbit, and clinical variables (age, sex, disease duration, anti-thyroid treatment, smoking habit, pre-treatment thyroid function, thyrotrophin receptor antibody, diplopia presence, activity and severity scores) were collected and compared between groups. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to assess the predictive value of identified independent variables for treatment response. RESULTS: The responsive group showed significantly shorter disease duration (p=0.003), while higher T2RTmin than unresponsive group (p<0.001). Multivariate analysis showed that T2RTmin and disease duration were independent predictors for responsive TAOs. ROC curve analyses indicated that setting a cut-off value of ≥54.3 for T2RTmin demonstrated the optimal predicting specificity for responsive TAOs (100%), while a combination of T2RTmin ≥54.3 and disease duration ≤4.5 showed optimal predicting efficiency and sensitivity (area under the curve, 0.820; sensitivity, 65%). CONCLUSIONS: Histogram analysis can help to exhibit the heterogeneity of T2RT at the EOMs. T2RTmin, together with disease duration may be the promising marker for predicting response to glucocorticoid therapy in the patients with active and moderate-severe TAO.


Assuntos
Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/diagnóstico por imagem , Oftalmopatia de Graves/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Ophthalmic Res ; 64(2): 337-344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32344402

RESUMO

INTRODUCTION: Paralytic strabismus involves a functional loss of extraocular muscles resulting from muscular or neuronal disorders. Currently, only a limited number of drugs are available for functional repair of extraocular muscles. Here, we investigated the effects of a novel drug, flavonoids sophoranone, on the differentiation of extraocular muscles as assessed in bothin vivo and in vitro models. MATERIALS AND METHODS: The effect of flavonoids sophoranone on C2C12 cells was examinedin vitro as evaluated with use of apoptosis, reactive oxygen species (ROS), and cell viability assays. Then, both in vivo and in vitro effects of this drug were examined on the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits. For these latter experiments, RT-PCR and Western blot assays were used to determine expression levels of markers for myogenic differentiation. RESULTS: With use of flavonoids sophoranone concentrations ranging from 0 to 10 µM, no effects were observed upon cell apoptosis, ROS, and cell cycle in C2C12 cells. Based on MTT assay results, flavonoids sophoranone was shown to increase C2C12 cell proliferation. Moreover, flavonoids sophoranone promoted the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits, which were verified as based on cell morphology and expression levels of mRNA and protein markers of myogenic differentiation. Finally, flavonoids sophoranone treatment also increased gene expressions of Myh3, Myog, and MCK. CONCLUSION: The capacity for flavonoids sophoranone to upgrade the differentiation of both C2C12 and satellite cells within extraocular muscles in rabbits at concentrations producing no adverse effects suggest that this drug may provide a safe and effective means to promote repair of damaged extraocular muscles.


Assuntos
Apoptose , Flavonoides/farmacologia , Desenvolvimento Muscular/genética , Mioblastos/efeitos dos fármacos , Músculos Oculomotores/citologia , Animais , Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais , Mioblastos/citologia , Mioblastos/metabolismo , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/metabolismo , Coelhos , Espécies Reativas de Oxigênio/metabolismo
5.
Int J Neurosci ; 131(6): 549-554, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32233985

RESUMO

AIM: The aim of the present study was to evaluate the effects of different doses of onabotulinum toxin A on the amplitude and latency values of the blink reflex and facial nerve in the pretarsal and preseptal portions of the orbicularis oculi muscle in patients with hemifacial spasm. MATERIALS AND METHODS: Thirty patients with hemifacial spasm were assigned in two equal groups: Pretarsal Group: Five units of onabotulinum toxin A were injected into each of 2 points of the pretarsal portion; Preseptal Group: Five units of onabotulinum toxin A was injected into 4 points of the preseptal portion. We compared the electromyographic features of the patients before and 5 weeks after botulinum toxin (BTX) injection. RESULTS: In comparison of pre- and post-treatment measurements of blink reflex amplitude responses, the decreases in R1 (p = 0.003), R2 (p < 0.001), and R2C amplitudes (p = 0.031) were found to be significant in the BTX injected side in the pretarsal group. In the comparison of pre- and post-treatment measurements of facial nerve compound action potential amplitude changes, decreases in the amplitudes of the BTX injected (ipsilateral), and uninjected (contralateral) side in the pretarsal group were found to be significant (p < 0.001 for both groups). Decreases in the amplitudes of the BTX injected, and uninjected side in the preseptal group were found to be significant (p < 0.001, and p = 0.008, respectively). CONCLUSION: According to our hypothesis, the smaller amount of BTX applied to the pretarsal portion was found to be more effective than higher amount of BTX injected into the preseptal portion of the orbicularis oculi muscle.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Espasmo Hemifacial/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Músculos Oculomotores/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Piscadela/efeitos dos fármacos , Eletromiografia/efeitos dos fármacos , Pálpebras/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
6.
Anesth Analg ; 130(5): 1351-1363, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30676353

RESUMO

Ophthalmic pediatric regional anesthesia has been widely described, but infrequently used. This review summarizes the available evidence supporting the use of conduction anesthesia in pediatric ophthalmic surgery. Key anatomic differences in axial length, intraocular pressure, and available orbital space between young children and adults impact conduct of ophthalmic regional anesthesia. The eye is near adult size at birth and completes its growth rapidly while the orbit does not. This results in significantly diminished extraocular orbital volumes for local anesthetic deposition. Needle-based blocks are categorized by relation of the needle to the extraocular muscle cone (ie, intraconal or extraconal) and in the cannula-based block, by description of the potential space deep to the Tenon capsule. In children, blocks are placed after induction of anesthesia by a pediatric anesthesiologist or ophthalmologist, via anatomic landmarks or under ultrasonography. Ocular conduction anesthesia confers several advantages for eye surgery including analgesia, akinesia, ablation of the oculocardiac reflex, and reduction of postoperative nausea and vomiting. Short (16 mm), blunt-tip needles are preferred because of altered globe-to-orbit ratios in children. Soft-tip cannulae of varying length have been demonstrated as safe in sub-Tenon blockade. Ultrasound technology facilitates direct, real-time visualization of needle position and local anesthetic spread and reduces inadvertent intraconal needle placement. The developing eye is vulnerable to thermal and mechanical insults, so ocular-rated transducers are mandated. The adjuvant hyaluronidase improves ocular akinesia, decreases local anesthetic dosage requirements, and improves initial block success; meanwhile, dexmedetomidine increases local anesthetic potency and prolongs duration of analgesia without an increase in adverse events. Intraconal blockade is a relative contraindication in neonates and infants, retinoblastoma surgery, and in the presence of posterior staphylomas and buphthalmos. Specific considerations include pertinent pediatric ophthalmologic topics, block placement in the syndromic child, and potential adverse effects associated with each technique. Recommendations based on our experience at a busy academic ophthalmologic tertiary referral center are provided.


Assuntos
Anestesia por Condução/métodos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Pediatria/métodos , Anestesia por Condução/instrumentação , Anestésicos Locais/administração & dosagem , Criança , Pré-Escolar , Humanos , Lactente , Músculos Oculomotores/anatomia & histologia , Músculos Oculomotores/efeitos dos fármacos , Procedimentos Cirúrgicos Oftalmológicos/instrumentação , Pediatria/instrumentação
7.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1287-1292, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32103334

RESUMO

PURPOSE: To examine the influence of epinephrine contained in local anesthetic on upper eyelid height in transconjunctival aponeurotic repair for aponeurotic blepharoptosis. METHODS: This retrospective study included 164 eyelids from 94 patients with aponeurotic blepharoptosis. Patients were divided according to the use of local anesthetic with (group A, n = 108) or without 1:100000 epinephrine (group B, n = 56). Margin reflex distance-1 (MRD-1) was measured before and after local anesthesia, and before, during, and 3 months after surgery. Change in MRD-1a (∆MRD-1a) was calculated by subtracting the postanesthetic MRD-1 value from the preanesthetic value, and we defined ∆MRD-1b by subtracting the postoperative 3-month MRD-1 value from the intraoperative value. RESULTS: ∆MRD-1a was positive in group A (0.57 ± 0.63 mm) and negative in group B (- 0.50 ± 0.45 mm; p < 0.001). Postoperative MRD-1 decreased significantly from intraoperative MRD-1 in group A (P < 0.001), although there was no significant difference between intraoperative and postoperative MRD-1 in group B (p = 0.255). The magnitude of ∆MRD-1b in group A (- 0.86 ± 0.63) was larger than that in group B (- 0.23 ± 0.26; p < 0.001). CONCLUSIONS: Epinephrine stimulates Müller's muscle during surgery, which leads to postoperative upper eyelid droop after the disappearance of the epinephrine effect. Using local anesthetics without epinephrine may allow more accurate estimation of postoperative eyelid height in transconjunctival aponeurotic repair.


Assuntos
Anestésicos Locais/administração & dosagem , Aponeurose/cirurgia , Blefaroptose/cirurgia , Epinefrina/farmacologia , Pálpebras/patologia , Midriáticos/farmacologia , Músculos Oculomotores/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Blefaroplastia , Pálpebras/inervação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Graefes Arch Clin Exp Ophthalmol ; 258(5): 1081-1086, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32060728

RESUMO

PURPOSE: The purpose of the study is to analyze the incidence, manifestations, and treatment of blepharoptosis caused by long-term use of corticosteroid eyedrops. METHODS: Retrospective case series include 46 patients with a history of using corticosteroid eyedrops unilaterally for at least 2 months. The palpebral fissure, MRD1, and levator function were evaluated. RESULTS: Among 46 patients, the differences of mean MRD1 (p < 0.0005), palpebral fissure height (p < 0.0005), and levator function (p = 0.003) between eyes with and without corticosteroid eyedrops application were significant. Ptosis existed in 40 out of 46 eyes with corticosteroid; the differences of the mean MRD1 (p < 0.0005) and palpebral fissure height (p = 0.001) between eyes with and without ptosis were significant. Nine patients underwent levator aponeurosis repair surgeries. Pathological examinations revealed mainly vascular fibers and few muscle fibers, as well as apoptosis of levator palpebrae muscle and Muller muscle. CONCLUSION: Blepharoptosis is frequently observed after chronic corticosteroid eyedrops use in Chinese population.


Assuntos
Blefaroptose/induzido quimicamente , Glucocorticoides/efeitos adversos , Atrofia Muscular/induzido quimicamente , Músculos Oculomotores/efeitos dos fármacos , Administração Oftálmica , Adolescente , Adulto , Idoso , Blefaroplastia , Blefaroptose/diagnóstico , Blefaroptose/cirurgia , Criança , Dexametasona/efeitos adversos , Feminino , Fluormetolona/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/diagnóstico , Atrofia Muscular/cirurgia , Músculos Oculomotores/patologia , Soluções Oftálmicas , Prednisolona/efeitos adversos , Prednisolona/análogos & derivados , Estudos Retrospectivos , Resultado do Tratamento
9.
BMC Anesthesiol ; 19(1): 36, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871507

RESUMO

BACKGROUND: The oculocardiac reflex (OCR), bradycardia that occurs during strabismus surgery is a type of trigemino-cardiac reflex (TCR) is blocked by anticholinergics and enhanced by opioids and dexmedetomidine. Two recent studies suggest that deeper inhalational anesthesia monitored by BIS protects against OCR; we wondered if our data correlated similarly. METHODS: In an ongoing, prospective study of OCR/TCR elicited by 10-s, 200 g square-wave traction on extraocular muscles (EOM) from 2009 to 2013, anesthetic depth was estimated in cohorts using either BIS or Narcotrend monitors. The depth of anesthesia was deliberately varied between first and second EOM tested. RESULTS: From 1992 through 2013, 2833 cases of OCR during strabismus surgery were monitored. Excluding re-operations and cases with anticholinergic, OCR from first EOM traction averaged - 20.2 ± 21.8% (S.D.) with a range from - 95 to + 25% in patients aged 0.2 to 90 (median 6.5) years. We did not find correlation between %OCR and brain wave for 97 patients with BIS monitoring and 91 with Narcotrend. With intra-patient controls between first and second muscle, the difference in brain wave did not correlate with difference in %OCR for BIS (r = 0.0002, 95% C. I -0.0002, 0.002, p = 0.30) or for Narcotrend (r = - 0.001, 95% C. I -0.004, 0.001, p = 0.32). Secondary multi-variable analysis demonstrated significant association on %OCR particularly with BIS monitor, opioid, propofol and nitrous oxide concentration in the second EOM tensioned. Sevoflurane concentration correlated better with BIS monitor in second and third EOM tension. %OCR correlated with younger age (p < 0.01). OCR with rapid onset was more profound than those with gradual onset (difference in means 18, 95% C. I 10, 26%). CONCLUSIONS: We were unable to confirm a direct correlation between brain wave monitor and OCR when using multifactorial anesthetic agents. The discrepency with other studies probably reflects direct impact of inhalational agent concentration and less deliberate quantification of EOM tension. We found no level of BIS or Entropy EEG monitoring that uniformly prevents OCR. TRIAL REGISTRY: NCT03663413. DATA: http://www.abcd-vision.org/OCR/OCR%20Brainwave%20de-identified.pdf .


Assuntos
Anestésicos Inalatórios/administração & dosagem , Ondas Encefálicas/efeitos dos fármacos , Reflexo Oculocardíaco/efeitos dos fármacos , Estrabismo/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Inalatórios/farmacologia , Bradicardia/epidemiologia , Bradicardia/etiologia , Criança , Pré-Escolar , Monitores de Consciência , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/efeitos dos fármacos , Estudos Prospectivos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia , Adulto Jovem
10.
Orbit ; 38(6): 511-513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30688154

RESUMO

Oculopharyngeal Muscular Dystrophy (OPMD) is a systemic progressive autosomal dominant myopathy which results in ptosis due to levator weakness. Surgical correction can be complicated by corneal exposure and a non-surgical alternative, such as ptosis props, can be uncomfortable in patients with preserved orbicularis function. We describe a case of a 57-year-old gentleman with OPMD, who declined surgical intervention, and self-manages his ptosis with cosmetic glue.


Assuntos
Blefaroptose/tratamento farmacológico , Distrofia Muscular Oculofaríngea/tratamento farmacológico , Músculos Oculomotores/efeitos dos fármacos , Adesivos Teciduais/uso terapêutico , Técnicas Cosméticas , Humanos , Masculino , Pessoa de Meia-Idade
11.
Biochem Biophys Res Commun ; 496(4): 1376-1381, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29421653

RESUMO

In active thyroid eye disease (TED), the extraocular muscles feature excessive hyaluronan (HA) accumulation and increased fibroblast proliferation. To investigate the effects of HA on proliferation, we cultured perimysial fibroblasts from extraocular muscles of active TED patients, and adopted IGF-1 and PH20 as modulators for HA concentration and HA polymer size. Based on the results, IGF-1 increased HA concentration, promoted high molecular weight HA (HMW-HA) proportion and stimulated fibroblast proliferation. Hyaluronidase PH20 decreased HA concentration, but caused HMW-HA accumulation and exaggerating proliferation as well. Combined treatment with both reagents resulted in retention of low molecular weight HA (LMW-HA), and suppressed fibroblast proliferation. Pearson correlation demonstrated no significance between HA concentration and proliferation. Mitogenic investigation unveiled the stimulatory effects of HMW-HA via membrane depolarization and inhibitive effects of LMW-HA via membrane hyperpolarization. Our findings offer insights into the essential role of HA molecular weight during TED pathogenesis.


Assuntos
Moléculas de Adesão Celular/administração & dosagem , Fibroblastos/patologia , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/metabolismo , Ácido Hialurônico/metabolismo , Hialuronoglucosaminidase/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Músculos Oculomotores/patologia , Adulto , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/efeitos dos fármacos , Oftalmopatia de Graves/patologia , Humanos , Ácido Hialurônico/química , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/efeitos dos fármacos , Tamanho da Partícula , Relação Estrutura-Atividade
12.
Exp Eye Res ; 171: 62-67, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29530812

RESUMO

To determine the changes in the cross-sectional area (CSA) of myofibers and their subtype distribution based on the myosin isoform expression after bupivacaine (BUP) injection in the EOM of rabbits and help the understanding of strabismus correction after BUP injection in the clinical practice. A total of 32 rabbits received 0.3 mL of 1.5% BUP in the superior rectus muscle (SR) of the right eye (OD) and were sacrificed at days 7, 28, 60, and 92. Additional eight untouched rabbits were included as controls. Hematoxylin and eosin staining was performed, and ImageJ software was used to measure CSA. Immunohistochemical analysis was performed to analyze the proportion of myofibers positive for myosin types 1 (slow), 2 (fast) and embryonic. Myofiber area measurement decreased 7 days after BUP injection [SR, 1271 ±â€¯412 µm2 (control) to 909 ±â€¯255 µm2 (day 7)] after BUP injection, followed by an increasing trend after 28 days and normalization after 92 days [SR; 1062 ±â€¯363 µm2 (day 28), 1492 ±â€¯404 µm2 (day 60), 1317 ±â€¯334 µm2 (day 92)]. The proportion of slow myosin-positive fibers increased in the 60-day group (88.5% ±â€¯16.2%). There was no statistically significant difference in fast myosin-positive fibers. The inferior rectus of both eyes showed an increase in CSA. No increase of endomysial fibrous tissue was observed after 60 and 92 days of BUP injection. Bupivacaine, when injected into the SR of rabbits, initially decreases the fiber area followed by a transient increasing trend and normalization. There is a transient increase in the proportion of slow myosin-positive fibers in the injected muscle. Muscle adaptation in untreated EOM was found with increased CSA. These findings help clarify the clinical effects of BUP in extraocular muscle.


Assuntos
Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/patologia , Animais , Colágeno/metabolismo , Imuno-Histoquímica , Injeções Intramusculares , Masculino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Miosina Tipo I/metabolismo , Miosina Tipo II/metabolismo , Músculos Oculomotores/metabolismo , Isoformas de Proteínas/metabolismo , Coelhos
13.
Exp Cell Res ; 361(1): 101-111, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29017757

RESUMO

One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7. EOM-derived and LEG-derived EECD34 cells were treated with vehicle, retinoic acid, the RXR agonist bexarotene, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG-derived cells expressed desmin and fused when treated with retinoic acid compared to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We hypothesize that retinoic acid signaling aids in the maintenance of large numbers of undifferentiated myogenic precursor cells in the EOM, which would be required to maintain EOM normalcy throughout a lifetime of myonuclear turnover.


Assuntos
Desenvolvimento Muscular/fisiologia , Músculo Esquelético/citologia , Mioblastos/citologia , Músculos Oculomotores/citologia , Receptores X de Retinoides/metabolismo , Tretinoína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas de Homeodomínio/metabolismo , Técnicas In Vitro , Ceratolíticos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/metabolismo , Fator de Transcrição PAX7/metabolismo , Fatores de Transcrição/metabolismo , Proteína Homeobox PITX2
14.
Ann Vasc Surg ; 49: 313.e1-313.e3, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29455019

RESUMO

The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism (VTE). A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary. The mechanism of MG development by rivaroxaban therapy is not completely understood. The development of rivaroxaban-induced autoimmune disease could be based on cross-reactivity between antibodies against rivaroxaban-derived antigens or by T-cell activation. To our knowledge, this report of ocular myasthenia by rivaroxaban administration is the first in the literature. Despite the benefits of rivaroxaban, it is important to recognize unexpected immune-related adverse events.


Assuntos
Inibidores do Fator Xa/efeitos adversos , Miastenia Gravis/induzido quimicamente , Músculos Oculomotores/efeitos dos fármacos , Rivaroxabana/efeitos adversos , Trombose Venosa/tratamento farmacológico , Acenocumarol/uso terapêutico , Administração Oral , Anticoagulantes/uso terapêutico , Autoanticorpos/sangue , Biomarcadores/sangue , Blefaroptose/induzido quimicamente , Blefaroptose/fisiopatologia , Inibidores da Colinesterase/administração & dosagem , Substituição de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/fisiopatologia , Músculos Oculomotores/fisiopatologia , Brometo de Piridostigmina/administração & dosagem , Receptores Colinérgicos/imunologia , Resultado do Tratamento , Trombose Venosa/diagnóstico
15.
Orbit ; 37(5): 325-330, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29319381

RESUMO

AIM: To examine the novel use of non-echo-planar diffusion weighted MRI (DWI) in depicting activity and treatment response in active Grave's orbitopathy (GO) by assessing, with inter-observer agreement, for a correlation between its apparent diffusion coefficients (ADCs) and conventional Short tau Inversion Recovery (STIR) MRI signal-intensity ratios (SIRs). METHOD AND MATERIALS: A total of 23 actively inflamed muscles and 30 muscle response episodes were analysed in patients with active GO who underwent medical treatment. The MRI orbit scans included STIR sequences and non-echo-planar DWI were evaluated. Two observers independently assessed the images qualitatively for the presence of activity in the extraocular muscles (EOMs) and recorded the STIR signal-intensity (SI), SIR (SI ratio of EOM/temporalis muscle), and ADC values of any actively inflamed muscle on the pre-treatment scans and their corresponding values on the subsequent post-treatment scans. Inter-observer agreement was examined. RESULTS: There was a significant positive correlation (0.57, p < 0.001) between ADC and both SIR and STIR SI of the actively inflamed EOM. There was also a significant positive correlation (0.75, p < 0.001) between SIR and ADC values depicting change in muscle activity associated with treatment response. There was good inter-observer agreement. CONCLUSION: Our preliminary results indicate that quantitative evaluation with non-echo-planar DWI ADC values correlates well with conventional STIR SIR in detecting active GO and monitoring its treatment response, with good inter-observer agreement.


Assuntos
Imagem de Difusão por Ressonância Magnética , Oftalmopatia de Graves/diagnóstico por imagem , Músculos Oculomotores/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Feminino , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/fisiopatologia , Humanos , Infusões Intravenosas , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Monitorização Fisiológica , Variações Dependentes do Observador , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/fisiopatologia , Órbita/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem
16.
Orbit ; 37(5): 381-384, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29381409

RESUMO

Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been used successfully for treatment of metastatic melanoma. Ipilimumab is a human monoclonal antibody against Cytotoxic T Lymphocyte Antigen 4 (CTLA4) receptor, which suppresses T-cell proliferation and stimulates an inflammatory response against cancer cells. Nivolumab is an IgG4 monoclonal antibody against the cytotoxic T lymphocyte associated programmed death 1 receptor (PD-1). Ipilimumab and Nivolumab combination treatment has been shown to induce remission and prolong survival in patients with metastatic melanoma. The side effect profile of these medications has not been well studied. One entity of the side effects reported in the literature is immune-related adverse events (irAEs). There have been few case reports where these events were serious and irreversible. In this case report, we describe a fatal and severe diffuse panmyositis that involved the cardiac, respiratory, and extraocular muscles in a patient with metastatic melanoma secondary to combination treatment with Ipilimumab/Nivolumab.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ipilimumab/efeitos adversos , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Músculos Oculomotores/efeitos dos fármacos , Oftalmoplegia/induzido quimicamente , Idoso , Evolução Fatal , Humanos , Masculino , Melanoma/secundário , Músculos Oculomotores/diagnóstico por imagem , Oftalmoplegia/diagnóstico por imagem , Órbita/diagnóstico por imagem , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X
17.
Curr Opin Ophthalmol ; 28(5): 460-464, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28650877

RESUMO

PURPOSE OF REVIEW: The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. RECENT FINDINGS: Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. SUMMARY: Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Estrabismo/tratamento farmacológico , Criança , Movimentos Oculares , Humanos , Injeções , Fármacos Neuromusculares/administração & dosagem , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/fisiopatologia
18.
Ophthalmic Plast Reconstr Surg ; 33(3S Suppl 1): S9-S11, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-25906333

RESUMO

A 66-year-old female presented for evaluation of progressively worsening edema and palpable masses in both lower eyelids. While she denied prior filler to the lower eyelid or tear trough, histopathology revealed degenerating striated muscle surrounding pools of hyaluronic acid. While cases of gradually enlarging masses associated with facial filler placement have been reported, there is no literature identifying muscle degeneration adjacent to hyaluronic acid filler.


Assuntos
Técnicas Cosméticas/efeitos adversos , Doenças Palpebrais/induzido quimicamente , Pálpebras/patologia , Ácido Hialurônico/efeitos adversos , Músculos Oculomotores/patologia , Idoso , Biópsia , Doenças Palpebrais/diagnóstico , Pálpebras/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Subcutâneas , Músculos Oculomotores/efeitos dos fármacos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Viscossuplementos/administração & dosagem , Viscossuplementos/efeitos adversos
19.
Nervenarzt ; 88(4): 415-418, 2017 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-28005144

RESUMO

Ocular myositis is a rare disease characterized by painful diplopia but loss of vision rarely occurs. The article reviews the literature focusing on the differential diagnostics. We report the case of an 80-year-old women suffering from slowly progressive loss of vision in the left eye. Diplopia was only present at the beginning and there was only moderate pain. Computed tomography and magnetic resonance imaging revealed a swelling of the left medial, lateral and inferior rectus muscles of the orbit leading to compression of the optic nerve in the orbital cone. An intravenous prednisolone stoss therapy (1000 mg per day for 3 consecutive days) was initiated, followed by oral medication of 100 mg per day then tapering over 10 weeks. Vision improved and no relapses were observed. Physicians should be aware of this rare disease to ensure quick diagnosis and treatment of ocular myositis.


Assuntos
Cegueira/etiologia , Miosite/complicações , Miosite/tratamento farmacológico , Músculos Oculomotores/efeitos dos fármacos , Doenças Orbitárias/complicações , Doenças Orbitárias/tratamento farmacológico , Prednisolona/administração & dosagem , Administração Oral , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Cegueira/diagnóstico , Cegueira/prevenção & controle , Diagnóstico Diferencial , Feminino , Humanos , Injeções Intravenosas , Miosite/diagnóstico , Músculos Oculomotores/patologia , Doenças Orbitárias/diagnóstico , Doenças Raras , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-25811162

RESUMO

PURPOSE: To determine the current practice pattern of ASOPRS members injecting onabotulinumtoxinA for Blepharospasm. METHODS: An invitation to participate in a web-based, anonymous survey was sent to current members of American Society of Ophthalmic Plastic and Reconstructive Surgeons (ASOPRS) via e-mail. The survey consisted of 9 questions and used the Research Electronic Data Capture online application. Institutional Review board approval was obtained for this study. RESULTS: Forty-one percent of ASOPRS members invited responded to the survey. The mean initial dose of onabotulinumtoxinA used was 22.5 units per side and the most common number of injection sites was greater than 7 per side. Only 12 of the 247 responding surgeons who treat benign essential blepharospasm with onabotulinumtoxinA reported that their initial injection pattern is with 3 or fewer sites per side as per the Food and Drug Administration (FDA)-approved recommendations. CONCLUSIONS: Survey of current trends in the management of blepharospasm with onabotulinumtoxinA by ASOPRS members showed that the mean initial dose used to treat blepharospasm patients was 22.5 (standard deviation ± 9.5 units, range 2.5 to 50 units per side). There is significant variation in the treatment doses. The majority of ASOPRS members do not follow the FDA-approved recommendation for dosing.


Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Músculos Oculomotores/efeitos dos fármacos , Padrões de Prática Médica , Adulto , Blefarospasmo/fisiopatologia , Inquéritos Epidemiológicos , Humanos , Injeções Intramusculares , Oftalmologia/organização & administração , Sociedades Médicas/organização & administração , Cirurgia Plástica/organização & administração , Inquéritos e Questionários
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