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1.
Mil Med ; 188(Suppl 6): 328-333, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37948268

RESUMO

PURPOSE: Orbital compartment syndrome (OCS) is an ocular emergency requiring prompt decompression with a lateral canthotomy and cantholysis (LCC) within 2 hours. This study evaluates the feasibility and effectiveness of a standardized LCC curriculum to train medical students to identify and treat OCS. METHODS: This was a prospective, non-randomized, non-comparative cohort study of 39 novice first-year medical students with no prior LCC training who underwent a standardized LCC curriculum incorporating both didactic and hands-on procedural training. Didactic knowledge of orbital anatomy and OCS was evaluated with written pre- and post-knowledge testing. Expert performance criteria were determined by expert consensus based on the performance of three oculoplastic surgeons and were defined as correctly performing all 12 critical checklist steps of an LCC within 3 minutes twice consecutively on a Sonalyst LCC training system eye model. Utilizing the principles of mastery learning, participants learned how to perform an LCC in a classroom environment and were evaluated on a final test of proficiency in a training lane designed to simulate an austere military environment. RESULTS: Participants required a median of 3.0 practice iterations to achieve expert performance in the classroom environment. During the testing phase, all participants correctly identified the eye with OCS, and 77% (n = 30) of learners successfully performed an LCC at the expert level within their first attempt. The median completion time of those who passed on their first testing was 130 seconds. The mean LCC knowledge test scores significantly improved from 48.7% to 71.2% (P < .001). CONCLUSION: This study successfully developed a standardized LCC curriculum utilizing the principles of hands-on mastery learning to train novice learners to perform an LCC efficiently and effectively.


Assuntos
Síndromes Compartimentais , Estudantes de Medicina , Humanos , Estudos Prospectivos , Estudos de Coortes , Currículo , Aprendizagem , Síndromes Compartimentais/cirurgia , Competência Clínica
2.
J Microsc ; 291(1): 119-127, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36542368

RESUMO

Cannabis glandular trichomes produce and store an abundance of lipidic specialised metabolites (e.g. cannabinoids and terpenes) that are consumed by humans for medicinal and recreational purposes. Due to a lack of genetic resources and inherent autofluorescence of cannabis glandular trichomes, our knowledge of cannabinoid trafficking and secretion is limited to transmission electron microscopy (TEM). Advances in cryofixation methods has resulted in ultrastructural observations closer to the 'natural state' of the living cell, and recent reports of cryofixed cannabis trichome ultrastructure challenge the long-standing model of cannabinoid trafficking proposed by ultrastructural reports using chemically fixed samples. Here, we compare the ultrastructural morphology of cannabis glandular trichomes preserved using conventional chemical fixation and ultrarapid cryofixation. We show that chemical fixation results in amorphous metabolite inclusions surrounding the organelles of glandular trichomes that were not present in cryofixed samples. Vacuolar morphology in cryofixed samples exhibited homogenous electron density, while chemically fixed samples contained a flocculent electron dense periphery and electron lucent lumen. In contrast to the apparent advantages of cryopreservation, fine details of cell wall fibre orientation could be observed in chemically fixed glandular trichomes that were not seen in cryofixed samples. Our data suggest that chemical fixation results in intracellular artefacts that impact the interpretation of lipid production and trafficking, while enabling greater detail of extracellular polysaccharide organisation.


Assuntos
Canabinoides , Cannabis , Humanos , Cannabis/química , Cannabis/metabolismo , Tricomas/química , Tricomas/metabolismo , Tricomas/ultraestrutura , Canabinoides/análise , Canabinoides/química , Canabinoides/metabolismo , Microscopia Eletrônica de Transmissão , Lipídeos/análise , Folhas de Planta
3.
Clin Case Rep ; 10(11): e6621, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36415714

RESUMO

We report a 51-year-old woman with thyroid eye disease and biopsy-proven pretibial myxedema that was subsequently treated with teprotumumab with improvement.

4.
Endocrinol Metab Clin North Am ; 51(2): 287-304, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35662442

RESUMO

The management of hyperthyroidism and extrathyroidal manifestations of Graves disease remains complex. Considerations that include patient preference, age, comorbidity, pregnancy, tobacco smoking, and social determinants of health must all be weaved into a cohesive management plan. A multidisciplinary team is required to manage all aspects of Graves disease, particularly thyroid eye disease, for which new therapeutic options are now available.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/tratamento farmacológico , Doença de Graves/terapia , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/epidemiologia , Oftalmopatia de Graves/etiologia , Humanos , Radioisótopos do Iodo/uso terapêutico , Gravidez , Tireoidectomia
5.
Orbit ; 41(6): 771-778, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34030590

RESUMO

Orbital venolymphatic malformations are rare vascular malformations that typically appear early in life and harbor acute and chronic threats to vision. Historically, there are four categories of management: observation, medication, sclerotherapy, and surgery. Currently, there is neither a gold standard for treatment nor randomized control trials comparing treatments.The authors present a 20-year-old male who presented with spontaneous hemorrhage of an orbital venolymphatic malformation occurring with increased frequency and involving more of the posterior orbit. Surgery and sclerotherapy were not feasible options due to the extensive intraorbital and intracranial involvement of the venolymphatic malformation. Systemic steroids treated symptoms but was not curative. To this end, a combination of sirolimus, an mTOR inhibitor, and rivaroxaban, a factor Xa inhibitor, were used to reduce the size of the lesion and minimize the risk of thromboembolic events. This treatment has successfully kept the patient's symptoms in remission for greater than 2 years.


Assuntos
Doenças Orbitárias , Malformações Vasculares , Masculino , Humanos , Adulto Jovem , Adulto , Sirolimo/uso terapêutico , Rivaroxabana/uso terapêutico , Escleroterapia , Doenças Orbitárias/tratamento farmacológico , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/tratamento farmacológico
6.
BMJ Case Rep ; 14(5)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972303

RESUMO

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.


Assuntos
Disfunção Cognitiva , Oftalmopatia de Graves , Idoso , Anticorpos Monoclonais Humanizados , Oftalmopatia de Graves/tratamento farmacológico , Humanos , Masculino
7.
Mil Med ; 185(9-10): e1876-e1879, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32426822

RESUMO

A 43-year-old white male sought treatment for swelling of the left brow, which started after sustaining direct blunt trauma to the left bony orbit 6 months prior. Magnetic resonance imaging with contrast showed a 5.6 × 2.7 mm T1 bright focus at the anterior aspect of the left supraorbital rim. On the postgadolinium fat-saturated axial T1 images, the lesion demonstrated fat signal but was not suppressed in T1 with fat suppression. Upon excision, the lesion was found to be an encapsulated orbital rim lipoma, which was unexpected given the hyperintensity on T1 with fat suppressed magnetic resonance imaging. The lesion did not return after excision. Orbital lipomas are rare benign neoplasms with only a handful of cases in literature. This is the first report of a posttraumatic encapsulated lipoma presenting on the brow or orbit. Although rare, lipomas should be on the differential of post-traumatic lesions affecting the orbit and the orbital rim.


Assuntos
Lipoma , Neoplasias Orbitárias , Adulto , Humanos , Lipoma/complicações , Lipoma/diagnóstico , Lipoma/cirurgia , Imageamento por Ressonância Magnética , Masculino
8.
Orbit ; 38(2): 166-168, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29742007

RESUMO

Silent sinus syndrome (SSS) is a rare disorder involving bony remodeling of the maxillary sinuses, including collapse of the orbital floor. It is typically unilateral and seen in the setting of chronic maxillary sinusitis. Patients present with enophthalmos and hypoglobus occasionally accompanied by diplopia. The condition is generally diagnosed with CT imaging and treated surgically. While SSS is most often reported as very slowly progressive, we report a patient with evidence of significant remodeling of the maxillary sinus over a period of 5.5 months.


Assuntos
Remodelação das Vias Aéreas/fisiologia , Seio Maxilar/fisiologia , Doenças dos Seios Paranasais/fisiopatologia , Diplopia/diagnóstico , Enoftalmia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Seio Maxilar/diagnóstico por imagem , Sinusite Maxilar/diagnóstico , Pessoa de Meia-Idade , Doenças dos Seios Paranasais/diagnóstico por imagem , Síndrome , Tomografia Computadorizada por Raios X
9.
J Exp Bot ; 69(8): 1849-1859, 2018 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-29481639

RESUMO

Lignin is an important phenolic biopolymer that provides strength and rigidity to the secondary cell walls of tracheary elements, sclereids, and fibers in vascular plants. Lignin precursors, called monolignols, are synthesized in the cell and exported to the cell wall where they are polymerized into lignin by oxidative enzymes such as laccases and peroxidases. In Arabidopsis thaliana, a peroxidase (PRX64) and laccase (LAC4) are shown to localize differently within cell wall domains in interfascicular fibers: PRX64 localizes to the middle lamella whereas LAC4 localizes throughout the secondary cell wall layers. Similarly, laccases localized to, and are responsible for, the helical depositions of lignin in protoxylem tracheary elements. In addition, we tested the mobility of laccases in the cell wall using fluorescence recovery after photobleaching. mCHERRY-tagged LAC4 was immobile in secondary cell wall domains, but mobile in the primary cell wall when ectopically expressed. A small secreted red fluorescent protein (sec-mCHERRY) was engineered as a control and was found to be mobile in both the primary and secondary cell walls. Unlike sec-mCHERRY, the tight anchoring of LAC4 to secondary cell wall domains indicated that it cannot be remobilized once secreted, and this anchoring underlies the spatial control of lignification.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Parede Celular/metabolismo , Lacase/metabolismo , Lignina/metabolismo , Peroxidases/metabolismo , Arabidopsis/química , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Parede Celular/química , Parede Celular/genética , Regulação da Expressão Gênica de Plantas , Lacase/química , Lacase/genética , Peroxidases/química , Peroxidases/genética , Domínios Proteicos , Transporte Proteico
10.
Ophthalmic Plast Reconstr Surg ; 34(3): 209-212, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28369020

RESUMO

PURPOSE: Loss of volume in the sub-brow fat pad with associated descent of the eyebrow is a common anatomical finding resulting in both functional and aesthetic consequences. A variety of techniques have been described to address brow position at the time of blepharoplasty. To our knowledge, none of these techniques treat the sub-brow fat pad as an isolated unit. Doing so enables the surgeon to stabilize and volumize the brow without resultant tension on the blepharoplasty wound. The authors describe a technique for addressing volume loss in the eyebrow with associated brow descent that treats the sub-brow fat pad as an isolated unit. METHODS: A retrospective review of all patients undergoing brow ptosis repair by a single surgeon (J.W.S.) over an 11-month period was performed. RESULTS: Eighteen patients and 33 brows underwent the technique described. Patients were followed for an average of 11 weeks (range: 4 weeks to 20 weeks). All patients preoperatively displayed both visually significant dermatochalasis and brow descent below the orbital rim. Evaluation of pre- and postoperative photos demonstrates successful volumization of the brow with skin redraping without focal dimpling or undue tension on the eyelid wound. CONCLUSIONS: Performing a dissection that allows the sub-brow fat pad to be elevated in isolation from the overlying orbicularis and underlying periosteum allows for volumization and of the brow without compromising closure. This technique is a safe and effective means of volumizing the brow and treating secondary brow descent.


Assuntos
Tecido Adiposo/cirurgia , Sobrancelhas , Pálpebras/cirurgia , Adulto , Idoso , Blefaroplastia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Ophthalmic Plast Reconstr Surg ; 34(3): 246-253, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28582369

RESUMO

PURPOSE: To compare revision rates for ptosis surgery between posterior-approach and anterior-approach ptosis repair techniques. METHODS: This is the retrospective, consecutive cohort study. All patients undergoing ptosis surgery at a high-volume oculofacial plastic surgery practice over a 4-year period. A retrospective chart review was conducted of all patients undergoing posterior-approach and anterior-approach ptosis surgery for all etiologies of ptosis between 2011 and 2014. Etiology of ptosis, concurrent oculofacial surgeries, revision, and complications were analyzed. The main outcome measure is the ptosis revision rate. RESULTS: A total of 1519 patients were included in this study. The mean age was 63 ± 15.4 years. A total of 1056 (70%) of patients were female, 1451 (95%) had involutional ptosis, and 1129 (74.3%) had concurrent upper blepharoplasty. Five hundred thirteen (33.8%) underwent posterior-approach ptosis repair, and 1006 (66.2%) underwent anterior-approach ptosis repair. The degree of ptosis was greater in the anterior-approach ptosis repair group. The overall revision rate for all patients was 8.7%. Of the posterior group, 6.8% required ptosis revision; of the anterior group, 9.5% required revision surgery. The main reason for ptosis revision surgery was undercorrection of one or both eyelids. Concurrent brow lifting was associated with a decreased, but not statistically significant, rate of revision surgery. Patients who underwent unilateral ptosis surgery had a 5.1% rate of Hering's phenomenon requiring ptosis repair in the contralateral eyelid. Multivariable logistic regression for predictive factors show that, when adjusted for gender and concurrent blepharoplasty, the revision rate in anterior-approach ptosis surgery is higher than posterior-approach ptosis surgery (odds ratio = 2.08; p = 0.002). CONCLUSIONS: The overall revision rate in patients undergoing ptosis repair via posterior-approach or anterior-approach techniques is 8.7%. There is a statistically higher rate of revision with anterior-approach ptosis repair.


Assuntos
Blefaroplastia/métodos , Blefaroptose/cirurgia , Pálpebras/cirurgia , Reoperação/estatística & dados numéricos , Adulto , Idoso , Blefaroplastia/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/cirurgia , Estudos Retrospectivos
12.
Orbit ; 36(1): 6-12, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28145798

RESUMO

The traditional use of the Crawford tube for lacrimal intubation during dacryocystorhinostomy (DCR) carries several drawbacks. We describe the use of the STENTube for DCR intubation and detail its advantages. Retrospective, noncomparative, interventional case series; 313 patients with nasolacrimal duct obstruction (NLDO) underwent 339 DCRs (216 external, 123 endonasal) with the STENTube from January 2007 - June 2013 by 5 surgeons (RS, QN, TS, SB, TN) across 3 institutions (SUNY Downstate Medical Center, Texas Oculoplastics Consultants, and Moorfields Eye Hospital). Study outcome measures included patient demographics, surgical complications, and epiphora improvement/resolution. 206 (66%) females and 107 (34%) males had a mean age of 63 years (range 2-94 years). Distribution of diagnoses included: 314 complete idiopathic acquired NLDO, 20 partial idiopathic acquired NLDO, and 5 congenital complete NLDO. 316 (93%) were primary DCRs and 23 (7%) were revisions. Epiphora improved in 312 (92%) cases with 294 (86%) experiencing resolution with patent lacrimal irrigation at a mean last follow-up of 9.4 months. Twenty-eight (8%) patients experienced surgical complications with 16 (5%) experiencing tube prolapse, and 20 (6%) requiring re-operation. The STENTube represents a simple method for lacrimal intubation during external or endonasal DCR at a comparable cost to the Crawford tube. It allows for low prolapse rates without the need for additional endonasal fixation procedures, resulting in a simple and comfortable post-operative extraction without risk of lacrimal trauma. The STENTube is our preferred intubation technique during DCR, and should be considered by oculofacial surgeons performing DCR with intubation.


Assuntos
Dacriocistorinostomia/métodos , Intubação , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Irrigação Terapêutica , Resultado do Tratamento
13.
Ophthalmic Plast Reconstr Surg ; 33(3S Suppl 1): S11-S12, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26108057

RESUMO

Injectable fillers have become a prevalent means of facial rejuvenation and volume expansion. While typically well tolerated, serious complications have been reported. The authors present a case in which an otherwise healthy female with a history of multiple filler injections including poly-L-lactic acid, developed 3 weeks of neuropathic pain in the left temporal fossa following injection. To the best of the authors knowledge, neuropathic pain has not been reported as a complication following poly-L-lactic acid injection. The patient was treated with an injection of steroid and long-acting anesthetic with resolution of symptoms.


Assuntos
Celulose/efeitos adversos , Ácido Láctico/efeitos adversos , Manitol/efeitos adversos , Neuralgia/induzido quimicamente , Ritidoplastia/efeitos adversos , Idoso , Celulose/administração & dosagem , Técnicas Cosméticas , Feminino , Humanos , Injeções , Ácido Láctico/administração & dosagem , Manitol/administração & dosagem , Neuralgia/diagnóstico , Medição da Dor
14.
Am J Ophthalmol ; 176: 134-140, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27993591

RESUMO

PURPOSE: To characterize the expression of vascular endothelial growth factor (VEGF) in a patient with retinopathy of prematurity (ROP) treated with ranibizumab (Case 1) and compare it with a case of ROP without treatment (Case 2), a case of a premature baby without ROP (Case 3), and a case of a baby without history of ROP or prematurity (Case 4). DESIGN: Observational case series. METHODS: The eyes of the deceased babies were removed postmortem and were sent to the Florida Lions Ocular Pathology Laboratory, where they were processed. The specimens were immunostained using an antibody against VEGF. RESULTS: All eyes except for the eyes in Case 4 disclosed positive VEGF staining. Positive staining was present within the nerve fiber layer, inner plexiform layer, and inner and outer nuclear layers and within the spindle-shaped cell population in the vanguard in Case 1. In the posterior pole, positive staining was only observed at the level of the nerve fiber layer. This case also demonstrated less positive staining when compared with Case 2, where positive staining was found within all layers of the retina. CONCLUSION: Less VEGF staining was observed within the retina of the eyes treated with ranibizumab when compared with the VEGF staining in Case 2. This supports the idea that anti-VEGF agents are effective in reducing the amount of VEGF present in the retina. Furthermore, the fact that some expression of VEGF remains in the immature retina after injection supports the idea that anti-VEGF agents can suppress uncontrolled neovascularization without completely blocking the vascular drive for the vascularization of the immature retina.


Assuntos
Recém-Nascido Prematuro , Ranibizumab/administração & dosagem , Retina/patologia , Retinopatia da Prematuridade/diagnóstico , Fator A de Crescimento do Endotélio Vascular/biossíntese , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Retina/metabolismo , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/metabolismo
15.
Ophthalmic Plast Reconstr Surg ; 33(2): 144-146, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27811633

RESUMO

PURPOSE: Pentagonal wedge resection is a technique used to address a wide variety of eyelid pathology. This procedure frequently results in excess skin at the apex of the wound, commonly known as a "dog ear." A variety of methods have been described to address the cutaneous redundancy, the most classic of which is the Burow's triangle repair. The authors present a technique to address the anterior lamellar excess that avoids placement of a vertical scar traversing the pretarsal and preseptal portion of the affected eyelid. The repair moves the preseptal closure of the wound temporally, away from the moving portion of the eyelid. The horizontal incision that transposes the vertical closure temporally is concealed in the eyelid crease. METHODS: A retrospective review of all patients undergoing this technique for eyelid reconstruction was undertaken. The surgical technique is described in detail. RESULTS: The procedure has been performed on 7 patients (8 eyelids). Patients were followed for an average of 12 weeks. Indications for surgery were floppy eyelid syndrome requiring horizontal shortening of the upper eyelid and neoplastic lesions involving the upper or lower eyelid. There were no complications. All patients had a satisfactory outcome with regard to function and cosmesis. CONCLUSIONS: Full-thickness excision of the central two-thirds of the lower and upper eyelid is used extensively to manage a wide variety of conditions. The authors present a technique for addressing the anterior lamellar closure with notable advantages over previously described methods. The major advantages of this technique are that it results in a vertical closure that is horizontally displaced from the primary action of the levator aponeurosis and avoids anterior and midlamellar scarring of the upper and lower eyelid that may inhibit vertical movement. In addition, the cutaneous scar is more easily concealed.


Assuntos
Blefaroplastia/métodos , Doenças Palpebrais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Am J Ophthalmol ; 160(2): 220-227.e2, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25935097

RESUMO

PURPOSE: To review our experience treating patients with the Hedgehog pathway inhibitor, vismodegib, in patients with orbital or periocular locally advanced or metastatic basal cell carcinoma (BCC) or basal cell nevus syndrome. DESIGN: Retrospective interventional case series. METHODS: We reviewed all patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome treated with the Hedgehog pathway inhibitor, vismodegib, at a comprehensive cancer center from 2009 through 2015. Reviewed data included age; sex; American Joint Commission on Cancer tumor, node, metastasis staging system designation; type and grade of drug-related side effects; response to treatment; duration of follow-up, and status at last follow-up. RESULTS: The study included 10 white men and 2 white women; the median age was 64.5 years. Ten patients had locally advanced BCC; 2 had basal cell nevus syndrome. Among the patients with locally advanced BCC, 5 had T3bN0M0 disease at presentation; 1 each had T3aN0M0, T3bN1M0, T2N1M1, T4N1M1, and T4N2cM1 disease. Overall, 3 patients had a complete response, 6 had a partial response, and 3 had stable disease at last follow-up. Two patients developed progressive disease after a complete response for 38 months and stable disease for 16 months, respectively. All patients developed grade I drug-related adverse effects, most commonly muscle spasms (12 patients), weight loss (10), dysgeusia (9), alopecia (9), decreased appetite (5), and fatigue (4). Five patients developed grade II adverse effects. At last follow-up, none of the 5 patients presenting with T3bN0M0, nor the patient with T3bN1M0 disease, had required orbital exenteration. CONCLUSION: Hedgehog pathway inhibition produces a significant clinical response in most patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome and can obviate orbital exenteration in some patients. Drug-related adverse effects are manageable in most patients.


Assuntos
Anilidas/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Síndrome do Nevo Basocelular/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Piridinas/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/metabolismo , Síndrome do Nevo Basocelular/metabolismo , Síndrome do Nevo Basocelular/patologia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
17.
Clin Plast Surg ; 42(1): 95-101, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25440746

RESUMO

The transeyelid approach to midface lift is an elegant approach for mild descent of malar soft tissue. The subciliary approach is the most commonly used and technically less challenging for surgeons experienced in facelift techniques. This technique in midface rejuvenation also has the advantage of ease of combining with other periocular and mid and upper face rejuvenation, such as blepharoplasty and forehead lift. Complication is rare with lid malposition, scaring, and temporary nerve function impairment being the most common.


Assuntos
Ritidoplastia/métodos , Testa/cirurgia , Humanos , Seleção de Pacientes , Cuidados Pós-Operatórios , Rejuvenescimento , Ritidoplastia/efeitos adversos , Envelhecimento da Pele
18.
Invest Ophthalmol Vis Sci ; 52(6): 3630-9, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21345991

RESUMO

PURPOSE: The recent FIELD study demonstrated that the lipid-lowering agent fenofibrate significantly reduces the development and progression of diabetic retinopathy (DR). These results suggest that lipids may play a causal role in DR. They also suggest that AMP-activated protein kinase (AMPK) activation could account for these findings given that fenofibrate is an AMPK activator. The authors previously demonstrated that free fatty acids, in addition to hyperglycemia, can induce apoptosis in retinal pericytes (PCs), the first cells lost in the diabetic retina. Incubation with the saturated fatty acid palmitate, but not the monounsaturated fatty acid oleate, elicited cytotoxicity in a manner dependent on oxidative stress, NF-κB activation, and ceramide accumulation. In this study, the authors explored whether AMPK can downregulate these pathways and, in doing so, protect PCs from apoptosis. METHODS: PCs were incubated with palmitate or oleate to determine whether the factors previously linked to lipotoxicity were uniquely increased by palmitate. The effects of AMPK activation on these parameters and on apoptosis were concurrently examined. RESULTS: Only palmitate increased NF-κB activation, ceramide and diacylglycerol mass, and apoptosis. Activation of AMPK with AICAR or, where used, expression of a constitutively active AMPK prevented all these effects. In contrast, both palmitate and oleate markedly increased oxidative stress, and the activation of AMPK did not prevent this. CONCLUSIONS: AMPK activation prevents the metabolic abnormalities and apoptosis specifically caused by palmitate in cultured PCs. Pharmacologic agents that activate AMPK in the diabetic retina may warrant consideration as a therapeutic option to avert PC apoptosis and to maintain microvascular homeostasis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ácido Oleico/toxicidade , Palmitatos/toxicidade , Pericitos/efeitos dos fármacos , Vasos Retinianos/citologia , Proteínas Quinases Ativadas por AMP/genética , Acetilcarnitina/farmacologia , Adenoviridae/genética , Animais , Apoptose/efeitos dos fármacos , Bovinos , Células Cultivadas , Citoproteção , Diglicerídeos/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica/fisiologia , Marcação In Situ das Extremidades Cortadas , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pericitos/enzimologia , Esfingolipídeos/metabolismo
19.
Invest Ophthalmol Vis Sci ; 51(12): 6803-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20592236

RESUMO

PURPOSE: Activation of phospholipase Cγ1 (PLCγ1) by vascular endothelial growth factor receptor (VEGFR)-2 is necessary for proliferation and tube formation of endothelial cells in vitro. Previous work has demonstrated that Casitas B-lineage lymphoma (c-Cbl) promotes ubiquitination of PLCγ1 and suppression of its tyrosine phosphorylation. This study was designed to evaluate the importance of PLCγ1 and c-Cbl in experimental choroidal neovascularization (CNV). METHODS: The role of PLCγ1 was studied in three models of angiogenesis: the endothelial cell culture system, the chorioallantoic membrane (CAM) assay, and the laser-induced CNV model. Endothelial cells were analyzed for the role of PLCγ1 in promoting tube formation. CAMs were incubated with pharmacologic agents that either inhibit or stimulate PLCγ1. CNV was induced in wild-type and c-Cbl-knockout mice, and the progression of CNV was evaluated by fluorescein angiography. RESULTS: Activation of PLCγ1 was necessary for tube formation of endothelial cells. PLCγ1 stimulation increased the growth of blood vessels and conversely, PLCγ1 inhibition decreased the growth of blood vessels in the CAM model. CNV lesions in the c-Cbl-knockout mice were significantly greater in number, more confluent, and increased in size with time, compared with those in the control wild-type mice. CONCLUSIONS: The data show that PLCγ1 plays an important role in angiogenesis. Loss of c-Cbl results in enhanced CNV in the eye. The study also shows that c-Cbl plays an important role in ocular angiogenesis, suggesting that modulation of c-Cbl activity or inhibition of PLCγ1 would be a compelling target for antiangiogenesis therapy.


Assuntos
Neovascularização de Coroide/enzimologia , Modelos Animais de Doenças , Fosfolipase C gama/metabolismo , Proteínas Proto-Oncogênicas c-cbl/fisiologia , Animais , Aorta Torácica/citologia , Vasos Sanguíneos/fisiologia , Western Blotting , Células Cultivadas , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Endotélio Vascular/metabolismo , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Angiofluoresceinografia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipase C gama/antagonistas & inibidores , Suínos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/farmacologia
20.
Diabetes ; 54(6): 1838-45, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15919807

RESUMO

Apoptosis of pericytes (PCs) is an early event in diabetic retinopathy. It is generally thought to be a consequence of sustained hyperglycemia. In keeping with this, long-term (>7 days) incubation of cultured PCs in a high-glucose media has been shown to increase apoptosis. We examine here whether the saturated free fatty acid palmitate, the concentration of which is often elevated in diabetes, has similar effects on cultured PCs. Incubation with 0.4 mmol/l palmitate for 24 h induced both oxidant stress and apoptosis, as evidenced by a sixfold increase in DCF fluorescence and a twofold increase in caspase-3 activation, respectively. NAD(P)H oxidase appeared to be involved in these responses, since overexpression of dominant-negative subunits of NAD(P)H oxidase, such as phox47(DN), diminished oxidant stress, and phox67(DN) and N-17 RAC1(DN) prevented the increase in caspase-3 activity. Likewise, overexpression of vRAC, a constitutively active RAC1, increased caspase-3 activity to the same extent as palmitate alone. The effects of vRAC and palmitate were not additive. In parallel with the increases in oxidative stress, the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB) was activated in cells incubated with 0.4 mmol/l palmitate. Furthermore, inhibition of NF-kappaB activation by various means inhibited caspase-3 activation. Finally, incubation with palmitate increased the cellular content of ceramide, a molecule linked to apoptosis and increases in oxidative stress and NF-kappaB activation in other cells. In keeping with such a role, in PCs both coincubation with fumonisin B1 (a ceramide synthase inhibitor) and overexpression of ceramidase I reversed the proapoptotic effect of palmitate. On the other hand, they increased rather than decreased DCF fluorescence. In conclusion, the results suggest that palmitate-induced apoptosis in PCs is associated with activation of NAD(P)H oxidase and NF-kappaB and an increase in ceramide. The precise interactions between these molecules in causing apoptosis and the importance of oxidant stress as a contributory factor remain to be determined.


Assuntos
Apoptose/efeitos dos fármacos , Ceramidas/fisiologia , NADPH Oxidases/metabolismo , Estresse Oxidativo , Ácido Palmítico/farmacologia , Pericitos/efeitos dos fármacos , Retina/citologia , Animais , Apoptose/fisiologia , Bovinos , Células Cultivadas , Retinopatia Diabética/metabolismo , Retinopatia Diabética/fisiopatologia , Expressão Gênica , NF-kappa B/metabolismo , Pericitos/fisiologia , Subunidades Proteicas
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