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1.
ANZ J Surg ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177292

RESUMO

We present a simple, yet effective, approach for surgically managing chronic gastrocutaneous fistulas. This procedure can be easily performed under local anaesthesia if needed. Our derived experience is largely based on gastrocutaneous fistulas, but we have also used this approach on small bowel fistulas.

2.
N Z Med J ; 137(1594): 43-53, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696831

RESUMO

AIM: Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. METHODS: This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. RESULTS: After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. CONCLUSION: Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.


Assuntos
Diabetes Mellitus Tipo 2 , Gastrectomia , Derivação Gástrica , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Feminino , Masculino , Gastrectomia/métodos , Método Duplo-Cego , Pessoa de Meia-Idade , Adulto , Obesidade Mórbida/cirurgia , Hipoglicemiantes/uso terapêutico , Redução de Peso , Laparoscopia/métodos , Resultado do Tratamento
3.
Sci Rep ; 12(1): 10623, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739142

RESUMO

Primary open angle glaucoma (POAG) features an optic neuropathy, elevated aqueous humor (AH) TGFß2, and major risk factors of central corneal thickness (CCT), increasing age and intraocular pressure (IOP). We examined Tight skin (Tsk) mice to see if mutation of fibrillin-1, a repository for latent TGFß, is associated with characteristics of human POAG. We measured: CCT by ocular coherence tomography (OCT); IOP; retinal ganglion cell (RGC) and optic nerve axon counts by microscopic techniques; visual electrophysiologic scotopic threshold responses (STR) and pattern electroretinogram (PERG); and AH TGFß2 levels and activity by ELISA and MINK epithelial cell-based assays respectively. Tsk mice had open anterior chamber angles and compared with age-matched wild type (WT) mice: 23% thinner CCT (p < 0.003); IOP that was higher (p < 0.0001), more asymmetric (p = 0.047), rose with age (p = 0.04) and had a POAG-like frequency distribution. Tsk mice also had RGCs that were fewer (p < 0.04), declined with age (p = 0.0003) and showed increased apoptosis and glial activity; fewer optic nerve axons (p = 0.02); abnormal axons and glia; reduced STR (p < 0.002) and PERG (p < 0.007) visual responses; and higher AH TGFß2 levels (p = 0.0002) and activity (p = 1E-11) especially with age. Tsk mice showed defining features of POAG, implicating aberrant fibrillin-1 homeostasis as a pathogenic contributor to emergence of a POAG phenotype.


Assuntos
Humor Aquoso , Fibrilina-1 , Glaucoma de Ângulo Aberto , Animais , Humor Aquoso/metabolismo , Fibrilina-1/genética , Fibrilina-1/metabolismo , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular , Camundongos , Células Ganglionares da Retina/patologia , Tonometria Ocular , Fator de Crescimento Transformador beta2
4.
Diabetes Care ; 45(7): 1503-1511, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35554515

RESUMO

OBJECTIVE: To determine whether silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) or laparoscopic sleeve gastrectomy (LSG) produces superior diabetes remission at 5 years. RESEARCH DESIGN AND METHODS: In a single-center, double-blind trial, 114 adults with type 2 diabetes and BMI 35-65 kg/m2 were randomly assigned to SR-LRYGB or LSG (1:1; stratified by age-group, BMI group, ethnicity, diabetes duration, and insulin therapy) using a web-based service. Diabetes and other metabolic medications were adjusted according to a prespecified protocol. The primary outcome was diabetes remission assessed at 5 years, defined by HbA1c <6% (42 mmol/mol) without glucose-lowering medications. Secondary outcomes included changes in weight, cardiometabolic risk factors, quality of life, and adverse events. RESULTS: Diabetes remission after SR-LRYGB versus LSG occurred in 25 (47%) of 53 vs. 18 (33%) of 55 patients (adjusted odds ratios 4.5 [95% CI 1.6, 15.5; P = 0.009] and 4.2 [1.3, 13.4; P = 0.015] in the intention-to-treat analysis). Percent body weight loss was greater after SR-LRYGB than after LSG (absolute difference 10.7%; 95% CI 7.3, 14.0; P < 0.001). Improvements in cardiometabolic risk factors were similar, but HDL cholesterol increased more after SR-LRYGB. Early and late complications were similar in both groups. General health and physical functioning improved after both types of surgery, with greater improvement in physical functioning after SR-LRYGB. People of Maori or Pacific ethnicity (26%) had lower incidence of diabetes remission than those of New Zealand European or other ethnicities (2 of 25 vs. 41 of 83; P < 0.001). CONCLUSIONS: SR-LRYGB provided superior diabetes remission and weight loss compared with LSG at 5 years, with similar low risks of complications.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Adulto , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/cirurgia , Método Duplo-Cego , Gastrectomia , Derivação Gástrica/métodos , Humanos , Laparoscopia/métodos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Resultado do Tratamento
5.
Ann Acad Med Singap ; 50(5): 390-401, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34100516

RESUMO

INTRODUCTION: Nutritional psychiatry is an emerging field of study that investigates the role of diet and nutrition in mental health. Studies conducted in the general population have linked depressive symptoms with poor dietary patterns. The aim of this study was to characterise the dietary intake and analyse the dietary pattern using the Dietary Approach to Stop Hypertension (DASH) in a sample of psychiatric patients in a multiethnic Asian nation. METHODS: Participants were recruited from an outpatient clinic and an inpatient unit at the Institute of Mental Health in Singapore. Self-reported dietary habits of a sample of psychiatric patients (N=380) were analysed using DASH. To examine the variables associated with DASH scores, a linear regression was conducted with the full sample and sociodemographic variables. RESULTS: Persons with depressive disorders had a mean DASH score of 21.3 (±4.2), while persons with psychotic disorders had a mean DASH score of 21.2 (±4.9). Respondents who were older (B=1.94, 95% confidence interval [CI] 0.91-2.96, P<0.001), female (B=1.09, 95% CI 0.07-2.11, P=0.04) and economically inactive (B=1.98, 95% CI 0.006-3.96, P=0.049) were more likely to report a higher diet quality compared with their respective counterparts, while smokers (B= -1.39, 95% CI -2.45 to -0.34, P=0.009) tended to report a lower diet quality compared with their non-smoking counterparts. CONCLUSION: Dietary patterns of persons with mental disorders were characterised. A host of sociodemographic factors, and not diagnosis of mental disorders, influenced the dietary quality of people with depressive and psychotic disorders. Clinicians treating psychiatric patients need to be aware of the nuanced reasons behind poor dietary choices and provide targeted psychoeducation to specific subgroups within the patient population.


Assuntos
Transtornos Mentais , Qualidade de Vida , Dieta , Feminino , Humanos , Transtornos Mentais/epidemiologia , Saúde Mental , Singapura/epidemiologia , Desemprego
6.
JCI Insight ; 5(13)2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641580

RESUMO

Glaucoma surgeries, such as trabeculectomy, are performed to lower intraocular pressure to reduce risk of vision loss. These surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. Here, we characterized the development and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed from a primary lymphatic vessel that grows from the nasal-side medial canthus region at birth. This primary lymphatic vessel immediately branches out, invades the limbus and conjunctiva, and bidirectionally encircles the cornea. As a result, the distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic sprouts are produced mainly from the nasal-side limbal lymphatics, posing the nasal side of the eye as more responsive to fluid drainage and inflammatory stimuli. Consistent with this polarized distribution of the ocular lymphatics, a higher drainage efficiency was observed in the nasal side than the temporal side of the eye when injected with a fluorescent tracer. In contrast, blood vessels are evenly distributed at the anterior surface of the eyes. Also, we found that these distinct vascular distribution patterns were conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a glaucoma surgery site to improve fluid drainage.


Assuntos
Túnica Conjuntiva/patologia , Sistema Linfático/patologia , Vasos Linfáticos/patologia , Organogênese/fisiologia , Animais , Humor Aquoso/metabolismo , Pressão Intraocular/fisiologia , Camundongos Transgênicos , Ratos Sprague-Dawley
7.
J Glaucoma ; 29(8): 627-638, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32459684

RESUMO

PURPOSE: The purpose of this study was to evaluate the efficacy of intraocular pressure (IOP) control after combined CyPass Micro-Stent implantation and cataract surgery (combined surgery). METHODS: All cases of combined surgery performed from February 2017 to July 2018 at Stein and Doheny Eye Institutes were reviewed. The primary outcome was a qualified success with stratified IOP targets based on criteria: final IOP (A) ≤18 mm Hg and reduction of 20%, (B) ≤15 mm Hg and reduction of 25%, (C) ≤12 mm Hg and reduction of 30%. Secondary outcome measures included postoperative IOP and number of medications, complications, additional glaucoma surgery, and postoperative refractive error. Predictive factors for failure were investigated. IOP spike was defined as a postoperative IOP ≥30 or >10 mm Hg increase from preoperative IOP. RESULTS: One hundred forty-one eyes (107 patients) were included. Mean (±SD) preoperative IOP was 15.4±3.4 mm Hg on an average of 2.2±1.1 medications. A statistically significant reduction in IOP and number of medications was seen at 12 months (13.8±4.2 mm Hg, 1.3±1.3 medications, P<0.001). Fifteen eyes (10.6%) had a postoperative IOP spike. Thirteen eyes (9.2%) experienced 17 complications (12.1%). Additional glaucoma surgery was performed in 3 eyes (2 patients). Cumulative success rates at 1 year based on criteria A, B, and C were 42%, 33%, and 28%, respectively. Lower preoperative IOP, greater preoperative medication number, the occurrence of postoperative IOP spike, and non-Caucasian ethnicity were associated with failure. CONCLUSION: Combined CyPass Micro-Stent implantation and cataract surgery may reduce glaucoma medication burden with a success rate of 28% to 42% at 1 year.


Assuntos
Corioide/cirurgia , Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto/cirurgia , Facoemulsificação , Implantação de Prótese , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Stents , Tonometria Ocular
8.
J Educ Health Promot ; 8: 231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867395

RESUMO

BACKGROUND: Cancer cervix is caused by human papillomavirus (HPV), oncogenic virus and has vaccines and screening as its preventive measures. This study analyzes the change in awareness and attitudes of nonmedical students toward the condition following the use of an educational module. METHODOLOGY: The study design was quasi-experimental. The interprofessional (IP) team implemented an educational module and analyzed the difference in awareness of young individuals toward the cancer cervix. A pretest and posttest written questionnaire, customized for both genders, was administered with the intervention of the educational module in between. The module consisted of a short educational presentation along with a group activity. A follow-up survey was also done after 2 months to check the attrition of awareness. The statistical analysis was done using MacNemar test using SPSS 12 IBM software and significance of differences were determined. RESULTS: There was a significant improvement of knowledge and awareness on linkage between HPV and cervical cancer (P < 0.001). There was also significant change with regard to attitudes toward cervical cancer vaccination (P = 0.004). The knowledge of HPV linkage to the malignancy was maintained after 2 months of gap. The subjects also wished for more future awareness program. CONCLUSIONS: There is improved awareness in the dental and foundation in science students, and this improved awareness will ensure favorable attitudes toward cervical cancer vaccines or will attend regular screening programs. Awareness program must be held at regular intervals at different locations to enhance the knowledge dissemination of this common yet preventable genital malignancy of females. The IP collaboration and practices will help in reducing the disease burden of the society in future.

9.
ACS Nano ; 13(10): 10961-10971, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31589023

RESUMO

While biologic drugs such as proteins, peptides, or nucleic acids have shown promise in the treatment of neurodegenerative diseases, the blood-brain barrier (BBB) severely limits drug delivery to the central nervous system (CNS) after systemic administration. Consequently, drug delivery challenges preclude biological drug candidates from the clinical armamentarium. In order to target drug delivery and uptake into to the CNS, we used an in vivo phage display screen to identify peptides able to target drug-uptake by the vast array of neurons of the autonomic nervous system (ANS). Using next-generation sequencing, we identified 21 candidate targeted ANS-to-CNS uptake ligands (TACL) that enriched bacteriophage accumulation and delivered protein-cargo into the CNS after intraperitoneal (IP) administration. The series of TACL peptides were synthesized and tested for their ability to deliver a model enzyme (NeutrAvidin-horseradish peroxidase fusion) to the brain and spinal cord. Three TACL-peptides facilitated significant active enzyme delivery into the CNS, with limited accumulation in off-target organs. Peptide structure and serum stability is increased when internal cysteine residues are cyclized by perfluoroarylation with decafluorobiphenyl, which increased delivery to the CNS further. TACL-peptide was demonstrated to localize in parasympathetic ganglia neurons in addition to neuronal structures in the hindbrain and spinal cord. By targeting uptake into ANS neurons, we demonstrate the potential for TACL-peptides to bypass the blood-brain barrier and deliver a model drug into the brain and spinal cord.


Assuntos
Vias Autônomas/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Neurônios/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Vias Autônomas/patologia , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Técnicas de Visualização da Superfície Celular/métodos , Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Injeções Intraperitoneais , Ligantes , Camundongos , Doenças Neurodegenerativas/tratamento farmacológico , Neurônios/patologia , Biblioteca de Peptídeos , Medula Espinal/efeitos dos fármacos
10.
F1000Res ; 8: 175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275564

RESUMO

Background: The indigenous people of Peninsular Malaysia, also known as Orang Asli, have gradually been urbanized. A shift towards non-communicable diseases commonly associated with sedentary lifestyles have been reported in many tribes. This study engaged with a semi-urbanized Temiar tribe from Kampong Pos Piah, Perak, who are experiencing an epidemiological transition. Methods:  Weight, height, waist circumference, blood pressure, HbA1C and lipid levels were measured as indicators of cardio-metabolic health. DNA was extracted from saliva using salting-out method followed by PCR amplification of the V3-V4 region of the 16S rRNA gene and sequencing on Illumina MiSeq. Microbiome analysis was conducted on Qiime v1.9. Statistical analysis was conducted using Qiime v1.9 and R.   Results: The study revealed that 60.4% of the Temiar community were overweight/obese, with a higher prevalence among women. HbA1C levels showed that 45% of Temiar had pre-diabetes. Insulin resistance was identified in 21% of Temiar by using a surrogate marker, TG/HDL. In total, 56.5% of Temiar were pre-hypertensive, and the condition was prevalent across all age-groups. The saliva microbiome profiles of Temiar revealed significant differences by gender, BMI, abdominal obesity as well as smoking status. The relative abundance of Bifidobacterium, bacteria commonly found in dairy products, was increased in men. Prevotella, associated with consumption of plant-rich diets, was increased in women. Mogibacteriacea and Mycoplasma levels were significantly elevated in overweight individuals. Proteobacteria was significantly depleted in smokers. Conclusions: Temiar from Pos Piah had a high prevalence of cardio-metabolic risks, including general and abdominal obesity, pre-diabetes, prehypertension and hypertension. This phenomenon has not been previously reported in this tribe. The saliva microbiome profiles were significantly different for individuals of different gender, BMI scores and abdominal obesity and smoking status.

11.
Ophthalmol Glaucoma ; 2(6): 402-412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32672572

RESUMO

PURPOSE: To assess the short-term efficacy and safety of micropulse transscleral diode laser cyclophotocoagulation (MP-TSCPC) in the management of refractory glaucoma and to compare outcomes based on prior glaucoma surgeries. DESIGN: Retrospective analysis. PARTICIPANTS: Patients with refractory glaucoma who underwent MP-TSCPC at a single institution by 1 of 4 surgeons. METHODS: Chart review of cases of MP-TSCPC using the Iridex Cyclo G6 (Mountain View, CA) laser with standard parameters and laser duration at the discretion of each treating physician. MAIN OUTCOME MEASURES: Probability of postoperative success was estimated by the Kaplan-Meier method. Success parameters included intraocular pressure (IOP) 6 to 21 mmHg with or without topical antihypertensive therapy, 20% or more IOP reduction from baseline for any 2 consecutive visits after 3 postoperative months, and no subsequent glaucoma surgery. RESULTS: One hundred sixteen eyes of 116 patients (mean age, 65.8±16.9 years) were included. Baseline IOP was 22.2±7.9 mmHg, and mean postoperative follow-up time was 6.3±3.4 months (range, 3-12 months.) Postoperative IOP at the final follow up was 15.3±6.6 mmHg (P < 0.01), corresponding to a reduction of approximately 6.9 mmHg (31.1%). Most eyes (66.4%) underwent at least 6 months of follow-up. Short-term probability of success was 93.1% at 3 months and 74.3% at 6 months. Eyes that had undergone prior traditional glaucoma surgery (trabeculectomy, tube shunt, excessive pressure-regulating shunt system miniature glaucoma shunt [Alcon, Fort Worth, TX], or a combination thereof) demonstrated a higher probability of success (67.6%) compared with eyes that had not (41.4%; P = 0.014). The most common complications were decline in best-corrected visual acuity (7.8%) and hypotony (1.7%). CONCLUSIONS: Micropulse transscleral diode laser cyclophotocoagulation has a significant short-term ocular hypotensive effect and favorable safety profile in eyes with refractory glaucoma. The probability of successful outcome was greater in eyes that had undergone prior traditional glaucoma surgery.


Assuntos
Corpo Ciliar/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular/fisiologia , Lasers Semicondutores/uso terapêutico , Procedimentos Cirúrgicos Oftalmológicos/métodos , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Fotocoagulação a Laser/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
J Glaucoma ; 27(2): 133-139, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29239864

RESUMO

PURPOSE: To evaluate outcomes of trabeculectomy with adjunctive mitomycin C in patients with uncontrolled intraocular pressure (IOP) after glaucoma drainage device implantation. MATERIALS AND METHODS: Consecutive patients who had undergone a trabeculectomy after GDD were reviewed. The primary outcome was surgical success with stratified IOP targets based on the following criteria: (A) IOP<18 mm Hg and IOP reduction of 20%; (B) IOP<15 mm Hg and IOP reduction of 25%; (C) IOP<12 mm Hg and IOP reduction of 30%. Secondary outcomes were number of glaucoma medications, complications, and need for additional glaucoma surgery. RESULTS: Twenty eyes (19 patients) were included for analysis. Median follow-up and age were 3.7 years (range, 1.1 to 10.2 y) and 64.2 years (range, 25.2 to 85.6 y), respectively. Mean IOP (±SD) has dropped from 19.3±4.2 mm Hg preoperatively to 9.8±2.2 mm Hg at 1 year, 8.8±3.2 mm Hg at 3 years and 8.4±1.5 mm Hg at 5 years (P<0.001 for all). Hypotony maculopathy was the only serious complication (2/19 patients; 10%) that needed surgical revision. The cumulative success rate (±SD) for criterion A and B were 73.2% (±10.0%) and 68.2% (±9.5%), respectively, between the first and fifth year of follow-up, for criterion C it was 49.1% (±10.8%) at the first year and 32.7% (±12%) between the second and fifth year of follow-up. CONCLUSIONS: Trabeculectomy is a viable surgical option to treat IOP that is uncontrolled after GDD implantation.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Implantação de Prótese , Trabeculectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alquilantes/administração & dosagem , Feminino , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Hipotensão Ocular/fisiopatologia , Hipotensão Ocular/cirurgia , Reoperação , Estudos Retrospectivos , Tonometria Ocular , Resultado do Tratamento , Acuidade Visual/fisiologia
15.
Sci Rep ; 7(1): 17071, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29213129

RESUMO

Outflow resistance in the aqueous drainage tract distal to trabecular meshwork is potentially an important determinant of intraocular pressure and success of trabecular bypass glaucoma surgeries. It is unclear how distal resistance is modulated. We sought to establish: (a) multimodal 2-photon deep tissue imaging and 3-dimensional analysis of the distal aqueous drainage tract (DT) in transgenic mice in vivo and ex vivo; (b) criteria for distinguishing the DT from blood and lymphatic vessels; and (c) presence of a DT wall organization capable of contractility. DT lumen appeared as scleral collagen second harmonic generation signal voids that could be traced back to Schlemm's canal. DT endothelium was Prox1-positive, CD31-positive and LYVE-1-negative, bearing a different molecular signature from blood and true lymphatic vessels. DT walls showed prominent filamentous actin (F-actin) labeling reflecting cells in a contracted state. F-actin co-localized with mesenchymal smooth muscle epitopes of alpha-smooth muscle actin, caldesmon and calponin, which localized adjacent and external to the endothelium. Our findings support a DT wall organization resembling that of blood vessels. This reflects a capacity to contract and support dynamic alteration of DT caliber and resistance analogous to the role of blood vessel tone in regulating blood flow.


Assuntos
Humor Aquoso/metabolismo , Malha Trabecular/metabolismo , Actinas/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Endotélio/metabolismo , Proteínas de Homeodomínio/metabolismo , Vasos Linfáticos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microscopia de Fluorescência por Excitação Multifotônica , Contração Muscular , Músculo Liso/patologia , Músculo Liso/fisiologia , Esclera/metabolismo , Esclera/ultraestrutura , Malha Trabecular/ultraestrutura , Proteínas Supressoras de Tumor/metabolismo , Calponinas
16.
Biomaterials ; 127: 89-96, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28284104

RESUMO

Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)-b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery.


Assuntos
Técnicas de Transferência de Genes , Ácidos Nucleicos/química , Poliaminas/química , Polímeros/química , Animais , Feminino , Células HeLa , Humanos , Hidrodinâmica , Concentração de Íons de Hidrogênio , Luciferases/metabolismo , Camundongos Endogâmicos C57BL , Polieletrólitos , Polímeros/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Transfecção
17.
Graefes Arch Clin Exp Ophthalmol ; 255(5): 1019-1025, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28176011

RESUMO

PURPOSE: To evaluate success rates in controlling intraocular pressure (IOP) after implantation of a second glaucoma drainage device (GDD) with a Baerveldt glaucoma implant in patients with refractory glaucoma, with a secondary aim of reducing the need for postoperative glaucoma medications. MATERIAL AND METHODS: This retrospective, noncomparative, interventional study included patients undergoing a second GDD for uncontrolled glaucoma from a tertiary care glaucoma service. Data were obtained from the medical records for the preoperative period and after the 1st, 15th, and 30th day, 3, 6, and 12 months, and then yearly until the last postoperative visit. Visual acuity, IOP, and number of glaucoma medications (NGM) from the follow-up visits were compared to baseline. Success and failure criteria were analyzed based on IOP level or need of glaucoma medications. RESULTS: Forty-nine patients were studied, with a mean follow-up time of 25 ± 21 months. The mean preoperative IOP was 23.7 ± 8.2 mmHg, and decreased to 14.8 ± 4.0 mmHg after 1 year, 14.4 ± 3.9 mmHg after 2 years, and 16.6 ± 8.5 mmHg after 3 years. The mean preoperative NGM was 3.4 ± 1.3, and decreased to 2.0 ± 1.8 after 1 year, 2.5 ± 1.6 after 2 years, and 2.8 ± 2.0 after 3 years. Absolute success was 9% after 1 year for a postoperative IOP between 5 and 18 mmHg, and 76% for a postoperative IOP between 5 and 21 mmHg. The qualified success was 88% at the first and second years and 83% at the third year. CONCLUSION: With up to 3 years of follow-up, a second glaucoma drainage device was successful in reducing IOP to below 21 mmHg, but not as successful below 18 mmHg. The success rate is improved with the use of glaucoma medications with up to 3 years of follow-up.


Assuntos
Cirurgia Filtrante/métodos , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Clin Exp Ophthalmol ; 45(3): 241-246, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27570215

RESUMO

BACKGROUND: To evaluate the efficacy in controlling intraocular pressure (IOP) with endoscopic cyclophotocoagulation (ECP) versus implantation of a second glaucoma drainage device (GDD-2) in the treatment of uncontrolled glaucoma with a prior aqueous tube shunt. DESIGN: A nonrandomized retrospective chart review. PARTICIPANTS: Patients with refractory glaucoma following a failed initial tube shunt (Baerveldt Glaucoma Implant 350), who underwent ECP or GDD-2 with Baerveldt Glaucoma Implant as a second surgery. Twenty-five eyes underwent ECP, and 48 eyes received a GDD-2. METHODS: ECP or second tube-shunt surgery. MAIN OUTCOME MEASURES: Reduction in IOP and antiglaucoma medications, and Kaplan-Meier survival with success defined as lOP ≥ 5 mmHg and ≤ 21 mmHg and ≥ 20% reduction from preoperative IOP. Secondary outcome measures were visual acuity and the presence of any postoperative complications. RESULTS: Both ECP and GDD-2 significantly lowered IOP (Student's t test) and number of antiglaucoma medications (Wilcoxon paired signed rank test). There were no significant differences in postoperative IOP (Student's t test) or antiglaucoma medications (Mann Whitney test) between ECP and GDD-2 at 6 and 12 months. There was also no difference in the Kaplan-Meier survival outcomes between the two groups. CONCLUSION: Both ECP and GDD-2 are both effective as second surgeries for refractory glaucoma that has failed a prior aqueous shunt.


Assuntos
Corpo Ciliar/cirurgia , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Fotocoagulação a Laser , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/fisiologia , Endoscopia , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Reoperação , Estudos Retrospectivos , Tonometria Ocular , Acuidade Visual/fisiologia
19.
Environ Sci Technol ; 50(20): 10951-10959, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27715012

RESUMO

The removal of arsenic from drinking water sources produces arsenic-bearing wastes, which are disposed of in a variety of ways. Several disposal options involve anaerobic environments, including mixing arsenic waste with cow dung, landfills, anaerobic digesters, and pond sediments. Though poorly understood, the production of gaseous arsenic species in these environments can be a primary goal (cow dung mixing) or an unintended consequence (anaerobic digesters). Once formed, these gaseous arsenic species are readily diluted in the atmosphere. Arsenic volatilization can be mediated by the enzyme arsenite S-adenosylmethionine methyltransferase (ArsM) or through the enzymes involved in methanogenesis. In this study, methanogenic mesocosms with arsenic-bearing ferric iron waste from an electrocoagulation drinking water treatment system were used to evaluate the role of methanogenesis in arsenic volatilization using methanogen inhibitors. Arsenic volatilization was highest in methanogenic mesocosms, but represented <0.02% of the total arsenic added. 16S rRNA cDNA sequencing, qPCR of mcrA transcripts, and functional gene array-based analysis of arsM expression, revealed that arsenic volatilization correlated with methanogenic activity. Aqueous arsenic concentrations increased in all mesocosms, indicating that unintended contamination may result from disposal in anaerobic environments. This highlights that more research is needed before recommending anaerobic disposal intended to promote arsenic volatilization.

20.
Invest Ophthalmol Vis Sci ; 57(11): 4558-65, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27588614

RESUMO

PURPOSE: To assess the ability of trabecular micro-bypass stents to improve aqueous humor outflow (AHO) in regions initially devoid of AHO as assessed by aqueous angiography. METHODS: Enucleated human eyes (14 total from 7 males and 3 females [ages 52-84]) were obtained from an eye bank within 48 hours of death. Eyes were oriented by inferior oblique insertion, and aqueous angiography was performed with indocyanine green (ICG; 0.4%) or fluorescein (2.5%) at 10 mm Hg. With an angiographer, infrared and fluorescent images were acquired. Concurrent anterior segment optical coherence tomography (OCT) was performed, and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative areas. Experimentally, some eyes (n = 11) first received ICG aqueous angiography to determine angiographic patterns. These eyes then underwent trabecular micro-bypass sham or stent placement in regions initially devoid of angiographic signal. This was followed by fluorescein aqueous angiography to query the effects. RESULTS: Aqueous angiography in human eyes yielded high-quality images with segmental patterns. Distally, angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Trabecular bypass but not sham in regions initially devoid of ICG aqueous angiography led to increased aqueous angiography as assessed by fluorescein (P = 0.043). CONCLUSIONS: Using sequential aqueous angiography in an enucleated human eye model system, regions initially without angiographic flow or signal could be recruited for AHO using a trabecular bypass stent.


Assuntos
Humor Aquoso/metabolismo , Angiofluoresceinografia/métodos , Verde de Indocianina/farmacocinética , Malha Trabecular/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/diagnóstico por imagem , Cadáver , Corantes/farmacocinética , Enucleação Ocular , Feminino , Fundo de Olho , Glaucoma/diagnóstico , Glaucoma/metabolismo , Glaucoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Tomografia de Coerência Óptica , Malha Trabecular/metabolismo , Malha Trabecular/cirurgia , Gravação em Vídeo
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