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Malaria is a significant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous antimalarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Artemisinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifically, mutations in the Kelch propeller domain on chromosome 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identified 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sample from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the central forest and south coastal regions, where transmission rates are lower. The observed mutations were not significantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongoing global surveillance of artemisinin resistance remains pivotal, and our findings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identification of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional significance.
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Antimaláricos , Artemisininas , Malaria Falciparum , Humanos , Plasmodium falciparum/genética , Artemisininas/farmacología , Artemisininas/uso terapéutico , Ghana/epidemiología , Resistencia a Medicamentos/genética , Proteínas Protozoarias/genética , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Polimorfismo Genético , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , MutaciónRESUMEN
Before ultraviolet (UV) radiation can be used as a horticultural management tool in commercial Cannabis sativa (cannabis) production, the effects of UV on cannabis should be vetted scientifically. In this study we investigated the effects of UV exposure level on photosynthesis, growth, inflorescence yield, and secondary metabolite composition of two indoor-grown cannabis cultivars: 'Low Tide' (LT) and 'Breaking Wave' (BW). After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈225 µmolâ m-2â s-1 in an 18-h light/6-h dark photoperiod, plants were grown for 9 weeks in a 12-h light/12-h dark "flowering" photoperiod under a canopy-level PPFD of ≈400 µmolâ m-2â s-1. Supplemental UV radiation was provided daily for 3.5 h at UV photon flux densities ranging from 0.01 to 0.8 µmolâ m-2â s-1 provided by light-emitting diodes (LEDs) with a peak wavelength of 287 nm (i.e., biologically-effective UV doses of 0.16 to 13 kJâ m-2â d-1). The severity of UV-induced morphology (e.g., whole-plant size and leaf size reductions, leaf malformations, and stigma browning) and physiology (e.g., reduced leaf photosynthetic rate and reduced Fv/Fm) symptoms intensified as UV exposure level increased. While the proportion of the total dry inflorescence yield that was derived from apical tissues decreased in both cultivars with increasing UV exposure level, total dry inflorescence yield only decreased in LT. The total equivalent Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) concentrations also decreased in LT inflorescences with increasing UV exposure level. While the total terpene content in inflorescences decreased with increasing UV exposure level in both cultivars, the relative concentrations of individual terpenes varied by cultivar. The present study suggests that using UV radiation as a production tool did not lead to any commercially relevant benefits to cannabis yield or inflorescence secondary metabolite composition.
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Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈425 µmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark "flowering" photoperiod under canopy-level PPFDs ranging from 120 to 1,800 µmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole-plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1,800 µmol·m-2·s-1, while leaf-level photosynthesis saturated well-below 1,800 µmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.
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The primary function of the urinary bladder is to store urine (continence) until a suitable time for voiding (micturition). These distinct processes are determined by the coordinated activation of sensory and motor components of the nervous system, which matures to enable voluntary control at the time of weaning. Our aim was to define the development and maturation of the nerve-organ interface of the mouse urinary bladder by mapping the organ and tissue distribution of major classes of autonomic (motor) and sensory axons. Innervation of the bladder was evident from E13 and progressed dorsoventrally. Increasing defasciculation of axon bundles to single axons within the muscle occurred through the prenatal period, and in several classes of axons underwent further maturation until P7. Urothelial innervation occurred more slowly than muscle innervation and showed a clear regional difference, from E18 the bladder neck having the highest density of urothelial nerves. These features of innervation were similar in males and females but varied in timing and tissue density between different axon classes. We also analysed the pelvic ganglion, the major source of motor axons that innervate the lower urinary tract and other pelvic organs. Cholinergic, nitrergic (subset of cholinergic) and noradrenergic neuronal cell bodies were present prior to visualization of these axon classes within the bladder. Examination of cholinergic structures within the pelvic ganglion indicated that connections from spinal preganglionic neurons to pelvic ganglion neurons were already present by E12, a time at which these autonomic ganglion neurons had not yet innervated the bladder. These putative preganglionic inputs increased in density prior to birth as axon terminal fields continued to expand within the bladder tissues. Our studies also revealed in numerous pelvic ganglion neurons an unexpected transient expression of calcitonin gene-related peptide, a peptide commonly used to visualise the peptidergic class of visceral sensory axons. Together, our outcomes enhance our understanding of neural regulatory elements in the lower urinary tract during development and provide a foundation for studies of plasticity and regenerative capacity in the adult system.
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Vejiga Urinaria/embriología , Vejiga Urinaria/inervación , Animales , Axones/metabolismo , Femenino , Ganglios Parasimpáticos/fisiología , Masculino , Ratones/embriología , Ratones Endogámicos C57BL , Neuronas Motoras/metabolismo , Neuronas Motoras/fisiología , Neuronas/fisiología , Pelvis/inervación , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Sistema Nervioso Simpático , Vejiga Urinaria/fisiologíaRESUMEN
While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS). MMS is an autosomal recessive condition described thus far in only a single First Nations population and causes intrauterine growth restriction, severe microcephaly, craniofacial anomalies, skeletal dysplasia, and neonatal lethality. Linkage analysis of affected families, including a very large pedigree, identified a single locus on Chromosome 21 linked to the disease (LOD > 9). Comprehensive genome sequencing did not reveal any pathogenic coding or canonical splicing mutations within the linkage region but identified several nonconserved noncoding variants. RNA-seq analysis detected aberrant splicing in DONSON due to one of these noncoding variants, showing a causative role for DONSON disruption in MMS. We show that DONSON is expressed in progenitor cells of embryonic human brain and other proliferating tissues, is co-expressed with components of the DNA replication machinery, and that Donson is essential for early embryonic development in mice as well, suggesting an essential conserved role for DONSON in the cell cycle. Our results demonstrate the utility of integrating transcriptomics into the study of human genetic disease when DNA sequencing alone is not sufficient to reveal the underlying pathogenic mutation.
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Proteínas de Ciclo Celular/genética , Replicación del ADN , Microcefalia/genética , Microcefalia/patología , Mutación , Proteínas Nucleares/genética , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Transcriptoma , Animales , Mapeo Cromosómico , Femenino , Ligamiento Genético , Inestabilidad Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Ratones , Ratones Noqueados , Microcefalia/etiología , Osteocondrodisplasias/etiología , Linaje , Embarazo , Empalme del ARN , Análisis de Secuencia de ARN , Secuenciación Completa del GenomaRESUMEN
The regulated proliferation and differentiation of neural stem cells before the generation and migration of neurons in the cerebral cortex are central aspects of mammalian development. Periventricular neuronal heterotopia, a specific form of mislocalization of cortical neurons, can arise from neuronal progenitors that fail to negotiate aspects of these developmental processes. Here we show that mutations in genes encoding the receptor-ligand cadherin pair DCHS1 and FAT4 lead to a recessive syndrome in humans that includes periventricular neuronal heterotopia. Reducing the expression of Dchs1 or Fat4 within mouse embryonic neuroepithelium increased progenitor cell numbers and reduced their differentiation into neurons, resulting in the heterotopic accumulation of cells below the neuronal layers in the neocortex, reminiscent of the human phenotype. These effects were countered by concurrent knockdown of Yap, a transcriptional effector of the Hippo signaling pathway. These findings implicate Dchs1 and Fat4 upstream of Yap as key regulators of mammalian neurogenesis.
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Cadherinas/genética , Corteza Cerebral/embriología , Células-Madre Neurales/metabolismo , Neurogénesis/genética , Proteínas Supresoras de Tumor/genética , Anomalías Múltiples/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Secuencia de Bases , Proteínas Relacionadas con las Cadherinas , Proteínas de Ciclo Celular , Diferenciación Celular , Proliferación Celular , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Anomalías Craneofaciales/genética , Deformidades Congénitas del Pie/genética , Técnicas de Silenciamiento del Gen , Deformidades Congénitas de la Mano/genética , Humanos , Discapacidad Intelectual/genética , Inestabilidad de la Articulación/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Heterotopia Nodular Periventricular/genética , Fosfoproteínas/genética , Análisis de Secuencia de ADN , Transducción de Señal/genética , Proteínas Señalizadoras YAPRESUMEN
PURPOSE: Foveal autofluorescence (AF) has been suggested to be a potential predictor of treatment outcome in choroidal neovascularization (CNV) secondary to age-related macular degeneration and could be a useful marker to help prognosticate for patients and for clinical trials. This retrospective study aims to determine if pretreatment foveal AF can predict treatment response to intravitreal bevacizumab monotherapy in CNV secondary to age-related macular degeneration. METHODS: Ninety-five eyes (85 patients) with naive CNV secondary to age-related macular degeneration, treated with intravitreal bevacizumab monotherapy were included in this study. Lesion size, CNV type on fluorescein angiography, pretreatment best-corrected visual acuity, and foveal AF pattern (intact/nonintact) were used as predictors. Multivariate linear regression and logistic regression were performed using best-corrected visual acuity change and anatomical response at 6 months as the dependent variables separately. RESULTS: Pretreatment foveal AF (intact or nonintact) did not predict visual outcome (P = 0.17) nor did lesion size (P = 0.2) or CNV type (P = 0.61). Foveal AF did correlate with the visual acuity but it did not predict any treatment response. Pretreatment best-corrected visual acuity was the only predictive factor for the visual outcome (P = 0.043). CONCLUSION: Pretreatment AF is not a predictor for the treatment response to intravitreal bevacizumab monotherapy in eyes with CNV secondary to age-related macular degeneration.
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Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neovascularización Coroidal/diagnóstico , Angiografía con Fluoresceína , Degeneración Macular/diagnóstico , Anciano , Anciano de 80 o más Años , Bevacizumab , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/fisiopatología , Exudados y Transudados , Femenino , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Oftalmoscopía , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiologíaRESUMEN
OBJECTIVES: To investigate the occurrence of antimicrobial resistance genes of human clinical relevance in Salmonella isolated from livestock in Great Britain. METHODS: Two hundred and twenty-five Salmonella enterica isolates were characterized using an antimicrobial resistance gene chip and disc diffusion assays. Plasmid profiling, conjugation experiments and identification of Salmonella genomic island 1 (SGI1) were performed for selected isolates. RESULTS: Approximately 43% of Salmonella harboured single or multiple antimicrobial resistance genes with pig isolates showing the highest numbers where 96% of Salmonella Typhimurium harboured one or more resistance genes. Isolates harbouring multiple resistances divided into three groups. Group 1 isolates harboured ampicillin/streptomycin/sulphonamide/tetracycline resistance and similar phenotypes. This group contained isolates from pigs, cattle and poultry that were from several serovars including Typhimurium, 4,[5],12:i:-, Derby, Ohio and Indiana. All Group 2 isolates were from pigs and were Salmonella Typhimurium. They contained a non-sul-type class 1 integron and up to 13 transferrable resistances. All Group 3 isolates harboured a class 1 integron and were isolated from all animal species included in the study. Most isolates were Salmonella Typhimurium and harboured SGI1. CONCLUSIONS: Salmonella isolated from livestock was shown to harbour antimicrobial resistance genes although no or little resistance to third-generation cephalosporins or ciprofloxacin, respectively, was detected. The preponderance in pigs of multidrug-resistant Salmonella Typhimurium makes it important to introduce control measures such as improved biosecurity to ensure that they do not pass through the food chain and limit human therapeutic options.
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Farmacorresistencia Bacteriana , Genes Bacterianos , Salmonelosis Animal/microbiología , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , Animales , Antibacterianos/farmacología , Conjugación Genética , ADN Bacteriano/genética , Islas Genómicas , Ganado , Análisis por Micromatrices , Pruebas de Sensibilidad Microbiana , Análisis de Secuencia por Matrices de Oligonucleótidos , Plásmidos/análisis , Salmonella enterica/efectos de los fármacos , Reino UnidoRESUMEN
The qnrS1 gene induces reduced susceptibility to fluoroquinolones in enterobacteria. We investigated the structure, antimicrobial susceptibility phenotype, and antimicrobial resistance gene characteristics of qnrS1 plasmids from hospitalized patients and community controls in southern Vietnam. We found that the antimicrobial susceptibilities, resistance gene characteristics, and plasmid structures of qnrS1 plasmids from the hospital differed from those from the community. Our data imply that the characteristics of the two plasmid groups are indicative of distinct selective pressures in the differing environments.
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Antibacterianos/farmacología , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/genética , Fluoroquinolonas/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/fisiología , Farmacorresistencia Bacteriana Múltiple/genética , Genotipo , Pruebas de Sensibilidad Microbiana , Plásmidos/genéticaRESUMEN
PURPOSE/OBJECTIVES: to evaluate a three-hour smoking cessation program and its effect on nurse knowledge, counseling behaviors, and confidence in counseling behaviors. DESIGN: program evaluation. SETTING: a Magnet-designated, 500-bed community hospital in Southern California. SAMPLE: 107 nurses. METHODS: program content included behavior counseling and pharmacotherapy along with role playing. Investigator-developed self-report surveys were completed on the day of the class and at 3, 6, and 12 months. MAIN RESEARCH VARIABLES: Short- and long-term changes in nurse knowledge, attitudes, and behaviors about tobacco cessation efforts. FINDINGS: knowledge significantly increased from baseline to post-test. Counseling skills improved. Nurses who completed all surveys exhibited no significant changes about asking patients to quit smoking but did demonstrate significant changes at three months regarding advising patients, assessing quit readiness, and providing assistance. Changes were maintained over the year. Nurses' average ability to counsel patients was rated "good or very good" after one year. At 3, 6, and 12 months, most respondents reported providing cessation counseling or referrals to at least one patient. CONCLUSIONS: these findings support tobacco cessation programs for bedside nurses as useful in enhancing nurse confidence in patient-counseling skills. IMPLICATIONS FOR NURSING: study findings demonstrated benefits to using the developed curriculum. Additional research is needed on tobacco cessation programs for hospital nurses, particularly with longitudinal outcomes and actual nurse behaviors.
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Educación Continua en Enfermería/métodos , Capacitación en Servicio/métodos , Personal de Enfermería en Hospital/educación , Educación del Paciente como Asunto/métodos , Cese del Uso de Tabaco/métodos , Consejo/métodos , Educación Continua en Enfermería/organización & administración , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Capacitación en Servicio/organización & administración , Evaluación de Programas y Proyectos de Salud , Estudios ProspectivosRESUMEN
Behaviors of patients with psychiatric illness who are hospitalized on nonbehavioral health units can be difficult to address by staff members. Instituting a rapid response team to proactively de-escalate potential volatile situations on nonpsychiatric units in a hospital allows earlier treatment of behavioral issues with these patients. The behavioral emergency response team (BERT) consists of staff members (registered nurses, social workers) from behavioral health services who have experience in caring for patients with acute psychiatric disorders as well as competence in management of assaultive behavior. BERT services were trialed on a medical pulmonary unit; gradual housewide implementation occurred over 2 years. Tools developed for BERT include an activation algorithm, educational cue cards for staff, and a staff survey. Results of a performance improvement survey reveal that staff nurses have had positive experiences with BERT but that many nurses are still not comfortable caring for psychiatric patients on their units.
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BACKGROUND: Antimicrobials are used to directly control bacterial infections in pet (ornamental) fish and are routinely added to the water these fish are shipped in to suppress the growth of potential pathogens during transport. METHODOLOGY/PRINCIPAL FINDINGS: To assess the potential effects of this sustained selection pressure, 127 Aeromonas spp. isolated from warm and cold water ornamental fish species were screened for tolerance to 34 antimicrobials. Representative isolates were also examined for the presence of 54 resistance genes by a combination of miniaturized microarray and conventional PCR. Forty-seven of 94 Aeromonas spp. isolates recovered from tropical ornamental fish and their carriage water were tolerant to > or =15 antibiotics, representing seven or more different classes of antimicrobial. The quinolone and fluoroquinolone resistance gene, qnrS2, was detected at high frequency (37% tested recent isolates were positive by PCR). Class 1 integrons, IncA/C broad host range plasmids and a range of other antibiotic resistance genes, including floR, bla(TEM-1), tet(A), tet(D), tet(E), qacE2, sul1, and a number of different dihydrofolate reductase and aminoglycoside transferase coding genes were also detected in carriage water samples and bacterial isolates. CONCLUSIONS: These data suggest that ornamental fish and their carriage water act as a reservoir for both multi-resistant bacteria and resistance genes.
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Aeromonas/genética , Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Peces/microbiología , Genes Bacterianos/genética , Microbiología del Agua , Aeromonas/efectos de los fármacos , Aeromonas/aislamiento & purificación , Animales , Clonación Molecular , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Integrones/genética , Pruebas de Sensibilidad Microbiana , Mutagénesis Insercional/efectos de los fármacos , Mutagénesis Insercional/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Plásmidos/genética , Reacción en Cadena de la Polimerasa , TemperaturaRESUMEN
PURPOSE: To compare high-resolution optical coherence tomography (OCT) and fluorescein angiography (FA) in detection of macular edema (ME) of various etiologies. METHODS: In a retrospective study over a 12-month period at one retina center, data for consecutive eyes that had undergone simultaneous conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients underwent additional examination with extremely high-resolution (6-microm)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc., Toronto, Ontario, Canada). RESULTS: Of 1,272 eyes, 1,208 (94.97%) had the finding of ME or subretinal fluid confirmed by both techniques. There were 49 eyes (3.86%) for which FA showed dye leakage in the macular area and OCT showed normal foveal contour. Of 10 eyes in this group that underwent imaging with ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and subretinal fluid, which was missed by FA. CONCLUSIONS: Both FA and high-resolution OCT are highly sensitive techniques and correlate well in detection of ME. However, there is a small chance that when performed alone they might miss existing subtle ME.
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Angiografía con Fluoresceína , Edema Macular/diagnóstico , Tomografía de Coherencia Óptica , Permeabilidad Capilar , Exudados y Transudados , Femenino , Humanos , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Oftalmoscopía , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To compare standardized visual outcomes and macular thickness changes associated with primary and secondary bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). METHODS: Eighteen eyes received primary bevacizumab treatment; 20 eyes received pegaptanib (Macugen; Eyetech/OSI Pharmaceuticals, New York, NY) as initial treatment followed by bevacizumab therapy. Both medications were injected at 6-week intervals. Best-corrected visual acuity was measured with the ETDRS chart. Three- and 6-month data were analyzed for all eyes. RESULTS: Mean visual acuity improvement in the primary bevacizumab treatment cohort was 1.5 ETDRS lines at 3 months (P = 0.0009) and 2.2 ETDRS lines at 6 months (P=0.0004) compared with -0.4 ETDRS line at 3 months (P=0.27) and 0.2 ETDRS line at 6 months (P=0.70) in the secondary bevacizumab treatment group. Mean decrease in retinal thickness was also higher in the primary bevacizumab treatment group (90.9 microm [P=0.0037] vs 43.8 microm [P=0.13], respectively) than in the secondary bevacizumab treatment group (73.72 microm [P=0.051] vs 33.0 microm [P=0.21], respectively) at 3 months and 6 months. CONCLUSION: Primary bevacizumab therapy resulted in significantly greater visual improvement than secondary bevacizumab treatment at 3 months or 6 months. To our knowledge, this is the first report comparing primary bevacizumab treatment of CNV in AMD with secondary bevacizumab treatment after multiple pegaptanib injections.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Aptámeros de Nucleótidos/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/complicaciones , Agudeza Visual/fisiología , Anciano , Anticuerpos Monoclonales Humanizados , Bevacizumab , Neovascularización Coroidal/etiología , Neovascularización Coroidal/fisiopatología , Femenino , Humanos , Inyecciones , Degeneración Macular/fisiopatología , Masculino , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Cuerpo VítreoRESUMEN
PURPOSE: To evaluate the use of intravitreal triamcinolone (IVTA) for the treatment of macular edema secondary to immune recovery uveitis (IRU) in patients with AIDS. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: Eight eyes of 7 patients receiving 13 injections. METHODS: Prospective, consecutive, interventional case series of 13 injections involving 8 eyes in 7 patients who underwent an intravitreal injection of 20 mg decanted triamcinolone acetate for fluorescein angiographically proven IRU-related macular edema. MAIN OUTCOME MEASURES: The primary outcome measure was vision (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included fluorescein angiography and optical coherence tomography. RESULTS: Visual acuity improved at all time points and was statistically significant at the 1-month and 3-month follow-up examinations. The average visual improvement was 3 lines at 3 months. Retinal volume and thickness improvement were statistically significant at all time points. All patients had a minimum follow-up of 9 months, and there were no cases of cytomegalovirus reactivation. CONCLUSIONS: Previous studies showed that treatment with sub-Tenon repository steroids for the treatment of macular edema of IRU was only marginally effective. However, the current study shows that IVTA can be an effective short-term treatment for macular edema secondary to IRU in patients with AIDS. Longer follow-up is needed to assess the durability of the effect and to monitor for longer-term complications and outcomes.
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Linfocitos T CD4-Positivos/inmunología , Glucocorticoides/uso terapéutico , Edema Macular/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Uveítis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Recuento de Linfocito CD4 , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/inmunología , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones , Edema Macular/diagnóstico , Edema Macular/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica , Uveítis/diagnóstico , Uveítis/inmunología , Agudeza Visual , Cuerpo VítreoAsunto(s)
Sistemas de Liberación de Medicamentos/instrumentación , Fibrinolíticos/administración & dosificación , Inyecciones/métodos , Degeneración Macular/complicaciones , Hemorragia Retiniana/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Humanos , Inyecciones/instrumentación , Hemorragia Retiniana/etiologíaRESUMEN
PURPOSE: To test the toxicity of intravitreal injections of benzyl alcohol. METHODS: Nine New Zealand rabbits were injected with either a control or a test article at elevating concentrations. The test article was benzyl alcohol calculated to give final injected concentrations of 0.0073%, 0.022%, 0.073%, 0.222%, and 0.733% benzyl alcohol. The 0.022% concentration corresponds to the concentration of benzyl alcohol in human eyes when 0.1 mL of commercial Kenalog (Bristol-Myers Squibb, Princeton, NJ) is used. Baseline examination of the rabbits was performed along with postinjection examinations on days 1, 3, 7, and 14. The eyes were enucleated and examined by light and electron microscopic examinations. RESULTS: Eyes injected with benzyl alcohol concentrations of 0.073%, 0.222%, and 0.733% displayed changes in the outer retina including loss of, and shortening of, outer segments and photoreceptors. CONCLUSIONS: Benzyl alcohol at concentrations modestly higher than what is present in commercial Kenalog is toxic to the rabbit eye. This has been shown in other organ systems. If commercial preserved Kenalog is to be used clinically, decanting the supernatant or using other means to remove the benzyl alcohol may be considered, especially if a volume of >0.1 mL of solution is used. We hypothesize that the noninfectious inflammation seen clinically after Kenalog injection is due to the presence of a toxic preservative at unsafe concentrations.
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Alcohol Bencilo/toxicidad , Glucocorticoides , Vehículos Farmacéuticos/toxicidad , Retina/efectos de los fármacos , Retina/patología , Enfermedades de la Retina/inducido químicamente , Triamcinolona Acetonida , Animales , Electrorretinografía , Inyecciones , Conejos , Enfermedades de la Retina/patología , Cuerpo VítreoRESUMEN
PURPOSE: To assess the efficacy of bioresorbable mesh in reconstruction of orbitocranial deformities. METHODS: A retrospective case series evaluating 6 orbits of 6 patients, ages 12 to 70 years old, with large multicontoured orbitocranial defects that were repaired using bioresorbable macroporous mesh. Both functional (presence of diplopia, ocular motility, exophthalmometry, and vertical globe position) and cosmetic outcomes were evaluated. RESULTS: Follow-up time ranged from 20 to 48 months (mean, 29.1 months). After surgery, all patients reported cosmetically pleasing results. Diplopia resolved in all patients. Ocular motility, exophthalmos, enophthalmos, and vertical globe positioning improved in all patients. One patient had new onset of mild enophthalmos and hypoglobus after surgery. No cases of implant exposure or instability occurred. Complications included one patient with skin breakdown over a previous site of irradiation and one patient with ptosis requiring surgical correction. CONCLUSIONS: Bioresorbable macroporous mesh combined with bone grafts is a useful and accurate method to reconstruct complex multicontoured orbitocranial defects.
Asunto(s)
Implantes Absorbibles , Modelos Anatómicos , Enfermedades Orbitales/cirugía , Implantes Orbitales , Procedimientos de Cirugía Plástica/métodos , Implantación de Prótesis/instrumentación , Mallas Quirúrgicas , Adolescente , Anciano , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Orbitales/diagnóstico por imagen , Diseño de Prótesis , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the percentage and risk indicators leading to retinal redetachment in HIV (human immunodeficiency virus) patients with CMV (cytomegalovirus) retinitis related retinal detachments that were repaired with silicone oil, and then subsequently underwent oil removal. DESIGN: Retrospective, noncomparative interventional case series. METHODS: The study cohort consisted of a series of 15 eyes in 14 patients with HIV and CMV retinitis with a retinal detachment (RD) repaired with silicone oil at a single center and followed from the time of the CMV retinitis diagnosis through the time of silicone oil removal. Patient- and eye-specific data regarding demographic and clinical characteristics were collected retrospectively and statistical analyses were performed to compare differences between the eyes that had retinal detachments versus the eyes that remained attached following removal of silicone oil. RESULTS: Eight eyes (53%) redetached after a median of 4.0 months following oil removal. Cataract surgery performed at the time of oil removal was a statistically significant risk factor for redetachment (P = .01). There was a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment. The use of a scleral buckle at the time of surgery (initial RD repair or at the time of oil removal) did not reduce the risk of redetachment. CONCLUSIONS: Approximately half of the eyes with CMV related retinal detachment may safely undergo oil removal. The risk factor for redetachment was simultaneous cataract extraction at the time of silicone oil removal. There was also a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment.