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1.
J Am Acad Dermatol ; 79(5): 869-877, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29864467

RESUMO

BACKGROUND: Approved topical treatments for seborrheic keratoses (SKs) are an unmet need. OBJECTIVE: To evaluate the safety and efficacy of 40% hydrogen peroxide topical solution (HP40) versus vehicle for the treatment of SKs (A-101-SEBK). METHODS: A total of 937 patients with 4 SKs each (≥1 lesion each on the face and on the trunk and/or an extremity) were randomized 1:1 to HP40 or vehicle. At each visit, SKs were graded using the Physician's Lesion Assessment (PLA) scale (0, clear; 1, nearly clear; 2, ≤1 mm thick; and 3, >1 mm thick). After 1 treatment, SKs with a PLA score higher than 0 were re-treated 3 weeks later. RESULTS: At day 106, significantly more patients treated with HP40 than with vehicle achieved a PLA score of 0 on all 4 SKs (study 1, 4% vs 0%; study 2, 8% vs 0% [both P < .01]) and on 3 of 4 SKs (study 1, 13% vs 0%; study 2, 23% vs 0% [both P < .0001]). A higher mean per-patient percentage of SKs were clear (study 1, 25% vs 2%; study 2, 34% vs 1%) and clear or nearly clear (study 1, 47% vs 10%; study 2, 54% vs 5%) with HP40 than with vehicle. Local skin reactions were largely mild and resolved by day 106. LIMITATIONS: The optimal number of treatment sessions was not evaluated. CONCLUSION: Application of HP40 was well tolerated and effective in the removal of SKs.


Assuntos
Peróxido de Hidrogênio/uso terapêutico , Ceratose Seborreica/diagnóstico , Ceratose Seborreica/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Medição de Risco , Resultado do Tratamento , Estados Unidos
2.
Dermatol Surg ; 44(3): 330-340, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28902028

RESUMO

BACKGROUND: Seborrheic keratosis (SK) is a common benign skin tumor, yet no topical treatments are approved in the United States. OBJECTIVE: To evaluate the proprietary, stabilized, high-concentration hydrogen peroxide-based topical solution A-101 (32.5% and 40% concentrations) for treatment of facial SK lesions. MATERIALS AND METHODS: In this multicenter, double-blind, vehicle-controlled study, eligible subjects were randomly assigned to receive up to 2 treatments of A-101 40%, A-101 32.5%, or vehicle solution applied to a single facial SK lesion. The primary efficacy assessment was the Physician's Lesion Assessment (PLA), a validated 4-ordinal scale. RESULTS: The primary end point, the mean reduction in PLA grade from baseline to Day 106 was 1.7 for A-101 40%, 1.4 for A-101 32.5%, and 0.1 for vehicle (p < .001, both concentrations vs vehicle). Lesions for 68%, 62%, and 5% of subjects, respectively, were judged to be clear or near clear (p < .001, both concentrations vs vehicle). Local skin reactions were predominantly mild and transient. No subjects discontinued because of treatment-related adverse events. CONCLUSION: A-101 solution demonstrated efficacy in treating SKs on the face. Greater magnitude of effect was seen with the 40% concentration than the 32.5% concentration. A-101 solution had a favorable safety and tolerability profile at both concentrations.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Peróxido de Hidrogênio/administração & dosagem , Ceratose Seborreica/tratamento farmacológico , Administração Tópica , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Sci Adv ; 10(18): eadk4946, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38691597

RESUMO

This phase 2a trial investigated the efficacy of NFX-179 Topical Gel, a metabolically labile MEK inhibitor, in the treatment of cutaneous neurofibromas (cNFs) in neurofibromatosis type 1. Forty-eight participants were randomized to four treatment arms: NFX-179 Topical Gel 0.05%, 0.15%, and 0.5% or vehicle applied once daily to five target cNFs for 28 days. Treatment with NFX-179 Topical Gel resulted in a dose-dependent reduction in p-ERK levels in cNFs at day 28, with a 47% decrease in the 0.5% NFX-179 group compared to the vehicle (P = 0.0001). No local or systemic toxicities were observed during the treatment period, and systemic concentrations of NFX-179 remained below 1 ng/ml. In addition, 20% of cNFs treated with 0.5% NFX-179 Topical Gel showed a ≥50% reduction in volume compared to 6% in the vehicle group by ruler measurement with calculated volume (P = 0.021). Thus, NFX-179 Topical Gel demonstrated significant inhibition of MEK in cNF with excellent safety and potential therapeutic benefit.


Assuntos
Neurofibromatose 1 , Inibidores de Proteínas Quinases , Neoplasias Cutâneas , Humanos , Neurofibromatose 1/tratamento farmacológico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neurofibroma/tratamento farmacológico , Neurofibroma/patologia , Neurofibroma/metabolismo , Adulto Jovem , Adolescente , Resultado do Tratamento , Administração Tópica , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
4.
PLoS Comput Biol ; 8(12): e1002845, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300425

RESUMO

The structural proteins of the extracellular matrix (ECM) form fibers with finely tuned mechanical properties matched to the time scales of cell traction forces. Several proteins such as fibronectin (Fn) and fibrin undergo molecular conformational changes that extend the proteins and are believed to be a major contributor to the extensibility of bulk fibers. The dynamics of these conformational changes have been thoroughly explored since the advent of single molecule force spectroscopy and molecular dynamics simulations but remarkably, these data have not been rigorously applied to the understanding of the time dependent mechanics of bulk ECM fibers. Using measurements of protein density within fibers, we have examined the influence of dynamic molecular conformational changes and the intermolecular arrangement of Fn within fibers on the bulk mechanical properties of Fn fibers. Fibers were simulated as molecular strands with architectures that promote either equal or disparate molecular loading under conditions of constant extension rate. Measurements of protein concentration within micron scale fibers using deep ultraviolet transmission microscopy allowed the simulations to be scaled appropriately for comparison to in vitro measurements of fiber mechanics as well as providing estimates of fiber porosity and water content, suggesting Fn fibers are approximately 75% solute. Comparing the properties predicted by single molecule measurements to in vitro measurements of Fn fibers showed that domain unfolding is sufficient to predict the high extensibility and nonlinear stiffness of Fn fibers with surprising accuracy, with disparately loaded fibers providing the best fit to experiment. This work shows the promise of this microstructural modeling approach for understanding Fn fiber properties, which is generally applicable to other ECM fibers, and could be further expanded to tissue scale by incorporating these simulated fibers into three dimensional network models.


Assuntos
Matriz Extracelular/química , Fibronectinas/química , Microscopia/métodos , Modelos Moleculares , Conformação Proteica , Desnaturação Proteica
5.
Biophys J ; 101(7): 1740-8, 2011 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-21961600

RESUMO

The extracellular matrix contains components with remarkable mechanical properties, including fibronectin (Fn) fibers with extensibilities of >700% strain. We utilized what we consider a novel technique to quantify the extent of molecular unfolding that contributes to Fn fiber extension, and we compared this behavior with stochastic models of Fn fibers with different molecular arrangements. In vitro unfolding as a function of strain was measured by fluorescently labeling cysteines in modules FnIII7 and III15 in artificial Fn fibers. A calibration technique we also consider novel made it possible to demonstrate that 44% of cysteines in these modules were exposed in Fn fibers strained to 421% extension, up from 8% exposure without strain. In silico unfolding was measured by applying a constant strain rate to a fiber represented by a network of wormlike chain springs, each representing an individual Fn molecule. Unfolding rates were calculated with a tension-dependent stochastic model applied to FnIII modules in each molecule. A comparison of these approaches revealed that only a molecular arrangement permitting unequal mechanical loading of Fn molecules recapitulates in vitro unfolding. These data have implications for Fn-dependent mechanotransduction and give insight into how the molecular architecture of natural materials permits such remarkable extensibility.


Assuntos
Fibronectinas/química , Desdobramento de Proteína , Biologia Computacional , Cisteína , Humanos , Método de Monte Carlo , Espectrometria de Fluorescência
6.
Acta Biomater ; 88: 78-85, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30780000

RESUMO

Viscoelasticity is a fundamental property of virtually all biological materials, and proteinaceous, fibrous materials that constitute the extracellular matrix (ECM) are no exception. Viscoelasticity may be particularly important in the ECM since cells can apply mechanical stress resulting from cell contractility over very long periods of time. However, measurements of ECM fiber response to long-term constant force loading are scarce, despite the increasing recognition that mechanical strain regulates the biological function of some ECM fibers. We developed a dual micropipette system that applies constant force to single fibers for up to 8 h. We utilized this system to study the time dependent response of fibronectin (Fn) fibers to constant force, as Fn fibers exhibit tremendous extensibility before mechanical failure as well as strain dependent alterations in biological properties. These data demonstrate the Fn fibers continue to stretch under constant force loading for at least 8 h and that this long-term creep results in plastic deformation of Fn fibers, in contrast to elastic deformation of Fn fibers under short-term, but fast loading rate extension. These data demonstrate that physiologically-relevant loading may impart mechanical features to Fn fibers by switching them into an extended state that may have altered biological functions. STATEMENT OF SIGNIFICANCE: Measurements of extracellular matrix (ECM) fiber response to constant force loading are scarce, so we developed a novel technique for applying constant force to single ECM fibers. We used this technique to measure constant force creep of fibronectin fibers since these fibers have been shown to be mechanotransducers whose functions can be altered by mechanical strain. We found that fibronectin fibers creep under constant force loading for the duration of the experiment and that this creep behavior resembles a power law. Furthermore, we found that constant force creep results in plastic deformation of the fibers, which suggests that the mechanobiological switching of fibronectin can only occur once after long-term loading.


Assuntos
Matriz Extracelular/química , Fibronectinas/química , Teste de Materiais , Estresse Mecânico , Elasticidade , Viscosidade
7.
J Periodontol ; 79(1): 33-41, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18166090

RESUMO

BACKGROUND: Previous studies showed that host modulation therapy (HMT) or topical antimicrobial therapy (TAT) provided significant adjunctive benefits to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). The purpose of this study was to evaluate a combination therapy involving SRP, HMT, and TAT in the treatment of moderate to severe CP. METHODS: A 6-month, randomized, multicenter, placebo-controlled, examiner-masked study was undertaken to evaluate the clinical usefulness of a combination treatment of systemically delivered doxycycline hyclate (HMT; 20 mg, twice a day) plus locally delivered doxycycline hyclate gel (TAT; 10%, in pockets > or =5 mm) in combination with SRP versus SRP plus placebo. Clinical outcomes included mean changes in probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and gingival index (GI) at baseline and at 3 and 6 months. RESULTS: In 171 subjects, combination therapy provided significantly greater clinical benefits than control therapy for all clinical measures at 3 and 6 months. In moderate CP (PD of 4 to 6 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.03), BOP (3 months: P <0.02; 6 months: P <0.05), and GI (3 months: P <0.01; 6 months: P <0.03). In severe CP (PD > or =7 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.02), BOP (3 months: P <0.01; 6 months: P >0.05), and GI (3 months: P <0.01; 6 months: P <0.01). CONCLUSION: Combination therapy, including SRP, HMT, and TAT, provided significantly greater clinical benefits than SRP alone in the treatment of moderate to severe CP.


Assuntos
Antibacterianos/administração & dosagem , Raspagem Dentária , Doxiciclina/administração & dosagem , Periodontite/terapia , Aplainamento Radicular , Administração Oral , Administração Tópica , Adolescente , Adulto , Idoso , Doença Crônica , Terapia Combinada , Feminino , Seguimentos , Hemorragia Gengival/tratamento farmacológico , Hemorragia Gengival/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/tratamento farmacológico , Perda da Inserção Periodontal/terapia , Índice Periodontal , Bolsa Periodontal/tratamento farmacológico , Bolsa Periodontal/terapia , Periodontite/tratamento farmacológico , Placebos , Método Simples-Cego , Resultado do Tratamento
8.
J Periodontol ; 79(3): 440-52, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18315426

RESUMO

BACKGROUND: Previous studies showed that adjunctive subantimicrobial dose doxycycline (SDD; 20 mg, twice daily) provides significant clinical benefits to scaling and root planing (SRP). A modified-release SDD formulation containing 40 mg doxycycline (SDD-40) to be taken once daily has been developed. The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis. METHODS: A 9-month, double-masked, randomized, placebo-controlled, multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis. Subjects were treated by SRP and randomized to receive SDD-40 or placebo for 9 months with evaluations at 3, 6, and 9 months. RESULTS: Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points. At month 9, at sites with baseline probing depths (PD) > or =6 mm, 72% to 76% of sites in the SDD-40 group demonstrated clinically significant PD reductions and clinical attachment level (CAL) gains > or =2 mm compared to 56% to 58% of sites in the placebo group (P <0.0001); 48% to 52% of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32% of sites in the placebo group (P <0.0001). In moderate sites (baseline PD 4 to 6 mm), adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL (all time points: P <0.05), PD (3 months: P = 0.002; 6 and 9 months: P = 0.001), and bleeding on probing (BOP) (3 months: P <0.01; 6 months: P <0.02; 9 months: P <0.05). In deep sites (baseline PD > or =7 mm), SDD-40 provided significant benefits over control for mean CAL (3 months: P <0.05; 6 and 9 months: P <0.01), PD (all time points: P <0.001), and BOP (3 months: P <0.05; 6 months: not statistically significant; 9 months: P <0.05). Compliance with study medication was high (>92%) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group. CONCLUSION: SDD-40 used as an adjunct to SRP resulted in significantly greater clinical benefits than SRP alone in the treatment of periodontitis.


Assuntos
Antibacterianos/administração & dosagem , Raspagem Dentária , Doxiciclina/administração & dosagem , Periodontite/tratamento farmacológico , Periodontite/terapia , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Bactérias Anaeróbias/isolamento & purificação , Contagem de Colônia Microbiana , Terapia Combinada , Placa Dentária/microbiologia , Método Duplo-Cego , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Estatísticas não Paramétricas
9.
Cognition ; 105(1): 237-45, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17069787

RESUMO

An object that moves is spotted almost effortlessly; it "pops out". When the observer is stationary, a moving object is uniquely identified by retinal motion. This is not so when the observer is also moving; as the eye travels through space all scene objects change position relative to the eye producing a complicated field of retinal motion. Without the unique identifier of retinal motion an object moving relative to the scene should be difficult to locate. Using a search task, we investigated this proposition. Computer-rendered objects were moved and transformed in a manner consistent with movement of the observer. Despite the complex pattern of retinal motion, objects moving relative to the scene were found to pop out. We suggest the brain uses its sensitivity to optic flow to "stabilise" the scene, allowing the scene-relative movement of an object to be identified.


Assuntos
Movimento/fisiologia , Retina/fisiologia , Percepção Visual , Atenção , Humanos
10.
J Am Acad Dermatol ; 56(5): 791-802, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17367893

RESUMO

BACKGROUND: Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea. OBJECTIVE: To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea. METHODS: In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count. RESULTS: The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%). LIMITATIONS: In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea. CONCLUSION: Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doxiciclina/administração & dosagem , Rosácea/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Skinmed ; 6(5): 221-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17786099

RESUMO

BACKGROUND: Two large clinical trials have recently demonstrated the efficacy of a 40-mg controlled-release formulation of doxycycline in the treatment of rosacea, a dose well below the conventional level of 100 to 200 mg/d. Since no formal dose-response studies have been conducted, the authors analyzed phase 3 data to determine whether a dose-efficacy relationship exists. METHODS: Standard parametric regression analyses were used to estimate the correlations between dose (mg/kg body weight) and overall drug exposure (area under the curve [AUC]) in a phase 1 pharmacokinetic study and between dose and efficacy (mean change from baseline in total inflammatory lesion count at week 16) in 2 pooled phase 3 clinical efficacy studies. Additional regressions were run at each visit for the clinical efficacy studies to determine whether results differed across visits. A regression analysis was also performed in a subset of patients who showed a greater efficacy response. RESULTS: We found overall drug exposure (AUC) to have a highly significant correlation with dose (mg/kg) (r=0.49; P=.006). In contrast, clinical efficacy did not correlate with dose at any of the visits at week 3 (r=0.01; P=.85), week 6 (r=0.04; P=.53), week 12 (r<0.01; P=.98), and week 16 (r=0.03; P=.64) or among the subset of patients who showed greater clinical benefit. CONCLUSIONS: Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti-inflammatory dose doxycycline (40-mg controlled-release formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doxiciclina/administração & dosagem , Rosácea/tratamento farmacológico , Anti-Inflamatórios/farmacocinética , Área Sob a Curva , Ensaios Clínicos Fase I como Assunto , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Doxiciclina/farmacocinética , Humanos , Modelos Lineares
12.
Vision Res ; 46(17): 2636-44, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16571356

RESUMO

Binocular disparity and motion parallax provide information about the spatial structure and layout of the world. Descriptive similarities between the two cues have often been noted which have been taken as evidence of a close relationship between them. Here, we report two experiments which investigate the effect of surface orientation and modulation frequency on (i) a threshold detection task and (ii) a supra-threshold depth-matching task using sinusoidally corrugated surfaces defined by binocular disparity or motion parallax. For low frequency corrugations, an orientation anisotropy was observed in both domains, with sensitivity decreasing as surface orientation was varied from horizontal to vertical. In the depth-matching task, for surfaces defined by binocular disparity the greatest depth was seen for oblique orientations. For surfaces defined by motion parallax, perceived depth was found to increase as surface orientation was varied from horizontal to vertical. In neither case was perceived depth for supra-threshold surfaces related to threshold performance in any simple manner. These results reveal clear differences between the perception of depth from binocular disparity or motion parallax, and between perception at threshold and supra-threshold levels of performance.


Assuntos
Percepção de Profundidade/fisiologia , Percepção de Movimento/fisiologia , Disparidade Visual/fisiologia , Sinais (Psicologia) , Humanos , Masculino , Orientação , Estimulação Luminosa/métodos , Limiar Sensorial/fisiologia , Visão Binocular
13.
Nat Commun ; 7: 13222, 2016 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-27782135

RESUMO

The no-cloning theorem states that an unknown quantum state cannot be cloned exactly and deterministically due to the linearity of quantum mechanics. Associated with this theorem is the quantitative no-cloning limit that sets an upper bound to the quality of the generated clones. However, this limit can be circumvented by abandoning determinism and using probabilistic methods. Here, we report an experimental demonstration of probabilistic cloning of arbitrary coherent states that clearly surpasses the no-cloning limit. Our scheme is based on a hybrid linear amplifier that combines an ideal deterministic linear amplifier with a heralded measurement-based noiseless amplifier. We demonstrate the production of up to five clones with the fidelity of each clone clearly exceeding the corresponding no-cloning limit. Moreover, since successful cloning events are heralded, our scheme has the potential to be adopted in quantum repeater, teleportation and computing applications.

14.
J Am Acad Dermatol ; 53(5): 791-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16243127

RESUMO

BACKGROUND: Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea. METHODS: Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16. RESULTS: Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy. CONCLUSION: Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy.


Assuntos
Anti-Infecciosos/administração & dosagem , Doxiciclina/análogos & derivados , Metronidazol/administração & dosagem , Rosácea/tratamento farmacológico , Administração Tópica , Adulto , Método Duplo-Cego , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Comprimidos
15.
Neuropsychologia ; 40(11): 1766-78, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12062888

RESUMO

Neuropsychological results support the proposal that the human visual system is organised into distinct processing pathways, one for conscious perception and one for the control of action. Here, we compare perceptual and action responses following a pre-response-delay. Experiment 1 required participants to reproduce remembered locations and found that although perceptual matches were unaffected by delays of up to 4 s, pointing responses were significantly biased after only 2 s. Experiment 2 examined whether both the transport and grasp components of a natural prehensile movement were similarly affected by delay. Both peak wrist velocities and peak grip-apertures were affected equivalently by delay, suggesting that the two components of a prehensile movement have similar temporal constraints. The results from both experiments are consistent with the general perception-action dichotomy as originally proposed by Milner and Goodale [The visual brain in action, Oxford: Oxford University Press, 1995].


Assuntos
Movimento , Tempo de Reação/fisiologia , Percepção Visual , Adulto , Feminino , Mãos , Humanos , Masculino , Memória , Processos Mentais
16.
Neuropsychologia ; 41(4): 415-20, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12559159

RESUMO

Binocular cues have been shown previously to make an important contribution to the control of natural prehensile movements in adults [Visual Cognition 4 (1997) 113, Vision Research 32 (1992) 1513, Neuropsychologia 38 (2000) 1473]. The present study examined the role of binocular vision in the control of prehension in middle childhood. Fourteen children aged 5-6 years, and 16 children aged 10-11 years reached out and grasped different sized objects at different distances, in either binocular or monocular viewing conditions. In contrast to adult data, many of the principal kinematic indices of the children's reaches were unaffected by the removal of binocular information. The older children, like adults, spent an increased amount of time in the final approach to the object when only monocular information was available. However, both peak wrist velocities and peak grip apertures were unaffected by the removal of binocular information and continued to scale with object properties in the normal way. These results suggest that the use of binocular cues to control prehensile movements is not yet mature at the age of 10-11 years.


Assuntos
Desempenho Psicomotor/fisiologia , Visão Binocular/fisiologia , Criança , Desenvolvimento Infantil , Pré-Escolar , Percepção de Distância/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Percepção de Tamanho/fisiologia , Visão Monocular/fisiologia
17.
Arch Dermatol ; 139(4): 459-64, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12707093

RESUMO

OBJECTIVE: To determine if treatment with subantimicrobial-dose (SD) doxycycline hyclate (20-mg tablets taken twice daily) improved clinical outcome, had any detectable effect on skin flora, led to overgrowth or colonization of skin by opportunistic pathogens, or resulted in an increase in antibiotic resistance by the surface skin microflora in patients with moderate acne compared with placebo. DESIGN: Multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. SETTING: Two university-based clinics. SUBJECTS: Adults (N = 51) with moderate facial acne. INTERVENTIONS: Patients were randomized to receive SD doxycycline (Periostat; CollaGenex Pharmaceuticals Inc, Newtown, Pa) or placebo twice daily for 6 months. MAIN EFFICACY OUTCOMES: Primary: changes from baseline in numbers of inflammatory, noninflammatory, and total lesions. Secondary: changes from baseline of individual counts of papules, pustules, and nodules and global assessments of clinical improvement by patient and physician. RESULTS: Forty patients completed 6 months of treatment. At 6 months, the SD doxycycline group had a significantly greater percent reduction in the number of comedones (P<.01), inflammatory and noninflammatory lesions combined (P<.01), and total inflammatory lesions (P<.05) than did the placebo group. They also had significantly greater improvement according to the clinician's global assessment (P =.03). There were no significant differences in microbial counts between groups and no evidence of change in antibiotic susceptibility or colonization by potential pathogens. The treatment was well tolerated. CONCLUSIONS: Twice-daily SD doxycycline treatment significantly reduced the number of inflammatory and noninflammatory lesions in patients with moderate facial acne, was well tolerated, had no detectable antimicrobial effect on the skin flora, and did not result in any increase in the number or severity of resistant organisms.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Doxiciclina/análogos & derivados , Doxiciclina/administração & dosagem , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Administração Oral , Adolescente , Adulto , Antibacterianos/efeitos adversos , Método Duplo-Cego , Doxiciclina/efeitos adversos , Feminino , Humanos , Masculino , Pele/microbiologia
18.
J Exp Psychol Hum Percept Perform ; 29(2): 404-15, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12760624

RESUMO

The primary visual sources of depth and size information are binocular cues and motion parallax. Here, the authors determine the efficacy of these cues to control prehension by presenting them in isolation from other visual cues. When only binocular cues were available, reaches showed normal scaling of the transport and grasp components with object distance and size. However, when only motion parallax was available, only the transport component scaled reliably. No additional increase in scaling was found when both cues were available simultaneously. Therefore, although equivalent information is available from binocular and motion parallax information, the latter may be of relatively limited use for the control of the grasp. Binocular disparity appears selectively important for the control of the grasp.


Assuntos
Percepção de Movimento/fisiologia , Destreza Motora/fisiologia , Movimento/fisiologia , Percepção Espacial/fisiologia , Visão Binocular/fisiologia , Adaptação Fisiológica , Adulto , Braço/fisiologia , Percepção de Profundidade/fisiologia , Percepção de Distância/fisiologia , Feminino , Mãos/fisiologia , Força da Mão/fisiologia , Humanos , Masculino , Disparidade Visual/fisiologia
19.
J Exp Psychol Hum Percept Perform ; 28(2): 469-76, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11999867

RESUMO

Observers are more sensitive to variations in the depth of stereoscopic surfaces in a vertical than in a horizontal direction; however, there are large individual differences in this anisotropy. The authors measured discrimination thresholds for surfaces slanted about a vertical axis or inclined about a horizontal axis for 50 observers. Orientation and spatial frequency discrimination thresholds were also measured. For most observers, thresholds were lower for inclination than for slant and lower for orientation than for spatial frequency. There was a positive correlation between the 2 anisotropies, resulting from positive correlations between (a) orientation and inclination thresholds and (b) spatial frequency and slant thresholds. These results support the notion that surface inclination and slant perception is in part limited by the sensitivity of orientation and spatial frequency mechanisms.


Assuntos
Anisotropia , Percepção de Profundidade , Individualidade , Orientação , Atenção , Sinais (Psicologia) , Discriminação Psicológica , Percepção de Forma , Humanos , Modelos Psicológicos , Desempenho Psicomotor , Tempo de Reação , Percepção Espacial , Disparidade Visual , Campos Visuais
20.
Vision Res ; 43(17): 1879-93, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12826111

RESUMO

This paper examines and contrasts motion-parallax analogues of the induced-size and induced-shear effects with the equivalent induced effects from binocular disparity. During lateral head motion or with binocular stereopsis, vertical-shear and vertical-size transformations produced 'induced effects' of apparent inclination and slant that are not predicted geometrically. With vertical head motion, horizontal-shear and horizontal-size transformations produced similar analogues of the disparity induced effects. Typically, the induced effects were opposite in direction and slightly smaller in size than the geometric effects. Local induced-shear and induced-size effects could be elicited from motion parallax, but not from disparity, and were most pronounced when the stimulus contained discontinuities in velocity gradient. The implications of these results are discussed in the context of models of depth perception from disparity and structure from motion.


Assuntos
Percepção de Profundidade/fisiologia , Percepção de Movimento/fisiologia , Disparidade Visual , Movimentos da Cabeça/fisiologia , Humanos , Visão Binocular/fisiologia
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