RESUMO
Although lectures are one of the most common methods of knowledge transfer in medicine, their effectiveness has been questioned. Passive formats, lack of relevance and disconnection from the student's needs are some of the arguments supporting this apparent lack of efficacy. However, many authors have suggested that applying adult learning principles (i.e., relevance, congruence with student's needs, interactivity, connection to student's previous knowledge and experience) to this method increases learning by lectures and the effectiveness of lectures. This paper presents recommendations for applying adult learning principles during planning, creation and development of lectures to make them more effective.
Assuntos
Educação de Pós-Graduação em Medicina/normas , Avaliação Educacional/métodos , Internato e Residência , Oftalmologia/educação , Aprendizagem Baseada em Problemas/métodos , Adulto , Competência Clínica/normas , HumanosRESUMO
PURPOSE: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in loss of central vision and dyschromatopsia, caused by mitochondrial DNA point mutations. However, only a subset of the mutation carriers becomes affected, with a higher penetrance in males. This study was conducted to investigate chromatic losses in asymptomatic carriers of the LHON mutation. METHODS: Monocular chromatic discrimination was studied with the Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK) along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15 men) belonging to the same LHON maternal lineage and 74 age-matched control subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and clear ocular media. A detailed neuro-ophthalmic examination was performed in all the LHON carriers. RESULTS: The differences in threshold between carriers and control subjects were significant for the three cone isolation axes at P < 0.0001. Sixty-five percent of the carriers had abnormal protan and/or deutan thresholds; some of those with higher thresholds also had elevated tritan thresholds (13%). The male thresholds were higher and more frequent than those of the women for the protan and deutan axes (ANOVA; P < 0.05), but not for tritan thresholds. In the most severe losses, the women had instances of diffuse defect whereas all the men displayed a red-green defect. CONCLUSIONS: Male LHON asymptomatic carriers had color vision losses with the red-green pattern of dyschromatopsia typical of patients affected with LHON, which includes elevation of tritan thresholds as well. This predominantly parvocellular (red-green) impairment is compatible with the histopathology of LHON, which affects mostly the papillomacular bundle. In contrast with male losses, female losses were less frequent and severe. These gender differences are relevant to understanding LHON pathophysiology, suggesting that hormonal factors may be of great importance.
Assuntos
Defeitos da Visão Cromática/genética , DNA Mitocondrial/genética , Heterozigoto , Atrofia Óptica Hereditária de Leber/genética , Mutação Puntual , Adulto , Brasil , Testes de Percepção de Cores , Defeitos da Visão Cromática/epidemiologia , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Linhagem , Prevalência , Reprodutibilidade dos Testes , Fatores SexuaisRESUMO
PURPOSE: The authors previously presented the results of their 2001 field investigation to rural Brazil to investigate a 336-member pedigree of Leber hereditary optic neuropathy (LHON). The present work describes the yearly field investigations 2001 to 2005, utilizing a variety of highly sophisticated psychophysical and electrophysiologic procedures, in asymptomatic LHON carriers, some of whom converted to affected status. METHODS: Careful, repeated examinations of 75 carriers of homoplasmic 11778 LHON mtDNA J-haplogroup mutants were performed as part of the field investigation of this pedigree. All subjects underwent a detailed neuro-ophthalmologic investigation, including formal visual fields (Humphrey; HVF) and fundus photography. In addition, many subjects underwent rigorous psychophysical examination, including Cambridge Research Systems color vision and contrast sensitivity testing, OCT, GDx, and multifocal visual evoked response (mfVER) and multifocal electroretinogram (mfERG). Two patients followed as nonsymptomatic LHON carriers converted to affected status. RESULTS: Many LHON carriers did, in fact, show subclinical or occult abnormalities. Focal edema was often seen involving the arcuate nerve fiber bundles, and this corresponded with areas of relative paracentral or arcuate scotomas on HVF testing. Compared to controls, LHON carriers had significant losses in color vision affecting mostly the red-green system and reduction in spatial but not temporal contrast sensitivity. The mfVER and mfERG data showed that most carriers had depressed central responses and abnormal interocular asymmetries. CONCLUSIONS: In this very large pedigree of 11778 LHON, the carriers frequently showed manifestations of optic nerve impairments. Their occult disease reflected low-grade compromise that waxed and waned. In two cases, these changes led to a crescendo of dramatic impairments that characterize conversion to affected status.
Assuntos
Atrofia Óptica Hereditária de Leber/diagnóstico , Nervo Óptico/patologia , Transtornos da Visão/diagnóstico , Adolescente , Adulto , Brasil , Portador Sadio , Criança , Testes de Percepção de Cores , Sensibilidades de Contraste , DNA Mitocondrial/genética , Eletrorretinografia , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Atrofia Óptica Hereditária de Leber/genética , Disco Óptico/patologia , Linhagem , Mutação Puntual , Estudos Prospectivos , População Rural , Órgão SubcomissuralRESUMO
PURPOSE: To determine whether asymptomatic 11778 LHON carriers demonstrated impairments in (1) chromatic red/green (R/G) and blue/yellow (B/Y) contrast sensitivity functions (CSF) and in (2) luminance contrast sensitivity functions in the spatial CSF (SCSF) and temporal CSF (TCSF) domains. METHODS: Twenty-five carriers (8 male, 17 female; 34.1 +/- 15.1 years of age) of homoplasmic 11778 LHON from the same well-described family and 30 age-matched controls (17 male, 13 female; 29.2 +/- 7.1 years of age) were tested in one eye, randomly selected. Of the 25 eyes tested, 18 had normal fundus, 5 had swelling and microangiopathy, and 2 had temporal pallor. The R/G and B/Y CSFs were obtained after equiluminance correction with bichromatic horizontal sinusoidal gratings at 0.3, 0.7, and 2 cycles per degree (cpd); the SCSFs were obtained with achromatic gratings at 0.3, 2, 6, and 12 cpd; and the TCSFs were obtained at 2, 10, 20, and 33 Hz with sinusoidal modulation of a 2.7 degrees field with a superimposed spatial Gabor function. RESULTS: Differences between carriers and controls were statistically significant for all spatial frequencies of chromatic and luminance SCSFs, but not for the TCSFs. R/G equiluminance settings of carriers differed from those of controls (P < 0.001), requiring higher luminance in the green; B/Y equiluminance settings were not statistically different in carriers and controls. Fundus findings did not correlate with CS results. CONCLUSIONS: Luminance and chromatic spatial CS losses that affected all tested spatial frequencies, are reported in LHON asymptomatic carriers with the mtDNA 11778 mutation. No losses were found in the temporal CSF. An intriguing finding is that the blue system is substantially spared in this LHON family. These represent subclinical visual impairments in otherwise asymptomatic LHON carriers.
Assuntos
Percepção de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , DNA Mitocondrial/genética , Mutação , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/fisiopatologia , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Fusão Flicker , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Óptica Hereditária de Leber/etnologia , Linhagem , Percepção Espacial , Acuidade VisualRESUMO
PURPOSE: To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN: Observational population cohort study. METHODS: A prospective investigation of an entire Brazilian LHON family. SETTING: A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION: We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES: We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS: We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS: Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.
Assuntos
Haplótipos , Atrofia Óptica Hereditária de Leber/epidemiologia , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Brasil/epidemiologia , Estudos de Coortes , Percepção de Cores , Sensibilidades de Contraste , Análise Mutacional de DNA , DNA Mitocondrial/genética , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Fatores de Risco , Acuidade Visual , Campos VisuaisRESUMO
PURPOSE: We conducted extensive epidemiological, neuro-ophthalmological, psychophysical, and blood examinations on a newly discovered, very large pedigree with molecular analysis showing mtDNA mutation for Leber's hereditary optic neuropathy (LHON). METHODS: Four patients representing four index cases from a remote area of Brazil were sent to Sao Paulo, where complete ophthalmological examinations strongly suggested LHON. Molecular analysis of their blood demonstrated that they were LHON, homoplasmic 11778, J-haplogroup. They had an extensive family that all lived in one rural area in Brazil. To investigate this family, we drew on a number of international experts to form a team that traveled to Brazil. This field team also included several members of the Federal University of Sao Paulo, and together we evaluated 273 of the 295 family members that were still alive. We conducted epidemiological interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmological examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for both mitochondrial genetic analysis and nuclear gene linkage analysis. RESULTS: The person representing the first-generation case immigrated from Verona, Italy, to Colatina. Subsequent generations demonstrated penetrance rates of 71%, 60%, 34%, 15%, and 9%. The percentages of males were 60%, 50%, 64%, 100%, and 100%. Age at onset varied from 10 to 64 years, and current visual acuities varied from LP to 20/400. CONCLUSIONS: Almost 95% of a nearly 300-member pedigree with LHON 11778 were comprehensively studied. Analysis of environmental risk factors and a nuclear modifying factor from this group may help address the perplexing mystery of LHON: Why do only some of the genetically affected individuals manifest the disease? This fully described database may also provide an excellent opportunity for future clinical trials of any purported neuroprotective agent.