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OBJECTIVE: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DESIGN: Secondary analysis of four prospective population-based studies. PARTICIPANTS: We included four European-ancestry cohorts: the United States (US) based Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. METHODS: PRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. MAIN OUTCOME MEASURES: The relative risk for POAG and Harrell's C-statistic (the equivalent of an area-under-the-curve for longitudinal models). RESULTS: Among 1,046 cases and 38,809⬠controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). CONCLUSIONS: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.
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INTRODUCTION: Kidney cancer, primarily renal cell carcinoma (RCC), ranks among the top 10 most common malignancies in the male population of Hong Kong. In 2019, members of two medical societies in Hong Kong formed an expert panel to establish a set of consensus statements for the management of metastatic RCC. On 22 June 2021, the same panel met to review recent evidence and reassess their positions regarding the management of advanced and metastatic RCC, with the aim of providing recommendations for physicians in Hong Kong. PARTICIPANTS: The panel included 12 experts (6 clinical oncologists and 6 urologists) who had extensive experience managing patients with RCC in Hong Kong. EVIDENCE: The panel reviewed randomised controlled trials, observational studies, systematic reviews/meta-analyses, and international clinical guidelines to address key clinical questions that were identified before the meeting. CONSENSUS PROCESS: In total, 15 key clinical questions were identified before the meeting, covering the surgical and systemic treatment of advanced or metastatic clear cell, sarcomatoid, and non-clear cell RCCs. At the meeting, the panellists voted on these questions, then discussed relevant evidence and practical considerations. CONCLUSIONS: The treatment landscape for advanced and metastatic RCC continues to evolve. More immune checkpoint inhibitor (ICI)-based combination regimens will be indicated for the treatment of metastatic clear cell RCC. There is increasing evidence concerning the benefit of adjuvant ICI treatment for resected advanced RCC. This article summarises recent evidence and expert insights regarding a series of key clinical questions about the management of advanced and metastatic RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Hong Kong/epidemiologia , Consenso , Sociedades MédicasRESUMO
INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.
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Demência/etiologia , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Apolipoproteínas E/genética , Encéfalo/diagnóstico por imagem , Demência/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/psicologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenantrolinas , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/psicologia , Tiazóis , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Social insects in general and leaf-cutting ants in particular have increased selection pressures on their innate immune system due to their social lifestyle and monoclonality of the symbiotic fungal cultivar. As this symbiosis is obligate for both parties, prophylactic behavioural defences against infections are expected to increase either ant survival or fungus-garden survival, but also to possibly trade off when specific infections differ in potential danger. We examined the effectiveness of prophylactic behaviours and modulations of innate immune defences by a combination of inoculation bioassays and genome-wide transcriptomic studies (RNA-Seq), using an ant pathogen (Metarhizium brunneum) and a fungus-garden pathogen (Escovopsis weberi) and administering inoculations both directly and indirectly (via the symbiotic partner). Upon detection of pathogen conidia, ant workers responded by increasing both general activity and the frequency of specific defence behaviours (self-grooming, allo-grooming, garden-grooming) independent of the pathogen encountered. This trend was also evident in the patterns of gene expression change. Both direct and indirect (via fungus garden) inoculations with Metarhizium induced a general up-regulation of gene expression, including a number of well-known immune-related genes. In contrast, direct inoculation of the fungus garden by Escovopsis induced an overall down-regulation of ant gene expression, whereas indirect inoculation (via the ants) did not, suggesting that increased activity of ants to remove this fungus-garden pathogen is costly and involves trade-offs with the activation of other physiological pathways.
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Formigas/genética , Regulação da Expressão Gênica/genética , Genoma de Inseto , Animais , Formigas/microbiologia , Regulação para Baixo , Hypocreales/patogenicidade , Metarhizium/patogenicidade , Simbiose , Regulação para CimaRESUMO
OBJECTIVES: The aim of this study was to analyze the value of performing laboratory tests, taking cultures, and imaging, a diagnostic approach for febrile seizures (FSs) still routinely performed despite the American Academy of Pediatrics recommendations not to. Another aim of this study was to identify the most common sources of fever in patients with FSs and to determine whether the occurrence of FSs correlates with the seasons of the year. METHODS: This is a retrospective study that included all patients diagnosed with simple or complex FSs who were seen in the emergency room or inpatient unit from January 2004 to December 2009. RESULTS: Of the 219 patients included in the study, 135 (61.4%) cases had the etiology of the FS diagnosed. Upper respiratory tract infection, otitis media, urinary infection, and pneumonia were the most common diagnoses attributed to the fever. Leukocytosis was present in 48 (24%) of 219, and neutrophilia in 199 (91%) of 219 cases. Low bicarbonate levels were common among every age group. Only 1 blood culture was positive for Salmonella. The incidence of FS was higher during the winter (49.3% of the cases), and it closely paralleled the seasonal variation of viral infections. CONCLUSIONS: Even though laboratory tests, taking cultures, and imaging are performed in daily practice when approaching FSs, the association of FSs with serious infectious disease is rare and usually overestimated. The diagnostic approach should be individualized to each case and correlated with available data like that shown in this study. Parents should be educated with the knowledge that the occurrence of FSs tends to be higher in winter.
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Técnicas de Laboratório Clínico/estatística & dados numéricos , Diagnóstico por Imagem/estatística & dados numéricos , Fidelidade a Diretrizes , Padrões de Prática Médica , Convulsões Febris/diagnóstico , Distribuição por Idade , Pré-Escolar , Medicina Defensiva , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Cidade de Nova Iorque/epidemiologia , Estudos Retrospectivos , Estações do Ano , Convulsões Febris/epidemiologia , Convulsões Febris/etiologiaRESUMO
BACKGROUND: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. AIM: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. METHODS: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes. RESULTS: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0-9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9-45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001). CONCLUSION: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.
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Fibrilação Atrial , AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Anticoagulantes , Fibrilação Atrial/epidemiologia , Hospitais , Humanos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. AIM: We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. METHODS: This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEÉ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. RESULTS: In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEÉ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. CONCLUSION: The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.
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Demência , Ataque Isquêmico Transitório , AVC Isquêmico , Isquemia Miocárdica , Acidente Vascular Cerebral , Estudos de Coortes , Demência/etiologia , Demência/genética , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/epidemiologia , Estudos Longitudinais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/psicologiaRESUMO
Telehealth has become a viable option for glaucoma screening and glaucoma monitoring due to advances in technology. The ability to measure intraocular pressure without an anesthetic and to take optic nerve photographs without pharmacologic pupillary dilation using portable equipment have allowed glaucoma screening programs to generate enough data for assessment. At home, patients can perform visual acuity testing, web-based visual field testing, rebound tonometry, and video visits with the physician to monitor for glaucomatous progression. Artificial intelligence will enhance the accuracy of data interpretation and inspire confidence in popularizing telehealth for glaucoma.
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PURPOSE: To study the effect of phacoemulsification on intraocular pressure (IOP) control in patients with preexisting glaucoma drainage implants (GDIs). DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 45 patients (51 eyes) with previously placed GDIs who underwent phacoemulsification between January 2013 and March 2018. METHODS: The list of patients was obtained from billing records. Clinical data were retrieved from the corresponding electronic medical records. MAIN OUTCOME MEASURES: Intraocular pressure, number of glaucoma medications before and after phacoemulsification (postoperative day 1, week 1, months 1, 3, 6, 12, 18, and 24), rate of failure (failure defined as IOP >18 mmHg and IOP increase >20% at 2 consecutive visits after month 1, need for additional glaucoma surgery, or loss of light perception vision), and postoperative complications. RESULTS: Mean follow-up was 23.0 ± 11.1 months. The average interval between GDI surgery and phacoemulsification was 9.4 ± 6.7 months. An Ahmed glaucoma valve (AGV; New World Medical) was implanted in 12 eyes, a Baerveldt glaucoma implant (BGI; Johnson & Johnson Surgical Vision) was implanted in 36 eyes, and a Molteno (Molteno Ophthalmic Limited) glaucoma implant was implanted in 3 eyes. Before phacoemulsification, the mean IOP was 14.4 ± 4.4 mmHg on 2.1 ± 1.3 glaucoma medications. At postoperative month 24, the mean IOP was 12.6 ± 4.4 mmHg (n = 29, P = 0.519) on 2.0 ± 1.6 (P = 0.457) glaucoma medications. The reduction in IOP was significant only at postoperative week 1 (P = 0.031). The cumulative failure rate was 3.9% at 1 year and 11.8% at 2 years. The AGV group had a significantly higher mean IOP before phacoemulsification than the BGI group (P = 0.016). Analysis of covariance, taking the baseline IOP as a covariate, revealed no differences in postoperative IOP and number of glaucoma medications between groups, except for month 18 (1 patient in the BGI group had uncontrolled IOP requiring surgery). Postoperative complications included cystoid macular edema (10%), corneal decompensation (6%), and choroidal effusion (4%). CONCLUSIONS: Phacoemulsification after GDI surgery resulted in a transient reduction in IOP at postoperative week 1. Patients with previously placed AGVs had similar postoperative outcomes compared with those with BGIs.
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Implantes para Drenagem de Glaucoma , Facoemulsificação , Implantes para Drenagem de Glaucoma/efeitos adversos , Humanos , Pressão Intraocular , Facoemulsificação/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
BACKGROUND: Human population growth has led to biodiversity declines in tropical cities. While habitat loss and fragmentation have been the main drivers of urban biodiversity loss, man-made interventions to reduce health risks have also emerged as an unintentional threat. For instance, insecticide fogging to control mosquito populations has become the most common method of preventing the expansion of mosquito-borne diseases such as Dengue. However, the effectiveness of fogging in killing mosquitoes has been called into question. One concern is the unintended effect of insecticide fogging on non-target invertebrates that are crucial for the maintenance of urban ecosystems. Here, we investigate the impacts of fogging on: (1) target invertebrate taxon (Diptera, including mosquitoes); (2) non-target invertebrate taxa; and (3) the foraging behavior of an invertebrate pollinator taxon (Lepidoptera) within an urban tropical forest. METHODS: We carried out fogging with Pyrethroid insecticide (Detral 2.5 EC) at 10 different sites in a forest situated in the state of Selangor, Peninsular Malaysia. Across the sites, we counted the numbers of knocked-down invertebrates and identified them based on morphology to different taxa. We constructed Bayesian hierarchical Poisson regression models to investigate the effects of fogging on: (1) a target invertebrate taxon (Diptera) 3-h post-fogging; (2) selected non-target invertebrate taxa 3-h post-fogging; and (3) an invertebrate pollinator taxon (Lepidoptera) 24-h post-fogging. RESULTS: A total of 1,874 invertebrates from 19 invertebrate orders were knocked down by the fogging treatment across the 10 sites. Furthermore, 72.7% of the invertebrates counted 3-h post-fogging was considered dead. Our regression models showed that given the data and prior information, the probability that fogging had a negative effect on invertebrate taxa 3-h post-fogging was 100%, with reductions to 11% of the pre-fogging count of live individuals for the target invertebrate taxon (Diptera), and between 5% and 58% of the pre-fogging count of live individuals for non-target invertebrate taxa. For the invertebrate pollinator, the probability that fogging had a negative effect 24-h post-fogging was also 100%, with reductions to 53% of the pre-fogging count of live individuals. DISCUSSION: Our Bayesian models unequivocally demonstrate that fogging has detrimental effects on one pollinator order and non-target invertebrate orders, especially taxa that have comparatively lower levels of chitinisation. While fogging is effective in killing the target order (Diptera), no mosquitos were found dead in our experiment. In order to maintain urban biodiversity, we recommend that health authorities and the private sector move away from persistent insecticide fogging and to explore alternative measures to control adult mosquito populations.
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BACKGROUND: Although serum measures of micronutrients are more specific than questionnaires in quantifying nutritional status, the reliability of serum measures depends on between- and within-person variability of circulating micronutrient levels. The extent to which multiple samples per person might improve reliability is useful information for planning studies and interpreting results. METHODS: We analyzed levels of 25 micronutrients in serum samples taken from 381 Hawaii women at 4-month intervals. For all subjects and for subjects at the low and high end of the micronutrient distributions, we calculated inter- and intraindividual variability, reliability coefficients, and the number of measurements required to limit attenuation in estimated parameters (ie, to keep estimates close to their true values). RESULTS: For 18 of the 25 micronutrients, a single measurement provided an estimate within 20% of the true value. For regression coefficients, 2 measurements were needed to limit attenuation to no more than 20% for nearly half of the micronutrients. To achieve no more than 10% attenuation, the number of measurements required ranged from 2 to 10 for correlation and from 3 to 20 for regression coefficients. To achieve no more than 5% attenuation, the corresponding ranges were 3 to 21 for correlation and 6 to 42 regression coefficients. In general, more measurements were required for adequate characterization of subjects with relatively high levels of micronutrients than for subjects with lower levels. CONCLUSIONS: Our analysis suggests that 2 or 3 blood measurements are enough to limit attenuation of regression coefficients within 20% of the true value for most carotenoids and tocopherols. For 10% attenuation or less, 4 or more micronutrient measurements may be needed.
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Micronutrientes/sangue , Estado Nutricional , Adolescente , Adulto , Idoso , Feminino , Havaí , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Annual surveillance mammography is commonly recommended after breast conservation therapy (BCT). We retrospectively reviewed its effectiveness on 511 invasive and non-invasive breast cancers treated with BCT between 1994 and 2003. The median follow-up was 5.9 years. The 5-year actuarial ipsilateral breast tumour recurrence (IBTR) rate was 4.5% and contralateral breast cancer (CBC) rate was 2.0% (representing eight times increase in risk). IBTR of 43% and 62% CBC were first detected by surveillance mammography. The IBTR detection rates per 1000 mammograms were 5.2 for patients (n=349) with one or more IBTR risk factors (age 45, positive/close margins or histological grade 3) and 0.6 for patients (n=162) without. No survival difference was observed between different modes of IBTR detection (p=0.342). In conclusion, a risk-adapted approach of limiting ipsilateral surveillance to patients with IBTR risk is possible but its implementation will be complicated by the continued need of contralateral surveillance.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Mamografia/economia , Mastectomia Segmentar , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Incorporating various new and conventional risk factors, the 2005 St Gallen risk categorization is a potentially useful prognostic tool for breast cancers. We conducted a retrospective study to evaluate its application in Hong Kong. Of the 902 included female breast cancers with median follow-up of 5.4 years, 7%, 63% and 30% patients were classified as low-, intermediate- and high-risk categories, respectively. Their corresponding 5-year distant disease-free survivals (DDFS) were 100%, 92% and 72%, respectively (p<0.00005). In the intermediate-risk category, node-positive patients had marginally inferior 5-year DDFS than node-negative patients (89% vs. 93%, p=0.0551). In the high-risk category, patients having HER2 overexpressed tumors and 1-3 positive nodes had significantly better DDFS than other patients with > or = 4 positive nodes (89% vs. 65%, p=0.0001). Overall, the 2005 St Gallen risk categorization had high prognostic value. However, the impact of HER2 overexpression might be affected by reproducibility of HER2 tests.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/patologia , Carcinoma/secundário , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Genes erbB-2 , Hong Kong/epidemiologia , Humanos , Metástase Linfática , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. DESIGN: Retrospective study. SETTING: Department of Clinical Oncology in a public hospital in Hong Kong. PATIENTS: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). RESULTS: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. CONCLUSIONS: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.
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Neoplasias da Mama/genética , Carcinoma Ductal/genética , Carcinoma Lobular/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Hibridização In Situ/métodos , Receptor ErbB-2/genética , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Ductal/epidemiologia , Carcinoma Ductal/patologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/patologia , Estudos Transversais , Feminino , Amplificação de Genes/genética , Regulação Neoplásica da Expressão Gênica/genética , Hong Kong , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: To introduce a technique using the Kahook Dual Blade for treatment of childhood glaucoma. PATIENT AND METHOD: An infant developed glaucoma after cataract extraction and anterior vitrectomy. Ab interno trabeculectomy was performed in both eyes using a dual-blade device. RESULTS: Description of technique to treat childhood glaucoma. Intraocular pressure reduced from 35 to 17 mm Hg in the right eye and from 52 to 18 mm Hg in the left eye after 7 to 10 weeks. There were no complications. CONCLUSIONS: This was a successful, minimally invasive procedure for treatment of childhood glaucoma.
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Glaucoma de Ângulo Aberto/cirurgia , Trabeculectomia/métodos , Extração de Catarata/efeitos adversos , Seguimentos , Glaucoma de Ângulo Aberto/etiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Lactente , Pressão Intraocular/fisiologia , Masculino , Tonometria Ocular , Trabeculectomia/instrumentação , Vitrectomia/efeitos adversosRESUMO
We report the case of a 66-year-old man with Takayasu arteritis who developed photic and postprandial amaurosis occurring at a corticosteroid dose <40 mg per day, despite concurrent methotrexate. The amaurosis resolved with correction of anemia by packed red blood cell transfusion. Marginal retinal perfusion in Takayasu arteritis may precipitate symptomatic hypoxia as a result of eating a meal or exposing the eye to bright lights. Correction of anemia improves oxygen delivery to the hypoxic retina and relieves recurrent amaurosis.
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Cegueira/etiologia , Período Pós-Prandial , Arterite de Takayasu/complicações , Idoso , Artéria Axilar/diagnóstico por imagem , Cegueira/diagnóstico , Cegueira/fisiopatologia , Diagnóstico Diferencial , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Angiografia por Ressonância Magnética , Masculino , Vasos Retinianos/diagnóstico por imagem , Artéria Subclávia/diagnóstico por imagem , Arterite de Takayasu/diagnóstico , Acuidade VisualRESUMO
Endoscopic cyclophotocoagulation is laser treatment of the ciliary processes with direct visualization using a small video camera for the purpose of lowering intraocular pressure. It was traditionally reserved for management of refractory glaucoma, but is now increasingly used as an adjunct to cataract surgery in less-advanced glaucoma. Here we present a review of the literature evaluating endoscopic cyclophotocoagulation's safety and efficacy in different forms of glaucoma with different degrees of progression.
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Corpo Ciliar/cirurgia , Endoscopia/métodos , Cirurgia Filtrante/métodos , Glaucoma/cirurgia , Pressão Intraocular , Fotocoagulação a Laser/métodos , Glaucoma/fisiopatologia , HumanosRESUMO
We have characterized the asymmetric effect of Ca2+ on passive K+ permeability in erythrocyte membranes, using inside out and right-side out vesicles. Ca2+, but not Mg2+, can induce an increase in K+ uptake in inside out vesicles. The half-maximal concentration of Ca2+ required to induce the K+ uptake is 0.2 mM, and the permeability increase is not specific for K+. Thus, the Ca2+- induced permeation process in inside out vesicles is changed from that in the energy-depleted intact cell which requires only micromolar concentrations of Ca2+ and is specific for K+. Removal of spectrin had no effect on the vesicle permeability increase due to Ca2+. Studies with N-ethylmaleimide show that the vesicle channel openings is mediated by a protein and passage is controlled by sulfhydryl groups; furthermore, the Ca2+-induced vesicle pathway is distinct from the normal channel for passive K+ leak in the absence of Ca2+. The protein is sensitive to its phospholipid environment since removal of easily accessible phospholipid head groups on the cytoplasmic face of the vesicles inhibits the Ca2+ -stimulated channel opening.
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Cálcio/farmacologia , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Potássio/sangue , Transporte Biológico/efeitos dos fármacos , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/ultraestrutura , Humanos , Canais Iônicos/metabolismo , Cinética , Magnésio/farmacologia , Permeabilidade , Rubídio/sangueRESUMO
The permeability of inside-out and right-side-out vesicles from erythrocyte membranes to inorganic cations was determined quantitatively. Using 86Rb as a K analog, we have measured the rate constant of 86Rb efflux from vesicles under equilibrium exchange conditions, using a dialysis procedure. The permeability coefficients of the vesicles to Rb are only about an order of magnitude greater than that of whole erythrocytes. Furthermore, we have measured many of the specialized transport systems known to exist in erythrocytes and have shown that glucose, sulfate, ATP-dependent Ca and ATP-dependent Na transport activities are retained by the vesicle membranes. These results suggest that inside-out and right-side-out vesicles can be used effectively to study transport properties of erythrocyte membranes.
Assuntos
Cátions Monovalentes/metabolismo , Permeabilidade da Membrana Celular , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Trifosfato de Adenosina/farmacologia , Cálcio/metabolismo , Glucose/metabolismo , Humanos , Cinética , Potássio/metabolismo , Rubídio , Sódio/metabolismo , Sulfatos/metabolismoRESUMO
Two biochemical types of Ca2+-pumping ATPases were distinguished in membranes that were isolated from carrot (Daucus carota) suspension-cultured cells. One type hydrolyzed GTP nearly as well as ATP, was stimulated by calmodulin, and was resistant to cyclopiazonic acid. This plasma membrane (PM)-type pump was associated with PMs and endomembranes, including vacuolar membranes and the endoplasmic reticulum (ER). Another pump ("ER-type") that was associated mainly with the ER hydrolyzed ATP preferentially, was insensitive to calmodulin, and was inhibited partially by cyclopiazonic acid, a blocker of the animal sarcoplasmic/ER Ca2+ pump. Oxalate stimulation of Ca2+ accumulation by ER-type, but not PM-type, pump(s) indicated a separation of the two types on distinct compartments. An endomembrane 120-kD Ca2+ pump was partially purified by calmodulin-affinity chromatography. The purified polypeptide bound calmodulin reacted with antibodies to a calmodulin-stimulated Ca2+ pump from cauliflower and displayed [32P]phosphoenzyme properties that are characteristic of PM-type Ca2+ pumps. The purified ATPase corresponded to a phosphoenzyme and a 120-kD calmodulin-binding protein on endomembranes. Another PM-type pump was suggested by a 127-kD PM-associated protein that bound calmodulin. Thus, both ER- and PM-type Ca2+ pumps coexist in most plant tissues, and each type can be distinguished from another by a set of traits, even in partially purified membranes.