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1.
ACS Sens ; 8(9): 3530-3537, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37505186

RESUMO

In process analytics or environmental monitoring, the real-time recording of the composition of complex samples over a long period of time presents a great challenge. Promising solutions are label-free techniques such as surface plasmon resonance (SPR) spectroscopy. They are, however, often limited due to poor reversibility of analyte binding. In this work, we introduce how SPR imaging in combination with a semi-selective functional surface and smart data analysis can identify small and chemically similar molecules. Our sensor uses individual functional spots made from different ratios of graphene oxide and reduced graphene oxide, which generate a unique signal pattern depending on the analyte due to different binding affinities. These patterns allow four purine bases to be distinguished after classification using a convolutional neural network (CNN) at concentrations as low as 50 µM. The validation and test set classification accuracies were constant across multiple measurements on multiple sensors using a standard CNN, which promises to serve as a future method for developing online sensors in complex mixtures.


Assuntos
Aprendizado Profundo , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Diagnóstico por Imagem , Purinas
2.
Photoacoustics ; 30: 100473, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36970564

RESUMO

Trace gas analysis in breath is challenging due to the vast number of different components. We present a highly sensitive quantum cascade laser based photoacoustic setup for breath analysis. Scanning the range between 8263 and 8270 nm with a spectral resolution of 48 pm, we are able to quantify acetone and ethanol within a typical breath matrix containing water and CO2. We photoacoustically acquired spectra within this region of mid-infra-red light and prove that those spectra do not suffer from non-spectral interferences. The purely additive behavior of a breath sample spectrum was verified by comparing it with the independently acquired single component spectra using Pearson and Spearman correlation coefficients. A previously presented simulation approach is improved and an error attribution study is presented. With a 3σ detection limit of 6.5 ppbv in terms of ethanol and 250 pptv regarding acetone, our system is among the best performing presented so far.

3.
Retina ; 38(11): 2253-2259, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28984736

RESUMO

PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.


Assuntos
Tomada de Decisões , Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Prontuários Médicos , Triagem Neonatal/métodos , Retinopatia da Prematuridade/diagnóstico , Peso ao Nascer , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Curva ROC , Retinopatia da Prematuridade/terapia , Telemedicina/métodos
4.
Lancet Haematol ; 2(11): e492-502, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26686259

RESUMO

BACKGROUND: Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. METHODS: In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. FINDINGS: Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1·015 [95% CI 1·006-1·024], p=0·0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1·077 [1·021-1·137], p=0·0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0·77), vincristine (p=0·36), and mean radiation dose to the left (p=0·41) or right (p=0·70) internal carotid artery did not predict for cardiovascular events. INTERPRETATION: Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients. FUNDING: Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doença de Hodgkin/complicações , Adulto , Idoso , Antraciclinas/efeitos adversos , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Sobreviventes , Alcaloides de Vinca/efeitos adversos , Adulto Jovem
5.
Am J Ophthalmol ; 160(3): 553-560.e3, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26004406

RESUMO

PURPOSE: To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). DESIGN: Prospective intra- and inter-rater reliability analysis. METHODS: In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. RESULTS: Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0-5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). CONCLUSIONS: ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.


Assuntos
Oftalmologia/normas , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Variações Dependentes do Observador , Fotografação , Estudos Prospectivos , Reprodutibilidade dos Testes
6.
Graefes Arch Clin Exp Ophthalmol ; 253(1): 151-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25303884

RESUMO

PURPOSE: The objective of this study was to evaluate the correlation between twin-twin transfusion syndrome (TTTS) and the development of retinopathy of prematurity (ROP) in premature infants. METHODS: Fifty-one infants who were less than 32 postmenstrual gestational weeks at birth or with a birth weight less than 1,501grams were included in this longitudinal observational study. The infants were matched by gestational age and birth weight, and divided into three groups: multiples with TTTS, multiples without TTTS, and singletons. The primary outcome variable was the incidence of ROP in infants affected by TTTS versus infants not affected by TTTS. Secondary outcome variables were multiple pregnancy, gestational age, and birth weight. RESULTS: Infants affected by TTTS showed a significantly higher incidence of ROP than infants not affected by TTTS (p < 0.01). TTTS donors and TTTS recipients were both at greater risk of developing ROP. ROP occurred in infants with TTTS whose gestational age at birth was significantly higher than that of infants with ROP who were not affected by TTTS (p = 0.01). Multiple pregnancy itself was not a risk factor for ROP disease. CONCLUSIONS: Infants affected by TTTS during pregnancy are at high risk of developing ROP, even if they were born at an older gestational age. Special awareness in ROP screening is necessary for these infants.


Assuntos
Transfusão Feto-Fetal/complicações , Retinopatia da Prematuridade/etiologia , Peso ao Nascer , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Gravidez , Gravidez Múltipla , Retinopatia da Prematuridade/diagnóstico , Fatores de Risco
7.
Neurology ; 83(15): 1337-44, 2014 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25186864

RESUMO

OBJECTIVE: We describe the 10-year follow-up in a cohort of 16 patients with genetically confirmed congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome, providing new insights in the clinical course of the disease. METHODS: We performed a detailed clinical and paraclinical characterization and 10-year follow-up study in 16 patients with molecularly defined CCFDN syndrome, illustrating that CCFDN is a severe disabling disorder. RESULTS: All patients initially presented with congenital cataracts along with strabismus, facial dysmorphism, short stature, and demyelinating neuropathy. In all patients, paresis of small hand muscles and foot extensors worsened with disease progression, while ataxia scores remained stable or improved. Nerve conduction velocity was normal in early infancy up to 18 months, decreased to approximately 20 m/s around age 10 years, and then remained stable; distal motor latency was prolonged. Sensory nerve conduction velocities were slowed, and initially of normal amplitude. With disease progression, both sensory and motor nerves showed reduction of amplitudes indicating axonal loss. In 6 patients, acute severe proximal weakness and myalgia after febrile infections, along with rhabdomyolysis, myoglobinuria, and hyperCKemia, led to a less favorable outcome and permanent loss of ambulation in 3 patients. CONCLUSIONS: CCFDN should be classified as a recessive demyelinating sensory-motor neuropathy, and axonal loss is a major determinant of long-term outcomes and disability. Patients benefit from early and ongoing physiotherapy, and should be thoroughly counseled regarding virus-triggered rhabdomyolysis and the risk of malignant hyperthermia. Whether supplementation with liposoluble vitamins results in a therapeutic benefit should be evaluated in further studies.


Assuntos
Catarata/congênito , Anormalidades Craniofaciais/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Adolescente , Adulto , Catarata/diagnóstico , Catarata/fisiopatologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neurônios Motores/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Condução Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Avaliação de Sintomas , Adulto Jovem
8.
Am J Cardiol ; 112(9): 1477-83, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23871676

RESUMO

Since 2008, when angiotensin II type I receptor blockade with losartan was introduced in the prevention of cardiovascular manifestation of Marfan syndrome (MFS), a specific treatment to address the cardiovascular lesions became available. The present study aimed to compare the response of such in an unselected cohort of patients with genotyped MFS. At a tertiary university children's hospital, 20 pediatric and adolescent patients aged 1.7 to 21.6 years with genetically proven MFS were enrolled in a prospective treatment study of losartan for evaluation of the aortic dimensions and elasticity indexes. The mean follow-up period was 33 ± 11 months. A significant reduction in the normalized aortic dimensions with losartan was observed in the valve, root, sinotubular junction, and ascending aortic segments (p = 0.008, p <0.001, p = 0.012, and p = 0.001, respectively). No correlation between elasticity behavior and the decrease in the aortic dimension with losartan therapy was detectable. A significant correlation between stronger improvement and younger age at onset (r = 0.643, p = 0.002) and a longer therapy duration (r = -0.532, p = 0.016) was verifiable. However, no correlation between improvement with therapy and the type of mutation or presentation of clinical forms was remarkable. Elasticity also seemed to improve but not significantly. In conclusion, in our cohort of young patients with MFS, a significant improvement with losartan monotherapy was proved in all affected proximal aortic segments, with a better response to therapy when started at an earlier age and with a longer therapy duration.


Assuntos
Aorta Torácica/diagnóstico por imagem , Losartan/administração & dosagem , Síndrome de Marfan/tratamento farmacológico , Seleção de Pacientes , Adolescente , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Aorta Torácica/efeitos dos fármacos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Síndrome de Marfan/diagnóstico por imagem , Tamanho do Órgão/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
9.
Br J Ophthalmol ; 97(2): 169-73, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23143909

RESUMO

BACKGROUND AND AIM: To describe the clinical and genetic characteristics of a mother and her son presenting with two distinct and rare forms of retinal degeneration. METHODS: Investigations in both patients comprised spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence imaging, non-contact biometry, ultrasonography, electroretinography (ERG) and analysis of the mutational status of the KCNV2 and MFRP genes in genomic DNA. RESULTS: The clinical course and typical ERG pattern indicated a 'cone dystrophy with supernormal rod electroretinogram' in the proband, and SD-OCT demonstrated a subfoveal optical gap with loss of the inner segment/outer segment junction line. The proband was homozygous for a c.782C>A (p.Ala261Asp) mutation in KCNV2. Her son's axial length was shortened with refractive errors of +16.75 dioptres in the right and +14.0 dioptres in the left eye; ERG evidenced a rod-cone dystrophy, OCT showed central macular thickening with cystoid changes and ultrasonography revealed optic disc drusen. MFRP analysis disclosed a 1 bp deletion (c.498delC) that predicts a truncated protein. CONCLUSIONS: Two distinct ocular phenotypes with pathogenic mutations in two different genes segregated in this family. The coexistence of two independent autosomal recessive disorders should be considered even when dealing with diseases that bear low carrier frequencies in the general population.


Assuntos
DNA/genética , Eletrorretinografia , Anormalidades do Olho/genética , Proteínas de Membrana/genética , Mutação , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Retinose Pigmentar/genética , Adulto , Criança , Análise Mutacional de DNA , Diagnóstico Diferencial , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/metabolismo , Feminino , Angiofluoresceinografia , Fundo de Olho , Heterozigoto , Humanos , Masculino , Proteínas de Membrana/metabolismo , Linhagem , Fenótipo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/metabolismo , Tomografia de Coerência Óptica , Turquia
10.
Pharmacology ; 86(1): 22-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20693822

RESUMO

The largest superfamily of membrane proteins that translate extracellular signals into intracellular messages are the 7-transmembrane-spanning (7TM) G protein-coupled receptors (GPCR). One of the ways in which their activity is controlled is by the process of desensitization and endocytosis, whereby agonist-activated receptors are rapidly and often reversibly silenced through removal from the cell surface. Indeed, following endocytosis, individual receptors can be sorted differentially between recycling endosomes and lysosomes, which controls the reversibility of the silencing. Thus, endocytosis can either serve as a mechanism for receptor resensitization by delivering receptors back to the plasma membrane or facilitate receptor downregulation by serving as the first step towards targeting the receptors to lysosomes for degradation. The sorting of receptors to the lysosomal pathway can be facilitated by interaction with an array of accessory proteins. One of these proteins is the GPCR-associated sorting protein 1 (GASP-1), which specifically targets several 7TM-GPCR to the lysosomal pathway after endocytosis. Furthermore, GASP-1 was recently found to directly affect the signaling capacity of a 7TM-GPCR. Importantly, the in vivo relevance of GASP-1-dependent receptor sorting has also begun to be verified in animal models. Here, we summarize the recent advances in elucidating GASP-1-dependent receptor sorting functions and their potential implications in vivo.


Assuntos
Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Transporte Vesicular/fisiologia , Animais , Regulação para Baixo , Endocitose , Humanos , Lisossomos/metabolismo , Transporte Proteico , Transdução de Sinais
11.
Traffic ; 11(5): 660-74, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20102549

RESUMO

Human cytomegalovirus (HCMV) encodes the seven transmembrane(7TM)/G-protein coupled receptor (GPCR) US28, which signals and endocytoses in a constitutive, ligand-independent manner. Here we show that, following endocytosis, US28 is targeted to the lysosomes for degradation as a consequence of its interaction with the GPCR-associated sorting protein-1 (GASP-1). We find that GASP-1 binds to US28 in vitro and that disruption of the GASP-1/US28 interaction by either (i) overexpression of dominant negative cGASP-1 or by (ii) shRNA knock-down of endogenous GASP-1 is sufficient to inhibit the lysosomal targeting of US28 and slow its post-endocytic degradation. Furthermore, we found that GASP-1 affects US28-mediated signalling. The knock-down of endogenous GASP-1 impairs the US28-mediated Galphaq/PLC/inositol phosphate (IP) accumulation as well as the activation of the transcription factors Nuclear Factor-kappaB (NF-kappaB) and cyclic AMP responsive element binding protein (CREB). Overexpression of GASP-1 enhances both IP accumulation and transcription factor activity. Thus, GASP-1 is an important cellular determinant that not only regulates the post-endocytic trafficking of US28, but also regulates the signalling capacities of US28.


Assuntos
Receptores de Quimiocinas/metabolismo , Receptores de Quimiocinas/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Transdução de Sinais , Quimiocinas/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citomegalovirus/genética , Citomegalovirus/metabolismo , Endocitose , Humanos , Fosfatos de Inositol/metabolismo , Ligantes , NF-kappa B/metabolismo , Proteínas/metabolismo , Receptores de Quimiocinas/genética , Receptores Acoplados a Proteínas G/metabolismo , Fosfolipases Tipo C/metabolismo
12.
Phytochemistry ; 66(12): 1472-5, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15921710

RESUMO

An investigation into the antibacterial properties of Hypericum foliosum Aiton. (Guttiferae) has led to the isolation of a new bioactive acylphloroglucinol natural product which by NMR spectroscopy and mass spectrometry was characterised as 1,3,5-trihydroxy-6-[2''',3'''-epoxy-3'''-methyl-butyl]-2-[2''-methyl-butanoyl]-4-[3'-methyl-2''-butenyl]-benzene and is described here for the first time. This metabolite was evaluated against a panel of multidrug-resistant strains of Staphylococcus aureus and minimum inhibitory values ranged from 16 to 32 microg/ml.


Assuntos
Antibacterianos/isolamento & purificação , Compostos de Epóxi/isolamento & purificação , Hypericum/química , Floroglucinol/análogos & derivados , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Compostos de Epóxi/farmacologia , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação
13.
Wien Klin Wochenschr ; 117 Suppl 6: 73-82, 2005.
Artigo em Alemão | MEDLINE | ID: mdl-16437337

RESUMO

Prophylaxis and treatment of catheter-related infections in patients undergoing peritoneal dialysis (PD) are the key to success of this type of renal replacement therapy. Prophylactic antibiotic therapy before catheter implantation significantly reduces the risk of peritonitis in the first month after operation. However, this strategy does not influence the risk of infections of the exit site and catheter tunnel. Although there are no studies showing any benefit in the use of povidon-iodine or sodium hypochlorite for care of exit sites in long-term PD patients, the use of a local disinfectant is recommended in recent guidelines. Another prophylactic approach is the use of local antibiotics, either intranasally or by application to the exit site. The use of mupirocin significantly reduces the rate of exit-site and tunnel infections and also the number of Staphylococcus aureus carriers. Gentamycin cream applied to the exit site is as effective as mupirocin in preventing S. aureus infections and in addition covers Pseudomonas aeruginosa. Both these local antibiotic therapies, however, carry the risk of selection of resistant bacterial strains. Guidelines mostly recommend the use of local antibiotics at least in S. aureus carriers. According to available data, oral antibiotic prophylaxis in long-term PD patients is not recommended, since a positive effect is unproven and systemic side effects have been reported in some studies. Family members and healthcare workers may be a source of S. aureus colonization in PD patients; however, there are no international protocols suggesting screening or treatment of these persons. There is no evidence favoring any dressing protocol (or a dressing change at all). Furthermore, because of lack of data, the question of whether face masks should be used during dressing changes or dialysate exchanges cannot yet be answered. There are no studies showing that it is safe for PD patients to go swimming or to a sauna. Only a few studies have focused on diagnosis and classification of exit-site infections and therefore no international standards exist. In cases of exit-site infection, ultrasonography of the catheter tunnel is a useful tool in the diagnosis of accompanying tunnel involvement and is also helpful in estimating the prognosis of these infections, depending on response to antibiotic therapy. Catheter-related infections should be treated with antibiotics for at least two weeks. With the exception of infection with methicillin-resistant S. aureus, the oral route is as effective as intraperitoneal administration. Currently there is no evidence of the ideal time-point for catheter removal after renal transplantation.


Assuntos
Antibacterianos/uso terapêutico , Cateterismo/efeitos adversos , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Guias de Prática Clínica como Assunto , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Cateterismo/métodos , Ensaios Clínicos como Assunto , Humanos , Falência Renal Crônica/complicações , Diálise Peritoneal/métodos , Padrões de Prática Médica , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/terapia , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/terapia , Resultado do Tratamento
14.
Ophthalmology ; 111(7): 1415-23, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15234148

RESUMO

OBJECTIVE: To determine the nature and course of ophthalmologic abnormalities in congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome in a genetically verified group of 9 patients. STUDY DESIGN: Observational case series. PARTICIPANTS: Nine affected male individuals of 5 pedigrees aged 1.3 to 16.8 years were examined. Four individuals were recruited during an ongoing prospective study of congenital cataracts; 5 individuals could be assigned to the CCFDN group on the basis of our retrospective data. MAIN OUTCOME MEASURES: Linkage and haplotype analysis, neurologic examinations, bilateral cataracts, axial length, corneal diameter, pupil diameter and pupillary reactions, intraoperative and postoperative complications, lid changes, aphakic correction problems, refractive results, and visual function. RESULTS: All families originated from the eastern part of Serbia, close to the border with Romania. The 8 tested individuals were homozygous for the conserved ancestral CCFDN haplotype in the telomeric region of chromosome 18q. All patients showed a peripheral, demyelinating neuropathy and varying degrees of ataxia. In the older patients, muscular atrophy in distal muscles and facial dysmorphism was evident. Early-onset bilateral congenital cataracts associated with microcornea, microphthalmos, and micropupil could be found in all patients. All children had floppy eyelid syndrome and pseudoptosis. An increased inflammatory reaction to contact lenses and intraocular lenses could be documented in all. All patients had syndrome-associated nystagmus and congenital esotropia. Distant visual acuity could be classified as severe to moderate impairment, whereas near visual acuity was much better (mild to moderate impairment). CONCLUSIONS: Early-onset congenital cataracts associated with microcornea, microphthalmos, and micropupil are essential ocular features of the CCFDN syndrome and are the first recognizable signs during early infancy. Awareness of this syndrome by pediatric ophthalmologists is important, because these typical findings, combined with information on ethnic origin, may lead to very early diagnosis at an age when the nature and severity of nonophthalmologic features are not apparent. Affected individuals may benefit from careful ophthalmologic treatment and follow-up, as well as from early management of the neurologic problems and developmental delay. Affected families will benefit from genetic counseling and predictive testing.


Assuntos
Catarata/congênito , Córnea/anormalidades , Anormalidades Craniofaciais/genética , Iris/anormalidades , Microftalmia/genética , Doenças do Sistema Nervoso Periférico/genética , Adolescente , Catarata/patologia , Extração de Catarata , Criança , Pré-Escolar , Anormalidades Craniofaciais/patologia , Esotropia/genética , Doenças Palpebrais/genética , Humanos , Lactente , Implante de Lente Intraocular , Masculino , Microftalmia/patologia , Nistagmo Patológico/genética , Linhagem , Doenças do Sistema Nervoso Periférico/patologia , Síndrome
15.
Ophthalmology ; 111(5): 906-13, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15121367

RESUMO

PURPOSE: To determine the significance of persistent fetal vasculature (PFV) and remnants of fetal vessels in the pathogenesis of pediatric unilateral cataracts. STUDY DESIGN: Prospective observational case series. PARTICIPANTS: Thirty-one children with unilateral cataract aged between 2 weeks and 15 years. METHODS: As part of an ongoing prospective clinical trial concerning treatment and etiology of pediatric cataracts, a subgroup of 31 children with unilateral cataracts was defined. The affected eyes received preoperative and intraoperative biomicroscopic examinations to identify characteristic features of PFV and even minimal fetal vascular remnants (MFVRs) at the level of the posterior lens capsule and anterior hyaloid face. In eyes with MFVRs, 3 different severity degrees were assumed, according to different posterior capsule abnormalities: mild, A; moderate, B; and severe, C. All observations were documented on video and analyzed in relation to age (group I, infants between 0 and 1.5 years; group II, preschool children between 1.6 and 5.9 years; group III, schoolchildren between 6 and 16 years). MAIN OUTCOME MEASURES: Frequency and morphology of characteristic features of PFV and MFVRs of the posterior lens capsule/anterior hyaloid face, lens clouding, and microphthalmos. RESULTS: All 31 eyes with unilateral congenital cataracts showed signs of PFV syndrome (100%). Characteristic features of PFV were found in 75% of group I eyes, in 8% of group II eyes, and in 67% of group III eyes. Minimal fetal vascular remnants were found in 25% of group I eyes (severity degree C in all eyes), in 92% of group II eyes (severity degree A in 36.4%, B in 27.2%, and C in 36.4%), and in 33% of group III eyes (severity degree A). Associated microphthalmos was found in all eyes in groups I and III and in 73% of group II, whereas axial lengths were equal in both eyes in 27% of group II children with MFVRs. CONCLUSIONS: Varying degrees of PFV seem to be a frequent cause of unilateral congenital cataracts. Although characteristic features of PFV occurred mainly in infants, eyes of preschool children were usually very mildly affected, showing MFVRs that were detected only by careful observation during surgery. Abnormalities of the central part of the posterior capsule, such as a translucent opacity or a lenticonic area leading to a spontaneous hole during lens aspiration, may be caused by minimal remnants of PFV.


Assuntos
Catarata/congênito , Anormalidades do Olho/etiologia , Cristalino/irrigação sanguínea , Corpo Vítreo/anormalidades , Corpo Vítreo/patologia , Adolescente , Catarata/diagnóstico , Extração de Catarata/métodos , Criança , Pré-Escolar , Anormalidades do Olho/diagnóstico , Sangue Fetal , Humanos , Hiperplasia , Lactente , Recém-Nascido , Cristalino/patologia , Microftalmia/diagnóstico , Estudos Prospectivos , Síndrome
16.
Am J Hum Genet ; 75(1): 138-45, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15154116

RESUMO

Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia. A Cohen syndrome locus was mapped to chromosome 8q22 in Finnish patients, and, recently, mutations in the gene COH1 were reported in patients with Cohen syndrome from Finland and other parts of northern and western Europe. Here, we describe clinical and molecular findings in 20 patients with Cohen syndrome from 12 families, originating from Brazil, Germany, Lebanon, Oman, Poland, and Turkey. All patients were homozygous or compound heterozygous for mutations in COH1. We identified a total of 17 novel mutations, mostly resulting in premature termination codons. The clinical presentation was highly variable. Developmental delay of varying degree, early-onset myopia, joint laxity, and facial dysmorphism were the only features present in all patients; however, retinopathy at school age, microcephaly, and neutropenia are not requisite symptoms of Cohen syndrome. The identification of novel mutations in COH1 in an ethnically diverse group of patients demonstrates extensive allelic heterogeneity and explains the intriguing clinical variability in Cohen syndrome.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 8/genética , Variação Genética , Proteínas de Membrana/genética , Mutação/genética , Anormalidades Múltiplas/etnologia , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Anormalidades Craniofaciais/etnologia , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/etnologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Deficiência Intelectual/etnologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/etnologia , Microcefalia/genética , Microcefalia/patologia , Repetições de Microssatélites , Linhagem , Filogenia , Síndrome , Proteínas de Transporte Vesicular
17.
J Cataract Refract Surg ; 30(3): 611-9, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15050257

RESUMO

PURPOSE: To document in detail the surgical management challenges over the wide spectrum of persistent fetal vasculature syndrome (PFVS). SETTING: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. METHODS: As part of an ongoing prospective clinical trial of the treatment and etiology of pediatric cataract, a subgroup of 31 children with unilateral cataract was defined. Standard surgical techniques were used based on age. Group 1 comprised infants between 0 and 1.5 years; Group 2, preschool children between 1.6 and 5.9 years; and Group 3, school-aged children between 6 and 16 years. Additional surgical procedures were used based on the degree of PFVS. RESULTS: All 31 eyes with unilateral cataract showed signs of PFVS. Characteristic features were found in 75% of eyes in Group 1, 8% of eyes in Group 2, and 67% of eyes in Group 3. Minimal fetal vascular remnants were found in 92%, 25%, and 33%, respectively. Correct diagnosis of PFVS was made preoperatively in 56% of eyes in Group 1, 8% in Group 2, and 67% in Group 3. Surgical procedures in addition to standard age-related techniques were necessary in all eyes with unilateral cataract. CONCLUSIONS: Results indicate that varying degrees of PFVS are a frequent cause of unilateral congenital cataract. Most severe cases were in infants, and preschool children were usually mildly affected. Vitreoretinal complications may lead to challenges in the surgical management in infants. In preschool children, cataract surgery must be performed in a guarded fashion because of the high risk for preexisting posterior capsule breaks due to minimal fetal vascular remnants.


Assuntos
Extração de Catarata/métodos , Catarata/congênito , Anormalidades do Olho/cirurgia , Cristalino/irrigação sanguínea , Corpo Vítreo/anormalidades , Adolescente , Fatores Etários , Criança , Pré-Escolar , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/etiologia , Sangue Fetal , Humanos , Hiperplasia , Lactente , Recém-Nascido , Cristalino/patologia , Estudos Prospectivos , Corpo Vítreo/patologia
18.
Planta Med ; 70(12): 1240-2, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15643566

RESUMO

Epicatechin gallate (1) and epigallocatechin gallate (2) were evaluated for their antibacterial and efflux inhibitory activity against a wild-type and three multidrug-resistant (MDR) strains of Staphylococcus aureus. Compound 2 was more active than 1 based on minimum inhibitory concentrations (MICs; 32-64 versus 64->512 microg/mL, respectively). When incorporated into the growth medium at 20 microg/mL, both compounds exhibited a four-fold potentiation of the activity of norfloxacin against a norfloxacin-resistant strain of S. aureus overexpressing the NorA multidrug efflux pump. Against this strain 1 was moderately more potent than 2 as an inhibitor of ethidium efflux, but at < or = 20 microM both compounds paradoxically stimulated efflux. This phenomenon has not been encountered previously in the analysis of inhibitors of multidrug efflux.


Assuntos
Antibacterianos/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Resistência a Múltiplos Medicamentos , Fitoterapia , Plantas Medicinais , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Catequina/administração & dosagem , Catequina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana
19.
J Cataract Refract Surg ; 29(2): 285-93, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12648639

RESUMO

PURPOSE: To evaluate the prevalence and severity of posterior capsule opacification (PCO) in pediatric eyes with a foldable acrylic AcrySof (Alcon) intraocular lens (IOL) and age-related surgical methods. SETTING: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. METHODS: This prospective randomized study comprised 50 eyes of 34 children aged between 2 and 16 years. Eyes of children between 2 and 5.9 years were consecutively randomized to Group 1a (primary posterior capsulotomy and anterior vitrectomy) or Group 1b (optic capture in addition). Eyes of children between 6 and 16 years were consecutively randomized to Group 2a (primary posterior capsulotomy without anterior vitrectomy), Group 2b (optic capture in addition), or Group 2c (in-the-bag IOL implantation without opening the posterior capsule). Main outcome parameters were the incidence and severity of PCO formation, early postoperative complications, pigmented cell deposits on the IOL surface, and cataract morphology. RESULTS: The visual axis was clear at the last follow-up in all eyes in Groups 1a, 1b, 2a, and 2b except in 1 eye in Group 1a. Sixty-percent of eyes in Group 2c had PCO. The incidence of early postoperative complications was significantly higher in eyes that developed PCO than in those that maintained a clear visual axis. There was no evidence that cataract morphology influenced PCO rates. CONCLUSIONS: The AcrySof IOL was well tolerated in pediatric eyes. Optic capture was not necessary to ensure a clear visual axis. Primary posterior capsulotomy should be performed in preschool and uncooperative children and in eyes expected to have relatively high postoperative inflammation. Implanting the AcrySof in the bag and leaving the posterior capsule intact is acceptable for school children and juveniles with isolated developmental cataract.


Assuntos
Resinas Acrílicas , Extração de Catarata/métodos , Cápsula do Cristalino/patologia , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Complicações Pós-Operatórias/patologia , Acuidade Visual/fisiologia , Adolescente , Materiais Biocompatíveis , Catarata/congênito , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Vitrectomia
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