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2.
BJA Educ ; 23(6): 208-211, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37223693
4.
Opt Express ; 27(8): A397-A403, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31052891

RESUMO

The fabrication and feasibility assessment of n-side up, thin-epilayer, AlGaInP-based vertical light-emitting-diodes (LEDs; emitting area: 1 mm × 1 mm) with a copper-invar-copper-composite metal (CIC) substrate was obtained by wafer bonding and epilayer transferring technologies. The structure of CIC substrate is a top Cu layer of 20 µm, a middle Invar layer of 64 µm, and a bottom Cu layer of 20 µm. The invar layer consists of Fe and Ni at a ratio of 70% to 30%. The coefficient of thermal expansion for CIC is about 6.1 × 10-6 /K, which is similar to that of the GaAs substrate (5.7 × 10-6 /K) and AlGaInP epilayers. Due to the high thermal conductivity (160 W/m-K) of 104-µm-thick CIC, the high performances of the packaged LEDs are obtained. They present a low red shift phenomenon (from 623 to 642 nm for 100 mA to 1 A) and a high output power 212 mW at 800 mA. The CIC substrate can be extended to fabricate high-efficiency thin film LEDs with conventional vertical electrodes.

5.
Public Health ; 168: 36-42, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30685596

RESUMO

OBJECTIVE: The objective of the study is to evaluate the pattern and predictors of medical care received by hepatitis B virus (HBV) carriers during pregnancy and after delivery in Hong Kong. STUDY DESIGN: The study is a retrospective analysis. METHODS: Pregnant HBV carriers and their infants were followed up for 9-12 months after delivery. Face-to-face interviews were conducted to investigate what medical care they received for HBV before, during and after pregnancy. RESULTS: Data were available for 412 HBV carriers. A total of 375 (91.0%) women were known HBV carriers before pregnancy. Routine antenatal screening picked out the remaining 37 (9.0%) HBV carriers; these women were younger, more likely to be smokers and had a lower level of education (P < 0.05) than known HBV carriers. In total, 356 of 412 (86.4%) HBV carriers did not receive any medical care for HBV during pregnancy. Known HBV carrier status, history of medical check-up and the use of antiviral treatment before pregnancy were significant predictors for HBV medical care during pregnancy (P < 0.05). The results show that 217 of 412 (52.6%) HBV carriers did not receive medical care for HBV after delivery. HBV medical care before pregnancy, use of antiviral treatment before pregnancy and a higher level of education were significant predictors for postpartum HBV medical care (P < 0.05). Multivariate analysis showed that HBV medical care before pregnancy (odds ratio [OR], 7.73; 95% confidence interval [CI], 3.21-18.65; P < 0.001) and the use of antiviral treatment (OR, 5.02; 95% CI, 1.41-17.81; P = 0.013) were associated with medical care during pregnancy. Medical care before pregnancy was also associated with postpartum HBV medical care (OR, 5.05; 95% CI, 3.29-7.51; P < 0.001). CONCLUSIONS: A significant proportion of HBV carriers did not receive HBV-related medical check-ups during and after pregnancy in Hong Kong despite the majority being aware of their carrier status. Medical care before pregnancy predicted antenatal and postpartum HBV medical care.


Assuntos
Antivirais/uso terapêutico , Portador Sadio/tratamento farmacológico , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Cuidado Pós-Natal/estatística & dados numéricos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Feminino , Antígenos de Superfície da Hepatite B/isolamento & purificação , Hong Kong , Humanos , Lactente , Gravidez , Estudos Retrospectivos
6.
BMC Med Genomics ; 11(1): 93, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359267

RESUMO

BACKGROUND: Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCAs) detected on prenatal ultrasound. METHOD: Thirty-three families with fetal SCAs on prenatal ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various fetal samples including amniotic fluid, chorionic villi, and placental tissue. Parental DNA was extracted from peripheral blood when available. We used WES to sequence the coding regions of parental-fetal trios and to identify the causal variants based on the ultrasonographic features of the fetus. RESULTS: Pathogenic mutations were identified in three families (n = 3/33, 9.1%), including mutations in DNAH11, RAF1 and CHD7, which were associated with primary ciliary dyskinesia, Noonan syndrome, and CHARGE syndrome, respectively. In addition, variants of unknown significance (VUSs) were detected in six families (18.2%), in which genetic changes only partly explained prenatal features. CONCLUSION: WES identified pathogenic mutations in 9.1% of fetuses with SCAs and normal chromosomal microarray results. Databases for fetal genotype-phenotype correlations and standardized guidelines for variant interpretation in prenatal diagnosis need to be established to facilitate the use of WES for routine testing in prenatal diagnosis.


Assuntos
Síndrome CHARGE/genética , Transtornos da Motilidade Ciliar/genética , Sequenciamento do Exoma , Síndrome de Noonan/genética , Líquido Amniótico/metabolismo , Dineínas do Axonema/genética , Síndrome CHARGE/diagnóstico , Transtornos da Motilidade Ciliar/diagnóstico , DNA/isolamento & purificação , DNA/metabolismo , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Feminino , Feto/metabolismo , Humanos , Síndrome de Noonan/diagnóstico , Fenótipo , Placenta/metabolismo , Gravidez , Diagnóstico Pré-Natal , Proteínas Proto-Oncogênicas c-raf/genética , Ultrassonografia Pré-Natal
7.
Sci Rep ; 7: 44429, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28290519

RESUMO

As a new class of non-volatile memory, resistive random access memory (RRAM) offers not only superior electronic characteristics, but also advanced functionalities, such as transparency and radiation hardness. However, the environmental tolerance of RRAM is material-dependent, and therefore the materials used must be chosen carefully in order to avoid instabilities and performance degradation caused by the detrimental effects arising from environmental gases and ionizing radiation. In this work, we demonstrate that AlN-based RRAM displays excellent performance and environmental stability, with no significant degradation to the resistance ratio over a 100-cycle endurance test. Moreover, transparent RRAM (TRRAM) based on AlN also performs reliably under four different harsh environmental conditions and 2 MeV proton irradiation fluences, ranging from 1011 to 1015 cm-2. These findings not only provide a guideline for TRRAM design, but also demonstrate the promising applicability of AlN TRRAM for future transparent harsh electronics.

8.
QJM ; 109(6): 425, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26961551
9.
Hong Kong Med J ; 22(1): 30-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26492926

RESUMO

INTRODUCTION: Several studies have shown that women with pre-existing diabetes mellitus have significantly lower pregnancy-associated plasma protein-A levels than those without. This study aimed to evaluate whether first-trimester pregnancy-associated plasma protein-A multiple of median is associated with gestational diabetes mellitus in Chinese pregnant women. METHODS: This prospectively collected case series was conducted in a regional hospital in Hong Kong. All consecutive Chinese women with a singleton pregnancy who attended the hospital for their first antenatal visit (before 14 weeks' gestation) from April to July 2014 were included. Pregnancy-associated plasma protein-A multiple of median was compared between the gestational diabetic (especially for early-onset gestational diabetes) and non-diabetic groups. The correlation between pregnancy-associated plasma protein-A level and glycosylated haemoglobin level in women with gestational diabetes was also examined. RESULTS: Of the 520 women recruited, gestational diabetes was diagnosed in 169 (32.5%). Among them, 43 (25.4%) had an early diagnosis, and 167 (98.8%) with the disease were managed by diet alone. The gestational diabetic group did not differ significantly to the non-diabetic group in pregnancy-associated plasma protein-A (0.97 vs 0.99, P=0.40) or free ß-human chorionic gonadotrophin multiple of median (1.05 vs 1.02, P=0.29). Compared with the non-gestational diabetic group, women with early diagnosis of gestational diabetes had a non-significant reduction in pregnancy-associated plasma protein-A multiple of median (median, interquartile range: 0.86, 0.57-1.23 vs 0.99, 0.67-1.44; P=0.11). Pregnancy-associated plasma protein-A and glycosylated haemoglobin levels were not correlated in women with gestational diabetes (r=0.027; P=0.74). CONCLUSIONS: Chinese women with non-insulin-dependent gestational diabetes did not exhibit significant changes to pregnancy-associated plasma protein-A multiple of median nor a correlation between pregnancy-associated plasma protein-A with glycosylated haemoglobin levels. Pregnancy-associated plasma protein-A multiple of median was not predictive of non-insulin-dependent gestational diabetes or early onset of gestational diabetes. There was a high prevalence of gestational diabetes in the Chinese population.


Assuntos
Diabetes Gestacional , Hemoglobinas Glicadas/análise , Proteína Plasmática A Associada à Gravidez , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Diagnóstico Precoce , Feminino , Hong Kong/epidemiologia , Humanos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Proteína Plasmática A Associada à Gravidez/análise , Proteína Plasmática A Associada à Gravidez/metabolismo , Prevalência , Estatística como Assunto
10.
Genet Mol Res ; 14(4): 17028-33, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26681050

RESUMO

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.


Assuntos
Aberrações Cromossômicas , Fatores de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Adulto Jovem
11.
BMC Public Health ; 15: 1131, 2015 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26572228

RESUMO

BACKGROUND: There is emerging evidence of the significance of paternal mental health problems among the expectant fathers during the antenatal and postnatal period. The present study aims at determining the prevalence of paternal perinatal anxiety and identifying its risk factors among the fathers. METHODS: A total of 622 expectant fathers were recruited in Hong Kong. The expectant fathers were assessed using standardized and validated psychological instruments on three time points including early pregnancy, late pregnancy and 6 week postnatal. Independent samples t-test, one way ANOVA, Pearson's correlation and multiple linear regression were used to examine the effect of hypothesized risk factors. Hierarchical multiple regression and mixed effect model were also conducted with potential confounding factors controlled for. RESULTS: Results showed that a significant proportion of expectant fathers experienced anxiety during the perinatal period. Low self-esteem and poor social support were found to be risk factors of paternal anxiety across pregnancy to postnatal period. Work-family conflict could significantly predict paternal anxiety in the pregnancy period. CONCLUSIONS: The present study points to the need for greater research and clinical attention to paternal anxiety, given that it is a highly prevalent problem and could be detrimental to their partner's well-being and children development. The present findings contributes to the theoretical understanding of the prevalence and risk factors of paternal perinatal anxiety and have implications for the design of effective identification, prevention, and interventions of these clinical problems.


Assuntos
Ansiedade/epidemiologia , Pai/psicologia , Saúde do Homem , Adulto , Feminino , Hong Kong/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Fatores de Risco , Autoimagem , Apoio Social , Inquéritos e Questionários , Adulto Jovem
12.
Opt Express ; 23(19): A1051-9, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26406735

RESUMO

Planar hybrid solar cells based on bulk GaAs wafers with a background doping density of 10(16) cm(-3) and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) ( PEDOT: PSS) demonstrated an excellent power conversion efficiency of 8.99%. The efficiency of the cell was enhanced to 9.87% with a back-surface field feature using a molecular beam epitaxially grown n-type GaAs epi-layer. The efficiency and fill factor reach 11.86% and 0.8 when an additional p + GaAs epi-layer is deposited on the surface of the solar cells, which provides a front-surface field. The interface between the high- and low-doped regions in the polymer/GaAs and GaAs formed an electric field that introduced a barrier to minority carriers flow to the substrate and effectively reduced front surface carrier recombination, thereby enhancing light-generated free carrier collection efficiency and open-circuit voltage. Compared with the device without the front- and back-surface field, the fill factor and open-circuit voltage of the hybrid solar cell were improved from 0.76 to 0.8 and from 0.68 V to 0.77V, respectively. The highest efficiency reaches a record 13% when the Zonyl fluorosurfactant-treated PEDOT: PSS is used as a hole-transporting conducting layer for hybrid cells.

13.
Hong Kong Med J ; 21(3): 243-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25999032

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of double balloon catheter for induction of labour in Chinese women with one previous caesarean section and unfavourable cervix at term. DESIGN: Retrospective cohort study. SETTING: A regional hospital in Hong Kong. PATIENTS: Women with previous caesarean delivery requiring induction of labour at term and with an unfavourable cervix from May 2013 to April 2014. MAJOR OUTCOME MEASURES: Primary outcome was to assess rate of successful vaginal delivery (spontaneous or instrument-assisted) using double balloon catheter. Secondary outcomes were double balloon catheter induction-to-delivery and removal-to-delivery interval; cervical score improvement; oxytocin augmentation; maternal or fetal complications during cervical ripening, intrapartum and postpartum period; and risk factors associated with unsuccessful induction. RESULTS: All 24 Chinese women tolerated double balloon catheter well. After double balloon catheter expulsion or removal, the cervix successfully ripened in 18 (75%) cases. The improvement in Bishop score 3 (interquartile range, 2-4) was statistically significant (P<0.001). Overall, 18 (75%) cases were delivered vaginally. The median insertion-to-delivery and removal-to-delivery intervals were 19 (interquartile range, 13.4-23.0) hours and 6.9 (interquartile range, 4.1-10.8) hours, respectively. Compared with cases without, the interval to delivery was statistically significantly shorter in those with spontaneous balloon expulsion or spontaneous membrane rupture during ripening (7.8 vs 3.0 hours; P=0.025). There were no major maternal or neonatal complications. The only factor significantly associated with failed vaginal birth after caesarean was previous caesarean section for failure to progress (P<0.001). CONCLUSIONS: This is the first study using double balloon catheter for induction of labour in Asian Chinese women with previous caesarean section. Using double balloon catheter, we achieved a vaginal birth after caesarean rate of 75% without major complications.


Assuntos
Catéteres , Trabalho de Parto Induzido/instrumentação , Nascimento Vaginal Após Cesárea/instrumentação , Adulto , Catéteres/efeitos adversos , Maturidade Cervical , Cesárea , China , Distocia/cirurgia , Feminino , Humanos , Ocitócicos , Ocitocina , Parto , Gravidez , Estudos Retrospectivos , Fatores de Tempo
14.
PLoS One ; 9(2): e87988, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24505343

RESUMO

OBJECTIVE: To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong. METHODS: Array CGH was performed on 220 samples recruited prospectively as the first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays. RESULTS: Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population. CONCLUSION: Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.


Assuntos
Cariótipo Anormal , Hibridização Genômica Comparativa/métodos , Doenças Genéticas Inatas , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino
16.
Hong Kong Med J ; 19(5): 424-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23603779

RESUMO

OBJECTIVE: The fetal fibronectin test is advocated to facilitate the management of women presenting with threatened preterm labour, but is underutilised in Hong Kong. This study aimed to provide experience with this test and evaluate its utility in a local setting. DESIGN: Prospective cohort study. SETTING: A university-affiliated hospital in Hong Kong. PATIENTS: Women presenting with symptoms of preterm labour were recruited from 1 January 2011 to 30 June 2012. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, and negative predictive value of the fetal fibronectin test to predict delivery within 24 hours, 48 hours, 7 days, and 14 days. RESULTS: A total of 22 women were recruited; 12 (55%) of whom had a negative fetal fibronectin test, none of whom delivered within 7 days; six received corticosteroids and tocolysis, one of whom delivered within 14 days. The 10 remaining women had a positive fetal fibronectin test. Five of whom delivered within 7 days and two within 14 days; all of them had received corticosteroids and tocolysis. For predicting delivery within 7 days, the sensitivity and negative predictive value of the test were both 100%. CONCLUSIONS: Our study demonstrated the high negative predictive value of the fetal fibronectin test in our local setting, which suggests that it should be utilised more readily in women presenting with threatened preterm labour.


Assuntos
Parto Obstétrico , Fibronectinas/análise , Trabalho de Parto Prematuro/metabolismo , Adulto , Estudos de Coortes , Feminino , Glucocorticoides/administração & dosagem , Hong Kong , Hospitais Universitários , Humanos , Projetos Piloto , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Tocolíticos/administração & dosagem
17.
Genet Mol Res ; 11(1): 317-21, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22370933

RESUMO

Chromosome evolution is one of the major mechanisms of disease progression and resistance in chronic myeloid leukemia (CML) patients. However, the clinical significance of chromosomal evolution in the Philadelphia (Ph)-negative clone during therapy is not fully understood. We evaluated 94 CML patients in the chronic phase of CML during treatment of the disease. Six of them had Ph-negative chromosome abnormalities during treatment. Four patients with a single abnormality and a good molecular response showed no obvious complications from the chromosomal changes, while two other patients who had complex abnormalities and previous treatment had poor outcomes. Our results highlight the need for close monitoring of this kind of patient, not only on a molecular level but also at the cytogenetic level.


Assuntos
Células da Medula Óssea/citologia , Aberrações Cromossômicas , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Transplante de Células-Tronco , Adulto , Idoso , Medula Óssea , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
18.
Ultrasound Obstet Gynecol ; 35(2): 149-54, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20047196

RESUMO

OBJECTIVE: To compare the predictive values of three ultrasonographic parameters: placental thickness (PT), fetal cardiothoracic ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV), alone or in combination, in pregnancies affected by homozygous alpha(0)-thalassemia at 12-20 weeks' gestation. METHODS: Pregnant women at risk of carrying a fetus affected by homozygous alpha(0)-thalassemia were studied from 1995 to 2006 using serial ultrasonography at 12-15 weeks, 16-20 weeks and 30 weeks' gestation. We measured CTR and PT from 1995, and MCA-PSV as well from 1997. An invasive prenatal test was offered if cardiomegaly with or without placentomegaly was detected but the MCA-PSV results were used only retrospectively for analysis. RESULTS: Of a total of 777 at-risk fetuses studied, 138 (17.8%) were affected by homozygous alpha(0)-thalassemia. At 12-15 weeks' gestation, 598 ultrasound examinations were performed. CTR was better than both PT and MCA-PSV in the prediction of affected pregnancies. The highest sensitivity (98.3%) was achieved by the combination of CTR and/or MCA-PSV at a false-positive rate of 15.8%. At 16-20 weeks' gestation, 410 ultrasound examinations were performed, 121 of which were at the patient's first visit and 289 of which were at a follow-up visit. Both CTR and MCA-PSV predicted the affected pregnancies equally well. The sensitivity of CTR was 100.0%, but the false-positive rate was 5.2%. In contrast, the false-positive rate of MCA-PSV alone was 1.4% and that of the combination of CTR and MCA-PSV was 0%, although their sensitivities were less than 65%. CONCLUSIONS: The data suggest that adding MCA-PSV to CTR in the prediction of homozygous alpha(0)-thalassemia can increase the sensitivity at 12-15 weeks and decrease the false-positive rate at 16-20 weeks' gestation.


Assuntos
Cardiomegalia/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Placenta/diagnóstico por imagem , Talassemia alfa/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Idade Gestacional , Homozigoto , Humanos , Artéria Cerebral Média/fisiopatologia , Placenta/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Fatores de Risco , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal/métodos , Talassemia alfa/genética , Talassemia alfa/fisiopatologia
20.
Br J Cancer ; 101(11): 1860-8, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19935799

RESUMO

BACKGROUND: SR4554 is a fluorine-containing 2-nitroimidazole, designed as a hypoxia marker detectable with 19F magnetic resonance spectroscopy (MRS). In an initial phase I study of SR4554, nausea/vomiting was found to be dose-limiting, and 1400 mg m(-2) was established as MTD. Preliminary MRS studies demonstrated some evidence of 19F retention in tumour. In this study we investigated higher doses of SR4554 and intratumoral localisation of the 19F MRS signal. METHODS: Patients had tumours > or = 3 cm in diameter and < or = 4 cm deep. Measurements were performed using 1H/19F surface coils and localised 19F MRS acquisition. SR4554 was administered at 1400 mg m(-2), with subsequent increase to 2600 mg m(-2) using prophylactic metoclopramide. Spectra were obtained immediately post infusion (MRS no. 1), at 16 h (MRS no. 2) and 20 h (MRS no. 3), based on the SR4554 half-life of 3.5 h determined from a previous study. 19Fluorine retention index (%) was defined as (MRS no. 2/MRS no. 1)*100. RESULTS: A total of 26 patients enrolled at: 1400 (n=16), 1800 (n=1), 2200 (n=1) and 2600 mg m(-2) (n=8). SR4554 was well tolerated and toxicities were all < or = grade 1; mean plasma elimination half-life was 3.7+/-0.9 h. SR4554 signal was seen on both unlocalised and localised MRS no. 1 in all patients. Localised 19F signals were detected at MRS no. 2 in 5 out of 9 patients and 4 out of 5 patients at MRS no. 3. The mean retention index in tumour was 13.6 (range 0.6-43.7) compared with 4.1 (range 0.6-7.3) for plasma samples taken at the same times (P=0.001) suggesting (19)F retention in tumour and, therefore, the presence of hypoxia. CONCLUSION: We have demonstrated the feasibility of using 19F MRS with SR4554 as a potential method of detecting hypoxia. Certain patients showed evidence of 19F retention in tumour, supporting further development of this technique for detection of tumour hypoxia.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Neoplasias/metabolismo , Nitroimidazóis/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Hipóxia Celular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitroimidazóis/efeitos adversos , Oxigênio/metabolismo , Pressão Parcial , Adulto Jovem
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