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1.
Hong Kong Med J ; 28(6): 438-446, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36261264

RESUMO

INTRODUCTION: This study was performed to examine the effects of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on neutropenic toxicity, chemotherapy delivery, and hospitalisation among Chinese patients with breast cancer in Hong Kong. METHODS: This retrospective study included patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy from November 2007 to October 2013 at Princess Margaret Hospital. Data were collected regarding the usage of G-CSF prophylaxis; incidences of grade 3 or 4 neutropenia, febrile neutropenia, non-neutropenic fever, and infection; hospital admissions, and chemotherapy dose delivery. Patients who began to receive G-CSF prophylaxis during the first cycle of chemotherapy and continued such prophylaxis in subsequent cycles were regarded as the primary G-CSF prophylaxis group. RESULTS: In total, 231 female Chinese patients with breast cancer were included in the analysis. Overall, 193 (83.5%) patients received primary G-CSF prophylaxis. The demographics and tumour characteristics were comparable between patients with and without primary G-CSF prophylaxis. Primary G-CSF prophylaxis significantly reduced febrile neutropenia incidence from 31.6% to 14.5% (relative risk=0.45, 95% confidence interval=0.25-0.81). Primary G-CSF prophylaxis also significantly reduced the incidence of grade 3 or 4 neutropenia from 57.9% to 24.7% (relative risk=0.43, 95% confidence interval=0.30-0.62) and the incidence of febrile neutropenia-related hospital admission from 31.6% to 12.4% (P=0.025). Finally, it enabled more patients to receive adequate chemotherapy dose delivery. CONCLUSION: Primary G-CSF prophylaxis effectively reduced the incidences of grade 3 or 4 neutropenia and febrile neutropenia, while enabling adequate chemotherapy dose delivery and reducing hospital admissions among Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy.


Assuntos
Neoplasias da Mama , Neutropenia Febril , Fator Estimulador de Colônias de Granulócitos , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/efeitos adversos , Docetaxel/efeitos adversos , População do Leste Asiático , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Estudos Retrospectivos
2.
Med J Malaysia ; 76(3): 414-416, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34031342

RESUMO

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
3.
Diabetologia ; 62(4): 732, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694351

RESUMO

The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

4.
Hong Kong Med J ; 19 Suppl 9: 21-5, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24473585

RESUMO

1. Prediction equations and normograms are established using incentive spirometry in a community cohort of 770 Hong Kong Chinese children aged 2 to 6 years. 2. All spirometric parameters depend mainly on standing height. Boys have higher values than girls. 3. Forced expiratory volumes depend on birth weight, place of birth, history of wheezing, and environmental tobacco smoke (ETS) exposure. 4. High urinary cotinine level as a biomarker of ETS exposure is noted in about one tenth of the children. 5. Urinary cotinine level is inversely associated with all spirometric parameters. This supports implementation of the smoking cessation programme.


Assuntos
Espirometria , Criança , Pré-Escolar , Feminino , Hong Kong , Humanos , Masculino , Padrões de Referência , Estudos de Amostragem
5.
Gene Ther ; 18(1): 82-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20739959

RESUMO

The ideal gene therapy vector should enable persistent expression without the limitations of safety and reproducibility. We previously reported that a prototype plasmid vector, containing a scaffold matrix attachment region (S/MAR) domain and the luciferase reporter gene, showed transgene expression for at least 6 months following a single administration to MF1 mice. Following partial hepatectomy of the animals, however, we found no detectable vector replication and subsequent propagation in vivo. To overcome this drawback, we have now developed an in vivo liver selection strategy by which liver cells transfected with an S/MAR plasmid are provided with a survival advantage over non-transfected cells. This allows an enrichment of vectors that are capable of replicating and establishing themselves as extra-chromosomal entities in the liver. Accordingly, a novel S/MAR plasmid encoding the Bcl-2 gene was constructed; Bcl-2 expression confers resistance against apoptosis-mediated challenges by the Fas-activating antibody Jo2. Following hydrodynamic delivery to the livers of mice and frequent Jo2 administrations, we demonstrate that this Bcl-luciferase S/MAR plasmid is indeed capable of providing sustained luciferase reporter gene expression for over 3 months and that this plasmid replicates as an episomal entity in vivo. These results provide proof-of-principle that S/MAR vectors are capable of preventing transgene silencing, are resistant to integration and are able to confer mitotic stability in vivo when provided with a selective advantage.


Assuntos
Vetores Genéticos/genética , Regiões de Interação com a Matriz/genética , Plasmídeos/metabolismo , Animais , Replicação do DNA/genética , Genes Reporter/genética , Genes bcl-2/genética , Terapia Genética/métodos , Luciferases/genética , Camundongos , Camundongos SCID , Proteínas Adaptadoras de Sinalização NOD/genética , Proteínas Adaptadoras de Sinalização NOD/metabolismo , Transgenes
6.
Diabetes Obes Metab ; 12(4): 360-3, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20380658

RESUMO

In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (x100) than R1 (x100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.


Assuntos
Gordura Intra-Abdominal/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Receptores de Adiponectina/metabolismo , Gordura Subcutânea/metabolismo , Adiponectina/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino
7.
Int J Obes (Lond) ; 33(3): 317-25, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19188925

RESUMO

OBJECTIVE: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. DESIGN: A randomized, double-blind, placebo-controlled study. PATIENTS: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)). INTERVENTIONS: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. MAIN OUTCOME MEASURES: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. RESULTS: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). CONCLUSIONS: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.


Assuntos
Estimulantes do Apetite/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Gastrectomia , Grelina/uso terapêutico , Fome/efeitos dos fármacos , Obesidade Mórbida/tratamento farmacológico , Adulto , Apetite/efeitos dos fármacos , Apetite/fisiologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Método Duplo-Cego , Metabolismo Energético/fisiologia , Feminino , Humanos , Fome/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Medição da Dor , Período Pós-Prandial , Resposta de Saciedade/efeitos dos fármacos , Resposta de Saciedade/fisiologia
8.
Assay Drug Dev Technol ; 7(1): 80-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19382890

RESUMO

Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly popular phytoestrogen formulations are commonly prescribed to improve menopausal health. These drugs are metabolized to numerous bioactive compounds, known or unknown, which may exert combinatorial estrogenic effects in vivo. The aim of this study is to develop and validate estrogen receptor (ER) alpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify serum estrogenic activities in a clinical trial setting. We measured changes in serum estrogenicity following ingestion of E2V and compared this to mass spectrometric measurements of its bioactive metabolites, estrone and 17beta-stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%) with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood ratio test, P < 0.0001), suggesting that the ERalpha assay reflects summated activity of compounds in serum. ERbeta correlated moderately (R = 0.52) with estrone and 17beta-estradiol, with an estrone/17beta-estradiol coefficient ratio that was twice that of ERalpha, indicating estrone was more active on a molar basis in the ERbeta assay. Unlike the ERalpha and ERbeta bioassays, MCF-7 cell proliferation was driven by 17beta-estradiol, and addition of estrone did not increase the predictive value of the model, suggesting that the driver or drivers for breast cancer cell proliferation were not the same as for ERalpha and ERbeta transactivation. In contrast, a decoction of the traditional Chinese medicinal herb Epimedium pubescens did not induce significant changes in estrogenic bioactivity over baseline. These data indicate that ERalpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays reflect different aspects of estrogenic activity and that these assays suggest that the Epimedium formulation tested is unlikely to exert significant estrogenic effects in humans.


Assuntos
Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/sangue , Fitoestrógenos/farmacologia , Adulto , Idoso , Androgênios/fisiologia , Bioensaio , Neoplasias da Mama/sangue , Calibragem , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Método Duplo-Cego , Epimedium/química , Feminino , Humanos , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Esteroides/farmacologia , Espectrometria de Massas em Tandem , Adulto Jovem
9.
J Clin Rheumatol ; 15(8): 389-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19955995

RESUMO

Drug-induced acute pneumonitis is a rare but potentially fatal adverse drug reaction. A high index of suspicion is needed for early diagnosis as it mimics community acquired pneumonia and interstitial lung disease that can occur in rheumatoid arthritis. We report a 32-year-old Chinese lady who suffered from leflunomide-induced pneumonitis and improved dramatically after receiving cholestyramine wash-out therapy. This case illustrates the need for clinical alertness to this potentially fatal complication. When in doubt, discontinuation of leflunomide and empirical wash-out therapy should be administered without delay.


Assuntos
Alveolite Alérgica Extrínseca/induzido quimicamente , Alveolite Alérgica Extrínseca/tratamento farmacológico , Resinas de Troca Aniônica/uso terapêutico , Antirreumáticos/efeitos adversos , Resina de Colestiramina/uso terapêutico , Isoxazóis/efeitos adversos , Adulto , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Leflunomida , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico
10.
Gene Ther ; 15(24): 1593-605, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18633447

RESUMO

An ideal gene therapy vector should enable persistent transgene expression without limitations of safety and reproducibility. Here we report the development of a non-viral episomal plasmid DNA (pDNA) vector that appears to fulfil these criteria. This pDNA vector combines a scaffold/matrix attachment region (S/MAR) with a human liver-specific promoter (alpha1-antitrypsin (AAT)) in such a way that long-term expression is enabled in murine liver following hydrodynamic injection. Long-term expression is demonstrated by monitoring the longitudinal luciferase expression profile for up to 6 months by means of in situ bioluminescent imaging. All relevant control pDNA constructs expressing luciferase are unable to sustain significant transgene expression beyond 1 week post-administration. We establish that this shutdown of expression is due to promoter methylation. In contrast, the S/MAR element appears to inhibit methylation of the AAT promoter thereby preventing transgene silencing. Although this vector appears to be maintained as an episome throughout, we have no evidence for its establishment as a replicating entity. We conclude that the combination of a mammalian, tissue-specific promoter with the S/MAR element is sufficient to drive long-term episomal pDNA expression of genes in vivo.


Assuntos
Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Fígado/metabolismo , Regiões de Interação com a Matriz/genética , Plasmídeos/administração & dosagem , alfa 1-Antitripsina/genética , Animais , Metilação de DNA/genética , Expressão Gênica , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Hepatectomia , Humanos , Imuno-Histoquímica , Injeções , Luciferases/análise , Luciferases/genética , Camundongos , Camundongos Endogâmicos , Plasmídeos/genética , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Fatores de Tempo , Transfecção/métodos , Transgenes
11.
Int J Obes (Lond) ; 32(1): 129-35, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17667911

RESUMO

OBJECTIVE: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. CONTEXT: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. STUDY DESIGN: Case-control study. SETTING: Hospital-based study. PATIENTS: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. INTERVENTION: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). MAIN OUTCOME MEASURE: The response of obestatin to a meal in the different groups. RESULTS: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.8+/-4 vs 17.2+/-2 pg/ml, P=0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.8+/-4 vs 21.9+/-3 pg/ml, P=0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.04+/-0.003 vs 0.05+/-0.009, P=0.32), but this was higher in the gastrectomy group (0.04+/-0.003 vs 0.1+/-0.01, P<0.001). CONCLUSIONS: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.


Assuntos
Gastrectomia , Grelina/sangue , Obesidade/sangue , Período Pós-Prandial/fisiologia , Magreza/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia
12.
Int J STD AIDS ; 19(12): 838-42, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19050215

RESUMO

SUMMARY: Syphilis testing guidelines in China are usually based on symptomatic criteria, overlooking risk assessment and ultimately opportunities for disease detection and control. We used data from 10,695 sexually transmitted disease (STD) clinic patients in Guangxi, China, to assess the efficacy of a potential screening tool inquiring about behavioural and health risk factors in identifying the STD patients who should not be triaged for syphilis testing under current guidelines, but on the contrary receive such testing. Validity testing of the screening tool was performed and receiver-operating characteristic curves were plotted to determine an optimal total risk score cut-off for testing. About 40.9% of patients with positive toluidine red unheated serum test and Treponema pallidum particle agglutination test did not show hallmark signs of syphilis. The screening tool was more sensitive in detecting infection in non-triaged male versus female patients (highest sensitivity = 90% vs. 55%) and the cut-off score to warrant testing was lower in non-triaged female patients than in non-triaged male patients (cut-off = 1 vs. 2). Most of the cases were missed among female STD patients. In spite of selective testing based on behavioural and health indicators that improve case detection, cases were still missed. Our study supports universal testing for syphilis in the STD population.


Assuntos
Inquéritos Epidemiológicos , Programas de Rastreamento/métodos , Infecções Sexualmente Transmissíveis/prevenção & controle , Sorodiagnóstico da Sífilis , Sífilis/prevenção & controle , China , Estudos Transversais , Feminino , Humanos , Masculino , Assunção de Riscos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Fatores Socioeconômicos , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/microbiologia , Treponema pallidum/isolamento & purificação
13.
Bone ; 41(3): 406-13, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17613297

RESUMO

BACKGROUND: Ghrelin is a gut-brain peptide that powerfully stimulates appetite and growth hormone secretion and is also known to directly regulate osteoblast cell function in vitro and in animal models. Little is known about the effects of ghrelin on bone turnover in humans. As the stomach is the main site of ghrelin synthesis, gastrectomy patients are deficient in ghrelin; they are also prone to osteopenia and osteomalacia. HYPOTHESIS: Ghrelin may play a role in bone regulation in humans; ghrelin deficiency following gastrectomy is associated with the disrupted regulation of bone turnover seen in these subjects. SUBJECTS AND METHODS: In a randomised, double-blind, placebo-controlled study 8 healthy controls and 8 post-gastrectomy subjects were infused with intravenous ghrelin (5 pmol/kg/min) or saline over 240 min on different days. Subjects were given a fixed energy meal during the infusion. Ghrelin, GH, type-1 collagen beta C-telopeptide (betaCTX), a marker of bone resorption, and procollagen type-1 amino-terminal propeptide (P1NP), a marker of bone formation, were measured. RESULTS: Fasting ghrelin was significantly lower in the gastrectomy group during the saline infusion (226.1+/-62.0 vs. 762+/-71.1 ng/l p<0.001). Growth hormone was significantly higher at 90 min after the ghrelin infusion, compared to saline in both healthy controls (61.1+/-8.8 vs. 1.4+/-0.6 mIU/l p<0.001) and gastrectomy subjects (61.1+/-11.8 vs. 0.9+/-0.2 mIU/l p<0.001) confirming the ghrelin was bioactive. Gastrectomy subjects were significantly older and had significantly higher plasma betaCTX than healthy controls at all time points (ANOVA p=0.009). After adjustment for age and BMI ghrelin was found to be a significant predictor of baseline plasma betaCTX and was inversely correlated with baseline plasma betaCTX (beta=-0.54 p=0.03 R2=26%). However, there was no significant effect of the ghrelin infusion on plasma betaCTX or P1NP in either subject group. CONCLUSIONS: Ghrelin infusion has no acute effect on markers of bone turnover in healthy controls and post-gastrectomy subjects, but is inversely correlated with bone resorption.


Assuntos
Remodelação Óssea/fisiologia , Gastrectomia , Hormônios Peptídicos/metabolismo , Adulto , Idoso , Colágeno Tipo I/sangue , Método Duplo-Cego , Feminino , Grelina , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue
14.
Novartis Found Symp ; 282: 173-88; discussion 188-91, 212-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17913231

RESUMO

Botanical extracts differ from conventional supplements in that they are complicated mixtures of many bioactive compounds. Here we describe our experience with a traditional Chinese medicinal plant Epimedium sp. to illustrate the scientific challenges of firstly, obtaining a standardized product from a complex mixture and secondly, evaluating that product for preclinical and clinical efficacy. In contrast, to its colloquial name 'Horny goat weed' and Internet advertisements as a herbal 'Viagra' for men, extracts of Epimedium are strongly oestrogenic due to the presence of novel potent phytoestrogens of the prenyl-flavone family. Since Epimedium is not cultivated, it was necessary to source for taxonomically identified samples and to authenticate their species by phylogenetic, chemical and bioresponse profiling. The feasibility of using a panel of oestrogen-responsive cell-based bioassays to measure summated oestrogenic effects at close time points for pharmacokinetic/pharmacodynamic (PK/PD) modelling was evaluated. We document proportionate oestrogenic responses in sera of animals fed oestrogenic drugs and botanical extracts, indicating that these target molecule responsive cell-based bioassays may have utility to capture the global effects of the myriad bioactive compounds in botanical extracts, informing the design of rigorous clinical trials for safety and efficacy.


Assuntos
Epimedium/química , Fitoestrógenos/farmacologia , Fitoterapia/normas , Extratos Vegetais/farmacologia , Animais , Bioensaio , Suplementos Nutricionais , Epimedium/classificação , Humanos , Modelos Animais , Filogenia , Fitoestrógenos/efeitos adversos , Fitoestrógenos/análise , Extratos Vegetais/efeitos adversos , Extratos Vegetais/análise , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Ultramicroscopy ; 107(9): 819-24, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17395377

RESUMO

In this work, Co ions were implanted into thermally oxidised SiO2 layers on silicon substrates. The implantation energy was 50 keV and the doses were 1, 3, 5 and 7 x 10(16) Co+/cm2. The field emission (FE) properties of these layers were studied and correlated with results from atomic force microscopy and transmission electron microscopy measurements. Other than that for the lowest dose sample, crystallised Co nanoclusters, with sizes ranging from 1.8 to 5.7 nm, are observed in these Co-implanted layers. The higher dose samples exhibit excellent FE properties and give an emission current of 1 nA at electric fields as low as 5 V/microm, for a dose of 5 x 10(16) Co+/cm2, compared with 120 V/microm for the lowest dose samples. We attribute the excellent FE properties of these layers to the formation of Co nanoclusters, with the electrical inhomogeneity giving rise to local field enhancement. Finally, repeatable staircase-like current-field (I-F) characteristics are observed in FE measurements of these higher dose samples as compared to conventional Fowler-Nordheim-type I-F characteristics in the lower dose sample. We believe this data may be a result of Coulomb blockade effects arising from the isolated low-capacitance metal quantum dots formed by controlled ion implantation.

16.
Med Biol Eng Comput ; 43(3): 325-30, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16035219

RESUMO

One of the main limitations in using inverse methods for non-invasively imaging cardiac electrical activity in a clinical setting is the difficulty in readily obtaining high-quality data sets to reconstruct accurately a patient-specific geometric model of the heart and torso. This issue was addressed by investigation into the feasibility of using a pseudo-3D ultrasound system and a hand-held laser scanner to reconstruct such a model. This information was collected in under 20 min prior to a catheter ablation or pacemaker study in the electrophysiology laboratory. Using the models created from these data, different activation field maps were computed using several different inverse methods. These were independently validated by comparison of the earliest site of activation with the physical location of the pacing electrodes, as determined from orthogonal fluoroscopy images. With an estimated average geometric error of approximately 8 mm, it was also possible to reconstruct the site of initial activation to within 17.3 mm and obtain a quantitatively realistic activation sequence. The study demonstrates that it is possible rapidly to construct a geometric model that can then be used non-invasively to reconstruct an activation field map of the heart.


Assuntos
Ecocardiografia Tridimensional/métodos , Coração/fisiologia , Modelos Anatômicos , Modelos Cardiovasculares , Estimulação Cardíaca Artificial , Humanos , Lasers
17.
Pediatrics ; 92(3): 431-5, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8361798

RESUMO

OBJECTIVE: This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C-reactive protein (CRP) response could be enhanced by serial rather than single determinations. We also sought to assess CRP responses to clinically identified noninfectious disorders. DESIGN: The CRP responses of 491 infants on 691 occasions of suspected infection were assessed. CRP levels were measured initially and twice again at 12-hour intervals (rate immunonephelometry). Assessments also included a blood culture, complete blood cell count, and chest radiograph and culture of spinal fluid when appropriate. CRP responses were correlated with four designated clinical groups: (1) positive blood or cerebrospinal fluid cultures (n = 190); (2) negative blood culture-definite infection (necrotizing enterocolitis stages 2 and 3, pneumonia, subcutaneous abscess) (n = 52); (3) negative blood culture-possible infection (antenatal risk factors, meconium aspiration, positive urine group B streptococcus antigen, necrotizing enterocolitis stage 1, febrile infants) (n = 287); and (4) negative blood culture-no infection (respiratory distress syndrome, transient tachypnea of the newborn, patent ductus arteriosus, tissue trauma) (n = 160). Diagnoses were made before CRP results were known. RESULTS: In all, 187 (27%) of the blood cultures were positive. A single organism was recovered from 174 of these; two organisms from 13. Among the single-organism cultures, 50 (29%) were Gram-negative, 120 (69%) were Gram-positive, and 4 (2%) were budding yeasts. CRP levels were elevated in various groups as follows: in the positive blood culture group (by organism), Gram-negative rods, 92% (46/50); group B streptococcus, 92% (12/13); Staphylococcus aureus, 89% (8/9); group D streptococcus, 71% (10/14); Streptococcus viridans, 60% (6/10); Staphylococcus epidermidis, 55% (40/73). In the negative blood culture-definite infection group, CRP levels were abnormal in 88%; in the negative culture-possible infection group, CRP was elevated in 33%; and in the negative blood culture-no infection group, CRP was elevated in 9%. Serial determinations of CRP resulted in enhanced sensitivity in the positive blood culture group, the negative blood culture-definite infection group, and the negative blood culture-possible infection group. Initial determinations by themselves were inadequately sensitive. Serial determinations did not enhance sensitivity of the negative blood culture-no infection group. High specificity (91%) is suggested by the low incidence of abnormal CRP levels among infants who were not infected. CONCLUSIONS: These data suggest that it would be appropriate to conduct a cautious, controlled trial to assess the safety of discontinuing antibiotic therapy if three serial CRP measurements are normal and if there are no other clinical factors suggestive of infection. The data also indicate the necessity for serial determinations of CRP for optimal sensitivity.


Assuntos
Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Infecções Bacterianas/sangue , Infecções Bacterianas/epidemiologia , Líquido Cefalorraquidiano/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Masculino , Nefelometria e Turbidimetria , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo
18.
J Gerontol A Biol Sci Med Sci ; 52(4): M241-6, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9224436

RESUMO

BACKGROUND: Despite considerable progress in the epidemiology of late life depression, little data have been documented in the scientific literature on depressive symptoms among elderly African Americans. The present investigation identifies characteristic symptoms of depression in African American community-resident elders. METHOD: Ninety-six African American men and women aged 60 years and older, with equal representation from urban and rural counties in west Tennessee, composed the sample. The sample was stratified in each of the two counties into three age categories; 60-69, 70-79, and 80 and older. Data from the Center for Epidemiological Studies-Depression scale were compared with the association of medical illness, medication use, social network, level of physical function in activities of daily living, and demographic characteristics. RESULTS: Residents screening positive for the presence of depressive symptoms showed an increased report of hypertension (p < .036), arteriosclerosis (p < .035), and circulatory problems (p < .008). There was an increased report of symptoms of depression among those who had six or more different chronic illnesses (p < .001) and among those who reported using four or more different prescription medications in the past month for chronic illnesses (p < .015). Regression analyses of data indicated that medical illness (p < .001) and social network (p < .041) were the most important predictors of depressive symptoms among residents. CONCLUSIONS: Considering the projected increase of African Americans reaching age 60, and because depressive illness is an important public heath concern, early identification of salient risk factors for depression is critical in instituting early intervention programs for the ethnic minority elderly population.


Assuntos
Envelhecimento/psicologia , Negro ou Afro-Americano/psicologia , Depressão/psicologia , Saúde da População Rural , Saúde da População Urbana , Idoso , Doenças Cardiovasculares/psicologia , Doença Crônica/tratamento farmacológico , Doença Crônica/psicologia , Doença/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social
19.
Obstet Gynecol ; 80(5): 831-7, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1407923

RESUMO

OBJECTIVE: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular-intraventricular hemorrhage in the neonate. METHODS: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. RESULTS: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. CONCLUSIONS: Active phase labor may predispose to early periventricular-intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage.


Assuntos
Hemorragia Cerebral/epidemiologia , Ventrículos Cerebrais , Cesárea , Forceps Obstétrico , Hemorragia Cerebral/etiologia , Cesárea/efeitos adversos , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Feminino , Humanos , Incidência , Recém-Nascido , Trabalho de Parto , Forceps Obstétrico/efeitos adversos , Razão de Chances , Gravidez , Análise de Regressão , Fatores de Tempo
20.
Ann Thorac Surg ; 69(6): 1846-50, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10892935

RESUMO

BACKGROUND: The Mosaic bioprosthesis is a new generation stented porcine valve. METHODS: Between May 1995 and April 1998, this valve was implanted in the aortic position in 98 patients (70 men; mean age, 69.2 years [34.2 to 83.6 years]). Preoperatively 35 patients were in New York Heart Association functional class 3 or 4. Fifty-nine patients underwent concomitant procedures. The mean duration at follow-up in January 1999 was 23.7 +/- 10.2 months (0.3 to 39.4 months) and totaled 193 patient-years. All but one survivor was in New York Heart Association class 1 or 2. RESULTS: Early complications included 1 death, 3 reoperations for bleeding, greater than mild regurgitation (paravalvar) in 1 patient and thromboembolism in 4 patients. Late complications included four deaths, study-valve endocarditis in 3 patients, more than mild regurgitation or hemolysis in 2, and thromboembolism in 2 patients. Late follow-up echocardiography in all survivors showed a mean transaortic gradient of 13.6 +/- 6.7 mm Hg, and an aortic valve area of 1.80 +/- 0.61 cm2. Valve replacement was followed by a significant and sustained decrease in left ventricular mass for all valve sizes. There has been no primary structural valve failure. CONCLUSIONS: The early experience with the Mosaic valve in the aortic position has been promising.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Próteses Valvulares Cardíacas , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Falha de Prótese , Reoperação , Taxa de Sobrevida
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