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1.
Br J Surg ; 108(7): 843-850, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-33638646

RESUMO

BACKGROUND: The aim was to determine the cost-effectiveness of radioguided occult lesion localization using 125I-labelled seeds (125I seeds) versus hookwire localization in terms of incremental cost per reoperation avoided for women with non-palpable breast cancer undergoing breast-conserving surgery. METHODS: This study was based on a multicentre RCT with eight study sites comprising seven public hospitals and one private hospital. An Australian public health system perspective was taken. The primary effectiveness outcome for this study was reoperations avoided. Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to explore uncertainty. The willingness to pay (additional cost of localization using 125I seeds justified by reoperation cost avoided) was set at the weighted, top-down cost of reoperation. Costs were in 2019 Australian dollars ($1 was equivalent to €0.62). RESULTS: The reoperation rate was 13.9 (95 per cent confidence interval 10.7 to 18.0) per cent for the 125I seed group and 18.9 (14.8 to 23.8) per cent for the hookwire localization group. The ICER for 125I seed versus hookwire localization was $4474 per reoperation averted. The results were most sensitive to uncertainty around the probability of reoperation. Accounting for transition probability and cost uncertainty for 125I seed localization, there was a 77 per cent probability that using 125I seeds would be cost-effective, with a willingness to pay of $7693 per reoperation averted. CONCLUSION: Radioguided occult lesion localization using 125I seeds is likely to be cost-effective, because the marginal (additional) cost compared with hookwire localization is less than the cost of reoperations avoided.


Assuntos
Neoplasias da Mama/economia , Radioisótopos do Iodo/uso terapêutico , Mastectomia Segmentar/métodos , Estadiamento de Neoplasias/economia , Palpação/economia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Mastectomia Segmentar/economia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Palpação/métodos , Cintilografia , Estudos Retrospectivos
3.
Child Care Health Dev ; 38(3): 435-40, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21668464

RESUMO

BACKGROUND: Regular assessment of growth is an important part of child health surveillance in the UK and most parents are very interested in their child's growth. UK parents are given a personal child health record (PCHR), including growth charts, which are plotted during baby clinic visits. Parents were consulted as part of the process of designing new UK charts to incorporate the World Health Organization growth standard. This paper describes the main themes that emerged and how they influenced the final design. METHOD: Three sets of consultations with 47 parents were conducted to collect preliminary information, and to evaluate proposed chart designs, instructions and written information for parents. RESULTS: At every consultation, the impact of the depiction of the 50th centile line in bold was mentioned spontaneously by parents. They also found aspects of the charts unclear, including the implications of a recorded weight on any particular centile, the difficulty of understanding existing text about charts in the PCHR, their preference for using pounds and ounces rather than metric weights and confusion about how frequently babies should be weighed. This led to the production of parental information including explanation of these issues which were then tested in two further sets of focus groups. CONCLUSION: Involving parents in the process of designing growth charts and information influenced the finished design and the text in the PCHR. Ensuring information meets parents' needs is important to ensure successful growth monitoring.


Assuntos
Antropometria/instrumentação , Gráficos de Crescimento , Pais/educação , Pais/psicologia , Organização Mundial da Saúde , Estatura , Peso Corporal , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Educação de Pacientes como Assunto , Publicações , Reino Unido
4.
Eur Respir J ; 38(4): 903-10, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21349912

RESUMO

The clinical applicability of screening surgically resected nonsmall cell lung cancer (NSCLC) tumour tissue and serum for activating epidermal growth factor receptor (EGFR) mutation is unknown. Furthermore, the comparative accuracy of inexpensive EGFR mutation tests, mutant-enriched (ME)-PCR and high-resolution melt (HRM) has not been determined. Lung tumour DNA from 522 surgically resected stage I-IV NSCLC and matched serum DNA from a subset of 64 subjects was analysed for EGFR mutations in exons 19 and 21 using ME-PCR and HRM. Additionally, 97 subjects had previous EGFR DNA sequencing data available for comparison. ME-PCR and HRM detected EGFR mutations in 5% (27 out of 522) of tumour samples. Compared to DNA sequencing, ME-PCR had a sensitivity of 100% and specificity of 99%, while HRM had 100% sensitivity and specificity. Six subjects with EGFR mutation tumours had matched serum, where ME-PCR detected mutations in three samples and HRM in two samples. In the cohort of never-smoker subjects, those with EGFR mutated tumours had worse survival compared with wild-type tumours (30 versus 49 months; p=0.017). ME-PCR and HRM have similar accuracy in detecting EGFR mutations but the prognostic implications of the mutations in resected NSCLC warrants further study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Análise Mutacional de DNA/normas , Receptores ErbB/genética , Testes Genéticos/métodos , Testes Genéticos/normas , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Éxons/genética , Feminino , Secções Congeladas , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Temperatura de Transição
5.
Int J Obes (Lond) ; 35(4): 510-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21224827

RESUMO

OBJECTIVE: To quantify how overweight children have to be for their mothers to classify them as overweight and to express concern about future overweight, and to investigate the adiposity cues in children that mothers respond to. DESIGN: Cross-sectional. SUBJECTS: A total of 531 children from the Gateshead Millennium Study cohort at 6-8 years and their mothers. MEASUREMENTS: In the mother: responses to two questions concerning the child's adiposity; height; weight; educational qualifications; and economic status. In the child: height; weight; waist circumference; skinfold thicknesses; bioelectrical impedance; and bone frame measurements. RESULTS: The body mass index (BMI) at which half the mothers classify their child as overweight was 21.3 (in the obese range for children of this age). The BMI at which half the mothers were concerned about their child becoming overweight in the future was 17.1 (below the overweight range). Waist circumference and skinfolds contributed most to mothers' responses. Although BMI and fat scores were important predictors individually, they did not contribute independently once waist circumference and skinfolds (their most visible manifestations) were included in the regression equations. Mothers were less likely to classify girls as overweight. Mothers with higher BMIs were less likely to classify their child as overweight, but were more likely to be concerned about future overweight. CONCLUSION: Health promotion efforts directed at parents of young primary school children might better capitalise on their concern about future overweight in their child than on current weight status, and focus on mothers' response to more visible characteristics than the BMI.


Assuntos
Índice de Massa Corporal , Mães/psicologia , Sobrepeso/psicologia , Peso Corporal/fisiologia , Criança , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Masculino , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Percepção , Inquéritos e Questionários , Reino Unido/epidemiologia
6.
Eur Respir J ; 35(1): 152-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19608585

RESUMO

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P(450), family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Citocromo P-450 CYP1A1/genética , Estudos de Associação Genética , Haplótipos/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
7.
Science ; 234(4779): 988-92, 1986 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-3490693

RESUMO

The human T-lymphotropic retrovirus HTLV-III/LAV encodes a trans-activator that increases viral gene expression. We expressed this trans-activator in animal cells and studied its structural and functional characteristics. The putative trans-activator protein was immunoprecipitated from overproducing stable cell lines and shown to migrate as a 14-kilodalton polypeptide on sodium dodecyl sulfate-polyacrylamide gels. S1 nuclease mapping experiments showed that the trans-activator increases the levels of steady-state messenger RNA transcribed from the viral long terminal repeat promoter. Sequences within the R region of the HTLV-III/LAV long terminal repeat are essential for trans-activation. Quantitations of messenger RNA and protein showed that the protein increase was greater than the messenger RNA increase in CV1 and HeLa cells, indicating that more than one mechanism was responsible for the trans-activation and that cell type-specific factors may determine the final level of trans-activation.


Assuntos
HIV/genética , Proteínas dos Retroviridae/metabolismo , Proteínas Virais/biossíntese , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Produtos do Gene rev , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , RNA Mensageiro/análise , Transfecção , Ativação Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana
8.
Colorectal Dis ; 11(5): 450-5, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19508517

RESUMO

AIM: The aim of the study was to investigate the frequency and detail of family history recorded for patients diagnosed with potentially high-risk colorectal cancer, and to determine the proportion of these patients referred to a high-risk assessment clinic. METHOD: Medical records of patients diagnosed with colorectal cancer under the age of 50 admitted to a major Sydney teaching hospital were reviewed. The proportion of records containing information about family history was calculated. Associations between recording of family history and demographic and clinical characteristics of patients were investigated. Logistic regression modelling was performed to identify significant, independent predictors of study outcomes. RESULTS: Of 113 patients with colorectal cancer diagnosed under the age of 50 years, 61 (54%, 95% CI: 44-63%) had an entry in their hospital medical record about family history. Family history was significantly less likely to be recorded for females, for those admitted via the Emergency Department, and for those with shorter lengths of stay. A significant family history was found in 51% of the 61 patients who had a family history recorded. Records of patients attending specialist colorectal surgeons were significantly more likely to contain information about family history than those who attended other specialists (P = 0.04). Only 14 patients (12%, 95% CI: 7-20%) were formally referred for further genetic assessment. CONCLUSION: These results suggest that family history is still being neglected in routine clinical practice, and high-risk assessment services are underutilized, implying the need for further dissemination of guidelines with regard to the recognition and management of hereditary colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Documentação/estatística & dados numéricos , Saúde da Família , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Documentação/normas , Feminino , Humanos , Masculino , Anamnese/estatística & dados numéricos , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Análise de Regressão , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais
9.
Community Dent Health ; 26(1): 38-42, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19385439

RESUMO

OBJECTIVES: The aim of the study was to examine whether the removal of carious teeth affected children's growth relative to that of a standard population. DESIGN: Longitudinal prospective observational study. SETTING: Manchester Dental Hospital (MDH), U.K. PARTICIPANTS: Five- and six-year-old children who attended for extraction of carious teeth under general anaesthesia. MAIN OUTCOME MEASURE: Change in height, weight and BMI standard deviation scores during the six months after extraction of carious teeth. METHODS AND MATERIALS: The children's dental caries levels, weight and height were measured prior to extraction using standard criteria and a single trained examiner and they were then re-measured six months later. The body mass index of the children was calculated and all measurements were converted to standard deviation scores (SDS) using the U.K. 1990 growth reference. Changes in growth SDS during the six months subsequent to the extractions were then calculated. RESULTS: Two hundred and eighteen children, mean (range) age 5.9 (5-6) were examined initially, of whom 131 were successfully followed up a mean 7.1 (0.13) months later. The participants had a mean dmft of 7.18 (SD 3.27) at baseline and were not shorter than expected (8.3% <10th percentile), or more underweight (6.9% <10th percentile for weight). At follow up children showed a statistically significant gain in BMI SDS (mean (SD) 0.26 (37) p < 0.001) and a small gain in height SDS (0.05 (0.38) p = 0.05). CONCLUSION: This study suggests that the extraction of carious teeth in five and six year old children promotes weight gain and possibly growth.


Assuntos
Estatura , Peso Corporal , Desenvolvimento Infantil , Cárie Dentária/terapia , Saúde Bucal , Extração Dentária/efeitos adversos , Criança , Pré-Escolar , Estudos Transversais , Índice CPO , Feminino , Humanos , Estudos Longitudinais , Masculino
10.
Eur J Clin Nutr ; 62(2): 210-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17356557

RESUMO

OBJECTIVES: (1) To develop a method of manipulating bioelectrical impedance (BIA) that gives indices of lean and fat adjusted for body size, using a large normative cohort of children. (2) To assess the discriminant validity of the method in a group of children likely to have abnormal body composition. DESIGN: Two prospective cohort studies. SETTING: Normative data: Avon Longitudinal Study of Parents and Children (ALSPAC), population based cohort; proof of concept study: tertiary feeding clinic and special needs schools. SUBJECTS: Normative data: 7576 children measured aged between 7.25 and 8.25 (mean 7.5) (s.d.=0.2) years; proof of concept study: 29 children with either major neurodisability or receiving artificial feeding, or both, mean age 7.6 (s.d.=2) years. MEASURES: Leg-to-leg (Z (T)) and arm-to-leg (Z (B)) BIA, weight and height. Total body water (TBW) was estimated from the resistance index (RI=height(2)/Z), and fat-free mass was linearly related to TBW. Fat mass was obtained by subtracting fat-free mass from total weight. Fat-free mass was log-transformed and the reciprocal transform was taken for fat mass to satisfy parametric model assumptions. Lean and fat mass were then adjusted for height and age using multiple linear regression models. The resulting standardized residuals gave the lean index and fat index, respectively. RESULTS: In the normative cohort, the lean index was higher and fat index lower in boys. The lean index rose steeply to the middle of the normal range of body mass index (BMI) and then slowly for higher BMI values, whereas the fat index rose linearly through and above the normal range. In the proof of concept study, the children as a group had low lean indices (mean (s.d.) -1.5 (1.7)) with average fat indices (+0.21 (2.0)) despite relatively low BMI standard deviation scores (-0.60 (2.3)), but for any given BMI, individual children had extremely wide ranges of fat indices. The lean index proved more stable and repeatable than BMI. CONCLUSIONS: This clinical method of handling BIA reveals important variations in nutritional status that would not be detected using anthropometry alone. BIA used in this way would allow more accurate assessment of energy sufficiency in children with neurodisability and may provide a more valid identification of children at risk of underweight or obesity in field and clinical settings.


Assuntos
Composição Corporal , Água Corporal/metabolismo , Transtornos da Nutrição Infantil/diagnóstico , Impedância Elétrica , Estado Nutricional , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/metabolismo , Índice de Massa Corporal , Peso Corporal/fisiologia , Criança , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/metabolismo , Estudos Prospectivos , Fatores Sexuais
11.
Pediatr Obes ; 13(10): 621-627, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29998577

RESUMO

OBJECTIVES: To investigate whether high weight in infancy predicts obesity in childhood. METHOD: Data from two UK cohorts (Newcastle Growth and Development N = 795, Gateshead Millennium N = 393) and one Finnish (Tampere N = 1262) were combined. Z scores of weight at 3 and 12 months and body mass index (BMI) at 5 and 8 years were categorized as raised/overweight (1 to <2 SD) or high/obese (≥2 SD). RESULTS: The majority of infants with raised or high weight at birth tended to revert to normal by 3 months and to track in the same category from 3 to 12 months. Although infants with high weight were five times more likely to have BMI ≥ 2 SD at 8 years (p < 0.001), only 22% went on to have BMI ≥ 2 SD, while 64% of infants with raised weight had normal BMI at 8 years. Of children with BMI ≥ 2 SD aged 8 years, only 22% had raised weight in infancy and half had BMI ≥ 2 SD for the first time at that age. CONCLUSIONS: Infants with raised weight in infancy tend to remain so, but most children who go on to have BMI ≥ 2 SD were not unusually heavy infants and the majority of infants with high weight reverted to overweight or normal weight in childhood.


Assuntos
Peso Corporal/fisiologia , Obesidade Infantil/etiologia , Medição de Risco/métodos , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Humanos , Lactente , Estudos Longitudinais , Masculino , Obesidade Infantil/epidemiologia , Fatores de Risco , Reino Unido/epidemiologia
12.
Br J Ophthalmol ; 90(7): 836-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16540485

RESUMO

BACKGROUND: Unilateral visual impairment (UVI) as a result of amblyopia or refractive error is common in childhood, but its functional significance remains largely unexplored. AIM: To investigate the influence of visual acuity and stereoacuity on the performance of preschool children on tasks requiring visuomotor skills and visuospatial ability. METHODS: Children with normal (6/6) visual acuity (VA) in both eyes and children with UVI ranging from 6/9 to 6/60, with no strabismus and normal vision in the fellow eye, were assessed on a neurodevelopmental test battery of visually guided tasks. RESULTS: 50 children (mean age (SD): 52.4 (5.7) months; median (range) VA: 6/9 (6/6 to 6/60); median (range) stereoacuity: 70 seconds arc (40-absent)) completed the test battery. UVI and stereoacuity correlated moderately (Pearson's r = 0.537, p < 0.001) but seven of 28 children with impaired VA had normal stereoacuity (< 70 seconds arc) while five of 22 with normal VA had abnormal stereoacuity. Stereoacuity correlated with performance on a task requiring fine hand-eye coordination and a task measuring visuomotor integration. UVI did not correlate with performance on any test battery items. CONCLUSIONS: UVI itself does not appear to relate to visuomotor actions, except when associated with reduced stereoacuity. Stereoacuity appears to have an influential role in fine visuomotor actions and spatial representation in preschool children.


Assuntos
Ambliopia/complicações , Erros de Refração/complicações , Pré-Escolar , Percepção de Profundidade , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Modelos Lineares , Masculino , Transtornos das Habilidades Motoras/diagnóstico , Disparidade Visual , Testes Visuais , Visão Binocular
13.
Scott Med J ; 51(3): 26-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16910048

RESUMO

BACKGROUND AND AIMS: Dental decay remains a major public health problem in Scottish children. The aim of this study was to investigate the relationship between diet, bowel habit, social class, and body mass index (BMI) in children with severe tooth decay. CHILDREN AND METHODS: A cross sectional study of 165 children aged 3 -11 years attending Glasgow Dental Hospital for extraction of teeth under dental general anaesthesia (DGA), was undertaken. A structured questionnaire was used to obtain information from each child on diet, bowel habit, and social status of their parents. Fibre and sugar scores were calculated from the frequency of consumption of a range of relevant foods. RESULTS: The children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An excess of children were from the most deprived parts of the city and they had the worst decay. Children with the worst decay were also significantly thinner. No relationship was found between tooth decay and bowel habit. CONCLUSIONS: In this selected group of children with poor dental health, those from deprived families were over-represented and had significantly more decay. Severe dental decay was also associated with underweight.


Assuntos
Cárie Dentária , Dieta , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos Transversais , Cárie Dentária/epidemiologia , Sacarose Alimentar/administração & dosagem , Humanos , Classe Social , Fatores Socioeconômicos
14.
Br J Pharmacol ; 68(1): 75-82, 1980 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6101977

RESUMO

1 Activity of six beta-adrenoceptor antagonists was studied on behavioural activity (delayed differentiation) in the monkey (Macaca mulatta). The drugs, three relatively lipophilic antagonists (propranolol, oxprenolol and metoprolol), and three relatively hydrophilic antagonists (acebutolol, atenolol and sotalol), were given by intraperitoneal injection (5 to 30 mg/kg).2 With atenolol (25 to 30 mg/kg), total response time was increased, but there was no effect on the number of correct responses. With acebutolol (25 to 30 mg/kg), the number of correct responses was reduced, but there was no effect on total response time. With metoprolol (25 to 30 mg/kg), there was an increase in total response time and a decrease in the number of correct responses, and correct responses were decreased 4 h after injection over the whole dose range (5 to 30 mg/kg).3 Some animals failed to respond or complete the task with 30 mg/kg oxprenolol, 25 mg/kg sotalol and 20 mg/kg propranolol. With 25 mg/kg oxprenolol, the total response time was increased and the number of correct responses was decreased. With 5-20 mg/kg sotalol, total response time was increased, but there was no effect on the number of correct responses. With 15 mg/kg of (+/-)-propranolol and its isomers, there were increases in total response time and decreases in correct responses.4 The studies suggest that lipophilic antagonists, such as propranolol, oxprenolol and metoprolol, are likely to have, at least, effects on the central nervous system, while hydrophilic antagonists may modify the peripheral nervous system. In the dose-ranges studied, propranolol had the greatest, and atenolol and acebutolol had the least effects. Atenolol and acebutolol may prove to be particularly useful in man when disturbances of the nervous system are to be avoided.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Discriminação Psicológica/efeitos dos fármacos , Animais , Comportamento de Escolha/efeitos dos fármacos , Haplorrinos , Frequência Cardíaca/efeitos dos fármacos , Macaca mulatta , Masculino , Tempo de Reação/efeitos dos fármacos , Estereoisomerismo , Fatores de Tempo
15.
Br J Pharmacol ; 61(3): 325-30, 1977 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-412540

RESUMO

1. Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey (Macaca mulatta). Diazepam and its metabolites (1.8 and 3.0 mg/kg) and clorazepate (2.6 and 4.3 mg/kg) were given by intraperitoneal injection. 2. Hydroxylation of diazepam (temazepam and oxazepam) led to a loss of, or a considerable reduction in, behavioural activity, whereas activity was preserved, though modified, by demethylation (nordiazepam). It was not possible to establish change in behaviour at specific time intervals after clorazepate, but combined performance data revealed an effect. 3. The maximum mean plasma concentrations of diazepam, temazepam, oxazepam and clorazepate were observed at 0.5 h, and the maximum mean plasma concentration of nordiazepam was observed at 1 hour. Plasma concentrations of nordiazepam were the highest and decreased monoexponentially. Plasma concenqrations of the other drugs declined rapidly at first but more slowly later, and these data were analysed as biexponential models. In the analysis for metabolites, nordiazepam reached measurable levels after the injection of diazepam and clorazepate. 4. It is suggested that differences in the effects of closely related benzodiazepines may not be due solely to their plasma pharmacokinetic properties, but may arise from differences in their intrinsic activity.


Assuntos
Comportamento Animal/efeitos dos fármacos , Diazepam/análogos & derivados , Diazepam/farmacologia , Animais , Clorazepato Dipotássico/metabolismo , Clorazepato Dipotássico/farmacologia , Diazepam/metabolismo , Discriminação Psicológica/efeitos dos fármacos , Meia-Vida , Haplorrinos , Cinética , Macaca mulatta , Masculino , Fatores de Tempo
16.
Eur J Clin Nutr ; 58(9): 1290-6, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15054405

RESUMO

OBJECTIVES: To describe the first-week feeding patterns for breast- vs bottle-fed babies, and their association with sustained breast-feeding and infant weight gain at 6 weeks. DESIGN: A longitudinal cohort study. SETTING: Feeding diaries were completed by mothers in an urban UK community shortly after birth; follow-up weight and feeding data were collected at routine health checks. SUBJECTS: Mothers of 923 full-term infants born during the recruiting period agreed to join the study. In all, 502 usable diaries were returned from 54% of the cohort. RESULTS: Breast-fed infants were fed more frequently (2.71 h between feeds) than bottle-fed infants (3.25 h between feeds) and mixed-fed infants (3.14 h between feeds) (P<0.001) in the first week of life, while duration of feeds was similar. Only exclusive breast-feeding in the first week (P<0.001) and maternal education (P=0.004) were related to continued breast-feeding at 6 weeks. Greater first-week feeding frequency (as measured by feed-to-feed interval, h) was associated with higher weight gain at 6 weeks for breast-feeders, but no analysed factors were associated with higher weight gain for bottle-feeders. CONCLUSIONS: This large-scale study of first-week feeding patterns sheds light on the important and complicated issues of breast-feeding continuation and infant weight gain, with implications for the feeding advice given to mothers. Supplementary bottle feeds were clearly associated with discontinued breast-feeding at 6 weeks. Over that period, higher weight gain was associated with more frequent feeding for breast-fed infants only. SPONSORSHIP: Henry Smith Charity, SPARKS, Child Growth Foundation.


Assuntos
Alimentação com Mamadeira/estatística & dados numéricos , Aleitamento Materno/estatística & dados numéricos , Recém-Nascido/crescimento & desenvolvimento , Mães/psicologia , Aumento de Peso , Adulto , Estudos de Coortes , Escolaridade , Ingestão de Energia , Feminino , Humanos , Lactente , Alimentos Infantis , Estudos Longitudinais , Masculino
17.
Chem Biol Interact ; 11(2): 121-31, 1975 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1139740

RESUMO

The uptake and binding of ring-labelled [-14C]aflatoxin B1 (AFB1) by rat and hamster liver and kidney has been studied, the former species being extremely sensitive to the carcinogenic action of AFB, whereas the latter is resistant. In contrast to an earlier report (Lijinsky et al, Cancer Res., 30 (1970) 2280-2283, binding of the carcinogen to nucleic acids was far greater than that to protein. Rat liver DNA bound ten times and rRNA twenty times more carcinogen than protein. There were also differences in the amount of carcinogen bound to rat liver nucleic acids compared to those of the hamster, the latter species binding lower amounts of the carcinogen. Rat liver DNA bound four times and rRNA ten times as much AFB1 6 h after carcinogen administration whereas liver protein bound AFB1 was similar for the two species. Not only was there a difference in the amount of AFB1 bound but whereas in the rat, liver nucleic acid bound carcinogen decayed with time, no such fall was seen in the hamster, this remaining at a low level throughout the 48-h time period studied. In contrast, reaction of the carcinogen with kidney macromolecules was similar for the two species. The much higher binding of AFB1 to nucleic acids than to protein might account for the potent carcinogenicity of this compound in the rat, particularly since liver protein binding does not differ between a susceptible and a resistant species. A further important factor in determining carcinogenic sensitivity may be the removal of nucleic acid bound radioactivity with time, a possible repair process.


Assuntos
Aflatoxinas/metabolismo , Rim/metabolismo , Fígado/metabolismo , Receptores de Droga , Animais , Sítios de Ligação , Radioisótopos de Carbono , Cricetinae , DNA/metabolismo , Cinética , Masculino , Especificidade de Órgãos , Ligação Proteica , Proteínas/metabolismo , RNA Ribossômico/metabolismo , Ratos , Especificidade da Espécie , Fatores de Tempo
18.
Arch Dis Child Fetal Neonatal Ed ; 89(3): F254-7, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15102731

RESUMO

BACKGROUND: Although it is a well known phenomenon, limited normative data on neonatal weight loss and subsequent gain are available, making it hard to assess individual children with prolonged weight loss. OBJECTIVE: To establish, using data from a large prospective population based cohort study, norms and limits for postnatal weight loss and its impact on current growth reference charts. METHOD: A cohort of 961 term infants were recruited at birth and followed using parental questionnaires and community nursing returns. Routine weights were collected for half the cohort at 5 days and for all at 12 days and 6 weeks. RESULTS: Less weight loss was seen than the 3-6% suggested by previous studies, but one in five infants had not regained their birth weight by 12 days. Those lightest at birth showed least weight loss. Twenty six (3%) children had more than 10% weight loss, but none showed evidence of major organic disease. Actual weights in the first fortnight are half to one centile space lower than growth charts suggest, while birthweight centiles for children born at 37 weeks were two centile spaces lower. CONCLUSIONS: Neonatal weight loss is brief, with few children remaining more than 10% below birth weight after 5 days. Growth charts are misleading in the first 2 weeks, because they make no allowance for neonatal weight loss.


Assuntos
Desenvolvimento Infantil/fisiologia , Redução de Peso/fisiologia , Fatores Etários , Humanos , Recém-Nascido , Valores de Referência , Sensibilidade e Especificidade
19.
Early Hum Dev ; 31(2): 157-62, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1292922

RESUMO

Heights, weights and head circumferences were obtained from two groups of primary school children: 1016 children from throughout Oxfordshire, a rural county with few areas of deprivation, and 219 children from an economically deprived part of the city of Newcastle on Tyne. Compared to Tanner and Whitehouse standards, Oxfordshire children were significantly taller, but not heavier, while the Newcastle children were significantly shorter and markedly lighter. Mean head circumference values were lower in the Newcastle than the Oxfordshire children. Existing national growth standards are outdated when applied to children in acceptably advantaged circumstances while impoverished children still fall below these standard in a pattern suggestive of under nutrition.


Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Cefalometria , Estudantes , Criança , Inglaterra , Humanos , Padrões de Referência , Fatores Socioeconômicos
20.
BMJ ; 317(7158): 571-4, 1998 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-9721113

RESUMO

OBJECTIVE: To evaluate the effectiveness of a health visitor led intervention for failure to thrive in children under 2 years old. DESIGN: Controlled trial, randomised by primary care practice. SETTING: Newcastle upon Tyne health district. INTERVENTION: Structured health visitor management, with dietetic, paediatric, and social work input as required. SUBJECTS: 229 children (120 in intervention practices and 109 in control practices) were identified as failing to thrive by population screening during the first 2 years of life. Follow up was by home visit of a research nurse and review of the childrens' records at age 3 years. MAIN OUTCOME MEASURES: Follow up weight and height and number of routinely collected weights. RESULTS: 95 of the 97 families offered intervention completed at least the initial assessment. At follow up, 187 (82%) records were reviewed, and these suggested that 15 (16%) controls were lost to follow up immediately after the screening weight was taken compared with only one child in the intervention group. In the 134 (58%) families who consented to home visits, children in the intervention group were significantly heavier and taller and were reported to have better appetites than childen in the control group, although both groups were equally satisfied by the services they had received. When the children were last weighed, 91 (76%) in the intervention group had recovered from their failure to thrive compared with 60 (55%) in the control group (P<0.001). CONCLUSION: In failure to thrive, health visitor intervention, with limited specialist support, can significantly improve growth compared with conventional management.


Assuntos
Enfermagem em Saúde Comunitária/métodos , Insuficiência de Crescimento/enfermagem , Estatura , Estudos de Coortes , Inglaterra , Insuficiência de Crescimento/dietoterapia , Seguimentos , Humanos , Lactente , Prognóstico , Aumento de Peso , Redução de Peso
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