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1.
Ann Oncol ; 32(2): 240-249, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33242536

RESUMO

BACKGROUND: The antitumor efficacy of PARP inhibitors (PARPi) for breast cancer patients harboring germline BRCA1/2 (gBRCA1/2) mutations is well established. While PARPi monotherapy was ineffective in patients with metastatic triple negative breast cancer (TNBC) wild type for BRCA1/2, we hypothesized that PARPi may be effective in primary TNBCs without previous chemotherapy exposure. PATIENTS AND METHODS: In the phase II PETREMAC trial, patients with primary TNBC >2 cm received olaparib for up to 10 weeks before chemotherapy. Tumor biopsies collected before and after olaparib underwent targeted DNA sequencing (360 genes) and BRCA1 methylation analyses. In addition, BRCAness (multiplex ligation-dependent probe amplification), PAM50 gene expression, RAD51 foci, tumor-infiltrating lymphocytes (TILs) and PD-L1 analyses were performed on pretreatment samples. RESULTS: The median pretreatment tumor diameter was 60 mm (range 25-112 mm). Eighteen out of 32 patients obtained an objective response (OR) to olaparib (56.3%). Somatic or germline mutations affecting homologous recombination (HR) were observed in 10/18 responders [OR 55.6%, 95% confidence interval (CI) 33.7-75.4] contrasting 1/14 non-responders (OR 7.1%; CI 1.3-31.5, P = 0.008). Among tumors without HR mutations, 6/8 responders versus 3/13 non-responders revealed BRCA1 hypermethylation (P = 0.03). Thus, 16/18 responders (88.9%, CI 67.2-96.9), in contrast to 4/14 non-responders (28.6%, CI 11.7-54.7, P = 0.0008), carried HR mutations and/or BRCA1 methylation. Excluding one gPALB2 and four gBRCA1/2 mutation carriers, 12/14 responders (85.7%, CI 60.1-96.0) versus 3/13 non-responders (23.1%, CI 8.2-50.3, P = 0.002) carried somatic HR mutations and/or BRCA1 methylation. In contrast to BRCAness signature or basal-like subtype, low RAD51 scores, high TIL or high PD-L1 expression all correlated to olaparib response. CONCLUSION: Olaparib yielded a high clinical response rate in treatment-naïve TNBCs revealing HR deficiency, beyond germline HR mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624973.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteína BRCA1/genética , Humanos , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
2.
Radiography (Lond) ; 26(4): 275-281, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32089493

RESUMO

INTRODUCTION: Radiography is a young discipline and having radiographers with a doctoral degree is central for its development. Academic development of this field in Sweden has been evolving. This study explored the diagnostic radiographers' prerequisites for doctoral studies, post-doctoral employment and research activities. METHODS: Data were collected through a questionnaire designed to give insight into doctoral radiographers' qualification paths, funding, doctoral status, employment and basic demography. Sixteen radiographers participated. A conventional content analysis was used. RESULTS: The median age at dissertation defence was 53 for doctorates and 60 for licentiates. This indicates that after receiving the doctorate, there is short time left in the profession, increasing the challenge to develop the field. Most doctorates were employed within educational establishments. Unfortunately, few had supervised doctoral students, but those employed within academia contributed significantly to academic research. CONCLUSION: Compared to other Nordic countries, Sweden is at the forefront with a positive development in obtained high academic degrees. Nevertheless, there is an urgent need for post-doctorate radiographers in order to maintain the workforce to meet current and future demands. Radiographers with doctorates need to be consulted when planning research projects to establish a clear radiographic perspective. Swedish radiographers with a doctorate or licentiate have limited research time, indicating that Sweden may not invest enough in radiographic research. IMPLICATIONS FOR PRACTICE: There is a need for more doctoral positions and doctorates radiographers to supervise doctoral students. Clinical departments should recognise the benefits of having radiographic clinical research.


Assuntos
Pessoal Técnico de Saúde , Humanos , Radiografia , Inquéritos e Questionários , Suécia , Recursos Humanos
3.
BJOG ; 127(2): 217-227, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31006170

RESUMO

OBJECTIVE: To evaluate the potential impact of intrapartum antibiotics, and their specific classes, on the infant gut microbiota in the first year of life. DESIGN: Prospective study of infants in the New Hampshire Birth Cohort Study (NHBCS). SETTINGS: Rural New Hampshire, USA. POPULATION OR SAMPLE: Two hundred and sixty-six full-term infants from the NHBCS. METHODS: Intrapartum antibiotic use during labour and delivery was abstracted from medical records. Faecal samples collected at 6 weeks and 1 year of age were characterised by 16S rRNA sequencing, and metagenomics analysis in a subset of samples. EXPOSURES: Maternal exposure to antibiotics during labour and delivery. MAIN OUTCOME MEASURE: Taxonomic and functional profiles of faecal samples. RESULTS: Infant exposure to intrapartum antibiotics, particularly to two or more antibiotic classes, was independently associated with lower microbial diversity scores as well as a unique bacterial community at 6 weeks (GUnifrac, P = 0.02). At 1 year, infants in the penicillin-only group had significantly lower α diversity scores than infants not exposed to intrapartum antibiotics. Within the first year of life, intrapartum exposure to penicillins was related to a significantly lower increase in several taxa including Bacteroides, use of cephalosporins was associated with a significantly lower rise over time in Bifidobacterium and infants in the multi-class group experienced a significantly higher increase in Veillonella dispar. CONCLUSIONS: Our findings suggest that intrapartum antibiotics alter the developmental trajectory of the infant gut microbiome, and specific antibiotic types may impact community composition, diversity and keystone immune training taxa. TWEETABLE ABSTRACT: Class of intrapartum antibiotics administered during delivery relates to maturation of infant gut microbiota.


Assuntos
Antibioticoprofilaxia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Vagina/microbiologia , Bacteroides/crescimento & desenvolvimento , Bacteroidetes , Bifidobacterium , Feminino , Humanos , Recém-Nascido , Lactobacillus , Exposição Materna , Mães , Gravidez , Estudos Prospectivos , RNA Ribossômico 16S , Análise de Sequência de RNA , Nascimento a Termo , beta-Lactamases
4.
Radiography (Lond) ; 25 Suppl 1: S25-S32, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31481184

RESUMO

INTRODUCTION: Radiographers have performed research since 1988 in Sweden. The amount of doctoral and licentiate dissertations written by registered diagnostic radiographers has increased considerably since 2000. How this new field of research was established and developed has facilitated understand of the boundaries that strengthen the professional evidence base. The aim of this dissertation review was to explore the nature and the current state of radiographic research, written by registered diagnostic radiographers in Sweden. METHODS: Dissertations published between 1988 and 2017 were analysed both deductively and inductively with content analysis. RESULTS: Radiographic research focused on structural factors, clinical radiography, radiographic technology and pedagogical approaches. The findings indicated a large interest in advancing patient information, wellbeing and care during examinations. The participants were predominantly clinical patients, followed by radiographers, adults/children and the general public. The most common study designs were descriptive with a trend towards interventional studies. Interviews and questionnaires were the most common data collection methods followed by clinical examinations and documents. CONCLUSION: The analyses demonstrate that the current radiographer research has its roots in clinical practice, focusing on pragmatic aspects and applied knowledge. The findings suggest that radiographer's dissertations meet the challenges of new technologies and working practise. If the knowledge is connected to the radiographic framework, radiography can be viewed as an independent discipline with its own philosophical base. When radiographers are encouraged to conduct research, evidence based knowledge increase which strengthens the profession. Radiography, as a scientific discipline is evolving in Sweden.


Assuntos
Dissertações Acadêmicas como Assunto , Pesquisa Biomédica/tendências , Radiografia/tendências , Ética em Pesquisa , Medicina Baseada em Evidências , Humanos , Radiografia/ética , Sujeitos da Pesquisa , Suécia
6.
Radiography (Lond) ; 23(4): 292-297, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28965891

RESUMO

INTRODUCTION: The expansion of the radiography profession in recent decades has widened the scope of radiographic practice. This has raised questions about which trends have had an impact on the profession over the years. The study aim was to explore trends that have influenced the radiography profession over the last four decades. METHODS: A qualitative design was used. Eleven focus group interviews inspired by the Scenario Planning Method were conducted at 11 diagnostic radiology departments in public hospitals in Sweden. The target group consisted of 48 registered radiographers. To analyse the data, qualitative content analysis was used. RESULTS: Thematic data analysis revealed three broad categories; technological development and radiation doses, current status of the radiography profession and specialisation leading to expert knowledge. Each category derived from two or three sub-categories. CONCLUSION: The results demonstrate significant trends of influences on the radiography profession in Sweden over the last four decades. New methods and technology and control of radiation doses have had a favourable effect on the development of the radiography profession. Nevertheless, current status such as shortage of radiographers has had an adverse way. Specialisation leading to expert knowledge has an influence on career advancement and a specialist education regulated by the law, might be a prerequisite for the development of the radiography profession.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Tecnologia Radiológica/tendências , Adulto , Atitude do Pessoal de Saúde , Mobilidade Ocupacional , Feminino , Grupos Focais , Humanos , Masculino , Pesquisa Qualitativa , Doses de Radiação , Proteção Radiológica , Suécia , Recursos Humanos
7.
Radiography (Lond) ; 23(4): 330-336, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28965897

RESUMO

INTRODUCTION: The rapid development within Interventional Radiology presents new challenges. Hybrid operating rooms consist of interventional radiology, open surgery, computed tomography, magnetic resonance imaging and other techniques. This means that several disciplines and professionals need to work in new constellations creating a multidisciplinary team around the patient. In accordance with this development, higher professional education must provide new pedagogic strategies to successfully address the knowledge expected in today's complex working life. AIM: To explore the use of Applied Drama as a learning medium, focusing on the use of Forum Theatre, to foster team work and collaboration in the field of radiography and learning. METHODS: A qualitative approach, closely related to Ethnography, was utilized. RESULT: The Drama Workshop utilising Forum Theatre created a dynamic learning environment and enabled the participants from three professions to understand each other's priorities better. The use of drama within health care education allows the students to take different roles in order to find the best way to co-operate. CONCLUSION: Forum Theatre is a useful learning medium in order to promote teamwork and collaboration in the radiological intervention field. By choosing a personal working experience, Forum Theatre seem to engage the participants at a deeper level and to experience various communication strategies and how the outcome changed depending on the approach. This can lead to improved teamwork and collaboration.


Assuntos
Pessoal Técnico de Saúde/educação , Drama , Educação de Pós-Graduação em Enfermagem , Relações Interprofissionais , Equipe de Assistência ao Paciente/organização & administração , Radiologia/educação , Adulto , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Suécia
8.
Osteoporos Int ; 28(12): 3373-3378, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28913570

RESUMO

The study investigates the effect of physical activity (PA) on a composite score for fracture risk in pre-pubertal children. Low PA in children is related to the composite score for fracture risk and the pre-pubertal years seem to be a period when PA positively affects the score. INTRODUCTION: This study evaluates if PA in children is related to clustering of risk factors for fracture. Research questions are the following: (i) What is the effect of physical activity (PA) on single traits and a composite score for fracture risk? (ii) Could this score be used to identify the level of PA needed to reach beneficial effects? METHODS: This prospective population-based study included 269 children, aged 7-9 years at baseline while 246 attended the 2-year follow-up. We estimated duration of PA by questionnaires and measured traits that independently predict fractures. We then calculated gender specific Z-scores for each variable. The mean Z-score of all traits was used as a composite score for fracture risk. We tested correlation between duration of PA, each trait, and the composite score and group differences between children in different quartiles of PA. RESULTS: At baseline, we found no correlation between duration of PA and any of the traits or the composite score. At follow-up, we found a correlation between PA and the composite score. Physical activity had an effect on composite score, and children in the lowest quartiles of PA had unbeneficial composite score compared to children in the other quartiles. CONCLUSION: Low PA in children is related to clustering of risk factors for fracture, and the pre-pubertal years seem to be a period when PA positively affects the composite score.


Assuntos
Exercício Físico/fisiologia , Fraturas Ósseas/etiologia , Absorciometria de Fóton/métodos , Antropometria/métodos , Densidade Óssea/fisiologia , Criança , Análise por Conglomerados , Feminino , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Força Muscular/fisiologia , Educação Física e Treinamento , Estudos Prospectivos , Fatores de Risco
9.
Breast ; 33: 166-177, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28415013

RESUMO

Breast cancer is the leading cause of cancer in women worldwide. Exercise interventions may improve physical and psychological factors during and after active breast cancer treatment. The aim of this systematic review was to assess the current knowledge regarding the efficacy of physical exercise with respect to fatigue and self-reported physical functioning. Systematic searches in Cochrane Library, Medline, Embase, Cinahl, PsycINFO, AMED and PEDro. After assessing the quality of the studies, we identified 25 randomized controlled trials that included 3418 breast cancer patients. An increase in physical functioning and a decrease in fatigue were observed after a physical exercise intervention, with an SMD of 0.27 (0.12, 0.41) and -0.32 (-0.49, - 0.14), respectively. There were slightly higher improvements in physical functioning and fatigue when the patients received the intervention after adjuvant breast cancer treatment. The 6-month follow-up data showed a small favourable difference for the physical exercise group for both physical functioning and fatigue. This systematic review found that an exercise intervention program can produce short-term improvements in physical functioning and can reduce fatigue in breast cancer patients. However, more studies are needed to confirm the time-dependent observations in this study.


Assuntos
Neoplasias da Mama/terapia , Terapia por Exercício/métodos , Fadiga/terapia , Efeitos Adversos de Longa Duração/terapia , Adulto , Neoplasias da Mama/psicologia , Exercício Físico , Fadiga/etiologia , Feminino , Seguimentos , Humanos , Efeitos Adversos de Longa Duração/etiologia , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Int J Oral Maxillofac Surg ; 38(2): 111-6, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19046851

RESUMO

Treatment of the atrophic edentulous maxilla is challenging especially when bone graft procedures are necessary. In this study an onlay bone graft, a saddle or veneer, with or without maxillary sinus floor inlay graft, harvested from the anterior iliac crest, in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae. The aim was to investigate treatment outcome, and the impact of gender and smoking, in 44 patients in a prospective, long-term, follow-up study concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant. Mean follow-up time was 11 years. Of 334 inserted Brånemark implants, with machined surface, 27 failed. Estimated implant survival rate was 90%. Marginal bone loss was 1.8 mm 1 year after implant surgery; 2.3 mm after 5 years; and 2.4 mm after 10 years. There was a significant difference between genders in implant survival. Marginal bone loss differed significantly between smokers and non-smokers up to the 5-year examination and between genders after the 4-year examination. The onlay bone graft, with or without a maxillary inlay graft, results in high implant survival rate, good oral function and stabilised marginal bone. All patients are still wearing their original fixed bridges.


Assuntos
Perda do Osso Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Sobrevivência de Enxerto , Arcada Edêntula/cirurgia , Maxila/patologia , Idoso , Perda do Osso Alveolar/patologia , Atrofia , Transplante Ósseo/métodos , Implantes Dentários , Prótese Total Superior , Feminino , Seguimentos , Humanos , Arcada Edêntula/patologia , Estimativa de Kaplan-Meier , Masculino , Maxila/cirurgia , Doenças Maxilares/patologia , Doenças Maxilares/cirurgia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Fatores Sexuais , Estatísticas não Paramétricas , Resultado do Tratamento
11.
Int J Oral Maxillofac Surg ; 38(1): 1-6, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19046853

RESUMO

A Le Fort I osteotomy and interpositional bone graft in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae. Surgery was performed in a two-stage procedure. The patients in this study had conditions with reversed intermaxillary relationships with or without increased vertical intermaxillary distance. The aim of the study was to investigate treatment outcome for patients in a prospective, long-term, follow-up with a mean of 13 years (range 11-16 years), concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant. The impact of gender and smoking was also investigated. Twenty-six patients were included in the study. Of 167 implants, 24 failed. The implant estimated survival rate was 85% at the end of the follow-up. There was no significant difference between smokers and non-smokers or genders concerning implant survival. Marginal bone loss was 2.5, 2.9, 3.0 and 3.1mm from the implant-abutment junction, after 1, 2, 5 and 10 years, respectively. The bone level stabilised after 2 years. This technique results in good facial morphology, good oral function and aesthetics. All patients are still wearing their original fixed bridges.


Assuntos
Perda do Osso Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endóssea , Implantes Dentários , Prótese Dentária Fixada por Implante , Maxila/cirurgia , Osteotomia de Le Fort , Adulto , Idoso , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologia , Transplante Ósseo , Implantes Dentários/efeitos adversos , Falha de Restauração Dentária , Prótese Parcial Fixa , Prótese Parcial Temporária , Feminino , Seguimentos , Humanos , Arcada Edêntula/reabilitação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fumar
12.
J Physiol Pharmacol ; 59(3): 617-32, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18953102

RESUMO

The anaesthetic propofol interacts with the GABA(A) receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 microg x ml-1), but not GABA (5 microM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABA(A) receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.


Assuntos
Citoesqueleto/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Neurônios/efeitos dos fármacos , Propofol/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Actinas/química , Actinas/metabolismo , Animais , Western Blotting , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Indicadores e Reagentes , Microscopia Confocal , Microscopia de Fluorescência , Proteínas do Tecido Nervoso/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Ratos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo
13.
J Colloid Interface Sci ; 326(2): 530-6, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18672251

RESUMO

The normal and friction forces between layers of three fatty acids (stearic, oleic, and linoleic acid) and a rosin acid (dehydroabietic acid) have been measured in n-hexadecane with a surface forces apparatus. Stearic, oleic, and dehydroabietic acid form loose-packed monolayers on mica surfaces when adsorbed from dry n-hexadecane. Linoleic acid forms an additional dimer layer between monolayer-covered surfaces, where it is stabilized by interactions between the double-bond-rich regions of the molecules. The monolayers formed by linoleic and dehydroabietic acid are thinner than the ones formed by stearic and oleic acid, but are not as easily removed from between the mica surfaces when the load or pressure is increased. The friction force increased linearly with load in all systems, and the friction coefficient increased with increasing unsaturation. Linoleic acid showed two regimes of linear friction with increasing load, corresponding to two different film thicknesses. Its friction was sensitive to sliding speed and adsorption time, and the thinner film observed at higher load had a lower friction coefficient. Such features were not observed for stearic and oleic acid, where the monolayers were removed and the friction coefficient changed to that of pure n-hexadecane at a pressure of 3.5 MPa.

14.
Eur J Surg Oncol ; 34(1): 6-12, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17881183

RESUMO

AIMS: To evaluate possible differences in effect on recurrence-free survival (RFS) and overall survival (OS) in node positive postmenopausal breast cancer patients receiving Tamoxifen or cyclic Tam and Megestrol acetate as adjuvant treatment. METHODS: Between 1989 and 1994, 489 patients with pT(1-2)pN+ hormone receptor positive or unknown tumours were included in a randomized national multicenter study to receive either Tam alone or cyclic Tam (8 weeks) and MA (8 weeks) for 2 years. Final follow-up was completed as of June 2002. Time from start of treatment to first recurrence and novel primary breast tumour, overall survival and cancer specific survival were estimated. RESULTS: No differences in RFS, OS or cancer specific survival were observed between the two treatment groups. CONCLUSIONS: Adjuvant treatment used as standard Tam alone, compared to Tam and MA, as employed in this group of patients gave similar outcomes. Side effects that led to cessation of study medication were observed in both arms.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Acetato de Megestrol/uso terapêutico , Pós-Menopausa , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Acetato de Megestrol/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Análise de Sobrevida , Tamoxifeno/efeitos adversos , Fatores de Tempo
15.
Ann Oncol ; 19(1): 56-61, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17947222

RESUMO

BACKGROUND: Tamoxifen is hydroxylated by cytochrome P450 (CYP) 2D6 to the potent metabolites 4-hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam), which are both conjugated by sulphotransferase (SULT)1A1. Clinical studies indicate that CYP2D6 and SULT1A1 genotypes are predictors for treatment response to tamoxifen. Therefore, we examined the relationship between CYP2D6 genotype, SULT1A1 genotype, SULT1A1 copy number and the pharmacokinetics of tamoxifen. PATIENTS AND METHODS: The serum levels of tamoxifen and metabolites of 151 breast cancer patients were measured by high-pressure liquid chromatography-tandem mass spectrometry. The CYP2D6 and SULT1A1 polymorphisms and SULT1A1 copy number were determined by long PCR, PCR-based restriction fragment length polymorphism, DNA sequencing and fluorescence-based PCR. RESULTS: The levels of 4OHtam, 4OHNDtam and N-demethyltamoxifen were associated with CYP2D6 predicted enzymatic activity (P < 0.05). The SULT1A1 genotype or copy number did not influence the levels of tamoxifen and its metabolites. However, the ratios of N-demethyltamoxifen/tamoxifen and N-dedimethyltamoxifen/N-demethyltamoxifen were related to SULT1A1 genotype. CONCLUSION: CYP2D6 and SULT1A1 genotypes may partly explain the wide inter-individual variations in the serum levels of tamoxifen and its metabolites. We propose that therapeutic drug monitoring should be included in studies linking CYP2D6 and SULT1A1 genotypes to clinical outcome.


Assuntos
Antineoplásicos Hormonais/farmacocinética , Arilsulfotransferase/genética , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2D6/genética , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Tamoxifeno/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Arilsulfotransferase/metabolismo , Biotransformação/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/enzimologia , Citocromo P-450 CYP2D6/metabolismo , Feminino , Dosagem de Genes , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Noruega , Polimorfismo de Fragmento de Restrição , Tamoxifeno/análogos & derivados , Tamoxifeno/sangue
16.
Langmuir ; 24(4): 1509-16, 2008 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-18085802

RESUMO

The effects of adhesion, contact area, and pressure on the lubricating properties of self-assembled monolayers on steel have been investigated with friction force microscopy. The adsorbed molecules were fatty acids with varying degrees of unsaturation (0-2 double bonds; stearic, oleic, and linoleic acid) and a rosin acid (dehydroabietic acid), adsorbed from n-hexadecane solution. The friction of these loose-packed monolayers was studied in dry N2 gas and in ethanol. Low adhesion (in ethanol) resulted in a linear increase in friction force at low loads, that is, F = muL, whereas higher adhesion (in N2 gas) gave an apparent area-dependence at low loads of the form F = S(c)A, where S(c) is the critical shear stress. A recent model for the contact mechanics of a compliant elastic film confined between stiffer substrates was applied to the data obtained in dry N2. Using this approach, we obtained interfacial energies of the compliant monolayers in good agreement with van der Waals-Lifshitz theory. With a low monolayer elastic modulus of E'(1)=0.2 GPa, we obtained a slightly higher value of Sc for stearic acid than that established for more close-packed stearic acid monolayers. An increase of mu and S(c) was found with increasing degree of unsaturation of the fatty acid.


Assuntos
Abietanos/química , Ácido Linoleico/química , Nanoestruturas/química , Ácido Oleico/química , Ácidos Esteáricos/química , Aço/química , Adesividade , Adsorção , Alcanos/química , Fricção , Microscopia de Força Atômica/métodos , Tamanho da Partícula , Pressão , Propriedades de Superfície
17.
Scand J Med Sci Sports ; 17(4): 340-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16774651

RESUMO

This non-randomized prospective controlled study evaluates a daily school-based exercise intervention program of 40 min/school day for 1 year in a population-based cohort of 81 boys aged 7-9 years. Controls were 57 age-matched boys assigned to the general school curriculum of 60 min/week. Bone mineral content (BMC; g) and areal bone mineral density (aBMD; g/cm(2)) were measured with dual X-ray absorptiometry (DXA) of the total body, the third lumbar vertebra (L3) and the femoral neck (FN). Bone width for L3 and FN was calculated from the lumbar spine and hip scan. No differences between the groups were found at baseline in age, anthropometrics or bone parameters. The mean annual gain in L3 BMC was 5.9 percentage points higher (P<0.001), L3 aBMD a mean 2.1 percentage points higher (P=0.01) and L3 width a mean 2.3 percentage points higher (P=0.001) in the cases than in the controls. When all individuals were included in one cohort, the total duration of exercise including both school-based and spare-time training correlated with L3 BMC (r=0.26, P=0.003), L3 aBMD (r=0.18, P=0.04) and L3 width (r=0.24, P=0.006). The study suggests that exercise in pre-pubertal boys influences the accrual of bone mineral and bone width and that a 1-year school-based exercise program confers skeletal benefits, at least in the lumbar spine.


Assuntos
Densidade Óssea/fisiologia , Exercício Físico/fisiologia , Osteoporose/prevenção & controle , Antropometria , Criança , Estudos de Coortes , Humanos , Masculino , Pediatria , Suécia
18.
Acta Radiol ; 47(5): 501-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16796315

RESUMO

PURPOSE: To investigate whether improvements in signal-to-noise ratio (SNR) and spectral resolution are found in spectra from patients with brain metastases obtained at higher magnetic field strengths using standard clinical instrumentation. MATERIAL AND METHODS: Six patients with brain metastases, 13 healthy volunteers, and a phantom containing brain metabolites were examined using two clinical MR instruments operating at 1.5T (Siemens) and 3T (Philips) with standard clinical head coils. Spectra were obtained using a point resolved spectroscopy pulse sequence, echo times (TE) 32 ms and 144 ms, and repetition time 2000 ms from a volume-of-interest (VOI) of size 15 x 15 x 15 mm3. SNR and spectral resolution of the metabolites N-acetylaspartate, choline, and creatine compounds in spectra from 3T were compared to the 1.5T spectra. RESULTS: In general, spectral resolution was improved by 25-30% at higher magnetic field strength. Only minor improvements in SNR were obtained at 3T using short echo time and 20-50% at long echo time. CONCLUSION: SNR and spectral resolution were improved at higher magnetic field strength, especially with TE 144 ms, including spectra from patients with heterogeneous brain tumors. However, differences in the defined effective VOI, particularly at short echo time, reduced the expected effect of increased magnetic field strength on the measured SNR.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Espectroscopia de Ressonância Magnética , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Colina/análise , Creatina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas
19.
Xenobiotica ; 35(3): 239-51, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16019949

RESUMO

The effects of cyclophosphamide (CPA) on CYP enzymes in vivo and its auto induction in rat were investigated in Wistar/Fu male rats at a single dose (40 or 200 mg kg(-1)) or as repeated dose of 200 mg kg(-1) CPA. After a single dose of CPA, mRNAs of CYPs 2B1, 2B2, 3A2, 2C11 were significantly induced up to 220-, 6.7-, 5.0- and 5.8-fold at the low dose CPA, and 4800-, 52-, 22- and 2.5-fold at the high dose. CYP2B1/2 and CYP3A proteins were increased by 4- and 2-fold (low dose) and by 28- and 1.7-fold (high dose). CYP2C11 protein levels were not altered. Microsomal activities of CYP2B, CYP3A and 2C11 were increased by 2-, 1.8- and 1.3-fold at low dose CPA, and 3.2-, 1.7- and 1.6-fold at high dose. A significant (p<0.05) decrease in CPA concentration and a significant (p<0.05) increase in 4-OH-CPA levels were observed with repeated administration of CPA. Acute induction effect on CYP2B1, 2B2, 2C11 and 3A2 and a substantial up regulation of CYP2B1 mRNA were observed after a single dose of CPA, auto induction was observed by repeated administration.


Assuntos
Ciclofosfamida/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , RNA Mensageiro/metabolismo , Animais , Células Cultivadas , Sistema Enzimático do Citocromo P-450/genética , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos WF
20.
Int J Oral Maxillofac Surg ; 34(3): 273-80, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15741036

RESUMO

The purpose of this prospective clinical study was to evaluate the 3-year outcome of 30 maxillary sinus floor augmentations with an autogenous bone-deproteinized bovine bone mixture (20:80). A total of 108 dental implants were placed after 6 months of graft healing. After another 6 months, the occlusion was restored with fixed prostheses and followed for 3 years of functional loading. Clinical and radiographic examinations of the sinuses and implants, including computerized tomography (CT) were performed. The stability of the implants was evaluated by means of resonance frequency analyses (RFA). After 3 years of functional loading with fixed bridges, 15 of 108 implants were lost giving a cumulative survival rate (CSR) of 86%. All followed patients, except one, had fixed bridges in function after 3 years of loading. The mean marginal bone loss was 1.3+/-1.1 mm after 3 years. RFA showed a mean implant stability quotient (ISQ) value of 66+/-4.1 after 3 years with no significant difference between implants in grafted and residual bone. Examination with CT showed that 67% of the maxillary sinuses were healthy prior to treatment and 71% after 3 years of loading. It was concluded that grafting of the maxillary sinus with a mixture of autogenous bone and deproteinized bovine bone is a reliable procedure.


Assuntos
Substitutos Ósseos , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Seio Maxilar/cirurgia , Procedimentos Cirúrgicos Pré-Protéticos Bucais , Idoso , Perda do Osso Alveolar/etiologia , Animais , Matriz Óssea/transplante , Transplante Ósseo , Bovinos , Implantação Dentária Endóssea , Implantes Dentários/efeitos adversos , Retenção em Prótese Dentária , Prótese Parcial Fixa , Feminino , Seguimentos , Humanos , Masculino , Seio Maxilar/diagnóstico por imagem , Pessoa de Meia-Idade , Minerais , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Vibração
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