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1.
Diabet Med ; 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29729052

RESUMO

AIMS: Adolescents with Type 2 diabetes are more likely to have cardiovascular disease (CVD) risk factors but there are few data available among adolescents with prediabetes. We characterized CVD risk factors among adolescents with prediabetes in the USA and compared levels of those risk factors with adolescents with normal glucose. METHODS: The 2005-2014 National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey, included 2843 adolescents aged 12-19 years after excluding those with diabetes. Prediabetes was based on an HbA1c , a fasting plasma glucose or a 2-h plasma glucose. We determined cardiometabolic risk factors in adolescents using age-appropriate cut-off points. We calculated odds ratios (OR) and 95% confidence intervals (CI) of these outcomes associated with having prediabetes compared with normal glucose levels. RESULTS: The weighted prevalence of prediabetes was 17.4%. After adjustment, prediabetes (vs. normal glucose) was associated with obesity (OR 1.86, 95% CI 1.35-2.55), low HDL-cholesterol (OR 1.62, 95% CI 1.08-2.44), high triglycerides (OR 1.61, 95% CI 1.12-2.30) and elevated liver transaminase (OR 2.09, 95% CI 1.19-3.67), but not with hypertension (OR 1.77, 95% CI 0.88-3.54), elevated total cholesterol (OR 1.30, 95% CI 0.82-2.06), elevated LDL-cholesterol (OR 1.59, 95% CI 0.88-2.88) or albuminuria (OR 1.24, 95% CI 0.76-2.02). CONCLUSIONS: US adolescents with prediabetes are more likely to have obesity, low HDL-cholesterol, high triglycerides and elevated liver transaminase than adolescents with normal glucose. Addressing prediabetes in youth is important for the prevention of Type 2 diabetes and long-term comorbidity.

2.
Nervenarzt ; 89(3): 290-299, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-29383410

RESUMO

In this article, the current literature on pharmacogenetics of antidepressants, antipsychotics and lithium are summarized by the section of Neurobiology and Genetics of the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN). The publications of international expert groups and regulatory authorities are reviewed and discussed. In Germany, a statement on pharmacogenetics was also made by the gene diagnostics committee of the Ministry of Health. The DGPPN supports two recommendations: 1) to perform CYP2D6 genetic testing prior to prescription of tricyclic antidepressants and 2) to determine the HLA-B*1502 genotype in patients of Asian origin before using carbamazepine. The main obstacle for a broad application of pharmacogenetic tests in psychiatry remains the lack of large prospective studies, for both single gene-drug pair and cobinatorial pharmacogenetic tests, to evaluate the benefits of genetic testing. Psychiatrists, geneticists and funding agencies are encouraged to increase their efforts for the future benefit of psychiatric patients.

3.
Int J Obes (Lond) ; 40(9): 1416-23, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27121255

RESUMO

BACKGROUND/OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed to investigate the effects of caspase-1 inhibition in the ongoing disease process, to mimic the clinical setting. SUBJECTS/METHODS: To investigate effects of caspase-1 inhibition under therapeutic conditions, male LDLR-/-.Leiden mice were fed a high-fat diet (HFD) for 9 weeks to induce a pre-diabetic state before start of treatment. Mice were then continued on HFD for another 12 weeks, without (HFD) or with (HFD-YVAD) treatment with the caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg(-1) per day). RESULTS: Nine weeks of HFD feeding resulted in an obese phenotype, with obesity-associated hypertriglyceridemia, hypercholesterolemia, hyperglycemia and hyperinsulinemia. Treatment with Ac-YVAD-cmk did not affect further body weight gain or dyslipidemia, but did attenuate further progression of insulin resistance. Histopathological analysis of livers clearly demonstrated prevention of NASH development in HFD-YVAD mice: livers were less steatotic and neutrophil infiltration was strongly reduced. In addition, caspase-1 inhibition had a profound effect on hepatic fibrosis, as assessed by histological quantification of collagen staining and gene expression analysis of fibrosis-associated genes Col1a1, Acta2 and Tnfa. CONCLUSIONS: Intervention with a caspase-1 inhibitor attenuated the development of NASH, liver fibrosis and insulin resistance. Our data support the importance of inflammasome/caspase-1 in the development of NASH and demonstrate that therapeutic intervention in the already ongoing disease process is feasible.


Assuntos
Hiperinsulinismo/tratamento farmacológico , Resistência à Insulina , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Serpinas/uso terapêutico , Proteínas Virais/uso terapêutico , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Dislipidemias/complicações , Dislipidemias/etiologia , Dislipidemias/metabolismo , Hiperinsulinismo/complicações , Hiperinsulinismo/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/complicações , Obesidade/etiologia , Obesidade/metabolismo , Serpinas/farmacologia , Proteínas Virais/farmacologia
4.
Andrology ; 2(3): 428-35, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24648111

RESUMO

Sex steroid hormones are associated with chronic diseases and mortality with risk associations that differ between racial and ethnic groups. However, it is currently unclear whether sex steroid hormone levels differ between black and white men. The aim of this study was to assess racial variation in circulating testosterone, free testosterone, sex hormone-binding globulin (SHBG) and estradiol levels in men. We searched PubMed for articles comparing circulating hormones in black and white men. A meta-analysis was performed using weighted mean differences (WMD) to compare hormones levels between black and white men. Fifteen eligible studies were identified; three did not report adjusted means. After age adjustment, free testosterone levels were significantly higher in black than in white men (WMD = 4.07 pg/mL, 95% CI 1.26, 6.88). Depending on the free testosterone concentration in white men, this WMD translates into a racial difference ranging from 2.5 to 4.9%. Total testosterone (WMD = 0.10 ng/mL, 95% CI -0.02, 0.22), estradiol (WMD = 0.67 pg/mL, 95% CI -0.04, 1.38) and SHBG (WMD = -0.45 nmol/L, 95% CI -1.75, 0.85) concentrations did not differ comparing blacks with whites. After adjustment for age, black men have a modestly but significantly 2.5 to 4.9% higher free testosterone level than white men. Based on previous studies on effects of sex steroid hormones on risk of chronic diseases or mortality, this modest difference is unlikely to explain racial differences in disease risk.


Assuntos
Afro-Americanos , Estradiol/sangue , Grupo com Ancestrais do Continente Europeu , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Genes Brain Behav ; 12(3): 289-96, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23406438

RESUMO

The FK506 binding protein 51 or FKBP5 has been implicated in the regulation of glucocorticoid receptor (GR) sensitivity, and genetic variants in this gene have been associated with mood and anxiety disorders. GR resistance and associated stress hormone dysregulation are among the most robust biological findings in major depression, the extent of which may be moderated by FKBP5 polymorphisms. FKBP5 mRNA expression in peripheral blood cells (baseline and following in vivo GR stimulation with 1.5 mg dexamethasone p.o.) was analyzed together with plasma cortisol, ACTH, dexamethasone levels and the FKBP5 polymorphism rs1360780 in 68 depressed patients and 87 healthy controls. We observed a significant (P = 0.02) interaction between disease status and FKBP5 risk allele carrier status (minor allele T) on GR-stimulated FKBP5 mRNA expression. Patients carrying the risk T allele, but not the CC genotype, showed a reduced induction of FKBP5 mRNA. This FKBP5 polymorphism by disease status interaction was paralleled by the extent of plasma cortisol and ACTH suppression following dexamethasone administration, with a reduced suppression only observed in depressed patients carrying the T allele. Only depressed patients carrying the FKBP5 rs1360780 risk allele showed significant GR resistance compared with healthy controls, as measured by dexamethasone-induced FKBP5 mRNA induction in peripheral blood cells and suppression of plasma cortisol and ACTH concentrations. This finding suggests that endocrine alterations in depressed patients are determined by genetic variants and may allow identification of specific subgroups.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Transtorno Depressivo Maior/genética , Hidrocortisona/sangue , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a Tacrolimo/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Transtorno Depressivo Maior/sangue , Dexametasona/farmacologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/agonistas , Proteínas de Ligação a Tacrolimo/metabolismo , Transcrição Genética
6.
Transl Psychiatry ; 2: e177, 2012 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-23092981

RESUMO

Despite the overt need for improved treatment modalities in depression, efforts to develop conceptually novel antidepressants have been relatively unsuccessful so far. Here we present a translational approach combining results from hypothesis-free animal experiments with data from a genetic association study in depression. Comparing genes regulated by chronic paroxetine treatment in the mouse hippocampus with genes showing nominally significant association with antidepressant treatment response in two pharmacogenetic studies, the activin pathway was the only one to show this dual pattern of association and therefore selected as a candidate. We examined the regulation of activin A and activin receptor type IA mRNA following antidepressant treatment. We investigated the effects of stereotaxic infusion of activin into the hippocampus and the amygdala in a behavioural model of depression. To analyse whether variants in genes in the activin signalling pathway predict antidepressant treatment response, we performed a human genetic association study. Significant changes in the expression of genes in the activin signalling pathway were observed following 1 and 4 weeks of treatment. Injection of activin A into the hippocampus exerts acute antidepressant-like effects. Polymorphisms in the betaglycan gene, a co-receptor mediating functional antagonism of activin signalling, significantly predict treatment outcome in our system-wide pharmacogenetics study in depression. We provide convergent evidence from mouse and human data that genes in the activin signalling pathway are promising novel candidates involved in the neurobiogical mechanisms underlying antidepressant mechanisms of action. Further, our data suggest this pathway to be a target for more rapid-acting antidepressants in the future.


Assuntos
Ativinas , Antidepressivos , Encéfalo , Transtorno Depressivo , Paroxetina/farmacologia , Proteoglicanas/genética , RNA Mensageiro/análise , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Ativinas Tipo I/genética , Receptores de Ativinas Tipo I/metabolismo , Ativinas/genética , Ativinas/metabolismo , Ativinas/farmacologia , Adulto , Idoso , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Giro Denteado/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
7.
Nutr Metab Cardiovasc Dis ; 22(9): 734-40, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21330119

RESUMO

BACKGROUND AND AIMS: Elevated iron biomarkers are associated with diabetes and other cardiometabolic abnormalities in the general population. It is unclear whether they are associated with an increased risk of all-cause or cause-specific mortality. The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. METHODS AND RESULTS: A prospective cohort study was conducted with 12,258 adults participating in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population. Study participants were recruited in 1988-1994 and followed through December 31, 2006 for all-cause, cardiovascular disease, and cancer mortality. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause mortality comparing the fourth versus the second quartiles of ferritin and transferrin saturation were 1.09 (0.82-1.44; p-trend across quartiles = 0.92) and 1.08 (0.82-1.43; p-trend across quartiles = 0.62), respectively, for men, 1.43 (0.63-3.23; p-trend across quartiles = 0.31) and 1.48 (0.70-3.11; p-trend across quartiles = 0.60), respectively, for premenopausal women, and 1.03 (0.79-1.34; p-trend across quartiles = 0.95) and 1.17 (0.92-1.49; p-trend across quartiles = 0.63), respectively, for postmenopausal women. Quartile of ferritin and transferrin saturation also showed no association between biomarkers of iron status and mortality. CONCLUSIONS: In a large nationally representative sample of US adults, within the spectrum of normal iron metabolism, ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer.


Assuntos
Biomarcadores/sangue , Anormalidades Cardiovasculares/mortalidade , Diabetes Mellitus/mortalidade , Ferro/sangue , Neoplasias/mortalidade , Adulto , Anormalidades Cardiovasculares/fisiopatologia , Intervalos de Confiança , Diabetes Mellitus/fisiopatologia , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/fisiopatologia , Inquéritos Nutricionais , Estado Nutricional , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Transferrina/análise , Transferrina/metabolismo , Estados Unidos
8.
Acta Psychiatr Scand ; 124(4): 317-28, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21838737

RESUMO

OBJECTIVE: To identify clinical variables and genetic variations within monoaminergic genes known to be implicated in pain perception that are associated with the occurrence of somatization symptoms in patients with major depression. METHOD: Somatization was evaluated using the respective subscale of the Symptom Checklist SCL-90-R. Six monoaminergic genes were identified showing an involvement in pain perception and somatization according to the literature: COMT, HTR2A, SLC6A2, SLC6A4, DRD4, and TPH1. One hundred and eighteen single nucleotide polymorphisms (SNPs) within these genes were genotyped using Illumina BeadChips in a sample of 398 at least moderately to severely depressed in-patients participating in the Munich Antidepressant Response Signature (MARS) project. RESULTS: Thirty SNPs exhibit nominally significant associations with somatization. One SNP (rs9534505) located in intron 2 of the HTR2A gene withstood correction for multiple testing. Clinical data provide further evidence for strong impact of somatization on the presentation of depressive symptoms and description of a patient subgroup with unfavorable clinical outcome. CONCLUSION: Our results demonstrate the influence of a HTR2A polymorphism on aspects of somatization in major depression, which co-occurs with an unfavorable antidepressant treatment outcome. These results confirm and expand previous findings on somatization as a risk factor for treatment outcome in major depression.


Assuntos
Transtorno Depressivo Maior/genética , Transtornos Somatoformes/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Catecol O-Metiltransferase/genética , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Percepção da Dor , Polimorfismo de Nucleotídeo Único/genética , Escalas de Graduação Psiquiátrica , Receptor 5-HT2A de Serotonina/genética , Receptores de Dopamina D4/genética , Transtornos Somatoformes/etiologia , Transtornos Somatoformes/psicologia , Resultado do Tratamento , Triptofano Hidroxilase/genética , Adulto Jovem
9.
Schmerz ; 25(4): 423-33, 2011 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-21818720

RESUMO

BACKGROUND: In order to provide efficient pain treatment clinicians need to know the latest developments in pain management and to implement this knowledge into clinical practice. The knowledge of pediatric nursing staff with regards to pediatric pain management has not yet been investigated. In this study we therefore investigated nurses' knowledge of pediatric pain management strategies. METHODS: Nursing staff knowledge was analyzed using the German version of the PNKAS-Sr2002. This questionnaire was distributed to 310 pediatric nurses and the response rate was 51.3% (n=159). Analyses of variance (ANOVA) were conducted to examine whether educational level and work experience had an influence on knowledge. Independent from work experience the educational level of nurses is important for their knowledge in pediatric pain management. RESULTS: On average nurses obtained a mean individual test score of 69.3%. Nurses with advanced qualification and nurses with 6-10 years work experience obtained the highest scores. CONCLUSION: Pediatric nurses must be trained more efficiently in pediatric pain management so that an adequate pain management is available for children and adolescents.


Assuntos
Prática Avançada de Enfermagem/educação , Dor Crônica/enfermagem , Competência Clínica , Enfermagem Pediátrica/educação , Adulto , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada/enfermagem , Estudos Transversais , Currículo , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Masculino , Medição da Dor/enfermagem , Inquéritos e Questionários
10.
Schmerz ; 24(1): 23-37, 2010 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-20108103

RESUMO

BACKGROUND: A multidimensional assessment of chronic pain is the most important tool for diagnosis and treatment. While the German Pain Questionnaire is routinely implemented in the treatment of adults with chronic pain, similar questionnaires are scarce for children and adolescents. It was the aim of the present study to report on the development and quality of a multimodal questionnaire assessing all relevant aspects of chronic pain in children and adolescents. The quality of the questionnaire was assessed (1) by implementing the questionnaire in a sample of children and adolescents suffering from chronic pain (aged 4-18 years), (2) by analysing missing items in the child, adolescent and parent version and (3) by analysing experts' ratings of the questionnaire. MATERIAL AND METHODS: The German Pain Questionnaire for Children, Adolescents and Parents (DSF-KJ) was developed on the basis of the biopsychosocial model of chronic pain in experts' meetings. The DSF-KJ entails an assessment of sociodemographic variables, pain characteristics, triggering factors, previous pain treatment, pain-related disability and cognitive and emotional factors related to the pain experience. A total of 284 children and adolescents who presented for pain treatment in our tertiary institute completed the DSF-KJ. Eleven pain experts rated the questionnaire regarding its utility for diagnosis and treatment. RESULTS: With the use of the DSF-KJ, a detailed sample description was derived on the basis of the biopsychosocial model. More adolescent girls than boys presented to the institute. The majority of the children and adolescents suffered from headache and were severely affected by their chronic pain. Children and adolescents displayed similar pain characteristics. However, adolescents were more disabled due to chronic pain and had already undergone a variety of pain treatments. These differences may reflect an ongoing chronification in adolescents. Children, adolescents and their parents filled in the questionnaire thoroughly with very few missing items. The experts rated the questionnaire as very useful for diagnosis and treatment. CONCLUSION: The DSF-KJ provides a standardized assessment and comprehensive description of paediatric chronic pain problems and facilitates medical and psychological diagnostic and therapeutic decisions. The preliminary results suggest that the questionnaire is a clinically useful and practical assessment tool for children and adolescents with chronic pain.


Assuntos
Medição da Dor/estatística & dados numéricos , Dor/classificação , Dor/diagnóstico , Inquéritos e Questionários , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Avaliação da Deficiência , Feminino , Alemanha , Transtornos da Cefaleia/classificação , Transtornos da Cefaleia/diagnóstico , Humanos , Masculino , Variações Dependentes do Observador , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes
11.
Mol Psychiatry ; 15(7): 736-47, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19125159

RESUMO

Major depression and the metabolic syndrome (MetS) are interacting clinical conditions influenced by genetic susceptibility. For both disorders, impaired serotonergic neurotransmission in specific brain areas has been suggested. This led us to investigate whether variants in the gene coding for tryptophan hydroxylase 2 (TPH2), the brain-specific and rate-limiting enzyme for serotonin biosynthesis, might be predictive for an increased liability for the development of MetS in depressed patients. In a case-control study consisting of 988 patients with recurrent unipolar depression (RUD) and 1023 psychiatric healthy controls, MetS components were ascertained according to the International Diabetes Foundation criteria. A total of 41 single nucleotide polymorphisms fully covering the TPH2 gene region were genotyped in stage 1 (300 patients/300 controls), resulting in significant genetic associations of polymorphisms located in exon 7 and intron 8 of TPH2 and the occurrence of MetS in depressed patients after correction for age, gender and multiple testing (51 RUD-MetS/179 RUD-non-MetS). We were able to confirm the significant association of rs17110690 in stage 2 (688 patients/723 controls; 110 RUD-MetS/549 RUD-non-MetS) and to link risk-genotypes and risk-haplotypes for MetS to lower TPH2 mRNA expression and to lower 5-hydroxyindoleacetic acid levels in cerebrospinal fluid previously reported in functional studies. Our findings suggest that TPH2 polymorphisms characterize a subgroup of depressed patients who are especially prone to develop metabolic disorders induced by a genotype-dependent impairment of serotonergic neurotransmission. Identifying depressed patients at high risk for MetS using genetic variants could have direct clinical impact on individualized disease management and prevention strategies.


Assuntos
Transtorno Depressivo/genética , Predisposição Genética para Doença/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Serotonina/genética , Triptofano Hidroxilase/genética , Estudos de Casos e Controles , Transtorno Depressivo/complicações , Transtorno Depressivo/enzimologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/enzimologia , Pessoa de Meia-Idade , Serotonina/biossíntese
12.
Klin Padiatr ; 220(3): 166-74, 2008 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18478489

RESUMO

BACKGROUND: In the present study, we investigated the situation of children who had succumbed to their malignancy in Germany as perceived by their parents. Specifically, we were interested in bereaved parents' perspective on five essential areas: 1) symptoms and quality of life, 2) characteristics of the child's death, 3) anticipation of their child's death and care delivery, 4) end-of-life decisions and 5) impact of the child's death on the parents and perceived social support by the health care team. MATERIALS AND METHODS: We contacted all existing departments for paediatric oncology in the German federal state of Nordrhein Westfalen and asked them to contact all parents for participation in our study who had lost their child to cancer in 1999 and 2000. Upon agreement, we interviewed the parents utilising a validated semi-structured interview on distressing symptoms and quality of life of their children during the end-of-life care period. RESULTS: Six of the 19 departments agreed to participate. Parents of 48 children (31 boys, 17 girls) were interviewed. The main distressing symptoms were fatigue, pain, loss of appetite, and dyspnoea according to the parents. While parents perceived pain and constipation to have been treated successfully, loss of appetite and anxiety were not treated effectively. 75% of the children died due to a progression of their malignancy. Of these, 50% obtained cancer-directed therapy at the end of life, which was negatively rated by the parents in hindsight. 48% of the children died at home even though 88% of the parents chose 'at home' as the most appropriate locale of death in hindsight. Parents anticipated their child's death on average 9 weeks prior to the child's death. 41% of the parents provided palliative home care for their child and the majority (88%) rated the quality of care as good or very good. 64% discussed end-of-life decisions with the health care team, 36% did not have a discussion. Parents were clearly affected by their child's death. However, 15% of the parents were not contacted by the health care team following the child's death. CONCLUSIONS: The present study demonstrated that psychological symptoms (e.g. anxiety) are frequent symptoms in the end-of-life care period and cause severe suffering in the children. Questions in terms of benefits and costs of cancer-directed therapy in the end-of-life care period need to be addressed in future prospective studies. Parents' perspective on their child's death and related end-of-life decisions highlighted the importance of communication between parents and the health care team. Future studies need to investigate potential barriers in the communication between parents and the team to optimise end-of-life decisions and hence, reduce parents' long-term distress. In line with the previous, the present data demonstrated that there is still a lack of routine contact from the health care team following the child's death despite existing guidelines. Research is therefore needed into the implementation of guidelines for routine contact into clinical practice following a child's death.


Assuntos
Atitude Frente a Morte , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Pais/psicologia , Qualidade de Vida/psicologia , Assistência Terminal/psicologia , Adolescente , Ansiedade/psicologia , Luto , Criança , Pré-Escolar , Comportamento do Consumidor , Progressão da Doença , Dispneia/psicologia , Fadiga/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Alemanha , Serviços de Assistência Domiciliar , Assistência Domiciliar/psicologia , Humanos , Lactente , Masculino , Neoplasias/terapia , Dor/psicologia , Equipe de Assistência ao Paciente , Relações Profissional-Família , Papel do Doente
13.
Schmerz ; 22(4): 442-57, 2008 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-18297316

RESUMO

Validated intruments for measuring coping in children and adolescents with chronic pain are rare in Germany. Using a sample of 180 out-patient children with chronic pain, a main component analysis was performed as well as cross-validations with out-patient and in-patient treated children. The scales of the PPCI-R showed significant relationships to pain characteristics and emotional stress. Different alterations were found in the PPCI-R scales in children with migraine and those with tension-type headache. The PPCI revised is therefore a validated instrument for measuring coping an can be implemented e.g. in treatment studies for children suffering from chronic pain.


Assuntos
Adaptação Psicológica , Dor/psicologia , Inventário de Personalidade/estatística & dados numéricos , Papel do Doente , Absenteísmo , Adolescente , Assistência Ambulatorial , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/psicologia , Manejo da Dor , Medição da Dor , Admissão do Paciente , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Cefaleia do Tipo Tensional/psicologia
14.
Int J Antimicrob Agents ; 29(3): 322-5, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17204403

RESUMO

The bactericidal activities of daptomycin, vancomycin, teicoplanin and linezolid at human peak free serum concentrations (C(max,free)) were determined against Staphylococcus aureus (one methicillin-susceptible and two methicillin-resistant strains), Enterococcus faecalis and Enterococcus faecium (one vancomycin-susceptible and one vancomycin-resistant strain of each). Daptomycin was rapidly bactericidal against 7/7 strains at C(max,free) of 22.0 mg/L (corresponding to 63% protein binding) and against 3/7 strains at 4.8 mg/L (corresponding to 92% protein binding). Vancomycin (18.0 mg/L) was bactericidal against only two strains. Both teicoplanin (4.5 mg/L) and linezolid (10.4 mg/L) were consistently bacteriostatic. Daptomycin is a useful option for the treatment of Gram-positive infections owing to its strong bactericidal activity.


Assuntos
Antibacterianos/administração & dosagem , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Acetamidas/administração & dosagem , Acetamidas/sangue , Antibacterianos/sangue , Daptomicina/administração & dosagem , Daptomicina/sangue , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Técnicas In Vitro , Linezolida , Testes de Sensibilidade Microbiana , Oxazolidinonas/administração & dosagem , Oxazolidinonas/sangue , Teicoplanina/administração & dosagem , Teicoplanina/sangue , Vancomicina/administração & dosagem , Vancomicina/sangue
15.
Oncogene ; 26(16): 2381-5, 2007 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-17043655

RESUMO

Pancreatic cancer is a devastating disease with poor prognosis. Production of large quantities of extracellular matrix and early metastasis are characteristics of this disease. One important step in the development of various cancers is the loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell-cell adhesion. It has been shown that collagen type I promotes downregulation of E-cadherin expression, which correlates with enhanced cell migration and invasiveness. In this context, we elucidated the role of Smad-interacting protein 1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene expression. We demonstrate that SIP1 upregulation shows an inverse relationship with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1 expression can be induced by exposure to collagen type I in a src-dependent manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein levels. Taken together, these results suggest that SIP1 is involved in the progression of pancreatic cancer and plays a role in mediating signal transduction from collagen type I to downregulate E-cadherin expression.


Assuntos
Caderinas/genética , Colágeno/fisiologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias Pancreáticas/genética , Proteínas Repressoras/genética , Humanos , RNA Mensageiro/genética , Transcrição Genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco
16.
Leukemia ; 19(8): 1318-23, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15920488

RESUMO

The transcription factor Wilms' tumour gene 1 (WT1) is important as a prognostic marker as well as in the detection and monitoring of minimal residual disease in leukaemia and myelodysplastic syndromes. Evidence has accumulated over the past decade to show that WT1 is a key molecule for tumour proliferation in a large number of human neoplasms most prominent in acute leukaemias, making it a suitable target for therapeutic strategies. Based on animal results, showing safety and efficacy of immunization with WT1 peptides and protein, early clinical trials in leukaemia have recently been initiated. The First International Conference on WT1 in Human Neoplasia was held in Berlin, March 11--12, 2004. This report reviews the current knowledge on the role of WT1 in tumour promotion and as a diagnostic and therapeutic target, and summarizes the data presented and discussed in this meeting.


Assuntos
Neoplasias/etiologia , Proteínas WT1/fisiologia , Animais , Genes do Tumor de Wilms , Humanos , Imunoterapia , Leucemia/diagnóstico , Leucemia/etiologia , Leucemia/terapia , Neoplasias/diagnóstico , Neoplasias/terapia
17.
Br J Cancer ; 90(2): 455-62, 2004 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-14735193

RESUMO

The human metastasis-associated protein 1 (MTA1) is a constituent of the nucleosome-remodelling and -deacetylation complex. Its expression has been correlated with the invasion and metastasis of epithelial neoplasms. To address the functional consequences of MTA1 expression in pancreatic carcinoma cells, we have established PANC-1 pancreatic carcinoma cells that stably express MTA1 as an enhanced green fluorescent fusion protein (EGFP-MTA1). Here, we demonstrate that heterologous expression of EGFP-MTA1 markedly enhanced the cellular motility and the invasive penetration of epithelial barriers by the cells. Expression of EGFP-MTA1 had no effect on substrate-independent growth, but reduced substrate-dependent cell proliferation. In addition, the organisation of the cytokeratin filament system and the localisation of the actin cytoskeleton-associated protein IQGAP1 were distinctly altered in EGFP-MTA1-expressing cells. These results indicate that enhanced expression of MTA1 promotes the acquisition of an invasive, metastatic phenotype, and thus enhances the malignancy of pancreatic adenocarcinoma cells by modulation of the cytoskeleton.


Assuntos
Adenocarcinoma/patologia , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/biossíntese , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Proteínas Repressoras/biossíntese , Divisão Celular , Citoesqueleto/fisiologia , Citoesqueleto/ultraestrutura , Humanos , Queratinas/metabolismo , Metástase Neoplásica , Fenótipo , Células Tumorais Cultivadas
18.
Semin Cell Dev Biol ; 14(4): 233-40, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14627122

RESUMO

The Wilms' Tumour 1 (WT1) gene plays an important role at three different stages of kidney development. The onset of kidney formation, the progression of kidney formation and the maintenance of normal kidney function. Disruption of WT1 may lead to a whole spectrum of kidney diseases ranging from tumour development to mild forms of renal failure. However, the underlying mechanisms are largely unknown. The WT1 proteins have been implicated in various cellular processes like proliferation, differentiation and apoptosis and in agreement with these diverse functions, the number of target genes is still mounting. The development of mouse models in recent years has contributed considerably to a better understanding of the biological activities of WT1, and in this article we will discuss the role of WT1 during kidney formation and kidney function.


Assuntos
Glomérulos Renais/embriologia , Rim/embriologia , Proteínas WT1/fisiologia , Animais , Apoptose , Diferenciação Celular , Divisão Celular , Modelos Animais de Doenças , Humanos , Rim/metabolismo , Glomérulos Renais/metabolismo , Camundongos , Modelos Biológicos , RNA Mensageiro/metabolismo , Insuficiência Renal/metabolismo , Proteínas WT1/metabolismo , Tumor de Wilms/metabolismo
19.
Virchows Arch ; 442(1): 56-65, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12536315

RESUMO

We tested the hypothesis whether allergic airway inflammation in ovalbumin sensitized and challenged Brown Norway rats is associated with intrinsic surfactant alteration and dysfunction. The determination of intra-alveolar surfactant subtypes and alveolar edema within their original microenvironment is only possible using an ultrastructural stereological approach. Therefore both lungs of control and asthmatic rats were fixed by vascular perfusion. The volume fractions of surfactant subtypes and the epithelial surface fraction covered with alveolar edema were determined by point and intersection counting. Furthermore, lung resistance was measured by means of whole-body plethysmography. The surface activity of surfactant from bronchoalveolar lavage was determined as minimum surface tension at minimal bubble size with a pulsating bubble surfactometer. Compared with controls, in asthmatics (1) the fraction of inactive unilamellar forms was significantly increased from 56% to 66%, (2) the fraction of alveolar epithelium covered with alveolar edema visible by light microscopy was significantly increased from 0.7% to 5.0%, (3) the fraction of alveolar epithelium covered with fluid seen by electron microscopy expanded significantly from 5% to 21%, (4) lung resistance was significantly elevated from 14% to 86% and (5) surface tension was enhanced from 6 mN/m to 12 mN/m. Thus, the inflammatory process after allergen challenge of sensitized Brown Norway rats causes intra-alveolar surfactant alterations. These surfactant alterations might contribute to small airway dysfunction.


Assuntos
Asma/metabolismo , Alvéolos Pulmonares/metabolismo , Surfactantes Pulmonares/metabolismo , Administração por Inalação , Aerossóis , Animais , Asma/imunologia , Asma/patologia , Barreira Alveolocapilar/imunologia , Modelos Animais de Doenças , Edema/imunologia , Edema/metabolismo , Edema/patologia , Imunização , Injeções Subcutâneas , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Alvéolos Pulmonares/ultraestrutura , Ratos , Ratos Endogâmicos BN , Testes de Função Respiratória
20.
Hepatology ; 34(4 Pt 1): 729-37, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11584369

RESUMO

Cumulating evidence suggests that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of chronic liver injury and fibrogenesis. We investigated the effects of oxidized low-density lipoproteins (oxLDL) on collagen and fibronectin synthesis of cultured human and rat hepatic stellate cells (HSC). As shown on protein and mRNA levels, oxLDL dose-dependently stimulated the synthesis of collagen types I and III and fibronectin of cultured HSC. The effect was biphasic, with a maximum between 5 and 25 microg/mL oxLDL (c-fibronectin concentration in HSC supernatants increased 3.9-fold; collagen type I increased 4-fold). Higher oxLDL concentrations were cytotoxic. LDL modified with malondialdehyde (MDA) was not toxic, but stimulated extracellular matrix synthesis as well. As demonstrated by immunofluorescence microscopy (double staining of CD36 and iso-alpha-smooth muscle actin [iso-alpha-sm actin]), immunoblot, and reverse-transcription polymerase chain reaction (RT-PCR), respectively, cultured human HSC express the oxLDL receptor, CD36 (glycoprotein IIIb). Colocalization of CD36 and iso-alpha-sm actin on sinusoidal lining cells was further demonstrated using sections of human fibrotic liver. Preincubation of cultured human HSC with the monoclonal antibody, OKM5, known to block CD36-mediated oxLDL uptake, resulted in a reduction of the oxLDL-stimulated collagen type I synthesis by 56%. In summary, our results demonstrate that low concentrations of modified lipoproteins (oxLDL and MDA-LDL) represent fibrogenic mediators that bind to CD36 and stimulate matrix synthesis of HSC.


Assuntos
Antígenos CD36/metabolismo , Proteínas da Matriz Extracelular/biossíntese , Lipoproteínas LDL/toxicidade , Fígado/metabolismo , Northern Blotting , Células Cultivadas , Imunofluorescência , Humanos , Lipoproteínas LDL/metabolismo , Fígado/citologia , Cirrose Hepática/etiologia
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